Periodontal disease increases the severity of chronic obstructive pulmonary disease: a Mendelian randomization study.

BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.

Chelation Behaviors of 3,4,3-LI(1,2-HOPO) with Lanthanides and Actinides Implicated by Molecular Dynamics Simulations.

The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) (denoted as t-HOPO) is a potential chelator agent for decorporation of in vivo actinides (An), while its coordination modes with actinides and the dynamics of the complexes (An(t-HOPO)) in aqueous phase remain unclear. Here, we report molecular dynamics simulations of the complexes with key actinides (Am3+, Cm3+, Th4+, U4+, Np4+, Pu4+) to study their coordination and dynamic behaviors. For comparison, the complexation of the ligand with a ferric ion and key lanthanides (Sm3+, Eu3+, Gd3+) was also studied. The simulations show that the nature of metal ions determines the properties of the complexes. The t-HOPO in the FeIII(t-HOPO)1- complex ion formed a compact and rigid cage to encapsulate the ferric ion, which was hexa-coordinated. Ln3+/An3+ cations were ennea-coordinated with eight ligating oxygen atoms from t-HOPO and one from an aqua ligand, and An4+ cations were deca-coordinated with a second aqua ligand. The t-HOPO shows strong affinity for metal ions (stronger for An4+ than Ln3+/An3+) benefited from its high denticity and its flexible backbone. Meanwhile, the complexes displayed different dynamic flexibilities, with the AnIV(t-HOPO) complexes more significant than the others, and in the AnIV(t-HOPO) complexes, the fluctuation of the t-HOPO ligand was highly correlated with that of the eight ligating O atoms. This is attributed to the more compact conformation of the ligand, which raises backbone tension, and the competition of the aqua ligand against the t-HOPO ligand in coordinating with the tetravalent actinides. This work enriches our understanding on the structures and conformational dynamics of the complexes of actinides with t-HOPO and is expected to benefit the design of HOPO analogues for actinide sequestering.

Salivary microbiome diversity in Chinese children with various caries states.

OBJECTIVE: This study aimed to explore oral microbiome diversity among children with various caries status based on dmft scores. METHODS: A total of 320 children aged 3-5 years were recruited, with 66 healthy children and 254 children affected by dental caries. According to dmft scores, these children with dental caries were classified as "mild group" (dmft score 1-3), "moderate group" (dmft score 4-6), and "severe group" (dmft score 7-14). Healthy children with dmft score of 0 served as control group. Illumina MiSeq sequencing was employed to analyze all salivary samples collected from these children. RESULTS: The salivary microbial diversity among four groups was similar (p > 0.05). A total of five bacterial genera were highly abundant in the control group including Bergeyella, Acidimicrobiales, Acidimicrobiia, Halomonas, and Blautia (p < 0.05). For mild group, there were nine bacterial genera identified to be predominant: Porphyromonadaceae, Porphyromonas, Enterobacteriales, Enterobacteriaceae, Weissella, Leuconostocaceae, Alphaproteobacteria, Stenotrophomonas, and Rhizobiales (p < 0.05). Only one genus, Aggregatibacter was predominant in moderate group (p < 0.05). There were six bacterial genera (Alistipes, Lachnoclostridium, Escherichia-Shigella, Romboutsia, Sphingomonadales, and Denitratisoma) enriched in severe group (p < 0.05). CONCLUSION: Oral microbial profile was different in children with various caries status based on dmft scores. CLINICAL RELEVANCE: The results might be beneficial to deeply understand microbiological diversity of early childhood caries (ECC) at various stages and inform effective strategies for ECC prevention.

UV-guided isolation of enantiomeric polyacetylenes from Bupleurum scorzonerifolium Willd. with inhibitory effects against LPS-induced NO release in BV-2 microglial cells.

UV-guided fractionation led to the isolation of thirteen new polyacetylenes (1-13) from the roots of Bupleurum scorzonerifolium Willd. All polyacetylenes were analyzed as racemates since the lack of optical activity and Cotton effects in the ECD spectra. The sequent chiral-phase HPLC resolution successfully gave twelve pairs of enantiomers 1a/1b and 3a/3b-13a/13b. Their structures were elucidated based on the HRESIMS and NMR data analyses. The absolute configurations were determined by the combination of Snatzke's method, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Using Griess methods and MTT assays, polyacetylenes 1a, 3a, 4a/4b-12a/12b, and 13a displayed inhibitory activities against LPS-induced NO release in BV-2 microglial cells.

Interface behavior changes of weathered polystyrene with ciprofloxacin in seawater environment.

With the progress of research on micro-nano plastics, the weathering degradation process in the natural environment has gradually become the focus of academic discussion. This study adopted the Fenton immersion method to accelerate the simulation of the weathering process of microplastics in nature, and explored the interface behavior of the weathered microplastics and hydrophilic antibiotics. It was found that the weathered polystyrene (PS) has a smaller crystallinity, increased oxygen-containing functional groups, and cracks appear on the surface, making it more likely to be weathered. At the same time, the rougher surface and stronger hydrophilicity of the weathered PS particles made it easier to adsorb hydrophilic antibiotics. Subsequent studies showed that the adsorption of ciprofloxacin (CIP·HCl) by weathered PS is much larger than that of original PS particles, whose maximum adsorption is 5.45 mg/g in the isotherm experiments. We found that the adsorption behavior of weathered PS particles with CIP in seawater would be weakened in the real seawater environment and humic acid, which might be due to the competitive adsorption of CIP by various ions. Further studies have shown that changes in the ionic strength and pH of the solution also affected the adsorption behavior to varying degrees. The results of dynamic adsorption were the same as the static adsorption, and the adsorption rate and capacity of weathered PS particles were enhanced compared with the original particles. The results of this article not only provided a data reference for studying the weathering process of microplastics but also helped to explore the ultimate fate of microplastics.

An association analysis for genetic factors for dental caries susceptibility in a cohort of Chinese children.

OBJECTIVE: To comprehensively investigate the effects of 25 variants in 15 genes on dental caries susceptibility in a cohort of Chinese children. METHODS: A total of 25 variants in 15 genes were genotyped with MassARRAY iPLEX system and analyzed in 265 healthy controls and 254 children affected by dental caries with different dmft scores. The children with dental caries were stratified into "mild group" (scores from 1 to 3), "moderate group" (scores from 4 to 6), and "severe group" (scores from 7 to 14). RESULTS: The association analysis revealed that rs11362 of defensin ß1 (DEFB1) was significantly associated with dental caries susceptibility (OR = 2.447, p = 1.165E-04). Furthermore, rs11362 was positively correlated with the severity of dental caries. For another selected variant of DEFB1, rs1799946 was significantly associated with dental caries susceptibility in the severe group (OR = 0.473, p = 3.70E-03) and also significant in the group consisted of moderate and severe subjects (OR = 0.623, p = .033). The results from logistic regression in additive, dominant, and recessive models also exhibited the similar patterns. CONCLUSION: Out of 25 selected variants, only 2 of DEFB1 gene (rs11362 and rs1799946) were significantly associated with dental caries susceptibility in children.

Accuracy of dental arch form in customized fixed labial orthodontic appliances.

INTRODUCTION: This study evaluated arch form accuracy with or without premolar extraction in customized fixed labial orthodontic appliance treatment. METHODS: Setup and posttreatment digital models of 27 samples (15 extractions and 12 nonextractions) were selected and superimposed by best-fit surface-based registration in both the maxilla and the mandible. The facial axis points were identified and converted into Cartesian coordinates. A sixth-order polynomial equation was used to fit dental arches. Arch discrepancies (the mean distance between 2 arch forms) and similarities were compared between extraction and nonextraction groups, maxilla and mandible, and anterior and posterior arches. RESULTS: The arch discrepancy between extraction and nonextraction groups showed no statistically significant difference, but a statistically significant difference in arch similarity was found in the mandible. There were statistically significant differences between anterior and posterior arch discrepancies in the extraction (mandible) and the nonextraction (maxilla and mandible) groups. However, no statistically significant correlation was shown between anterior and posterior arch discrepancies. The arch similarities were 96.18% and 97.38% in the maxilla and 96.01% and 97.49% in the mandible between extraction and nonextraction groups. Arch form discrepancies and similarities showed a moderate correlation but no statistically significant differences between the maxilla and the mandible. CONCLUSIONS: In customized fixed labial orthodontic appliance treatment, arch form setup can be accurately achieved with and without premolar extraction. Anterior arch form acquires fewer discrepancies than the posterior arch, and overcorrection should be added to the end of the customized archwire to reduce posterior arch discrepancies. The discrepancy of the maxillary and mandibular arches is interrelated, and adjustments should be made on both maxillary and mandibular archwires to correct single-jaw transverse malposition.

Establishment of a C57BL/6 Mandibular Critical-Size Bone Defect Model.

PURPOSE: The goal of this study was to identify bone defects of critical size in C57BL/6 mouse mandibles. MATERIALS AND METHODS: Twenty-four male mice were included in this study. All mice underwent surgeries on their left mandibles. Mandibular defects of 1.0 mm (n = 8), 1.6 mm (n = 8), and 2.3 mm (n = 8) were created. For the investigation of bone healing after an 8-week period, micro-computed tomography scans and histomorphology were performed. RESULTS: Mandibular bone nonunions were seen 0/8 in the 1.0-mm group, 6/8 in the 1.6-mm group, and 8/8 in the 2.3-mm group. The outcome of micro-computed tomography showed that, after 8 weeks, the bone mineral density and the bone volume to total volume ratio were significantly different among the 3 groups. The defect gaps in the nonunion 1.6- and 2.3-mm groups were filled with connective tissue, and no obvious bone formation was found. Additionally, in quantitative analysis, according to the new bone fill calculations, the percentages were 91.85% ±â€Š8.03% in the 1.0-mm group, 59.84% ±â€Š20.60% in the 1.6-mm group, and 15.36% ±â€Š8.28% in the 2.3-mm group, which indicated statistically significantly lower defect healing in the 2.3-mm group. CONCLUSIONS: The creation of 2.3-mm mandibular defects produces osseous nonunion in C57BL/6 mice.

Comparison of crown fit and operator preferences between tooth preparation with electric and air-turbine handpieces.

STATEMENT OF PROBLEM: Tooth preparations for ceramic crowns require precision and accuracy, which may be influenced by the choice of dental handpiece. However, comparisons of the accuracy of tooth preparations made with traditional air-turbine handpieces and electric handpieces are lacking. PURPOSE: The purpose of this in vitro study was to evaluate operator preferences and tooth preparation performance by using electric and air-turbine handpieces with self-reported preferences, sound levels, surface roughness, and the fit of the crown produced. MATERIAL AND METHODS: Twenty dentists were asked to use the air-turbine or the electric handpiece. Feedback on the noise, weight, feel of grip, flexibility, and tooth preparation in general was scored according to a visual analog scale (VAS). Additionally, the dentists were asked to complete a questionnaire on their handpiece preference. The noise of the 2 handpieces was measured by using a precision sound level meter. The surface roughness of 10 teeth was measured by using a profilometer. The other 18 teeth were prepared to measure the marginal and internal fit of ceramic crowns by the replica technique. The VAS scores of operator preferences were analyzed with the Wilcoxon signed ranks test. Decibel levels were analyzed with the Mann-Whitney U test. The McNemar test was used to compare the ratio of preferred handpiece. The surface roughness and marginal and internal fit were analyzed with the independent t test to determine significant differences (all α=.05). RESULTS: The electric handpiece was heavier, had a poorer grip feel, was less flexible (P<.001), produced lower noise and better feeling of the tooth preparation in general (P<.001), and was preferred in the finishing stage for its greater smoothness (P<.05). The noise produced by the electric handpiece was lower during both idling and tooth preparation at 15-cm, 30-cm, and 45-cm distances (P<.01). The electric handpiece produced surface roughness values (Sa) similar to those of the air-turbine handpiece (P>.05). No significant differences were noted for the marginal and internal crown fit between the air-turbine handpiece and electric handpiece groups (P>.05). CONCLUSIONS: Despite its heavier weight, poorer grip feel, and less flexibility, the electric handpiece emitted lower noise, produced better feeling of the tooth preparation in general, and was preferred in the finishing step of tooth preparation for its greater smoothness than the air-turbine handpiece. The surface roughness of the prepared teeth and the crown fit between the tooth and ceramic crown were not affected by the air-turbine or electric handpiece.

Dysbiosis of saliva microbiome in patients with oral lichen planus.

BACKGROUND: Oral microbiota is not only important for maintaining oral health but also plays a role in various oral diseases. However, studies regarding microbiome changes in oral lichen planus (OLP) are very limited. To the best of our knowledge, there has been only two studies investigating salivary microbiome changes in OLP. Therefore, the purpose of this study was to identify the characteristic microbial profile in the saliva of OLP patients, with or without erosive lesions, and compare that with recurrent aphthous ulcer (RAU), a common oral immunological disorder that also shows multiple erosive/ulcerative lesions. Whole saliva samples were collected from 20 patients with OLP (erosive E, n = 10 and non-erosive NE, n = 10), 10 patients with RAU (U) and 10 healthy controls (C). DNA was extracted from the saliva samples, and the 16S rDNA gene V4 hypervariable region was analyzed using Illumina sequencing. RESULTS: We obtained 4949 operational taxonomic units (OTUs) from the V4 region in all saliva samples. Community composition analysis showed a clear decreased relative abundance of genera Streptococcus and Sphingomonas in saliva from RAU patients when compared to the other three groups. Relative abundance of Lautropia and Gemella were higher in E group, whereas relative abundance of Haemophilus and Neisseria were higher in NE group when compared to C group. Abiotrophia and Oribacterium were higher in OLP (combining E and NE groups), while Eikenella and Aggregatibacter were lower when compared to C group. There was statistically significance in α-diversity between E and RAU groups(p < 0.05). Significant differences in ß-diversity were detected in bacteria between E and C; NE and C; as well as E and NE groups. The LDA effect size algorithm identified the g_Haemophilus might be the potential biomarker in NE group. CONCLUSIONS: We found that salivary microbiome in erosive OLP was significantly different from that found in RAU; and these changes may be related to the underlying disease process rather than presence of ulcerative/erosive lesions clinically. In addition, our findings in bacterial relative abundance in OLP were significantly different from the previously reported findings, which points to the need for further research in salivary microbiome of OLP.

An electrochemical aptasensing platform for carbohydrate antigen 125 based on the use of flower-like gold nanostructures and target-triggered strand displacement amplification.

An electrochemical aptasensing method is described for the determination of the biomarker CA125. It combines aptamer recognition and target-triggered strand displacement amplification. Flower like gold nanostructures were electrodeposited on a screen-printed carbon electrode to increase the sensor surface, to assemble more toehold-containing hairpin probe 1 (Hp1), and to improve the accessibility for DNA strands. Under the optimal conditions, this assay has a linear response in the 0.05 to 50 ng•mL-1 CA125 concentration range, with a low detection limit of 5.0 pg•mL-1. This method is specific and stable. It was successfully applied to the detection of CA125 in spiked biological samples, with recoveries between 82.5% and 104.1%. Graphical abstract.

Cyclam-Modified PEI for Combined VEGF siRNA Silencing and CXCR4 Inhibition To Treat Metastatic Breast Cancer.

Chemokine receptor CXCR4 plays an important role in cancer cell invasion and metastasis. Recent findings suggest that anti-VEGF therapies upregulate CXCR4 expression, which contributes to resistance to antiangiogenic therapies. Here, we report the development of novel derivatives of polyethylenimine (PEI) that effectively inhibit CXCR4 while delivering anti-VEGF siRNA. PEI was alkylated with different amounts of a CXCR4-binding cyclam derivative to prepare PEI-C. Modification with the cyclam derivatives resulted in a considerable decrease in cytotoxicity when compared with unmodified PEI. All the PEI-C showed significant CXCR4 antagonism and the ability to inhibit cancer cell invasion. Polyplexes of PEI-C prepared with siVEGF showed effective silencing of the VEGF expression in vitro. In vivo testing in a syngeneic breast cancer model showed promising antitumor and antimetastatic activity of the PEI-C/siVEGF polyplexes. Our data demonstrate the feasibility of using PEI-C as a carrier for simultaneous VEGF silencing and CXCR4 inhibition for enhanced antiangiogenic cancer therapies.

Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis.

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.

Broadening the versatility of lentiviral vectors as a tool in nucleic acid research via genetic code expansion.

With the aim of broadening the versatility of lentiviral vectors as a tool in nucleic acid research, we expanded the genetic code in the propagation of lentiviral vectors for site-specific incorporation of chemical moieties with unique properties. Through systematic exploration of the structure-function relationship of lentiviral VSVg envelope by site-specific mutagenesis and incorporation of residues displaying azide- and diazirine-moieties, the modifiable sites on the vector surface were identified, with most at the PH domain that neither affects the expression of envelope protein nor propagation or infectivity of the progeny virus. Furthermore, via the incorporation of such chemical moieties, a variety of fluorescence probes, ligands, PEG and other functional molecules are conjugated, orthogonally and stoichiometrically, to the lentiviral vector. Using this methodology, a facile platform is established that is useful for tracking virus movement, targeting gene delivery and detecting virus-host interactions. This study may provide a new direction for rational design of lentiviral vectors, with significant impact on both basic research and therapeutic applications.

Effect of "phase change" complex on postoperative adhesion prevention.

BACKGROUND: Postsurgical peritoneal adhesion is a major clinical problem. Numerous anti-adhesion products have been studied, but none could be easily used to provide a physical barrier. In this study, we developed a "phase change" anti-adhesion barrier for reducing peritoneal adhesion by cross-linked copolymerization of O-carboxymethyl chitosan (CMC) and CaCl2 and addition of cyclosporin A (CsA). MATERIALS AND METHODS: The CMC-CaCl2-CsA compound was characterized by equilibrium swelling rate, weight loss, releasing effect, and coagulation test, and its biosafety was characterized by acute oral toxicity, hemolysis, and cytotoxicity. Intestinal adhesion model was applied on 64 Sprague-Dawley rats, which received CMC, CMC-CaCl2, or CMC-CaCl2-CsA treatment. At postoperative days 7 and 14, the rats were euthanized, and adhesions were graded by an investigator blinded to the treatment groups, using a predetermined adhesion scoring system. The cecum and adhesion tissue were stained with hematoxylin and eosin and antibodies for matrix metalloproteinase-9 and TIMP-1 for further histopathologic examination. RESULTS: The phase change anti-adhesive material exhibited effective blood clotting and were nontoxic in clotting experiments and acute toxicity test. The degradation rate could be adjusted using phosphate-buffered solution with varying pH. Adhesions were significantly reduced in the CMC-CaCl2-CsA treatment group compared with the control group (P < 0.001). Expression of matrix metalloproteinase-9 was stronger in CMC-CaCl2-CsA treatment group at 7 days after surgery. CONCLUSIONS: "Phase-change" adhesive can undergo changes after application, and it inhibits the formation of abdominal adhesions after surgery. The material is convenient for using by surgeons and provides an effective tool for intestinal adhesion prevention.

CCL17 combined with CCL19 as a nasal adjuvant enhances the immunogenicity of an anti-caries DNA vaccine in rodents.

AIM: CCL19 and its receptor CCR7 are essential molecules for facilitating the trafficking of mature dendritic cells (DCs) and helping to establish a microenvironment in lymphoid tissues to initiate primary immune responses, whereas CCL17 is required in the CCR7-CCL19-dependent migration of DCs. In this study we examined whether co-administration of CCL17 and CCL19 could enhance the immunogenicity of an anti-caries DNA vaccine, pCIA-P, in rodents. METHODS: Plasmids encoding CCL17 (pCCL17/VAX) and CCL19 (pCCL19/VAX) were constructed. BALB/c mice were intranasally administered pCCL17/VAX, pCCL19/VAX, or pCCL17/VAX plus pCCL19/VAX, the migration of DCs to the spleen and draining lymph nodes (DLNs) was assessed with flow cytometry. The mice were co-administered pCIA-P; and the anti-PAc antibodies in the serum and saliva were detected with ELISA. Wistar rats were orally challenged with Streptococcus mutans and then administered pCIA-P in combination with pCCL17/VAX, pCCL19/VAX, or pCCL17/VAX plus pCCL19/VAX. The amount of S mutans sustained on rat molar surfaces was assessed using a colony forming assay. Caries activity was scored with the Keyes method. RESULTS: Co-administration of the CCL17 and CCL19 genes in mice caused a greater increase in the number of mature DCs in the spleen and DLNs compared with administration of CCL17 or CCL19 genes alone. CCL17 and CCL19 double-adjuvant plus pCIA-P induced significantly higher levels of anti-PAc salivary IgA and anti-PAc serum IgG antibody in mice, and strengthened the ability of pCIA-P in inhibiting the colonization of S mutans on rat tooth surfaces. The caries activity of the combined adjuvant group was significantly lower than that of the pCCL17/VAX or the pCCL19/VAX group. CONCLUSION: A nasal adjuvant consisting of a combination of CCL17 and CCL19 attracts more mature DCs to secondary lymphoid tissues, inducing enhanced antibody responses against the anti-caries DNA vaccine pCIA-P and reducing S mutans infection in rodents.

Fabrication of Waterproof, Breathable Composite Liquid Dressing and Its Application in Diabetic Skin Ulcer Repair.

OBJECTIVES: Diabetic patients are at increased risk of severe skin infections. Covering the wound as early as possible can prevent infection and shorten the course of treatment. In this study, the authors fabricated a waterproof and breathable composite liquid dressing (CLD) that formed a barrier to bacteria and shortened healing time of diabetic rat skin ulcers. METHODS: The CLD was prepared in a formulation that, on evaporation of the liquid carrier, acts as a waterproof, breathable coating on injured skin. The coating was analyzed for water resistance, moisture vapor transmission rate (MVTR), bacterial barrier properties, sustained-release function, and biosafety. A chemically induced rat model of diabetic foot ulcers was used to examine the wound healing effect of CLD and CLD that contained Dermlin (Yensen Biotech Co, Jiangyin, Jiangsu, China). The wound healing rate, histologic changes, and epidermal growth factor expression were also evaluated. RESULTS: The CLD functioned as an effective barrier against infection, was waterproof, had a suitable MVTR, and had effective biosafety. The synergistic effects of CLD and Dermlin had a rapid wound closure rate. Histologic analysis and measurement of epidermal growth factor expression through an in vivo test revealed that the possible mechanism of the CLD effects included the reduction of inflammation and promotion of cell proliferation. CONCLUSIONS: Early treatment with the CLD can prevent infection. In combination with Dermlin, the CLD may promote better wound closure in diabetic skin ulcers. The authors' study suggests a novel strategy for ulcer healing.

Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.

The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy.

Recovery of energy and iron from oily sludge pyrolysis in a fluidized bed reactor.

In the steel industry, about 0.86 ton of oily sludge is produced for every 1000 tons of rolling steel. Due to the adverse impact on human health and the environment, oily sludge is designated as a hazardous waste in the Resource Conservation and Recovery Act (RCRT). In this paper, the pyrolysis treatment of oily sludge is studied in a fluidized bed reactor at a temperature range of 400-600 °C. During oily sludge pyrolysis, a maximum oil yield of 59.2% and a minimum energy loss of 19.0% are achieved at 500 °C. The energy consumption of treating 1 kg oily sludge is only 2.4-2.9 MJ. At the same time, the energy of produced oil, gas and solid residue are 20.8, 6.32, and 0.83 MJ, respectively. In particular, it is found that the solid residue contains more than 42% iron oxide, which can be used as the raw material for iron production. Thus, the simultaneous recovery of energy and iron from oil sludge by pyrolysis is feasible.

Randomized trial of asunaprevir plus peginterferon alfa and ribavirin for previously untreated genotype 1 or 4 chronic hepatitis C.

BACKGROUND & AIMS: Asunaprevir is a selective HCV NS3 protease inhibitor, active against genotypes 1, 4, 5, and 6 in vitro. We evaluated asunaprevir plus peginterferon alfa-2a/ribavirin (PegIFNα/RBV) for genotype 1 and 4 chronic HCV. METHODS: In this phase 2b, double-blind, placebo-controlled study, treatment-naive adults with genotype 1 (n=213) or 4 (n=25) were randomly assigned (3:1) to asunaprevir 200mg or placebo twice daily plus PegIFNα/RBV. Asunaprevir recipients, achieving protocol-defined response (HCV-RNA below quantification limit at week 4 and undetectable at week 10), were rerandomized at week 12 to continue asunaprevir-based triple therapy or receive placebo plus PegIFNα/RBV for weeks 13-24. Patients without protocol-defined response (PDR) and placebo recipients continued PegIFNα/RBV through week 48. Co-primary end points were undetectable HCV-RNA at week 4 and 12 (eRVR) and 24 weeks posttreatment (SVR24). RESULTS: Most patients were male (64.3%), white (83.6%), and had non-CC IL28B genotypes (71.3%). Among genotype 1 patients, eRVR rates (asunaprevir vs. placebo) were 67% (80% CI 62, 72) vs. 6% (80% CI 2, 10); corresponding SVR24 rates were 64% (80% CI 59, 68) vs. 44% (80% CI 36, 53). SVR24 among genotype 4 patients was 89% (asunaprevir) vs. 43% (placebo). Rates of rash and haematologic adverse events were similar between treatment groups. Five asunaprevir-treated patients had grade 4 alanine aminotransferase elevations that resolved following discontinuation (n=4) or with continued dosing (n=1). CONCLUSIONS: Addition of asunaprevir to PegIFNα/RBV in treatment-naive genotype 1- or 4-infected patients improves response rates and is well tolerated, with aminotransferase elevations that were manageable with appropriate monitoring. ClinicalTrials.gov ID: NCT01030432.