Lithium-Doped Titanium Dioxide-Based Multilayer Hierarchical Structure for Accelerating Nerve-Induced Bone Regeneration.

Despite considerable advances in artificial bone tissues, the absence of neural network reconstruction in their design often leads to delayed or ineffective bone healing. Hence, we propose a multilayer hierarchical lithium (Li)-doped titanium dioxide structure, constructed through microarc oxidation combined with alkaline heat treatment. This structure can induce the sustained release of Li ions, mimicking the environment of neurogenic osteogenesis characterized by high brain-derived neurotrophic factor (BDNF) expression. During in vitro experiments, the structure enhanced the differentiation of Schwann cells (SCs) and the growth of human umbilical vein endothelial cells (HUVECs) and mouse embryo osteoblast progenitor cells (MC3T3-E1). Additionally, in a coculture system, the SC-conditioned media markedly increased alkaline phosphatase expression and the formation of calcium nodules, demonstrating the excellent potential of the material for nerve-induced bone regeneration. In an in vivo experiment based on a rat distal femoral lesion model, the structure substantially enhanced bone healing by increasing the density of the neural network in the tissue around the implant. In conclusion, this study elucidates the neuromodulatory pathways involved in bone regeneration, providing a promising method for addressing bone deformities.

Unraveling the Effects of Cold Stratification and Temperature on the Seed Germination of Invasive Spartina alterniflora Across Latitude.

Seed germination is critical to the life history of plants, playing an important role in the successful recruitment, colonization, and even invasion of new individuals within and outside population distribution ranges. Cold stratification and temperature are the key factors affecting seed germination traits. Studying how these two factors drive geographical variation in seed germination is essential to analyze and predict the geographical distribution range of alien plants in novel habitats. Spartina alterniflora, native to the United States, was introduced into China in 1979 and has spread over 20° of latitude along the eastern coast of China. Germination plays a crucial role in S. alterniflora's large-scale invasion and diffusion across latitude. To evaluate the effects of cold stratification and temperature on seed germination of S. alterniflora across latitude, we collected seeds at seven locations across latitude in China. We exposed these provenances to cold stratification at 4°C (0, 1, 3, and 5 months) and germination temperature (5°C, 15°C, 25°C, and 35°C) treatments in growth chambers. Seed germination was observed for 98 days, and we calculated germination rate, germination index, and germination time. Results indicated that longer cold stratification significantly promoted germination rate and germination index, but decreased germination time. Similarly, higher germination temperature significantly promoted germination rate and germination index, but decreased germination time. Moreover, there were significant interactive effects on germination traits between cold stratification and temperature. Seed germination traits showed linear relationships with latitude, indicating that S. alterniflora seeds from different provenances germinated at different times and adopted different germination strategies. The stratification and temperature are the most important factors regulating the dormancy and germination seeds, so they can be important drivers of this variation along latitude. Under scenarios of warmer regional temperature, seeds at higher latitudes could germinate earlier and have higher germination rate, which would favor a potential northern expansion of this invasive plant.

The dynamic cellular and molecular features during the development of radiation proctitis revealed by transcriptomic profiling in mice.

BACKGROUND: Radiation proctitis (RP) is the most common complication of radiotherapy for pelvic tumor. Currently there is a lack of effective clinical treatment and its underlying mechanism is poorly understood. In this study, we aimed to dynamically reveal the mechanism of RP progression from the perspective of RNomics using a mouse model, so as to help develop reasonable therapeutic strategies for RP. RESULTS: Mice were delivered a single dose of 25 Gy rectal irradiation, and the rectal tissues were removed at 4 h, 1 day, 3 days, 2 weeks and 8 weeks post-irradiation (PI) for both histopathological assessment and RNA-seq analysis. According to the histopathological characteristics, we divided the development process of our RP animal model into three stages: acute (4 h, 1 day and 3 days PI), subacute (2 weeks PI) and chronic (8 weeks PI), which could recapitulate the features of different stages of human RP. Bioinformatics analysis of the RNA-seq data showed that in the acute injury period after radiation, the altered genes were mainly enriched in DNA damage response, p53 signaling pathway and metabolic changes; while in the subacute and chronic stages of tissue reconstruction, genes involved in the biological processes of vessel development, extracellular matrix organization, inflammatory and immune responses were dysregulated. We further identified the hub genes in the most significant biological process at each time point using protein-protein interaction analysis and verified the differential expression of these genes by quantitative real-time-PCR analysis. CONCLUSIONS: Our study reveals the molecular events sequentially occurred during the course of RP development and might provide molecular basis for designing drugs targeting different stages of RP development.

Virtual versus jaw simulation in Oral implant education: a randomized controlled trial.

BACKGROUND: This research aims to investigate the evaluation methods of teaching oral implant clinical courses and estimate the effectiveness of a virtual simulation platform. METHODS: Eighty second- and third-year undergraduates in Lanzhou University were recruited and randomized to either three experimental groups or one control group. The subjects undertook theoretical examinations to test their basic level of knowledge after training in similarly unified knowledge courses. Each student group then participated in an eight-hour operating training session. An operation test on pig mandible was conducted, followed by a second theoretical examination. The assessment consists of three distinct parts: a subjective operating score by a clinical senior teacher, an implant accuracy analysis in cone-beam computed tomography (angular, apical, and entrance deviation), and comparison of the two theoretical examinations. Finally, students completed a questionnaire gauging their understanding of the virtual simulation. RESULTS: There was no significant difference between the four groups in first theoretical examination (P > 0.05); the second theoretical scores of the V-J and J-V group (62.90 ± 3.70, 60.05 ± 2.73) were significantly higher than the first time (57.05 ± 3.92, P < 0.05), while no difference between the V (57.10 ± 3.66) and J (56.89 ± 2.67) groups was found. Thus, the combination of V-J was effective in improving students' theoretical scores. The V-J and J-V groups had higher scores on operation (73.98 ± 4.58, 71.85 ± 4.67) and showed better implant precision. CONCLUSION: Virtual simulation education, especially with a jaw simulation model, could improve students' implantology achievements and training. Currently study found that the V-J group may performed better than the J-V group in oral implant teaching.

Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation.

BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) is overexpressed in many squamous cell carcinomas and promotes tumor development and invasion. The association between TROP2 expression and occurrence and development of oral squamous cell carcinoma (OSCC) remains to be understood. METHODS: We investigated the role of TROP2 in OSCC patients using a combination of biophysical approaches. A total of 108 OSCC patient specimens with varying degrees of differentiation were subjected to hematoxylin and eosin staining, immunohistochemistry, Kaplan-Meier survival curve analysis, and atomic force microscopy to analyze TROP2 expression, morphology, and mechanical properties of OSCC tissues. RESULTS: TROP2 was overexpressed in 34% of poorly differentiated OSCC samples. High levels of TROP2 were associated with 10.2% survival rate lower than 45.4% and patient age (odds ratio [OR] = 0.437, P = 0.039, 95% confidence interval [CI, 0.198-0.966]), tumor size (OR = 13.148, P = 0.000, 95% CI [5.060-34.168]), and TNM stage (OR = 0.141, P = 0.000, 95% CI [0.082-0.244]). Average surface roughness of low, medium, and highly differentiated OSCC tissues were 448.9 ± 54.8, 792.7 ± 83.6, and 993.0 ± 104.3 nm, respectively. The Pearson coefficient revealed a negative association between tumor stiffness and TROP2 expression (r = - 0.84, P < 0.01). CONCLUSION: Overexpression of TROP2 negatively associated with patient survival, degree of tumor differentiation, and tissue mechanics. Taken together, our findings demonstrated that TROP2 may be an indicator of OSCC differentiation leading to the altered mechanical properties of OSCC tissues.

[Effects of Different Concentrations of Tetracycline in Sludge on Ammonia Oxidizers During Vermicomposting].

Dewatered sludge often contains abundant antibiotics, and such contaminants can potentially affect the nitrogen fertilizer value of sludge-derived vermicompost. For this purpose, the aims of this study were to investigate the effects of different tetracycline concentrations in sludge on the nitrification rate and abundance and community characteristics of ammonia oxidizers during vermicomposting. Four sludge treatments with different concentrations of tetracycline (0, 100, 500, and 1000 mg·kg-1) were used, and data were collected to reveal the mechanism regarding the ammonia oxidization of sludge in the vermicomposting system. The results showed that the high concentration of tetracycline (1000 mg·kg-1) significantly inhibited the nitrification rate of vermicomposting (P<0.05), but no significant effect was observed in the low concentration treatments. Compared with ammonia-oxidizing bacteria (AOB), ammonia oxidizing archaea (AOA) were detected as the dominant microorganisms involved in the ammonia oxidation process during vermicomposting. In addition, the abundances of amoA genes were significantly elevated (P<0.05) in the treatments with 100 mg·kg-1 tetracycline, but values significantly decreased with the further increments of tetracycline concentrations (P<0.05). The results obtained from high-throughput sequencing revealed that the community diversity and structure of AOA and AOB were strongly modified by tetracycline concentrations, and a negative correlation relationship was detected between the tetracycline concentrations and the α diversity of AOA.

Asymmetric Structure Design of Electrolytes with Flexibility and Lithium Dendrite-Suppression Ability for Solid-State Lithium Batteries.

Solid polymer electrolytes can be used to construct solid-state lithium batteries (SSLBs) using lithium metals as the anode. However, the lifespan and safety problems of SSLBs caused by lithium dendrite growth have hindered their practical application. Here, we have designed and prepared a rigid-flexible asymmetric solid electrolyte (ASE) that is used in building SSLBs. The ASE can inhibit efficiently the growth of lithium dendrites and lead to a long cycle life of SSLBs due to the hierarchical structure of a combination of "polymer-in-ceramic" (i.e., rigid ceramic layer of Li6.4La3Zr1.4Ta0.6O12) and "LiBOB-in-polymer" (i.e., soft polymer-layer of polyethylene oxide and LiBOB components). The results demonstrated that a symmetrical battery with ASE (Li|ASE|Li) can be steadily cycled for more than 2000 h and yielded a flat plating/stripping voltage profile under a current density of 0.1 mA cm-2. As a consequence, the SSLB of LiFePO4|ASE|Li delivered a specific capacity of 155.1 mA h g-1 with a capacity retention rate up to 90.2% after 200 cycles with the Coulombic efficiency over 99.6% per cycle. This asymmetric structure combines the advantages of ceramics and polymers, providing an ingenious solution for building rigid and flexible solid electrolytes.

Efficacy of a new oncolytic adenovirus armed with IL-13 against oral carcinoma models.

PURPOSE: The efficacy of traditional therapies for oral carcinoma (OC) is limited. Oncolytic adenovirus, a novel strategy of cancer therapy, shows potential use in OC treatment. However, its clinical application is limited by pre-existing neutralizing antibodies. Thus, this study aimed to examine the efficacy of a new modified adenovirus against OC in vitro and in vivo. MATERIALS AND METHODS: A multiple modified adenovirus (MMAD) armed with IL-13 (MMAD-IL-13) was constructed, and its effect on Cal-27 cells was examined. The potency of MMAD-IL-13 was examined in vitro and in vivo. For in vitro experiment, CCK-8 kit was used to determine the IC50 of MMAD-IL-3 in OC cell lines. For in vivo experiment, Cal-27 xenograft models were used to determine the antitumor effect of MMAD-IL-13. Apoptosis was measured in Cal-27 cells by Western blotting assay. Immunity response was detected in Cal-27 xenograft models 7 days after intratumoral injection with MMAD-IL-13. The potency of MMAD and MMAD-IL-13 was compared in Cal-27 peripheral blood mononuclear cells (PBMCs) models. RESULTS: MMAD-IL-13 was successfully constructed; the harvested virus could be replicated and they overexpressed human IL-13 in Cal-27 cells. Compared with MMAD, MMAD-IL-13 showed enhanced antitumor effect in vitro by inducing apoptosis and reducing percentage of M2 macrophages in tumor environment in vivo. MMAD-IL-13 also showed potent antitumor effect in Cal-27, SCC-4, and Tca8113 cells in vitro and in Cal-27 xenograft models in vivo. However, MMAD-IL13 did not harm normal human oral epithelial cells in vitro and exhibited no effect on body weight in Cal-27 xenograft models. In Cal-27 PBMC models, MMAD-IL-13 showed stronger antitumor effect than MMAD. CONCLUSION: A new oncolytic adenovirus carrying the human IL-13 gene was constructed. This virus effectively led to remission of tumor development and death of OC cells in vivo and in vitro, showing its potential as a clinical cancer therapy.

Biocompatibility and antibacterial properties of pure titanium surfaces coated with yttrium-doped hydroxyapatite.

The repair and regeneration of peri-implant soft tissues is essential for the long-term clinical successes of implants. Surface modification of implants using coatings is an effective approach to improving their biocompatibility and antibacterial properties. In this study, we introduced a novel implant material by modifying the surface of pure titanium (Ti). Hydroxyapatite (HA) and HA doped with different concentrations of yttrium (Y) via layer by layer self-assembly method (LBL). Surface morphology, roughness, element composition, and hydrophilicity indicated that the coatings could improve the biological activity without significantly increasing surface roughness. We also examined its biocompatibility with human gingival fibroblasts (HGFs) (proliferation, adhesion, morphology, spreading, and Type I collagen (Col-1) synthesis) and antibacterial properties against Streptococcus mutans. The modified coatings significantly enhanced the proliferative, adhesive, and spreading capacities of HGFs compared to the pure Ti substrate. Col-1 secretion by HGFs positively increased with increased Y doping and duration of cell cultivation, suggesting that the coatings may promote connective tissue formation. Furthermore, increased Y doping significantly reduced the number of adherent S. mutans. Thus, Y-doped HA coatings improve biocompatibility and antibacterial properties, suggesting they have high potential for improving the repair, regeneration, and integration of soft tissues on the surfaces of Ti implants.