In vivo evaluation of T-Scan in quantifying occlusal contact.

BACKGROUND: The T-scan system has been used previously to analyse occlusion, but the quantitative analysis of occlusal contact by T-Scan system has yet to be reported. OBJECTIVES: To evaluate the reliability and validity of T-Scan system for quantitatively measuring occlusal contact area and occlusal contact number. METHODS: Twenty-two individuals with normal occlusion, 11 men and 11 women, were recruited for the study. Two occlusal analysis methods, including silicone transmission analysis method (STA) and T-Scan occlusion analysis method (TSO), were used to make quantitative analysis to measure occlusal contact area (OCA) and occlusal contact number (OCN). A test-retest check was performed with an interval of 2 weeks. The values of intraclass correlation coefficients (ICC) between test-retest of each method were calculated for reliability evaluation. Pearson correlations analysis, paired t-tests, regression analysis and Bland-Altman analysis were performed for validity evaluation. RESULTS: The ICC values of STA were greater than those of TSO for OCA while for OCN, ICC values of TSO were greater than STA. The higher OCA and OCN values were found in TSO compared with STA. Pearson's correlation coefficient indicated strong relations between TSO and STA (0.730-0.812) for OCA, while good relations between then (0.569-0.583) for OCN. Paired t-test showed a significant difference between the OCA and OCN values between TSO and STA. Bland-Altman analysis showed good agreement between OCA and OCN values of TSO and STA both in men and women. Regression analysis identified a linear correlation between OCA values obtained from these two methods. CONCLUSIONS: T-Scan method showed strong reliability for measuring OCA and OCN quantitatively. Strong correlations were found between OCA values from TSO and STA method, but the validity of TSO for measuring OCN needs to be promoted. CLINICAL SIGNIFICANCE: T-Scan system demonstrates good potential in quantitative analysis of occlusion, which will expand its clinical application.

Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer.

Background: Severe radiation pneumonitis (RP), one of adverse events in patients with lung cancer receiving thoracic radiotherapy, is more likely to lead to more mortality and poor quality of life, which could be predicted by clinical information and treatment scheme. In this study, we aimed to explore the clinical predict model for severe RP. Methods: We collected information on lung cancer patients who received radiotherapy from August 2020 to August 2022. Clinical features were obtained from 690 patients, including baseline and treatment data as well as radiation dose measurement parameters, including lung volume exceeding 5 Gy (V5), lung volume exceeding 20 Gy (V20), lung volume exceeding 30 Gy (V30), mean lung dose (MLD), etc. Among them, 621 patients were in the training cohort, and 69 patients were in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their predictive power. Overoptimism in the training cohorts was evaluated by four validation methods, including hold-out, 10-fold, leave-one-out, and bootstrap methods, and test cohort was used to evaluate the predictive performance of the model. Model calibration, decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: Severe RP was up to 9.4%. The results of multivariate analysis of logistics regression in all patients showed that patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD) could increase the risk of severe RP, and patients with a better lung diffusion function and received standardized steroids treatment could decrease the risk of severe RP. The three models built by MLR, BSR, and RFR all had good accuracy (>0.850) and moderate κ value (>0.4), and the model 2 built by BSR had the highest area under the receiver operating characteristic (ROC) curve (AUC) in three models, which was 0.958 [95% confidence interval (CI): 0.932-0.985]. The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the model 2 which drew the nomogram. The model 2 included subclinical ILD, diffusing capacity of the lung for carbon monoxide (DLCO), ipsilateral lung V20, and standardized steroid treatment, which could affect the incidence of severe RP. Conclusions: Subclinical ILD, DLCO, ipsilateral lung V20, and with or not standardized steroid treatment could affect the incidence of severe RP. Strict lung dose limitation and standardized steroid treatment could contribute to a decrease in severe RP.

Identification of priority areas for territorial space ecological restoration in arid area of Northwest China: A case study of Zhangye City in Heihe River basin.

Determining priority areas for territorial ecological restoration in the arid region of Northwest China based on the holistic protection and systematic governance is an important measure to build solid national ecological security barrier and promote the construction of territorial ecological civilization. Taking Zhangye City, a typical arid area city in Northwest China, as an example, we constructed the research framework of "ecological network-ecological sensitivities-ecological degradation" from two aspects of internal defects and external threats of ecological networks by using circuit theory and assessment methods of ecological service function importance, ecological sensitivity, and ecological degradation. We then identified the priority areas of territorial ecological restoration in northwest arid region and put forward the restoration strategies. The results showed that the priority areas of ecological restoration in Zhangye City were concentrated in the artificial shelterbelt along rivers and the plain-desert-oasis transition zone with fragile ecology and strong human interference. The ecological network of the study area included 39 ecological sources and 99 ecological corridors, and the highly sensitive and degraded areas were 1595.40 and 6.65 km2. Based on the internal defects and external threats of the ecological network, we identified 31 ecological pinch points, 7 obstacle points, and 753.56 km2 ecological source areas in the territorial spatial ecological restoration priority area. These areas were related to the connectivity of the ecological network internally and the stability maintenance of the ecosystem outwards, and were the areas to restoration in the future. Following the concept of overall protection and system restoration of territorial space, we put forward the idea of territorial space restoration by integrating internal defects and external threats of ecological network, which could provide scientific decision-making basis for comprehensive ecosystem management and territorial optimization of Zhangye City.

Accuracy of implant placement using CAD-CAM tooth-supported surgical guides for an auricular prosthesis in vitro.

PURPOSE: To evaluate the accuracy of tooth-supported surgical guides used to place implants in auricular prostheses. The accuracy (trueness and precision) of the implant positions was evaluated, and the difference between the surgical guide with and without retention of the external auditory canal (EAC) was compared. MATERIALS AND METHODS: This study simulated implant placement in vitro for the treatment of right auricle malformation. Surgical guides and other casts were fabricated using additive manufacturing technology. The casts were divided into 2 groups according to the surgical guide, with 10 bone blocks in each group (with or without the EAC plug (Guides 1 and 2)). Three implant positions (Implants 1-3) were prepared for each bone block using surgical guides. Implant positions were registered using light-body silicone impressions combined with optical surface scans to measure the coronal, apical, depth, and angular deviations. Four deviations of trueness and precision were reported as the mean ± standard deviation, which was analyzed by Student's t-test. RESULTS: Each group of 10 bone blocks with 30 implant positions was successfully prepared and digitally reproduced as implants. The accuracies of implant position with surgical guides were acceptable when compared with the preoperatively planned implant positions. Compared with the Guide 2 group, there was a significant difference in the apical, depth, and angular deviations of Guide 1 group in terms of precision (p = 0.001). There was a significant difference in the depth deviation of Implant 1 (p = 0.028) and apical deviation of Implant 2 (p < 0.001) compared two groups in terms of trueness. In terms of precision, there was a significant difference in the coronal (p = 0.002), apical (p = 0.001), and depth (p < 0.001) deviation of Implant 1; apical (p = 0.036) and angular (p < 0.001) deviation of Implant 2 also existed significant difference; the coronal deviation of Implant 3 (p = 0.018) also existed significant difference. Moreover, the group with the EAC plug showed lower deviation in precision and a smaller volume in the 95% confidence ellipsoid. CONCLUSION: Both types of tooth-supported surgical guides can provide acceptable accuracy. A surgical guide with an EAC plug was considered to be more precise.

Correlation between intraosseous thermal change and drilling impulse data during osteotomy within autonomous dental implant robotic system: An in vitro study.

OBJECTIVES: This study aims at examining the correlation of intraosseous temperature change with drilling impulse data during osteotomy and establishing real-time temperature prediction models. MATERIALS AND METHODS: A combination of in vitro bovine rib model and Autonomous Dental Implant Robotic System (ADIR) was set up, in which intraosseous temperature and drilling impulse data were measured using an infrared camera and a six-axis force/torque sensor respectively. A total of 800 drills with different parameters (e.g., drill diameter, drill wear, drilling speed, and thickness of cortical bone) were experimented, along with an independent test set of 200 drills. Pearson correlation analysis was done for linear relationship. Four machining learning (ML) algorithms (e.g., support vector regression [SVR], ridge regression [RR], extreme gradient boosting [XGboost], and artificial neural network [ANN]) were run for building prediction models. RESULTS: By incorporating different parameters, it was found that lower drilling speed, smaller drill diameter, more severe wear, and thicker cortical bone were associated with higher intraosseous temperature changes and longer time exposure and were accompanied with alterations in drilling impulse data. Pearson correlation analysis further identified highly linear correlation between drilling impulse data and thermal changes. Finally, four ML prediction models were established, among which XGboost model showed the best performance with the minimum error measurements in test set. CONCLUSION: The proof-of-concept study highlighted close correlation of drilling impulse data with intraosseous temperature change during osteotomy. The ML prediction models may inspire future improvement on prevention of thermal bone injury and intelligent design of robot-assisted implant surgery.

Accuracy and Feasibility of Synthetic CT for Lung Adaptive Radiotherapy: A Phantom Study.

OBJECTIVES: The respiratory variations will lead to inconsistency between the actual delivery dose and the planning dose. How the minor interfractional amplitude changes affect the geometry and dose delivery accuracy remains to be investigated in the context of lung adaptive radiotherapy. METHODS: Planning 4-dimensional-computed tomography and kV-cone beam computed tomography were scanned based on the Computerized Imaging Reference Systems phantom, which was employed to simulate the minor interfractional amplitude variations. The corresponding synthetic computed tomography for a particular motion pattern can be generated from Velocity program. Then a clinically meaningful synthetic computed tomography was analyzed through the geometrical and dosimetric assessment. RESULTS: The image quality of synthetic computed tomography was improved obviously compared with cone beam computed tomography. Mean absolute error was minimized when no significant interfractional motion occurs and Velocity can be qualified for dealing with the regular breathing motion patterns. The mean percent hounsfield unit difference of the synthetic hounsfield unit values per organ relative to the planning 4-dimensional-computed tomography image was 22.3%. Under the same conditions, the mean percent hounsfield unit difference of the cone beam computed tomography hounsfield unit values per organ, relative to the planning 4-dimensional-computed tomography image was 83.9%. Overall, the accuracy of hounsfield unit in synthetic computed tomography was improved obviously and the variability of the synthetic image correlates with the planning 4-dimensional-computed tomography image variability. Meanwhile, the dose-volume histograms between planning 4-dimensional-computed tomography and synthetic computed tomography almost coincided each other, which indicates that Velocity program can qualify lung adaptive radiotherapy well when there were no interfractional respiratory variations. However, for cases with obvious interfractional amplitude change, the volume covered at least by 100% of the prescription dose was only 59.6% for that synthetic image. CONCLUSION: The synthetic computed tomography images generated from Velocity were close to the real images in anatomy and dosimetry, which can make clinical lung adaptive radiotherapy possible based on the actual patient anatomy during treatment.

Arthrospira promotes plant growth and soil properties under high salinity environments.

Salt stress detrimentally impacts plant growth, imperiling crop yield and food quality. Ameliorating plant resilience and productivity in saline environments is critical for global food security. Here, we report the positive effect of Arthrospira (Spirulina) on plant growth and salt tolerance in Arabidopsis and sweet sorghum. Arthrospira application greatly promotes seed germination and seedling growth in both species under salt stress conditions in a dosage-dependent manner. Application of 6 mg Arthrospira per plate significantly enhances K+/Na+ equilibrium and reactive oxygen species (ROS) scavenging in Arabidopsis, reducing salt-induced toxicity. The primary root length, survival rate, chlorophyll content, photosynthesis, plant height, biomass and yield were all improved in both species. Concurrently, Arthrospira demonstrated the synthesis of compatible solutes, such as trehalose (Tre) and glucosylglycerol (GG), contributing to heightened stress tolerance when co-cultivated with Arabidopsis on plates. Transcriptome analysis revealed dramatic up-/down- regulation of genes involved in phytohormone signal transduction, chlorophyll and photosynthesis metabolism, and phenylpropanoid metabolism in Arabidopsis. Furthermore, the application of Arthrospira exerted a positive influence on the rhizosphere bacteriome structure in sweet sorghum, crucial for nutrient cycling and soil health enhancement. Our findings uncovered the underlying mechanisms of algae-plants interaction in saline soil, proposing strategies to enhance crop productivity and soil quality, thereby addressing the urgent need for sustainable agriculture practices to mitigate salinity's repercussions amidst climate change challenges.

[Establishment and evaluation of rabbit model of closed tibial fracture].

OBJECTIVE: To explore the effect of a modified three-point bending fracture device for establishing a rabbit model of closed tibial fracture. METHODS: The model of closed tibial fracture was established in 40 6-month-old male New Zealand white rabbits with a body weight of 2.5 to 3.0 kg, and the model was verified at 6 weeks after operation. Five rabbits underwent pre modeling without temporary external fixation before modeling, and then were fractured with a modified three-point bending fracture device;35 rabbits underwent formal modeling. Before modeling, needles were inserted, and splints were fixed externally, and then the fracture was performed with a modified three-point bending fracture device. The fracture model and healing process were evaluated by imaging and histopathology at 2 hours, 4 weeks, and 6 weeks after operation. RESULTS: Two hours after modeling, the prefabricated module showed oblique fracture in varying degrees and the broken end shifted significantly;Except for 1 comminuted fracture, 2 curved butterfly fractures and 2 without obvious fracture line, the rest were simple transverse and oblique fractures without obvious displacement in formal modeling group. According to the judgment criteria, the success rate of the model was 85.71%. Four weeks after modeling, the fixed needle and splint of the experimental rabbits were in good position, the fracture alignment was good, the fracture line was blurred, many continuous callus growths could be seen around the fracture end, and the callus density was high. Six weeks after modeling, many thick new bone trabeculae at the fracture, marginal osteoblasts attached, and a small number of macrophages were seen under the microscope. The intramembrane osteogenesis area was in the preparation bone stage, the medullary cavity at the fracture had been partially reopened, the callus was in the absorption plastic stage, and many osteoclasts were visible. The X-ray showed that the fracture line almost disappeared, part of the medullary cavity had been opened, the external callus was reduced around, the callus was in the plastic stage, and the bone cortex was continuous. It suggests that the fracture model showed secondary healing. CONCLUSION: The improved three-point bending fracture device can establish a stable rabbit model of closed tibial fracture, and the operation is simple, which meets the requirements of closed fracture model in basic research related to fracture healing.

Identification of priority pollutants and key factors affecting environmental risks of lead­zinc mine tailing sites.

Lead­zinc mine tailing sites are widely distributed in China. Tailing sites with different hydrological settings tend to have different susceptibilities toward pollution and hence different priority pollutants and environmental risks. This paper aims to identify priority pollutants and key factors influencing environmental risks of lead­zinc mine tailing sites with different types of hydrological settings. A database with detailed information on hydrological settings, pollution, etc. of 24 typical lead­zinc mine tailing sites in China was built. A rapid classification method of hydrological settings was proposed considering the groundwater recharge and migration of pollutants in the aquifer. Priority pollutants in leach liquor of tailings, soil, and groundwater of sites were identified using the osculating value method. The key factors affecting environmental risks of lead­zinc mine tailing sites were identified using the random forest algorithm. Four types of hydrological settings were classified. Pb/Zn/As/Cd/Sb, Fe/Pb/As/Co/Cd, and nitrate/iodide/As/Pb/Cd are identified as priority pollutants of leach liquor, soil, and groundwater, respectively. The lithology of the surface soil media, slope, and groundwater depth were identified as the top 3 key factors that affect the environmental risks of sites. Priority pollutants and key factors identified in this study can provide benchmarks for the risk management of lead­zinc mine tailing sites.

Mechanical Alloying Behavior and Thermal Stability of CoCrCuFeMnNix High-Entropy Alloy Powders Prepared via MA.

CoCrCuFeMnNix (x = 0, 0.5, 1.0, 1.5, 2.0 mol, named as Ni0, Ni0.5, Ni1.0, Ni1.5, and Ni2.0, respectively) high-entropy alloy powders (HEAPs) were prepared via mechanical alloying (MA), and XRD, SEM, EDS, and vacuum annealing were used to study the alloying behavior, phase transition, and thermal stability. The results indicated that the Ni0, Ni0.5, and Ni1.0 HEAPs were alloyed at the initial stage (5-15 h), the metastable BCC + FCC two-phase solid solution structure was formed, and the BCC phase disappeared gradually with the prolonging of ball milling time. Finally, a single FCC structure was formed. Both Ni1.5 and Ni2.0 alloys with high nickel content formed a single FCC structure during the whole mechanical alloying process. The five kinds of HEAPs showed equiaxed particles in dry milling, and the particle size increased with an increase in milling time. After wet milling, they changed into lamellar morphology with thickness less than 1 µm and maximum size less than 20 µm. The composition of each component was close to its nominal composition, and the alloying sequence during ball milling was Cu→Mn→Co→Ni→Fe→Cr. After vacuum annealing at 700~900 °C, the FCC phase in the HEAPs with low Ni content transformed into FCC2 secondary phase, FCC1 primary phase, and a minor σ phase. The thermal stability of HEAPs can be improved by increasing Ni content.

A completely digital workflow to fabricate a double-layered template for anterior esthetic veneers.

In the esthetic restoration of anterior teeth, trial restorations are an efficient way of communicating among patients, doctors, and dental laboratory technicians. Although the development of digital technologies has made it popular to design digital diagnostic waxing in a software program, problems such as the polymerization inhibition of silicone materials and time-consuming trimming remain. The silicone mold based on a 3-dimensionally printed resin cast still has to be transferred to the digital diagnostic waxing and to the patient's mouth to generate a trial restoration. A digital workflow is proposed to fabricate a double-layer guide to reproduce the digital diagnostic waxing in the patient's mouth. This technique is suitable for esthetic restorations of anterior teeth.

MicroRNA miR-34a-5p inhibition restrains oxidative stress injury of macrophages by targeting MDM4.

OBJECTIVE: Atherosclerosis is a chronic cardiovascular disease associated with oxidative stress damage, which is caused by excessive oxidation of low-density lipoprotein (ox-LDL). The role of microRNA miR-34a-5p on oxidative stress in ox-LDL-treated macrophages was investigated in this study. METHODS: Flow cytometry was prepared for assessing THP1-derived macrophage apoptosis. The protein and expression levels of miR-34a-5p and MDM4 were examined by Western blot and RT-qPCR, respectively. We also measured the levels of total cholesterol (TC) and triglyceride to determine the lipid accumulation. Subsequently, the activities of superoxide dismutase, malondialdehyde, and reactive oxygen species revealed the level of oxidative stress injury after miR-34a-5p and MDM4 knockdown. RESULTS: After ox-LDL treatment, cell apoptosis of macrophages increased in a dose-dependent and time-dependent manner. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of miR-34a-5p was upregulated. Next, interfering with miR-34a-5p inhibited lipid accumulation and oxidative stress injury in ox-LDL-stimulated macrophages. MDM4 was a target gene of miR-34a-5p and was upregulated in ox-LDL-stimulated macrophages. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of MDM4 was downregulated. Importantly, MDM4 knockdown partially counteracted the inhibitory effect of miR-34a-5p on oxidative stress injury. CONCLUSION: MicroRNA miR-34a-5p knockdown suppressed oxidative stress injury via MDM4 in ox-LDL-treated macrophages.

Effects of sponge iron dosage on nitrogen removal performance and microbial community structure in sequencing batch reactors.

The application of sponge iron (SI) carriers can improve the biochemical treatment performance of sequencing batch reactors (SBR) during wastewater treatment. This study used SBR reactors to explore the effects of SI dosage on the nitrogen removal performance and reactor stability and microbial community structure under low temperature and ultra-low load. In contrast to conventional SBR, the average removal rate of total nitrogen (TN) in the biological sponge iron system (BSIS) was increased by 5.38 % for 45 g/L, 18.93 % for 90 g/L, and 13.52 % for 135 g/L, respectively. The nitrogen removal performance and reactor stability showed the best performance under the SI dosage of 90 g/L. The addition of SI formed the anaerobic-anoxic-aerobic microenvironments, which facilitate the propagation of denitrifying bacteria (Saccharimonadales, Hydrogenophaga) and iron bacteria (Rhodoferax and Acinetobacter) in the BSIS. This study provides a new insight on the application of SI in the wastewater treatment.

A digital workflow for fabricating an interim obturator after partial maxillary resection.

This article describes a digital workflow for fabricating an interim obturator after partial maxillectomy which utilizes the radiopacity of iodoform gauze, a common surgical packing material, to simulate postoperative oronasal defect cavities through a computer-aided design and computer-aided manufacturing (CAD-CAM) workflow and to generate the interim obturator by 3-dimensional printing. This technique may serve as a promising alternative technique for the fabrication of an interim obturator and, in particular, benefit patients who have not seen a prosthetic specialist before surgery and present without a surgical obturator.

Clinical Applications of Polyetheretherketone in Removable Dental Prostheses: Accuracy, Characteristics, and Performance.

The high-performance thermoplastic polyetheretherketone (PEEK) has excellent mechanical properties, biocompatibility, chemical stability, and radiolucency. The present article comprehensively reviews various applications of PEEK in removable dental prostheses, including in removable partial dentures (RPDs) (frameworks and clasps), double-crown RPDs, and obturators. The clinical performance of PEEK in removable dental prostheses is shown to be satisfactory and promising based on the short-term clinical evidence and technical complications are scarce. Moreover, the accuracy of RPDs is a vital factor for their long-term success rate. PEEK in removable dental prostheses is fabricated using the conventional lost-wax technique and CAD/CAM milling, which produces a good fit. Furthermore, fused deposition modeling is considered to be one of the most practical additive techniques. PEEK in removable prostheses produced by this technique exhibits good results in terms of the framework fit. However, in light of the paucity of evidence regarding other additive techniques, these manufacturers cannot yet be endorsed. Surface roughness, bacterial retention, color stability, and wear resistance should also be considered when attempting to increase the survival rates of PEEK removable prostheses. In addition, pastes represent an effective method for PEEK polishing to obtain a reduced surface roughness, which facilitates lower bacterial retention. As compared to other composite materials, PEEK is less likely to become discolored or deteriorate due to wear abrasion.

Effects of Periodontal Splints on Biomechanical Behaviors in Compromised Periodontal Tissues and Cement Layer: 3D Finite Element Analysis.

BACKGROUND: In this study, we evaluated the effect of periodontal splints made from different materials on the stress distributions in compromised periodontal tissues and cement layers, using a computer simulation of mastication. METHODS: Twenty-five 3D models were created for a segment of mandibular teeth with different periodontal splints bilaterally extended to the canines. The models were divided into five groups according to the different materials and thicknesses (mm) of the splints: the non-splinted group, PEEK 0.7 group, PEEK 1.0 group, FRC group, and titanium group. Each group was subdivided based on five bone loss levels. Tooth 41 of each model was subjected to vertical and oblique (θ = 45°) static loads of 100 N, respectively, onto the incisal edge. The von Mises stresses and maximum principal stress were analyzed using Abaqus software. RESULTS: Oblique loading resulted in higher stresses on periodontal tissues, cement layers, and splints than those caused by vertical loading. The lower the supporting bone level, the greater the stress difference between the splinted groups and the non-splinted group. In model 133,331, with severe bone loss, the maximum von Mises stress values on the alveolar bone in tooth 41 under oblique loading dramatically decreased from 406.4 MPa in the non-splinted group to 28.62 MPa in the PEEK group and to 9.59 MPa in the titanium group. The four splinted groups presented similar stress distributions in periodontal tissues. The lowest stress level on the splint was observed in the PEEK 0.7 group, and the highest stress level was transferred to the cement layer in this group. Stress concentrations were primarily exhibited at the connectors near the load-carrying area. CONCLUSIONS: The tested splinted groups were all effective in distributing the loads on periodontal tissues around splinted teeth with similar patterns. Using splinting materials with low elastic moduli reduced the stress concentration at the splint connectors, whereas the tensile stress concentration was increased in the cement layer. Thus, the use of adhesive cement with a higher elastic modulus is recommended when applying less rigid PEEK splints.

The association between disruption of the circadian rhythm and aggravation of colitis in mice.

Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation. The circadian rhythm controls cell proliferation and energy metabolism. However, the role of circadian genes in inflammatory bowel disease is largely unknown. The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism. Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days, whereas those in the control group were not. Subsequently, half of the mice in the control and jet-lagged groups were given dextran sodium sulfate (DSS) to induce colitis. Mice in each group were euthanized at zeitgeber time (ZT)0, ZT4, ZT8, ZT12, ZT16, and ZT20. To investigate the effects of jet lag on the mice, colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2, and Nr1d1). We analysed the mitochondrial morphology, adenosine triphosphate (ATP) levels, and the expression of dynamin-related protein 1 (Drp1) and ser637-phosphorylated (p)-Drp1, which are closely related to ATP production. We further investigated the effect of PER2 knock-down in the colon epithelial cells (CCD 841 CoN) by measuring ATP and cell proliferation levels. Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice, altered the mitochondrial morphology of the colon specimens, decreased the expression of p-Drp1, reduced ATP production, and exacerbated inflammatory responses in mice with DSS-induced colitis. Additionally, silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation. Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis.

Microstructure and oxidation behavior of CoCrxCuFeMnNi high-entropy alloys fabricated by vacuum hot-pressing sintering.

Herein, CoCrxCuFeMnNi (x = 0, 0.5, 1.0, 1.5, and 2.0, in molar ratio) high-entropy alloys (HEAs) are fabricated by vacuum hot-pressing sintering (VHPS). The effect of Cr content on the microstructure and oxidation behavior are studied. When x ≤ 1.5 mol, the phases of the four alloys were all composed of FCC2 major phase and FCC1 secondary phase, while Cr2.0 alloy consisted of a small amount of FCC1 phase and ρ phase in addition to FCC2 main phase. The elemental segregation increased with the increase of Cr content. Cr2.0 alloy exhibited the lowest oxidation rate constants in the oxidation stage and the slow oxidation stage, which were 2.29 × 10-11 and 3.46 × 10-12 g2 cm-4 s-1, respectively, showing the best oxidation resistance. The oxidation products of CoCrxCuFeMnNi HEA system were mainly Mn4O3, Mn3O2, Cr2O3 and (M,Cr)3O4-type spinel oxides. The oxidation mechanism is mainly selective oxidation, that is, the outward diffusion of metal cations and the inward diffusion of oxygen ions. The oxidation resistance of the Cr-rich FCC1 and ρ phases is better than that of the copper-rich FCC2 phase.

Engineered neutrophil apoptotic bodies ameliorate myocardial infarction by promoting macrophage efferocytosis and inflammation resolution.

Inflammatory response plays a critical role in myocardial infarction (MI) repair. The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration, while the therapeutic strategy that simulates and enhances this natural process has not been established. Here, we constructed engineered neutrophil apoptotic bodies (eNABs) to simulate natural neutrophil apoptosis, which regulated inflammation response and enhanced MI repair. The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties, and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride (HAL). The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release, thereby further enhancing the anti-inflammation effects. In in vivo studies, the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function. This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.