Study on the role of MYCN in retinoblastoma by inhibiting p53 and activating wnt/ßcatenin/Fra-1 signaling pathway by reducing DKK3.

Retinoblastoma (RB) is a pediatric malignancy, typically diagnosed at birth or during early childhood. The pathogenesis of RB is marked by the amplification of the Basic Helix-Loop-Helix (BHLH) Transcription Factor MYCN, which serves as a transcriptional regulator capable of binding to Dickkopf 3 (DKK3). However, the precise role of DKK3 in the malignant progression of RB cells caused by MYCN remains elusive. In the present study, the expression of MYCN was either overexpressed or interfered in RB cells. Subsequently, the expression level of DKK3 was assessed through quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation was evaluated using the Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine staining, while cell cycle progression and apoptosis were analyzed by flow cytometry and western blot analysis, respectively. Additionally, the expression of proteins involved in the Wnt/ß-catenin/Fra-1/p53 signaling pathway was evaluated via western blot analysis. To gain further insights, Wnt agonists and the P53 inhibitor PFT-α were introduced into exploration. The current investigation revealed a negative correlation between the expression levels of MYCN and DKK3 in RB cells. Additionally, DKK3 overexpression inhibited cell proliferation, promoted cell apoptosis, and arrested cell cycle in RB cells with high expression of MYCN. Moreover, enhanced DKK3 expression inhibited proliferation, promoted cell cycle arrest and apoptosis of RB cells by modulating the wnt/ßcatenin/Fra-1/p53 signaling pathway. Furthermore, in vivo experiments revealed that overexpression of DKK3 inhibits the growth of RB tumors. Collectively, our findings elucidate that MYCN stimulates the Wnt/ß-catenin/Fra-1 pathway by suppressing DKK3 expression, ultimately suppressing p53 activity and contributing to malignant progression of RB.

Power system fault diagnosis with quantum computing and efficient gate decomposition.

Power system fault diagnosis is crucial for identifying the location and causes of faults and providing decision-making support for power dispatchers. However, most classical methods suffer from significant time-consuming, memory overhead, and computational complexity issues as the scale of the power system concerned increases. With rapid development of quantum computing technology, the combinatorial optimization method based on quantum computing has shown certain advantages in computational time over existing methods. Given this background, this paper proposes a quantum computing based power system fault diagnosis method with the quantum approximate optimization algorithm. The proposed method reformulates the fault diagnosis problem as a Hamiltonian by using Ising model, which completely preserves the coupling relationship between faulty components and various operations of protective relays and circuit breakers. Additionally, to enhance problem-solving efficiency under current equipment limitations, the symmetric equivalent decomposition method of multi-z-rotation gate is utilized. Furthermore, the small probability characteristics of power system events is utilized to reduce the number of qubits. Simulation results based on the test system show that the proposed methods can achieve the same optimal results with a faster speed compared with the classical higher-order solver provided by D-Wave.

NECA alleviates inflammatory responses in diabetic retinopathy through dendritic cell toll-like receptor signaling pathway.

Introduction: This study examined the impact of 5'-(N- ethylcarboxamido)adenosine (NECA) in the peripheral blood of healthy individuals, those with diabetes mellitus, diabetic retinopathy (DR), and C57BL/6 mice, both in vivo and in vitro. Methods: Enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to evaluate the effects of NECA on dendritic cells (DCs) and mouse bone marrow-derived dendritic cells (BMDCs) and the effects of NECA-treated DCs on Treg and Th17 cells. The effect of NECA on the Toll-like receptor (TLR) pathway in DCs was evaluated using polymerase chain reaction (PCR) and western blotting (WB). Results: FCM and ELISA showed that NECA inhibited the expression of surface markers of DCs and BMDCs, increased anti-inflammatory cytokines and decreased proinflammatory cytokines. PCR and WB showed that NCEA decreased mRNA transcription and protein expression in the TLR-4-MyD88-NF-kß pathway in DCs and BMDCs. The DR severity in streptozocin (STZ) induced diabetic mice was alleviated. NECA-treated DCs and BMDCs were co-cultivated with CD4+T cells, resulting in modulation of Treg and Th17 differentiation, along with cytokine secretion alterations. Conclusion: NECA could impair DCs' ability to present antigens and mitigate the inflammatory response, thereby alleviating the severity of DR.

Schottky Junction Enhanced Photosynthesis of Hydrogen Peroxide by Ultrathin Porous Carbon Nitride Supported Ni Nanoparticles.

Artificial photosynthesis for high-value hydrogen peroxide (H2O2) through a two-electron reduction reaction is a green and sustainable strategy. However, the development of highly active H2O2 photocatalysts is impeded by severe carrier recombination, ineffective active sites, and low surface reaction efficiency. We developed a dual optimization strategy to load dense Ni nanoparticles onto ultrathin porous graphitic carbon nitride (Ni-UPGCN). In the absence and presence of sacrificial agents, Ni-UPGCN achieved H2O2 production rates of 169 and 4116 µmol g-1 h-1 with AQY (apparent quantum efficiency) at 420 nm of 3.14% and 17.71%. Forming a Schottky junction, the surface-modified Ni nanoparticles broaden the light absorption boundary and facilitate charge separation, which act as active sites, promoting O2 adsorption and reducing the formation energy of *OOH (reaction intermediate). This results in a substantial improvement in both H2O2 generation activity and selectivity. The Schottky junction of dual modulation strategy provides novel insights into the advancement of highly effective photocatalytic agents for the photosynthesis of H2O2.

Extension domain of amyloid processor protein inhibits amyloidogenic cleavage and balances neural activity in a traumatic brain injury mouse model.

BACKGROUND: Mechanisms underlying cognitive dysfunction following traumatic brain injury (TBI) partially due to abnormal amyloid processor protein (APP) cleavage and neural hyperactivity. Binding of the extension domain of APP (ExD17) to the GABAbR1 receptor results in reduced neural activity, which might play a role in the mechanisms of cognitive dysfunction caused by TBI. METHODS: Stretch-induced injury was utilized to establish a cell injury model in HT22 cells. The TBI model was created by striking the exposed brain tissue with a free-falling weight. Topical or intraperitoneal administration of ExD17 was performed. Cell viability was assessed through a cell counting kit-8 assay, while intracellular Ca2+ was measured using Fluo-4. Western blotting was used to investigate the expression of APP amyloidogenic cleavage proteins, GABAbR1, phospholipase C (PLC), PLCB3, and synaptic proteins. ELISA was performed to analyze the levels of Aß42. Seizures were assessed using electroencephalography (EEG). Behaviors were evaluated through the novel object recognition test, open field test, elevated plus maze test, and nest-building test. RESULTS: ExD17 improved cell viability and reduced intracellular calcium in the cell injury model. The treatment also suppressed the increased expression of APP amyloidogenic cleavage proteins and Aß42 in both cell injury and TBI models. ExD17 treatment reversed the abnormal expression of GABAbR1, GRIA2, p-PLCG1/PLCG1 ratio, and p-PLCB3/PLCB3 ratio. In addition, ExD17 treatment reduced neural activity, seizure events, and their duration in TBI. Intraperitoneal injection of ExD17 improved behavioral outcomes in the TBI mouse model. CONCLUSIONS: ExD17 treatment results in a reduction of amyloidogenic APP cleavage and neuroexcitotoxicity, ultimately leading to an improvement in the behavioral deficits observed in TBI mice.

Developing Ni single-atom sites in carbon nitride for efficient photocatalytic H2O2 production.

Photocatalytic two-electron oxygen reduction to produce high-value hydrogen peroxide (H2O2) is gaining popularity as a promising avenue of research. However, structural evolution mechanisms of catalytically active sites in the entire photosynthetic H2O2 system remains unclear and seriously hinders the development of highly-active and stable H2O2 photocatalysts. Herein, we report a high-loading Ni single-atom photocatalyst for efficient H2O2 synthesis in pure water, achieving an apparent quantum yield of 10.9% at 420 nm and a solar-to-chemical conversion efficiency of 0.82%. Importantly, using in situ synchrotron X-ray absorption spectroscopy and Raman spectroscopy we directly observe that initial Ni-N3 sites dynamically transform into high-valent O1-Ni-N2 sites after O2 adsorption and further evolve to form a key *OOH intermediate before finally forming HOO-Ni-N2. Theoretical calculations and experiments further reveal that the evolution of the active sites structure reduces the formation energy barrier of *OOH and suppresses the O=O bond dissociation, leading to improved H2O2 production activity and selectivity.

Visual impairment and blindness caused by retinal diseases: A nationwide register-based study.

Background: Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care planning and allocation of medical resources. The purpose of this study is to describe the proportion of visual impairment and blindness caused by major retinal diseases in China. Methods: A nationwide register-based study of vitreoretinal disease covering all 31 provinces (51 treating centres) of mainland China. A total of 28 320 adults diagnosed with retinal diseases were included. Participants underwent standardised ocular examinations, which included best-corrected visual acuity (BCVA), dilated-fundus assessments, and optical coherence tomography. Visual impairment and blindness are defined using BCVA according to the World Health Organization (WHO) (visual impairment: <20/63-≥20/400; blindness: <20/400) and the United States (visual impairment: <20/40-≥20/200; blindness: <20/200) definitions. The risk factors of vision loss were explored by logistic regression analyses. Results: Based on the WHO definitions, the proportions for unilateral visual impairment and blindness were 46% and 18%, respectively, whereas those for bilateral visual impairment and blindness were 31% and 3.3%, respectively. Diabetic retinopathy (DR) accounts for the largest proportion of patients with visual impairment (unilateral visual impairment: 32%, bilateral visual impairment: 60%) and blindness (unilateral blindness: 35%; bilateral blindness: 64%). Other retinal diseases that contributed significantly to vision loss included age-related macular degeneration, myopic maculopathy, retinal vein occlusion, and rhegmatogenous retinal detachment and other macular diseases. Women (bilateral vision loss: P = 0.011), aged patients (unilateral vision loss: 45-64 years: P < 0.001, ≥65 years: P < 0.001; bilateral vision loss: 45-64 years: P = 0.003, ≥65 years: P < 0.001 (reference: 18-44 years)) and those from Midwest China (unilateral and bilateral vision loss: both P < 0.001) were more likely to suffer from vision loss. Conclusions: Retinal disorders cause substantial visual burden among patients with retinal diseases in China. DR, the predominant retinal disease, is accountable for the most prevalent visual disabilities. Better control of diabetes and scaled-up screenings are warranted to prevent DR. Specific attention should be paid to women, aged patients, and less developed regions.

5α-Hydroxycostic acid inhibits choroidal neovascularization in rats through a dual signalling pathway mediated by VEGF and angiopoietin 2.

BACKGROUND: 5α-Hydroxycostic acid is a eudemane sesquiterpene that is isolated from the natural plant, Laggera alata. It exerts anti-inflammatory and anti-angiogenic effects on human breast cancer cells, but its role and underlying mechanism in choroidal neovascularization (CNV) are still unclear. We conducted a study to verify that 5α-Hydroxycostic acid can inhibit the formation and leakage of CNV, and describe the possible dual pathway by which it exerts its inhibitory effects in this process. METHODS: An in vitro model of choroidal neovascularization was established using VEGF164, while a rat model of choroidal neovascularization was established using a 532 nm laser. In both models, the effects of 5α-Hydroxycostic acid in vivo and in vitro were evaluated to determine its inhibitory effect on abnormal cell proliferation, migration and tubule formation, as well as its effect on pathological changes in choroidal tissues and the area of neovascularization leakage in rats. The levels of components in the VEGF/VEGFR and Ang2/Tie2 signaling pathways were measured in tissues and cells. RESULTS: In vitro experiments have shown that 5α-Hydroxycostic acid can inhibit abnormal cell proliferation, migration and angiogenesis. Additionally, 5α-Hydroxycostic acid enhances cell adhesion by inhibiting the phosphorylation pathways of VEGFR2 and Tie2. In vivo experiments demonstrated that 5α-Hydroxycostic acid has a positive therapeutic effect on choroidal neovascularization in rats. It can effectively reduce vascular leakage, consistent with the results of the cell experiments. CONCLUSION: 5α-Hydroxycostic acid can inhibit choroidal neovascularization by interfering with the VEGF- and Ang2/Tie2-related pathways, and it may be a good candidate drug for treating CNV.

Comorbidity and drug resistance of smear-positive pulmonary tuberculosis patients in the yi autonomous prefecture of China: a cross-sectional study.

BACKGROUND: Tuberculosis (TB) has a high morbidity and mortality rate, and its prevention and treatment focus is on impoverished areas. The Liangshan Yi Autonomous Prefecture is a typical impoverished area in western China with insufficient medical resources and high HIV positivity. However, there have been few reports of TB and drug resistance in this area. METHODS: We collected the demographic and clinical data of inpatients with sputum smear positive TB between 2015 and 2021 in an infectious disease hospital in the Liangshan Yi Autonomous Prefecture. Descriptive analyses were used for the epidemiological data. The chi-square test was used to compare categorical variables between the drug-resistant and drug-susceptible groups, and binary logistic regression was used to analyse meaningful variables. RESULTS: We included 2263 patients, 79.9% of whom were Yi patients. The proportions of HIV (14.4%) and smoking (37.3%) were higher than previously reported. The incidence of extrapulmonary TB (28.5%) was high, and the infection site was different from that reported previously. When drug resistance gene detection was introduced, the proportion of drug-resistant patients became 10.9%. Patients aged 15-44 years (OR 1.817; 95% CI 1.162-2.840; P < 0.01) and 45-59 years (OR 2.175; 95% CI 1.335-3.543; P < 0.01) had significantly higher incidences of drug resistance than children and the elderly. Patients with a cough of ≥ 2 weeks had a significantly higher chance of drug resistance than those with < 2 weeks or no cough symptoms (OR 2.069; 95% CI 1.234-3.469; P < 0.01). Alcoholism (OR 1.741; 95% CI 1.107-2.736; P < 0.05) and high bacterial counts on sputum acid-fast smears (OR 1.846; 95% CI 1.115-3.058; P < 0.05) were significant in the univariate analysis. CONCLUSIONS: Sputum smear-positive TB predominated in Yi men (15-44 years) with high smoking, alcoholism, and HIV rates. Extrapulmonary TB, especially abdominal TB, prevailed. Recent drug resistance testing revealed higher rates in 15-59 age group and ≥ 2 weeks cough duration. Alcohol abuse and high sputum AFB counts correlated with drug resistance. Strengthen screening and supervision to curb TB transmission and drug-resistant cases in the region.

Efficacy and Safety of Dupilumab in Older Patients (Aged 80 Years and Above) with Atopic Dermatitis: A Prospective Study.

BACKGROUND: Atopic dermatitis presents unique challenges in the older population owing to age-related changes in skin barrier function and immune regulation. However, there is limited evidence on the efficacy and safety of dupilumab, an anti-interleukin-4Rα monoclonal antibody, in patients with atopic dermatitis aged 80 years and above. OBJECTIVE: We aimed to assess the clinical efficacy and safety of dupilumab treatment in patients with atopic dermatitis aged 80 years and above. METHODS: Twenty-eight older patients received dupilumab and were evaluated based on several clinical parameters, including the Eczema Area and Severity Index (EASI), Numeric Rating Scale (NRS), Dermatology Life Quality Index (DELI), and AD Control Tool (ACT). Safety assessments and monitoring of concomitant medication use were conducted. RESULTS: Twenty-six patients completed 16 weeks of treatment, 13 completed 28 weeks, and two completed more than 36 weeks. Dupilumab treatment resulted in a significant improvement in atopic dermatitis symptoms after 16 weeks as demonstrated by reduced EASI, NRS, DLQI, and ADCT scores. Dupilumab had no significant impact on underlying diseases or medication use. No common adverse reactions, such as conjunctivitis and erythema of the face and neck, were identified. Among the 26 patients receiving dupilumab treatment during the COVID-19 pandemic, 17 remained uninfected or experienced milder COVID-19 symptoms than experienced in the general population. CONCLUSIONS: Dupilumab treatment showed significant efficacy in improving atopic dermatitis symptoms in patients aged 80 years and above with a high level of safety. Larger long-term clinical trials are needed to validate these results and provide further evidence for the use of dupilumab in older patients with atopic dermatitis.

Targeted long-term noninvasive treatment of choroidal neovascularization by biodegradable nanoparticles.

Choroidal neovascularization (CNV) is the main cause of vision loss in patients with wet age-related macular degeneration (AMD). Currently, treatment of these conditions requires repeated intravitreal injections, which may lead to complications such as infection and hemorrhage. So, we have developed a noninvasive method for treating CNV with nanoparticles, namely, Angiopoietin1-anti CD105-PLGA nanoparticles (AAP NPs), which targets the CNV to enhance drug accumulation at the site. These nanoparticles, with PLGA as a carrier, can slowly release encapsulated Angiopoietin 1 (Ang 1) and target the choroidal neovascularization marker CD105 to enhance drug accumulation, increases vascular endothelial cadherin (VE-cadherin) expression between vascular endothelial cells, effectively reduce neovascularization leakage and inhibit Angiopoietin 2(Ang 2) secretion by endothelial cells. In a rat model of laser-induced CNV, intravenous injection of AAP NPs exerted a good therapeutic effect in reducing CNV leakage and area. In short, these synthetic AAP NPs provide an effective alternative treatment for AMD and meet the urgent need for noninvasive treatment in neovascular ophthalmopathy. STATEMENT OF SIGNIFICANCE: This work describes the synthesis, injection-mediated delivery, in vitro and in vivo efficacy of targeted nanoparticles with encapsulated Ang1; via these nanoparticles, the drug can be targeted to choroidal neovascularization lesions for continuous treatment. The release of Ang1 can effectively reduce neovascularization leakage, maintain vascular stability, and inhibit Ang2 secretion and inflammation. This study provides a new approach for the treatment of wet age-related macular degeneration.

Dupilumab and the potential risk of eosinophilic pneumonia: case report, literature review, and FAERS database analysis.

Eosinophilic pneumonia (EP) is a rare but noteworthy adverse effect linked to dupilumab, an interleukin-4 (IL-4) and IL-13 inhibitor used in the managing atopic diseases. The underlying mechanisms, potential predisposing factors, clinical characteristics, and optimal management strategies for dupilumab-induced EP remain unclear. We report a 71-year-old patient who developed acute EP after the first 600-mg dose of dupilumab. Eosinophils (EOSs) were also transiently increased (up to 1,600 cells/µl). After the acute EP was effectively treated with glucocorticoids, dupilumab treatment was continued. Rash, itching, and immunoglobulin E levels continued to decrease in the patient, and no further pulmonary adverse events occurred. We combined this case with a literature review of nine articles and analyzed data from 93 cases reported in the FDA Adverse Event Reporting System (FAERS) database of patients developing EP after dupilumab use. Our findings imply that dupilumab may induce EP, particularly in individuals over 45 years old, those with a history of respiratory diseases, and those who have previously used inhaled or systemic steroids. Vigilance is required, especially when there is a persistent elevation in peripheral blood EOSs during treatment. Although steroid treatment can effectively manage EP, more data are needed to determine the safety of resuming dupilumab treatment after controlling pneumonia.

The temperature-sensitive receptors TRPV4 and TRPM8 have important roles in the pruritus of rosacea.

BACKGROUND: Certain sensations are the secondary phenotypes of rosacea and affect patients' quality of life. Transient receptor potential (TRP) channels may be involved in its occurrence. However, there is a lack of research independently discussing itch in rosacea. OBJECTIVES: Our study aimed to investigate risk factors for pruritus in rosacea patients and to discover the molecular mechanism of pruritus. METHODS: A binary logistic regression model was used to identify significant variables affecting pruritus in 782 rosacea patients. The LL-37 was injected intradermally into the face of mice to establish the animal model. qRT-PCR, immunohistochemistry and immunofluorescence were used to analyse the expression differences in pruritus-related molecules in mouse skin and the corresponding trigeminal ganglion (TG) between pruritus and nonpruritus groups. RESULTS: The incidence of pruritus in rosacea was 42.46%, and the incidence of other symptoms increased with pruritus. Temperature effects were prominently related to the itch sensation of rosacea. Intradermal injection of LL-37 not only caused rosacea-like facial lesions but also induced a behavioural pattern indicative of pruritus. Increased expression of the temperature-sensitive receptors TRPV4 and TRPM8 was found in pruritic mouse skin and TG and human skin samples. CONCLUSIONS: In rosacea patients, pruritus occurs frequently along with burning, flushing and sensitivity, most likely due to changes in temperature. The temperature-sensitive receptors TRPV4 and TRPM8 are both involved in the mechanism of pruritus in rosacea.

Development and validation of a predictive risk model based on retinal geometry for an early assessment of diabetic retinopathy.

Aims: This study aimed to develop and validate a risk nomogram prediction model based on the retinal geometry of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate its clinical application value. Methods: In this study, we collected the clinical data of 410 patients with T2DM in the Second Affiliated Hospital of Chongqing Medical University between October 2020 and March 2022. Firstly, the patients were randomly divided into a development cohort and a validation cohort in a ratio of 7:3. Then, the modeling factors were selected using the least absolute shrinkage and selection operator (LASSO). Subsequently, a nomogram prediction model was built with these identified risk factors. Two other models were constructed with only retinal vascular traits or only clinical traits to confirm the performance advantage of this nomogram model. Finally, the model performances were assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA). Results: Five predictive variables for DR among patients with T2DM were selected by LASSO regression from 33 variables, including fractal dimension, arterial tortuosity, venular caliber, duration of diabetes mellitus (DM), and insulin dosage (P< 0.05). A predictive nomogram model based on these selected clinical and retinal vascular factors presented good discrimination with an AUC of 0.909 in the training cohort and 0.876 in the validation cohort. By comparing the models, the retinal vascular parameters were proven to have a predictive value and could improve diagnostic sensitivity and specificity when combined with clinical characteristics. The calibration curve displayed high consistency between predicted and actual probability in both training and validation cohorts. The DCA demonstrated that this nomogram model led to net benefits in a wide range of threshold probability and could be adapted for clinical decision-making. Conclusion: This study presented a predictive nomogram that might facilitate the risk stratification and early detection of DR among patients with T2DM.

Synthesis of Silver Nanoparticles-Modified Graphitic Carbon Nitride Nanosheets for Highly Efficient Photocatalytic Hydrogen Peroxide Evolution.

As a promising metal-free photocatalyst, graphitic carbon nitride (g-C3N4) is still limited by insufficient visible light absorption and rapid recombination of photogenerated carriers, resulting in low photocatalytic activity. Here, we adjusted the microstructure of the pristine bulk-g-C3N4 (PCN) and further loaded silver (Ag) nanoparticles. Abundant Ag nanoparticles were grown on the thin-layer g-C3N4 nanosheets (CNNS), and the Ag nanoparticles decorated g-C3N4 nanosheets (Ag@CNNS) were successfully synthesized. The thin-layer nanosheet-like structure was not only beneficial for the loading of Ag nanoparticles but also for the adsorption and activation of reactants via exposing more active sites. Moreover, the surface plasmon resonance (SPR) effect induced by Ag nanoparticles enhanced the absorption of visible light by narrowing the band gap of the substrate. Meanwhile, the composite band structure effectively promoted the separation and transfer of carriers. Benefiting from these merits, the Ag@CNNS reached a superior hydrogen peroxide (H2O2) yield of 120.53 µmol/g/h under visible light irradiation in pure water (about 8.0 times higher than that of PCN), significantly surpassing most previous reports. The design method of manipulating the microstructure of the catalyst combined with the modification of metal nanoparticles provides a new idea for the rational development and application of efficient photocatalysts.

Dual-Target Multifunctional Superparamagnetic Cationic Nanoliposomes for Multimodal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy of Retinoblastoma.

Background: With high malignancy, retinoblastoma (RB) commonly occurs in infants and has incredible difficulty with the early diagnosis. In recent years, the integrated theranostics of multimodal imaging-guided therapy has shown promising potential for oncotherapy. Purpose: To prepare folate/magnetic dual-target theranostic nanoparticles integrating with US/PA/MR imaging and the synergistic photothermal treatment (PTT)/photodynamic treatment (PDT) for the early diagnosis and timely intervention of RB cancer. Methods: Folate/magnetic dual-target cationic nanoliposomes (CN) encapsulating indocyanine green (ICG) and perfluorohexane(PFH)(FA-CN-PFH-ICG-Fe3O4, FCNPIFE) were synthesized and characterized. Then we evaluated their targeting ability, US/PA/MR imaging effects, and the efficacy of synergistic PTT/PDT in vitro and in vivo. Finally, we explored the mechanism of synergistic PTT/PDT in Y79 tumor-bearing mice. Results: FCNPIFEs were stable and uniform in 7 days. They showed excellent in vitro targeting ability with a 95.29% cell uptake rate. The in vitro US/PA/MRI imaging results of FCNPIFEs showed a concentration-dependent manner, and in vitro therapy FCNPIFEs exhibited an enhanced anticancer efficacy against Y79 cells. In vivo analysis confirmed that FCNPIFEs enabled a targeted synergistic PTT/PDT under US/PA/MR imaging guidance in Y79 tumor-bearing mice, achieving almost complete tumor regression. Immunofluorescence results displayed weaker fluorescence intensity compared with other single treatment groups, confirming that PTT/PDT synergistic therapy effect was achieved by down-regulating the expression of HIF-1α and HSP70. Conclusion: FCNPIFEs were verified as promising theranostic nanoliposomes for RB oncotherapy and showed great potential in clinical application.

Ultrasound-targeted cationic microbubble-mediated gene transfection and inhibition of retinal neovascularization.

AIM: To investigate whether ultrasound-targeted cationic microbubbles (CMBs) destruction could deliver endostatin-green fluorescent protein (GFP) plasmids efficiently to the human retinal endothelial cells (HRECs) and inhibit retinal neovascularization in mice. METHODS: CMBs were prepared and the presentation of GFP reporter was confirmed by flow cytometry and laser confocal microscopy. Experiments assessing HRECs migration and vascular formation were performed to evaluate gene therapy's efficiency in vitro. A mouse model of oxygen-induced retinopathy was employed and the expression of Bcl-xl, Bcl-2, vascular endothelial growth factor (VEGF) and endostatin in the retina of mice were determined by Western blotting and quantitative polymerase chain reaction (qPCR). The expression of endostatin-GFP in the retina was examined by laser confocal microscopy at 5, 14, and 28d after treatment. RESULTS: The gene expression of endostatin was the highest in the group of the CMBs. Besides, the inhibition and antiangiogenesis effect of the migration and development of HRECs were improved following treatment with CMBs compared with the other groups in vitro. In vivo, retinal neovascularization was significantly inhibited and the fluorescence intensity of endostatin-GFP in the mouse retina was importantly higher in the group of CMBs than that in other groups. CONCLUSION: The research illustrates ultrasound-targeted CMBs destruction possessed distinct effect on the inhibition of the vascular formation and the development of retinal neovascularization both in vitro and in vivo.

The application prospects of honokiol in dermatology.

Honokiol is one of the natural extracts of Magnolia officinalis. It is a small molecule, lipophilic compound with extensive biological effects. It has been used in the treatment of multisystem diseases, including digestive diseases, endocrine diseases, nervous system diseases, and various tumors. This paper reviews the biological effects of honokiol on the treatment of skin diseases in recent years, including anti-microbial, anti-oxidant, anti-inflammatory, anti-tumor, anti-fibrosis, anti-allergy, photo-protection, and immunomodulation. Most current researches are focused on the effects of anti-melanoma and photo-protection. Therefore, we summarized the specific mechanisms about these two effects. On the other side of treating skin diseases, the advantages of topical drugs cannot be replaced. As a small molecule fat-soluble compound, honokiol is suitable for external use. We reviewed the advantages and disadvantages of the topical mixed cream and various improved methods. These improvements include physical and chemical penetration enhancers, drug carriers, and chemical derivatives. In conclusion, honokiol has a wide range of effects, and its topical preparation provides a safe and effective way for treating skin diseases.

Multimodal imaging and photothermal synergistic immunotherapy of retinoblastoma with tuftsin-loaded carbonized MOF nanoparticles.

Retinoblastoma (Rb) represents 3% of all childhood malignancies and seriously endangers children's lives and quality of life. Early diagnosis and treatment can save children's vision as much as possible. Multifunctional nanoparticles have become a research hotspot in recent years and are expected to realize the integration of early diagnosis and early treatment. Therefore, we report a nanoparticle with dual-mode imaging, photothermal therapy, and immune activation: carbonized MOF nanoparticles (CM NPs) loaded with the immune polypeptide tuftsin (CMT NPs). The dual-mode imaging ability, antitumor effect, and macrophage immunity activation ability of these nanoparticles combined with laser irradiation were studied. The biosafety of CMT NPs was detected. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA) and magnetic resonance (MR) imaging in vivo and in vitro, facilitating diagnosis and efficacy evaluation. The combined effect of CMT NPs and laser irradiation was recorded and verified. Through the accumulation of magnetic field nanoparticles in tumors, the photothermal conversion of nanoparticles under laser irradiation led directly to tumor apoptosis/necrosis, and the release of tuftsin induced macrophage M1-type activation, resulting in antitumor immune effects. Enhanced PA/MR imaging CMT NPs have great potential in dual-mode image-guided laser/immune cotherapy. The nanoparticles have high biosafety and have potential in cancer treatment.

Long non-coding RNA UCA1 promotes retinoblastoma progression by modulating the miR-124/c-myc axis.

The long non-coding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1), belongs to cancer-related lncRNAs implicated in various carcinomas, including colorectal and gastric cancers. Nonetheless, the role and underlying mechanisms of UCA1 in retinoblastoma are still unclear. This study found that UCA1 expression in retinoblastoma tissues and cells was dramatically upregulated relative to that of healthy controls. Functionally, UCA1 knockdown could suppress retinoblastoma cells' proliferation, migration and invasion, and facilitate their apoptosis. Knockdown of UCA1 also retarded the growth of xenograft tumors in vivo. Mechanistically, UCA1 promoted c-myc expression through sponging miR-124. miR-124 inhibition or c-myc overexpression partially reversed the effects of UCA1 knockdown on retinoblastoma cells. Overall, lncRNA UCA1 may exert an oncogenic effect on retinoblastoma progression through the miR-124/c-myc axis, which might serve as a promising retinoblastoma treatment target.