Lactic acid induced defense responses in tobacco against Phytophthora nicotianae.

Induced resistance is considered an eco-friendly disease control strategy, which can enhance plant disease resistance by inducing the plant's immune system to activate the defense response. In recent years, studies have shown that lactic acid can play a role in plant defense against biological stress; however, whether lactic acid can improve tobacco resistance to Phytophthora nicotianae, and its molecular mechanism remains unclear. In our study, the mycelial growth and sporangium production of P. nicotianae were inhibited by lactic acid in vitro in a dose-dependent manner. Application of lactic acid could reduce the disease index, and the contents of total phenol, salicylic acid (SA), jasmonic acid (JA), lignin and H2O2, catalase (CAT) and phenylalanine ammonia-lyase (PAL) activities were significantly increased. To explore this lactic acid-induced protective mechanism for tobacco disease resistance, RNA-Seq analysis was used. Lactic acid enhances tobacco disease resistance by activating Ca2+, reactive oxygen species (ROS) signal transduction, regulating antioxidant enzymes, SA, JA, abscisic acid (ABA) and indole-3-acetic acid (IAA) signaling pathways, and up-regulating flavonoid biosynthesis-related genes. This study demonstrated that lactic acid might play a role in inducing resistance to tobacco black shank disease; the mechanism by which lactic acid induces disease resistance includes direct antifungal activity and inducing the host to produce direct and primed defenses. In conclusion, this study provided a theoretical basis for lactic acid-induced resistance and a new perspective for preventing and treating tobacco black shank disease.

Towards more tolerable subcutaneous administration: Review of contributing factors for improving combination product design.

Subcutaneous (SC) injections can be associated with local pain and discomfort that is subjective and may affect treatment adherence and overall patient experience. With innovations increasingly focused on finding ways to deliver higher doses and volumes (≥2 mL), there is a need to better understand the multiple intertwined factors that influence pain upon SC injection. As a priority for the SC Drug Development & Delivery Consortium, this manuscript provides a comprehensive review of known attributes from published literature that contribute to pain/discomfort upon SC injection from three perspectives: (1) device and delivery factors that cause physical pain, (2) formulation factors that trigger pain responses, and (3) human factors impacting pain perception. Leveraging the Consortium's collective expertise, we provide an assessment of the comparative and interdependent factors likely to impact SC injection pain. In addition, we offer expert insights and future perspectives to fill identified gaps in knowledge to help advance the development of patient-centric and well tolerated high-dose/high-volume SC drug delivery solutions.

Differential expression and prognostic value of TLR4 in kidney renal clear cell carcinoma.

Human Toll-like receptor (TLR) family plays a crucial role in immunity and cancer progression. However, the specific role of human Toll-like receptor 4 (TLR4) in kidney renal clear cell carcinoma (KIRC) remains obscure. Thus, we used single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies to evaluate the expression and prognostic value of TLR4 in KIRC. In our study, we observed that TLR4 was over expressed in KIRC tissues compared to normal renal tissues. And the expression of TLR4 was higher in macrophages/monocytes than other cell types. Besides, there is a close association between TLR4 expression and immune cell infiltration (Neutrophils, Macrophages, T cells and B cells) in KIRC. Immunohistochemical staining also showed that TLR4 was overexpressed in inflammatory infiltration renal tissue compared with normal tissue. Meanwhile, high expression of TLR4 exhibited correlations with improved survival, lower tumor grade and stage. Interestingly, the protective significance of TLR4 only showed in female patients (HR = 0.37, P < 0.01), other than male patients (HR = 0.71, P = 0.08) with KIRC. Consistently, KIRC samples with lymph node metastasis showed lower expression of TLR4. Knockdown of TLR4 in 786-O cell line increased cell proliferation and clonogenic capacity. In summary, this study found TLR4 could inhibit the progression of kidney cancer and was associated with improved survival in KIRC. The overexpression of TLR4 in macrophages and the close association between TLR4 and immune cell infiltration also underline the critical role of TLR4 in building the immune microenvironment for kidney cancer. These results may offer insights into the mechanism and immune microenvironment of kidney cancer.

Highly efficient clustering of long-read transcriptomic data with GeLuster.

MOTIVATION: The advancement of long-read RNA sequencing technologies leads to a bright future for transcriptome analysis, in which clustering long reads according to their gene family of origin is of great importance. However, existing de novo clustering algorithms require plenty of computing resources. RESULTS: We developed a new algorithm GeLuster for clustering long RNA-seq reads. Based on our tests on one simulated dataset and nine real datasets, GeLuster exhibited superior performance. On the tested Nanopore datasets it ran 2.9-17.5 times as fast as the second-fastest method with less than one-seventh of memory consumption, while achieving higher clustering accuracy. And on the PacBio data, GeLuster also had a similar performance. It sets the stage for large-scale transcriptome study in future. AVAILABILITY AND IMPLEMENTATION: GeLuster is freely available at https://github.com/yutingsdu/GeLuster.

A 3D-FEA study on the impact of different preparation forms and materials on posterior occlusal veneers.

OBJECTIVES: To study the stress distribution and bonding performance in posterior occlusal veneers and tooth bodies under different preparation forms and materials. METHODS: An isolated lower right first molar was prepared with non-retention type (type A), cavity-retained type (type B), and encircling-retention type (type C) forms. MicroCT images of the tooth were obtained and digitally converted into three-dimensional solid models. Three-dimensional models of veneers for the three abutment teeth were designed, fabricated, and divided into nine models (AEM, ALU, AVE, BEM, BLU, BVE, CEM, CLU, and CVE) according to the material used (E.max CAD [EM], Lava Ultimate [LU] and Vita Enamic [VE]). Three-dimensional finite element stress analysis was performed by applying vertical and oblique forces (200 N) to simulate chewing loads using ABAQUS. Finally, an adhesive stiffness degradation diagram was obtained using the rotatory dislocation simulation method. RESULTS: The BEM model had the largest equivalent stress extreme value (160.50 MP A) when a vertical load was applied to the veneers, while there was no significant difference when it was applied to dental tissues. The equivalent stress extreme values of each part under an oblique load were significantly greater than those under a vertical load. The AEM model had the largest values when the loads were applied to the veneers (350.60 MP A) and the dental tissues (40.13 MP A). The equivalent stress extreme values of the veneers were ranked as LU < VE < EM for different materials, and LU > VE > EM for dental tissues. Bonding performance results were C > B ≈ A and LU > VE > EM. CONCLUSIONS: The cavity-retained type better protected the veneers and dental tissues than the non-retention and encircling-retention types under lateral forces. E.max CAD material, with a high elastic modulus, reduced the stress transmitted to the remaining dental tissues. Lava Ultimate exhibited the best bonding performance.

Machine learning based on SPECT/CT to differentiate bone metastasis and benign bone lesions in lung malignancy patients.

BACKGROUND: Bone metastasis is a common event in lung cancer progression. Early diagnosis of lung malignant tumor with bone metastasis is crucial for selecting effective treatment strategies. However, 14.3% of patients are still difficult to diagnose after SPECT/CT examination. PURPOSE: Machine learning analysis of [99mTc]-methylene diphosphate (99mTc-MDP) SPECT/CT scans to distinguish bone metastases from benign bone lesions in patients with lung cancer. METHODS: One hundred forty-one patients (69 with bone metastases and 72 with benign bone lesions) were randomly assigned to the training group or testing group in a 7:3 ratio. Lesions were manually delineated using ITK-SNAP, and 944 radiomics features were extracted from SPECT and CT images. The least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomics features in the training set, and the single/bimodal radiomics models were established based on support vector machine (SVM). To further optimize the model, the best bimodal radiomics features were combined with clinical features to establish an integrated Radiomics-clinical model. The diagnostic performance of models was evaluated using receiver operating characteristic (ROC) curve and confusion matrix, and performance differences between models were evaluated using the Delong test. RESULTS: The optimal radiomics model comprised of structural modality (CT) and metabolic modality (SPECT), with an area under curve (AUC) of 0.919 and 0.907 for the training and testing set, respectively. The integrated model, which combined SPECT, CT, and two clinical features, exhibited satisfactory differentiation in the training and testing set, with AUC of 0.939 and 0.925, respectively. CONCLUSIONS: The machine learning can effectively differentiate between bone metastases and benign bone lesions. The Radiomics-clinical integrated model demonstrated the best performance.

Chromatin remodeling analysis reveals the RdDM pathway responds to low-phosphorus stress in maize.

Chromatin in eukaryotes folds into a complex three-dimensional (3D) structure that is essential for controlling gene expression and cellular function and is dynamically regulated in biological processes. Studies on plant phosphorus signaling have concentrated on single genes and gene interactions. It is critical to expand the existing signaling pathway in terms of its 3D structure. In this study, low-Pi treatment led to greater chromatin volume. Furthermore, low-Pi stress increased the insulation score and the number of TAD-like domains, but the effects on the A/B compartment were not obvious. The methylation levels of target sites (hereafter as RdDM levels) peaked at specific TAD-like boundaries, whereas RdDM peak levels at conserved TAD-like boundaries shifted and decreased sharply. The distribution pattern of RdDM sites originating from the Helitron transposons matched that of genome-wide RdDM sites near TAD-like boundaries. RdDM pathway genes were upregulated in the middle or early stages and downregulated in the later stages under low-Pi conditions. The RdDM pathway mutant ddm1a showed increased tolerance to low-Pi stress, with shortened and thickened roots contributing to higher Pi uptake from the shallow soil layer. ChIP-seq results revealed that ZmDDM1A could bind to Pi- and root development-related genes. Strong associations were found between interacting genes in significantly different chromatin-interaction regions and root traits. These findings not only expand the mechanisms by which plants respond to low-Pi stress through the RdDM pathway but also offer a crucial framework for the analysis of biological issues using 3D genomics.

MYO5A overexpression promotes invasion and correlates with low lymphocyte infiltration in head and neck squamous carcinoma.

Head and neck squamous carcinoma (HNSC) poses a significant public health challenge due to its substantial morbidity. Nevertheless, despite advances in current treatments, the prognosis for HNSC remains unsatisfactory. To address this, single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies were conducted to examine the role of MYO5A (Myosin VA) in HNSC. Our investigation revealed an overexpression of MYO5A in HNSC that promotes HNSC migration in vitro. Remarkably, knockdown of MYO5A suppressed vimentin expression. Furthermore, analyzing the TCGA database evidenced that MYO5A is a risk factor for human papillomavirus positive (HPV+) HNSC (HR = 0.81, P < 0.001). In high MYO5A expression HNSC, there was a low count of tumor infiltrating lymphocytes (TIL), including activated CD4+ T cells, CD8+ T cells, and B cells. Of note, CD4+ T cells and B cells were positively associated with improved HPV+ HNSC outcomes. Correlation analysis demonstrated a decreased level of immunostimulators in high MYO5A-expressing HNSC. Collectively, these findings suggest that MYO5A may promote HNSC migration through vimentin and involve itself in the process of immune infiltration in HNSC, advancing the understanding of the mechanisms and treatment of HNSC.

High PGAP3 expression is associated with lymph node metastasis and low CD8+T cell in patients with HER2+ breast cancer.

BACKGROUND: Breast cancer (BC) stands as the most prevalent malignancy among women and ranks as the second most frequently diagnosed cancer globally among newly identified cases. Post-GPI attachment to proteins factor 3（PGAP3）was reported to involve in lipid remodeling. However, its specific role in breast cancer remains inadequately elucidated. Consequently, the principal objective of this study was to investigate the clinical significance of PGAP3 in breast cancer. METHODS: We conducted an extensive analysis using both public databases and our own sample cohort to assess the role of PGAP3 in breast cancer. Immunohistochemistry was employed to assess PGAP3 expression, immune markers, and the co-expression of PGAP3 with key susceptibility genes. Data analysis was performed using the R programming language. RESULTS: Our findings revealed that PGAP3 is significantly overexpressed in breast cancer, particularly in human epidermal growth factor 2 positive (HER2 +) breast cancer cases (p < 0.001). Co-expression analyses demonstrated a significant correlation between PGAP3 and susceptibility genes associated with breast cancer, including BRCA1, BRCA2, PALB2, ATM, CHEK2, RAD51C, and RAD51D (p < 0.05). Logistic regression analysis identified PGAP3 as a significant predictor of estrogen receptor (ER), progesterone receptor (PR), HER2, and lymph node metastasis status (p < 0.01). Furthermore, higher PGAP3 expression was associated with decreased infiltration of CD8 + T cells in breast cancer samples. CONCLUSION: Our study sheds light on the clinical significance of PGAP3 in breast cancer. PGAP3 is not only overexpressed in breast cancer but also correlates with key susceptibility genes, lymph node metastasis, and CD8 + T cell infiltration. These findings provide valuable insights into the potential role of PGAP3 as a biomarker in breast cancer and may contribute to our understanding of the disease's pathogenesis.

Solvent Quality and Aggregation State of Asphaltenes on Interfacial Mechanics and Jamming Behavior at the Oil/Water Interface.

The formation of highly stable water-in-oil emulsions results in complications in both upstream and downstream processing. Emulsion stability in these systems has been connected to the adsorption of surface-active asphaltenes that are assumed to form a rigidified film at the oil/water (o/w) interface. Full characterization of this behavior is needed to allow for engineered solutions for enhanced oil recovery. Interfacial properties, such as surface pressure and interfacial elasticity, are implicated in the stabilizing mechanism for these observed films. Asphaltenes are known to be interfacially active in both good solvents (aromatics) and poor solvents (high ratio of aliphatic to aromatic). However, due to inherent complexities present in asphaltene studies, the details of the mechanical properties of the interface remain poorly understood. Despite the widely accepted perception that asphaltenes form persistent rigid films at fluid-fluid interfaces, the connection between bulk solution properties and interfacial mechanics has not been resolved. Here, the effects of solvent quality on the interfacial properties of asphaltene dispersions are determined by using a well-defined asphaltene/solvent system. Interfacial rigidity is observed only under poor solvent conditions, while the good solvent system remains fluid-like. The interfacial rheology under good and poor solvent conditions is measured simultaneously with surface pressure measurements to track interfacial development. It is shown that surface pressure and dilatational modulus measurements are not indicators of whether an interface demonstrates rigid behavior under large compressions. Finally, conditions required for asphaltene-coated interfaces to exhibit the mechanical behavior associated with a rigidified interface are defined. This work provides a framework for quantifying the impact of the aggregation state of asphaltenes on the stability and mechanics at the o/w interface.

Synchronous Improvement of Mechanical and Damping Properties of Structural Damping Composites with Polyetherimide Non-Woven Fabric Interlayers Loaded with Polydopamine and Carbon Nanotubes.

Structural damping composites exhibit considerable potential in aerospace and other fields due to their excellent damping and vibration reduction performance, as well as their structural carrying capacity. However, conventional structural damping composite materials generally do not combine excellent mechanical and damping properties at the same time, which makes it difficult for them to meet the practical demand in engineering. In this paper, polyetherimide (PEI) non-woven fabric interlayer materials loaded with quantified polydopamine (PDA) and carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) were used to prepare carbon fiber-reinforced bismaleimide composites through the co-curing process. The mechanical and damping properties of the composites were systematically studied. The results demonstrate that PEI non-woven fabric interlayers loaded with PDA and MWCNTs-COOH can synchronously improve the mechanical and damping properties of the co-cured composites. The incorporation of carbon nanotubes and polydopamine during the co-curing process synergistically improves the flexural strength, flexural modulus, interlaminar shear strength, and impact fracture toughness of the composites. Most importantly, damping properties show an increase of 45.0% in the loss factor of the co-cured composites. Moreover, the reinforcement mechanism was investigated using the optical microscopy and scanning electron microscopy, which indicated that the PEI interlayers loaded with carbon nanotubes and polydopamine form a rich resin area between the layers of the composites.

New Numerical Method Based on Linear Damage Evolution Law for Predicting Mechanical Properties of TiB2/6061Al.

In order to study the effect of TiB2 particles on the mechanical properties of TiB2/6061Al composites, a series of 3D TiB2/6061Al representative volume elements (RVEs) were established based on SEM photos. This model took into account the ductile damage of the matrix and the traction separation behavior of the interface, and the linear damage evolution law was introduced to characterize stiffness degradation in the matrix elements. Mixed boundary conditions were used in the RVE tensile experiments, and the accuracy of the predicted result was verified by the agreement of the experimental stress-strain curve. The results showed that the addition of TiB2 particles can effectively promote the load-bearing capacity of the composite, but elongation is reduced. When the weight fraction of TiB2 increased from 2.5% to 12.5%, the elastic modulus, yield strength, and tensile strength increased by 8%, 10.37%, and 11.55%, respectively, while the elongation decreased by 10%. The clustering rate of the TiB2 particles is also an important factor affecting the toughness of the composites. With an increase in the clustering rate of TiB2 particles from 20% to 80%, the load-bearing capacity of the composites did not improve, and the elongation of the composites was reduced by 8%. Moreover, the high-strain region provides a path for rapid crack propagation, and particle spacing is a crucial factor that affects the stress field.

Radiomics­Clinical model based on 99mTc-MDP SPECT/CT for distinguishing between bone metastasis and benign bone disease in tumor patients.

BACKGROUND: To establish a radiomics-clinical model based on 99mTc-MDP SPECT/CT for distinguishing between bone metastasis and benign bone disease in tumor patients. METHODS: We retrospectively analyzed 256 patients (122 with bone metastasis and 134 with benign bone disease) and randomized them in the ratio of 6:2:2 into training, test and validation sets. All patients underwent 99mTc-labeled methylene diphosphonate (99mTc-MDP) SPECT/CT. We manually outlined the volumes of interest (VOIs) of lesions using ITK-SNAP from SPECT and CT images. In the training set, radiomics features were extracted using PyRadiomics and selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Then, we established three radiomics models (CT, SPECT and SPECT-CT models) using support vector machine (SVM). In addition, a radiomics-clinical model was constructed using multivariable logistic regression analysis. The four models' performance was assessed using the area under the receiver operating characteristic curve (AUC). Using DeLong test to make comparisons between the ROC (receiver operating characteristic) curves of different models. The clinical utility of the models was evaluated using decision curve analysis (DCA). RESULTS: The radiomics-clinical displayed excellent performance, and its AUC was 0.941 and 0.879 in the training and test sets. The DCA of radiomics-clinical model showed the highest clinical utility. CONCLUSIONS: The radiomics-clinical nomogram for identifying bone metastasis and benign bone disease in tumor patients was suitable to assist in clinical decision.

Catalytic Oxidation of Acetone on SmMn2O5: Effect of Acid Etching and Loading Treatment.

The key of catalytic oxidation technology is to develop a stable catalyst with high activity. It is still a serious challenge to achieve high conversion efficiency of acetone with an integral catalyst at low temperature. In this study, the SmMn2O5 catalyst after acid etching was used as the support, and the manganese mullite composite catalyst was prepared by loading Ag and CeO2 nanoparticles on its surface. By means of SEM, TEM, XRD, N2-BET, XPS, EPR, H2-TPR, O2-TPD, NH3-TPD, DRIFT, and other characterization methods, the related factors and mechanism analysis of acetone degradation activity of the composite catalyst were discussed. Among them, the CeO2-SmMn2O5-H catalyst has the best catalytic activity at 123 and 185 °C for T50 and T100, respectively, and shows excellent water and thermal resistance and stability. In essence, the surface and lattice defects of highly exposed Mn sites were formed by acid etching, and the dispersibility of Ag and CeO2 nanoparticles was optimized. Highly dispersed Ag and CeO2 nanoparticles have a highly synergistic effect with the support SmMn2O5, and the reactive oxygen species provided by CeO2 and the electron transfer brought by Ag further promote the decomposition of acetone on the carrier SMO-H. In the field of catalytic degradation of acetone, a new catalyst modification method of high-quality active noble metals and transition metal oxides supported by acid-etched SmMn2O5 has been developed.

Responsive manganese-based nanoplatform amplifying cGAS-STING activation for immunotherapy.

BACKGROUND: The activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway has attracted great attention for its ability to up-regulate innate immune response and thus enhance cancer immunotherapy. However, many STING agonists limit the further advancement of immunotherapy due to weak tumor responsiveness or low activation efficiency. The responsive and effective activation of cGAS-STING signaling in tumors is a highly challenging process. METHODS: In this study, a manganese-based nanoplatform (MPCZ NPs) was constructed that could responsively and efficiently generate more manganese ions (Mn2+) and reactive oxygen species (ROS) to activate cGAS-STING signaling pathway. Briefly, manganese dioxide (MnO2) was loaded with zinc protoporphyrin IX (ZPP) molecule and coated by polydopamine (PDA) embedded with NH4HCO3 to obtain MPCZ NPs. Additionally, MPCZ NPs were evaluated in vitro and in vivo for their antitumor effects by methyl thiazolyl tetrazolium (MTT) assay and TUNEL assays, respectively. RESULTS: In this system, tumor responsiveness was achieved by exogenous (laser irradiation) and endogenous (high levels GSH) stimulation, which triggered the collapse or degradation of PDA and MnO2. Moreover, the release of Mn2+ augmented the cGAS-STING signaling pathway and enhanced the conversion of hydrogen peroxide (H2O2) to hydroxyl radical (·OH) under NIR laser irradiation. Furthermore, the release of ZPP and the elimination of GSH by MPCZ NPs inhibited HO-1 activity and prevented ROS consumption, respectively. CONCLUSIONS: This adopted open source and reduce expenditure strategy to effectively generate more ROS and Mn2+ to responsively activate cGAS-STING signaling pathway, providing a new strategy for improving immunotherapy.

Ionic Liquids Facilitate the Dispersion of Branched Polyethylenimine Grafted ZIF-8 for Reinforced Epoxy Composites.

Metal-organic frameworks (MOFs) have been previously shown as an emerging modified class of epoxy resin. In this work, we report a simple strategy for preventing zeolitic imidazolate framework (ZIF-8) nanoparticles from agglomerating in epoxy resin (EP). Branched polyethylenimine grafted ZIF-8 in ionic liquid (BPEI-ZIF-8) nanofluid with good dispersion was prepared successfully using an ionic liquid as both the dispersant and curing agent. Results indicated that the thermogravimetric curve of the composite material had no noticeable change with increasing BPEI-ZIF-8/IL content. The glass transition temperature (Tg) of the epoxy composite was reduced with the addition of BPEI-ZIF-8/IL. The addition of 2 wt% BPEI-ZIF-8/IL into EP effectively improved the flexural strength to about 21.7%, and the inclusion of 0.5 wt% of BPEI-ZIF-8/IL EP composites increased the impact strength by about 83% compared to pure EP. The effect of adding BPEI-ZIF-8/IL on the Tg of epoxy resin was explored, and its toughening mechanism was analyzed in combination with SEM images showing fractures in the EP composites. Moreover, the damping and dielectric properties of the composites were improved by adding BPEI-ZIF-8/IL.

A Microbial Community Cultured in Gradient Hydrogel for Investigating Gut Microbiome-Drug Interaction and Guiding Therapeutic Decisions.

Despite the recognition that the gut microbiota acts a clinically significant role in cancer chemotherapy, both mechanistic understanding and translational research are still limited. Maximizing drug efficacy requires an in-depth understanding of how the microbiota contributes to therapeutic responses, while microbiota modulation is hindered by the complexity of the human body. To address this issue, a 3D experimental model named engineered microbiota (EM) is reported for bridging microbiota-drug interaction research and therapeutic decision-making. EM can be manipulated in vitro and faithfully recapitulate the human gut microbiota at the genus/species level while allowing co-culture with cells, organoids, and isolated tissues for testing drug responses. Examination of various clinical and experimental drugs by EM reveales that the gut microbiota affects drug efficacy through three pathways: immunological effects, bioaccumulation, and drug metabolism. Guided by discovered mechanisms, custom-tailored strategies are adopted to maximize the therapeutic efficacy of drugs on orthotopic tumor models with patient-derived gut microbiota. These strategies include immune synergy, nanoparticle encapsulation, and host-guest complex formation, respectively. Given the important role of the gut microbiota in influencing drug efficacy, EM will likely become an indispensable tool to guide drug translation and clinical decision-making.

Ultrasound activatable microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy.

Chemodynamic therapy (CDT) employs Fenton catalysts to kill bacteria by converting hydrogen peroxide (H2O2) into toxic hydroxyl radical (•OH). Among them, Fenton-type metal peroxide nanoparticles fascinate nanomaterials with intriguing physiochemical properties, but research on this antibacterial agent is still in its infancy. Herein, a distinct CuO2/TiO2 heterostructure constituted of ultrasmall copper peroxide (CuO2) nanoclusters and sonosensitized ultrathin oxygen vacancy-rich porous titanium oxide (OV-TiO2) nanosheets was developed and was incorporated into microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy. Engineering CuO2 nanoclusters on the surface of TiO2 nanosheets not only endows the Fenton catalytic activity for sono-chemodynamic therapy (SCDT), but also improves the sonodynamic and sonothermal performance of TiO2 by narrowing the bandgap of TiO2 and suppressing the recombination of electron-hole pairs. The high efficacy of this CuO2/TiO2 integrated microneedle (CTMN) patch was systematically demonstrated both in vitro and in vivo with the eliminating rate >99.9999% against multidrug resistant (MDR) pathogens in 5 min as well as accelerated wound tissue healing. This work highlights a promisingly new and efficient strategy for the development of sonosensitive and chemoreactive nanomedicine for non-antibiotic therapies. STATEMENT OF SIGNIFICANCE: Feton-type metal peroxides, a novel nanomaterial with self-supplied oxygen and hydrogen peroxide, can achieve effective antimicrobial activity in vitro. However, there is a lack of effective nanomaterial delivery systems and suitable means for in vivo activation/enhancement of antimicrobial activity during bacterial infected skin wound treatment. In this study, we designed and prepared efficient ultrasound activable microneedles that effectively addressed the deficiencies mentioned above and established a new paradigm for efficient utilization of metal peroxide nanomaterials and ultrasound based strategies. Noticeably, copper peroxide nanoclusters/oxygen vacancy-rich porous titanium oxide nanosheets (CuO2/TiO2) integrated microneedle (CTMN) patch combines advantages of both sono-chemodynamic and sonothermal antibacterial therapy, achieving one of the most instant and effective antibacterial efficacy (>99.9999% in 5 min) in vivo reported till now.

The accuracy of using guided endodontics in access cavity preparation and the temperature changes of root surface: An in vitro study.

BACKGROUND: Guided endodontics is a successful technique that has been gradually applied to endodontic therapy in recent years without being affected by the operator's experience. However, the guided bur produces excessive heat during continuous rotation and friction with root canal walls, it is not clear whether the degree of temperature increase may lead to the periodontal ligament and alveolar bone damage. METHODS: A total of 58 teeth were used, of which 40 teeth were not grouped, all used to evaluate the accuracy. 40 single-rooted premolars were scanned using CBCT and an intra-oral scanner, and 3D-printed guided plates were made with the pre-designed access. A custom-made guided bur was used to prepare the access cavities. The postoperative CBCT data and pre-designed pathways were matched to evaluate the deviation between the planned and virtual paths. The other 18 teeth were randomly divided into three groups (ET20 and ProTaper F3 as the control group, guided endodontics as the test group), with 6 teeth in each group. The temperature changes on the root surfaces were inspected with a thermocouple thermometer. RESULTS: The average deviation on the tip and the base of the bur was 0.30 mm and 0.28 mm (mesial/distal), and 0.28 mm and 0.25 mm (buccal/lingual). The average angle deviation was 3.62°. The mean root surface temperature rise of the guided endodontics group was the lowest (5.07 °C) (P < 0.05). CONCLUSIONS: The access cavity preparation performed with guided endodontics has feasible accuracy and low-temperature rise on the root surfaces. Due to the limitations of the study, whether it has high reliability and safety in clinical applications needs to be further studied in vivo.

Insights into AIE materials: A focus on biomedical applications of fluorescence.

Aggregation-induced emission (AIE) molecules have garnered considerable interest since its first appearance in 2001. Recent studies on AIE materials in biological and medical areas have demonstrated that they show their promise as biomaterials for bioimaging and other biomedical applications. Benefiting from significant advantages of their high sensitivity, excellent photostability, and good biocompatibility, AIE-based materials provide dramatically improved analytical capacities for in vivo detection and demonstration of vital biological processes. Herein, we introduce the development history of AIE molecules and recent progress in areas of biotesting and bioimaging. Additionally, this review also offers an outlook for the potential applications of versatile AIE materials for tracing and treating pathological tissues, including overcoming challenges and feasible solutions.