Cascade Enzymes Confined in DNA Nanoanchors for Antitumor Therapy.

Cascade-enzyme reaction systems have emerged as promising tools for treating malignant tumors by efficiently converting nutrients into toxic substances. However, the challenges of poor localized retention capacity and utilization of highly active enzymes often result in extratumoral toxicity and reduced therapeutic efficacy. In this study, we introduced a cell membrane-DNA nanoanchor (DNANA) with a spatially confined cascade enzyme for in vivo tumor therapy. The DNANAs are constructed using a polyvalent cholesterol-labeled DNA triangular prism, ensuring high stability in cell membrane attachment. Glucose oxidase (GOx) and horseradish peroxidase (HRP), both modified with streptavidin, are precisely confined to biotin-labeled DNANAs. Upon intratumoral injection, DNANA enzymes efficiently colonize the tumor site through cellular membrane engineering strategies, significantly reducing off-target enzyme leakage and the associated risks of extratumoral toxicity. Furthermore, DNANA enzymes demonstrated effective cancer therapy in vitro and in vivo by depleting glucose and producing highly cytotoxic hydroxyl radicals in the vicinity of tumor cells. This membrane-engineered cascade-enzyme reaction system presents a conceptual approach to tumor treatment.

Source apportionment and wet scavenging ability of atmospheric black carbon during haze in Northeast China.

Seasonal variations in black carbon (BC) pollution characteristics during haze episodes in Benxi city, Liaoning province, were analyzed using year-long measurements of BC, carbon monoxide (CO), and PM2.5. Haze frequencies were recorded to be 0.07, 0.03 and 0.14 in spring, autumn, and winter respectively. Solid fuel contributions increased notably by 7%-8% during haze events compared to clean periods in all seasons. Transitioning from clean to haze periods led to ΔBC/ΔCO increases of 16% in spring and autumn, and 6.8% in winter, while BC/PM2.5 ratios decreased by approximately 33%, 50%, and 24% for spring, autumn, and winter respectively, likely indicating enhanced residential and industrial contributions. These further led to an increase in BC absorption capacities by factors of around 2.2 in spring and autumn, and up to 2.6 in winter during haze periods. Despite liquid fuel sources dominating BC emissions, certain haze episodes (frequency <10%) showed solid fuel contributions of up to 65%, highlighting BC pollution complexity in the region during haze. Backward trajectories analysis revealed local air masses from Liaoning province arrived consistently with the most occurrence of haze events across all seasons, while long-range air masses from Mongolian regions, though with less frequent occurrence during haze periods, significantly elevated BC loadings from solid fuel sources, particularly in spring and autumn due to biomass burning. Despite higher BC wet scavenging rates (WSR) in long-range air masses (0.072 ng m-3 ppbv-1 mm-1) compared to local air masses (0.039 ng m-3 ppbv-1 mm-1), significant BC transport persisted due to limited precipitation along transport pathways, especially during haze periods. These findings provide crucial insights for policymakers, highlighting the need for targeted haze prevention and control strategies focusing on mitigating BC emissions in Northeast China.

Hyaluronic acid-poly(glyceryl)10-stearate nanoemulsion for co-delivery of fish oil and resveratrol: Enhancing bioaccessibility and antioxidant potency.

Hyaluronic acid (HA), an endogenous polysaccharide comprising alternating D-glucuronic acid and N-acetylglucosamine units, is renowned for its high hydrophilicity, biocompatibility, and biodegradability. These attributes have rendered HA invaluable across medical and drug delivery fields. HA can be altered through physical, chemical, or enzymatic methods to improve the properties of the modified substances. In this work, we synthesized a derivative via the esterification of HA with poly(glyceryl)10-stearate (PG10-C18), designated as HA-PG10-C18. This novel derivative was employed to fabricate a nano co-delivery system (HA-PG10-C18@Res-NE) for fish oil and resveratrol (Res), aiming to enhance their stability and bioaccessibility. An exhaustive investigation of HA-PG10-C18@Res-NE revealed that the HA-modified system displayed superior physicochemical stability, notably in withstanding oxidation and neutralizing free radicals. Moreover, in vitro simulated digestion underscored the system's enhanced bioaccessibility of Res and more efficient release of free fatty acids. These outcomes underscore the strategic advantage of HA in modifying PG10-C18 for nanoemulsion formulation. Consequently, HA-PG10-C18 stands as a promising emulsifier for encapsulating lipophilic bioactives in functional foods, nutraceuticals, and pharmaceuticals.

Sirolimus combined with glucocorticoids in the treatment of Kasabach-Merritt phenomenon in a neonate: A case report.

RATIONALE: Kaposiform hemangioendothelioma is an aggressive vascular tumor that is often associated with life-threatening coagulopathies and Kasabach-Merritt phenomenon. Pathologic biopsies can provide a good basis for diagnosis and treatment. Therapy with srolimus combined with glucocorticoids may offer patients a favorable prognosis. PATIENT CONCERNS: A large purplish-red mass on the knee of a child with extremely progressive thrombocytopenia and refractory coagulation abnormalities. Conventional doses of glucocorticoids alone failed to improve coagulation abnormalities and the child developed large cutaneous petechiae and scalp hematomas. DIAGNOSIS: Kaposiform hemangioendothelioma combined with Kasabach-Merritt phenomenon. INTERVENTIONS: The patient received prednisolone 2.0 mg/kg*d for 4 days. Blood products were transfused to ensure vital signs and to complete the pathologic biopsy. Sirolimus combined with prednisolone was given after clarifying the diagnosis of Kaposiform hemangioendothelioma. OUTCOMES: The tumor basically disappeared on examination and the ultrasound showed a subcutaneous hyperechoic mass with normal blood flow. LESSONS: Sirolimus combined with glucocorticoids is effective in controlling Kasabach-Merritt phenomenon and pathologic biopsy is important for definitive diagnosis.

Historical and contemporary management of infantile hemangiomas: a single-center experience.

Objective: This study explores the 22-year evolution of Infantile Hemangiomas (IHs) treatment strategies at a single-center hospital, aiming to establish an individualized IHs management protocol. Methods: Retrospective review of IHs infants 2000-2022 at the Department of Plastic Surgery, Jiangxi Provincial Children's Hospital. Results: In our study of 27,513 IHs cases, 72.2% were female, with the median age at first hospital visit being 25 days. The majority of cases had localized and superficial lesions primarily on the head, face, and neck (67.5%). Ulceration rates fell from 21.1% to 12.6% with the introduction of propranolol. Management strategies have shifted over time, with the proportion of cases undergoing expectant management dropping from 32.9% to 12.4%. Since 2008, 26.1% of patients were treated with oral propranolol, largely replacing corticosteroids. Topical ß-blockers have been used in 12.1% of cases, leading to a reduction in local injection therapy from 20.8% to 13.2%. Laser therapy, introduced in 2016, has been used in 13.8% of cases, while surgical excision has dropped from 25.0% to 8.5% due to alternative treatment options. Combination therapy was used in 8.8% of cases post-2015, indicating a rising trend. Drawing from the evolution of IHs management strategies, an individualized protocol for the management of IHs was successfully established. Conclusion: Treatment for IHs has evolved over recent decades, with less invasive medical interventions increasingly replacing more invasive methods. Furthermore, a personalized treatment protocol established in this study could boost the cure rate of IHs while minimizing potential side effects and complications.

Improved physicochemical stability of fish oil nanoemulsion via a dense interfacial layer formed by hyaluronic acid-poly(glyceryl)10-stearate.

This study aimed to synthesize a novel emulsifier, hyaluronic acid-poly(glyceryl)10-stearate (HA-PG10-C18), and employ it for the fabrication of nanoemulsions incorporating deep-sea fish oil to improve their apparent solubility and physicochemical stability. 1H NMR and FT-IR analyses indicated successful synthesis of HA-PG10-C18. Nanoemulsions of deep-sea fish oil loaded with HA-PG10-C18 (HA-PG10-C18@NE) were successfully fabricated by ultrasonic emulsification. The fixed aqueous layer thickness (FALT) of PG10-C18@NE and HA-PG10-C18@NE was determined and the FALT of both nanoemulsions was similar, while the surface density of HA-PG10-C18@NE (4.92 × 10-12 ng/nm2) is 60 % higher than that of PG10-C18@NE (3.07 × 10-12 ng/nm2). Notably, HA-PG10-C18@NE demonstrated an exceptional physicochemical stability when exposed to various stressed environmental conditions, especially its freeze-thaw stability. Moreover, after simulated in vitro digestion, the HA-PG10-C18@NE exhibited a comparatively greater liberation of free fatty acids (94.0 ± 1.7 %) when compared to the release observed in PG10-C18@NE (85.5 ± 2.2 %).

Safety of oral propranolol for neonates with problematic infantile hemangioma: a retrospective study in an Asian population.

Although the efficacy of propranolol in the treatment of infantile hemangioma (IH) has been well established, clinical data on the safety and tolerability of propranolol in neonates are still lacking. In this work, clinical data of 112 neonates with IH were analyzed retrospectively. All of the patients were evaluated in the hospital at the beginning of the treatment and later in outpatient settings during the treatment. Each time, the following monitoring methods were applied: physical examination, ultrasound echocardiography (UCG), electrocardiography (ECG), blood pressure (BP), heart rate (HR), and basic laboratory tests including blood glucose (BG), liver function, blood potassium, thyroid function. There was a significant reduction in BP and HR at the initiation of treatment. The incidences of bradycardia and hypoglycemia were observed to be increased with the prolong duration of treatment, but not prolonged PR interval. During the course of the therapy, the risk of hyperkalemia and hypothyroidism was reached maximum at the 2 months and 3 months, respectively. Physical growth index including average height, weight and head circumference was not influenced by the treatment. The observed adverse effects were majority mild and only 3 patients needed to rest for 7 days due to severe diarrhea before restarting treatment. This study demonstrated that propranolol is safe and well-tolerated by properly selected young infants with IH. No serious adverse events were observed.

Effects of black carbon aerosol on air quality and vertical meteorological factors in early summer in Beijing.

Black carbon (BC) aerosols have effects on the atmospheric thermal vertical structure due to its radiation absorption characteristics, hereby influencing the boundary layer characteristics and pollutant diffusion. This study focuses on the BC effects under different atmospheric conditions on air quality and vertical meteorological conditions. Four days flight observation combined with surface wind profiler radar data were used to investigate the vertical profiles of BC and wind speed over Beijing urban area in early summer. The vertical profiles of BC concentration and wind speed in the boundary layer had a negative correlation, both having abrupt changes near the boundary layer height under stagnant weather conditions. The chemical transport model showed the increase of BC under stagnant conditions could cause aggravation of the stability of the boundary layer, thereby increasing the accumulation of pollutants. In particular, BC leads to the changes in the temperature profile, which will modify relative humidity and indirectly lead to the changes in the vertical profile of aerosol optical properties. However, if the early accumulation of BC was absent under more turbulent conditions, the effects of BC on air quality and meteorological conditions were limited.

Evolution of Aerosol Optical Properties from Wood Smoke in Real Atmosphere Influenced by Burning Phase and Solar Radiation.

Emissions of light-absorbing black carbon (BC) and organic aerosol (OA) from biomass burning are presented as complex mixtures, which introduce challenges in modeling their absorbing properties. In this study, we chose typical residential wood burning emission and used a novel designed chamber to investigate the early stage evolution of plumes from different burning phases under real ambient conditions. The detailed mixing state between BC and OA was evaluated, on the basis of which optical modeling was performed to achieve a closure of aerosol-absorbing properties. Intensive secondary OA (SOA) formation was observed under solar radiation. OA from flaming conditions showed a higher absorptivity than from smoldering conditions, as OA is mostly internally and externally mixed with BC, respectively. For flaming (smoldering), the imaginary refractive index of OA (kOA) was initially at 0.03 ± 0.01 (0.001) and 0.15 ± 0.02 (0.05 ± 0.02) at λ = 781 and 405 nm, respectively, with a half-decay time of 2-3 h in light but a <40% decrease under dark within 5 h. The production of less-absorbing SOA in the first 1-2 h and possible subsequent photobleaching of chromophores contributed to the decrease of kOA. The enhanced abundance but decreased absorptivity of coatings on BC resulted in a relatively maintainable absorptivity of BC-containing particles during evolution.

Estimating radiative impacts of black carbon associated with mixing state in the lower atmosphere over the northern North China Plain.

Black carbon (BC) exerts important radiative effects over regions with intensive emissions. This study presents in-situ aircraft measurements of BC vertical profiles including mass loading, size distribution and mixing state, spanning a range of pollution levels in both warm and cold seasons over Beijing. The development of planetary boundary layer (PBL) influenced the properties of pollutants at low levels, and regional transport from the southwest elevated the pollution at higher altitudes. Thicker coatings of BC were associated with higher pollution in the PBL, where interactions between BC and other substances intensively took place. Considering the mixing state of BC, the absorption efficiency could be potentially increased by up to 86% and 60% in the PBL and lower free troposphere, respectively. Including a column-integrated absorption enhancement, the in-situ constrained absorption aerosol optical depth at wavelength 870 nm (AAOD870) improved the agreement with AERONET by 28%, but the in-situ measurement remained 19% lower. A radiative transfer model finds a BC heating rate of 0.1-0.3 K/d and 0.5-3.1 K/d for less and more polluted environments respectively, and the BC coating effect could positively introduce a +0.1-4.2 Wm-2 radiative forcing. The presence of aerosol layer enhanced the positive vertical gradient of heating rate by redistributing the actinic flux. In particular, this gradient was further enhanced by introducing thickly-coated BC at higher level during the regional transport events, which may promote the temperature inversion and further depress the PBL development on polluted days.

Internalized gold nanoparticles do not affect the osteogenesis and apoptosis of MG63 osteoblast-like cells: a quantitative, in vitro study.

The long-term toxicity effects of gold nanoparticles (GNPs) on the proliferation and differentiation of a progenitor cell line, MG63 osteoblast-like cells, was investigated. These cells were treated for 20 hours with two media that contained 10 nm GNPs at concentrations of 1 ppm and 10 ppm. The mitosis of the GNP-treated MG63 was observed after at least 21 hours using dark-field and fluorescence microscopy. The TEM, LSCM and dark-field hyperspectral images indicated that the late endosomes in cells that contained aggregated GNPs were caused by vesicle fusion. Subsequently, after 21 days of being cultured in fresh medium, the specific nodule-like phenotypes and bone-associated gene expression of the treated MG63 cells exhibited the same behaviors as those of the control group. Statistically, after 21 days, the viability of the treated cells was identical to that of the untreated ones. During the cell death program analysis, the apoptosis and necrosis percentages of cells treated for 8 or fewer days were also observed to exhibit no significant difference with those of the untreated cells. In summary, our experiments show that the long-term toxicity of GNPs on the osteogenetic differentiation of MG63 is low. In addition, because of their low toxicity and non-biodegradability, GNPs can potentially be used as biomarkers for the long-term optical observation of the differentiation of progenitor or stem cells based on their plasmonic light-scattering properties.