Clinical and radiographic outcomes of implant-supported fixed prostheses with cantilever extension in anterior mandible: A retrospective study.

OBJECTIVES: The objective of this study is to analyze the clinical and radiographic outcomes of implant-supported fixed protheses with cantilever extensions (ISFPCs) in the partially edentulous anterior mandible. MATERIALS AND METHODS: Patients who received anterior mandible implant restoration between January 2016 and December 2021 were included. Patients with two, three, or four continuous missing teeth receiving adjacent implant supported single-unit crowns (ISSCs), ISFPCs, implant-supported fixed protheses without cantilever extensions (ISFPNs) were divided into groups: ISSC+ISSC, ISFPC, ISSC+ISFPC, three-unit ISFPN, ISFPC+ISFPC, or four-unit ISFPN, respectively. We recorded and evaluated survival rates, mechanical and biological complications, peri-implant marginal bone loss (MBL), esthetic outcomes, and patient perceptions. Statistical analysis was performed using linear mixed models (LMM). RESULTS: The study included 87 patients and 152 implants. No implant loss occurred during an average follow-up of 3.48 ± 1.85 years (range: 1-7 years). According to LMM models, prosthetic type had a statistically significant impact on MBL during follow-up periods, in favor of the ISFPC and ISFPC+ISFPC groups (0.16 ± 0.48 mm vs. 0.51 ± 0.49 mm, p = .034; 0.22 ± 0.49 mm vs. 0.60 ± 0.62 mm, p = .043, respectively). Mechanical and biological complications were relatively low and comparable. The four-unit ISFPC group had higher subjective esthetic scores compared with the ISSC+ISSC group (98.6 vs. 83.8, p < .05), and patients in the ISFPC+ISFPC group expressed greater satisfaction with cleanability than the ISFPN group (98.8 vs. 80.6). CONCLUSION: ISFPCs offer a highly predictable treatment option in the anterior mandible, characterized by high survival rates, and comparable complication rates, peri-implant bone stability and esthetics to adjacent ISSCs or ISFPNs.

Transforming a Toxic Non-Ionizable Drug into an Efficacious Liposome via Ionizable Prodrug and Remote Loading Strategies against Malignant Breast Tumors.

Liposomes (lipos), one of the most successful nanotherapeutics in the clinic, have made a rapid advance over the past few years. However, still, several challenges exist for lipos for clinical practice, such as low drug loading and premature drug leakage during in vivo circulation. Paclitaxel (PTX), a commonly used first-line drug for cancer chemotherapy, was chosen as the model drug. Due to its non-ionizable and water-insoluble characteristics, the drug-loading efficiency of the marketable PTX lipos, Lipusu, is only 6.76%. Herein, we designed an ionizable PTX prodrug (PTXP) by modifying phenylboronic acid on the C2' hydroxyl group of PTX for the remote loading of liposomal formulations through the pH gradient method. Compared with Lipusu, PTXP lipos displayed a 34% higher loading efficiency and an encapsulation efficiency of approximately 95%. A series of in vitro/vivo experiments indicated that PTXP lipos possess colloidal stability, prolonged blood circulation, high tumor site accumulation, potent anti-tumor effects, and safety. A combination of ionizable prodrugs and remote loading has proved to be an effective and simple strategy to achieve high liposomal encapsulation efficiency of poorly soluble non-ionizable drugs for clinical application.

Promoting Co-Crystallization in Poly(butylene succinate) and Poly(butylene fumarate) Blends via End-Group Functionalization.

Co-crystallization plays a crucial role in the integration and regulation of thermal and mechanical properties in polymer blends, but the poor compatibility of the components in the crystal phase has always been a major obstacle to co-crystallization, which puts forward stricter requests for linkage and interaction between different entities. On the basis of the hydrogen-bonding interaction that can promote chain stacking and thus improve miscibility, we propose that crystalline/crystalline blends of 2-ureido-4[1H]-pyrimidinone (UPy)-functionalized poly(butylene succinate) and poly(butylene fumarate) (PBS-UPy/PBF-UPy) where UPy groups with quadruple hydrogen-bonding interaction are employed to connect different chain ends, could inhibit phase separation and improve co-crystallization. PBS-UPy/PBF-UPy blends exhibit complex component-dependent and cooling-rate-dependent co-crystallization behavior. A high level of co-crystallization occurs in the range of PBS-UPy-rich fractions, and the proportion could approach over 98% under optimized conditions with the aid of UPy quadruple hydrogen bonds interaction. This work enriches the understanding of co-crystallization in crystalline/crystalline polymer blends and provides more possibility for the design of structures and properties of polymer materials.

Donnan Dialysis-Osmotic Distillation (DD-OD) Hybrid Process for Selective Ammonium Recovery Driven by Waste Alkali.

This work proposed an innovative and energy-efficient Donnan Dialysis (DD) and Osmotic Distillation (OD) hybrid process for alkali-driven ammonium recovery from wastewater. The efficiency and feasibility of ammonium removal and recovery from synthetic and real wastewater using NaOH and waste alkali were investigated. Ammonium in the feed first transported across the cation exchange membrane and accumulated in the receiver chamber. It is then deprotonated as ammonia, passing through the gas permeable membrane and finally is fixed as ammonium salt in the acid chamber. Our results indicated that employing waste alkali (red mud leachate) as driving solution led to excellent ammonium recovery performances (recovery efficiency of >80%), comparable to those of NaOH solution. When the initial ammonium concentration was 5 and 50 mM, the waste alkali driven DD-OD process achieved acceptable NH4+-N flux density of 16.8 and 169 g N m-2 d-1, at energy cost as low as 8.38 and 2.06 kWh kg-1 N, respectively. Since this alkali driven DD-OD hybrid process is based on solute concentration (or partial pressure) gradient, it could be an energy-effective technology capable of treating wastewaters containing ammonium using waste alkali to realize nutrients recovery in a sustainable manner.

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation-dependent probe amplification (MLPA) testing in all patients and next-generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.

Engineered IrO2@NiO Core-Shell Nanowires for Sensitive Non-enzymatic Detection of Trace Glucose in Saliva.

Hierarchical core-shell IrO2@NiO nanowires (NWs) have been designed through two simple steps, which combined electrospinning of IrO2 conductive core and chemical bath deposition growth of ultracontinuous NiO nanoflakes. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectrometry mapping, and X-ray photoelectron spectroscopy were employed to characterize the morphologies and structures of the as-prepared samples, and the results were also carefully compared with that of pure NiO nanoflowers and IrO2 NWs. Electrochemical studies indicate that the as-prepared core-shell IrO2@NiO NWs exhibited excellent nonenzymatic detection ability to glucose. At 0.35 V, it offered a sensitivity of 1439.4 µA mM-1 cm-2 (one order higher than pure NiO) with a wider linear range from 0.5 µM to 2.5 mM, a low detection limit of 0.31 µM (signal-to-noise ratio = 3, and moreover, good resolution in low glucose concentration, reproducibility, and long-term performance stability. Owing to the high sensitivity and performance, application of the proposed sensor in monitoring saliva glucose was also demonstrated; the results indicated that the sensor can effectively distinguish the diabetes from the healthy people and even the varying degrees of diabetic.

Fenofibrate nanoliposome: Preparation and its inhibitory effects on nonalcoholic fatty liver disease in mice.

The aim was to prepare fenofibrate nanoliposome (FNB-Nanolipo) and investigate its characterizations, oral pharmacokinetic (PK) profiles as well as preventive and therapeutic effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The prepared FNB-Nanolipo showed high drug loading capacity and sustained in vitro FNB release profile. Compared to FNB crude drug at equal doses, the FNB-Nanolipo given at 20 mg/kg/day (beginning on the same day when the MCD diet feeding started and lasted for 7 days) or 40 mg/kg/day (beginning after 7 days of the MCD diet feeding and lasting for another 7 days together with the MCD diet) increased plasma FNB concentration of the mice by 11.8-fold (P<0.05) or 57.3-fold (P<0.001), respectively, and reduced 54.7% (P<0.05) or 35.5% (P<0.05) of excessive hepatic lipid, respectively. The results suggest that the FNB-Nanolipo could not only significantly prevent but also efficiently treat NAFLD.

Preventive effects of simvastatin nanoliposome on isoproterenol-induced cardiac remodeling in mice.

In this study, simvastatin (SMV) and SMV nanoliposome (SMV-Lipo) were given to male BALB/c mice by either intragastric (i.g.) or intraperitoneal (i.p.) administration, and their effects on isoproterenol (ISO)-induced cardiac remodeling were compared. The results indicate that by i.p. administration, the SMV-Lipo at an equal SMV dose exhibited more significant inhibitory effects than the crude SMV on cardiac hypertrophy, fibrosis and inflammation. Comparing the SMV-Lipo on different administration regimens, i.p. group showed more significant inhibitory effects on cardiac remodeling than i.g. group. In addition, pharmacokinetic studies revealed that SMV-Lipo administrated by either i.p. or i.g. more significantly improved the plasma SMV concentration than the crude SMV. Therefore, the SMV-Lipo significantly enhanced the inhibitory effects of SMV on cardiac remodeling resulted from the enhanced absorption of SMV by nanoliposome formulation, and i.p. was better than i.g. administration.

Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified nanoliposomes.

Probucol (PB), an antioxidant drug, is commonly used as a lipid concentration lowering drug to reduce blood plasma cholesterol levels in the clinic. However, the therapeutic effects of this drug are negatively impacted by its poor water solubility and low oral absorption efficiency. In this study, a PEGylated G5 PAMAM dendrimer (G5-PEG) modified nanoliposome was employed to increase water solubility, transepithelial transport, and oral absorption of PB. The uptake mechanism was explored in vitro in Caco-2 cells with the results suggesting that the absorption improvement of G5-PEG modified PB-liposome (PB-liposome/G5-PEG) was related to P-glycoprotein (P-gp) efflux pump but was independent of caveolae endocytosis pathways. Additionally, plasma lipid concentration lowering effects of PB-liposome/G5-PEG were evaluated in vivo in a LDLR-/- hyperlipidemia mouse model. Compared with saline treated group, treatment with PB-liposome/G5-PEG significantly inhibited the increase of plasma total cholesterol (TC) and triglyceride (TG) of mice induced by a high fat diet. Moreover, its lipid concentration lowering effects and plasma drug concentration were greater than PB alone or commercial PB tablets. Our results demonstrated that PB-liposome/G5-PEG significantly increased the oral absorption of PB and therefore significantly improved its pharmacodynamic effects.

G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin.

This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery. FROM THE CLINICAL EDITOR: Various carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems.

Magnetic resonance tracking of endothelial progenitor cells labeled with alkyl-polyethylenimine 2 kDa/superparamagnetic iron oxide in a mouse lung carcinoma xenograft model.

The potential of using endothelial progenitor cells (EPCs) in novel anticancer therapy and the repair of vascular injury has been increasingly recognized. In the present study, EPCs were labeled with N-alkyl-polyethylenimine 2 kDa (PEI2k)-stabilized superparamagnetic iron oxide (SPIO) to facilitate magnetic resonance imaging (MRI) of EPCs in a mouse lung carcinoma xenograft model. EPCs derived from human peripheral blood were labeled with alkyl-PEI2k/SPIO. The viability and activity of labeled cells were evaluated using proliferation, migration, and tubulogenesis assays. Alkyl-PEI2k/SPIO-labeled EPCs were injected intravenously (group 1) or mixed and injected together with A549 cells subcutaneously (group 2) into groups of six mice with severe combined immunodeficiency. The labeling efficiency with alkyl-PEI2k/SPIO at 7 µg Fe/mL concentration was approximately 100%. Quantitative analysis of cellular iron was 6.062 ± 0.050 pg/cell. No significant effects on EPC proliferation, migration, or tubulogenesis were seen after labeling. Seven-tesla micro-MRI showed the presence of schistic or linear hypointense regions at the tumor margins starting from days 7 to 8 after EPC administration. This gradually extended into the inner tumor layers in group 1. In group 2, tumor growth was accompanied by dispersion of low-signal intensity regions inside the tumor. Iron-positive cells identified by Prussian blue dye were seen at the sites identified using MRI. Human CD31-positive cells and mouse CD31-positive cells were present in both groups. Labeling EPCs with alkyl-PEI2k/SPIO allows noninvasive magnetic resonance investigation of EPC involvement in tumor neovasculature and is associated with excellent biocompatibility and MRI sensitivity.

Relationship between the mandibular curve of Spee and the maxillary compensating curve with dentoskeletal morphology : A cross-sectional study in Chinese young adults with normal occlusion.

PURPOSE: The purpose of this cross-sectional study was to use multiple regression analysis to evaluate the relationship between the mandibular curve of Spee (COS) and the maxillary compensating curve with dentoskeletal morphology in young Chinese adults with normal occlusion. METHODS: This study comprised 62 young adults (31 males, mean age: 24.1 ± 2.2 years; 31 females, mean age: 23.3 ± 3.3 years) with Angle class I normal occlusion. For every subject, intraoral scan models of the maxillary and mandibular arches and lateral cephalograms were acquired. The depth of the COS and compensating curve were assessed on the intraoral scan models. Multiple dental arch dimensional and cephalometric variables were screened by univariate analysis. Subsequently, a multiple linear regression model (forward stepwise selection) was constructed to determine which variables were significantly correlated with the two curve depths. RESULTS: In the mandible, the COS depth was deepest at the mesiobuccal cusp of the first molar. Overjet, mandibular arch width and mandibular-occlusal plane angle significantly correlated with the COS depth (P < 0.05), accounting for 33.1% of the variation in the mandibular COS. In the maxilla, the deepest point of the compensating curve was at the distobuccal cusp of the first molar. Mandibular arch perimeter and overbite significantly correlated with the maxillary compensating curve (P < 0.05), explaining 23.3% of the variation. CONCLUSIONS: Overjet, overbite, mandibular-occlusal plane angle, mandibular arch width and perimeter should be considered when reconstructing occlusal curves in clinical orthodontic treatment and in prosthetic restoration.

Radiographic evaluation of the tenting screw technique in horizontal alveolar bone augmentation: A retrospective study.

OBJECTIVES: To radiographically analyze the effects of tenting screw technique (TS) and onlay bone grafts (OG) in horizontal bone augmentation. MATERIALS AND METHODS: Patients receiving horizontal bone augmentation by TS or OG were selected. The clinical outcomes and cone beam computed tomography (CBCT) data were documented pre-grafting, immediately post-grafting, before and after implantation. The survival rates, clinical complications, alveolar bone width, and volumetric bone augmentation were evaluated and statistically analyzed. RESULTS: A total of 25 patients and 41 implants were involved in this study, with no grafting failures observed in either the TS group (n = 20) or the onlay group (n = 21). Volumetric bone resorption rate in the TS group (21.34%) was significantly lower than that of the OG group (29.38%). In addition, significant horizontal bone gain was achieved in both groups (TS: 6.15 ± 2.12 mm; OG: 4.86 ± 1.40 mm) during the recovery period, with higher gain in the TS group. No apparent statistical difference in terms of volumetric bone gain was observed between the TS (748.53 mm3 , 607.47 mm3 ) and OG group (811.77 mm3 , 508.49 mm3 ) immediately post-grafting or after the recovery period. CONCLUSION: Both TS and OG achieved satisfactory bone augmentation effects, yet TS resulted in more bone augmentation and better stability than OG, with a reduced use of autogenous bone. Overall, the tenting screw technique can serve as an effective alternative to autogenous bone grafts.

Integrated dual-channel electrochemical immunosensor for early diagnosis and monitoring of periodontitis by detecting multiple biomarkers in saliva.

Periodontitis, as the sixth prevalence chronic inflammation worldwide, has inconspicuous and often-overlooked symptoms at early stage, eventually leading to permanent damage to the teeth and supporting tissues. The timely and accurate diagnosis of periodontitis and monitoring its progress appear to be particularly important for clinical treatment. Herein, a dual-channel electrochemical immunosensor was developed for the synchronized detection of two periodontitis-related biomarkers in saliva: interleukin-1ß (IL-1ß) and matrix metalloproteinase-8 (MMP-8). Owing to its miniaturization, detachability, and portability, this sensor has the potential to detect multiple biomarkers in a point-of-care manner for the early diagnosis and monitoring of periodontitis. The nanocomposites consisted of iridium oxide nanotubes and two-dimensional MXene nanosheets enhance the electrochemical performance of the sensor, achieving excellent sensitivity with wide detection ranges of 0.1-100 and 1-200 ng mL-1, low limits of detection of 0.014 and 0.13 ng mL-1, and relatively high correlation coefficients of 0.9911 and 0.9990 for IL-1ß and MMP-8, respectively. Furthermore, this device possesses excellent selectivity in complex samples without cross-talk, as well as high recovery and accuracy in spiked artificial saliva. Importantly, the dual-channel device achieves higher diagnostic accuracy for different stages of periodontitis when MMP-8 and IL-1ß were simultaneously monitored within clinicopathological saliva. This work proposes a considerable potential for early diagnosis and severity distinguishment of periodontitis in a point-of-care manner, which would be beneficial for progression prediction, treatment guidance, and prognosis assessment of periodontitis.

Pollution characteristics and source analysis of microplastics in the Qiantang River in southeastern China.

Microplastic pollution resulting from industrialization and urbanization is increasingly serious. Hangzhou is a city with high industrial/urban growth in Southeast China. Focusing on the microplastic pollution in the Hangzhou section Qiantang River, six samples were collected and analyzed during different hydrological periods (normal, wet, and dry periods) and the relationship between microplastic pollution and economic development was investigated. Results showed that more microplastics were found during the dry period than that of the wet period (49.8 vs. 13.2%). Microplastic abundance was 1.5-9.4 items L-1, showing significant spatial differences in sampling sites. Among the collecting microplastics, debris and fibers accounted for 36.4 and 30.9%. Polyethylene terephthalate and polyvinyl chloride were the main polymers, accounting for 48.3 and 31.8%, respectively. Microplastics with size <1 mm accounted for 60% of the microplastics in surface water samples. Spatially, microplastic abundance was the highest in the middle of the river. Redundant analysis revealed that the per capita GDP (p = 0.002), high-end equipment industry (p = 0.028) and fashion manufacturing (p = 0.006) influenced microplastic abundance. Urbanization coupled with rapid economic development led to increase in local microplastic pollution. Our results provide insight into microplastic distribution patterns in urban river systems in China.

Development of predictive quantitative retention-activity relationship models of alkaloids by mixed micellar liquid chromatography.

The mixed micellar liquid chromatography is a mode that uses mixed micellar system of Brij35/SDS (85 : 15) as a mobile phase under adequate experimental conditions, can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains remains unchanged. In this article, the applications of biopartitioning micellar chromatography, using mixed micellar system to describe and estimate bioactivities of alkaloids, has been focused. The BMC(Brij35/SDS)-QRAR models of half-life time, volume of distribution, plasma clearance and area under concentration-time curve were obtained using Brij35-SDS retention data. The aim is to take a look at the capability of the mixed micellar liquid chromatography model to describe and/or estimate the bioactivity of alkaloids.

Identification and functional characterization of novel GDAP1 variants in Chinese patients with Charcot-Marie-Tooth disease.

OBJECTIVE: To identify and characterize the pathogenicity of novel variants in Chinese patients with Charcot-Marie-Tooth disease. METHODS: Multiplex ligation-dependent probe amplification (MLPA) and whole-exome sequencing (WES) were performed in 30 unrelated CMT patients. Minigene assay was used to verify the effect of a novel splicing variant (c.694+1G>A) on pre-mRNA. Primary fibroblast cell lines were established from skin biopsies to characterize the biological effects of the novel variants p.L26R and p.S169fs. The mitochondrial structure was observed by an electron microscope. The expression level of protein was analyzed by Western Blotting. Mitochondrial dynamics and mitochondrial membrane potential (MMP, Δψm) were analyzed via immunofluorescence study. Mitochondrial ATP levels were analyzed via bioluminescence assay. The rate of oxygen consumption was measured with a Seahorse Bioscience XF-96 extracellular flux analyzer. RESULTS: We identified 10 pathogenic variants in three known CMT related genes, including three novel variants (p.L26R, p.S169fs, c.694+1G>A) and one known pathogenic variant (p.R120W) in GDAP1. Further, we described the clinical features of patients carrying pathogenic variants in GDAP1 and found that almost all Chinese CMT patients with GDAP1 variants present axonal type. The effect of c.694+1G>A on pre-mRNA was verified via minigene splice assay. Cellular biological effects showed ultrastructure damage of mitochondrial, reduced protein levels, different patterns of mitochondrial dynamics, decreased mitochondrial membrane potential (Δψm), ATP content, and defects in respiratory capacity in the patient carrying p.L26R and p.S169fs in GDAP1. INTERPRETATION: Our results broaden the genetic spectrum of GDAP1 and provided functional evidence for mitochondrial pathways in the pathogenesis of GDAP1 variants.

Physiologic Factors Affecting the Circulatory Persistence of Copolymer Microbubbles and Comparison of Contrast-Enhanced Effects between Copolymer Microbubbles and Sonovue.

Ultrasound contrast agents have been widely used in clinical diagnosis. Knowledge of the physiologic factors affecting circulatory persistence is helpful in preparing long-lasting microbubbles (MBs) for blood perfusion and drug delivery research. In the study described here, we prepared copolymer MBs, compared their characteristics and contrast-enhanced effects with those of SonoVue and investigated the influence of external pressure, temperature, plasma components, renal microcirculation and cardiac motion on their circulatory persistence. The mean size of the copolymer MBs was 3.57 µm, larger than that of SonoVue. The copolymer MBs had longer circulatory persistence than SonoVue. At external pressures of 110 and 150 mm Hg, neither the quantity nor the morphology of the copolymer MBs changed. Further, their quantity and size were similar after incubation at 4°C and 39.4°C and when rabbit plasma and saline were compared. In vivo contrast-enhanced ultrasonography revealed a slightly larger area under the curve for the renal artery than for the renal vein. Thus, copolymer MBs exhibited good stability. However, the quantity of copolymer MBs decreased significantly after 180 s of circulation in an isolated toad heart perfusion model, indicating that cardiac motion was the main factor affecting their circulatory persistence.

Co-immunizing with PD-L1 induces CD8+ DCs-mediated anti-tumor immunity in multiple myeloma.

Tumor therapeutic vaccines have faced a challenge for effective protection against malignant tumors by inducing tumor-specific CD8+ T cell responses. Here, we designed a DNA vaccine containing a tumor-specific antigen of Dickkopf-1 (DKK-1) and an immune checkpoint of programmed death ligand 1 (PD-L1) delivered by PLGA/PEI nanoparticle-mediated delivery system for multiple myeloma therapy. Murine subcutaneous tumor model established with human DKK1 (hDKK-1)-SP2/0 cells were intramuscularly immunized with PLGA/PEI-pPD-L1/pDDK-1 vaccine and equal amount of control 3 times at 10 day-intervals. Compared with PLGA/PEI-pDKK1 immunization group, PLGA/PEI-pPD-L1/pDKK-1 co-immunization enhanced the induction and mature of CD11c+ DCs and CD8+CD11c+ DCs, and promoted antigen-specific Th1 responses and cytotoxic T lymphocyte (CTL) responses. The reduced tumor volume and weight as well as increased tumor inhibition rate were observed in PLGA/PEI-pPD-L1/pDKK-1 vaccine co-immunization group, indicated that the vaccine could effectively inhibit the tumor growth of multiple myeloma. The anti-tumor activity of PLGA/PEI-pPD-L1/pDKK-1 vaccine was abrogated by CD8 cell depletion accompanied with the reduced percentages of CD8+CD11c+ DCs and CD8+ T cells in the spleen and TILs. These results indicated that the anti-tumor efficacy of PLGA/PEI-pPD-L1/pDKK-1 vaccine was required for CD8+CD11c+ DCs-mediated CD8+ T cell immunity responses. This vaccine strategy may represent a potential and promising approach for hematological malignancy treatment.

Mixed micellar liquid chromatography methods: modelling quantitative retention-activity relationships of angiotensin converting enzyme inhibitors.

The capability of biopartitioning micellar chromatography (BMC), using pure Brij35 solution and mixed micellar system of Brij35-SDS (85:15) as mobile phase, to describe and estimate bioactivities of angiotensin converting enzyme inhibitors at different pH has been studied. Quantitative retention-activity relationships (QRAR) in BMC were investigated for these compounds. The obtained BMC(Brij35-SDS)-QRAR models were compared with the traditional BMC(Brij35)-QRAR, and better statistically models were obtained using Brij35-SDS retention data. The superiority of BMC(Brij35-SDS)-QRAR is due to the fact that the mixed micellar mobile phase can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains remains unchanged.