A Semi-Supervised Learning Framework for Classifying Colorectal Neoplasia Based on the NICE Classification.

Labelling medical images is an arduous and costly task that necessitates clinical expertise and large numbers of qualified images. Insufficient samples can lead to underfitting during training and poor performance of supervised learning models. In this study, we aim to develop a SimCLR-based semi-supervised learning framework to classify colorectal neoplasia based on the NICE classification. First, the proposed framework was trained under self-supervised learning using a large unlabelled dataset; subsequently, it was fine-tuned on a limited labelled dataset based on the NICE classification. The model was evaluated on an independent dataset and compared with models based on supervised transfer learning and endoscopists using accuracy, Matthew's correlation coefficient (MCC), and Cohen's kappa. Finally, Grad-CAM and t-SNE were applied to visualize the models' interpretations. A ResNet-backboned SimCLR model (accuracy of 0.908, MCC of 0.862, and Cohen's kappa of 0.896) outperformed supervised transfer learning-based models (means: 0.803, 0.698, and 0.742) and junior endoscopists (0.816, 0.724, and 0.863), while performing only slightly worse than senior endoscopists (0.916, 0.875, and 0.944). Moreover, t-SNE showed a better clustering of ternary samples through self-supervised learning in SimCLR than through supervised transfer learning. Compared with traditional supervised learning, semi-supervised learning enables deep learning models to achieve improved performance with limited labelled endoscopic images.

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

Removal of diclofenac sodium from water using a polyacrylonitrile mixed-matrix membrane embedded with MOF-808.

MOF-808, owing to the synergistic effect of its large surface area and surface charge matching, showed a diclofenac sodium (DCF) removal capacity as high as 630 mg g-1, and the ability to adsorb 436 mg g-1 DCF in two hours, outperforming many common Zr-MOFs under the same conditions. Importantly, a series of free-standing mixed-matrix membranes made by combining polyacrylonitrile with MOF-808 were fabricated and exhibited high efficiency of removing DCF from water via an easily accessible filtration method.

Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing.

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.

Remote Ischemic Postconditioning-Mediated Neuroprotection against Stroke by Promoting Ketone Body-Induced Ferroptosis Inhibition.

Neuronal death resulting from ischemic stroke is the primary cause of adult mortality and disability, and effective neuroprotective agents for poststroke intervention are still lacking. Remote ischemic postconditioning (RIPostC) has demonstrated significant protective effects against ischemia in various organs; however, the specific mechanisms are not fully understood. This study investigated the potential neuroprotective mechanisms of RIPostC in the context of ischemic stroke. Using a rat model of middle cerebral artery occlusion, we found that RIPostC mitigated neurological damage, improved movement in the open-field test, and protected against neuronal apoptosis. In terms of energy metabolism, RIPostC enhanced ATP levels, suppressed lactate content, and increased the production of ketone bodies (KBs). In the ferroptosis assay, RIPostC protected against lipoperoxidation, reversed the reduction of glutathione peroxidase 4 (GPX4), and mitigated the excessive expression of long-chain acyl-CoA synthetase family member 4 (ACSL4). In oxygen-glucose deprivation/reoxygenation-treated HT22 cells, KBs maintained GPX4 levels, suppressed ACSL4 expression, and preserved the mitochondrial cristae number. However, the effect of KBs on the expression of GPX4, ACSL4, and the number of mitochondrial cristae was blocked by erastin. Moreover, both RIPostC and KBs reduced total iron and ferrous ion content by repressing iron transporters both in vitro and in vivo. In conclusion, KBs-induced mitigation of ferroptosis could represent a new therapeutic mechanism for RIPostC in treating stroke.

Dihydroartemisinin is an inhibitor of trained immunity through Akt/mTOR/HIF1α signaling pathway.

Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.

Cation/Anion-Dual regulation in Na3MnTi(PO4)3 cathode achieves the enhanced electrochemical properties of Sodium-Ion batteries.

Na3MnTi(PO4)3 (NMTP) emerges as a promising cathode material with high-performance for sodium-ion batteries (SIBs). Nevertheless, its development has been limited by several challenges, including poor electronic conductivity, the Mn3+ Jahn-Teller effect, and the presence of a Na+/Mn2+ cation mixture. To address these issues, we have developed a cation/anion-dual regulation strategy to activate the redox reactions involving manganese, thereby significantly enhancing the performance of NMTP. This strategy simultaneously enhances the structural dynamics and facilitates rapid ion transport at high rates by inducing the formation of sodium vacancy. The combined effects of these modifications lead to a substantial improvement in specific capacity (79.1 mAh/g), outstanding high-rate capabilities (35.9 mAh/g at 10C), and an ultralong cycle life (only 0.040 % capacity attenuation per cycle over 250 cycles at 1C for Na3.34Mn1.2Ti0.8(PO3.98F0.02)3) when used as a cathode material in SIBs. Furthermore, its performance in full cell demonstrates impressive rate capability (44.4 mAh/g at 5C) and exceptional cycling stability (with only 0.116 % capacity decay per cycle after 150 cycles at 1C), suggesting its potential for practical applications. This work presents a dual regulation strategy targeting different sites, offering a significant advancement in the development of NASICON phosphate cathodes for SIBs.

Noninvasively Deciphering the Immunosuppressive Tumor Microenvironment Using Galectin-1 PET to Inform Immunotherapy Responses.

Immune checkpoint blockade (ICB) has achieved groundbreaking results in clinical cancer therapy; however, only a subset of patients experience durable benefits. The aim of this study was to explore strategies for predicting tumor responses to optimize the intervention approach using ICB therapy. Methods: We used a bilateral mouse model for proteomics analysis to identify new imaging biomarkers for tumor responses to ICB therapy. A PET radiotracer was synthesized by radiolabeling the identified biomarker-targeting antibody with 124I. The radiotracer was then tested for PET prediction of tumor responses to ICB therapy. Results: We identified galectin-1 (Gal-1), a member of the carbohydrate-binding lectin family, as a potential negative biomarker for ICB efficacy. We established that Gal-1 inhibition promotes a sensitive immune phenotype within the tumor microenvironment (TME) for ICB therapy. To assess the pre-ICB treatment status of the TME, a Gal-1-targeted PET radiotracer, 124I-αGal-1, was developed. PET imaging with 124I-αGal-1 showed the pretreatment immunosuppressive status of the TME before the initiation of therapy, thus enabling the prediction of ICB resistance in advance. Moreover, the use of hydrogel scaffolds loaded with a Gal-1 inhibitor, thiodigalactoside, demonstrated that a single dose of thiodigalactoside-hydrogel significantly potentiated ICB and adoptive cell transfer immunotherapies by remodeling the immunosuppressive TME. Conclusion: Our study underscores the potential of Gal-1-targeted PET imaging as a valuable strategy for early-stage monitoring of tumor responses to ICB therapy. Additionally, Gal-1 inhibition effectively counteracts the immunosuppressive TME, resulting in enhanced immunotherapy efficacy.

Application of TNB in dual photo-controlled release of phenamacril, imidacloprid, and imidacloprid synergist.

Pesticides can improve crops' yield and quality, but unreasonable applications of pesticides lead to waste of pesticides which are further accumulated in the environment and threaten human health. Developing the release of controlled drugs can improve the utilization rate of pesticides. Among these methods, light-controlled release is a new technology of controlled release, which can realize spatiotemporal delivery of drugs by light. Four compounds, named Imidacloprid-Thioacetal o-nitrobenzyl-Phenamacril (IMI-TNB-PHE), Imidacloprid-Thioacetal o-nitrobenzyl- Imidacloprid (IMI-TNB-IMI), Phenamacril-Thioacetal o-nitrobenzyl-Phenamacril (PHE-TNB-PHE), and Imidacloprid-Thioacetal o-nitrobenzyl-Imidacloprid Synergist (IMI-TNB-IMISYN), were designed and synthesized by connecting thioacetal o-nitrobenzyl (TNB) with pesticides TNB displaying simple and efficient optical properties in this work. Dual photo-controlled release of pesticides including two molecules of IMI or PHE, both IMI and PHE, as well as IMI and IMISYN were, respectively, studied in this paper. Insecticidal/fungicidal activities of the photosensitive pesticides showed 2-4 times increments if they were exposed to light. In addition, a synergistic effect was observed after the light-controlled release of IMI-TNB-IMISYN, which was consistent with the effect of IMISYN. The results demonstrated whether dual photo-controlled release of the same or different pesticide molecules could be achieved with a TNB linker with spatiotemporal precision. We envisioned that TNB will be an innovative photosensitive protective group for light-dependent application of agrochemicals in the future.

Is the expression of different discrete emotions related to time? Evidence from online Chinese reviews using sentiment analysis and human behavior dynamics.

Objectives: The online behavior of online users has taken on complex and diverse characteristics, and posting product reviews on e-commerce platforms is no exception. In fact, reviews contain rich and multi-dimensional discrete emotional information, and whether there is a relationship between the expression of these different discrete emotions and the time interval between product purchase and review posting as well as their related characteristics are the issues that this study needs to analyze and solve in depth. Methods: Based on the OCC model (named after three proposers) of psychological emotional cognitive evaluation theory as the basis for emotion classification, the study used the massive amounts of Chinese reviews of mobile phones on the Chinese e-commerce platform Jingdong Mall as the research object, applied supervised machine learning methods to classify discrete emotions, and constructed a large corpus containing satisfaction, disappointment, admiration, reproach, love, and hate; then the study delved into the distribution and behavioral dynamics characteristics of consumers' comments containing the different discrete emotions at different "purchase-comment" time intervals. Results: The results showed that the first peak of the distribution curves of the six discrete emotions at different "purchase-comment" time intervals occurs on the first day after purchase and then decreases gradually but at different rates. The three curves for satisfaction, love, and hate emotions also show a second peak on the eleventh day, which is more similar to the bimodal distribution, implying that the corresponding product reviews are more objective. In addition, the distribution of reviews containing the six discrete emotions at different "purchase-comment" time intervals follows a power-law distribution and has the temporal characteristics of human behavioral dynamics, that is, "strong paroxysms and weak memory". However, the reviews containing the admiration and reproach emotions were most intensively written by consumers after the purchase, indicating that the service provided by the seller, logistics, and e-commerce platform stimulates more consumers to give quick responses and detailed reviews. Conclusion: This study is not only of great significance for exploring the internal mechanisms of consumer discrete emotional expression but also provides important decision-making references for potential consumer purchasing decisions, product updates for developers, marketing strategy formulation for marketing teams, and service improvement for sellers, logistics companies, and e-commerce platforms.

Semi-supervised generative adversarial learning for denoising adaptive optics retinal images.

This study presents denoiseGAN, a novel semi-supervised generative adversarial network, for denoising adaptive optics (AO) retinal images. By leveraging both synthetic and real-world data, denoiseGAN effectively addresses various noise sources, including blur, motion artifacts, and electronic noise, commonly found in AO retinal imaging. Experimental results demonstrate that denoiseGAN outperforms traditional image denoising methods and the state-of-the-art conditional GAN model, preserving retinal cell structures and enhancing image contrast. Moreover, denoiseGAN aids downstream analysis, improving cell segmentation accuracy. Its 30% faster computational efficiency makes it a potential choice for real-time AO image processing in ophthalmology research and clinical practice.

A highly susceptible hACE2-transgenic mouse model for SARS-CoV-2 research.

Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter. Overexpression of hACE2 did not pose a significant effect on weight growth. After SARS-CoV-2 inoculation, mice showed obvious viral replication and production of inflammation within 7 days, with a gradual decrease in body weight until death. Virological testing found that the virus can replicate in the respiratory system, small intestine, and brain. Additionally, this mouse model was applied to compare two antibody drug candidates, the anti-RBD antibody (MW06) and the mouse CD24-conjugated anti-RBD antibody (mCD24-MW06). Differences in antiviral effects between these two antibodies can be demonstrated in this mouse model when a challenge dose that invalidates the anti-RBD antibody treatment was used. This study provided a new mouse model for studying SARS-CoV-2 pathogenesis and evaluating potential interventions.

[Development of a Three-Wavelength Brain Tissue Oxygen Monitoring System Based on Near Infrared Spectrum].

In the past 20 years, near infrared spectrum technology has been widely used in human body monitoring due to its non-invasive and real-time characteristics. Oxygen, as the main metabolic substance of the human body, is consumed the most in brain tissue. In order to prevent complications caused by a decrease in brain tissue oxygen during treatment, the patient's brain tissue blood oxygen saturation needs to be monitored in real time. Currently, most of the clinically used non-invasive cerebral blood oxygen detection equipments use dual wavelengths. Other substances on the detection path will cause errors in the measurement results. Therefore, this article proposes a three-wavelength method based on the basic principle of non-invasive monitoring of cerebral blood oxygen using near-infrared spectrum. The brain tissue oxygen saturation monitoring method of detecting light sources was initially verified through the built system, laying the foundation for subsequent system engineering.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. METHODS: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. RESULTS: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. CONCLUSION: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Prodigiosin as an Antibiofilm Agent against the Bacterial Biofilm-Associated Infection of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is known to generate bacterial biofilms that increase antibiotic resistance. With the increase of multi-drug resistance in recent years, the formulation of a new therapeutic strategy has seemed urgent. Preliminary findings show that Prodigiosin (PG), derived from chromium-resistant Serratia marcescens, exhibited efficient anti-biofilm activity against Staphylococcus aureus. However, its anti-biofilm activity against P. aeruginosa remains largely unexplored. The anti-biofilm activity of PG against three clinical single drug-resistant P. aeruginosa was evaluated using crystal violet staining, and the viability of biofilms and planktonic cells were also assessed. A model of chronic lung infection was constructed to test the in vivo antibiofilm activity of PG. The results showed that PG inhibited biofilm formation and effectively inhibited the production of pyocyanin and extracellular polysaccharides in vitro, as well as moderated the expression of interleukins (IL-1ß, IL-6, IL-10) and tumor necrosis factor (TNF-α) in vivo, which might be attributed to the downregulation of biofilm-related genes such as algA, pelA, and pslM. These findings suggest that PG could be a potential treatment for drug-resistant P aeruginosa and chronic biofilm infections.

Reorganizing Helmholtz Adsorption Plane Enables Sodium Layered-Oxide Cathode Beyond High Oxidation Limits.

Sodium layered-oxides (Nax TMO2 ) sustain severe interfacial stability issues when subjected to battery applications. Particularly at high potential, the oxidation limits including transition metal dissolution and SEI reformation are intertwined upon the cathode, resulting in poor cycle ability. Herein, by rearranging the complex and structure of Helmholtz absorption plane adjacent to Nax TMO2 cathodes, the mechanism of constructing stable cathode/electrolyte interphase to push up oxidation limits is clarified. The strong absorbent fluorinated anions replace the solvents into the inner Helmholtz plane, thereby reorganizing the Helmholtz absorption structure and spontaneously inducing an anion-dominated interphase to envelop more active sites for layered oxides. More importantly, such multi-component cathode/electrolyte interphase proves effective for long-term durability of a series of manganese-based oxide cathodes, which achieves 1500-cycles lifetime against high oxidation voltage limit beyond 4.3 V. This work unravels the key role of breaking high-oxidation limits in attaining higher energy density of layered-oxide systems. This article is protected by copyright. All rights reserved.

Allelopathic effects of phenolic acid extracts on Morchella mushrooms, pathogenic fungus, and soil-dominant fungus uncover the mechanism of morel continuous cropping obstacle.

The prominent problem of continuous cropping obstacle has been frustrating the morel farming. To deepen the understanding on morel continuous cropping obstacle, the allelopathic effects of phenolic acid extracts from morel continuous cropping soils on growth and development of Morchella sextelata, M. eximia, M. importuna, pathogenic fungus Fusarium sp. and soil-dominant fungus Chaetomium sp. were investigated. These effects were expressed as response index (RI). Under actual content of phenolic acids (6.150 µg/g fresh mixed continuous cropping soil), the mycelial growth of all tested morel strains was inhibited (RI < 0), while the allelopathic effect of control phenolic acids (4.252 µg/g fresh mixed control soil) was between promotion and inhibition, which suggested that the phenolic acid extracts from morel continuous cropping soils may exhibit certain extent of autotoxicity for the existence of morel-specific allelochemicals. In addition, the aggravated pigmentation and reduced occurrence of sclerotium in three Morchella fungi at growth inhibitory concentrations of phenolic acids indicated the induction of morel strain aging. Meanwhile, most concentrations of phenolic acids showed stimulatory effects on sporulation of Fusarium sp. and Chaetomium sp. (RI > 0), manifesting the enrichment of soil-borne pathogenic fungi and dominance of certain fungal population in soil ecosystem. Collectively, the allelopathic effects of phenolic acid extracts play an instrumental role in morel continuous cropping obstacle. The study will be beneficial for healthy development of morel artificial cultivation.

Hydrogen-bonded organic frameworks in solution enables continuous and high-crystalline membranes.

Hydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10-7 mol·s-1·m-2·Pa-1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.

Magnesium promotes vascularization and osseointegration in diabetic states.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Cyclometalated gold(III)-hydride under oriented external electric fields: a new strategy to modulate its reactivity?

Selected gold complexes have been regarded as promising anti-cancer agents because they can bind with protein targets containing thiol or selenol moieties, but their clinical applications were hindered by the unbiased binding towards off-target thiol-proteins. Recently, a novel gold(III)-hydride complex (abbreviated as 1) with visible light-induced thiol reactivity has been reported as potent photo-activated anticancer agents (Angew. Chem. Int. Ed., 2020, 132, 11139). To explore new strategies to stimuli this potential antitumor drug, the effect of oriented external electric fields (OEEFs) on its geometric structure, electronic properties, and chemical reactivity was systematically investigated. Results reveal that imposing external electric fields along the Au-H bond of 1 can effectively activate this bond, which is conducive to its dissociation and the binding of Au site to potential targets. Hence, this study provides a new OEEF-strategy to activate this reported gold(III)-hydride, revealing its potential application in electrochemical therapy. We anticipate this work could promote the development of more electric field-activated anticancer agents. However, further experimental research should be conducted to verify the conclusions obtained in this work.