ROS-Responsive Bola-Lipid Nanoparticles as a Codelivery System for Gene/Photodynamic Combination Therapy.

The nonviral delivery systems that combine genes with photosensitizers for multimodal tumor gene/photodynamic therapy (PDT) have attracted much attention. In this study, a series of ROS-sensitive cationic bola-lipids were applied for the gene/photosensitizer codelivery. Zn-DPA was introduced as a cationic headgroup to enhance DNA binding, while the hydrophobic linking chains may facilitate the formation of lipid nanoparticles (LNP) and the encapsulation of photosensitizer Ce6. The length of the hydrophobic chain played an important role in the gene transfection process, and 14-TDZn containing the longest chains showed better DNA condensation, gene transfection, and cellular uptake. 14-TDZn LNPs could well load photosensitizer Ce6 to form 14-TDC without a loss of gene delivery efficiency. 14-TDC was used for codelivery of p53 and Ce6 to achieve enhanced therapeutic effects on the tumor cell proliferation inhibition and apoptosis. Results showed that the codelivery system was more effective in the inhibition of tumor cell proliferation than individual p53 or Ce6 monotherapy. Mechanism studies showed that the production of ROS after Ce6 irradiation could increase the accumulation of p53 protein in tumor cells, thereby promoting caspase-3 activation and inducing apoptosis, indicating some synergistic effect. These results demonstrated that 14-TDC may serve as a promising nanocarrier for gene/PDT combination therapy.

Cobalt doped Prussian blue modified hollow polydopamine for enhanced antibacterial therapy.

Give the emergence of drug resistance in bacteria resulting from antibiotic misuse, there is an urgent need for research and application of novel antibacterial approaches. In recent years, nanoparticles (NPs) have garnered significant attention due to their potential to disrupt bacteria cellular structure through loading drugs and special mechanisms, thus rendering them inactive. In this study, the surface of hollow polydopamine (HPDA) NPs was utilized for the growth of Prussian blue (PB), resulting in the formation of HPDA-PB NPs. Incorporation of Co element during the preparation process led to partial doping of PB with Co2+ions. The performance test results demonstrated that the HPDA-PB NPs exhibited superior photothermal conversion efficiency and peroxidase-like activity compared to PB NPs. HPDA-PB NPs have the ability to catalyze the formation of hydroxyl radicals from H2O2in a weakly acidic environment. Due to the tiny PB particles on the surface and the presence of Co2+doping, they have strong broad-spectrum antibacterial properties. Bothin vitroandin vivoevaluations confirm their efficacy against various bacterial strains, particularlyStaphylococcus aureus, and their potential to promote wound healing, making them a promising candidate for advanced wound care and antimicrobial applications.

Activatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone Metastasis.

Bone metastases are secondary malignant tumors that commonly occur after the spread of advanced cancer cells. We herein report the activatable semiconducting polymer nanoinducers (ASPNFP) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPNFP are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles into singlet oxygen (1O2)-responsive nanocarriers. ASPNFP generate 1O2 under ultrasound (US) irradiation via a sonodynamic effect to destroy the stability of 1O2-responsive nanocarriers, allowing US-triggered releases of SPNP and Fe3O4 nanoparticles. SPNP decompose polyamines in tumor cells to produce acrolein and hydrogen peroxide (H2O2), in which H2O2 promotes Fenton reaction mediated by Fe3O4 nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (•OH). The generated acrolein, 1O2, and •OH can simultaneously amplify the oxidative damage. ASPNFP thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.

Assessment of bidirectional relationships between systemic lupus erythematosus and anxiety disorder: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies have demonstrated that there was a significant correlation between systemic lupus erythematosus (SLE) and anxiety disorder, but the causal relationship between them is not so clearly established. This study aims to reveal the potential causal link between SLE and anxiety disorder. METHODS: Summary statistical data of SLE and anxiety disorder were from two large-scale genome-wide association studies (GWAS) of European ancestry, followed by a bidirectional two-sample Mendelian randomization (MR) analysis. The inverse variance-weighted (IVW) method was used as the main method to evaluate causal effects, while MR-Egger, weighted median, simple mode, and weighted mode were supplementary methods. Outliers were excluded by MR-pleiotropy residual sum and outlier (MR-PRESSO). Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used to evaluate the stability of the results. RESULTS: According to the results of IVW, we did not observe that there was a statistically significant causal association between genetically predicted SLE and the risk of anxiety disorder (OR = 1.000, 95%CI = 0.992 to 1.008, p =.997). Conversely, there were no causal effects between anxiety disorder and SLE risk (OR = 1.000, 95%CI = 0.992 to 1.008, p = .997). A similar result was obtained by supplementing the MR method. In addition, sensitivity analysis indicated high stability of the result. CONCLUSION: Bidirectional two-sample MR study does not support the causal relationship between SLE and anxiety disorder.

Effect of Plasticization on Stretching Stability of Poly(Vinyl Alcohol) Films: A Case Study Using Glycerol and Water.

Adding small molecular plasticizers is the most common route to tailor the stretchability of poly(vinyl alcohol) (PVA). However, how the plasticization along with the nature of the plasticizer governs the structural homogeneity during stretching remains an open question to answer. Herein, two representative plasticizers, glycerol (GLY) and water, are chosen to endow the PVA films with ductility. It is found that large strain cavitations cause obvious stress whitening in the PVA/H2 O films; on the contrary, most of the PVA/GLY films maintain transparent undergoing tensile deformation. Through a combination of experimental inspections and molecular dynamic simulation, it is revealed that partial water molecules that behave as free water will aggregate into microdomains, which serve as mechanical defects responsible for yielding voids. Whereas, the GLY plasticizer homogeneously disperses at a molecular level and interacts with PVA chains through strong hydrogen bonds. More interestingly, it is illustrated that the dispersion and bound states of plasticizers are closely related to the mechanical character of the plasticized PVA films. These findings offer new insight into the working mechanism of plasticization on the structural stability during stretching, and guide the design of PVA/plasticizer system to obtain excellent comprehensive mechanics.

Can industrial symbiosis policies be effective? Evidence from the nationwide industrial symbiosis system in China.

Policies directly or indirectly influence the development of industrial symbiosis (IS). Quantitatively analyzing the effects of policies on IS at a national level is necessary, but current research has lagged. Focusing on the symbiotic system that includes the thermal power industry, cement industry, iron and steel industry, and social sector in China, this paper assesses the efficacy of policies on this nationwide IS system between 2015 and 2022. A policy influence framework is proposed, combining a cost-benefit analysis, agent-based model, and comparative analysis. Results show: (1) the symbiosis probability of the nationwide IS system experiences a fluctuating increase. The maximum increments of the symbiosis probability are 5%, and the resulting environmental benefits are equivalent to an emission reduction of 6.99 Mt from blast furnace slag, 20.97 Mt from iron mine tailing, 36.02 Mt from household waste, 25.01 Mt from steel slag, and 22.95 Mt from fly ash. However, the stimulation effects of policies vary across different subsystems. (2) Thermal power-chemical subsystems, thermal power-environmental protection subsystems, iron and steel-environmental protection subsystems, and social sector-cement subsystems need policy support in the future. (3) Approximately 50% of fields in this nationwide IS system is insensitive to current policies; policy approaches should shift from economic stimulation to symbiotic guidance. This paper fills the research gap by quantitatively studying the IS policy efficacy from a national level. The findings can contribute to the improvement of the Chinese IS policy system.

[Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis"].

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

Protein-Inspired Polymers with Metal-Site-Regulated Ordered Conformations.

Metal ions play critical roles in facilitating peptide folding and inducing conformational transitions, thereby impacting on the biological activity of many proteins. However, the effect of metal sites on the hierarchical structures of biopolymers is still poorly understood. Herein, inspired by metalloproteins, we report an order-to-order conformational regulation in synthetic polymers mediated by a variety of metal ions. The copolymers are decorated with clinically available desferrioxamine (DFO) as an exogenous ligand template, which presents a geometric constraint toward peptide backbone via short-range hydrogen bonding interactions, thus dramatically altering the secondary conformations and self-assembly behaviors of polypeptides and allowing for a controllable ß-sheet to α-helix transition modulated by metal-ligand interactions. These metallopolymers could form ferritin-inspired hierarchical structures with high stability and membrane activity for efficient brain delivery across the blood-brain barrier (BBB) and long-lasting magnetic resonance imaging (MRI) in vivo.

The ketone body ß-hydroxybutyrate alleviates CoCrMo alloy particles induced osteolysis by regulating NLRP3 inflammasome and osteoclast differentiation.

BACKGROUND: Aseptic Loosening (AL) following periprosthetic osteolysis is the main long-term complication after total joint arthroplasty (TJA). However, there is rare effective treatment except for revision surgery, which is costly and painful to the patients. In recent years, the ketone body ß-hydroxybutyrate (BHB) has attracted much attention and has been proved to be beneficial in many chronic diseases. With respect to the studies on the ketone body ß-hydroxybutyrate (BHB), its anti-inflammatory ability has been widely investigated. Although the ketone body ß-hydroxybutyrate has been applied in many inflammatory diseases and has achieved considerable therapeutic efficacy, its effect on wear particles induced osteolysis is still unknown. RESULTS: In this work, we confirmed that the anti-inflammatory action of ß-hydroxybutyrate (BHB) could be reappeared in CoCrMo alloy particles induced osteolysis. Mechanistically, the ketone body ß-hydroxybutyrate (BHB) deactivated the activation of NLRP3 inflammasome triggered by CoCrMo alloy particles. Of note, this inhibitory action was independent of Gpr109a receptor as well as histone deacetylase (HDAC) suppression. Furthermore, given that butyrate, one kind of short chain fatty acid (SCFA) structurally related to ß-hydroxybutyrate (BHB), has been reported to be an inhibitor of osteoclast, thus we also investigate the effect of ß-hydroxybutyrate (BHB) on osteoclast, which was contributed to bone resorption. It was found that ß-hydroxybutyrate (BHB) did not only affect osteoclast differentiation, but also inhibit its function. Unlike the inflammasome, the effect of ß-hydroxybutyrate (BHB) on osteoclast may mainly rely on histone deacetylase (HDAC) suppression. CONCLUSIONS: In general, our study showed that the alleviation of osteolysis may owe to the effect of ß-hydroxybutyrate (BHB) on inflammasome deactivation and osteoclast.

Study on the controlled release and synergistic anti-oxidant activity in vitro and ex vivo of ligustrazine hydrochloride encapsulated into liposomes.

Ligustrazine with good antioxidant activity is one of the main active components of chuanxiong. We designed ligustrazine hydrochloride-loaded liposomes (LTH-L) by the thin film dispersion method. The particle size and zeta potential of liposomes was 118±10.61nm and -39.3±3.7mV, entrapment efficiency (EE%) was 75.05±10.67%. In vitro permeation across the dialysis membrane, the release rate (R%) of ligustrazine hydrochloride (LTH) and LTH-L were reached 80% and 60%. Ex Vivo transdermal behavior experiment showed the R% of LTH and LTH-L were between 30%-40%, the R% of LTH-L was slightly lower, because liposomes played the role on the sustained and controlled release of LTH. In addition, LTH, LTH-L and BL reacted with 2,2-diphenyl-1-picrylhydrazyl (DPPH) solution for two hours, the scavenge rates (SR%) were 55.06±2.73%, 11.3±0.03% and 37.25±1.12% respectively (P<0.001) and the SR% of LTH, LTH-L and BL reacted with H2O2 were 4.13±0.02%, 0.52±0.01% and 75.15±6.10%. The inhibit rate (IR%) of LTH, LTH-L and BL on malondialdehyde (MDA) in liver homogenate were 35.44±1.79%, 1.22±0.01% and 17.92±0.29% (P<0.001), the IR% were 30.82±0.93%, 1.7±0.01% and 25.19±0.60% (P<0.001) in anti-low density lipoprotein (LDL) oxidation experiments, perhaps LTH prepared into LTH-L can play a better antioxidant role.

Peg-interferon alpha add-on Tenofovir disoproxil fumarate achieved more HBsAg loss in HBeAg-positive chronic hepatitis B naïve patients.

Several studies have showed that combining peg-interferon alpha (Peg-IFNα) with nucleotide analogues has complementary effects in chronic hepatitis B (CHB), but the optimal regimen and potential mechanisms remain unclear. This was a prospective, longitudinal and multicentre clinical trial (NCT03013556). HBeAg-positive CHB naïve patients were randomly assigned to three groups: tenofovir disoproxil fumarate (TDF) monotherapy for 96 weeks, TDF alone for 48 weeks and sequentially Peg-IFNα added for 48 weeks, TDF de novo combination with Peg-IFNα for 48 weeks then TDF alone for 48 weeks. The primary endpoint was HBeAg seroconversion at week 96 and HBsAg loss as the secondary endpoint. Furthermore, the levels of 12 cytokines in serum were assessed at different time points. A total of 133 patients were included in the analysis. The rates of HBeAg seroconversion at 96 weeks were not significant different among the three groups (p = 0.157). Interestingly, patients in the Peg-IFNα add-on group showed markedly lower HBsAg level compared with the other two groups at week 96. In addition, only three patients in the Peg-IFNα add-on group achieved HBsAg loss. For the following 24 weeks from week 96, no HBsAg reappearance in the three patients and no new patients with HBsAg loss were observed in the three groups. Serum cytokine analysis showed that the baseline level of interferon-inducible protein-10 (IP-10) was strongly higher in HBeAg conversion patients and HBsAg loss patients. Compared with de novo combination and TDF alone, the addition of Peg-IFNα in TDF-treated group might be an effective strategy for HBsAg loss in HBeAg-positive CHB naïve patients.

Quantitative Segmentation Analysis of the Radiological Changes by Using ITK-SNAP: Risk Assessment of the Severity and Recurrence of Medication-related Osteonecrosis of the Jaw.

Background and purpose: Medication-related osteonecrosis of the jaw (MRONJ) severely impairs patients' quality of life and is remarkably refractory to treatment. There are lots of studies about identification of the radiographic features of MRONJ, yet reports about quantitative radiographic analysis for the risk assessment of the severity and recurrence of MRONJ are rarely heard. The aim of this study was to investigate the volumes of osteolytic lesions and radiodensity values of osteosclerotic lesions in MRONJ patients by using ITK-SNAP for severity prediction and prognosis evaluation. Materials and methods: Of 78 MRONJ patients (78 lesions) involved in this retrospective study, 53 were presented as osteolytic lesions and 25 were presented as osteosclerotic changes alone. Comprehensive CBCT images, demographics and clinical data of patients were investigated. The volumetric analysis and radiodensity measurement were performed by ITK-SNAP. SPSS 25.0 were used for statistical analysis. Results: The osteolytic lesion volumes in MRONJ patients receiving intravenous bisphosphonates (P=0.004) and patients without osteoporosis (P=0.027) were significantly large. No significant correlation between the volumes and bisphosphonates duration was found (P=0.094). The radiodensity values of osteosclerotic lesions was significantly correlated with bisphosphonates duration (P=0.040). The surrounding area of post-surgical lesions in MRONJ patients with recurrence showed significantly great radiodensity values (P=0.025). No significant correlation between the radiodensity values and the transformation from osteosclerotic lesions to osteolytic lesions was observed (P=0.507). Conclusion: MRONJ patients receiving intravenous bisphosphonates develop into large volumes of osteolytic lesions more easily. Long-term bisphosphonates duration is possibly related with higher bone density of osteosclerotic lesions, while higher density is not associated with the transformation from osteosclerotic lesions to osteolytic lesions. A rise of bone mineral density nearby post-surgical lesions is probably a predictor for MRONJ recurrence.

MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC.

BACKGROUND: The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as "self", evade the surveillance of the immune system, and accumulate to the tumor sites actively. RESULTS: Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate-an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. CONCLUSIONS: These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

A novel missense mutation of LRP6 identified by whole-exome sequencing in a Chinese family with non-syndromic tooth agenesis.

OBJECTIVE: The aim of this study was to explore the genetic basis of non-syndromic tooth agenesis (TA) in a Chinese family of five individuals using whole-exome sequencing (WES) analysis. SETTINGS AND SAMPLE POPULATION: Five participants/Family-based study of a non-syndromic TA proband. METHODS: The proband, proband's mother and grandmother displayed congenital tooth deficiency. Genomic DNA was extracted from the peripheral blood or saliva samples of the proband, her parents and her grandmother, and WES was utilized to identify the causal genetic mutation. The identified mutation was further verified by Sanger sequencing and analysed using bioinformatics tools. RESULTS: A novel missense mutation, c.G711T (p.L237F), was identified in the low-density lipoprotein receptor-related protein 6 (LRP6) gene in all affected individuals. Bioinformatics analysis predicted the mutation to be deleterious, with the mutant LRP6 protein displaying a tertiary structural change that might disturb the Wnt/ß-catenin signalling pathway. CONCLUSIONS: The identification of the mutation in the LRP6 gene and autosomal dominant inheritance with TA in the generations is consistent with the mutation being responsible for TA in the family, and furthers the association of LRP6 with nonsyndromic TA.

Recent Advances in Processing of Stereocomplex-Type Polylactide.

Over the past two decades, biomass-derived and biodegradable polylactide (PLA) has sparked tremendous attention as a sustainable alternative to traditional petroleum-derived polymers for diverse applications. Unfortunately, the current applications of PLA have been mainly limited to biomedical and commodity fields, mostly because the poor heat resistance (resulting from low melting temperature) and hydrolysis stability make it hard to use as an engineering plastic. Stereocomplexation between enantiomeric poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) opens a new avenue toward PLA-based engineering plastics with improved properties. The formation, crystal structure, properties, and potential applications of stereocomplex-type PLA (SC-PLA) are summarized by some research groups. However, since it is challenging to achieve full stereocomplexation from high-molecular-weight PLLA/PDLA blends and to avoid serious thermal degradation of the PLAs after complete melting, the advances and progress in the processing of SC-PLA into useful products are quite rare in open publication. In this review, some important strategies for enhancing stereocomplex crystallization in practical processing operations are presented and recently developed processing technologies for SC-PLA are highlighted, such as low-temperature sintering. Furthermore, major challenges and future developments are briefly discussed. This review is expected to potentially open up new research activities in the processing of SC-PLA.

Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study).

UNLABELLED: Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding on pegylated interferon (Peg-IFN) to ETV therapy enhances serological response rates. In this global investigator-initiated, open-label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg-IFN add-on therapy (180 µg/week) from week 24 to 48 (n = 85) or to continue ETV monotherapy (n = 90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16 of 85 (19%) patients allocated to the add-on arm versus 9 of 90 (10%) in the monotherapy arm (P = 0.095). Adjusted for HBV DNA levels before randomized therapy, Peg-IFN add-on was significantly associated with response (odds ratio: 4.8; 95% confidence interval: 1.6-14.0; P = 0.004). Eleven (13%) of the add-on-treated patients achieved disease remission after ETV cessation versus 2 of 90 (2%) of those treated with monotherapy (P = 0.007), which was 79% (11 of 14) versus 25% (2 of 8) of those who discontinued ETV (P = 0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (P = 0.036). Peg-IFN add-on led to significantly more decline in hepatitis B surface antigen, HBeAg, and HBV DNA (all P < 0.001). Combination therapy was well tolerated. CONCLUSION: Although the primary endpoint was not reached, 24 weeks of Peg-IFN add-on therapy led to a higher proportion of HBeAg response, compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence, Peg-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogs.

Drag-reducing polyethylene oxide improves microcirculation after hemorrhagic shock.

BACKGROUND: Despite resuscitation after trauma, microcirculatory abnormalities are known to persist in post-shock multiorgan dysfunction. The high-molecular weight polymer polyethylene oxide (PEO) (>10(6) Da), a classic drag-reducing polymer, can improve hemorrhagic shock (HS)-induced hemodynamic abnormalities in rats. MATERIALS AND METHODS: We examined the effects of PEO on microcirculation and on changes in multiple organs after shock. After the spinotrapezius muscle was prepared, HS was induced in Sprague-Dawley rats. Drug administration (normal saline or PEO) was performed 2 h after shock followed by infusion of shed blood. RESULTS: The velocity, blood flow, and functional capillary density in the shock + PEO group were significantly higher than those in the shock + normal saline group. Moreover, the kidney, liver, and lung function was improved, resulting in prolonged survival time. Our findings indicate that intravenous infusion of PEO can ameliorate shock-associated organ dysfunction and prolong survival time in severe HS, which may be a result of increased arteriolar blood velocity, blood flow, and functional capillary density. CONCLUSIONS: PEO could have potential clinical application in the treatment of shock-induced multiorgan dysfunction.

Bio-reducible polycations from ring-opening polymerization as potential gene delivery vehicles.

Synthetic polycations show great potential for the construction of ideal non-viral gene delivery systems. Several cationic polymers were synthesized by the epoxide ring-opening polymerization between diepoxide and various polyamines. Disulfide bonds were introduced to afford the polymers bio-reducibility, while the oxygen-rich structure might enhance the serum tolerance and biocompatibility. The polycations have much lower molecular weights than PEI 25 kDa, but still could well bind and condense DNA into nano-sized particles. DNA could be released from the polyplexes by addition of reductive DTT. Compared to PEI, the polycations have less cytotoxicity possibly due to their lower molecular weights and oxygen-rich structure. More significantly, these materials exhibit excellent serum tolerance than PEI, and up to 6 times higher transfection efficiency than PEI could be obtained in the presence of serum. The transfection mediated by was seldom affected even at a high concentration of serum. Much lower protein adsorption of polycations than PEI was proved by bovine serum albumin adsorption experiments. Flow cytometry also demonstrates their good serum resistance ability.

Effects of interaction between a polycation and a nonionic polymer on their cross-assembly into mixed micelles.

In this paper, to investigate the effects of interactions between poly(quaternary ammonium) salts (PQAs) and poly(ethylene glycol) on their mixed micellar surface structures and properties under spontaneous conditions, a series of PQAs were first designed and synthesized by atom transfer radical polymerization (ATRP) using 2-(dimethylamino) ethyl methacrylate (DMAEMA) quaternized by bromobutane, bromooctane, and bromododecane, respectively. Poly(poly(ethylene glycol) methyl ether methacrylate) (PPEG) with a similar degree of polymerization was also prepared using poly(ethylene glycol) methyl ether methacrylate by ATRP. Next, these PQAs were mixed with an equal weight of PPEG in water to cross-assemble into mixed micelles. The structures and features of these mixed micelles were characterized by fluorescence measurements, transmission electron microscopy (TEM), dynamic light scattering (DLS), phase analysis light scattering (PALS), proton nuclear magnetic resonance ((1)H NMR), and hydrogen-hydrogen correlation spectroscopy nuclear magnetic resonance (H-H COSY NMR). These results suggest that PQAs and PPEG mixtures can cross-assemble into mixed micelles with low CMC. The surface structures, particle sizes, size distributions, and zeta potentials of PQAs and PPEG mixtures can be tailored by varying the alkyl chain length in quaternary ammonium salts, and the alkyl chain length also influences the distribution and the alkyl chain orientation of quaternary ammonium salts on mixed micelle surfaces. In addition, cytotoxicity of these mixed micelles can be markedly reduced by PPEG compared with their corresponding PQAs, but their good antibacterial activities are still maintained to a certain degree, as evaluated by methyl tetrazolium assay (MTT) and minimum inhibitory concentration (MIC). Our present work provides a new avenue for the preparation of biocompatible and antibacterial materials for biomedical applications.

Significantly improving oxygen barrier properties of polylactide via constructing parallel-aligned shish-kebab-like crystals with well-interlocked boundaries.

Recently, some attempts have been made to enhance the gas barrier properties of semicrystalline polymers by precisely controlling the arrangement of their impermeable crystalline lamellae. However, it is still a great challenge to achieve regular arrangement of the lamellae along the direction perpendicular to the gas diffusion path, especially using conventional polymer processing technologies. This work presents a novel and simple strategy to dramatically improve oxygen barrier performance of biobased and biodegradable polylactide (PLA) through constructing parallel-aligned shish-kebab-like crystals with well-interlocked boundaries with the aid of a highly active nucleating agent. The nucleating agent was introduced into PLA by melting compounding and the sheet-like specimens were fabricated by compression molding. We demonstrate that the fibrillar nucleating agent dispersed in PLA melt can serve as shish to induce the change of crystallization habit of PLA from isotopic spherulitic crystals to unique shish-kebab-like crystals and the shear flow in the compression molding can induce the highly ordered alignment of the nucleating agent fibrils as well as the subsequent shish-kebab-like crystals along the direction parallel to the sheet surface. More importantly, the growing lamellae are found to interpenetrate and tightly interlock with each other at the boundary regions of the shish-kebab-like crystals in the later stage of the crystallization, forming a densely packed nanobrick wall structure to prevent gas molecules from permeating through the crystals and thus imparting the PLA sheets with unprecedentedly low oxygen permeability. This work provides not only a successful example of preparing semicrystalline polymer with super gas barrier properties by tailoring crystal superstructure but also a promising route to rapidly fabricate high-performance food packaging materials via industrially meaningful melt processing.