Control and surveillance of redox potential for 233Pa dissolution in 2LiF-BeF2 molten salt.

233Pa, the precursor nuclide of 233U in the thorium-uranium conversion is prone to reductive deposition in 2LiF-BeF2 (66 : 34 mol%, FLiBe) molten salt. We explored the adjustment and control of the redox potential of the FLiBe melt to avoid the 233Pa reduction deposition. The experimental data indicated that the deposited 233Pa can be completely dissolved and reentered into the molten salt with the addition of oxidant NiF2, and the distribution and behaviour of uranium, thorium, neptunium, and most fission products did not have any significant change in the NiF2-oxidised FLiBe molten salt, showing the feasibility of this manner to make 233Pa exist stably in the melt. The effects of NiF2-addition on the behaviour of the fission products 95Nb and 131I in the FLiBe molten salt were also investigated. It was found that 131I could be used as a redox indicator to monitor the redox potential of the oxidation-enhanced FLiBe molten salt. All the information drawn from this study could provide significant support for the control and surveillance of the redox potential of the FLiBe molten salt in the upcoming thorium molten salt reactor (TMSR).

A Cancer Nanovaccine Based on an FeAl-Layered Double Hydroxide Framework for Reactive Oxygen Species-Augmented Metalloimmunotherapy.

The complexity and heterogeneity of individual tumors have hindered the efficacy of existing therapeutic cancer vaccines, sparking intensive interest in the development of more effective in situ vaccines. Herein, we introduce a cancer nanovaccine for reactive oxygen species-augmented metalloimmunotherapy in which FeAl-layered double hydroxide (LDH) is used as a delivery vehicle with dihydroartemisinin (DHA) as cargo. The LDH framework is acid-labile and can be degraded in the tumor microenvironment, releasing iron ions, aluminum ions, and DHA. The iron ions contribute to aggravated intratumoral oxidative stress injury by the synergistic Fenton reaction and DHA activation, causing apoptosis, ferroptosis, and immunogenic cell death in cancer cells. The subsequently released tumor-associated antigens with the aluminum adjuvant form a cancer nanovaccine to generate robust and long-term immune responses against cancer recurrence and metastasis. Moreover, Fe ion-enabled T1-weighted magnetic resonance imaging can facilitate real-time tumor therapy monitoring. This cancer-nanovaccine-mediated metalloimmunotherapy strategy has the potential for revolutionizing the precision immunotherapy landscape.

In Vitro Investigation of Gelatin/Polycaprolactone Nanofibers in Modulating Human Gingival Mesenchymal Stromal Cells.

The aesthetic constancy and functional stability of periodontium largely depend on the presence of healthy mucogingival tissue. Soft tissue management is crucial to the success of periodontal surgery. Recently, synthetic substitute materials have been proposed to be used for soft tissue augmentation, but the tissue compatibility of these materials needs to be further investigated. This study aims to assess the in vitro responses of human gingival mesenchymal stromal cells (hG-MSCs) cultured on a Gelatin/Polycaprolactone prototype (GPP) and volume-stable collagen matrix (VSCM). hG-MSCs were cultured onto the GPP, VSCM, or plastic for 3, 7, and 14 days. The proliferation and/or viability were measured by cell counting kit-8 assay and resazurin-based toxicity assay. Cell morphology and adhesion were evaluated by microscopy. The gene expression of collagen type I, alpha1 (COL1A1), α-smooth muscle actin (α-SMA), fibroblast growth factor (FGF-2), vascular endothelial growth factor A (VEGF-A), transforming growth factor beta-1 (TGF-ß1), focal adhesion kinase (FAK), integrin beta-1 (ITG-ß1), and interleukin 8 (IL-8) was investigated by RT-qPCR. The levels of VEGF-A, TGF-ß1, and IL-8 proteins in conditioned media were tested by ELISA. GPP improved both cell proliferation and viability compared to VSCM. The cells grown on GPP exhibited a distinct morphology and attachment performance. COL1A1, α-SMA, VEGF-A, FGF-2, and FAK were positively modulated in hG-MSCs on GPP at different investigation times. GPP increased the gene expression of TGF-ß1 but had no effect on protein production. The level of ITG-ß1 had no significant changes in cells seeded on GPP at 7 days. At 3 days, notable differences in VEGF-A, TGF-ß1, and α-SMA expression levels were observed between cells seeded on GPP and those on VSCM. Meanwhile, GPP showed higher COL1A1 expression compared to VSCM after 14 days, whereas VSCM demonstrated a more significant upregulation in the production of IL-8. Taken together, our data suggest that GPP electrospun nanofibers have great potential as substitutes for soft tissue regeneration in successful periodontal surgery.

Cyclic tensile strain-induced yes-associated protein activity modulates the response of human periodontal ligament mesenchymal stromal cells to tumor necrosis factor-α.

OBJECTIVES: This study aimed to evaluate the role of yes-associated protein (YAP) in the inflammatory processes induced in human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) by cyclic tensile strain (CTS). DESIGN: hPDL-MSCs from five periodontally healthy individuals were stimulated with 12% CTS and/or TNF-α for 24 h. YAP activity was determined by analyzing the YAP nuclear localization and the target genes expression, using immunofluorescence and qPCR, respectively. Verteporfin was used to inhibit the activation of YAP. The gene expression of interleukin (IL)-6, IL-8, vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1 was analyzed by qPCR. RESULTS: In the absence of TNF-α, application of CTS resulted in the nuclear YAP translocation and upregulation of YAP target genes. Verteporfin inhibited the activation of YAP pathway and upregulated the basal expression of IL-6 and IL-8. TNF-α induced the activation of YAP pathway, which was inhibited by verteporfin. However, application of CTS under these conditions diminished TNF-α-induced YAP activation. TNF-α-induced expression of IL-6, VCAM-1, and ICAM-1 was inhibited after the application of CTS. Inhibition of YAP activation by verteporfin diminished TNF-α-induced gene expression of IL-6, VCAM-1, and ICAM-1, and under these conditions no inhibitory effect of CTS on these parameters was observed. CONCLUSIONS: YAP is at least partially involved in the CTS-activated mechanotransduction pathway. The effects of CTS and YAP on the inflammatory responses depend on the inflammatory environment. A better understanding of the inflammatory modulation by mechanical stress may help improve the orthodontic strategies, especially in the patient with periodontitis.

Immunomodulatory Activities of Periodontal Ligament Stem Cells in Orthodontic Forces-Induced Inflammatory Processes: Current Views and Future Perspectives.

Orthodontic tooth movement (OTM) is induced by applying active mechanical forces, causing a local non-infectious inflammatory response in the periodontal ligament (PDL). As a prerequisite for OTM, the inflammation status is associated with increased levels of various cytokines and involves the interaction between immune cells and periodontal ligament stem cells (hPDLSCs). It is well established that hPDLSCs respond to orthodontic forces in several ways, such as by secreting multiple inflammatory factors. Another essential feature of hPDLSCs is their immunomodulatory activities, which are executed through cytokine (e.g., TNF-α and IL-1ß)-induced production of various soluble immunomediators (e.g., indoleamine-2,3-dioxygenase-1, tumor necrosis factor-inducible gene 6 protein, prostaglandin E2) and direct cell-to-cell contact (e.g., programmed cell death ligand 1, programmed cell death ligand 2). It is well known that these immunomodulatory abilities are essential for local periodontal tissue homeostasis and regeneration. So far, only a handful of studies provides first hints that hPDLSCs change immunological processes during OTM via their immunomodulatory activities. These studies demonstrate the pro-inflammatory aspect of immunomodulation by hPDLSCs. However, no studies exist which investigate cytokine and cell-to-cell contact mediated immunomodulatory activities of hPDLSCs. In this perspective article, we will discuss the potential role of the immunomodulatory potential of hPDLSCs in establishing and resolving the OTM-associated non-infectious inflammation and hence its potential impact on periodontal tissue homeostasis during OTM.

Activity Measurement of Iodine Fission Products in 2LiF-BeF2 Salt and Its Application in Redox Potential Surveillance for a Thorium Molten Salt Reactor.

The activities of 131I, 132I, 133I, and 135I produced by neutron-induced fission of 235U in 2LiF-BeF2 (FLiBe) eutectic salt and their dependence on the redox potential were studied. The dependence observed experimentally suggested that the activity ratio for 131I to 132I could be used as an indicator of the redox potential for FLiBe salt. Relying on the selective adsorption of iodine ions on the activated silver probe by ion exchange, a novel method for activity distribution measurement of the iodine isotopes in FLiBe salt was founded. The method is simple, fast, and easy to operate and would be suitable particularly to in situ monitor the redox potential of a thorium molten salt reactor, where the redox potential should keep at a high level to avoid possible safety risk induced by 233Pa deposition in the reactor.

Evaporation behavior of 233Pa in FLiBeZr molten salt.

In thorium molten salt reactors (TMSR), 233Pa is an important intermediate nuclide in the conversion chain of 232Th to 233U, its timely separation from the fuel salt is critically important for both the thorium-uranium (Th-U) fuel cycle and the neutron economy of the reactor. In this study, the evaporation behavior of 233Pa in the FLiBeZr molten salt was investigated during a vacuum distillation process. The separation characteristics between 233Pa and the major components of the fuel (salt and fission products) were evaluated in a calculation of the separation factors between these components. It was found that 233Pa5+ evaporated more readily than 233Pa4+ and the other components of the fuel, the relatively low temperature and medium pressure were much more beneficial to the separation of 233Pa5+ from FLiBeZr salt in the evaporation process, with the maximum value of the separation factor achieving more than 102. Results of distillation experiments also show that increasing the temperature and decreasing the ambient pressure enhances the separation between 233Pa5+ and most of the fission product nuclides due to the 233Pa5+ volatility more strongly depending on the process conditions. These results will be utilized to design a concept for a process for 233Pa separation from the fuel of a molten salt reactor.

Cyclic tensile strain affects the response of human periodontal ligament stromal cells to tumor necrosis factor-α.

OBJECTIVES: Orthodontic treatment in adult patients predisposed to mild or severe periodontal disease is challenging for orthodontists. Orthodontic malpractice or hyper-occlusal forces may aggravate periodontitis-induced destruction of periodontal tissues, but the specific mechanism remains unknown. In the present study, the combined effect of mechanical stress and tumor necrosis factor (TNF)-α on the inflammatory response in human periodontal ligament stromal cells (hPDLSCs) was investigated. MATERIALS AND METHODS: hPDLSCs from 5 healthy donors were treated with TNF-α and/or subjected to cyclic tensile strain (CTS) of 6% or 12% elongation with 0.1 Hz for 6- and 24 h. The gene expression of interleukin (IL)-6, IL-8 and cell adhesion molecules VCAM and ICAM was analyzed by qPCR. The protein levels of IL-6 and IL-8 in conditioned media was measured by ELISA. The surface expression of VCAM-1 and ICAM-1 was quantified by immunostaining followed by flow cytometry analysis. RESULTS: TNF-α-induced IL-6 gene and protein expression was inhibited by CTS, whereas TNF-α-induced IL-8 expression was decreased at mRNA expression level but enhanced at the protein level in a magnitude-dependent manner. CTS downregulated the gene expression of VCAM-1 and ICAM-1 under TNF-α stimulation, but the downregulation of the surface expression analyzed by flow cytometry was observed chiefly for VCAM-1. CONCLUSIONS: Our findings show that mechanical force differentially regulates TNF-α-induced expression of inflammatory mediators and adhesion molecules at the early stage of force application. The effect of cyclic tensile strain is complex and could be either anti-inflammatory or pro-inflammatory depending on the type of pro-inflammatory mediators and force magnitude. CLINICAL RELEVANCE: Orthodontic forces regulate the inflammatory mediators of periodontitis. The underlying mechanism may have significant implications for future strategies of combined periodontal and orthodontic treatment.

China county-based prostate specific antigen screening for prostate cancer and a cost-effective analysis.

BACKGROUND: Prostate cancer is one of the most common malignant tumors worldwide, and is the third-leading cause of cancer death in men. Nearly 70% of new prostate cancer patients in China are locally advanced or widely metastatic with poor prognosis. Providing active treatment to early stage prostate cancer patients can improve the prognosis of prostate cancer patients. Thus, this study sought to evaluate the economy of early prostate specific antigen (PSA) screening for high-risk prostate cancer. METHODS: Based on the data collected from the PSA screening activities of 11 county hospitals from October 2019 to April 2021, this study evaluated a high-risk prostate cancer population who received PSA screening and their quality of life and economy. The screening population comprised males aged over 50 years. All screening patients were tested for PSA. If the PSA value is unnormal, a further diagnosis based on magnetic resonance imagining (MRI) or a transrectal ultrasound-guided prostate biopsy were performed. The decision-tree and Markov model was used to simulate the process of disease development of high-risk prostate cancer patients who underwent screenings and those who did not, and the incremental cost-effectiveness ratio was also evaluated. RESULTS: A total of 13,726 men received a PSA screening. Of these, 1,062 men had abnormal PSA values, and 73 of these were diagnosed with prostate cancer. Of these 73 patients, 40, 21, and 12 had early stage, mid-stage, and late-stage prostate cancer, respectively. Compared to the patients unscreened, the 1,000 patients who received an early PSA screening increased their quality-adjusted life year (QALY) by 15.69 years; however, each QALY had an additional cost of 38,550 yuan, which was lower than the willingness to pay threshold of 72,447 yuan (per capita gross domestic product in 2020). CONCLUSIONS: For high-risk prostate cancer patients, early screenings have a cost-effective advantage over no screenings. Thus, early screening should be vigorously promoted for high-risk prostate cancer patients.

Transient release of radioactive iodine from the fission of UF4 in 2LiF-BeF2 salt.

In this study, the behavior of fission product iodine released from the melting process of a mixture consisting of UF4 irradiated with neutrons and 2LiF-BeF2 (FLiBe) salt was studied. The experiment showed that a large amount of iodine was released immediately during melting and captured by Ni metal foils. The transient release of iodine observed in this experiment is attributed to the redox reaction between the hot atoms of the fission product iodine that cumulated due to long-time irradiation. The effect of the redox status of the molten salt on the transient release of iodine was also investigated. Based on this investigation, it was proposed that the activity ratios of 131I to salt-seeking fission products in the fuel salt, as an effective diagnostic criterion, may be used for the surveillance of the redox potential of fuel salts in a molten salt reactor.

Distribution and behaviour of 233Pa in 2LiF-BeF2 molten salt.

Distribution and behavior of 233Pa, essential in the thorium-uranium nuclear fuel cycle, were studied in 2LiF-BeF2 (66 : 34 mole%, FLiBe) molten salt by γ-ray spectrometry. The experiments showed that 233Pa deposited slightly on the surface of graphite crucible. The addition of Hastelloy and metallic lithium decreased the 233Pa specific activity in the salt by 1 to 2 orders of magnitude rapidly. Analysis indicated that reductive deposition of 233Pa was responsible for the rapid decrease of 233Pa specific activity in the salt. Additional experiments strongly supported the mechanism of reductive deposition of 233Pa induced by Hastelloy and metallic lithium. In view of the large deposition of 233Pa on Hastelloy, the possible influence of fissile nuclide 233U produced from 233Pa decay on the operation of thorium-based molten salt reactor was discussed.

Evaporation behavior of 2LiF-BeF2-ZrF4 molten salt with irradiated nuclear fuel.

The evaporation behaviours of various components were investigated by using a low pressure distillation method in a 2LiF-BeF2-ZrF4 mixture containing irradiated ThF4 and UF4. The experiment showed that BeF2 and ZrF4 were found to mainly condensate at the outer cover, the coolest zone, and their relative volatilities vs. LiF were 9.8 and 32.2, respectively, while for ThF4 and UF4, at four different temperature zones the values were almost constant, at 0.1 and 0.3. The radioactivity of various nuclides was further detected using gamma spectrometer analysis. 137Cs was hardly observed due to long half-time decay. 233Pa was found to co-evaporate with the carrier salt, while 239Np mainly remained in the residual salt as 237U. In different temperature zones, the decontamination factors of rare earth in receiver salts ranged from 10 to 103. On the basis of the investigation, it was proposed that the distribution of various nuclides after distillation, may be helpful to design the feasible condensate system to recover the carried salt in a molten salt reactor.

In vitro biocompatibility of biohybrid polymers membrane evaluated in human gingival fibroblasts.

The biohybrid polymer membrane (BHM) is a new biomaterial designed for the treatment of soft periodontal tissue defects. We aimed to evaluate the in vitro biocompatibility of the membrane in human gingival fibroblasts and the capability to induce cell adhesion, migration, differentiation and improving the production of the extracellular matrix. BHM and Mucograft® collagen matrix (MCM) membranes were punched into 6 mm diameter round discs and placed in 96-well plates. Human primary gingival fibroblasts were seeded on the membranes or tissue culture plastic (TCP) serving as the control. Cell proliferation/viability and morphology were evaluated after 3, 7, and 14 days of culture by cell counting kit (CCK)-8 assay and scanning electron microscopy, respectively. Additionally, the gene expression of transforming growth factor (TGF)-ß1, focal adhesion kinase (FAK), collagen type 1 (Col1), alpha-smooth muscle actin (α-SMA), and fibroblasts growth factor (FGF)-2 was analyzed at 3, 7, and 14 days of culture by qPCR. Cell proliferation on BHM was significantly higher than on MCM and similar to TCP. Gene expression of TGF-ß1, FAK, Col1, and α-SMA were significantly increased on BHM compared to TCP at most investigated time points. However, the gene expression of FGF-2 was significantly decreased on BHM at Day 7 and recovered at Day 14 to the levels similar to TCP. The finding of this study showed that BHM is superior for gingival fibroblasts in terms of adhesion, proliferation, and gene expression, suggesting that this membrane may promote the healing of soft periodontal tissue.

[The inhibition activity of chemical constituents in hawthorn fruit and their synergistic action to HMG-CoA reductase].

OBJECTIVE: To study the hypolipidemic active compounds from Crataegus pinnatifida and mechanism of action of those. METHOD: Guided by the inhibitory activity to HMG-CoA reductase, the active compounds were separated and purified with macroporous resin and silica gel. RESULT: Four active compounds were obtained, which were quercetin, hyperoside, rutin and chlorogenic acid, the sum of their inhibitory rate was 50.01%, and the total inhibitory rate of the mixture of four active compounds matched was 79.48%. CONCLUSION: Quercetin and hyperoside were the principle active components inhibiting HMG-CoA reductase in Hawthorn fruit, and there were synergistic action among them.

[Metabolism, transformation and distribution of Coptis chinensis total alkaloids in rat].

OBJECTIVE: To determine the pharmacokinetics, distribution and mutual transformation of the total alkaloids, jatrorrhizine, coptisine, berberine and palmatine from Coptis chinensis in rats. METHOD: After the total alkaloids and berberine were fed into rats, their contents in plasma, tissues and gastrointestinal tract were determined by reversed-phase HPLC. RESULT: The peak times of berberine in blood were 2.0 h (Cmax 3.7 mg x L(-1)) and 5.0 h Cmax 2.8 mg x L(-1)), respectively. Berberine in rat blood can be transformed into jatrorrhizine. After the rats were fed with the total alkaloids by gavage, the content of berberine was decreased monotonously, while coptisine, palmatine and jatrorrhizine contents were increased gradually in the stomach, it speculated that berberine may be transformed into jatrorrhizine in the stomach. Animal experiments showed that berberine and palmatine were mainly distributed in the lungs of animals, followed by the distribution in the liver, while jatrorrhizine and coptisine was mainly in the liver, then in the lungs. CONCLUSION: Berberine could transform into jatrorrhizine. The mechanism on the appearance of two maximum blood concentration of berberine in blood could be explained with the propulsion of the gastrointestinal tract partly.

Synergetic effect and structure-activity relationship of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors from Crataegus pinnatifida Bge.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors from hawthorn fruit ( Crataegus pinnatifida Bge.) were isolated and evaluated for their antihyperlipidemic effect induced by high-fat diet in mice. After being further purified with silica and polyamide column chromatography from the fractions (fractions A, F, H, and G) with a high inhibitory rate (IR) to HMGR, 24 chromatographic fractions were obtained, including 8 active fractions with a high IR to HMGR. However, the total inhibitory activity of 24 fractions was decreased by about 70%. From eight active fractions, four compounds were obtained by recrystallization and identified as quercetin (a), hyperoside (b), rutin (c), and chlorogenic acid (d), the contents of which in hawthorn EtOH extract were 0.16, 0.32, 1.45, and 0.95%, respectively. The IR values of compounds a-d to HMGR were 6.28, 9.64, 23.53, and 10.56% at the corresponding concentrations of 0.16, 0.32, 1.45, and 0.95 mg/mL, respectively. It was discovered that the IR of a mixture (2.85 mg/mL) matching the original percentage of compounds a-d in hawthorn EtOH extract was up to 79.5%, much higher than that of the single compound and the total IR of these four compounds (50.01%). The in vivo results also revealed that the mixture had a more significant lipid-lowering efficacy than the monomers. Structure-activity relationship revealed the inhibitory activity and lowering-lipid ability of compounds a-c decreased with increasing glycoside numbers. It was concluded that there were synergetic effects on inhibiting HMGR and lowering lipid among compounds a-d, and the weak hydrophilic ability benefits the inhibition to HMGR and lowering-lipid efficacy.