Mechanistic study of the Ni-catalyzed hydroalkylation of 1,3-dienes: The origins of regio- and enantioselectivities and a further rational design.

The development of the catalytic regio- and enantioselective hydrofunctionalization of 1,3-dienes remains a challenge and requires deep insight into the reaction mechanisms. We herein thoroughly studied the reaction mechanism of the Ni-catalyzed hydroalkylation of 1,3-dienes with ketones by density functional theory (DFT) calculations. It reveals that the reaction is initiated by stepwise oxidative addition of EtO-H followed by 1,3-diene migratory insertion to generate the alkylnickel(II) intermediate, rather than the experimentally proposed ligand-to-ligand hydrogen transfer (LLHT) mechanism. In addition, we rationalized the role of t BuOK in the subsequent addition of enolate of ketone and transmetalation process. Based on the whole catalysis, the CC reductive elimination step, turns out to be the rate- and enantioselectivity-determining step. Furthermore, we disclosed the origins of the regio- and enantioselectivity of the product, and found that the 1,2-selectivity lies in the combination effects of the ligand-substrate electrostatic interactions, orbital interactions and Pauli repulsions, while the enantioselectivity mainly arises from substrate-ligand steric repulsions. Based on mechanistic study, new biaryl bisphosphine ligands affording higher enantioselectivity were designed, which will help to improve current catalytic systems and develop new transition-metal-catalyzed hydroalkylations.

Magnesium-Mediated Cross-Electrophile Couplings of Aryl 2-Pyridyl Esters with Aryl Bromides for Ketone Synthesis through In Situ-Formed Arylmagnesium Intermediates.

Aryl 2-pyridyl esters could efficiently undergo cross-electrophile couplings with aryl bromides with the aid of magnesium as a reducing metal in the absence of a transition-metal catalyst, leading to the unsymmetrical diaryl ketones in modest to good yields with wide functionality compatibility. In addition, the reaction could be easily scaled up and applied in the late-stage modification of biologically active molecules. Preliminary mechanistic study showed that the coupling reaction presumably proceeds through the in situ formation of arylmagnesium reagents as key intermediates.

Novel Strategy to Combat the Procoagulant Phenotype in Heparin-Induced Thrombocytopenia Using 12-LOX Inhibition.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a major concern for all individuals that undergo cardiac bypass surgeries or require prolonged heparin exposure. HIT is a life- and limb-threatening adverse drug reaction with an immune response following the formation of ultra-large immune complexes that drive platelet activation through the receptor FcγRIIA. Thrombotic events remain high following the standard of care treatment with anticoagulants, while increasing risk of bleeding complications. This study sought to investigate a novel approach to treatment of HIT. Recent reports demonstrate increased procoagulant activity in HIT; however, these reports required analysis ex vivo, and relevance in vivo remains unclear. METHODS: Using human and mouse model systems, we investigated the cooperativity of PARs (protease-activated receptors) and FcγRIIA in HIT. We challenged humanized FcγRIIA transgenic mice with or without endogenous mouse Par4 (denoted as IIA-Par4+/+ or IIA-Par4-/-, respectively) with a well-established model IgG immune complex (anti [α]-CD9). Furthermore, we assessed the procoagulant phenotype and efficacy to treat HIT utilizing inhibitor of 12-LOX (12[S]-lipoxygenase), VLX-1005, previously reported to decrease platelet activation downstream of FcγRIIA and PAR4, using the triple allele HIT mouse model. RESULTS: IIA-Par4+/+ mice given αCD9 were severely thrombocytopenic, with extensive platelet-fibrin deposition in the lung. In contrast, IIA-Par4-/- mice had negligible thrombocytopenia or pulmonary platelet-fibrin thrombi. We observed that pharmacological inhibition of 12-LOX resulted in a significant reduction in both platelet procoagulant phenotype ex vivo, and thrombocytopenia and thrombosis in our humanized mouse model of HIT in vivo. CONCLUSIONS: These data demonstrate for the first time the need for dual platelet receptor (PAR and FcγRIIA) stimulation for fibrin formation in HIT in vivo. These results extend our understanding of HIT pathophysiology and provide a scientific rationale for targeting the procoagulant phenotype as a possible therapeutic strategy in HIT.

Robust Catalytic SEAr H/D Exchange of Arenes with D2O: Metal-Free Deuteration of Natural Complexes and Drugs.

A catalytic metal-free approach for the H/D exchange in aromatic compounds using D2O as the terminal deuterating reagent has been developed. This metal-free protocol employs a triaryl carbenium as the mediator and showcases a wide applicability in the late-stage deuteration of various natural products and small-molecule drugs. Gram-scale deuteration was successfully demonstrated with ß-Estradiol, highlighting the method's practicability. Detailed mechanistic insights, supported by DFT calculations, unveiled the essential role of in situ generated acidic species in this electrophilic aromatic substitution process. This newly developed method offers a sustainable and versatile alternative to traditional metal-catalyzed H/D exchange techniques, addressing challenges such as the use of expensive metals, impurity formation, and the necessity for residual metal removal from the final products.

One-Step, On-Site Chemical Printing of a 3D Plasmon-Coupled Silver Nanocoral Substrate toward SERS-Based POCT.

Surface-enhanced Raman scattering (SERS) with the advantages of high sensitivity, nondestructive analysis, and a unique fingerprint effect shows great potential in point-of-care testing (POCT). However, SERS faces challenges in rapidly constructing a substrate with high repeatability, homogeneity, and sensitivity, which are the key factors that restrict its practical applications. In this study, we propose a one-step chemical printing strategy for synthesizing a three-dimensional (3D) plasmon-coupled silver nanocoral (AgNC) substrate (only need about 5 min) without any pretreatments and complex instruments. The galvanic replacement between AgNO3 and Cu sheets will provide both Ag0 for the formation of silver nanostructures and Cu2+ for the polymerization of fish sperm DNA (FSDNA). The protection of AgNCs is facilitated by the crosslinked FSDNA, which can improve the stability of the substrate and promote the control of its coral-like morphology. The obtained substrate displays excellent capacity of signal enhancement due to the 3D plasmon coupling both between nanocoral tentacles and between nanocorals and Cu sheets as well. Therefore, the AgNC substrates display high activity (enhancement factor = 1.96 × 108) and uniformity (RSD < 6%). Food colorants have been widely used in various foods to improve their color, but the inevitable toxicity of colorants seriously threatens food safety. Therefore, the proposed AgNC substrates were used to directly quantify three kinds of weak-affinity food colorant molecules including Brilliant Blue, Allura Red, and Sunset Yellow assisted by the capture by cysteamine hydrochloride (CA), showing the detection limits (S/N = 3) of 0.053, 0.087, and 0.089 ppm, respectively. The SERS method has been further applied in the detection of the three kinds of food colorants in both complex food samples and urine with recoveries of 91-119%. The satisfactory detection results suggest that the facile preparation strategy of AgNC substrates will be widely used in SERS-based POCT to promote the development of food safety and on-site healthcare.

Associations between apolipoprotein B and bone mineral density: a population-based study.

BACKGROUND: Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers. METHODS: The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship. RESULTS: A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [ß = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [ß = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD. CONCLUSIONS: Our findings suggest that apo B is associated with BMD in a site-specific manner.

Effect of muscone on anti-apoptotic ability of muskrat prostate primary cells.

Muskrat is a small fur animal with a pair of scent glands that can secrete muskrat musk during breeding season. The consensus is muskrat musk functions as a pheromone, but we hypothesized it has a broader role. In previous research, we found the presence of muscone in muskrat musk. To study whether the muscone can affect the apoptosis of muskrat prostate, we carried out the following investigations. Primary muskrat prostate cells were cultured and treated with muscone. Then we drew cell proliferation curves by applying the CCK-8 and used TdT-mediated dUTP nick end labeling (TUNEL) to detect apoptosis. Levels of mRNA transcription and protein expression of Bcl-2 as well as Bax were detected by qRT-PCR and the Western blot. Meanwhile, we collected tissue samples of muskrat prostates and froze sections to analyze the fluorescence signal intensity of BCL-2 and BAX via immunofluorescence. Under the treatment of 30 µmol/L muscone, the proliferation rate of the experimental group exceeded that of the control group, and the proportion of cells undergoing apoptosis was lower in the experimental group. The qRT-PCR and Western blot result showed that, in the experimental group, the ratio of Bcl-2 to Bax mRNA transcription levels increased by 2.85 times and their corresponding protein expression ratio increased by 2.37 times (P < 0.05). Immunofluorescence results were consistent with the cell experiment's results. The fluorescence signal intensity of BCL-2 was higher in the breeding season than nonbreeding season but vice versa for BAX. Based on these results, we speculate that the muscone could regulates prostate development by inhibiting apoptosis.

Computational Mechanistic Study of Brønsted Acid-Catalyzed Unsymmetrical 1,2,4,5-Tetrazines Synthesis.

Density functional theory (DFT) calculations were conducted to gain insight into the reaction mechanism of the Brønsted acid-catalyzed unsymmetrical 1,2,4,5-tetrazine synthesis. Various possible reaction pathways were considered, and the most favorable one can be characterized via sequential six steps, including addition of DCM to hydrazine 1 giving complex IM4, N-H bond activation in IM4 mediated by sulfur, AcOH-assisted substitution of 3 with sulfur-activated hydrazine 2, HNO2-assisted addition of nitrile to intermediate 8, cyclization, and intramolecular elimination leading to the final product 7. Among the six steps, sulfur activation of IM4 N-H bond is found to be the rate-determining step (RDS). The mechanism rationalizes the experimental observation that 2 equiv of sulfur leads to the best yield of product. Furthermore, we disclosed that the Brønsted acid additives (i.e., acetic acid and nitrous acid) served triple roles as catalyst, proton shuttle, and hydrogen bond donor and acceptor in the whole catalysis.

Iron-Catalyzed Tertiary Alkylation of Terminal Alkynes with 1,3-Diesters via a Functionalized Alkyl Radical.

Direct oxidative C(sp)-H/C(sp3 )-H cross-coupling offers an ideal and environmentally benign protocol for C(sp)-C(sp3 ) bond formations. As such, reactivity and site-selectivity with respect to C(sp3 )-H bond cleavage have remained a persistent challenge. Herein is reported a simple method for iron-catalyzed/silver-mediated tertiary alkylation of terminal alkynes with readily available and versatile 1,3-dicarbonyl compounds. The reaction is suitable for an array of substrates and proceeds in a highly selective manner even employing alkanes containing other tertiary, benzylic, and C(sp3 )-H bonds alpha to heteroatoms. Elaboration of the products enables the synthesis of a series of versatile building blocks. Control experiments implicate the in situ generation of a tertiary carbon-centered radical species.

Humanin analogue, HNG, inhibits platelet activation and thrombus formation by stabilizing platelet microtubules.

HNG, a highly potent mutant of the anti-Alzheimer peptide-humanin, has been shown to protect against ischaemia-reperfusion (I/R) injury. However, the underlying mechanism related to platelet activation remains unknown. We proposed that HNG has an effect on platelet function and thrombus formation. In this study, platelet aggregation, granule secretion, clot retraction, integrin activation and adhesion under flow conditions were evaluated. In mice receiving HNG or saline, cremaster arterial thrombus formation induced by laser injury, tail bleeding time and blood loss were recorded. Platelet microtubule depolymerization was evaluated using immunofluorescence staining. Results showed that HNG inhibited platelet aggregation, P-selectin expression, ATP release, and αIIb ß3 activation and adhesion under flow conditions. Mice receiving HNG had attenuated cremaster arterial thrombus formation, although the bleeding time was not prolonged. Moreover, HNG significantly inhibited microtubule depolymerization, enhanced tubulin acetylation in platelets stimulated by fibrinogen or microtubule depolymerization reagent, nocodazole, and inhibited AKT and ERK phosphorylation downstream of HDAC6 by collagen stimulation. Therefore, our results identified a novel role of HNG in platelet function and thrombus formation potentially through stabilizing platelet microtubules via tubulin acetylation. These findings suggest a potential benefit of HNG in the management of cardiovascular diseases.

Molecular docking-assisted screening reveals tannic acid as a natural protein disulphide isomerase inhibitor with antiplatelet and antithrombotic activities.

Protein disulphide isomerase (PDI) promotes platelet activation and constitutes a novel antithrombotic target. In this study, we reported that a PDI-binding plant polyphenol, tannic acid (TA), inhibits PDI activity, platelet activation and thrombus formation. Molecular docking using plant polyphenols from dietary sources with cardiovascular benefits revealed TA as the most potent binding molecule with PDI active centre. Surface plasmon resonance demonstrated that TA bound PDI with high affinity. Using Di-eosin-glutathione disulphide fluorescence assay and PDI assay kit, we showed that TA inhibited PDI activity. In isolated platelets, TA inhibited platelet aggregation stimulated by either GPVI or ITAM pathway agonists. Flow cytometry showed that TA inhibited thrombin- or CRP-stimulated platelet activation, as reflected by reduced granule secretion and integrin activation. TA also reduced platelet spreading on immobilized fibrinogen and platelet adhesion under flow conditions. In a laser-induced vascular injury mouse model, intraperitoneal injection of TA significantly decreased the size of cremaster arteriole thrombi. No prolongation of mouse jugular vein and tail-bleeding time was observed after TA administration. Therefore, we identified TA from natural polyphenols as a novel inhibitor of PDI function. TA inhibits platelet activation and thrombus formation, suggesting it as a potential antithrombotic agent.

The Roles of GRKs in Hemostasis and Thrombosis.

Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, we will summarize recent findings on the role of GRKs in platelet biology and how one specific GRK, GRK6, regulates the hemostatic response to vascular injury. Furthermore, we will discuss the potential role of GRKs in thrombotic disorders, such as thrombotic events in COVID-19 patients. Studies on the function of GRKs during platelet activation and thrombus formation have just recently begun, and a better understanding of the role of GRKs in hemostasis and thrombosis will provide a fruitful avenue for understanding the hemostatic response to injury. It may also lead to new therapeutic options for the treatment of thrombotic and cardiovascular disorders.

Bulky Ytterbium Formamidinates Stabilise Complexes with Radical Ligands, and Related Samarium "Tetracyclone" Chemistry.

Divalent [Yb(DippForm)2 (thf)n ] (n=2 (1 a), or 1 (1 b), DippForm=N,N'-bis(2,6-diisopropylphenyl)formamidinate) complexes were treated with the ketones: 9-fluorenone (fn), or 2,3,4,5-tetraphenylcyclopentadienone (tpc, tetracyclone), giving ketyl complexes: [Yb(DippForm)2 (fn. -O)(thf)] (2), and [Yb(DippForm)2 (tpc. -O)] (3), respectively (ketyl=a radical anion containing a C. -O(-) group. By contrast, when perfluorobenzophenone (pfb) was treated with either 1 a or 1 b, transitory ketyl formation was followed by rapid decomposition through a C-F activation pathway, giving [YbF(DippForm)2 (thf)] (4 a) and a highly unusual fluoride/oxide-bridged species: [Yb5 F6 O2 (DippForm)5 ] (4 b). The reduction of diketones: 3,5-di-tert-butyl-1,2-benzoquinone (tbbq), 9,10-phenanthrenequinone (phen), or 1,2-acenaphthenequinone (acen), was also examined giving ketyl complexes: [Yb(DippForm)2 (tbbq. -O2 )] (5), [Yb(DippForm)2 (phen. -O2 )] (6), and [Yb(DippForm)2 (acen. -O2 )(thf)] (7). An unsolvated derivative of 7, namely [Yb(DippForm)2 (acen. -O2 )] (8), was obtained from PhMe. All ketyl complexes had suitably elongated C. -O bonds, were stable in both polar and non-polar solvents-an uncommon trait for rare-earth ketyl complexes-and, with the exception of 3, showed radical signals in ESR spectra. To investigate the reactivity of the tpc. -O ketyl complex, 3 was treated with oxidants (CS2 , Se) and reducing agents (Mg0 , KH, or [SmI2 (thf)2 ]). Thus 3 was oxidised to tpc by Se. Treatment of 3 with KH led to a ligand exchange process giving an unusual diketyl species [Yb(DippForm)(tpc. -O)2 (thf)2 ] (10), which has two cisoid tpc. -O- ligands in very close proximity. When treated with [SmI2 (thf)2 ], the tpc. -O ketyl was further reduced to a dianion (1-oxido-2,3,4,5-tetraphenylcyclopentadianide2- ), ({C5 Ph4 }-O)2- by [SmI2 (thf)2 ], giving dimeric [{SmI({C5 Ph4 }-O)(thf)2 }2 ] (Sm11) and monomeric complexes [YbI(DippForm)2 (thf)] (11 b) and [YbI2 (DippForm)(thf)2 ] (11 c). Activated Sm metal reduced neutral tetracyclone to the dianion, ({C5 Ph4 }-O)2- , in THF, giving tetranuclear [{SmII2 ({C5 Ph4 }-O)2 (thf)3 }2 ] (Sm13). Treatment of Sm13 with iodine in situ provided access to [{SmI({C5 Ph4 }-O)(thf)2 }2 ] (Sm11), in good yield.

The feasibility of laparoscopic management of incarcerated obturator hernia.

BACKGROUND: Obturator hernia (OH), a rare cause of acute small bowel obstruction, requires immediate surgical intervention to prevent serious complications and mortality. We assessed the safety and efficacy of laparoscopic surgery in patients with incarcerated OH presenting with acute abdomen in an emergency setting. METHODS: Data pertaining to patients diagnosed with incarcerated OH between 2011 and April 2015 at our hospital were reviewed. Patients' characteristics, operation details and postoperative outcomes were retrospectively analyzed. RESULTS: All ten patients diagnosed with incarcerated obturator hernia during the reference period were females (average age 72.1 ± 11.8 years; average weight 44.1 ± 6.9 kg; average body mass index 17.8 ± 2.1 kg/m2; average operating time 63 ± 15 min; average hospital stay 6.2 ± 6.6 days). Twelve occult hernias, including six contralateral OHs, two ipsilateral femoral hernias and two bilateral femoral hernias were detected in six patients (60 %), which were simultaneously repaired after laparoscopic exploration. Nine patients (90 %) were successfully treated with synthetic mesh by laparoscopic technique. Only one case required intraoperative conversion to open surgery due to strangulated intestine with perforation. Wound infection was reported in one patient who had undergone bowel resection, but with an eventual complete recovery. Postoperative period was uneventful in the other nine patients. No recurrence or complications were reported on follow-up (mean duration of follow-up: 6-54 months). CONCLUSION: In this study, laparoscopic technique was associated with a reduced duration of hospital stay and fewer complications. In addition to being a safe and minimally invasive strategy, it allowed for simultaneous diagnosis and treatment of occult hernias during the same procedure. The approach may be a better option for the treatment of incarcerated OH and occult hernias in selected patients.

Non-Pincer-Type Mononuclear Scandium Alkylidene Complexes: Synthesis, Bonding, and Reactivity.

The first non-pincer-type mononuclear scandium alkylidene complexes were synthesized and structurally characterized. These complexes exhibited short Sc-C bond lengths and even one of the shortest reported to date (2.1134(18) Å). The multiple character of the Sc-C bond was highlighted by a DFT calculation. This was confirmed by experimental reactivity study where the complex underwent [2+1] cycloaddition with elemental selenium and [2+2] cycloaddition with imine. DFT calculation also revealed a strong nucleophilic behavior of the alkylidene complex that was experimentally demonstrated by the C-H bond activation of phenylacetylene.

Utilization of pyrolytic substrate by microalga Chlamydomonas reinhardtii: cell membrane property change as a response of the substrate toxicity.

Acetic acid derived from fast pyrolysis of lignocellulosic biomass is a promising substrate for microalgae fermentation for producing lipid-rich biomass. However, crude pyrolytic acetic acid solution contains various toxic compounds inhibiting algal growth. It was hypothesized that such an inhibition was mainly due to the cell membrane damage. In this work, the cell membrane property of algal cells was evaluated at various conditions to elucidate the mechanisms of inhibition caused by the pyrolytic substrate solution. It was found that acetic acid itself served a carbon source for boosting algal cell growth but also caused cell membrane leakage. The acetic acid concentration for highest cell density was 4 g/L. Over-liming treatment of crude pyrolytic acetic acid increased the algal growth with a concurrent reduction of cell membrane leakage. Directed evolution of algal strain enhanced cell membrane integrity and thus increased its tolerance to the toxicity of the crude substrate. Statistical analysis shows that there was a significant correlation between the cell growth performance and the cell membrane integrity (leakage) but not membrane fluidity. The addition of cyto-protectants such as Pluronic F68 and Pluronic F127 enhanced the cell membrane integrity and thus, resulted in enhanced cell growth. The transmission electron microscopy (TEM) of algal cells visually confirmed the cell membrane damage as the mechanism of the pyrolytic substrate inhibition. Collectively, this work indicates that the cell membrane is one major reason for the toxicity of pyrolytic acetic acid when being used for algal culture. To better use this pyrolytic substrate, cell membrane of the microorganism needs to be strengthened through either strain improvement or addition of membrane protectant reagents.

Effect of continuous ozone injection on performance and biomass accumulation of biofilters treating gaseous toluene.

Biofilters treating high-concentration gaseous volatile organic compounds (VOC) can be subject to bed clogging induced by excess biomass accumulation. In this study, O3 was continuously injected into biofilters to control biomass. Its effects on the performance of the biofilters and on biomass accumulation were investigated. Four identical biofilters designed to treat gaseous toluene were operated for 70 days, and three of them were continuously injected with O3 at different concentrations (from 80 to 320 mg/m(3)). The results showed that continuous O3 injection could effectively keep the bed pressure drop stable and had no adverse effect on toluene removal when O3 concentrations were 180-220 mg/m(3). The maximum toluene elimination capacity of the four biofilters was 140 g-toluene/m(3)/h, and the bed pressure drop of the biofilter fed with 180-220 mg/m(3) O3 remained below 3 mmH2O/m throughout the operation period. The biomass accumulation rates of the three biofilters with O3 at 80-320 mg/m(3) were lowered by 0.15-0.25 g/L/day compared with the biofilter without O3. The decreases in biomass accumulation resulted in higher void fractions of the filter beds with O3 injection. Carbon balance analysis indicated that CO2 production had increased while biomass accumulation and leachate waste production decreased in response to O3 injection. Based on the experimental results, it was concluded here that continuous O3 injection can reduce increases in bed pressure effectively, preserve VOC removal capacity, and prevent production of extra leachate waste.

PEG-b-PCL copolymer micelles with the ability of pH-controlled negative-to-positive charge reversal for intracellular delivery of doxorubicin.

The application of PEG-b-PCL micelles was dampened by their inherent low drug-loading capability and relatively poor cell uptake efficiency. In this study, a series of novel PEG-b-PCL copolymers methoxy poly(ethylene glycol)-b-poly(ε-caprolactone-co-γ-dimethyl maleamidic acid -ε-caprolactone) (mPEG-b-P(CL-co-DCL)) bearing different amounts of acid-labile ß-carboxylic amides on the polyester moiety were synthesized. The chain structure and chemical composition of copolymers were characterized by (1)H NMR, Fourier transform infrared spectroscopy (FT-IR), and gel permeation chromatography (GPC). mPEG-b-P(CL-co-DCL) with critical micellar concentrations (CMCs) of 3.2-6.3 µg/mL could self-assemble into stable micelles in water with diameters of 100 to 150 nm. Doxorubicin (DOX), a cationic hydrophobic drug, was successfully encapsulated into the polymer micelles, achieving a very high loading content due to electrostatic interaction. Then the stability, charge-conversional behavior, loading and release profiles, cellular uptake and in vitro cytotoxicity of free drug and drug-loaded micelles were evaluated. The ß-carboxylic amides functionalized polymer micelles are negatively charged and stable in neutral solution but quickly become positively charged at pH 6.0, due to the hydrolysis of ß-carboxylic amides in acidic conditions. The pH-triggered negative-to-positive charge reversal not only resulted in a very fast drug release in acidic conditions, but also effectively enhanced the cellular uptake by electrostatic absorptive endocytosis. The MTT assay demonstrated that mPEG-b-P(CL-co-DCL) micelles were biocompatible to HepG2 cells while DOX-loaded micelles showed significant cytotoxicity. In sum, the introduction of acid-labile ß-carboxylic amides on the polyester block in mPEG-b-P(CL-co-DCL) exhibited great potentials for the modifications in the stability in blood circulation, drug solubilization, and release properties, as well as cell internalization and intracellular drug release.

Effects of the electric field on the properties of ZnO-graphene composites: a density functional theory study.

In this work, the effects of the electric field on the properties of ZnO-graphene composites were theoretically studied using density functional theory calculations. Three types of ZnO-graphene composites including composites of pristine graphene, graphene with defects as well as graphene oxide and a ZnO bilayer were studied. We calculated and analyzed the binding energies, charge transfer, band structures and work functions of the above composites under the external electric fields. The DFT calculation results demonstrate that the binding energies are sensitive to the electric field, and increasing the external electric field gives rise to stronger binding energies. The extent of charge transfer is correlated with the magnitude of the external electric field, but the band gaps are hardly affected by the external electric field. The work functions vary depending on the different structures of the composites and surface sides, and they are also tunable by the external electric field.

Effect of continuous ozone injection on performance and biomass accumulation of biofilters treating gaseous toluene.

Biofilters treating high-concentration gaseous volatile organic compounds (VOC) can be subject to bed clogging induced by excess biomass accumulation. In this study, O3 was continuously injected into biofilters to control biomass. Its effects on the performance of the biofilters and on biomass accumulation were investigated. Four identical biofilters designed to treat gaseous toluene were operated for 70 days, and three of them were continuously injected with O3 at different concentrations (from 80 to 320 mg/m(3)). The results showed that continuous O3 injection could effectively keep the bed pressure drop stable and had no adverse effect on toluene removal when O3 concentrations were 180-220 mg/m(3). The maximum toluene elimination capacity of the four biofilters was 140 g-toluene/m(3)/h, and the bed pressure drop of the biofilter fed with 180-220 mg/m(3) O3 remained below 3 mmH2O/m throughout the operation period. The biomass accumulation rates of the three biofilters with O3 at 80-320 mg/m(3) were lowered by 0.15-0.25 g/L/day compared with the biofilter without O3. The decreases in biomass accumulation resulted in higher void fractions of the filter beds with O3 injection. Carbon balance analysis indicated that CO2 production had increased while biomass accumulation and leachate waste production decreased in response to O3 injection. Based on the experimental results, it was concluded here that continuous O3 injection can reduce increases in bed pressure effectively, preserve VOC removal capacity, and prevent production of extra leachate waste.