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Silver nanoparticles (AgNPs) have drawn a lot of attention from a variety of fields, particularly the biological and biomedical sciences. As a result, it is acknowledged that AgNPs' direct interactions with macromolecules such as DNA, proteins, and enzymes are essential for both therapeutic and nanotoxicological applications. Enzymes as important catalysts may interact with AgNP surfaces in a variety of ways. Therefore, mechanistic investigation into the molecular effects of AgNPs on enzyme conformation and function is necessary for a comprehensive assessment of their interactions. In this overview, we aimed to overview the various strategies for producing AgNPs. We then discussed the enzyme activity inhibition (EAI) mechanism by nanostructured particles, followed by an in-depth survey of the interaction of AgNPs with different enzymes. Furthermore, various parameters influencing the interaction of NPs and enzymes, as well as the antibacterial and anticancer effects of AgNPs in the context of the enzyme inhibitors, were discussed. In summary, useful information regarding the biological safety and possible therapeutic applications of AgNPs-enzyme conjugates may be obtained from this review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Long-time hypoxia induced cardiomyocyte apoptosis is an important mechanism of myocardial ischemia (MI) injury. Interestingly, long noncoding RNA myocardial infarction-associated transcript (LncMIAT) has been involved in the regulation of MI injury; however, the underlying mechanism by which LncMIAT affects the progression of hypoxia-induced cardiomyocyte apoptosis remains unclear. In the present study, hypoxia was found to promote cardiomyocyte apoptosis through an increased expression of LncMIAT in vitro . Biological investigations and dual-luciferase gene reporter assay further revealed that LncMIAT was able to bind with miR-708-5p to upregulate the p53-mediated cell death of the cardiomyocytes. Silencing of LncMIAT or overexpression of miR-708-5p led to a significant reduction in p53-mediated cardiomyocyte apoptosis. The methylated RNA immunoprecipitation (MeRIP)-qPCR results showed that hypoxia exerted its effects on LncMIAT through AKLBH5-N 6 -methyladenosine (m 6 A) methylation and therefore hypoxia was shown to trigger HL-1 cardiomyocyte apoptosis via the m 6 A methylation-mediated LncMIAT/miR-708-5p/p53 axis. Silencing of AKLBH5 significantly alleviated the m 6 A methylation-mediated LncMIAT upregulation and p53-mediated cardiomyocyte apoptosis, while promoted miR-708-5p expression. Taken together, the present study highlighted that LncMIAT could act as a key biological target during hypoxia-induced cardiomyocyte apoptosis. In addition, it was shown that hypoxia could promote cardiomyocyte apoptosis through regulation of the m 6 A methylation-mediated LncMIAT/miR-708-5p/p53 signaling axis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Free radical damage and oxidative stress are thought to play a crucial role in the development of neurodegenerative diseases. Walnut peptides, especially walnut oligopeptides, have been shown to protect nerve cells from oxidative stress and inflammatory damage, as well as improve memory function. In this study, walnut peptides were obtained from walnut meal through enzymatic hydrolysis, ultrafiltration, and gel filtration chromatography. A novel oligopeptide called AQ was successfully isolated and its chemical structure was identified as AASCDQ using ESI-MS/MS. AQ demonstrated remarkable scavenging activity against O 2 - free radicals (81.00%), DPPH free radicals (79.40%), and ABTS free radicals (67.09%) at a concentration of 1 mg mL -1 . Furthermore, AQ exhibited strong neuroprotective effects against hydrogen peroxide-induced damage in SH-SY5Y cells, reducing cell injury and apoptosis. AQ also effectively inhibited the secretion of pro-inflammatory factors NO (IC 50 = 46.03 ± 0.32 μM) and suppressed the expression of IL-6 and TNF-α in RAW264.7 cells stimulated by LPS. In vivo experiments demonstrated that AQ promoted angiogenesis in the quail chick chorioallantoic membrane assay and reduced ROS accumulation in Caenorhabditis elegans , thereby extending its lifespan. The anti-inflammatory mechanism of AQ was further confirmed by western blotting. In summary, the novel oligopeptide AQ possesses potential neuroprotective effects, including antioxidant, anti-inflammatory, angiogenic, and anti-aging properties, making it a promising candidate for the development of functional foods and pharmaceutical products.

Background: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM., Materials and Methods: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models., Results: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models., Conclusions: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes., (© 2024 John Wiley & Sons Ltd.)

Background: Myocardial infarction (MI) remains one of the major causes of high morbidity and mortality worldwide. Danggui Buxue Decoction (DBD)-an ancient Chinese herbal decoction-has been used to prevent coronary heart disease, which was called "chest palsy" in ancient clinics. However, the mechanism of DBD in the treatment of MI remains unclear. The aim of this study was to explore the effect and mechanism of DBD on MI by combining network pharmacology with in vivo experiments., Materials and Methods: First, public databases were used to identify the key active chemicals and possible targets of DBD. The MI targets were obtained from the Therapeutic Target Database, and the function of the target genes in relation to linked pathways was investigated. Subsequently, Cytoscape software was used to build a target-signaling pathway network. Finally, the efficacy of DBD therapy on MI was validated using in vivo investigations combined with molecular docking., Results: In traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), 27 bioactive compounds were screened from DBD. A total of 213 common targets were obtained, including 507 DBD targets and 2566 MI targets. Enrichment analysis suggests that PI3K/AKT is a potential signaling pathway for DBD-based protection. Immunofluorescence and protein blotting confirmed PI3K/AKT1, ERK2, and CASPASE-9 as the target proteins. Molecular docking analysis showed that quercetin, kaempferol, isoflavanones, isorhamnetin, hederagenin, and formononetin had high binding affinity to AKT1, ERK2, and CASPASE-9., Conclusions: This study demonstrated that the therapeutic benefit of DBD on MI may be mediated via target proteins in the PI3K/AKT pathway, such as AKT1, ERK2, and CASPASE-9. Our study data can help to provide ideas and identify new treatment targets for MI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Dilated cardiomyopathy (DCM) is a leading cause of heart failure. Cuproptosis is involved in various diseases, although its role in DCM is still unclear. Here, this study aims to investigate the feasibility of using genes related to cuproptosis as diagnostic biomarkers for DCM and the association of their expression with immune infiltration and drug target in cardiac tissue., Methods: Gene expression data from nonfailure (NF) and DCM samples were retrieved from the GEO database. Cuproptosis scores were calculated using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA) was used to screen key modules associated with DCM and cuproptosis. Random forest and least absolute shrinkage and selection operator (LASSO) were applied to identify signature genes. Finally, immune cell infiltration was assessed using ssGSEA. mRNA-miRNA-lncRNA regulatory networks and chemical-drug regulatory networks based on signature genes were analyzed by Cytoscape., Results: 8 modules were aggregated by WGCNA, among which MEblue was significantly associated with cuproptosis scores and DCM. A diagnostic model made up of six signature genes including SEPTIN1, CLEC11A, ISG15, P3H3, SDSL, and INKA1 was selected. Furthermore, immune infiltration studies showed significant differences between DCM and NF. Drugs networks and ceRNA regulatory network based on six signature genes were successfully constructed., Conclusion: Six signature genes (SEPTIN1, CLEC11A, ISG15, P3H3, SDSL, and INKA1) were identified as novel diagnostic biomarkers in DCM. In addition, the expression of these genes was associated with immune cell infiltration, suggesting that cuproptosis may be involved in the immune regulation of DCM., Competing Interests: Declaration of Competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration of articular cartilage. A challenge in the development of disease-modifying drugs is effective delivery to chondrocytes. The unique structure of the joint promotes rapid clearance of drugs through synovial fluid, and the dense and avascular cartilage extracellular matrix (ECM) limits drug penetration. Here, we show that poly(lactide- co -glycolic acid) nanoparticles coated in chondrocyte membranes (CM-NPs) were preferentially taken up by rat chondrocytes ex vivo compared with uncoated nanoparticles. Internalization of the CM-NPs was mediated primarily by E-cadherin, clathrin-mediated endocytosis, and micropinocytosis. These CM-NPs adhered to the cartilage ECM in rat knee joints in vivo and penetrated deeply into the cartilage matrix with a residence time of more than 34 days. Simulated synovial fluid clearance studies showed that CM-NPs loaded with a Wnt pathway inhibitor, adavivint (CM-NPs-Ada), delayed the catabolic metabolism of rat and human chondrocytes and cartilage explants under inflammatory conditions. In a surgical model of rat OA, drug-loaded CM-NPs effectively restored gait, attenuated periarticular bone remodeling, and provided chondroprotection against cartilage degeneration. OA progression was also mitigated by CM-NPs-Ada in a canine model of anterior cruciate ligament transection. These results demonstrate the feasibility of using chondrocyte membrane-coated nanoparticles to improve the pharmacokinetics and efficacy of anti-OA drugs.

Recent studies on osteosarcoma and matrix stiffness are still mostly performed in a 2D setting, which is distinct from in vivo conditions. Therefore, the results from the 2D models may not reflect the real effect of matrix stiffness on cell phenotype. Here, we employed a 3D bioprinted osteosarcoma model, to study the effect of matrix stiffness on osteosarcoma cells. Through density adjustment of GelMA, we constructed three osteosarcoma models with distinct matrix stiffnesses of 50, 80, and 130 kPa. In this study, we found that osteosarcoma cells proliferated faster, migrated more actively, had a more stretched morphology, and a lower drug sensitivity in a softer 3D matrix. When placed in a stiffer matrix, osteosarcoma cells secrete more MMP and VEGF, potentially to fight for survival and attract vascular invasion. Transcriptomic analysis showed that matrix stiffness could impact the signaling pathway of integrin α5-MAPK. The transplantation of 3D printed models in nude mice showed that cells encapsulated in the softer hydrogel were more likely to form subcutaneous tumors. These results suggest that matrix stiffness plays an important role in the development of osteosarcoma in a 3D environment and that inhibition of integrin α5 could block the signal transduction of matrix stiffness., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of overdiagnosis (0-91%), the purpose of this review was to identify and analyse assumptions made in modelling studies on the natural history of DCIS in women., Methods: A systematic review of English full-text articles using PubMed, Embase, and Web of Science was conducted up to February 6, 2023. Eligibility and all assessments were done independently by two reviewers. Risk of bias and quality assessments were performed. Discrepancies were resolved by consensus. Reader agreement was quantified with Cohen's kappa. Data extraction was performed with three forms on study characteristics, model assessment, and tumour progression., Results: Thirty models were distinguished. The most important assumptions regarding the natural history of DCIS were addition of non-progressive DCIS of 20-100%, classification of DCIS into three grades, where high grade DCIS had an increased chance of progression to invasive breast cancer (IBC), and regression possibilities of 1-4%, depending on age and grade. Other identified risk factors of progression of DCIS to IBC were younger age, birth cohort, larger tumour size, and individual risk., Conclusion: To accurately model the natural history of DCIS, aspects to consider are DCIS grades, non-progressive DCIS (9-80%), regression from DCIS to no cancer (below 10%), and use of well-established risk factors for progression probabilities (age). Improved knowledge on key factors to consider when studying DCIS can improve estimates of overdiagnosis and optimization of screening., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:BvdV declares advisory board/consultancy (on request) for Visiopharm, Philips, MSD /Merck, Daiichi-Sankyo/AstraZenica and speaker's fee from Visiopharm, Diaceutics, MSD /Merck. All honoraria to UMCG. All unrelated to the current manuscript., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Senile osteoporosis is characterized by age-related bone loss and bone microarchitecture deterioration. However, little is known to date about the mechanism that maintains bone homeostasis during aging. In this study, we identify adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1) as a critical factor regulating the senescence and lineage commitment of mesenchymal stem cells (MSCs). A phospho-mutant mouse model shows that constitutive AMPKα1 activation prevents age-related bone loss and promoted MSC osteogenic commitment with increased bone-derived insulin-like growth factor 1 (IGF-1) secretion. Mechanistically, upregulation of IGF-1 signalling by AMPKα1 depends on cAMP-response element binding protein (CREB)-mediated transcriptional regulation. Furthermore, the essential role of the AMPKα1/IGF-1/CREB axis in promoting aged MSC osteogenic potential is confirmed using three-dimensional (3D) culture systems. Taken together, these results can provide mechanistic insight into the protective effect of AMPKα1 against skeletal aging by promoting bone-derived IGF-1 secretion., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice., (© 2023. Springer Nature Limited.)

Previous findings have shown a strong relationship between sports and interpersonal cooperative behavior. Physical activity is the basic form of sport. In this study, we investigated the effect of physical activity on interpersonal cooperative behavior and its inter-brain correlates. Eighty college students were recruited and randomly divided into the experimental or control group (20 dyads per each). The experimental group performed a 30-min of moderate intensity single-person cycling exercise, while the control group performed a 30-min single-person sitting. Interpersonal cooperative behavior was measured by a Prisoner's Dilemma task before and after the intervention, while neural activities in the frontal cortex in each dyad were measured by the near-infrared spectroscopy-based hyperscanning approach. The results showed that the average cooperation rate and cooperation efficiency of the experimental dyads were significantly higher after the exercise intervention compared to that before intervention, but not in control group. Meanwhile, the interpersonal neural synchronization (INS) in the left frontal cortex was significantly increased after intervention only in experimental dyads. Moreover, the INS increased in left frontal cortex was positively correlated with the cooperation improvement. Taken together, these results indicate that one single-person bicycling can improve interpersonal cooperation behavior, which may be associated with enhanced interpersonal neural synchronization in the left frontal cortex., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Whether and how shared intentionality (SI) influences the establishment of a novel interpersonal communication system is poorly understood. To investigate this issue, we designed a coordinating symbolic communication game (CSCG) and applied behavioral, functional near-infrared spectroscopy (fNIRS)-based hyperscanning, and hyper-transcranial alternating current stimulation (hyper-tACS) methods. Here we show that SI is a strong contributor to communicative accuracy. Moreover, SI, communicative accuracy, and interpersonal neural synchronization (INS) in the right superior temporal gyrus (rSTG) are higher when dyads successfully establish a novel communication system. Furthermore, the SI influences communicative accuracy by increasing INS. Additionally, using time series and long short-term memory neural network analyses, we find that the INS can predict communicative accuracy at the early formation stage of the communication system. Importantly, the INS partially mediates the relationship between the SI and the communicative accuracy only at the formation stage of the communication system. In contrast, when the communication system is established, SI and INS no longer contribute to communicative accuracy. Finally, the hyper-tACS experiment confirms that INS has a causal effect on communicative accuracy. These findings suggest a behavioral and neural mechanism, subserved by the SI and INS, that underlies the establishment of a novel interpersonal communication system., (© 2023. Springer Nature Limited.)

Analogical reasoning is important for human. We have found that a short executive attention intervention improved analogical reasoning performance in healthy young adults. Nevertheless, previous electrophysiological evidence was limited for comprehensively characterizing the neural mechanisms underlying the improvement. And although we hypothesized that the intervention improved active inhibitory control and attention shift first and then relation integration, it is still unclear whether there are two sequential cognitive neural activities were indeed changed during analogical reasoning. In the present study, we combined hypothesis with multivariate pattern analysis (MVPA) to explore the effects of the intervention on electrophysiology. Results showed that in the resting state after the intervention, alpha and high gamma power and the functional connectivity between the anterior and middle in the alpha band could discriminate the experimental group from the active control group, respectively. These indicated that the intervention influenced the activity of multiple bands and the interaction of frontal and parietal regions. In the analogical reasoning, alpha, theta, and gamma activities could also fulfill such discrimination, and furthermore, they were sequential (alpha first, theta, and gamma later). These results directly supported our previous hypothesis. The present study deepens our understanding about how executive attention contributes to higher-order cognition., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Osteosarcoma is the most prevalent bone malignant tumor in children and teenagers. The bone defect, recurrence, and metastasis after surgery severely affect the life quality of patients. Clinically, bone grafts are implanted. Primary bioceramic scaffolds show a monomodal osteogenesis function. With the advances in three-dimensional printing technology and materials science, while maintaining the osteogenesis ability, scaffolds become more patient-specific and obtain additional anti-tumor ability with functional agents being loaded. Anti-tumor therapies include photothermal, magnetothermal, old and novel chemo-, gas, and photodynamic therapy. These strategies kill tumors through novel mechanisms to treat refractory osteosarcoma due to drug resistance, and some have shown the potential to reverse drug resistance and inhibit metastasis. Therefore, multifunctional three-dimensional printed bioceramic scaffolds hold excellent promise for osteosarcoma treatments. To better understand, we review the background of osteosarcoma, primary 3D-printed bioceramic scaffolds, and different therapies and have a prospect for the future., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Cognitive impairments are common in patients with schizophrenia. Changes in total cholesterol (TC) may be involved in the development of schizophrenia and associated with cognitive function. This study aimed to investigate differences in serum TC level and cognitive function between schizophrenia patients and healthy controls and explore the relationship between serum TC level and cognitive function in patients with schizophrenia. A total of 105 schizophrenia patients and 105 healthy controls were recruited. Results showed that patients with schizophrenia had significantly lower scores on the overall RBANS scale and subscales (i.e., immediate memory, language, attention, and delayed memory) than those of healthy controls. Pearson's correlation analyses showed that in patients with schizophrenia, serum TC levels were positively associated with RBANS subscale scores of immediate memory and language. Furthermore, multivariate regression analyses showed that serum TC level was positively associated with the immediate memory index in patients with schizophrenia. However, no significant association was found between serum TC level and RBANS score in the healthy control group. Our results suggest that elevated serum TC level may be related to improved cognitive function in patients with schizophrenia, especially that of immediate memory., Competing Interests: Declaration of competing interest Nil., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To observe the effect of Danzhi Jiangtang capsule (DJC) on the clinical indexes and vascular endothelial function indexes in patients with impaired glucose tolerance (IGT)., Methods: A total of 106 patients were enrolled and randomly assigned to the treatment group and control group following a four-week washout period. The patients in the control group received a general lifestyle intervention, while those in the treatment group received DJC (2.0 g 3× a day) in conjunction with the intervention given to the control group patients. The physiological and biochemical levels, vascular endothelial function indices, and traditional Chinese medicine (TCM) syndrome ratings of the patients in the two groups were compared after 12 weeks of therapy., Results: In the control group, the diastolic blood pressure (DBP) was significantly improved compared with those before treatment (83.31 ± 6.47 vs. 79.21 ± 6.17, p  < .01) (CI: 1.45, 6.73; Cohen's d : 10.51), as was the case with the nitric oxide (NO) levels and TCM syndrome points (35.71 ± 4.58 vs. 43.96 ± 5.17, 9.57 ± 2.63 vs. 5.38 ± 1.79, p  < .001) (CI: -10.28, -6.24; 3.12, 5.18; Cohen's d : 0.90). In the treatment group, the levels of fasting blood glucose, endothelin and vascular endothelial growth factor were significantly improved compared with control group (4.92 ± 0.21 vs. 5.59 ± 0.31, 59.37 ± 13.25 vs. 72.13 ± 12.37, 19.25 ± 2.80 vs. 26.76 ± 1.88, p  < .001) (CI: 0.55, 0.78; 7.40, 18.13; 6.52, 8.50; Cohen's d : 4.94, 0.41, 1.32), as was the case with 2-h post-load plasma glucose and total cholesterol (TC) (8.33 ± 0.62 vs. 8.89 ± 1.55, 4.61 ± 1.05 vs. 5.22 ± 1.12, p  < .05) (CI: 0.07, 1.07; 0.15, 1.06; Cohen's d : 0.40, 0.51)., Conclusions: Treatment with DJC could significantly improve the physiological and biochemical indicators, vascular endothelial function, and TCM syndrome points of IGT patients, indicating that DJC could be a potential drug to treat patients with IGT of Qi-Yin deficiency type.

Psychological pain is a robust predictor of suicide attempts in patients with major depressive disorder (MDD). However, whether suicide and psychological pain share a common neural basis remains unclear. Patients with MDD (n = 64) and healthy controls (HC) (n = 35) were recruited and patients were allocated to two groups: those with a history of suicide attempts (MDD-SA) (n = 25) and those without such a history (MDD-NSA) (n = 39). All participants completed the measurements and underwent functional magnetic resonance imaging to investigate the resting-state static and dynamic brain functional networks in default mode (DMN), central executive (CEN), salience (SN), and basal ganglia (BGN) networks. The MDD-SA group scored higher in pain avoidance than the MDD-NSA and HC groups. Functional connectivity within the dorsal DMN in the MDD-SA group was greater than that in the MDD-NSA and HC groups, and was significantly correlated with pain avoidance and suicide attempts. Dynamic functional connectivity analysis revealed that the proportion of State I in the fraction windows in the MDD-SA group was higher than those in the MDD-NSA and HC groups. Therefore, the increased functional connectivity within the dorsal DMN and segregation of networks may represent potential biological markers for suicide attempts related to psychological pain processing., Competing Interests: Declarations of Competing Interest None, (Copyright © 2022. Published by Elsevier B.V.)

Analogical reasoning improvement is important in educational outcome improvement. Inspired by recent ideas and evidence, we applied anti-saccade task training as an executive attention intervention and tested whether it could improve analogical reasoning performance. A serial-task paradigm was applied where participants performed an anti-saccade followed by an analogical reasoning task including a perception condition. The experimental group finished the anti-saccade task in which the ratio of anti-saccade trials to pro-saccade trials was 5:1 while the counterpart was 1:1 in the active control group. Also, a blank control group was established where participants merely finished the analogical reasoning task. Event-related electroencephalographic (EEG) data were recorded when participants were performing the executive attention and analogical reasoning tasks. In addition, their resting state EEG was collected before and after the executive attention intervention. Behaviorally, the experimental group reacted significantly faster than the other two groups in analogical reasoning but not in perception. At the neural level, in the experimental group alone, the anti-saccade trials elicited a smaller N2 than pro-saccade trials and the resting alpha power was improved after executive attention intervention. No significant difference in P2 was found between the two groups in analogical reasoning or perception but the experimental group showed a larger late positive component than the active control group in analogical reasoning. We also found that the late positive component mediated the relationship between the N2 of anti-saccade trials and analogical reasoning reaction times in the experimental group. We further discussed the role of executive attention in the analogical reasoning process, which may pave the way for the future reliable improvement of fluid intelligence., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Coronary heart disease is the most common heart disease, it can induce myocardial infarction, and the cause of the disease has a lot to do with life and eating habits. The results of a large number of epidemiological studies at home and abroad show that the incidence of coronary heart disease has an obvious familial tendency. However, little is known about the genetic factors of coronary heart disease. Although genome-wide association analysis and gene knockout experiments have found some genes related to coronary heart disease, there are still a large number of genes potentially related to coronary heart disease that have not been discovered. If it is confirmed by biological experimental means, the time and money cost is too high. Therefore, it is urgent to identify genes related to coronary heart disease on a large scale by computational means, so as to conduct targeted biological experimental verification. This paper proposes a deep learning method based on biological networks for the identification of coronary heart disease-related genes. We constructed gene interaction networks and extracted gene expression levels in different tissues as features. Through the association information and expression characteristics between genes, we constructed a model of coronary heart disease-related genes. Through cross-validation, we found that our proposed GCN-GENE that has AUC as 0.75 and AUPR as 0.78, which is more accurate than other methods and is a reliable method for predicting coronary heart disease-related genes., Competing Interests: Declarations of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Detecting and correcting execution errors is crucial for safe and efficient goal-directed behavior. Despite intensive investigations on error processing, the cognitive foundations of this process remain unclear. Based on the presumed relation between executive attention (EA) and error processing, we implemented a seven-day EA intervention by adopting the Posner cueing paradigm to test the potential causal link from EA to error processing in healthy adults. The experimental group (high EA, HEA) was trained on the Posner cueing paradigm, with a ratio of invalid cue (IC) trials to valid cue (VC) trials of 5:1 and a corresponding ratio of 1:1 in the active control group (low EA, LEA). We found that the EA intervention improved EA across intervention sessions. Critically, after the EA intervention, the HEA group showed that post-error accuracy (PEA) was restored to the same level as the post-correct accuracy (in comparison with the LEA group). However, post-error slowing and the flanker effect were not modulated by the EA intervention. Furthermore, we observed that the changes in the accuracy of VC trials positively predicted the changes in PEA and that the two groups were classified according to the changes in PEA with a 61.3% accuracy. Based on these results, we propose that EA causally drives error processing. And the capabilities of the "actively catch" more attention resources and the automatic mismatch processing developed after EA intervention is transferable to error processing, thereby directly resulting in the gains in post-error adjustments. Our work informs the potential cognitive mechanisms underlying this causal link., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Lin, Wang, Zhang, Stonier and Chen.)

Objective: To evaluate the interbody fusion efficacy and biocompatibility of a graft-free cage made of polyetheretherketone/calcium silicate composite/porous tantalum (PEEK/CS/pTa cage) compared with a PEEK/CS cage with an autogenous bone graft in a goat model., Methods: PEEK/CS/pTa and PEEK/CS cages were prepared through an injection-moulding method. The PEEK/CS composites and porous tantalum were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) mapping. Then, adult goats were chosen for C2/C3 and C3/C4 discectomy via the anterior cervical approach and randomly implanted with PEEK/CS/pTa and PEEK/CS/cages with autogenous bone grafts. The fusion performance and osseointegration of the cages were evaluated by X-ray imaging, magnetic resonance imaging (MRI) scanning, and bone histomorphometry analysis. Moreover, the concentrations of Ca and Si in urine, serum, tissue around the fusion segments and major organs of the goats were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES). Histological observation of major organs of the goats was used to evaluate the biosafety of PEEK/CS/pTa and PEEK/CS cages., Results: X-ray and MRI imaging suggested that both PEEK/CS/pTa cages and PEEK/CS cages maintained similar average intervertebral space heights. The tissue volumes in the fusion area were comparable between the two groups of cages at 26 weeks after surgery. Histological morphometric data showed that PEEK/CS/pTa cages and PEEK/CS cages with autogenous bone grafts had similar bone contact and osseointegration at 12 and 26 weeks. Element determination of serum, urine, spinal cord, dura matter, bone and organs showed that the CS/PEEK cages did not cause abnormal systemic metabolism or accumulation of calcium and silicon in local tissues and major organs of goats after implantation. No obvious pathological changes were found in the heart, liver, spleen, liver or kidney tissues., Conclusion: Overall, these results suggested that the graft-free PEEK/CS/pTa cage showed similar bony fusion performance to the PEEK/CS cages with autogenous bone grafts. The cages releasing calcium and silicon had good biological safety in vivo.The translational potential of this article: This study provided a new graft-free interbody fusion solution to patients with degenerative disc diseases, which could avert potential donor-site complications. This study also provided a detailed assessment of element excretion and accumulation of Ca and Si in vivo, which validated the biosafety of this new type of bioactive interbody fusion cage., Competing Interests: The authors report no conflicts of interest related to this work., (© 2022 The Authors.)

Diabetic neuropathic pain (DNP) is one of the most common chronic peripheral neuropathies in diabetes mellitus (DM). Objective . To observe the underlying mechanism of the effects of Yiqi Huoxue Tongluo Decoction (YQHX) on DNP rats. Methods . SD rats were intraperitoneally injected with 35 mg/kg streptozotocin (STZ) to prepare DNP models and were treated with YQHX for 8 weeks. Results . Studies have shown that the drug restores some levels of MWT, TWL, and MNCV, downregulates the levels of inflammatory factors IL-6, IL-1 β , and TNF- α , downregulates the levels of ASK1-MKK3-p38, and weakens the level of OX42 activation. Conclusion . Yiqi Huoxue Tongluo Decoction can relieve DNP by affecting the activity of spinal cord microglia and the ASK1-MKK3-p38 signaling pathway, thereby reducing the central sensitization caused by the inflammatory response of DNP rats., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Fanjing Wang et al.)

Background: Urinary iodine concentration (UIC) is routinely used to evaluate the population iodine status while the uniform method for the individual level assessment is uncertain., Objectives: To explore the 24-h urinary iodine excretion (UIE) in five different periods of the day and the corresponding prediction equations respect by the use of creatinine-corrected UIC., Methods: We collected 24-h, spot and fasting urine in five periods of the day to estimate 24-h UIE by the six different prediction equations. We compared the estimated creatinine-corrected UIC to the collected 24-h UIE and identified the most suitable equations in each period of the day., Results: Among the six different prediction equations, the equation of Kawasaki T was the best to estimate the 24-h UIE by fasting urine among Chinese adults. Among the five periods of time, the equation of Knudsen N was the best to estimate the 24-h UIE in the non-morning period., Conclusion: Urinary iodine status at the individual level could be estimated by different creatinine-based equations at different periods of the day., (© 2022. The Author(s).)

Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models and tumour spheroids, our 3DBPO model showed significant changes in cell cycle, metabolism, adherens junctions, and other pathways associated with epigenetic regulation. The 3DBPO model was more sensitive to therapies targeted to the autophagy pathway. We showed that simulating ECM yielded different osteosarcoma cell metabolic characteristics and drug sensitivity in the 3DBPO model compared with classical models. We suggest 3D printed osteosarcoma models can be used in osteosarcoma fundamental and translational research, which may contribute to novel therapeutic strategy discovery., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Diabetic osteoporosis (DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1 (HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment., (© 2022. The Author(s).)

Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on Escherichia coli cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8 + T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To investigate the potential mechanism of action of Yi-Qi-Huo-Xue-Tong-Luo formula (YQHXTLF) in the treatment of diabetic peripheral neuropathy (DPN)., Methods: Network pharmacology and molecular docking techniques were used in this study. Firstly, the active ingredients and the corresponding targets of YQHXTLF were retrieved using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform; subsequently, the targets related to DPN were retrieved using GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmgkb, Therapeutic Target Database (TTD) and Drugbank databases; the common targets of YQHXTLF and DPN were obtained by Venn diagram; afterwards, the "YQHXTLF Pharmacodynamic Component-DPN Target" regulatory network was visualized using Cytoscape 3.6.1 software, and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the potential targets using R 3.6.3 software. Finally, molecular docking of the main chemical components in the PPI network with the core targets was verified by Autodock Vina software., Results: A total of 86 active ingredients and 229 targets in YQHXTLF were screened, and 81 active ingredients and 110 targets were identified to be closely related to diabetic peripheral neuropathy disease. PPI network mapping identified TP53, MAPK1, JUN, and STAT3 as possible core targets. KEGG pathway analysis showed that these targets are mostly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the main chemical components of YQHXTLF have a stable binding activity to the core pivotal targets., Conclusion: YQHXTLF may act on TP53, MAPK1, JUN, and STAT3 to regulate inflammatory response, apoptosis, or proliferation as a molecular mechanism for the treatment of diabetic peripheral neuropathy, reflecting its multitarget and multipathway action, and providing new ideas to further uncover its pharmacological basis and mechanism of action., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yixuan Lin et al.)

Diabetic neuropathy (DN) is one of the chronic complications of diabetes which can cause severe harm to patients. In order to determine the key genes and pathways related to the pathogenesis of DN, we downloaded the microarray data set GSE27382 from Gene Expression Omnibus (GEO) and adopted bioinformatics methods for comprehensive analysis, including functional enrichment, construction of PPI networks, central genes screening, TFs-target interaction analysis, and evaluation of immune infiltration characteristics. Finally, we examined quantitative real- time PCR (qPCR) to validate the expression of hub genes. A total of 318 differentially expressed genes (DEGs) were identified, among which 125 upregulated DEGs were enriched in the mitotic nuclear division, extracellular region, immunoglobulin receptor binding, and p53 signaling pathway, while 193 downregulated DEGs were enriched in ion transport, membrane, synapse, sodium channel activity, and retrograde endocannabinoid signaling. GSEA plots showed that condensed nuclear chromosome kinetochore were the most significant enriched gene set positively correlated with the DN group. Importantly, we identified five central genes (Birc5, Bub1, Cdk1, Ccnb2, and Ccnb1), and KEGG pathway analysis showed that the five hub genes were focused on progesterone-mediated oocyte maturation, cell cycle, and p53 signaling pathway. The proportion of immune cells from DN tissue and normal group showed significant individual differences. In DN samples, T cells CD4 memory resting and dendritic cells resting accounted for a higher proportion, and macrophage M2 accounted for a lower proportion. In addition, all five central genes showed consistent correlation with immune cell infiltration levels. qPCR showed the same expression trend of five central genes as in our analysis. Our research identified key genes related to differential genes and immune infiltration related to the pathogenesis of DN and provided new diagnostic and potential therapeutic targets for DN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Wang, Cheng, Fang and Shen.)

Graphene oxide (GO) and polystyrene nanoplastic (PSNP) are typical carbonaceous nanomaterials which likely co-exist in soil and sediment. Here, we describe the transport of GO, irradiation reduced GO (RGO) and PSNP in saturated quartz sand both in single and binary systems. In the single transport system, the materials exhibited mobility in the order of GO > RGO > PSNP, due to increased hydrophobicity and decreased negative surface charges. Nevertheless, the co-transport of (R)GO and PSNP in the binary transport system was much more intricate. In Na + saturated porous media, PSNP preferred to interact with (R)GO relative to the highly negatively charged quartz sand, thus (R)GO carried PSNP to break through the sand column. However, in Ca 2+ saturated porous media, the transport of both (R)GO and PSNP was depressed, attributed to the particle-collector and particle-particle bridging effects between Ca 2+ and the metal-complexing moieties of the nanoparticles and sand grains. Moreover, GO influenced the co-transport of PSNP to a larger extent than RGO, especially at relatively high ionic strength, because of the more abundant surface O-functional groups on GO providing more complexion sites with Ca 2+ . These results demonstrated that the transport of negatively charged nanomaterials was greatly related to the hydrophobicity and surface O-functional groups., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The electroactive β-phase in Poly (vinylidene fluoride, PVDF) is the most desirable conformation due to its highest pyro- and piezoelectric properties, which make it feasible to be used as flexible sensors, wearable electronics, and energy harvesters etc. In this study, we successfully developed a method to obtain high-content β-phase PVDF films and nanofiber meshes by mechanical stretching and electric spinning. The phase transition process and pyro- and piezoelectric effects of stretched films and nanofiber meshes were characterized by monitoring the polarized light microscopy (PLM) images, outputting currents and open-circuit voltages respectively, which were proved to be closely related to stretching ratio (λ) and concentrations. This study could expand a new route for the easy fabrication and wide application of PVDF films or fibers in wearable electronics, sensors, and energy harvesting devices.

Background: Universal salt iodization program was introduced to China to eliminate iodine deficiency disorders in 1995. In 2012, Fujian Province decreased the concentration of iodized table salt according to the national unified requirement. This study aimed to assess the effect on iodine status after the adjustment, providing evidence for further adjustment in Fujian Province., Methods: Sampling units were selected by multistage cluster sampling method. In each sampling unit, table salt was collected from 30 households. A total of 2,471 people in 2009 and 4,806 people in 2017 provided urine samples and were included in this cross-sectional analysis. Median iodized salt concentration and median urine iodine concentration were present by median and interquartile range., Results: Median iodized salt decreased from 29.8 mg/kg in 2009 to 23.9 mg/kg in 2017. The median urinary iodine concentrations for school-age children in 2017 in coastal urban area, non-coastal urban area, coastal rural area and non-coastal rural area were 163.6µg/L (interquartile range = 100.1-252.0µg/L), 198.9µg/L (interquartile range = 128.0-294.0µg/L), 181.8µg/L (interquartile range = 114.1-257.0µg/L) and 218.2µg/L (interquartile range = 148.1-306.5µg/L), respectively. The median urinary iodine concentrations for adults in 2017 in these areas were 151.1µg/L (interquartile range = 98.3-231.7µg/L), 168.7µg/L (interquartile range = 109.6-242.0µg/L), 167.7µg/L (interquartile range = 105.7-245.7µg/L) and 182.7µg/L (interquartile range = 117.1-258.9µg/L). The median urinary iodine concentrations for pregnant women in 2017 in these areas were 157.7µg/L (interquartile range = 106.9-223.8µg/L), 141.5µg/L (interquartile range = 97.7-207.6µg/L), 127.3µg/L (interquartile range = 90.0-184.5µg/L) and 144.8µg/L (interquartile range = 99.9-184.5µg/L). The median urinary iodine concentrations for lactating women in 2017 in these areas were 122.7µg/L (interquartile range = 84.1-172.0µg/L), 123.7µg/L (interquartile range = 70.7-184.7µg/L), 105.8µg/L (interquartile range = 67.1-152.3µg/L) and 110.2µg/L (interquartile range = 74.1-170.3µg/L)., Conclusions: The overall urinary iodine concentrations among school-age children, adults and lactating women dramatically decreased after implementing the new standard. Almost all of them were iodine adequate, suggesting we reached the expected aim of iodized salt adjustment. However, pregnant women were iodine insufficient after adjustment. Therefore, we should continue the surveillance of iodine status of populations and focus on the additional iodine supplement strategies for pregnant women.

Black phosphorus (BP) nanosheets with excellent features have been broadly employed for cancer therapy. BPs in blood were known to form BP nanomaterial-corona complexes, yet not explored their biological effects. In this study, BPs as delivery vehicles loaded with doxorubicin (DOX) (BP-DOX) by electrostatic interaction had been successfully prepared for photo-thermal/chemotherapy with a tumor inhibition rate of 81.47% more than the rates of BPs (69.50%) and free DOX (51.91%) in the Hela-bearing mice model by a pH/photo-responsive controlled drug release property. Then, in vivo experiments demonstrated that the treatment of healthy mice with BPs led to mild inflammation in the body and oxidative stress in the liver and lung which caused cell apoptosis. In vitro studies further showed that oxidative stress and metabolic disorders could be induced by BPs in A549, HepG2, Beas-2B, and LO2 cells. Lastly, the RGD peptide-conjugated red blood cell (RBC) membrane-coated BPs (RGD-RBC@BP) was prepared by lipid insertion and co-ultrasound methods for efficient photo-thermal therapy (PTT) cancer via a tumor-targeted strategy. RGD-RBC@BP showed positive biocompatibility, photo-thermal properties, and increased cellular uptake by Hela cells benefited by the long circulation property of RBC and RGD peptides. Pharmacokinetics and bio-distribution study of RGD-RBC@BP were found to prolong circulation time and tended to accumulate in the tumors, which overexpression of ανβ3 integrin rather than livers after intravenous injection 24 h in vivo . After 808 nm laser irradiation, RGD-RBC@BP nanoparticles exhibited a better PTT than PEGylated BPs (BP-PEG). The active-targeting strategy of biomimetic nanomaterials based on the tumor microenvironment have been proved to have favorable biological prospects in cancer PTT.

Ethnopharmacological Relevance: Cicer arietinium L., which belongs to Cicer genus, was not only a kind of traditional Chinese medicines (TCM) recorded in Pharmacopoeia of the People's Republic of China (version 2015), but also a kind of Uighur antidiabetic medicines. It has been used as an adjuvant drug or functional food for thousand years in Xinjiang province, China. However, the mechanisms of C. arietinium treatment in T2D have not been fully understood especially on the perspective of metabolomics., Aim of the Study: To clarify the potential mechanisms of C. arietinium treatment in T2D from the perspective of metabolomics since T2D is indeed a kind of metabolic syndromes., Materials and Methods: T2D rat model was built by HFD for 4 weeks, combining with STZ administration. T2D rats were administrated C. arietinium extraction or metformin (positive control) for 4 weeks. UPLC-Q-TOF-MS was applied to screen and identify differential metabolites among groups., Results: After 4 weeks of treatments, IR and inflammation were greatly ameliorated in C. arietinium group. And the therapeutic efficiency of C. arietinium treatment was comparable to metformin treatment. Differential metabolites related to C. arietinium treatment, including acylcarnitines, amino acid related metabolites and organic acids, were further used to indicate relevant pathways in T2D rats, including glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, vitamin B6 metabolism and energy metabolism., Conclusions: In summary, C. arietinium treatment could effectively alleviate diabetic symptoms and regulate metabolic disorders in T2D rats., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Systemic chemotherapy for treating tumors often leads to serious systemic side effects and affects patient compliance. Although the emerging technology of drug delivery systems (DDSs) can deliver the required cargo to tumor sites, DDSs are limited due to insufficient targeting ability or deficient pharmacokinetics. Herein, we assembled a novel targeting DDS for precision tumor therapy by applying a tumor-targeting polypeptide cyclic RGD (cRGD)-modified erythrocyte membrane (eM-cRGD) cloaked on zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) with encapsulated doxorubicin (DOX). For a mass ratio of ZIF-8:DOX = 1:1, the loading capacity was up to 49%. The nanoscale-sized targeting DDS promoted NP accumulation in tumor tissues via enhanced permeability and retention (EPR) effects, and the NPs actively targeted ligands and were then transferred to endosomes. The pH-sensitive carriers released higher DOX levels under the low pH mimicking that of a tumor microenvironment and tumor intracellular organelles, allowing enhanced inhibition of cancer cell growth. The cumulative release rate of DOX from DOX@ZIF-8 NPs reached 82.8% at 48 h in acidic conditions of pH = 5.0, while the cumulative release rate of DOX from the DOX@ZIF-8 NPs reached only 24.92% at pH = 7.4. The internalization of the DDS was approximately 44.35% that of the unmodified DDS by immune cells, as confirmed by flow cytometry. In vivo studies verified that the RGD-modified DDS had the ability to prolong blood circulation ( t 1/2 = 6.81 h), enhancing the tumor-specific accumulation of NPs by means of the integrin αvβ3 receptor-mediated pathway, which was further valuated in mice bearing human cervical cancer (HeLa) cells, and yielding a significant antitumor effect; the tumor inhibition rate was as high as 85.46%. Under the same conditions, the blood circulation half-life of the unmodified DDS was only 3.22 h, and the tumor inhibition rate of free DOX was 81.34%. Moreover, the RGD modified with a carrier could achieve a satisfactory chemotherapeutic effect while minimizing side effects. In summary, our novel targeting DDS could contribute to the development of intelligent DDSs for tumor precision therapy.

Osteocytes, essential regulators of bone homeostasis, are embedded in the mineralized bone matrix. Given the spatial arrangement of osteocytes, bioprinting represents an ideal method to biofabricate a 3D osteocyte network with a suitable surrounding matrix similar to native bone tissue. Here, we reported a 3D bioprinted osteocyte-laden hydrogel for biomimetic mineralization in vitro with exceptional shape fidelity, a high cell density (10 7 cells per ml) and high cell viability (85%-90%). The bioinks were composed of biomimetic modified biopolymers, namely, gelatine methacrylamide (GelMA) and hyaluronic acid methacrylate (HAMA), with or without type I collagen. The osteocyte-laden constructs were printed and cultured in mineralization induction media. After 28 d, increased dendritic cell connections and enhanced mineralized matrix production were observed after the addition of type I collagen. These results were further confirmed by the expression of osteocyte-related genes, markers of osteocyte morphology (Connexin43 and E11/Podoplanin), markers of mineralization (dentin matrix acidic phosphoprotein 1 (Dmp1)) and the cellular response to parathyroid hormone (PTH). Moreover, the 3D bioprinting constructs outperformed the 2D monolayer culture and they were at least comparable to 3D casted hydrogels in mimicking the natural osteocyte phenotype. All results indicated that the 3D bioprinting osteocyte network shows promise for mechanistic studies and pharmaceutical screening in vitro.

Background: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in the world with complicated pathogenesis. This study aimed to identify differentially expressed genes (DEGs) and molecular pathways in T2DM using bioinformatics analysis., Materials and Methods: To explore potential therapeutic targets for T2DM, we analyzed three microarray datasets (GSE50397, GSE38642, and GSE44035) acquired from the Gene Expression Omnibus (GEO) database. DEGs between T2DM islet and normal islet were picked out by the GEO2R tool and Venn diagram software. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to identify the pathways and functional annotation of DEGs. Then, protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes/Proteins (STRING)., Results: In total, we identified 36 DEGs in the three datasets, including 32 up-regulated genes and four down-regulated genes. The improved functions and pathways of the DEGs enriched in cytokine-cytokine receptor interaction, pathways in cancer, PI3K-Akt signaling pathway, and Rheumatoid arthritis. Among them, ten hub genes with a high degree of connectivity were selected. Furthermore, via the re-analysis of DAVID, four genes ( IL6, MMP3, MMP1, and IL11 ) were significantly enriched in the Rheumatoid arthritis pathway., Conclusion: Our study, based on the GEO database, identified four significant up-regulated DEGs and provided novel targets for diagnosis and treatment of T2DM., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Lin et al.)

LiNbO 3 (LN) crystal has been widely used as a pyroelectric material due to its spontaneous electric polarization, which could be recharged easily and can directly convert heat energy into electricity. LN crystal's heat-resistant, low-cost, and low dielectric loss properties make it possible for its applications in room-temperature pyroelectric devices and thermal sensors. However, LN crystal suffers from fragility, inflexibility, and other mechanical properties, which limit its suitability for many applications in various fields. In this study, the LN modified flexible pyroelectric films, composed of LN micro-particles, polypropylene (PP) matrix, and multiwalled carbon nanotubes (MWCNTs), are successfully fabricated. The pyroelectric effects of LN crystal and LN/PP/MWCNT composite films are characterized by monitoring the patterned self-assembly of nanoparticles and the output pyroelectric currents. The excellent pyroelectric properties of the composites have potential applications in energy harvesters or sensors.

Background and Aim: Inflammatory bowel disease results from a dysregulated immune response to intestinal microbial flora in individuals with genetic predisposition(s). This study aimed to determine the effects of compound polysaccharides (CP) containing yam polysaccharide and inulin on the rat model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and to explain the mechanism in terms of gut microbiota composition and function., Methods: Male SD rats were divided into three groups: the control group, the model group, and the CP group. Disease activity index, serum myeloperoxidase level, and the composition and function of gut microbiota were analyzed., Results: The data in the study showed CP reduced inflammation in the rat model of colitis induced by TNBS and ameliorated the experimental colitis. The results also indicated that CP not only reversed TNBS-induced gut dysbiosis-indexed by increased short-chain fatty acids (SCFAs)-producing bacteria, lactic acid-producing bacteria, and decreased Bacteroides, Proteobacteria as well as sulfate-reducing bacteria, but also restored the dysregulated microbiota function of colitic rats into a normal condition, including an improvement on basic metabolism and a reduction on oxidative stress, cell motility, signal transduction, xenobiotics biodegradation, and metabolism as well as pathogenesis processes., Conclusions: Compound polysaccharides ameliorated the experimental colitis of rats induced by TNBS by modulating the gut microbiota composition and function profiles, which makes it possible to be used as prebiotic agents to treat gut dysbiosis in colitis individuals., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The fast-growing production and application of carbon nanotube (CNT) materials in a variety of industrial products inevitably lead to their release to wastewater and surface water. CNT would experience oxidization in wastewater treatment plant due to the presence of large amount of disinfectants, such as H 2 O 2 and O 3 , which in turn affects the environmental fates and risks of CNT. In this study, oxidized CNT materials (O-CNTs) were prepared by treating CNT with H 2 O 2 /UV and O 3 (denoting as H 2 O 2 -CNT and O 3 -CNT, respectively). A variety of characterizations indicated that oxygen containing groups were generated on CNT surface upon the oxidation, and the O/C ratio increased in the order of pristine CNT < H 2 O 2 -CNT < O 3 -CNT. In the presence of Na + , K + and Mg 2+ , the O-CNTs displayed better colloidal stability than the pristine CNT, and the stability increased with the oxidation degree (indicated by O/C ratio). This could be explained by the more negative surface charge and stronger hydrophilicity of the O-CNTs. Unexpectedly, in the presence of Ca 2+ , the most oxidized O 3 -CNT exhibited the poorest colloidal stability. The abundant carboxyl groups in O 3 -CNT provided effective binding sites for cation bridging effect through Ca 2+ and led to stronger aggregation. Increasing pH was more favorable to disperse CNTs (both O-CNT and pristine CNT) in the presence of Na + , but much less effective in inhibiting the aggregation of O 3 -CNT in presence of Ca 2+ . This could be explained by the stronger cation bridging effect due to enhanced deprotonation the -COOH groups at higher pH conditions. The calculated Hamaker constants of the CNTs decreased with the oxidation degree, implying that there was lower van der Waals force between the O-CNTs. The Derjaguin-Landau-Verwey-Overbeek (DLVO) calculation confirmed that O-CNTs had to overcome higher energy barrier and thus showed better colloidal stability than the pristine CNT in the presence of Na + ., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Increasing production and application of nanomaterials lead to their environmental release possible. The nanomaterials with different properties may transport together in porous media, and consequently affect their environmental fates. In this study, column experiments were conducted to investigate the co-transport of two typical nanomaterials, graphene oxide (GO) and nano-titanium dioxide (nTiO 2 ), in saturated quartz sand in NaCl and CaCl 2 electrolyte solutions under both favorable and unfavorable conditions. The breakthrough curves as well as the retained profiles of single and binary nanoparticles were examined. The results indicated that nTiO 2 significantly enhanced the GO retention under all examined conditions, especially at lower pH, higher ionic strength and the presence of divalent cation Ca 2+ . This might be attributed to the formation of less negatively charged and larger-sized GO-nTiO 2 agglomerates as well as the increased retention sites on sand surface by preferentially deposited nTiO 2 . However, GO merely slightly enhanced the transport of nTiO 2 in NaCl solutions, whereas had negligible effect on nTiO 2 transport and retention in CaCl 2 solutions. The highly hydrophilic and mobile GO served as a carrier and facilitated the transport of nTiO 2 in NaCl solutions. In CaCl 2 solutions, the strong attachment affinity between positively charged nTiO 2 and negatively charged quartz sand (at pH 4.5), and dramatical accumulation of large nTiO 2 agglomerates near the column inlets (at pH 6.5) led to significant deposition of nTiO 2 on quartz sand. The co-presence of GO failed to counteract the retention of nTiO 2 particles on sand., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Gut microbiota-host co-metabolites play an essential role in maintaining homeostasis, and their concentration changes are closely related to a variety of diseases. Developing a targeted metabolomics analytical platform for these co-metabolites will help to elucidate the relationship between intestinal flora and host. Here we present a simple and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of nine gut microbiota-host co-metabolites in rat serum, urine and feces. The compounds were separated on a reversed-phase C 18 column using gradient elution with a solvent system consisting of methanol and water (containing 0.05% formic acid) and a 7-min run time. All of the calibration curves exhibited good linear relationships (R 2  ≥ 0.9984, Percent Residual Accuracy ≥93.27%). The intra- and interday precision, expressed as relative standard deviation (RSD), was ≤ 14.84%. The accuracy was within 100 ± 13.16% for all analytes. The recovery of the nine compounds in biological samples was ≥ 85.80% with an appropriate RSD (≤12.04%). The validated method was successfully applied to monitor the global changes of these metabolites in obesity. Taken together, these results demonstrate that the method can simultaneously determine the nine co-metabolites in multiple biological matrices and is an essential part of the targeted metabolomics analytical platform, which may become an approach to evaluate the occurrence, development and therapeutic effects of metabolic diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Endothelial dysfunction is a key pathophysiological step in early stage diabetes mellitus (DM) macrovascular complications and is also crucial in the inflammatory mechanisms of macrovascular complications. However, there is currently no effective intervention to improve endothelial dysfunction associated with DM macrovascular complications. Astragaloside IV (AS‑IV), which can be extracted from the traditional Chinese medicine Astragalus membranaceus, has potential therapeutic effects on DM and its complications. The present study evaluated the effect of AS‑IV on high glucose‑induced human umbilical vein endothelial cell (HUVEC) injury and its possible mechanism. The result indicated that AS‑IV has a significant protective effect on high glucose‑induced HUVEC injury. AS‑IV could significantly promote cell proliferation, reduce apoptosis and decrease the protein and mRNA expression levels of tumor necrosis factor‑α and interleukin‑1β in HUVECs. Furthermore, AS‑IV could decrease the expression of phosphorylated c‑Jun NH2‑terminal kinase (JNK) phosphorylated apoptosis signal‑regulating kinase 1, cytochrome c, cleaved‑caspase‑9, cleaved‑caspase‑3 and the relative ratio of B‑cell lymphoma‑2 associated X protein/B‑cell lymphoma‑2 in HUVECs. In conclusion, the present study demonstrated that AS‑IV could suppress apoptosis and inflammatory reactions promoted by high glucose conditions in HUVECs by inhibiting the JNK signaling pathway. These findings suggest that AS‑IV could inhibit the process of endothelial dysfunction in diabetic macrovascular complications.

Zengye decoction (ZYD), a traditional Chinese medicinal formula, has been used in the treatment of various chronic diseases, such as constipation and skin dryness syndrome. Clinically, the specific mechanisms and targets of ZYD for treating disease remain unclear. The present study was undertaken to investigate the effects of ZYD on the gut microbiota and host metabolites in aged constipated rats and the relationship between the intestinal microbiota and the host. Rats were divided randomly into three groups, the control group (n = 10), recovery group (n = 10) and ZYD group (n = 10). First, the aged constipation model was established for the ZYD group and recovery group. Then, rats in the ZYD group were treated with ZYD. Urinary and faecal samples of each animal were collected in microcentrifuge tubes. Next, 16s rRNA gene sequencing was employed to analyse the composition of the gut microbiome in faecal samples and afterwards the metabolic function of the altered gut microbiota was predicted. Additionally, 1 H NMR profiling was used to detect the alterations of host metabolites in urine and faecal samples to verify the metabolic function results obtained from sequencing. As a result, ZYD reduced the level of harmful bacteria, such as Desulfovibrio, Ruminococcus, Prevotella and Dorea, and increased the abundance of Oxalobacter, Clostridium and Roseburia. The functional prediction of changes in the gut microbiota induced by ZYD revealed that ZYD promoted energy storage, regulated amino acid metabolism, inhibited methane metabolism, strengthened the physiological function of glutathione and reduced bacterial toxin. The 1 H NMR profiles revealed that ZYD regulated the carbohydrates, short chain fatty acids, amino acids and amines in the aged constipated rats. In addition, most metabolic changes observed were related to the function of intestinal microbiota. These results suggest that ZYD can regulate the intestinal microbiota of constipated rats to normal levels and change the endogenous metabolites of the host through the intestinal microbiota to achieve therapeutic effects., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In previously reported work, Au III complexes coordinated with 2-benzoylpyridine ligand, BPy-Au, were prebound to a protein and used to discover a novel protein-directed labeling approach with propargyl ester functional groups. In this work, further examination discovered that gold catalysts devoid of the 2-benzoylpyridine ligand (e.g., NaAuCl4) had significantly reduced levels of protein labeling. Mechanistic investigations then revealed that BPy-Au and propargyl esters undergo a rare example of C(sp 2 )-C(sp) aryl-alkynyl cross-coupling, likely through spontaneous reductive elimination. Overall, these observations appear to suggest that BPy-Au-mediated, propargyl ester-based protein labeling acts via an activated ester intermediate, which contributes to our understanding of this process and will aid the expansion/optimization of gold-catalyst usage in future bioconjugation applications, especially in vivo., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The present study aimed to explore the effects of psychological pain theory-based cognitive therapy (PPTBCT) on suicide among depressed patients, compared with a control group who received usual psychological care (UPC). The sample consisted of 32 depressed patients and 32 healthy control subjects. All participants completed the Beck Scale for Suicide Ideation (BSI), Beck Depression Inventory, Three-Dimensional Psychological Pain Scale (TDPPS), and Problem Solving Inventory(PSI), and Automatic Thoughts Questionnaire (ATQ). All measures differed significantly between depressed patients and healthy controls. Then clinical participants were assigned randomly to the PPTBCT (n=19) and control (n=13) groups. During the 8-week intervention, scores related to depression, suicidal ideation, psychological pain, and automatic thoughts were decreased in both groups at the post-intervention and 4-week follow-up time points, compared with pre-intervention scores. BSI scores remained low at follow up and did not differ significantly from post-intervention scores in the PPTBCT group, but were significantly higher at follow up than at post-intervention in the control group. PPTBCT may effectively reduce suicide risk in patients with major depressive disorder, although the effects of its application need to be confirmed., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)