Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.

A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.

Mussel-Inspired Two-Dimensional Halide Perovskite Facilitated Dopamine Polymerization and Self-Adhesive Photoelectric Coating.

Polydopamine (PDA) is a good adhesion agent for lots of gels inspired by the mussel, whereas hybrid organic-inorganic perovskites (HOIPs) usually exhibit extraordinary optoelectronic performance. Herein, mussel-inspired chemistry has been integrated with two-dimensional HOIPs first, leading to the preparation of new crystal (HDA)2PbBr4 (1) (DA = dopamine). The organic cation dopamine can be introduced into PDA resulting in a thin film of (HPDA)2PbBr4 (PDA-1). The dissolved inorganic components of layered perovskite in DMF solution together with H2O2 addition can facilitate DA polymerization greatly. More importantly, PDA-1 can inherit an excellent semiconductor property of HOIPs and robust adhesion of the PDA hydrogel resulting in a self-adhesive photoelectric coating on various interfaces.

Investigation of periodontal status and bacterial composition aroundmini-implants.

INTRODUCTION: Mini-implants are now widely used in orthodontic treatment. Soft-tissue inflammation around the mini-implant is an important factor affecting its stability. This study aimed to investigate the periodontal status and the bacterial composition around mini-implants. METHODS: A total of 79 mini-implants in 40 patients (aged 18-45 years) were evaluated in this study. The mini-implant probing depth (mPD), mini-implant gingival sulcus bleeding index (mBI), mini-implant plaque index (mPLI), and the composition of the supragingival and subgingival plaque around the mini-implants were recorded. After Congo red staining, the bacteria were classified and counted under a light microscope. RESULTS: The mPLI and mBI around mini-implants in the infrazygomatic crest were higher than those in the buccal shelf and interradicular area. The mPD was higher on the coronal site of the mini-implant than on the mesial, distal, and apical sites in the infrazygomatic crest. The mPLI around the mini-implant was positively correlated with the mBI, and the mBI was positively correlated with the mPD. The supragingival and subgingival bacterial composition around the mini-implants was similar to that of natural teeth. Compared with supragingival bacterial composition, the subgingival bacteria of mini-implants had a significantly lower proportion of cocci and a higher proportion of bacilli and spirochetes. CONCLUSIONS: The bacteria composition of the plaque and the location are important factors in the inflammation around mini-implants. Similar to natural teeth, mini-implants require health maintenance to prevent inflammation of the surrounding soft tissue and maintain stability.

Feasibility of mini-implant insertion between mesial and distal buccal roots of a maxillary first molar: A cone-beam computed tomography imaging study.

INTRODUCTION: Mini-implant insertion in the maxillary posterior region can be influenced by anatomic limitations, thus increasing the failure rate. We explored the feasibility of a new implantation site: the region between the mesial and distal buccal roots of the maxillary first molar. METHODS: Cone-beam computed tomography data from 177 patients were collected from a database. The maxillary first molars were morphologically classified by analyzing the angle and morphology of the mesial and distal buccal roots. Next, 77 subjects were randomly selected from the 177 patients to measure and analyze the hard-tissue morphology in the maxillary posterior region. RESULTS: We devised the Morphological Classification on the Mesial and Distal Buccal Roots of Maxillary First Molar (MCBRMM), divided into 3 types: MCBRMM-I, II, and III. In all subjects, MCBRMM-I, II, and III accounted for 43%, 25%, and 32%, respectively. At 8 mm from the mesial cementoenamel junction of maxillary first molars, the interradicular distance between the maxillary first molar's mesiodistal buccal roots of MCBRMM-I was 2.6 mm, showing an upward trend from the cementoenamel junction to the apex. The distance from the buccal bone cortex to the palatal root was >9 mm. The buccal cortical thickness was >1 mm. CONCLUSIONS: This study provided a potential site for mini-implant insertion in the maxillary posterior region: the alveolar bone of maxillary first molars in MCBRMM-I.

Evaluation of the accuracy of cone-beam computed tomography image segmentation of isolated tooth roots based on the dynamic threshold method.

OBJECTIVE: Accurate quantification of the root surface area (RSA) plays a decisive role in the advancement of periodontal, orthodontic, and restorative treatment modalities. In this study, we aimed to develop a dynamic threshold-based computer-aided system for segmentation and calculation of the RSA of isolated teeth on cone-beam computed tomography (CBCT) and to assess the accuracy of the measured data. METHOD: We selected 24 teeth to be extracted, including single-rooted and multi-rooted teeth, from 22 patients who required tooth extraction. In the experimental group, we scanned 24 isolated teeth using CBCT with a voxel size of 0.3 mm. We designed a computer-aided system based on a personalized dynamic threshold algorithm to automatically segment the roots of 24 isolated teeth in CBCT images and calculate the RSA. In the control group, we employed digital intraoral scanner devices to perform optical scanning on 24 isolated teeth and subsequently manually segmented the roots using 3-matic software to calculate the RSA. We used the paired t-test (P < 0.05) and Bland-Altman plots to analyze the consistency of the two measurement methods. RESULTS: The results of the paired t-test showed that there was no significant difference in the RSAs obtained using the dynamic threshold method and the optical scanning image reconstruction (t = 1.005, P = 0.325 > 0.05). As per the Bland-Altman plot, the results were evenly distributed within the region of ± 1.96 standard deviations of the mean, with no increasing or decreasing trends and good consistency. CONCLUSION: In this study, we designed a computer-aided root segmentation system based on a personalized dynamic threshold algorithm to automatically segment the roots of isolated teeth in CBCT images with a voxel size of 0.3 mm. We found that the RSA calculated using this approach was highly accurate, and a voxel of 0.3 mm in size could accurately display the surface area data in CBCT images. Overall, our findings in this study provide a foundation for future work on accurate automatic segmentation of tooth roots in full-mouth CBCT images and the computation of RSA.

[Weidiao-3 Mixture Improves the Clinical Efficacy of Immunotherapy for Advanced Gastric Cancer by Regulating Intestinal Flora].

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and ß diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and ß diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.

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.

[Effect of Lipoteichoic Acid Synthesis-Related Gene dltD on Acid Tolerance of Highly Cariogenic Strains of Streptococcus mutans].

Objective: To study the role and possible mechanism of dltD in the acid tolerance of Streptococcus mutans 593 (SM593), and to provide a theoretical basis for the ecological prevention and control of dental caries by constructing the dltD gene deletion strain of SM593 (SM593-ΔdltD). Methods: 1) SM593-Δ dltD was constructed by homologous recombination. 2) The growth curve of SM593 dltD and SM593-Δ dltD under different pH culture conditions was drawn by the automatic growth curve analyzer to compare their acid tolerance. Colony forming unit (CFU) at different time points was used to calculate the survival rate and to compare the acid tolerance response (ATR) of SM593 and SM593-Δ dltD. 3) Under different pH conditions, glycolysis experiments, proton permeability test and H +-ATPase activity test were conducted to make preliminary exploration into the mechanisms of how dltD gene deletion may affect acid tolerance. Results: 1) PCR and sequencing results showed that the SM593-Δ dltD was constructed successfully. 2) With decreasing pH value of the culture medium, the growth of SM593-Δ dltD slowed down. When the pH value of the culture medium was 5.0, SM593-Δ dltD was not allowed to grow, and its acid tolerance was lower than that of SM593. Compared with SM593, the ATR capability of SM593-Δ dltD was decreased. 3) SM593 dltD and SM593-Δ dltD did not show obvious difference in their glycolysis ability under different pH conditions. Compared with SM593 dltD, the proton permeability of SM593-Δ dltD under different pH conditions was increased significantly (P<0.05), and H +-ATPase activity decreased significantly (P<0.05). Conclusion: Compared with SM593 dltD, SM593-Δ dltD showed obvious decrease in acid tolerance, which may be caused by the significant increase in proton permeability and significant decrease in the H +-ATPase activity induced by the deletion of the dltD gene, hence reducing its ability to maintain intracellular pH homeostasis.

Enhancement of cytotoxicity and induction of apoptosis by cationic nano-liposome formulation of n-butylidenephthalide in breast cancer cells.

Breast cancer is the second most common malignancy in women. Current clinical therapy for breast cancer has many disadvantages, including metastasis, recurrence, and poor quality of life. Furthermore, it is necessary to find a new therapeutic drug for breast cancer patients to meet clinical demand. n-Butylidenephthalide (BP) is a natural and hydrophobic compound that can inhibit several tumors. However, BP is unstable in aqueous or protein-rich environments, which reduces the activity of BP. Therefore, we used an LPPC (Lipo-PEG-PEI complex) that can encapsulate both hydrophobic and hydrophilic compounds to improve the limitation of BP. The purpose of this study is to investigate the anti-tumor mechanisms of BP and BP/LPPC and further test the efficacy of BP encapsulated by LPPC on SK-BR-3 cells. BP inhibited breast cancer cell growth, and LPPC encapsulation (BP/LPPC complex) enhanced the cytotoxicity on breast cancer by stabilizing the BP activity and offering endocytic pathways. Additionally, BP and LPPC-encapsulated BP induced cell cycle arrest at the G0/G1 phase and might trigger both extrinsic as well as intrinsic cell apoptosis pathway, resulting in cell death. Moreover, the BP/LPPC complex had a synergistic effect with doxorubicin of enhancing the inhibitory effect on breast cancer cells. Consequently, LPPC-encapsulated BP could improve the anti-cancer effects on breast cancer in vitro. In conclusion, BP exhibited an anti-cancer effect on breast cancer cells, and LPPC encapsulation efficiently improved the cytotoxicity of BP via an acceleration of entrapment efficiency to induce cell cycle block and apoptosis. Furthermore, BP/LPPC exhibited a synergistic effect in combination with doxorubicin.

A 5-year molecular epidemiology survey of human enterovirus 71 before vaccine application in Yunnan Province, China.

Enterovirus A71 (EV-A71) infection is known to cause hand, foot, and mouth disease (HFMD). Last year, an inactivated EV-A71 whole virus vaccine was used to prevent this disease in Yunnan, China. To obtain a viral genetic background for evaluating vaccine protection and monitor the adaptive evolution of the virus after the vaccination, a 5-year molecular epidemiology survey was performed before the vaccination. Twenty-six EV-A71 strains were separated from 561 stool specimens of patients with serious HFMD. The whole-genomic sequences of these strains were sequenced. Phylogenetic trees were constructed, and the mutation spectra were analyzed based on these viral sequences. There was no obvious mutation for the circular EV-A71 strains of the same year. Pathogenic EV-A71 strains may arise from a "subgroup" randomly each year. Whole-genomic analyses showed that a hotspot nonsynonymous substitution potentially affecting the immunogenicity of vaccines was found in the 2A gene, but not in genes of the viral capsid proteins, and the genetic diversity of whole viral genomes associated with the incidence of HFMD. Therefore, it will be valuable to monitor the genome-wide changes of EV-A71 to detect the adaptive mutations affecting immunogenicity or perform investigations using genetic diversity as a parameter.

Preparation and application of a novel magnetic molecularly imprinted polymer for simultaneous and rapid determination of three trace endocrine disrupting chemicals in lake water and milk samples.

Exposure to endocrine disruptor substances will alter the function of the endocrine system and then cause adverse effects on human health. Among these endocrine disrupting chemicals, hexestrol, nonylphenol, and bisphenol A are most commonly used worldwide. In this study, we aim to develop a simple, rapid, and efficient analytical method for the simultaneous determination of trace hexestrol, nonylphenol, and bisphenol A in lake water and milk samples. A magnetic molecularly imprinted polymer-assisted magnetic solid-phase extraction technique was applied. The magnetic molecularly imprinted polymer was prepared and characterized by electron scanning microscopy and Fourier transform infrared spectroscopy. Subsequently, different experiments were conducted to optimize the magnetic solid-phase extraction conditions. High-performance liquid chromatography with UV detection was employed to determine hexestrol, nonylphenol, and bisphenol A. Limits of detection of the developed method were from 0.1 to 0.3 µg L-1 and spiked recoveries ranged from 89.9 to 102.5%, with a relative standard deviation of < 2.5% (intraday). Results obtained from this study showed that the proposed magnetic solid-phase extraction method was a simple, rapid, and sensitive sample pre-treatment method for the determination of trace hexestrol, nonylphenol, and bisphenol in different aqueous samples.

Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules.

BACKGROUND: The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. RESULTS: LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. CONCLUSIONS: The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.

Estimation of stress distribution and risk of failure for maxillary premolar restored by occlusal veneer with different CAD/CAM materials and preparation designs.

OBJECTIVES: To compare stress distribution and failure probability in maxillary premolars restored by simple occlusal veneer (SOV) and buccal-occlusal veneer (BOV) with 3 different CAD/CAM materials. MATERIALS AND METHODS: A maxillary premolar was digitized by a micro-CT scanner. Three-dimensional dynamic scan data were transformed, and finite element models of 2 different models (SOV and BOV restored teeth) were designed. Three different CAD/CAM materials, including lithium disilicate glass ceramic (LD) IPS e.max CAD, polymer-infiltrated ceramic-network (PICN) Vita Enamic, and resin nano-ceramic (RNC) Lava Ultimate, were designated to both veneers. Maximum principle stresses were determined by applying a 300-N axial load to the occlusal surface. Weibull analyses were performed to calculate the failure probability of the models. RESULTS: LD-restored teeth showed the highest stress in the veneer, lowest stress in substrate teeth, and lowest failure probability for the overall system; RNC-restored teeth showed the lowest stress in the veneer, highest stress in substrate teeth, and highest failure probability. No significant differences were found in the cement layer among the different models. No significant differences of stress and failure probability existed between SOV and BOV preparations. CONCLUSIONS: CAD/CAM composite resin occlusal veneers bear lower maximum stress than ceramic veneers. Teeth restored by composite veneers are more prone to failure than those restored by ceramic veneers. Additional reduction of the buccal surface did not increase the stress on the occlusal veneer under axial load. CLINICAL RELEVANCE: Both occlusal veneers could be used under physiological masticatory force. CAD/CAM glass ceramic was safer than composite resins.

Antitumor Effects of N-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells.

Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. N-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unstable structure, the activity of BP is quickly lost after dissolution in an aqueous solution. A polycationic liposomal polyethylenimine and polyethylene glycol complex (LPPC), a new drug carrier, encapsulates both hydrophobic and hydrophilic compounds, maintains the activity of the compound, and increases uptake of cancer cells. The purpose of this study is to investigate the antitumor effects and protection of BP encapsulated in LPPC in CRC cells. The LPPC encapsulation protected BP activity, increased the cytotoxicity of BP and enhanced cell uptake through clathrin-mediated endocytosis. Moreover, the BP/LPPC-regulated the expression of the p21 protein and cell cycle-related proteins (CDK4, Cyclin B1 and Cyclin D1), resulting in an increase in the population of cells in the G0/G1 and subG1 phases. BP/LPPC induced cell apoptosis by activating the extrinsic (Fas, Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways. Additionally, BP/LPPC combined with 5-FU synergistically inhibited the growth of HT-29 cells. In conclusion, LPPC enhanced the antitumor activity and cellular uptake of BP, and the BP/LPPC complex induced cell cycle arrest and apoptosis, thereby causing death. These findings suggest the putative use of BP/LPPC as an adjuvant cytotoxic agent for colorectal cancer.

Rapid determination of antiviral medication ribavirin in different feedstuffs using a novel magnetic molecularly imprinted polymer coupled with high-performance liquid chromatography.

A novel magnetic molecularly imprinted polymer adsorbing material was successfully synthesized to detect ribavirin in animal feedstuff. Molecularly imprinted polymer was prepared through surface polymerization by using ribavirin as template molecule, methyl methacrylate, and γ-methacryloxypropyl trimethoxy silane functionalized magnetic mesoporous silica as bifunctional monomers, and ethylene diglycidyl ether as crosslinking agent. The prepared magnetic molecularly imprinted polymer was characterized by scanning electron microscopy and infrared spectroscopy. Static and dynamic adsorption experiments and selective adsorption analysis were performed to evaluate the adsorption and selectivity of magnetic molecularly imprinted polymer. Different experiments were conducted to optimize the magnetic solid-phase extraction conditions. Under optimal experimental conditions, a magnetic molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography method was successfully developed for ribavirin detection. The established method achieved a satisfactory linear range of 0.20-50 mg/L (R2  > 0.99) and a low detection limit (0.081 mg/kg). An average recovery of 92-105% with relative standard deviation of <6.5% was obtained upon the application of the developed method to detect ribavirin in real feedstuff samples. Thus, established method can be used for the rapid and simple separation and detection of added ribavirin in feedstuff.

Evaluation of fixed-jaw IMRT and tangential partial-VMAT radiotherapy plans for synchronous bilateral breast cancer irradiation based on a dosimetric study.

PURPOSE: To investigate the fixed-jaw intensity-modulated radiotherapy (F-IMRT) and tangential partial volumetric modulated arc therapy (tP-VMAT) treatment plans for synchronous bilateral breast cancer (SBBC). MATERIALS AND METHOD: Twelve SBBC patients with pTis-2N0M0 stages who underwent whole-breast irradiation after breast-conserving surgery were planned with F-IMRT and tP-VMAT techniques prescribing 42.56 Gy (2.66 Gy*16f) to the breast. The F-IMRT used 8-12 jaw-fixed tangential fields with single (sF-IMRT) or two (F-IMRT) isocenters located under the sternum or in the center of the left and right planning target volumes (PTVs), and tP-VMAT used 4 tangential partial arcs with two isocenters located in the center of the left and right PTVs. Plan evaluation was based on dose-volume histogram (DVH) analysis. Dosimetric parameters were calculated to evaluate plan quality; total monitor units (MUs), and the gamma analysis for patient-specific quality assurance (QA) were also evaluated. RESULTS: For PTVs, the three plans had similar Dmean and conformity index (CI) values. F-IMRT showed a slightly better target coverage according to the V100% values and demonstrated an obvious reduction in V105% and Dmax compared with the values observed for sF-IMRT and tP-VMAT. Compared with tP-VMAT, sF-IMRT was slightly better in terms of V100% , V105% and Dmax . In addition, F-IMRT achieved the best homogeneity index (HI) values for PTVs. Concerning healthy tissue, tP-VMAT had an advantage in minimizing the high dose volume. The MUs of the tP-VMAT plan were decreased approximately 1.45 and 1 times compared with the sF-IMRT and F-IMRT plans, respectively, and all plans passed QA. For the lungs, heart and liver, F-IMRT achieved the smallest values in terms of Dmean and showed a significant difference compared with tP-VMAT. Simultaneously, sF-IMRT was also superior to tP-VMAT. For the coronary artery, tP-VMAT achieved the lowest Dmean , while the value for F-IMRT was 2.24% lower compared with sF-IMRT. For all organs at risk (OARs), tP-VMAT was superior at the high dose level. In contrast, sF-IMRT and F-IMRT were obviously superior at the low dose level. The sF-IMRT and F-IMRT plans showed consistent trends. CONCLUSION: All treatment plans for the provided techniques were of high quality and feasible for SBBC patients. However, we recommend F-IMRT with a single isocenter as a priority technique because of the tremendous advantage of local hot spot control in PTVs and the reduced dose to OARs at low dose levels. When the irradiated dose to the lungs and heart exceed the clinical restriction, two isocenter F-IMRT can be used to maximize OAR sparing. Additionally, tP-VMAT can be adopted for improving cold spots in PTVs or high-dose exposure to normal tissue when the interval between PTVs is narrow.

Preoperative localisation of pulmonary ground-glass opacity using medical adhesive before thoracoscopic resection.

OBJECTIVES: To evaluate the safety and efficiency of computed tomography (CT)-guided medical adhesive, α-cyanoacrylate, for preoperative localisation of pulmonary ground-glass opacity (GGO) used for guiding the video-assisted thoracoscopic surgical (VATS) excision METHODS: The procedure was performed on 188 consecutive patients with solitary GGO (pure GGO = 90 cases; mixed GGO = 98 cases) prior to the thoracoscopic procedure. The complications and efficacy of this method were analysed. The resected GGO was analysed pathologically. RESULTS: The mean duration of the procedure was 16.3 ± 5.2 min. The preoperative localisation was 100% successful. All GGOs were successfully resected by VATS. Asymptomatic pneumothorax was developed in 16/188 patients (8.5%) and mild pulmonary haemorrhage occurred in 15 cases (7.9%) post-localisation. None of the patients required any further treatment for the complications. CONCLUSION: Preoperative localisation using CT-guided medical adhesive, α-cyanoacrylate, is a safe and short-duration procedure, with high accuracy and success rates with respect to VATS resection of GGO. KEY POINTS: • Preoperative localisation is crucial for successful resection of GGO by VATS. • Preoperative adhesive localisation provides an up to 100% successful localisation rate with few complications. • Preoperative adhesive localisation enabled VATS resection in 100% of the GGO. • Preoperative adhesive localisation is safe and effective for VATS resection of GGO.

Biodegradation of alkali lignin by a newly isolated Rhodococcus pyridinivorans CCZU-B16.

Based on the Prussian blue spectrophotometric method, one high-throughput screening strategy for screening lignin-degrading microorganisms was built on 24-well plate at room temperature. One high activity of alkali lignin-degrading strain Rhodococcus pyridinivorans CCZU-B16 was isolated from soil. After the optimization of biodegradation, 30.2% of alkali lignin (4 g/L) was degraded under the nitrogen-limited condition (30/1 of C/N ratio; g/g) at 30 °C for 72 h. It was found that syringyl (S) units and guaiacyl (G) in lignin decreased after biodegradation. Moreover, the accumulated lipid in cells had a fatty acid profile rich in C16 and C18 with four major constituent fatty acids including palmitic acid (C16:0; 22.4%), palmitoleic acid (C16:1; 21.1%), stearic acid (C18:0; 16.2%), and oleic acid (C18:1; 23.1%). In conclusion, Rhodococcus pyridinivorans CCZU-B16 showed high potential application in future.

Antitumor Effect of n-Butylidenephthalide Encapsulated on B16/F10 Melanoma Cells In Vitro with a Polycationic Liposome Containing PEI and Polyethylene Glycol Complex.

Advanced melanoma can metastasize to distal organs from the skin and yield an aggressive disease and poor prognosis even after treatment with chemotherapeutic agents. The compound n-Butylidenephthalide (BP) is isolated from Angelica sinensis, which is used to treat anemia and gynecological dysfunction in traditional Chinese medicine. Studies have indicated that BP can inhibit cancers, including brain, lung, prostate, liver, and colon cancers. However, because BP is a natural hydrophobic compound, it is quickly metabolized by the liver within 24 h, and thus has limited potential for development in cancer therapy. This study investigated the anticancer mechanisms of BP through encapsulation with a novel polycationic liposome containing polyethylenimine (PEI) and polyethylene glycol complex (LPPC) in melanoma cells. The results demonstrated that BP/LPPC had higher cytotoxicity than BP alone and induced cell cycle arrest at the G0/G1 phase in B16/F10 melanoma cells. The BP/LPPC-treated cell indicated an increase in subG1 percentage and TUNEL positive apoptotic morphology through induction of extrinsic and intrinsic apoptosis pathways. The combination of BP and LPPC and clinical drug 5-Fluorouracil had a greater synergistic inhibition effect than did a single drug. Moreover, LPPC encapsulation improved the uptake of BP values through enhancement of cell endocytosis and maintained BP cytotoxicity activity within 24 h. In conclusion, BP/LPPC can inhibit growth of melanoma cells and induce cell arrest and apoptosis, indicating that BP/LPPC has great potential for development of melanoma therapy agents.

Enhanced In Vitro Zinc Bioavailability through Rational Design of a Dual Zinc plus Arginine Dentifrice.

OBJECTIVES: To investigate bioavailability enhancement of zinc on model oral surfaces and in oral biofilms in vitro through strategic formulation with two sources of zinc and L-arginine. METHODS: To modulate the bioavailability of active zinc ions in a zinc citrate dentifrice, an additive research strategy was pursued. A series of zinc citrate dentifrice formulations were prepared with increasing replacement of zinc citrate with zinc oxide (a water insoluble source of zinc ions) to generate a Dual Zinc active system. A screening of isolated zinc and amino acid effects in simple solutions using zeta potential and uptake to model oral surfaces was performed in an effort to determine the effect of particle charge on zinc bioavailability. Zinc delivery and antibacterial efficacy of the Dual Zinc plus Arginine dentifrice formula were tested using in vitro oral epithelial tissue and saliva-derived biofilm models. Furthermore, zinc penetration and retention were determined by subjecting in vitro biofilms to dynamic flow after treatment with the Dual Zinc plus Arginine dentifrice with treated biofilms evaluated for zinc using imaging mass spectrometry (I-MS). Bacterial adhesion to gingival epithelial cells treated with the Dual Zinc plus Arginine dentifrice was imaged upon challenging with Streptococcus gordonii. RESULTS: Addition of zinc oxide into a zinc citrate dentifrice formula enhanced the efficacy of the system against anaerobic biofilms in a concentration- dependent manner. L-arginine further provided a significant positive charge (+36 mV) to the zinc oxide suspension (+16 mV) as measured by zeta potential. Simple solutions of the Dual Zinc active showed increased zinc uptake on model oral surfaces as a direct function of L-arginine concentration. Antibacterial efficacy of a Dual Zinc plus Arginine dentifrice was evaluated through multiple mechanisms. Enhanced antibacterial performance was observed through significant reductions in metabolic activity as measured through bacterial glycolytic function (p = 0.0001) and total oxygen consumption (p = 0.0001). Greater penetration and retention of zinc was observed in bacterial biofilms treated with the Dual Zinc plus Arginine dentifrice in comparison to treatment with a Dual Zinc dentifrice after twelve hours of dynamic flow (10 mL/hour) in an in vitro drip flow biofilm culture. Confocal microscopy showed adherent bacteria on cheek cells treated with the Dual Zinc plus Arginine dentifrice formula. CONCLUSIONS: The combination of zinc citrate, zinc oxide, and the amino acid L-arginine in a dentifrice formula enhances the bioavailability of zinc to model oral tissue surfaces, resulting in unique physicochemical effects. The significant antimicrobial control associated with the Dual Zinc plus Arginine dentifrice provides a unique vehicle toward achieving whole mouth health.