TGF-ß1/Smad3 Signaling Is Required to Alleviate Fluoride-Induced Enamel Hypomineralization.

Excessive fluoride intake during enamel development can affect enamel mineralization, leading to dental fluorosis. However, its potential mechanisms remain largely unexplored. In the present study, we aimed to investigate the impact of fluoride on the expressions of RUNX2 and ALPL during mineralization and the effect of TGF-ß1 administration on fluoride treatment. A dental fluorosis model of newborn mice and an ameloblast cell line ALC were both used in the present study. The mice of the NaF group, including the mothers and newborns, were fed with water containing 150 ppm NaF after delivery to induce dental fluorosis. The mandibular incisors and molars showed significant abrasion in the NaF group. Immunostaining, qRT-PCR, and Western blotting analysis indicated that exposure to fluoride markedly down-regulated RUNX2 and ALPL in mouse ameloblasts and ALCs. Besides, fluoride treatment significantly decreased the mineralization level detected by ALP staining. Furthermore, exogenous TGF-ß1 up-regulated RUNX2 and ALPL and promoted mineralization, while the addition of SIS3 could block such TGF-ß1-induced up-regulation. In TGF-ß1 conditional knockout mice, the immunostaining of RUNX2 and ALPL was weaker compared with wild-type mice. Exposure to fluoride inhibited the expressions of TGF-ß1 and Smad3. Co-treatment of TGF-ß1 and fluoride up-regulated RUNX2 and ALPL compared with the fluoride alone treatment, promoting mineralization. Collectively, our data indicated that TGF-ß1/Smad3 signaling pathway was necessary for the regulatory effects of fluoride on RUNX2 and ALPL, and the fluoride-induced suppression of ameloblast mineralization was mitigated by activating TGF-ß1/Smad3 signaling pathway.

Sucrose-delaying flower color fading associated with delaying anthocyanin accumulation decrease in cut chrysanthemum.

As fresh ornamental crops, vase life and post-harvested quality of cut flowers have attracted much attention. Flower color fading is the prominent defect in red and purple cut flowers, especially in cut chrysanthemum which have a relative long vase life. Here, the effect of sucrose on change in anthocyanin contents during the vase life of 'Dante Purple' cut chrysanthemum was studied. Results showed that 500 mM sucrose as holding solution could significantly delay the decrease in anthocyanin content and maintain the ornamental value for as long as 38 vase days. Moreover, the sucrose also increased the flower diameter, soluble sugar contents and total antioxidant capacity, while decreasing the malondialdehyde contents. Further studies suggested that the transcript levels of anthocyanin biosynthetic genes and transcription factors, CmMYB6 and CmMYB#7, had continuously decreased during the vase life. The changes in these genes expression patterns was retarded by the sucrose treatment, except for CmMYB#7 which is a repressor of anthocyanin biosynthesis gene expression. The decline in relative expression of CmMYB#7 was accelerated by sucrose. These results have supplied clues to study the mechanism whereby sucrose serves as a signal molecule to regulate anthocyanin biosynthesis.

Phenotypic, Physiological, and Molecular Response of Loropetalum chinense var. rubrum under Different Light Quality Treatments Based on Leaf Color Changes.

Light quality is a vital environmental signal used to trigger growth and to develop structural differentiation in plants, and it influences morphological, physiological, and biochemical metabolites. In previous studies, different light qualities were found to regulate the synthesis of anthocyanin. However, the mechanism of the synthesis and accumulation of anthocyanins in leaves in response to light quality remains unclear. In this study, the Loropetalum chinense var. rubrum "Xiangnong Fendai" plant was treated with white light (WL), blue light (BL), ultraviolet-A light (UL), and blue light plus ultraviolet-A light (BL + UL), respectively. Under BL, the leaves were described as increasing in redness from "olive green" to "reddish-brown". The chlorophyll, carotenoid, anthocyanin, and total flavonoid content were significantly higher at 7 d than at 0 d. In addition, BL treatment also significantly increased the accumulation of soluble sugar and soluble protein. In contrast to BL, ultraviolet-A light increased the malondialdehyde (MDA) content and the activities of three antioxidant enzymes in the leaves, including catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), in varying degrees over time. Moreover, we also found that the CRY-like gene, HY5-like gene, BBX-like gene, MYB-like gene, CHS-like gene, DFR-like gene, ANS-like gene, and UFGT-like gene were significantly upregulated. Furthermore, the SOD-like, POD-like, and CAT-like gene expressions related to antioxidase synthesis were found under ultraviolet-A light conditions. In summary, BL is more conducive to reddening the leaves of "Xiangnong Fendai" and will not lead to excessive photooxidation. This provides an effective ecological strategy for light-induced leaf-color changes, thereby promoting the ornamental and economic value of L. chinense var. rubrum.

Point-of-care detection of Neisseria gonorrhoeae based on RPA-CRISPR/Cas12a.

Gonorrhea, caused by Neisseria gonorrhoeae (N. gonorrhoeae), is a persistent global public health threat. The development of low-cost, point-of-care testing is crucial for gonorrhea control, especially in regions with limited medical facilities. In this study, we integrated CRISPR/Cas12a reaction with recombinase polymerase amplification (RPA) to provide a simple and adaptable molecular detection method for N. gonorrhoeae. The RPA-Cas12a-based detection system developed in this study enables rapid detection of N. gonorrhoeae within 1 h without the use of specialized equipment. This method is highly specific for identifying N. gonorrhoeae without cross-reactivity with other prevalent pathogens. Furthermore, in the evaluation of 24 clinical samples, the detection system demonstrates a 100% concordance rate with traditional culture, which is being used clinically as a reference method. Overall, the RPA-Cas12a-based N. gonorrhoeae detection has the advantages of rapidity, portability, low-cost, no special equipment required, and strong operability, and has a high potential for application as a self-testing and point-of-care diagnosis, which is critical for the clinical management of gonorrhea in developing countries lacking medical equipment.

Leaf color change and photosystem function evaluation under heat treatment revealed the stress resistance variation between Loropetalum chinense and L. chinense var. rubrum.

This research mainly focused on the leaf color change and photosystem function differentiation between Loropetalum chinense and its variety L. chinense var. rubrum under heat stress, which were tightly concerned about their ornamental traits and growth. L. chinense 'Xiangnong Xiangyun' (X) and L. chinense var. rubrum 'Xiangnong Fendai' (F) and L. chinense var. rubrum 'Hei Zhenzhu' (H) were chosen to be experimented on to investigate whether leaf color morphology and pigment composition could influence the adaptability of plants to high temperature in order to select foliage plants which posses stable leaf color and better adaptability for hot regions. The plants were cultured in hot environment (40 °C/33 °C, day/night) and normal environment (25 °C/18 °C, day/night). Phenotype and anatomic observation of three cultivars were made and leaf color indices and pigment contents were measured. During the experiment, H and F gradually turned green, total anthocyanins contents significantly decreased in them, however, chlorophyll b contents increased in all three cultivars. In addition, the initial fluorescence (Fo) decreased in X, while increased in H and F. For the maximum fluorescence (Fm) and maximum photochemical efficiency of PSII (Fv/Fm), they only increased in H and decreased in both F and X. The non-photochemical chlorophyll fluorescence quenching (NPQ) also increased in H and decreased in F. For X, it increased at first then gradually decreased. The coefficient of photochemical quenching all increased at first then gradually decreased. Correlation analysis between showed that there was relatively strong connection between anthocyanins, flavonoids and chlorophyll fluorescence parameters, especially NPQ, proved anthocyanins and flavonoids might not only involved in enriching leaf color, but also interfered with the protection of photosystem. Generally speaking, we found higher anthocyanin and flavonoids content level not only dramatically enriched the leaf color of L. chinense var. rubrum cultivars, but also offered more potential antioxidant to keep their normal growth when encountered heat stress.

Effects of low temperature on flowering and the expression of related genes in Loropetalum chinense var. rubrum.

Introduction: Loropetalum chinense var. rubrum blooms 2-3 times a year, among which the autumn flowering period has great potential for exploitation, but the number of flowers in the autumn flowering period is much smaller than that in the spring flowering period. Methods: Using 'Hei Zhenzhu' and 'Xiangnong Xiangyun' as experimental materials, the winter growth environment of L. chinense var. rubrum in Changsha, Hunan Province was simulated by setting a low temperature of 6-10°C in an artificial climate chamber to investigate the effect of winter low temperature on the flowering traits and related gene expression of L. chinense var. rubrum. Results: The results showed that after 45 days of low temperature culture and a subsequent period of 25°C greenhouse culture, flower buds and flowers started to appear on days 24 and 33 of 25°C greenhouse culture for 'Hei Zhenzhu', and flower buds and flowers started to appear on days 21 and 33 of 25°C greenhouse culture for 'Xiangnong Xiangyun'. The absolute growth rate of buds showed a 'Up-Down' pattern during the 7-28 days of low temperature culture; the chlorophyll fluorescence decay rate (Rfd) of both materials showed a 'Down-Up-Down' pattern during this period. The non-photochemical quenching coefficient (NPQ) showed the same trend as Rfd, and the photochemical quenching coefficient (QP) fluctuated above and below 0.05. The expression of AP1 and FT similar genes of L. chinense var. rubrum gradually increased after the beginning of low temperature culture, reaching the highest expression on day 14 and day 28, respectively, and the expression of both in the experimental group was higher than that in the control group. The expressions of FLC, SVP and TFL1 similar genes all decreased gradually with low temperature culture, among which the expressions of FLC similar genes and TFL1 similar genes in the experimental group were extremely significantly lower than those in the control group; in the experimental group, the expressions of GA3 similar genes were all extremely significantly higher than those in the control group, and the expressions all increased with the increase of low temperature culture time. Discussion: We found that the high expression of gibberellin genes may play an important role in the process of low temperature promotion of L. chinense var. rubrum flowering, and in the future, it may be possible to regulate L. chinense var. rubrum flowering by simply spraying exogenous gibberellin instead of the promotion effect of low temperature.

miR-877-5p Inhibits Epithelial Mesenchymal Transformation of Breast Cancer Cells by Targeting FGB.

Purpose: This present study is aimed at exploring the FGB expression in breast cancer (BC) and the role of FGB in BC. Methods: A total of 150 pairs of BC tissues and adjacent tissues from BC surgery patients were collected. RT-qPCR was utilized to evaluate the mRNA expression of FGB and miR-877-5p. Immunohistochemistry was applied to evaluate the protein expression of FGB. Chi-square test was performed to evaluate the relationship between FGB expression level and clinical characteristics. Cell proliferation was examined using CCK-8 assay. Cell invasion was evaluated by transwell assay. Flow cytometry assay was applied to measure cell apoptosis. The protein expression was evaluated by western blot. BALB/C nude mice were used to establish the xenograft tumor model. Results: FGB was more highly expressed in BC tumor, and the expression of FGB was relevant to TNM stage and lymph node metastasis and showed a positive correlation. FGB was proved to be directly regulated via miR-877-5p and enhanced proliferation and invasion of BC cells. FGB downregulation markedly inhibited the tumor growth, including tumor weight and volume. In addition, the Ki-67 expression was observably declined in the sh-FGB group. The protein expression of E-cadherin was markedly raised in the sh-FGB group while the protein expression of N-cadherin and vimentin was markedly declined in the sh-FGB group. Conclusion: In conclusion, miR-877-5p inhibits epithelial mesenchymal transformation, cell proliferation, and invasion of BC cells via downregulating FGB.

Clinical Value of PET.CT Based on Big Data in Colorectal and Peritoneal Metastatic Cancer.

This study focuses on the evaluation of the clinical utility of PET-CT imaging in peritoneal metastases and colorectal cancer. One hundred patients with colorectal peritoneal metastases, who underwent whole-body PET-CT imaging from January 2015 to December 2019, were selected as the experimental group, and 20 healthy individuals were selected as the control group. The SUVmax of the two groups of patients was 5.73 ± 3.84 and 2.70 ± 2.32, respectively, and the difference was statistically significant. The SUVmax AUC was 0.720, and the AUC of serum AFP, CEA, CA125, and CA199 were 0.596, 0.677, 0.642, and 0.696, respectively. Conclusion. 100 patients with colorectal and peritoneal metastatic cancer underwent PET/CT examination. The follow-up or other imaging examinations confirmed the diagnosis. Analysis of the ROC curve in this study found that with a peritoneal SUVmax> 3.2 as the diagnostic index for colorectal peritoneal metastatic cancer, the sum of sensitivity and specificity reached the maximum.

Investigation of atropisomeric transformation of a novel PDE4 inhibitor with tetrahydroisoquinoline-based amide group and its primary study of binding to HSA.

In this study a kinetic and thermodynamic atropisomeric transformation due to a hindered rotation around the tetrahydroisoquinoline-based amide group was investigated. Quantum chemistry calculations were applied to investigate the transformation under the gas phase and several solvents with different polarity, and then evaluated by dynamic HPLC determination. It was found that the transformation rate of constants and the half-life time varied under the influence of solvent polarity and temperature and the energies of rotational barrier were determined ranging between 87 and 92 kJ∙mol-1. A primary binding study with HSA confirmed a rapid interconversion under the simulated physiological conditions. It is therefore suggested to take this atropisomeric compound as a racemic mixture for its future drug development.

Validated quantitative 31P NMR spectroscopy for positional isomeric impurity determination in L-α-glycerylphosphorylcholine (L-α-GPC).

In this study a quantitative 31P nuclear magnetic resonance (31P NMR) spectroscopy method was described to determine positional isomeric impurity ß-GPC in commercial products of L-α-GPC. The samples were dissolved in D2O and trimethyl phosphate (TMP) was selected as an internal calibrant. The measurements were performed on a Bruker 500 MHz spectrometer and the spectra were recorded under optimized process conditions. A good linear relationship was constructed for ß-GPC in the range of 62.7-528.0 µg·mL-1, i.e. 0.03-0.25 % (w/w %, in relative to L-α-GPC) with a correlative coefficient of 0.9996. The limit of quantification (LOQ) and limit of detection (LOD) were 62.7 µg·mL-1 and 20.9 µg·mL-1 with signal to noise of 3 and 10, respectively. The spiked recoveries were in the range of 98.17-99.78 % with the relative standard deviation (RSD %) less than 1.0 %. Therefore, it could be supposed that the 31P NMR was a promising alternative method for sensitive determination of ß-GPC for strict quality control of L-α-GPC.

A retrospective study based on SEER database: not all high-risk factors are equal for stage II colon cancer.

Background: For stage II colon cancer, understanding of high-risk factors (HRFs) that affect the overall survival (OS) and the benefit of chemotherapy is limited. Meanwhile, no stable predictor can effectively predict OS of stage II colon cancer to date. Our study is aimed to identify HRFs associated with OS of stage II colon cancer, to quantify the risk conferred by each HRF, and to evaluate OS benefit gained by chemotherapy. Meanwhile, we attempt to establish a nomogram model for stage II colon cancer. Methods: The clinical variables of patients with stage II colon cancer between 2000 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analysis were performed to filtered out all the HRFs. We calculated the hazard ratios (HR) and evaluated the survival benefit of adjuvant chemotherapy for each HRF and combinations of HRFs. Then, a nomogram model based on all HRFs was established and verified. Results: A total of 39,103 patients with stage II colon cancer were included. T4b tumors were the highest risk for reduced OS [HR =2.821; 95% confidence interval (CI): 1.949-4.082], mucin-producing tumors (HR =2.412; 95% CI: 1.326-4.388) the second, and lymph node (LN) examined less than 12 (HR =2.200; 95% CI: 1.786-2.710) the third. T4 tumors (HR =0.790; 95% CI: 0.542-1.151), poorly/undifferentiated tumors (HR =0.468; 95% CI: 0.237-0.924), and some combinations of HRFs containing either could benefit from adjuvant chemotherapy. Meanwhile, we established an effective nomogram model based on the identified HRFs. Conclusions: The study has identified several novel HRFs for stage II colon cancer. Adjuvant chemotherapy has considerable OS benefit for stage II colon cancers with some specific HRFs, and treatment plans need to be individualized. Type and number of HRFs should be taken into consideration when recommending adjuvant chemotherapy. Our new nomogram model has better predictive ability and stability than the tumor-node-metastasis (TNM) stage system of American Joint Committee on Cancer (AJCC) staging system.

Epidemiology and Antimicrobial Resistance Profiles of the Nocardia Species in China, 2009 to 2021.

The genus Nocardia includes ubiquitous environmental saprophytes and the most frequently isolated aerobic actinomycete human pathogen responsible for localized or disseminated infection. Herein, the species distribution and antimicrobial susceptibility profiles of 441 nonrepetitive Nocardia strains are reported, collected from 21 provinces/cities in China over 13 years (from 2009 to 2021). These isolates were identified to species level by mass spectrometry or targeted DNA sequencing. The susceptibility profiles of Nocardia species for 15 antibiotics were determined by the broth microdilution method. Among these Nocardia isolates, Nocardia farcinica was the most commonly isolated species (39.9%, 176 of 441), followed by Nocardia cyriacigeorgica (28.6%, 126), Nocardia abscessus (6.6%, 29), and Nocardia otitidiscaviarum (5.9%, 26). Furthermore, 361 Nocardia strains (81.9%) were collected from lower respiratory tract (sputum, lung tissue, and bronchoalveolar lavage fluid), 50 (11.3%) were collected from skin and soft tissues, 9 were collected from blood, 9 were collected from eye, 4 were collected from cerebrospinal fluid and brain abscesses, and 2 were collected from pleural effusion. All of the Nocardia strains were susceptible to linezolid, followed by amikacin (99.3%) and trimethoprim-sulfamethoxazole (TMP-SMX) (99.1%). The antibiotic resistance profiles of other antibiotics varied tremendously among different Nocardia species. This demonstrated that accurate species identification and/or antibiotic susceptibility testing should be performed before the usage of these antibiotics. In summary, this is the largest study on the species and antibiotic resistance profiles of the genus Nocardia circulating in China, and our data will contribute to a better understanding of clinical nocardiosis. IMPORTANCE The genus Nocardia has the potential to cause nocardiosis, which might be underrecognized and underdiagnosed. Herein, the demographical features of 441 nonrepetitive nocardiosis cases and species distribution of their Nocardia strains in China, 2009 to 2021, are summarized. The susceptibility profiles for 15 antibiotics against all of the above Nocardia strains were also determined by the broth microdilution method. To date, this is the largest study on the genus Nocardia contributing to nocardiosis in China. Our study will be helpful for understanding the species diversity of Nocardia isolates distributed in China and for decision-making in the context of nocardiosis diagnosis and treatment.

Comparative Transcriptome Analysis Revealed Two Alternative Splicing bHLHs Account for Flower Color Alteration in Chrysanthemum.

'Jimba' is a white chrysanthemum cultivar, which occasionally and spontaneously produces red flower petals under natural cultivation due to cyanidin-based anthocyanin accumulation. To investigate the underlying mechanism of this process, a comparative transcriptome was analyzed between white and turning red 'Jimba'. The structural and regulatory genes of anthocyanin pathway were significantly up-regulated in turning red 'Jimba'. Among them, two alternative splicings, CmbHLH2 and CmbHLH2.1, showed the most significantly up-regulated in turning red tissue. Transiently over-expressed 35S::CmMYB6-CmbHLH2 strongly induced anthocyanin accumulation in 'Jimba' flower petals, while moderate amount of anthocyanin was detected when over-expressed 35S::CmMYB6-CmbHLH2.1. Both CmbHLH2 and CmbHLH2.1 could interact with CmMYB6 to activate CmDFR promoter according to Yeast two-hybrid and dual-luciferase assay. Moreover, CmMYB6-CmbHLH2 but not CmMYB6-CmbHLH2.1 could activate the CmbHLH2 promoter to provide positive feedback loop regulation. Taken together, it suggested that both CmbHLH2 and CmbHLH2.1 involved in regulation flower color alteration in turning red 'Jimba', and CmbHLH2 played a predominant role in this process.

[Effect of electroacupuncture preconditioning on myocyte apoptosis in myocardial ischemia-reperfusion injury rats based on FXR/SHP pathway].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on left-cardiac function, contents of serum TNF-α and IL-6 and expression of myocardial farnesoid X receptor(FXR), small heterodimer partner (SHP), apoptosis inducing factor (AIF) and heat shock proteins 70 (HSP70) genes in myocardial ischemia-reperfusion injury (MIRI) rats, so as to explore its mechanisms underlying improvement of ischemic myocardial injury. METHODS: Forty male Wistar rats were randomly divided into normal control, sham operation, MIRI model and EA pretreatment groups, with 10 rats in each group. Rats of the sham operation group received exposure of the thorax and heart. The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery (LAD). EA (2 Hz/100 Hz and 1 mA) was applied to bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, once a day for 7 days. The left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP)and maximal rates of rise and fall of left ventricular pressure (±dp/dtmax) were detected, the contents of serum TNF-α and IL-6 were detected by using enzyme-linked immunosorbent assay (ELISA), and the expression of FXR, SHP, AIF and HSP70 apoptotic genes in the myocardial tissue were measured by fluorescent quantitative RT-PCR. RESULTS: Compared with the normal control group, the LVEDP, contents of serum TNF-α and IL-6, and the expression levels of myocardial FXR, SHP, AIF and HSP70 mRNAs were significantly increased (P<0.05), while LVSP and ±dp/dtmax levels were obviously decreased in the model group (P<0.05). In comparison with the model group, MIRI-induced increases of LVEDP, TNF-α and IL-6 contents, and FXR, SHP and AIF mRNA expression and decreases of ±dp/dtmax and LVSP levels were reversed(P<0.05), except HSP70 mRNA expression with significantly increased (P<0.05) in the EA pretreatment group. CONCLUSION: EA pretreatment can protect the left ventricular function of the ischemic heart in MIRI rats, which may be related to its effects in reliving peripheral inflammation and regulating the expression levels of apoptosis-related factors FXR, SHP, AIF and HSP70 in the myocardium.

Psychosocial risk factors associated with esophageal cancer in Chinese cohort: A systematic review and meta-analysis.

ABSTRACT: Previous studies were controversial about the role of psychosocial factors in the pathogenesis of esophageal cancer (EC). This study aimed to systematically evaluate the effect size of psychosocial risk factors for EC in Chinese cohort.A literature search was conducted in both English and Chinese databases, and odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled using a random-effects model.28 studies were identified with a total of 6951 EC cases and 7469 controls. The meta-analysis indicated a higher risk of EC among the individuals with psychological trauma (OR: 2.36, 95% CI: 1.71-3.26), Type A behavior (OR: 1.40, 95% CI: 1.17-1.67), depression (OR: 4.00, 95% CI: 2.44-6.55), melancholy (OR: 2.06, 95% CI: 1.32-3.20), always in sulks (OR: 2.49, 95% CI: 1.21-5.12), and irritable personality (OR: 2.13, 95% CI: 1.58-2.89). A lower EC risk was found in the individuals with good interpersonal relationship (OR: 0.35, 95% CI: 0.17-0.70) and outgoing personality (OR: 0.39, 95% CI: 0.19-0.78).This meta-analysis suggested a potential association between psychosocial factors and EC risk. For the individuals with psychosocial risk factors, physicians should pay more attention to EC screening.

Maturation stage enamel defects in Odontogenesis-associated phosphoprotein (Odaph) deficient mice.

BACKGROUND: Mutation in Odontogenesis-associated phosphoprotein (ODAPH) has been reported to cause recessive hypomineralized amelogenesis imperfecta (AI) in human. However, the exact role of ODAPH in amelogenesis is still unknown. RESULTS: ODAPH was identified as a novel constituent of the atypical basal lamina located at the interface between maturation ameloblasts and the enamel by dual immunofluorescence staining of ODAPH and LAMC2. Odaph knockout mice were generated to explore the function of ODAPH in amelogenesis. Odaph-/- mice teeth showed severely attrition and reduced enamel mineralization. Histological analysis showed from transition or early-maturation stage, ameloblasts were rapidly shortened, lost cell polarity, and exhibited cell pathology. Abundant enamel matrix marked by amelogenin was retained. Temporary cyst-like structures were formed between flattened epithelial cells and the enamel from maturation stage to eruption. The integrity of the atypical basal lamina was impaired indicated by the reduced diffuse expression of LAMC2 and AMTN. The expression of maturation stage related genes of Amtn, Klk4, Integrinß6 and Slc24a4 were significantly decreased. CONCLUSIONS: Our results suggested Odaph played vital roles during amelogenesis by maintaining the integrity of the atypical basal lamina in maturation stage, which may contribute to a better understanding of the pathophysiology of human AI.

Intrinsic stability study of L-α-glycerylphosphorylcholine with HPLC method development and validation.

L-α-Glycerylphosphorylcholine (L-α-GPC) is effective to control the symptoms of cognitive decline for the patients of Alzheimer's disease. In this study, an HPLC method coupled with a refractive index detector was developed to evaluate the intrinsic stability of L-α-GPC. The separation of L-α-GPC and its major potential degradation products was achieved on a normal-phase silica gel column (4.6 mm × 250 mm) with the mobile phase consisting of methanol-20 mM ammonium formate aqueous solution (pH 3.2) (65:35, v/v) in isocratic mode. The HPLC method was validated satisfactorily with respect to precision, accuracy and robustness. It is found that L-α-GPC is stable under the photolytic, thermal, oxidative and acidic conditions, while relatively sensitive to alkaline condition due to the specific breakage of phosphate ester bond in the moiety of L-α-GPC. A preliminary kinetics study for the alkaline degradation was conducted with the corresponding kinetics parameters obtained. It can be concluded that the developed HPLC method is capable of distinguishing the stability difference between the two phosphate ester bonds characterized on the L-α-GPC chemical structure.

64Cu-labeled melanin nanoparticles for PET/CT and radionuclide therapy of tumor.

Melanin is a group of natural pigments found in living organism. It can be used for positron emission tomography (PET) imaging due to its inherent chelating ability to radioactive cupric ion. This study was to prepare 64Cu-labeled PEGylated melanin nanoparticles (64Cu-PEG-MNPs), and to further take advantage of the enhanced permeability and retention (EPR) effect of radiolabeled nanoparticles to realize the integration of tumor diagnosis and treatment. We successfully synthesized PEG-MNPs. Saline and serum stability experiments demonstrated good stability. PET/CT showed high tumor aggregation. Moreover, 64Cu-PEG-MNPs resulted in a therapeutic effect on the A431 tumor-bearing mice in the treatment group. The pathological results further confirmed that the therapeutic doses of 64Cu-PEG-MNPs cause pathological changes of tumor tissues while showing minimal toxicity to normal tissues. Our data successfully demonstrate the good imaging performance of 64Cu-PEG-MNPs on A431 tumors and further proved its therapeutic effect, highlighting a great potential in targeted radionuclide therapy.

CircPRMT5 circular RNA promotes proliferation of colorectal cancer through sponging miR-377 to induce E2F3 expression.

CircPRTM5 is associated with cell proliferation and migration in many kinds of malignancies. However, the functions and mechanisms of CircPRTM5 in CRC progression remain unclear. We explored the role and the mechanisms of CircPRTM5 in the development of CRC. Tissues of CRC patients and matched adjacent non-tumour tissues were collected to evaluate the expression of CircPRTM5. The expression of CircPRTM5 in CRC tissues was significantly higher than that in adjacent tissues. The biological functions of CircPRTM5 in CRC were determined by overexpression and down-regulation of CircPRTM5 in CRC cells in vitro and in vivo. The results indicate that knockdown of CircPRTM5 can significantly inhibit the proliferation of CRC cells. The potential mechanisms of CircPRTM5 in CRC development were identified by RT-qPCR, Western blotting analysis and luciferase reporter assay. CircPRTM5 competitively regulates the expression of E2F3 by capillary adsorption of miR-377. CircPRMT5 regulates CRC proliferation by regulating the expression of E2F3, which affects the expression of the cell cycle-associated proteins cyclinD1 and CDK2. CircPRTM5 exerts critical regulatory role in CRC progression by sponging miR-377 to induce E2F3 expression.