A Facile Determination of Herbicide Residues and Its Application in On-Site Analysis.

Abuse of herbicides in food safety is a vital concern that has an influence on the sustainable development of the world. This work presents, a modified ionization method with separation of the sample and carrier gas inlets, which was utilized for efficient ionization and analyte transfer of herbicides in crops. The working parameters of voltage, injective distance, desorption temperature, and the carrier gas flow rate were optimized to achieve the high efficiency of the transfer and ionization of the analyte. When it was applied in the analysis of herbicides in laboratory, the method exhibited excellent performance in achieving the quantitative detection of herbicides in solutions and residues spiked in an actual matrix with a limit of quantification of 1-20 µg/kg and relative standard deviations of less than 15%. Although a simple QuEchERS process was used, the programmable heating platform ensured efficient gasification and transfer of the target analyte, with the advantages of high speed and selectivity, avoiding the noted matrix effect. The method exhibited a relatively acceptable performance by using air as the discharged gas (open air). It could be used to monitor herbicide residues in the growth stage via on-site non-destructive analysis, which obtained low LODs by dissociating the herbicides from the crops without any pretreatment. It showed great potential for the supervision of the food safety market by achieving non-destructive detection of crops anytime and anywhere. This finding may provide new insights into the determination of pesticide emergence and rice quality assessment.

The synergistic effect of curcumin and mitoquinol mesylate on cognitive impairment and the neuropathology of Alzheimer's disease.

Given the complexity and heterogeneity of Alzheimer's disease (AD) pathology, targeted monotherapy drugs may not be effective. Therefore, synergistic combination therapy of curcumin and Mito Q was proposed and evaluated in a triple-transgenic AD model mice (3 × Tg-AD mice). The cognitive ability was assessed using behavioral tests and typical pathological changes were observed through Western blotting and histological analysis. The results demonstrated a significant enhancement in cognitive ability along with the mitigation of typical AD pathological features such as Aß aggregation, tau phosphorylation, and synaptic damage. Notably, the combination therapy demonstrated superior efficacy over individual drugs alone. These findings provide valuable insights for optimizing the development of AD drugs.

Se-methylselenocysteine ameliorates mitochondrial function by targeting both mitophagy and autophagy in the mouse model of Alzheimer's disease.

Background: Alzheimer's disease (AD) exerts tremendous pressure on families and society due to its unknown etiology and lack of effective treatment options. Our previous study had shown that Se-methylselenocysteine (SMC) improved the cognition and synaptic plasticity of triple-transgenic AD (3 × Tg-AD) mice and alleviated the related pathological indicators. We are dedicated to investigating the therapeutic effects and molecular mechanisms of SMC on mitochondrial function in 3 × Tg-AD mice. Methods: Transmission electron microscopy (TEM), western blotting (WB), mitochondrial membrane potential (ΔΨm), mitochondrial swelling test, and mitochondrial oxygen consumption test were used to evaluate the mitochondrial morphology and function. Mitophagy flux and autophagy flux were assessed with immunofluorescence, TEM and WB. The Morris water maze test was applied to detect the behavioral ability of mice. Results: The destroyed mitochondrial morphology and function were repaired by SMC through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in 3 × Tg-AD mice. In addition, SMC ameliorated mitochondria by activating mitophagy flux via the BNIP3/NIX pathway and triggering autophagy flux by suppressing the Ras/Raf/MEK/ERK/mTOR pathway. SMC remarkably increased the cognitive ability of AD mice. Conclusions: This research indicated that SMC might exert its therapeutic effect by protecting mitochondria in 3 × Tg-AD mice.

Gut microbiota and its metabolites in Alzheimer's disease: from pathogenesis to treatment.

Introduction: An increasing number of studies have demonstrated that altered microbial diversity and function (such as metabolites), or ecological disorders, regulate bowel-brain axis involvement in the pathophysiologic processes in Alzheimer's disease (AD). The dysregulation of microbes and their metabolites can be a double-edged sword in AD, presenting the possibility of microbiome-based treatment options. This review describes the link between ecological imbalances and AD, the interactions between AD treatment modalities and the microbiota, and the potential of interventions such as prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and dietary interventions as complementary therapeutic strategies targeting AD pathogenesis and progression. Survey methodology: Articles from PubMed and china.com on intestinal flora and AD were summarized to analyze the data and conclusions carefully to ensure the comprehensiveness, completeness, and accuracy of this review. Conclusions: Regulating the gut flora ecological balance upregulates neurotrophic factor expression, regulates the microbiota-gut-brain (MGB) axis, and suppresses the inflammatory responses. Based on emerging research, this review explored novel directions for future AD research and clinical interventions, injecting new vitality into microbiota research development.

Research hotspots and trends of nanomaterials in stomatology: A bibliometric analysis from 2000 to 2023.

Background: Nanomaterials (NMs) have emerged as highly promising candidates for stomatology due to their excellent quality and remarkable progress in recent years. However, with the rapid expansion of the research scale, challenges arise in the technological decision-making and research management processes, and therefore difficulty for researchers to understand the knowledge structure and research hotspots has increased significantly. This study aims to make a comprehensive summary of authors, institutions, journals, research topics, development trends, and research hotspots of NMs in stomatology through bibliometric analysis for the sake of providing references for scientific decision-making, research management, and academic exploration in this filed. Methods: Studies on research and application of NMs in stomatology were retrieved from the Web of Science Core Collection (WoSCC) from January 1, 2000 to April 27, 2023. Bibliometric analysis and visualization were conducted using CiteSpace and VOSviewer. Results: A total of 620 articles were included in this study, showing a gradual increase in the number of publications focusing on NMs in stomatology. Globally, China ranked first with 130 publications, and the United States (US) enjoyed the highest citation count (n = 5218) and average citation per paper (ACP) (n = 52.18). The top three institutions with the highest publication output were the University of Sao Paulo (n = 22), the Chinese Academy of Sciences (n = 20), and Shanghai Jiaotong University (n = 13). The journals MATERIALS and NANOMATERIALS emerged as the most popular in this field (n = 20), and BIOMATERIALS had the highest co-citations (n = 1597). The most prolific author was Dos Reis and Andrea Candido (n = 7), while Thomas J. Webster enjoyed the highest co-citations (n = 94). Burstness analysis of the references revealed a prominent research focus on nanoparticle drug delivery systems (specifically lipid nanoparticles). Keyword burstness analysis identified "oxide nanoparticle" as the primary frontier keyword in this field. Conclusion: This is the first study of using bibliometric analysis to summarize the research trends and frontiers of NMs in stomatology. With progressive advancements in the research and application of NMs in oral healthcare, their academic impact is steadily increasing. China and the US maintain a leading position in this field. Future directions could primarily focus on the development and application of nanoparticle drug delivery systems (especially lipid nanoparticles) and metal oxide nanoparticles (especially in antibacterial aspects). We hope that this bibliometric analysis could provide researchers with a panoramic view and useful references for future research, thus promoting the development of NMs in stomatology.

An effective electricity worker identification approach based on Yolov3-Arcface.

To address the issues of low efficiency and high complexity of detection models for electric power workers in distribution rooms, the electric power worker identification approach is proposed. The ArcFace loss function is used as the coordinate regression loss of the target box. According to the score, the template box with the highest score is selected for prediction, which speeds up the rate of convergence. Dimensional clustering is used to set template boxes for bounding box prediction. The experimental results show that the improved YOLOv3 is a high-performance and lightweight model. The electric power worker identification approach proposed in this paper has a high-speed recognition process, accurate recognition results. The effectiveness of the approach is verified with better detection performance and robustness.

The development and training effect of innovative undergraduate dental talents training project: A 6-year retrospective study.

INTRODUCTION: To summarize the development of Innovative Undergraduate Dental Talents Training Project (IUDTTP) and investigate the training effect of this extracurricular dental basic research education activity from 2015 to 2020 to obtain educational implications. MATERIALS AND METHODS: The Guanghua School of Stomatology established the IUDTTP in 2015. The authors recorded the development process and analysed the participation situation, training effect, academic performance and overall satisfaction during 2015-2020 through documental analysis, questionnaire and quiz. The t-test, chi-square test and ANOVA were used to test the difference. RESULTS: The educational goal, education module and assessment system of IUDTTP evolved and developed every year. A total of 336 students and 79 mentors attended the IUDTTP from 2015 to 2020, with the participation rate increasing from 45.1% to 73.5%. The participants exhibited favourable basic research abilities, manifesting as the increase of funded projects and published papers and satisfying quiz scores. Almost all students (94.94%) admitted their satisfaction with the IUDTTP. Moreover, the attended students surpassed the non-participants in terms of GPA, the number of acquired scholarships and outstanding graduates (p < .05). Likewise, the enrolment rate of postgraduate participants was significantly higher than non-participants. CONCLUSIONS: To date, the training effect indicated that the IUDTTP has fulfilled the education aim. It brought positive effects on promoting research interest, cultivating research capacities and enhancing academic performance. The potential deficiencies of extracurricular educational activities, including inflexibility in schedule and insufficiency in systematisms, may be remedied by more systematic educational settings in the future.

The influence of guide stabilizers and their application sequences on trueness and precision of surgical guides in free end situations: An in vitro analysis.

OBJECTIVES: To evaluate the impact of guide stabilizers and their application sequences on implant placement accuracy of guided implant surgery in multiple teeth loss at free end. MATERIALS AND METHODS: In this study, 96 implants were placed in the regions of #34, #36, and #37 of 32 identical mandibular models. The influence of using guide stabilizers or not (group A and group B) and various guide stabilizers application sequences (group B: #34 → #36 → #37; group C: #36 → #34 → #37; group D: #37 → #34 → #36) on implant placement trueness and precision was investigated. Data were analyzed using T-tests and one-way ANOVA. RESULTS: Group B showed significant benefits in enhancing implant placement precision. Compared to group A, it resulted in reducing 3D-deviation at crest and 2D deviation in vestibular-oral direction at both crest and apex. Furthermore, group D demonstrated greater improvement in global implant placement precision by reducing 2D deviation in mesial-distal direction at both crest and apex. Among the three different stabilizer application sequences, group D exhibited the highest level of implant placement precision. CONCLUSIONS: In cases of missing teeth at distal free end, the use of guide stabilizers and their application sequences does not have a significant impact on implant placement trueness. However, they do improve implant placement precision compared to methods that do not utilize guide stabilizers. Specifically, applying a guide stabilizer first at the furthest implant site to change teeth loss classification from free end to edentulous space with posterior support is the most reliable sequence.

Balance between the CMC/ACP Nanocomplex and Blood Assimilation Orchestrates Immunomodulation of the Biomineralized Collagen Matrix.

Calcium phosphate-based biomineralized biomaterials have broad application prospects. However, the immune response and foreign body reactions elicited by biomineralized materials have drawn substantial attention recently, contrary to the immune microenvironment optimization concept. Therefore, it is important to clarify the immunomodulation properties of biomineralized materials. Herein, we prepared the biomineralized collagen matrix (BCM) and screened the key immunomodulation factor carboxymethyl chitosan/amorphous calcium phosphate (CMC/ACP) nanocomplex. The immunomodulation effect of the BCM was investigated in vitro and in vivo. The BCM triggered evident inflammatory responses and cascade foreign body reactions by releasing the CMC/ACP nanocomplex, which activated the potential TLR4-MAPK/NF-κB pathway, compromising the collagen matrix biocompatibility. By contrast, blocking the CMC/ACP nanocomplex release via the blood assimilation process of the BCM mitigated the inflammation and foreign body reactions, enhancing biocompatibility. Hence, the immunomodulation of the BCM was orchestrated by the balance between the CMC/ACP nanocomplex and the blood assimilation process. Controlling the release of the CMC/ACP nanocomplex to accord the biological effects of ACP with the temporal regenerative demands is key to developing advanced biomineralized materials.

Measuring the binary thickness of buccal bone of anterior maxilla in low-resolution cone-beam computed tomography via a bilinear convolutional neural network.

Background: The thickness of the buccal bone of the anterior maxilla is an important aesthetic-determining factor for dental implant, which is divided into the thick (≥1 mm) and thin type (<1 mm). However, as a micro-scale structure that is evaluated through low-resolution cone-beam computed tomography (CBCT), its thickness measurement is error-prone under the circumstance of enormous patients and relatively inexperienced primary dentists. Further, the challenges of deep learning-based analysis of the binary thickness of buccal bone include the substantial real-world variance caused by pixel error, the extraction of fine-grained features, and burdensome annotations. Methods: This study built bilinear convolutional neural network (BCNN) with 2 convolutional neural network (CNN) backbones and a bilinear pooling module to predict the binary thickness of buccal bone (thick or thin) of the anterior maxilla in an end-to-end manner. The methods of 5-fold cross-validation and model ensemble were adopted at the training and testing stages. The visualization methods of Gradient Weighted Class Activation Mapping (Grad-CAM), Guided Grad-CAM, and layer-wise relevance propagation (LRP) were used for revealing the important features on which the model focused. The performance metrics and efficacy were compared between BCNN, dentists of different clinical experience (i.e., dental student, junior dentist, and senior dentist), and the fusion of BCNN and dentists to investigate the clinical feasibility of BCNN. Results: Based on the dataset of 4,000 CBCT images from 1,000 patients (aged 36.15±13.09 years), the BCNN with visual geometry group (VGG)16 backbone achieved an accuracy of 0.870 [95% confidence interval (CI): 0.838-0.902] and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.924 (95% CI: 0.896-0.948). Compared with the conventional CNNs, BCNN precisely located the buccal bone wall over irrelevant regions. The BCNN generally outperformed the expert-level dentists. The clinical diagnostic performance of the dentists was improved with the assistance of BCNN. Conclusions: The application of BCNN to the quantitative analysis of binary buccal bone thickness validated the model's excellent ability of subtle feature extraction and achieved expert-level performance. This work signals the potential of fine-grained image recognition networks to the precise quantitative analysis of micro-scale structures.

Numerical simulation of strength and failure analysis of heterogeneous sandstone under different loading rates.

Natural rock masses often contain heterogeneous structures with varying sizes, non-uniform distributions, and strengths, which influence the mechanical response characteristics and crack propagation modes under loading. Furthermore, heterogeneous structures can affect the stability of the rock mass, in serious cases, leading to geotechnical and mining engineering disasters. In the present work, a parallel-bond model (PBM)-based numerical simulation using Particle Flow Code (PFC) was carried out to study the strength and failure characteristics of sandstone specimens with heterogeneous structures under different loading rates. The results show that the peak strength increases with the increasing loading rate. In addition, all of the initial cracks occurred at the edges of the heterogeneous structures of specimens under different loading rates. The greater the loading rate, the greater the stress concentration degree at the edge of the heterogeneous structures, the greater the dissipated energy as the sandstone specimens with heterogeneous structures suffer damage, the more intense the acoustic emission activity, and the greater the damage degree of the specimens. The number of cracks generated in sandstone specimens with heterogeneous structures increases gradually with the increasing loading rate during the initial loading stage, and gradually decreases after the specimens are damaged. Cracks propagate and develop from the upper right region to the lower right region of the specimens, forming crack groups that rapidly penetrate the specimens, leading to failure. Under different loading rates, the final failure behavior of the sandstone specimens with heterogeneous structures changes from an inverted V-type to θ-type, then gradually evolves to O-type failure.

Abnormal maxillary sinus diagnosing on CBCT images via object detection and 'straight-forward' classification deep learning strategy.

BACKGROUND: Pathological maxillary sinus would affect implant treatment and even result in failure of maxillary sinus lift and implant surgery. However, the maxillary sinus abnormalities are challenging to be diagnosed through CBCT images, especially for young dentists or dentists in grassroots medical institutions without systematical education of general medicine. OBJECTIVES: To develop a deep-learning-based screening model incorporating object detection and 'straight-forward' classification strategy to screen out maxillary sinus abnormalities on CBCT images. METHODS: The large area of background noise outside maxillary sinus would affect the generalisation and prediction accuracy of the model, and the diversity and imbalanced distribution of imaging manifestations may bring challenges to intellectualization. Thus we adopted an object detection to limit model's observation zone and 'straight-forward' classification strategy with various tuning methods to adapt to dental clinical need and extract typical features of diverse manifestations so that turn the task into a 'normal-or-not' classification. RESULTS: We successfully constructed a deep-learning model consist of well-trained detector and diagnostor module. This model achieved ideal AUROC and AUPRC of 0.953 and 0.887, reaching more than 90% accuracy at optimal cut-off. McNemar and Kappa test verified no statistical difference and high consistency between the prediction and ground truth. Dentist-model comparison test showed the model's statistically higher diagnostic performance than dental students. Visualisation method confirmed the model's effectiveness in region recognition and feature extraction. CONCLUSION: The deep-learning model incorporating object detection and straightforward classification strategy could achieve satisfying predictive performance for screening maxillary sinus abnormalities on CBCT images.

Regulating Blood Clot Fibrin Films to Manipulate Biomaterial-Mediated Foreign Body Responses.

The clinical efficacy of implanted biomaterials is often compromised by host immune recognition and subsequent foreign body responses (FBRs). During the implantation, biomaterials inevitably come into direct contact with the blood, absorbing blood protein and forming blood clot. Many studies have been carried out to regulate protein adsorption, thus manipulating FBR. However, the role of clot surface fibrin films formed by clotting shrinkage in host reactions and FBR is often ignored. Because of the principle of fibrin film formation being relevant to fibrinogen or clotting factor absorption, it is feasible to manipulate the fibrin film formation via tuning the absorption of fibrinogen and clotting factor. As biological hydroxyapatite reserved bone architecture and microporous structure, the smaller particle size may expose more microporous structures and adsorb more fibrinogen or clotting factor. Therefore, we set up 3 sizes (small, <0.2 mm; medium, 1 to 2 mm; large, 3 to 4 mm) of biological hydroxyapatite (porcine bone-derived hydroxyapatite) with different microporous structures to investigate the absorption of blood protein, the formation of clot surface fibrin films, and the subsequent FBR. We found that small group adsorbed more clotting factors because of more microporous structures and formed the thinnest and sparsest fibrin films. These thinnest and sparsest fibrin films increased inflammation and profibrosis of macrophages through a potential signaling pathway of cell adhesion-cytoskeleton-autophagy, leading to the stronger FBR. Large group adsorbed lesser clotting factors, forming the thickest and densest fibrin films, easing inflammation and profibrosis of macrophages, and finally mitigating FBR. Thus, this study deepens the understanding of the role of fibrin films in host recognition and FBR and demonstrates the feasibility of a strategy to regulate FBR by modulating fibrin films via tuning the absorption of blood proteins.

Quantification of the apical palatal bone index for maxillary incisor immediate implant assessment: A retrospective cross-sectional study.

BACKGROUND: Apical palatal bone is important in immediate implant evaluation. Current consensus gives qualitative suggestions regarding it, limiting its clinical decision-making value. OBJECTIVES: To quantify the apical palatal bone dimension in maxillary incisors and reveal its quantitative correlation with other implant-related hard tissue indices to give practical advice for pre-immediate implant evaluation and design. MATERIAL AND METHODS: A retrospective analysis of immediate implant-related hard tissue indices in maxillary incisors obtained by cone beam computed tomography (CBCT) was conducted. Palatal bone thickness at the apex level (Apical-P) on the sagittal section was selected as a parameter reflecting the apical palatal bone. Its quantitative correlation with other immediate implant-related hard tissue indices was revealed. Clinical advice of pre-immediate implant assessment was given based on the quantitative classification of Apical-P and its other correlated immediate implant-related hard tissue indices. RESULTS: Apical-P positively correlated with cervical palatal bone, whole cervical buccal-palatal bone, sagittal root angle, and basal bone width indices. while negatively correlated with apical buccal bone, cervical buccal bone, and basal bone length indices. Six quantitative categories of Apical-P are proposed. Cases with Apical-P below 4 mm had an insufficient apical bone thickness to accommodate the implant placement, while Apical-P beyond 12 mm should be cautious about the severe implant inclination. Cases with Apical-P of 4-12 mm can generally achieve satisfying immediate implant outcomes via regulating the implant inclination. CONCLUSIONS: Quantification of the apical palatal bone index for maxillary incisor immediate implant assessment can be achieved, providing a quantitative guide for immediate implant placement in the maxillary incisor zone.

Optimized osteogenesis of porcine bone-derived xenograft through surface coating of magnesium-doped nanohydroxyapatite.

As one of the key factors influencing the outcome of guided bone regeneration, the currently used xenografts possess insufficient capability in osteogenesis. With the aim of improving the osteogenic performance of xenografts, porcine bone-derived hydroxyapatite (PHA) was prepared and subsequently coated by magnesium-doped nano hydroxyapatite (nMgHA, 10%, 20%, and 30% of Mg/Ca + Mg) through a straightforward and cost-efficient approach. The physiochemical and biological properties of nMgHA/PHAs were examinedin vitroandin vivo. The inherent three-dimensional (3D) porous framework with the average pore size of 300 µm was well preserved in nMgHA/PHAs. Meanwhile, excess magnesium released from the so-called 'surface pool' of PHA was verified. In contrast, slower release of magnesium at lower concentrations was detected for nMgHA/PHAs. Significantly more newly-formed bone and microvessels were observed in 20%nMgHA/PHA than the other specimens. With the limitations of the present study, it could be concluded that PHA coated by 20%nMgHA may have the optimized osteogenic performance due to the elimination of the excess magnesium from the 'surface pool', the preservation of the inherent 3D porous framework with the favorable pore size, and the release of magnesium at an appropriate concentration that possessed osteoimmunomodulatory effects on macrophages.

Inducing the "re-development state" of periodontal ligament cells via tuning macrophage mediated immune microenvironment.

INTRODUCTION: Periodontal regeneration, specifically the restoration of the cementum-periodontal ligament (PDL)-alveolar bone complex, remains a formidable challenge in the field of regenerative dentistry. In light of periodontal development, harnessing the multi-tissue developmental capabilities of periodontal ligament cells (PDLCs) and reinitiating the periodontal developmental process hold great promise as an effective strategy to foster the regeneration of the periodontal complex. OBJECTIVES: This study aims to delve into the potential effects of the macrophage-mediated immune microenvironment on the "developmental engineering" regeneration strategy and its underlying molecular mechanisms. METHODS: In this study, we conducted a comprehensive examination of the periodontium developmental process in the rat mandibular first molar using histological staining. Through the induction of diverse immune microenvironments in macrophages, we evaluated their potential effects on periodontal re-development events using a cytokine array. Additionally, we investigated PDLC-mediated periodontal re-development events under these distinct immune microenvironments through transcriptome sequencing and relevant functional assays. Furthermore, the underlying molecular mechanism was also performed. RESULTS: The activation of development-related functions in PDLCs proved challenging due to their declined activity. However, our findings suggest that modulating the macrophage immune response can effectively regulate PDLCs-mediated periodontium development-related events. The M1 type macrophage immune microenvironment was found to promote PDLC activities associated with epithelial-mesenchymal transition, fiber degradation, osteoclastogenesis, and inflammation through the Wnt, IL-17, and TNF signaling pathways. Conversely, the M2 type macrophage immune microenvironment demonstrated superiority in inducing epithelium induction, fibers formation, and mineralization performance of PDLCs by upregulating the TGFß and PI3K-Akt signaling pathway. CONCLUSION: The results of this study could provide some favorable theoretical bases for applying periodontal development engineering strategy in resolving the difficulties in periodontal multi-tissue regeneration.

Identification of bioactive compounds and potential mechanisms of scutellariae radix-coptidis rhizoma in the treatment of atherosclerosis by integrating network pharmacology and experimental validation.

OBJECTIVE: This study aims at investigating the potential targets and functional mechanisms of Scutellariae Radix-Coptidis Rhizoma (QLYD) against atherosclerosis (AS) through network pharmacology, molecular docking, bioinformatic analysis and experimental validation. METHODS: The compositions of QLYD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature, where the main active components of QLYD and corresponding targets were identified. The potential therapeutic targets of AS were excavated using the OMIM database, DrugBank database, DisGeNET database, CTD database and GEO datasets. The protein-protein interaction (PPI) network of common targets was constructed and visualized by Cytoscape 3.7.2 software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to analyze the function of core targets in the PPI network. Molecular docking was carried out using AutoDockTools, AutoDock Vina, and PyMOL software to verify the correlation between the main components of QLYD and the core targets. Mouse AS model was established and the results of network pharmacology were verified by in vivo experiments. RESULTS: Totally 49 active components and 225 corresponding targets of QLYD were obtained, where 68 common targets were identified by intersecting with AS-related targets. Five hub genes including IL6, VEGFA, AKT1, TNF, and IL1B were screened from the PPI network. GO functional analysis reported that these targets had associations mainly with cellular response to oxidative stress, regulation of inflammatory response, epithelial cell apoptotic process, and blood coagulation. KEGG pathway analysis demonstrated that these targets were correlated to AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, and NF-kappa B signaling pathway. Results of molecular docking indicated good binding affinity of QLYD to FOS, AKT1, and TNF. Animal experiments showed that QLYD could inhibit inflammation, improve blood lipid levels and reduce plaque area in AS mice to prevent and treat AS. CONCLUSION: QLYD may exert anti-inflammatory and anti-oxidative stress effects through multi-component, multi-target and multi-pathway to treat AS.

Nanotopographic micro-nano forces finely tune the conformation of macrophage mechanosensitive membrane protein integrin ß2 to manipulate inflammatory responses.

Finely tuning mechanosensitive membrane proteins holds great potential in precisely controlling inflammatory responses. In addition to macroscopic force, mechanosensitive membrane proteins are reported to be sensitive to micro-nano forces. Integrin ß2, for example, might undergo a piconewton scale stretching force in the activation state. High-aspect-ratio nanotopographic structures were found to generate nN-scale biomechanical force. Together with the advantages of uniform and precisely tunable structural parameters, it is fascinating to develop low-aspect-ratio nanotopographic structures to generate micro-nano forces for finely modulating their conformations and the subsequent mechanoimmiune responses. In this study, low-aspect-ratio nanotopographic structures were developed to finely manipulate the conformation of integrin ß2. The direct interaction of forces and the model molecule integrin αXß2 was first performed. It was demonstrated that pressing force could successfully induce conformational compression and deactivation of integrin αXß2, and approximately 270 to 720 pN may be required to inhibit its conformational extension and activation. Three low-aspect-ratio nanotopographic surfaces (nanohemispheres, nanorods, and nanoholes) with various structural parameters were specially designed to generate the micro-nano forces. It was found that the nanorods and nanohemispheres surfaces induce greater contact pressure at the contact interface between macrophages and nanotopographic structures, particularly after cell adhesion. These higher contact pressures successfully inhibited the conformational extension and activation of integrin ß2, suppressing focal adhesion activity and the downstream PI3K-Akt signaling pathway, reducing NF-κB signaling and macrophage inflammatory responses. Our findings suggest that nanotopographic structures can be used to finely tune mechanosensitive membrane protein conformation changes, providing an effective strategy for precisely modulating inflammatory responses. Electronic Supplementary Material: Supplementary material (primer sequences of target genes in RT-qPCR assay; the results of solvent accessible surface area during equilibrium simulation, the ligplut results of hydrogen bonds, and hydrophobic interactions; the density of different nanotopographic structures; interaction analysis of the downregulated leading genes of "focal adhesion" signaling pathway in nanohemispheres and nanorods groups; and the GSEA results of "Rap 1 signaling pathway" and "regulation of actin cytoskeleton" in different groups) is available in the online version of this article at 10.1007/s12274-023-5550-0.

Tailoring the multiscale mechanics of tunable decellularized extracellular matrix (dECM) for wound healing through immunomodulation.

With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.

Seasonal variations of soil bacterial and fungal communities in a subtropical Eucalyptus plantation and their responses to throughfall reduction.

Climatic change causes obvious seasonal meteorological drought in southern China, yet there is a lack of comprehensive in situ studies on the effects of drought in Eucalyptus plantations. Here, a 50% throughfall reduction (TR) experiment was conducted to investigate the seasonal variations of soil bacterial and fungal communities and functions in a subtropical Eucalyptus plantation and their responses to TR treatment. Soil samples were collected from control (CK) and TR plots in the dry and rainy seasons and were subjected to high-throughput sequencing analysis. Results showed that TR treatment significantly reduced soil water content (SWC) in the rainy season. In CK and TR treatments, fungal alpha-diversity decreased in the rainy season while bacterial alpha-diversity did not change significantly between dry and rainy seasons. Moreover, bacterial networks were more affected by seasonal variations compared with fungal networks. Redundancy analysis showed that alkali hydrolyzed nitrogen and SWC contributed the most to the bacterial and fungal communities, respectively. Functional prediction indicated that the expression of soil bacterial metabolic functions and symbiotic fungi decreased in the rainy season. In conclusion, seasonal variations have a stronger effect on soil microbial community composition, diversity, and function compared with TR treatment. These findings could be used to develop management practices for subtropical Eucalyptus plantations and help maintain soil microbial diversity to sustain long-term ecosystem function and services in response to future changes in precipitation patterns.