Characterization and regulation of 2D-3D convertible lipid membrane transformation.

Micro-nanomaterials that can adopt different structures are powerful tools in the fields of biological and medical sciences. We previously developed a lipid membrane that can convert between 2D nanosheet and 3D vesicle forms using cationic copolymer polyallylamine-graft-polyethylene glycol and the anionic peptide E5. The properties of the membrane during conversion have been characterized only by confocal laser scan microscopy. Furthermore, due to the 2D symmetry of the lipid nanosheet, the random folding of the lipid bilayer into either the original or the reverse orientation occurs during sheet-to-vesicle conversion, compromising the structural consistency of the membrane. In this study, flow cytometry was applied to track the conversion of more than 5000 lipid membranes from 3D vesicles to 2D nanosheets and back to 3D vesicles, difficult with microscopies. The lipid nanosheets exhibited more side scattering intensity than 3D vesicles, presumably due to free fluctuation and spin of the sheets in the suspension. Furthermore, by immobilizing bovine serum albumin as one of the representative proteins on the outer leaflet of giant unilamellar vesicles at a relatively low coverage, complete restoration of lipid membranes to the original 3D orientation was obtained after sheet-to-vesicle conversion. This convertible membrane system should be applicable in a wide range of fields. Our findings also provide experimental evidence for future theoretical studies on membrane behavior.

Short-term effects of nitrogen dioxide on inpatient acute myocardial infarction in Lanzhou, China.

Nitrogen dioxide (NO2) represents a deleterious effect on acute myocardial infarction (AMI), but few relevant studies have been conducted in China. We aim to evaluate the acute effects of NO2 exposure on hospitalization for AMI in Lanzhou, China. In this study, we applied a distributional lag nonlinear model (DLNM) to assess the association between NO2 exposure and AMI hospitalization. We explored the sensitivity of various groups through stratified analysis by gender, age, and season. The daily average concentration of NO2 is 47.50 ± 17.38 µg/m3. We observed a significant exposure-response relationship between NO2 concentration and AMI hospitalization. The single pollutant model analysis shows that NO2 is positively correlated with AMI hospitalization at lag1, lag01, lag02, and lag03. The greatest lag effect estimate occurs at lag01, where a 10 µg/m3 increase in NO2 concentrations is significantly associated with a relative risk (RR) of hospitalization due to AMI of 1.027 [95% confidence interval (CI): 1.013, 1.042]. The results of the stratified analysis by gender, age, and season indicate that males, those aged ≥65 years, and the cold season are more sensitive to the deleterious effects caused by NO2 exposure. Short-term exposure to NO2 can enhance the risk of AMI hospitalization in urban Lanzhou.Implications: Exposure to particulate matter can lead to an increased incidence of AMI. Our study once again shows that NO2 exposure increases the risk of AMI hospital admission. AMI is a common and expensive fatal condition. Reducing NO2 exposure will benefit cardiovascular health and save on healthcare costs.

Short-term association between air pollution and daily genitourinary disorder admissions in Lanzhou, China.

The aim of this study was to determine the relationship between short-term exposure to ambient air pollution and the number of daily hospital admissions for genitourinary disorders in Lanzhou. Hospital admission data and air pollutants, including PM2.5, PM10, SO2, NO2, O38h and CO, were obtained from the period 2013 to 2020. A generalized additive model (GAM) combined with distribution lag nonlinear model (DLNM) based on quasi-Poisson distribution was used by the controlling for trends, weather, weekdays and holidays. Short-term exposure to PM2.5, NO2 and CO increased the risk of genitourinary disorder admissions with RR of 1.0096 (95% CI 1.0002-1.0190), 1.0255 (95% CI 1.0123-1.0389) and 1.0686 (95% CI 1.0083-1.1326), respectively. PM10, O38h and SO2 have no significant effect on genitourinary disorders. PM2.5 and NO2 are more strongly correlated in female and ≥ 65 years patients. CO is more strongly correlated in male and < 65 years patients. PM2.5, NO2 and CO are risk factors for genitourinary morbidity, and public health interventions should be strengthened to protect vulnerable populations.

Short-term effects of air pollution on hospitalization of children with acute upper respiratory infections: A time series analysis in Lanzhou, China.

OBJECTIVE: Short-term air pollution exposure is correlated with childhood acute upper respiratory infections (AURI) hospitalizations. We surveyed the relationship between AURI hospitalizations and air pollutant concentrations in children aged 0-14 years from 1 January 2014 to 31 December 2019 in Lanzhou City. METHODS: We collected both data on air pollutant concentrations and children's AURI hospitalizations during the study period. Distributional lagged nonlinear models were adopted to assess the short-term effects of air pollutants on children's AURI hospitalizations. We also performed subgroup analysis and sensitivity analysis. RESULTS: A total of 15,881 children were hospitalized for AURI during the study period. The results showed that for each 10 µg/m3 increase in PM2.5 , SO2 , and NO2 concentrations at lag0-6, the relative risk (RR) values for children hospitalized for AURI were RR = 1.0247 (95% CI: 1.0092,1.0405), RR = 1.0928 (95% CI: 1.0562, 1.1308), and RR = 1.0715 (95% CI: 1.0495, 1.0940), respectively. PM10 was significantly associated with AURI hospitalization in children only at lag0, RR = 1.0028 (95% CI: 1.0000, 1.0056). CONCLUSION: Short-term exposures to PM2.5 , PM10 , SO2 , and NO2 all increase the risk of AURI hospitalization in children variously.

Association between air temperature and risk of hospitalization for genitourinary disorders: An environmental epidemiological study in Lanzhou, China.

OBJECTIVES: The aim of this study was to investigate the relationship between air temperature and the risk of hospitalization for genitourinary disorders. METHODS: Distributed lag non-linear models (DLNM) were used to estimate the association between air temperature and the risk of hospitalization for genitourinary disorders, with subgroup analysis by gender and age to identify the susceptible population of temperature-sensitive genitourinary system diseases. RESULTS: Low mean temperature (MT) (RR = 2.001, 95% CI: 1.856~2.159), high MT (RR = 2.884, 95% CI: 2.621~3.173) and low diurnal temperature range (DTR) (RR = 1.619, 95% CI: 1.508~1.737) were all associated with the increased risk of hospitalization for genitourinary disorders in the total population analysis, and the high MT effect was stronger than the low MT effect. Subgroup analysis found that high MT was more strongly correlated in male (RR = 2.998, 95% CI: 2.623~3.427) and those <65 years (RR = 3.003, 95% CI: 2.670~3.344), and low DTR was more strongly correlated in female (RR = 1.669, 95% CI: 1.510~1.846) and those <65 years (RR = 1.643, 95% CI: 1.518~1.780). CONCLUSIONS: The effect of high MT on the risk of hospitalization for genitourinary disorders is more significant than that of low MT. DTR was independently associated with the risk of hospitalization for genitourinary disorders.

Short-term effects of air pollution on hospitalization for acute lower respiratory infections in children: a time-series analysis study from Lanzhou, China.

BACKGROUND: Short-term exposure to air pollution is associated with acute lower respiratory infections (ALRI) in children. We investigated the relationship between hospitalization for ALRI in children and air pollutant concentrations from January 1, 2014 to December 31, 2020 in Lanzhou City. METHODS: We collected data on air pollutant concentrations and children's hospitalization data during the study period. A time series regression analysis was used to assess the short-term effects of air pollutants on ALRI in children, and subgroup analyses and sensitivity analyses were performed. RESULTS: A total of 51,206 children with ALRI were studied, including 40,126 cases of pneumonia and 11,080 cases of bronchiolitis. The results of the study revealed that PM2.5, PM10, SO2 and NO2 were significantly associated with hospitalization for ALRI in children aged 0-14 years. For each 10 µg/m3 increase in air pollutant concentration in lag0-7, the relative risk of ALRI hospitalization in children due to PM2.5, PM10, SO2 and NO2 increased by 1.089 (95%CI:1.075, 1.103), 1.018 (95%CI:1.014, 1.021), 1.186 (95%CI:1.154. 1.219) and 1.149 (95%CI:1.130, 1.168), respectively. CONCLUSIONS: PM2.5, PM10, SO2 and NO2 short-term exposures were positively associated with ALRI, pneumonia and bronchiolitis hospitalizations in Lanzhou, China. Local governments should make efforts to improve urban ambient air quality conditions to reduce hospitalization rates for childhood respiratory diseases.

2D-3D-Convertible, pH-Responsive Lipid Nanosheets.

2D nanosheets self-assembled with amphiphilic molecules are promising tools for biomedical applications; yet, there are challenges to form and stabilize these nanosheets under complex physiological conditions. Here, the development of lipid nanosheets with high structural stability that can be reversibly converted to cell-sized vesicles by changes in pH within the physiological range robustly, are described. The system is controlled by the membrane disruptive peptide E5 and a cationic copolymer anchored on lipid membranes. It is envisioned that nanosheets formed using the dual anchoring peptide/cationic copolymer system can be employed in dynamic lipidic nanodevices, such as the vesosomes described here, drug delivery systems, and artificial cells.

Time Series Analysis of the Acute Effect of Atmospheric Fine Particulate Matter on Hospitalization for Heart Failure in Lanzhou, China.

OBJECTIVE: The purpose of this study was to investigate the correlation between environmental PM 2.5 and heart failure (HF) hospitalization in Lanzhou, China. METHOD: The correlation between atmospheric PM 2.5 and HF hospitalization was evaluated using a distributed lag nonlinear model. RESULT: During the study period, 16,122 HF patients were hospitalized. The average concentration of PM 2.5 is 45.24 µg/m 3 . PM 2.5 was positively correlated with HF hospitalization with single lag (lag0) and cumulative lag (lag01, lag02, lag03). The maximum lag effect is estimated to occur in lag03, and with the PM 2.5 concentration increasing by 10 µg/m 3 , HF hospitalization risk increased by 1.023 (95% confidence interval, 1.006-1.039). The risk of hospitalization for HF in the male group, the age group 65 years or older, and the cold season was statistically significant and more positively correlated. CONCLUSION: PM 2.5 exposure increases the risk of HF admission in Lanzhou.

Acute effects of air pollution on type II diabetes mellitus hospitalization in Lanzhou, China.

Studies on the effects of short-term air pollution exposure on hospitalization for type 2 diabetes mellitus (T2DM) are relatively scarce in developing regions. The time-series study was used to explore the acute effects of air pollutants on hospitalization for T2DM in Lanzhou, China. A distribution lag nonlinear model based on the generalized additive model was used to analyze the hospitalization impact of air pollution on T2DM. Stratified analysis by gender, age and season was obtained. The results were indicated as the relative risk (RR) with 95% confidence interval (CI) for single-day lags (from lag0 to lag7) and cumulative lag days (from lag0-1 to lag0-7). The strongest correlations (RR, 95% CI) of hospitalization for T2DM and PM10 (RR = 1.003, 95% CI 1.000, 1.001) at lag7 and NO2 (RR = 1.022, 95% CI 1.000, 1.045) at lag0-4 were observed for an increase of 10 µg/m3 in the concentrations and CO (RR = 1.091, 95% CI 1.017, 1.170) at lag0-4 for an increase of 1 mg/m3 in the concentration. The hazardous impacts of PM10, NO2 and CO were greater for females, people aged ≥ 65 years and in the cold season. However, there was no significant association between PM2.5, SO2 and O38h and the number of hospitalizations for T2DM.

[Effect of Diurnal Temperature Range on the Number of Residents Hospitalized Due to Stroke in Lanzhou].

Objective To analyze the relationship between diurnal temperature range (DTR) and the hospitalization of stroke in Lanzhou,so as to provide a scientific basis for probing into the mechanism of temperature changes in inducing stroke and formulating comprehensive prevention and control measures for stroke by relevant departments.Methods The information of the patients hospitalized due to stroke in Lanzhou during January 2014 to December 2019 and the air pollutants (PM10,SO2,and NO2) and meteorological data in the same period were collected for statistical analysis.Spearman rank correlation analysis was performed to analyze the correlations between air pollutants and meteorological factors.The distributed lag nonlinear model was adopted to fit the relationship between DTR and the number of stroke inpatients,and three-dimensional diagrams and the correlation diagrams of DTR against stroke risk were established.The stratified analysis was performed according to gender and age (< 65 years and ≥65 years).Results From 2014 to 2019,a total of 92 812 stroke patients were hospitalized in Lanzhou,with a male-to-female ratio of 1.35:1.There was a nonlinear relationship between DTR and the number of stroke inpatients in Lanzhou,which presented a lag effect.The low DTR at 4.5 ℃ had the largest RR value of 1.25 (95%CI=1.16-1.35) for stroke inpatients at a cumulative lag of 18 d.The effect of high DTR (18.5 ℃) on the hospitalization of stroke patients peaked at a cumulative lag of 21 d,with an RR value of 1.09 (95%CI=1.01-1.18).The stratified analysis results suggested that low levels of DTR had greater effects on the hospitalization of male stroke patients and stroke patients <65 years.Conclusions Short-term exposure to different levels of DTR had an impact on the number of stroke inpatients,and low levels of DTR had a slightly greater impact on stroke inpatients than high levels of DTR.Importance should be attached to the protection of males and people aged <65 years at low levels of DTR.

In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion.

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2123-144 peptide, which showed "super-affinity" to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ.

Bioactive Sr2+/Fe3+co-substituted hydroxyapatite in cryogenically 3D printed porous scaffolds for bone tissue engineering.

Developing multi-doped bioceramics that possess biological multifunctionality is becoming increasingly attractive and promising for bone tissue engineering. In this view innovative Sr2+/Fe3+co-substituted nano-hydroxyapatite with gradient doping concentrations fixed at 10 mol% has been deliberately designed previously. Herein, to evaluate their therapeutic potentials for bone healing, novel gradient SrFeHA/PCL scaffolds are fabricated by extrusion cryogenic 3D printing technology with subsequent lyophilization. The obtained scaffolds exhibit desired 3D interconnected porous structure and rough microsurface, along with appreciable release of bioactive Sr2+/Fe3+from SrFeHA components. These favorable physicochemical properties render printed scaffolds realizing effective biological applications bothin vitroandin vivo, particularly the moderate co-substituted Sr7.5Fe2.5HA and Sr5Fe5HA groups exhibit remarkably enhanced bioactivity that not only promotes the functions of MC3T3 osteoblasts and HUVECs directly, but also energetically manipulates favorable macrophages activation to concurrently facilitate osteogenesis/angiogenesis. Moreover,in vivosubcutaneous implantation and cranial defects repair outcomes further confirm their superior capacity to dictate immune reaction, implants vascularization andin situbone regeneration, mainly dependent on the synergetic effects of released Sr2+/Fe3+. Accordingly, for the first time, present study highlights the great potential of Sr7.5Fe2.5HA and Sr5Fe5HA for ameliorating bone regeneration process by coupling of immunomodulation with enhanced angio- and osteogenesis and hence may provide a new promising alternative for future bone tissue engineering.

Growth of Porous Ag@AuCu Trimetal Nanoplates Assisted by Self-Assembly.

The self-assembly process of metal nanoparticles has aroused wide attention due to its low cost and simplicity. However, most of the recently reported self-assembly systems only involve two or fewer metals. Herein, we first report a successful synthesis of self-assembled Ag@AuCu trimetal nanoplates in aqueous solution. The building blocks of multibranched AuCu alloy nanocrystals were first synthesized by a chemical reduction method. The growth of Ag onto the AuCu nanocrystals in the presence of hexadecyltrimethylammonium chloride (CTAC) induces a self-assembly process and formation of Ag@AuCu trimetal nanoplates. These nanoplates with an average side length of over 2 µm show a porous morphology and a very clear boundary with the branches of the as-prepared AuCu alloy nanocrystals extending out. The shape and density of the Ag@AuCu trimetal nanoplates can be controlled by changing the reaction time and the concentration of silver nitrate. The as-assembled Ag@AuCu nanoplates are expected to have the potential for wide-ranging applications in surface-enhanced Raman scattering (SERS) and catalysis owing to their unique structures.

Impact of structural features of Sr/Fe co-doped HAp on the osteoblast proliferation and osteogenic differentiation for its application as a bone substitute.

The potential of external ions doped biomaterials has been extensively explored; however, the co-doped biomaterials remain typically unexplored for their biological properties for precise biomedical applications. The current study was aimed to explore the impact of structural features of Sr/Fe co-doped hydroxyapatite (HAp) bionanomaterial on osteoblastic proliferation and osteogenic differentiation for its application as a bone substitute. A 10 mol% isomorphous co-doping of strontium and iron with respect to calcium was carried into HAp in the solid solution. Raman spectroscopy verified the presence of major functional groups of apatite structure together with the carbonate peaks. The Sr/Fe co-doped HAp bionanomaterials showed slightly negative zeta potential (at neutral pH), versatile DLS particle size (140-205 nm), high BET surface area (186 m2/g), and narrow width pore size (13-19 nm). TG/DTA analysis showed low thermal stability of the Sr/Fe co-doped HAp groups. The nanoparticles showed an initial burst release of amoxicillin for 15 h followed by extended-release up to 81 h and demonstrated an excellent antibacterial activity by producing inhibition zones of 17.6 ± 0.3 mm and 19.5 mm ± 0.4 mm for Escherichia coli and Staphylococcus aureus. Live/dead cell staining and MTT assay confirmed the non-toxic nature of Sr/Fe co-doped HAp bionanomaterial towards MC3T3-E1 cells. Further, an improved ALP activity, increased calcium deposition, enhanced RUNX2 expression, and regulated OPN and OCN expression levels suggest in MC3T3-E1 cells demonstrate the maturation of osteoblasts. This study provides the unique advantages of the co-doping approach for the applications Sr/Fe co-doped HAp bionanomaterials as a bone substitute.

Development of Cryogenic Electrohydrodynamic Jet Printing for Fabrication of Fine Scaffolds with Extra Filament Surface Topography.

Electrohydrodynamic jet printing (EJP) is a developing additive manufacture technology that enables the fabrication of fine scaffolds directly from polymer solutions or melt. Timely solidification of the polymer jet is the key factor for the success of EJP process. In conventional solution-based EJP methods, it is usually achieved by rapid solvent evaporation and producing a scaffold with smooth filaments. In current study, by combining solution-based EJP with a cryogenic workbench, a cryogenic electrohydrodynamic jet printing (CEJP) system was developed, in which the polymer jet was frozen and solidified quickly at the freezing temperature rather than solvent evaporation. The feasibility and versatility of the CEJP system were verified by successful printing of scaffolds with different hole shapes and pore sizes. Meanwhile, the resulting scaffolds not only had a resolution in the range of 50-80 µm but also possessed oriented "ridges" and "valleys" on surface of the filaments, which was conductive to cell orientation. Therefore, this work provides a novel method to print fine scaffolds with extra surface topography.

Synthesis and Characterization of Sintered Sr/Fe-Modified Hydroxyapatite Bioceramics for Bone Tissue Engineering Applications.

In the current study, Sr/Fe co-substituted hydroxyapatite (HAp) bioceramics were prepared by the sonication-assisted aqueous chemical precipitation method followed by sintering at 1100 °C for bone tissue regeneration applications. The sintered bioceramics were analyzed for various structural and chemical properties through X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy, which confirmed the phase purity of HAp and Sr/Fe co-substitution into its lattice. The Vickers hardness measurement, high blood compatibility (less than 5% hemolysis), and ability to support the adhesion, proliferation, and osteogenic differentiation of human mesenchymal stem cells suggest the suitability of Sr/Fe:HAp bioceramics for bone implant applications. The physicochemical analysis revealed that the developed Sr/Fe:HAp bioceramics exhibited a polyphasic nature (HAp and ßTCP) with almost identical structural morphology having a particle size less than 0.8 µm. The dielectric constant (ε') and dielectric loss (ε″) were potentially affected by the incorporated foreign ions together with the polyphasic nature of the material. The Sr/Fe co-substituted samples demonstrated extended drug (5-fluorouracil and amoxicillin) release profiles at the pH of physiological medium. The multifunctional properties of the developed HAp bioceramics enabled them to be an auspicious candidate for potential biomedical applications, including targeted drug-delivery applications, heating mediator in hyperthermia, and bone tissue repair implants.

Cryogenic free-form extrusion bioprinting of decellularized small intestinal submucosa for potential applications in skin tissue engineering.

A novel strategy of cryogenic 3D bioprinting assisted by free-from extrusion printing has been developed and applied to printing of a decellularized small intestinal submucosa (dSIS) slurry. The rheological properties, including kinetic viscosity, storage modulus (G'), and loss modulus (G″), were appropriate for free-from extrusion printing of dSIS slurry. Three different groups of scaffolds, including P500, P600, and P700, with filament distances of 500, 600, and 700 µm, respectively were fabricated at a 5 mm s-1 working velocity of the platform (V xy) and 25 kPa air pressure of the dispensing system (P) at -20 °C. The fabricated scaffolds were crosslinked via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) which resulted in a polyporous microstructure. The variations in the filament diameter and pore size were evaluated in the initial frozen state after printing, the lyophilized state, and after immersion in a PBS solution. The Young's modulus of the P500, P600, and P700 scaffolds was measured in wet and dry states for EDC-crosslinked scaffolds. The cell experiment results showed improved cell adhesion, viability, and proliferation both on the surface and within the scaffold, indicating the biocompatibility and suitability of the scaffold for 3D cell models. Further, gene and protein expression of normal skin fibroblasts on dSIS scaffolds demonstrated their ability to promote the production of some extracellular matrix proteins (i.e. collagen I, collagen III, and fibronectin) in vitro. Overall, this study presents a new potential strategy, by combining cryogenic 3D bioprinting with decellularized extracellular matrix materials, to manufacture ideal scaffolds for skin tissue engineering applications.