Preparation of near-infrared photoacoustic imaging and photothermal treatment agent for cancer using a modifiable acid-triggered molecular platform.

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dual-modality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules.

Design and Assessment of Convolutional Neural Network Based Methods for Vitiligo Diagnosis.

Background: Today's machine-learning based dermatologic research has largely focused on pigmented/non-pigmented lesions concerning skin cancers. However, studies on machine-learning-aided diagnosis of depigmented non-melanocytic lesions, which are more difficult to diagnose by unaided eye, are very few. Objective: We aim to assess the performance of deep learning methods for diagnosing vitiligo by deploying Convolutional Neural Networks (CNNs) and comparing their diagnosis accuracy with that of human raters with different levels of experience. Methods: A Chinese in-house dataset (2,876 images) and a world-wide public dataset (1,341 images) containing vitiligo and other depigmented/hypopigmented lesions were constructed. Three CNN models were trained on close-up images in both datasets. The results by the CNNs were compared with those by 14 human raters from four groups: expert raters (>10 years of experience), intermediate raters (5-10 years), dermatology residents, and general practitioners. F1 score, the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity metrics were used to compare the performance of the CNNs with that of the raters. Results: For the in-house dataset, CNNs achieved a comparable F1 score (mean [standard deviation]) with expert raters (0.8864 [0.005] vs. 0.8933 [0.044]) and outperformed intermediate raters (0.7603 [0.029]), dermatology residents (0.6161 [0.068]) and general practitioners (0.4964 [0.139]). For the public dataset, CNNs achieved a higher F1 score (0.9684 [0.005]) compared to the diagnosis of expert raters (0.9221 [0.031]). Conclusion: Properly designed and trained CNNs are able to diagnose vitiligo without the aid of Wood's lamp images and outperform human raters in an experimental setting.

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis.

BACKGROUND: Researches validate that circular RNAs (circRNAs) are dysregulated in a variety of malignancies and play an important role in regulating the malignant phenotype of tumor cells. Nevertheless, the role of circ_0000527 in retinoblastoma (RB) and its regulatory mechanisms remain largely unknown. METHODS: Real-time PCR (RT-PCR) was used to detect circ_0000527 and miR-646 expression in RB tissues and cells. The LRP6 expression in RB cells was detected by Western blot. The relationship between circ_0000527 expression and the clinicopathological parameters of RB patients was analyzed. Cell proliferation, apoptosis and metastasis were monitored by cell counting kit-8 (CCK-8), flow cytometry, and Transwell assay. The dual-luciferase reporter gene assay and RIP assay were employed to verify the targeting relationship between circ_0000527 and miR-646, miR-646 and LRP6. RESULTS: Circ_0000527 was highly expressed in both RB and RB cell lines, whose high expression level and degree of differentiation were significantly correlated with the increase in cTNM staging level. Overexpression of circ_0000527 contributed to RB cell proliferation, migration, invasion and suppressed cell apoptosis, while knocking down circ_0000527 inhibited the above malignant biological behavior. The underlying mechanism suggested that functioning as a endogenous competitive RNA, circ_0000527 directly targeted miR-646 and positively regulated LRP6 expression. CONCLUSION: Circ_0000527 enhances the proliferation and metastasis of RB cells by modulating the miR-646/LRP6 axis.

MCM3AP-AS1/miR-876-5p/WNT5A axis regulates the proliferation of prostate cancer cells.

BACKGROUND: Although the fact that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) is oncogenic in several cancers is well documented, very few researchers investigate its expression and function in prostate cancer. METHODS: Paired prostate cancer samples were selected, and expressions of MCM3AP-AS1, miR-876-5p and WNT5A were examined by qRT-PCR. MCM3AP-AS1 shRNA was transfected into LNCaP and PC-3 cell lines, and then the proliferative activity and apoptosis of cancer cells were detected by CCK-8 assay, EdU assay and flow cytometry analysis, respectively. qRT-PCR and Western blot were used to analyze the changes of miR-876-5p and WNT5A. Luciferase reporter gene assay was employed to determine the regulatory relationship between miR-876-5p and MCM3AP-AS1, miR-876-5p and WNT5A. RESULTS: MCM3AP-AS1 was significantly up-regulated in cancerous tissues of prostate cancer samples, positively correlated with the expression of WNT5A, while negatively related with miR-876-5p. After transfection of MCM3AP-AS1 shRNA into prostate cancer cells, the proliferative ability of cancer cells was signally inhibited, but the apoptosis of cancer cells was increased. MCM3AP-AS1 shRNA could reduce the expression of WNT5A on both mRNA and protein levels. Besides, MCM3AP-AS1 was identified as a sponge of miR-876-5p. WNT5A was validated as a target gene of miR- 876-5p. CONCLUSION: MCM3AP-AS1 is abnormally up-regulated in prostate cancer tissues and can modulate the proliferation and apoptosis of prostate cancer cells, which has the potential to be the "ceRNA" to regulate the expression of WNT5A by targeting miR-876-5p.

Effect of different doses of aspirin on the early osseointegration of titanium alloy implants in rats / 口腔疾病防治

Objective@#To investigate the effects of different doses of aspirin on the early osteointegration of titanium alloy implants in the femurs of rats to provide a reference for dental implantation in patients who take aspirin.@*Methods @#Forty-eight 8-week-old SD male rats were randomly divided into four groups, namely, the control, A, B, and C groups. Forty-eight Ti-6Al-4 V implants with a diameter of 1.4 mm and a length of 6 mm were implanted at the distal end of the right femur. In the A, B, and C groups, dosages of aspirin of 8.93 mg/kg/d, 17.86 mg/kg/d, and 26.79 mg/kg/d were administered by gavage starting on the day of surgery, and the control group was given similar doses of 0.9% saline. HE, Masson, BMP-2 immunohistochemical and TRAP staining evaluations were performed in the 2nd and 4th weeks after surgery.@*Results @#Compared with the results in the control group, the HE staining results showed that the amount of new bone formation was reduced, the trabeculae were more sparse, and the bone marrow cavity was enlarged around the implants in the B and C groups, with the C group showing the most obvious effects. The Masson staining results showed that, compared with that in the control group, the red-stained area in the new bone tissue around the implant was reduced in groups B and C, and the reduction in group C was more significant. However, there was no significant difference between group A and the control group. The BMP-2 staining results indicated that the expression of BMP-2 was not significantly different between the control group and the A group (P > 0.05), and the expression in group C was lower than that in the other groups (P < 0.05). The TRAP staining results demonstrated that the number of positive cells per unit area was decreased sequentially in the control, A, B, and C groups, and the difference was statistically significant (P < 0.05).@*Conclusion@#Aspirin may reduce the formation of bone tissue by inhibiting the activity of osteoblasts and expression in osteoclasts. This effect on osteogenesis was aspirin dose-dependent, and large doses of aspirin can inhibit osteogenesis more significantly.

Oral health status of adult heart transplant recipients in China: A cross-sectional study.

Limited information on the oral health status of adult heart transplant recipients (HTRs) is known, and no available data exist in China. A prerequisite dental evaluation is usually recommended for patients' postorgan transplantation because lifelong immunosuppression may predispose them to infection spread.The aim of this study was to investigate the oral health status of Chinese adult HTRs and determine the association between oral health status and history of heart transplantation (HT).We carried out a cross-sectional study to collect clinical, demographic, socioeconomic, and behavioral data from 81 adult patients who received heart transplantation during 2014 to 2015 in China. Clinical examinations for the presence of dental plaque, dental calculus, dental caries, and periodontal health conditions were performed in a standardized manner by one trained examiner. Sociodemographic, socioeconomic, and behavioral data were self-reported using questionnaires. The prevalence of the above conditions was compared with 63 age- and sex-matched controls. General liner regression analysis was used to assess associations between mean number of decayed, missing, and filled teeth (DMFT) and mean community periodontal index of treatment needs (CPITN) scores and history of heart transplant.Mean age of the HT group was 47.7 ±â€Š12.2 years and men accounted for 69.1% of the sample. The overall median DMFT score in the HT group was 3 (1-5) and caries prevalence was 80.2%, which were similar to the control group (P > .05). The overall mean CPITN score of the HT group was 1.84, which was significantly higher than the control group (1.07, P = .001). Participants in the HT group had worse oral hygiene status and more teeth with probing depth ≥ 4 mm than controls (P = .043). Compared with participants who had no history of heart transplantation, HTRs presented worse periodontal health conditions (mean CPITN score, adjusted odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.12-1.71, P = .003) and similar dental caries status (DMFT score, adjusted OR = 0.58, 95% CI = 0.37-0.91, P = .058).Periodontal health status was positively associated with history of heart transplantation in Chinese adult HTRs.

Oral hygiene and periodontal conditions in the Chinese patients with aortic aneurysm.

BACKGROUND: This cross-sectional study aims to evaluate the association of periodontal conditions and oral hygiene habits in the Chinese patients with an aortic aneurysm (AA). METHODS: A questionnaire and periodontal examinations were carried out in the AA patients and non-AA volunteers recruited from the Center for Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University between August 2011 and June 2016. General information (e.g., height and weight), history of systemic diseases, and oral hygiene habits (e.g., brushing methods and regular oral examinations) were collected in the self-reported survey. Periodontal examinations, such as plaque index and bleeding index, were conducted in all the subjects. The correlation between periodontal indices and AA was further explored using univariate and multivariate analyses. RESULTS: Our analyses revealed that 87.6% of AA patients have chronic periodontitis, which is significantly higher than that of the non-AA patients (55.8%). In addition, AA patients demonstrated more severe periodontal damages with 69.3% moderate and severe periodontitis, compared to only 16.0% in the non-AA group. Using AA as the dependent variable and all the potential risk factors as covariates (e.g., gender, age, smoking, obesity, diabetes, hypertension, and hyperlipidemia), a logistic regression analysis was performed to show clinical attachment loss (CAL) being an independent risk factor for AA (OR = 2.309, 95% CI: 1.623-3.284, p = 0.000). In comparison with the non-AA patients, more AA patients have poor oral hygiene habits and don't have regular dental appointments for supra-gingival cleaning. CONCLUSION: Poor periodontal condition and dental hygiene were identified in the AA patients, suggesting that periodontitis-induced CAL may play a role in AA disease mechanisms.

Dual-Responsive Molecular Probe for Tumor Targeted Imaging and Photodynamic Therapy.

The precision oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging and therapeutics. In this study, a first small-molecule theranostic probe, RhoSSCy is constructed by conjugating 5'-carboxyrhodamines (Rho) and heptamethine cyanine IR765 (Cy) using a reducible disulfide linker and pH tunable amino-group to realize thiols/pH dual sensing. In vitro experiments verify that RhoSSCy is highly sensitive for quantitative analysis and imaging intracellular pH gradient and biothiols. Furthermore, RhoSSCy shows superb tumor targeted dual-modal imaging via near-infrared fluorescence (NIRF) and photoacoustic (PA). Importantly, RhoSSCy also induces strongly reactive oxygen species for tumor photodynamic therapy (PDT) with robust antitumor activity both in vitro and in vivo. Such versatile small-molecule theranostic probe may be promising for tumor targeted imaging and precision therapy.

Decoration of heparin and bovine serum albumin on polysulfone membrane assisted via polydopamine strategy for hemodialysis.

Renal failure brings about abnormality of waste and toxins and deposition in the body. In clinic, the waste and toxins in vitro are eliminated by hemodialysis device with polysulfone (PSF) porous membranes. In the work, decoration of heparin (Hep) and bovine serum albumin (BSA) on PSF membranes would be beneficial to improve the hemocompatibility and reduce the anaphylatoxin formation during hemodialysis. The PSF porous membranes are surface-modified by simply dipping them into dopamine aqueous solution for 8 h. Then, Hep and BSA are immobilized covalently onto the resultant membrane. Attenuated total reflectance Fourier transform infrared spectra (ATR-FTIR) confirms that Hep and BSA are successfully introduced onto the surface of PSF membranes. Scanning electronic microscopy (SEM) and atomic force microscopy (AFM) display the changes of surface morphologies after modification. The result of water contact angle measurement shows that the hydrophilicity of PSF membranes is remarkably improved after coating polydopamine (pDA) and binding Hep and BSA. The experiments of hemocompatibility indicate that Hep and BSA grafted onto membranes suppress the adhesion of platelet and enhance the anticoagulation ability of PSF membranes. Furthermore, the protein adsorption tests reveal that Hep and BSA immobilized onto membranes depress the protein absorption and develop antifouling-protein ability of pristine membrane. This study proves a convenient and simple approach to graft two functional organic polymers which, respectively, play a vital role and then improve the hemocompatibility and biocompatibility of PSF membranes for their biomedical and blood-contacting applications.

Characterization, corrosion behavior, cellular response and in vivo bone tissue compatibility of titanium-niobium alloy with low Young's modulus.

ß-Type titanium alloys with a low elastic modulus are a potential strategy to enhance bone remodeling and to mitigate the concern over the risks of osteanabrosis and bone resorption caused by stress shielding, when used to substitute irreversibly impaired hard tissue. Hence, in this study, a Ti-45Nb alloy with low Young's modulus and high strength was developed, and microstructure, mechanical properties, corrosion behaviors, cytocompatibility and in vivo osteo-compatibility of the alloy were systematically investigated for the first time. The results of mechanical tests showed that Young's modulus of the Ti-Nb alloy was reduced to about 64.3GPa (close to human cortical bone) accompanied with higher tensile strength and hardness compared with those of pure Ti. Importantly, the Ti-Nb alloy exhibited superior corrosion resistance to Ti in different solutions including SBF, MAS and FAAS (MAS containing NaF) media. In addition, the Ti-Nb alloy produced no deleterious effect to L929 and MG-63 cells, and cells performed excellent cell attachment onto Ti-Nb surface, indicating a good in vitro cytocompatibility. In vivo evaluations indicated that Ti-Nb had comparable bone tissue compatibility to Ti determined from micro-CT and histological evaluations. The Ti-Nb alloy with an elasticity close to human bone, thus, could be suitable for orthopedic/dental applications.