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Abstract Background Chronic inflammation and fibrosis are characteristics of silicosis, and the inflammatory mediators involved in silicosis have not been fully elucidated. Recently, macrophage-derived exosomes have been reported to be inflammatory modulators, but their role in silicosis has not been explored. The purpose of the present study was to investigate the role of macrophage-derived exosomal high mobility group box 3 (HMGB3) in silica-induced pulmonary inflammation. Methods The induction of the inflammatory response and the recruitment of monocytes/macrophages were evaluated by immunofluorescence, flow cytometry and transwell assays. The expression of inflammatory cytokines was examined by RT–PCR and ELISA, and the signalling pathways involved were examined by western blot analysis. Results HMGB3 expression was increased in exosomes derived from silica-exposed macrophages. Exosomal HMGB3 significantly upregulated the expression of inflammatory cytokines, activated the STAT3/MAPK (ERK1/2 and p38)/NF-κB pathways in monocytes/macrophages, and promoted the migration of these cells by CCR2. Conclusions Exosomal HMGB3 is a proinflammatory modulator of silica-induced inflammation that promotes the inflammatory response and recruitment of monocytes/macrophages by regulating the activation of the STAT3/MAPK/NF-κB/CCR2 pathways.

Distant hybridization is a well-established technique in genetic breeding for cultivation of superior traits. Previous studies have shown that, hybrids derived from the cross between Schizothorax wangchiachii (♀) and Percocypris pingi (♂) are significantly different from their parents in terms of growth performance, feeding behavior and disease resistance. Both cellular and plasma components of blood are integral to immune system, and erythrocytes serve as the sole cells for transporting oxygen which makes energy available for the growth, development, immune responses and all other physiological activities. In order to understand ecological adaptive strategies and also the underlying physiological and biochemical mechanisms of fish with different characteristics, the present study used offsprings and hybrids produced by artificial reproduction of the same batch of domesticated S. wangchiachii, P. pingi broodstock as the experimental fish, and analyses of biochemical indexes, differential leucocytes counts and histological examination of liver sections were performed. Results showed that the proportions of lymphocytes and thrombocytes in P. pingi were significantly higher than those in S. wangchiachii (P

A finite element model (FEM) of the electromagnetic-thermal coupling is developed to study the integral induction heating of the backup roll. The method of calling different B–H curves of the material at different temperature moments is proposed to consider the change of the relative permeability of the backup roll in the temperature rise process. The magneto-thermal two-way coupling simulation of backup rolls was carried out in ANSYS with consideration of the heating power or current change, and the field test verifies the result. The influence of critical heating process parameters, such as the effective heating length of the coil, the chamfer radial, and the diameter of the backup roll on the temperature distribution, is studied. The results reflect that the length of the induction coil above the roll on one side should be controlled between 100 mm and 200 mm. Temperature near the end of the backup roll increases significantly when the length of one side of the coil exceeds 200 mm. The coils with the same diameter can heat the rolls with different diameters. The diameter difference between the coil to the roll should control around 200 mm to ensure uniformity of temperature distribution along the axial direction. The current value needs to be increased to confirm that the temperature near the end of the roll meets the requirement when the diameter difference between the coil and the roll exceeds 200 mm. The results provide a possibility for pre-evaluating the rationality of induction heating processes in production.

PurposeThis study was based on the Global Burden of Disease (GBD) database and aimed to analyze the trend of disease burden for complete edentulism in Chinese adults between 1990 and 2030, and to provide valuable information for the development of more effective management and preventive measures.MethodsData on Chinese adults with complete edentulism from 1990 to 2019 was analyzed using GHDx data. Descriptive analyses were used to analyze changes in the prevalence and burden of complete edentulism, gender and age distribution between 1990 and 2019. In addition, we used an autoregressive integrated moving average (ARIMA) model to predict the trend of disease burden for Chinese adults with complete edentulism between 2020 and 2030.ResultsThe incidence, prevalence, and rate of YLDs in adults with complete edentulism in China showed an increasing trend from 1990 to 2019. In 2019, the incidence was 251.20 per 100,000, the prevalence was 4512.78 per 100,000, and the YLDs were 123.44 per 100,000, marking increases of 20.58, 94.18, and 93.12% from 1990. Males experienced a higher increase than females. However, the standardized rates decreased over the same period. The ARIMA model predicts a subsequent upward and then downward trend for all indicators between 2019 and 2030, except for the standardized incidence rate which remained essentially unchanged. Specifically, the incidence is predicted to decrease from 388.93 to 314.40 per 100,000, prevalence from 4512.78 to 3049.70 per 100,000, and YLDs from 123.44 to 103.44 per 100,000. The standardized prevalence and YLDs rates are also expected to decrease.ConclusionThe burden of complete edentulism in China is projected to show an increasing trend from 2020 to 2022 and a decreasing trend from 2023 to 2030. Despite the decline in the burden of disease associated with complete edentulism in China, many problems remain to be solved.

Copper (Cu) is a key cofactor in ammonia monooxygenase functioning responsible for the first step of nitrification, but its excess availability impairs soil microbial functions and plant growth. Yet, the impact of Cu on nitrogen (N) cycling and process-related variables in cropland soils remains unexplored globally. Through a meta-analysis of 1209-paired and 319-single observations from 94 publications, we found that Cu (Cu addition or Cu-polluted soil) reduced soil potential nitrification by 33.8% and nitrite content by 73.5% due to reduced soil enzyme activities of nitrification and urease, microbial biomass content, and ammonia oxidizing archaea abundance. The response ratio of potential nitrification decreased with increasing Cu concentration, soil total N, and clay content. We further noted that soil potential nitrification inhibited by 46.5% only when Cu concentration was higher than 150 mg kg−1, while low Cu concentration (less than 150 mg kg−1) stimulated soil nitrate by 99.0%. Increasing initial soil Cu content stimulated gross N mineralization rate due to increased soil organic carbon and total N, but inhibited gross nitrification rate, which ultimately stimulated gross N immobilization rate as a result of increased the residence time of ammonium. This resulted in a lower ratio of gross nitrification rate to gross N immobilization rate, implying a lower potential risk of N loss as evidenced by decreased nitrous oxide emissions with increasing initial soil Cu content. Our analysis offers initial global evidence that Cu has an important role in controlling soil N availability and loss through its effect on N production and consumption.

Two-dimensional phase unwrapping (2-D PU) is vital for reconstructing Earth’s surface topography and displacement from interferometric synthetic aperture radar (InSAR) data. Conventional algorithms rely on the postulate, but this assumption is often insufficient due to abrupt topographic changes and severe noise. To address this challenge, our research proposes a novel approach utilizing deep convolutional neural networks inspired by the U-Net architecture to estimate phase gradient information. Our approach involves downsampling the input data to extract crucial features, followed by upsampling to restore spatial resolution. We incorporate two attention mechanisms—feature pyramid attention (FPA) and global attention upsample (GAU)—and a residual structure in the network’s structure. Thus, we construct ResDANet (residual and dual attention net). We rigorously train ResDANet utilizing simulated datasets and employ an L1-norm objective function to minimize the disparity between unwrapped phase gradients and those calculated by ResDANet, yielding the final 2-D PU results. The network is rigorously trained using two distinct training strategies and encompassing three types of simulated datasets. ResDANet exhibits excellent robust performance and efficiency on simulated data and real data, such as China’s Three Gorges and an Italian volcano.

Dynamic decision-making is the process of seeking optimal choice with multiple related attributes under the multi-time-point situation. Considering that the time-varying nature of decision information can have a specific impact on the psychology of decision makers, in this paper, a dynamic decision-making method based on the cumulative prospect theory is proposed. Combining this with infinite parameterization of fuzzy soft sets, a time series interval triangular fuzzy soft set is presented, which has characteristics of boundedness, monotonicity, and symmetry. Then, based on the new information priority principle, the exponential decay model is used to determine the time weight coefficient, and a static fuzzy soft matrix is obtained. Furthermore, a method of calculating psychological utility values is proposed, in which the threshold-reference point set is introduced to analyze the psychological “profit and loss” values. Simultaneously, the time probability of the decision-making scenario is transformed into the corresponding weight function. On the basis of prospect maximization theory and maximum entropy theory, an optimization model for determining the weight of decision parameters is established. The cumulative prospect values of the alternatives are given to achieve the best choice for the alternatives. Finally, an example showed the feasibility and effectiveness of this method.

Biological nitrogen fixation (BNF) can reduce synthetic N fertilizer application and improve N-use efficiency. However, knowledge about the effect of biochar and water management regimes on soil diazotrophic microorganisms in tropical paddy fields remains only rudimentary. A field trial was started in the early rice season in 2019 and ended in the late rice season in 2020. We studied the effects of five treatments comprising different water management and biochar applications on the diazotrophic abundance and community composition: no N fertilizer + conventional water management, conventional fertilization + conventional water management, no N fertilizer + flooding, conventional fertilization + flooding, and application of 40 t ha−1 biochar + conventional fertilization + conventional water management. According to the results, biochar increased soil pH and organic carbon (SOC), whereas flooding decreased the soil available phosphorus (P) content. However, the addition of biochar and flooding as well as N application treatments increased nifH abundance. The nifH abundance negatively correlated with available N and P, whereas it significantly positively correlated with SOC (p < 0.05). The results of redundancy analysis unveiled that biochar stimulated the relative abundance of Pelomonas and changed the diazotrophic microbial community structure by increasing soil pH, while flooding stimulated the relative abundance of Azospirllum. Conclusively, both flooding and biochar affect soil diazotrophic microbial community and abundance in paddy fields. Reducing N and P fertilizer application clubbed with biochar amendment and flooding may be beneficial for soil N-fixing in tropical paddy fields.

BackgroundTo investigate secular trends in edentulism incidence, prevalence, and years lived with disability (YLDs) rates in Chinese men and women from 1990 to 2019.MethodsData were obtained from the Global Burden of Disease Study 2019. The annual percentage change and average annual percentage change were calculated using Joinpoint regression analysis. The age-period-cohort (APC) analysis estimated the independent age, period, and cohort effects.ResultsFrom 1990 to 2019, the crude incidence, prevalence, and YLDs of edentulism in the Chinese population increased year by year, while the age-standardized incidence, prevalence, and YLDs decreased, and the latter was higher in women than in men. The APC analysis showed that the age effect increased in men and women from age 20 to 74 and decreased thereafter. The risk of tooth loss increased with age. However, the relationship was not linear. The temporal effect showed a gradual increase; the risk of missing teeth gradually increased with the changing modern living environment. The cohort effect showed a single decreasing trend, with the early birth cohort having a higher risk of tooth loss than the later birth cohort population. The age, period, and cohort effects were consistent for both sexes.ConclusionAlthough the standardized incidence, prevalence, and YLD rate and cohort effect of dentition loss in China are declining, they are still causing a severe burden to China due to the continued aging of the population and the rising period effect. Despite the decreasing trends of the standardized incidence and prevalence of dentition loss and the rate of YLDs, China should develop more effective oral disease prevention and control strategies to reduce the increasing burden of edentulism in the older adult, especially in older women.

Abstract Allergic asthma is an allergic inflammatory disease of the airways, in which numerous cell types and cytokines have been shown to contribute to pathogenesis of the disease. Although increased expression of IL-9 has been shown to influence the activity of structural as well as eosinophils and mast cells in asthma, the influence of IL-9 on function of ILC2 and Th2 cells remains unclear. This study therefore aimed to elucidate the role of IL-9 on ILC2 and Th2 cells using a murine model of asthma. A murine model of asthma was established using wild type (WT) and IL-9-deficient (Il9 −/− ) transgenic mice sensitized to house dust mite (HDM). Bronchoalveolar lavage fluid (BALF) and lung tissues were collected, and analysed for inflammatory cells (eosinophils, mast cells, Th2 cells and ILC2 cells), histopathological changes, and several cytokines. HDM challenge significantly increased accumulation of ILC2 cells, Th2 cells and mast cells, as well as goblet cell hyperplasia, and the expression of cytokines IL-4, IL-5 and IL-13, but not IFN-γ, in WT mice compared to saline-challenged control group. In contrast, all pathological changes, including infiltration of ILC2 cells, Th2 cells and mast cells, were significantly attenuated in HDM-challenged Il9 −/− mice. Furthermore, the number of Ki67+ILC2 cells, Ki67+Th2 cells and Ki67+mast cells were significantly reduced in the absence of IL-9 signalling. These data suggest that IL-9 promotes the proliferation and type 2 cytokine production of type 2 cells in the murine models of asthma, and therefore might be a potential therapeutic target for asthma treatment.

Due to the influence of the ground stress, mining disturbance, and other factors, the roadway surrounding rock in deep underground engineering such as mines, tunnels, and underground caverns is prone to looseness and deformation with the excavation of roadways. In such engineering, the bolt support is frequently employed to stabilize the surrounding rock. In this work, a part of the anchor and the surrounding rock were taken as a simplified model of the anchorage rock mass, and the laboratory compression test was performed on the similitude model. Then, the FLAC3D software was used to simulate varying numbers of bolts and different lateral pressure conditions, and the peak stress, the maximum principal stress field, and the anchor stress field distribution of the anchorage rock mass were obtained. The influence of bolt pretightening force and row spacing on the stability of surrounding rock was discussed using the combined arch theory. The results show that increasing the number of bolts and lateral pressure in the anchorage rock mass can significantly improve the stress value and distribution range of the maximum principal stress field and the anchorage stress field. The fluctuation of the anchorage stress field at different anchorage distances can be lessened by increasing the number of bolts (bolt density). When the lateral pressure exceeds 3 MPa, the anchorage mechanical characteristics of the anchorage rock mass tend to remain stable. The coverage of the effective anchorage stress field and the thickness of the surrounding rock anchorage composite arch can be increased by increasing the bolt pretightening force and decreasing row spacing, consequently improving the anchorage mechanical characteristics of the anchorage rock mass. The research results can be used as a theoretical reference for choosing appropriate bolt support parameters for the roadway surrounding rock.

Objective: To investigate the burden of untreated dental caries in 204 countries and territories over 30 years. Methods: Data of untreated dental caries from 1990 to 2019, including the incidence, prevalence, and years lived with disability, were extracted from the Global Burden of Disease 2019 database. Estimated annual percentage changes were calculated to assess the changes in the age-standardized incidence, prevalence, and years lived with disability rates. Results: Globally, in 2019, there were 3.09 billion (95% uncertainty interval [UI]: 2.76–3.39 billion) new cases of untreated dental caries in permanent teeth (48.00% increase), 2.03 billion (1.77–2.33) prevalent cases (46.07% increase), and 2.00 million (0.93–3.88) YLDs (45.64% increase), all since 1990. From 1990 to 2019, the age-standardized incidence rate (ASIR) of untreated dental caries in permanent teeth showed an upward trend (estimated annual percentage changes [EAPC] = 0.01), but age-standardized prevalence rate (ASPR) (EAPC = −0.13) and age-standardized YLD rate (ASYR) (EAPC = −0.13) decreased. There were 1.15 billion (0.79–1.52) new cases of untreated dental caries in deciduous teeth (11.74% increase), 0.52 billion (0.41–0.63) prevalent cases (5.89% increase), and 0.20 million (0.09–0.43) YLDs (6.03% increase), all since 1990. From 1990 to 2019, the ASIR of untreated dental caries in permanent teeth showed a stable trend (EAPC = 0), but the ASPR (EAPC = −0.15) and ASYR (EAPC = −0.14) decreased. The incidence of untreated dental caries peaked at the ages of 5–9 and 20–24 years, and the prevalence and years lived with disability at 1–4, 20–24, and 60–64 years. Conclusion: Untreated dental caries remains a major global public health challenge, but demographic, sex, and regional differences in trends remain. Proactive intervention strategies, at both administrative and academic levels, based on dynamic changes, are needed.

Oral submucosal fibrosis (OSF) is a chronic, progressive and potentially malignant oral disorder with a high regional incidence and malignant rate. With the development of the disease, the normal oral function and social life of patients are seriously affected. This review mainly introduces the various pathogenic factors and mechanisms of OSF, the mechanism of malignant transformation into oral squamous cell carcinoma (OSCC), and the existing treatment methods and new therapeutic targets and drugs. This paper summarizes the key molecules in the pathogenic and malignant mechanism of OSF, the miRNAs and lncRNAs with abnormal changes, and the natural compounds with therapeutic effects, which provides new molecular targets and further research directions for the prevention and treatment of OSF.

Abstract Background The plant-specific valine-glutamine (VQ) protein family with the conserved motif FxxxVQxLTG reportedly functions with the mitogen-activated protein kinase (MAPK) in plant immunity. However, the roles of VQ proteins in MAPK-mediated resistance to disease in rice remain largely unknown. Results In this study, two rice VQ proteins OsVQ14 and OsVQ32 were newly identified to function as the signaling components of a MAPK cascade, OsMPKK6-OsMPK4, to regulate rice resistance to Xanthomonas oryzae pv. oryzae (Xoo). Both OsVQ14 and OsVQ32 positively regulated rice resistance to Xoo. In vitro and in vivo studies revealed that OsVQ14 and OsVQ32 physically interacted with and were phosphorylated by OsMPK4. OsMPK4 was highly phosphorylated in transgenic plants overexpressing OsMPKK6, which showed enhanced resistance to Xoo. Meanwhile, phosphorylated OsVQ14 and OsVQ32 were also markedly accumulated in OsMPKK6-overexpressing transgenic plants. Conclusions We discovered that OsVQ14 and OsVQ32 functioned as substrates of the OsMPKK6-OsMPK4 cascade to enhance rice resistance to Xoo, thereby defining a more complete signal transduction pathway for induced defenses.

Tibetans are one of the oldest ethnic groups in China and South Asia. Based on the analysis of 1,059 Tibetans in the Minjiang River basin at an altitude of 500–4,001 m, we found that the dominant phyla of the Tibetan population were Bacteroidota and Firmicutes, and the main genera were Prevotella and Bacteroides, which were mostly in consistent with other nationalities. We further evaluated in total 115 parameters of seven categories, and results showed that altitude was the most important factor affecting the variation in the microbial community. In the process of emigration from high altitudes to the plain, the gut microbial composition of late emigrants was similar to that of plateau aborigines. In addition, regarding immigration from low altitude to high altitude, the microbial community became more similar to that of high altitude population with the increase of immigration time. Changes in these microbes are related to the metabolism, disease incidence and cell functions of the Tibetan population. The results of other two cohorts (AGP and Z208) also showed the impact of altitude on the microbial community. Our study demonstrated that altitude of habitation is an important factor affecting the enterotype of the microflora in the Tibetan population and the study also provided a basis to explore the interaction of impact parameters with gut microbiome for host health and diseases.

The cleavage stimulation factor subunit complex is involved in the cleavage and polyadenylation of 3′-end pre-mRNAs that regulate mRNA formation and processing. However, cleavage stimulation factor subunit 2 (CSTF2) was found to play a more critical regulatory role across cancers. General cancer data sets from The Cancer Genome Atlas and Genotype-Tissue Expression project were thus downloaded for differential analysis, and the possible functions and mechanisms of CSTF2 in general cancer were analyzed using the Compartments database, cBioPortal database, Tumor Immune Single-cell Hub database, and Comparative Toxigenomics database using gene set enrichment analysis and R software. The results showed that CSTF2 could affect DNA repair and methylation in tumor cells. In addition, CSTF2 was associated with multiple tumor immune infiltrates in a wide range of cancers, and its high expression was associated with multiple immune checkpoints; therefore, it could serve as a potential target for many drug molecules. We also proved that CSTF2 promotes oral cell proliferation and migration. The high diagnostic efficacy of CSTF2 suggested that this gene may act as a new biomarker and personalized therapeutic target for a variety of tumors.

Magnetoelectric composites have attracted much attention due to their strong magnetoelectric coupling effect. In this paper, PbTiO3-NiFe2O4 (PTO/NFO) composite ceramics were prepared by sol-gel method. Effect of sintering temperatures on the structure, dielectric properties and multiferroic properties were studied. XRD results show that PTO/NFO ceramics have been successfully prepared. When the sintering temperature is 1050 °C, the secondary phase PbO2 exists in the ceramics. SEM results show that there were two kinds of grains with different sizes. EDS analysis suggested that the large particles are NFO and the small particles are PTO. The sintering temperature has a great influence on the dielectric and ferroelectric properties of the prepared ceramics. When the sintering temperature is 950 °C, the ceramics show the maximum dielectric constant at low frequency. When the sintering temperature is 1150 °C, the maximum residual polarization is 1.236 μC/cm2. The conductive mechanism of ceramics is dominated by Space Charge – Limited Conduction. The remanent magnetization and coercive field decrease with increasing the sintering temperature. The magnetoelectric coupling coefficient shows that ceramics have strong magnetoelectric coupling performance (5.7 V/cm·Oe).

In this paper, xPbTiO3/(1-x)NiFe2O4 (PTO/NFO, x = 0.1, 0.2, 0.3, 0.4 and 0.5) ceramic composites were prepared by mixing of sol-gel synthesized PTO and NFO powders, followed by their uniaxial pressing and sintering at 1150 °C. The effects of PTO/NFO composition on crystal structure, surface morphology, electrical, magnetic and magnetoelectric coupling properties were studied. XRD results showed that the prepared ceramics contain only PTO and NFO phases without any impurity phase. The samples were relatively dense while the grains were evenly distributed. The dielectric constant and loss varied monotonically with the frequency for different molar ratios. The hysteresis loop of the composites with high amount of high resistance NFO phase (x = 0.1, 0.2) has the shape characteristic for a material with large leakage current. The samples with x = 0.1 showed the largest saturated magnetization, while the sample with x = 0.2 had the maximum remnant magnetization. It was also shown that the polarization was affected by the external magnetic field of 1 mT and the strongest ME coupling (relative polarization change of 15.4%) was observed for the 0.5PbTiO3/0.5NiFe2O4 composite. In addition, the relevant calculation showed that the leakage mechanism may not be the main factor affecting the polarization of the obtained ceramics.

Co0.5Zn0.5Fe2O4/Ba0.8Sr0.2TiO3 (CZFO/BST) composite ceramics with different molar ratios (1:3, 1:2, 1:1, 2:1 and 3:1) were prepared by combining chemical co-precipitation and sol-gel method. Effects of molar ratio on the microstructure, dielectric and multiferroic properties were investigated. The formation of the individual phases and the composites was confirmed by XRD results and small amount of secondary phase (Ba2Fe2Ti4O13) was observed. The grain sizes of magnetic (CZFO) and ferroelectric phase (BST), measured by SEM, were about 5 µm and 0.5 µm, respectively. The sample with molar ratio (1:2) has the largest dielectric constant, while the sample with molar ratio (3:1) shows the lowest dielectric constant. A distinct loss peak can be observed for all the samples. Both the peak position and peak intensity increase with the frequency, indicating relaxation polarization process generated by space charge or interface polarization. The ceramics with molar ratio (1:1) shows the smallest leakage current (∼ 10−7 A/cm at 1.5 kV/cm), while the leakage current (∼ 10−5 A/cm at 1.5 kV/cm) of the sample with molar ratio (3:1) is the largest. The ferroelectric hysteresis loop is not apparent due to the low Curie temperature of the ferroelectric phase, but the sample with molar ratio (2:1) shows the best ferroelectric properties. It was found that with the increase of CZFO content, the values of saturation (Ms) and remnant (Mr) magnetization increase at first and then decrease. The sample with molar ratio (3:1) has the maximum Ms value (about 50.34 emu/g), while the sample with molar ratio (1:2) shows the minimal Mr value (about 0.46 emu/g). This anomalous magnetic property is induced by the interface interaction between the two phases.

Pitting, which results from contact fatigue, is a common failure mode in gear transmission systems and is influenced by the material strength and stress state of the contact area, which is further influenced by lubrication and roughness because of stress fluctuations. In this study, a comparative contact-fatigue test was conducted on two types of gears with different terminal machining processes. The contact stress of the tooth surface considering the microtopography was analyzed using the fractal method based on surface microtopography data measured from the surface formed by the two processes. Test results show that the average service life of gears machined using the barrel-finishing process was approximately 5–7 times that of gears machined using grinding. The pitting morphologies of gears fabricated using different processes exhibited evident differences. The maximum stress level of the gears machined with barrel finishing was approximately twice that of the gears machined through grinding. Different stress levels resulted in different micropitting load-bearing capacities, which could be attributed to the different service lives of gears manufactured through different machining processes. The different presence features of the pitting morphology were due to the different micromorphologies of the surface formed by the different finishing processes. In particular, the randomly distributed pitting morphology of the gear surface machined using the barrel-finishing process was due to its flattening and polishing effect. Optimization of the surface-microgeometry distribution via the finishing process is an effective method for prolonging the service life of gears.

As a laboratory-on-a-chip application tool, digital microfluidics (DMF) technology is widely used in DNA-based applications, clinical diagnosis, chemical synthesis, and other fields. Additional components (such as heaters, centrifuges, mixers, etc.) are required in practical applications on DMF devices. In this paper, a DMF chip interconnection method based on electrowetting-on-dielectric (EWOD) was proposed. An open modified slippery liquid-infused porous surface (SLIPS) membrane was used as the dielectric-hydrophobic layer material, which consisted of polytetrafluoroethylene (PTFE) membrane and silicone oil. Indium tin oxide (ITO) glass was used to manufacture the DMF chip. In order to test the relationship between the splicing gap and droplet moving, the effect of the different electrodes on/off time on the minimum driving voltage when the droplet crossed a splicing gap was investigated. Then, the effects of splicing gaps of different widths, splicing heights, and electrode misalignments were investigated, respectively. The experimental results showed that a driving voltage of 119 V was required for a droplet to cross a splicing gap width of 300 μm when the droplet volume was 10 μL and the electrode on/off time was 600 ms. At the same time, the droplet could climb a height difference of 150 μm with 145 V, and 141 V was required when the electrode misalignment was 1000 μm. Finally, the minimum voltage was not obviously changed, when the same volume droplet with different aqueous solutions crossed the splicing gap, and the droplet could cross different chip types. These splicing solutions show high potential for simultaneous detection of multiple components in human body fluids.

Exploiting gut mucosal immunity to design new antitumor vaccination strategy remains unexplored. Tumor cell-derived microparticles (T-MP) are natural biomaterials that are capable of delivering tumor antigens and innate signals to dendritic cells (DC) for tumor-specific T cell immunity. Here, we show that T-MPs by oral vaccination route effectively access and activate mucosal epithelium, leading to subsequent antitumor T cell responses. Oral vaccination of T-MPs generated potent inhibitory effect against the growth of B16 melanoma and CT26 colon cancer in mice, which required both T cell and DC activation. T-MPs, once entering intestinal lumen, were mainly taken up by ileac intestinal epithelial cells (IEC), where T-MPs activated NOD2 and its downstream MAPK and NF-κB, leading to chemokine releasing, including CCL2, from IECs to attract CD103+ CD11c+ DCs. Furthermore, ileac IECs could transcytose T-MPs to the basolateral site, where T-MPs were captured by those DCs for cross-presentation of loaded antigen contents. Elucidating these molecular and cellular mechanisms highlights T-MPs as a novel antitumor oral vaccination strategy with great potential of clinical applications.

Two new platinum(II)-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA), which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2) were evaluated and compared with cisplatin (CDDP). Though the antitumor efficacies of new complexes are lower than that of CDDP, they show higher selectivity against the HepG2 hepatoma cell line than the L02 normal liver cell line. Morphology studies exhibited typical characteristics of cell apoptosis and the cell cycle distribution analysis indicated that the complexes can inhibit cancer cells by inducing cell cycle arrest at the G2/M phase, a similar mechanism of action to CDDP.