Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals.

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.

Porous phenolic resin regulated by alcohol-based deep eutectic solvent for selective extraction and separation of tanshinones from Salvia miltiorrhiza.

Deep eutectic solvents (DES), regarded as promising green solvents, have gained attention due to their distinctive properties, particularly in analytical chemistry. While the use of DES in solvent extraction and separation has been extensively studied, its application in the synthesis of adsorbents has just begun. Phenolic resin, with its polyhydroxy structure and stable spherical morphology, could serve as an effective as adsorbents for enrichment of active ingredients in herbal medicine. Designing adsorbents with high selectivity and adsorption capacity presents a critical challenge in the enrichment of active ingredients in herbal medicine. In this study, alcohol-based DESs were employed as regulators of morphology and structure instead of organic solvents, facilitating the creation of polyhydroxy structure, adjustable pores and high specific surface areas. The resulting DES-regulated porous phenolic resin demonstrated enhanced extraction and separation capacity for active ingredients compared to conventional spherical phenolic resin owing to the alcohol-based DES offering more interaction modes with the analytes.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus.

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

SOCS-1 promoter methylation and treatment response in chronic hepatitis C patients receiving pegylated-interferon/ribavirin.

PURPOSE: Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of the Janus kinase/signal transducer and activation of transcription pathway. The purpose of this study was to investigate the relationship between methylation of SOCS-1 and sustained virologic response (SVR) in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN)-alpha and ribavirin (RBV). METHODS: In total, 106 CHC patients treated with PEG-IFN-alpha and RBV were included. Serum samples were obtained at baseline (P), end of treatment (EOT), and 6 months post treatment (F6). Methylation status of the promoter region of SOCS-1 was examined by quantitative methylation specific PCR (qMSP). RESULTS: Median baseline methylation level of SOCS-1 was -0.95 log10 copies/mL, which increased to 0.57 log10 copies/mL at EOT and then returned to -0.57 log10 copies/mL at F6 (baseline vs EOT, P < 0.001; EOT vs F6, P < 0.001). The overall SVR was 75.5%. Univariate analysis indicated that SVR was significantly associated with genotype, baseline HCV RNA, body mass index (BMI) and higher EOT SOCS-1 methylation. Multivariate analysis confirmed that the SVR was significantly associated with genotype (OR: 13.40, 95% CI: 1.73-103.58, P = 0.013), baseline HCV RNA (OR: 0.19, 95% CI: 0.06-0.59, P = 0.004), BMI (OR: 0.73, 95% CI: 0.56-0.96, P = 0.022), and EOT SOCS-1 methylation (OR: 1.71, 95% CI: 1.11-2.62, P = 0.014). CONCLUSION: CHC patients with significantly higher SOCS-1 methylation at the end of treatment had better SVRs. The role of SOCS-1 methylation in affecting treatment response deserves further investigation.

Occurrence and risks of 23 tire additives and their transformation products in an urban water system.

Tire wear particles (TWPs) enter road surface with the friction between tires and road surfaces. Under the volatilization, leaching, and transformation action on TWPs by sunlight and rain, tire additives are released into urban water systems, such as surface rainfall runoff, wastewater treatment plants (WWTPs), receiving surface waters, and drinking water treatment plant (DWTP). In this study, we investigated the occurrence of 23 tire additives and their transformation products in the urban water system of the Pearl River Delta region, South China. Nineteen target compounds were detected in the surface runoff, with 1,3-Diphenylguanidine (DPG) showing highest maximum concentration of 58780 ng/L. Benzothiazole and its transformation products are detected at the frequency of 100 % with the total concentrations of 480-42160 ng/L. The antioxidant derivative N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) was also detected up to 1562 ng/L, which was considerably higher than that of the parent compound 6PPD (the maximum concentration of 7.52 ng/L). Eleven and 8 compounds were detected in WWTPs influents and effluents, respectively, with removal rates of - 62-100 %. Seventeen compounds were detected in the receiving Zhujiang and Dongjiang rivers, while 9 compounds were detected in drinking water sources and DWTP samples. Road runoff, with total concentrations of target compounds up to 79200 ng/L, is suggested as the main non-point source for receiving rivers, while WWTPs effluents are the point sources due to incomplete removal of target compounds after accepting the initial runoff. 6PPD-Q and other 10 compounds displayed median to high ecological risks in surface waters, and the human daily intake of tire additives was estimated to be 2.63 × 10-8-3.16 × 10-5 mg/(kg d) via drinking water. This is the first report of the 6PPD-Q and 1,3-Diphenylurea levels in surface waters in China.

Plastic pollution from takeaway food industry in China.

China's takeaway food industry is growing rapidly, and bringing unprecedented demand for plastic packaging, which results in serious plastic pollution and increasing emissions of plasticizers of phthalate esters (PAEs) and greenhouse gases (GHGs). This study assesses the current and future situation of plastic usage for takeaway food packaging in China, and also analyzes the PAEs and GHG emissions brought by these plastics under different scenarios. From 2010 to 2020, the plastic usage grew from 2.92 to 101 × 104 tons, and brought 112-3845 kg PAEs and 43.6-1438 kt CO2e GHG emissions. Their distribution exhibited a clear 'two-line' pattern: higher features mostly located in Beijing-Guangzhou and Beijing-Shanghai railways. The socio-economic factors model performed better than the growth rate model for plastic usage prediction from 2021 to 2060. It is predicted that 40.6 Mt. plastic would be consumed in 2060, and they will bring 155 tons PAEs and 37.0 Mt. CO2e GHGs. At that time, biodegradable plastic replaced or plastic cycling cannot significantly contribute to national carbon reduction, unless using a temperature change of 2 °C scenario. Our work improves the understanding of PAEs and GHG emission from plastic pollution, and provides insight into long-term dynamics in the plastics management of takeaway food industry.

Influence of microplastics on triclosan bioaccumulation and metabolomics variation in Tilapia fish tissues.

Microplastics (MPs) and chemical pollutants usually coexist in aquatic environments. The bioaccumulation and metabolism of pollutants in aquatic organisms can be influenced by MPs. In this study, the bioaccumulation of triclosan (TCS) in tilapia tissues was determined, and metabolomics in the liver, gills, and gut were investigated after 10-day exposure to micro-sized polystyrene (PS) and TCS in water. The results showed that TCS bioaccumulated in various tissues, with the highest average concentration of 2728 ± 577 ng g-1 in the gut. The log bioaccumulation factors (BAFs) for TCS in these tissues were in the range of 0.99-3.56. Compared to the TCS treatment alone, MPs showed enhancement on the bioaccumulation of TCS in tilapia skin, liver, gut, gills, and stomach tissues in the TCS plus MP exposure. Especially in the skin and liver, the TCS concentrations were up to 2.06 and 1.38 times higher in the co-exposure of TCS and MPs, respectively. Based on the metabolomic analysis, MPs mainly disturbed the lipid and energy metabolism in tilapia fish. The altered metabolites between treatment with TCS alone and TCS + MPs were consistent, indicating that TCS has stronger disturbance in lipid and energy metabolism than MPs. This implies that the metabolism influence by the mixture of MPs and compounds is complicated in fish tissues.

Legumain protease-sheddable PEGylated, tuftsin-modified nanoparticles for selective targeting to tumour-associated macrophages.

Tumour-associated macrophages (TAMs) represent an attractive cell target for anticancer therapy. However, selective and efficient targeting of TAMs remains difficult. Here, we constructed a novel dually functionalised nanoparticle platform (s-Tpep-NPs) by surface co-modification of nanoparticles (NPs) with tuftsin (Tpep) and legumain protease-sheddable polyethylene glycol 5k (PEG5k) to achieve selective targeted delivery to TAMs. The fluorescence resonance energy transfer experiment and in vitro cellular uptake assay confirmed that s-Tpep-NPs can responsively shed PEG5k and transform into active Tpep-NPs upon the cleavage of legumain that is overexpressed on TAM surfaces, which then promotes TAM phagocytosis through Fc receptor-mediated pathways. Owing to the shielding effect by legumain-sheddable PEG5k, s-Tpep-NPs can effectively decrease the Tpep-induced non-specific accumulation in mononuclear phagocyte system (MPS) organs during systemic circulation. Moreover, s-Tpep-NPs can significantly enhance the tumoural accumulation and improve the specificity and efficiency of targeting to TAMs, as compared with both controls of Tpep-NPs and non-sheddable ns-Tpep-NPs. Overall, this study provides a robust nanoplatform with a novel avenue for improved selectivity of targeted delivery to TAMs.

Influence of biofilms on the adsorption behavior of nine organic emerging contaminants on microplastics in field-laboratory exposure experiments.

Microplastics (MPs) are ubiquitous in aquatic environments, which are important carriers of emerging contaminants (ECs). Biofilms can be attached to the surface of MPs in a natural aquatic environment, which may influence chemical adsorption; however, knowledge of its impact is still limited. This study investigated the effect of biofilms on MPs on the adsorption of ECs through field-laboratory exposure experiments. Three types of MPs were naturally colonized with biofilms in lake. Then, biofilm-absent/biofilm-attached MPs were exposed to nine EC solutions at a concentration of 8 µg/L of each compound in laboratory. Most compounds exhibited 3.8 times lower concentrations on biofilm-attached MPs than on biofilm-absent MPs; only a few compounds showed enhanced adsorption. Pseudo-equilibrium was achieved within 72 h based on adsorption kinetics, implying fast adsorption of ECs on biofilm-attached MPs. The partition coefficients (Kd) for biofilm-attached MPs were 0.14 (diclofenac) to 535 (miconazole) L/kg and were positively correlated with octanol/water partition coefficients (Kow). This indicated that chemical properties (such as Kow) of the compounds determined their final adsorption amounts on MPs, although these were influenced by the presence of the biofilm. Hence, multiple influencing factors should be considered when evaluating the carrier potential of MPs for ECs in aquatic environments.

Identification of H-2d restricted T cell epitope of foot-and-mouth disease virus structural protein VP1.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious and devastating disease affecting livestock that causes significant financial losses. Therefore, safer and more effective vaccines are required against Foot-and-mouth disease virus(FMDV). The purpose of this study is to screen and identify an H-2d restricted T cell epitope from the virus structural protein VP1, which is present with FMD. We therefore provide a method and basis for studying a specific FMDV T cell epitope. RESULTS: A codon-optimized expression method was adopted for effective expression of VP1 protein in colon bacillus. We used foot-and-mouth disease standard positive serum was used for Western blot detection of its immunogenicity. The VP1 protein was used for immunizing BALB/c mice, and spleen lymphocytes were isolated. Then, a common in vitro training stimulus was conducted for potential H-2Dd, H-2Kd and H-2Ld restricted T cell epitope on VP1 proteins that were predicted and synthesized by using a bioinformatics method. The H-2Kd restricted T cell epitope pK1 (AYHKGPFTRL) and the H-2Dd restricted T cell epitope pD7 (GFIMDRFVKI) were identified using lymphocyte proliferation assays and IFN-γ ELISPOT experiments. CONCLUSIONS: The results of this study lay foundation for studying the FMDV immune process, vaccine development, among other things. These results also showed that, to identify viral T cell epitopes, the combined application of bioinformatics and molecular biology methods is effective.

Surgical resection and liposomal amphotericin B to treat cavitary pulmonary zygomycosis in a patient with diabetes.

We describe a 24-year-old man with type 1 diabetes mellitus and a cavitary lesion in the right upper lobe, caused by a zygomycete. Surgical resection plus liposomal amphotericin B therapy was successful. We discuss predisposing condition, clinical findings, diagnosis, and treatment of pulmonary zygomycosis.

Selective diffusive gradients in thin-films with molecularly imprinted polymer for measuring fluoroquinolone antibiotics in waters.

Fluoroquinolones (FQs) have raised significant concerns due to their ubiquitous occurrence and promoting of antimicrobial resistance (AMR). In this study, a molecularly imprinted polymer-diffusive gradient in thin-films (MIP-DGT) sampler is developed for selective measurement of FQs in waters by using a commercial available MIP material as the binding agent. The MIP-DGT shows selective adsorption of the FQs and linearly accumulates the FQs over the deployment time. MIP-DGT measurement is independent of pH (6-8) and ionic strength (IS) (0.01-0.5 M) but is affected by DOM at higher concentrations (~10 mg•L-1), which is due to the altered diffusion coefficients and reduced adsorption on the MIP binding gel. Significant interaction effects of DOM with pH or IS indicate that this is the predominant influence on the MIP-DGT performance, which results in a lower measurement by the MIP-DGT but this is curtailed to some extend with increasing IS or pH. The MIP-DGT measurements, however, correlate well with those by grab sampling in a wastewater treatment plant, suggesting it is reliable for measuring FQs in waters. For the first time, we demonstrate that key water chemistry parameters do have interaction effects on the DGT measurements, which should be considered for the data interpretation. The MIP-DGT is a promising tool to understand the interaction effects of the environmental parameters on the fate, behaviours and bioavailability/toxicity of organic contaminants and improve environmental risk assessments in the environment and modelling.

Comparison of Face-Touching Behaviors Before and During the Coronavirus Disease 2019 Pandemic.

Importance: There is insufficient evidence on the efficacy of masks in the general population for the prevention of coronavirus disease 2019 (COVID-19) in public areas. Therefore, it is imperative to investigate the association of mandatory mask-wearing policies with behaviors associated with the transmission of COVID-19. Objective: To assess the association of mask wearing with face-touching behavior among the general population in public areas. Design, Setting, and Participants: This cross-sectional study used videos recorded in public transportation stations, streets, and parks among the general population in China, Japan, South Korea, Western Europe (ie, England, France, Germany, Spain, and Italy), and the US to analyze mask-wearing and face-touching behavior in public areas. Videos before the COVID-19 pandemic were defined as those recorded from January 2018 to October 2019, and those during the COVID-19 pandemic were defined as those recorded during February 2020 to March 2020 in China, Japan, and South Korea and during March 2020 in Western Europe and the US. Individuals who clearly displayed their face and face-touching behavior were included, and those whose behaviors were influenced by filming or public events were excluded. Exposures: Mandatory mask-wearing policies enacted at various time points in China, Japan, South Korea, Western Europe, and the US. Main Outcomes and Measures: Proportion of individuals wearing masks and incidence of face touching. Results: This study included 4699 individuals before the COVID-19 pandemic and 2887 individuals during the pandemic. During the periods studied, mask wearing increased in all regions except the US, from 20 of 1745 individuals (1.1%) to 1090 of 1097 individuals (99.4%) in mainland China (P < .001), 44 of 1422 individuals (3.1%) to 346 of 893 individuals (38.7%) in Japan (P < .001), 6 of 717 individuals (0.8%) to 277 of 324 individuals (85.5% ) in South Korea (P < .001), 1 of 546 individuals (0.2%) to 6 of 379 individuals (1.6%) in Western Europe (P = .02), and 1 of 269 individuals (0.4%) to 4 of 194 individuals (2.1%) in the US (P = .17). Surgical masks were predominant in China (989 masks [89.1%]), and fabric masks were predominant in the other regions (Japan: 371 masks [95.1%]; South Korea: 240 masks [84.8%]; Western Europe: 6 masks [85.7%]; US: 5 masks [100%]). Face-touching behaviors decreased from before COVID-19 to during COVID-19 among individuals in China (72 incidences of 1745 observations [4.1%] to 12 incidences of 1097 observations [1.1%]; P < .001), South Korea (80 incidences of 717 observations [11.2%] to 7 incidences of 324 observations [2.2%]; P < .001), and Europe (62 incidences of 546 observations [11.4%] to 23 incidences of 379 observations [6.1%]; P = .01). Logistic regression found that mask wearing was associated with a reduction in face touching in China (odds ratio [OR], 3.91; 95% CI, 2.11-7.24) and South Korea (OR, 6.69; 95% CI, 2.69-16.69) and of touching the nose, mouth, and eyes (China: OR, 8.60; 95% CI, 2.65-27.86; South Korea: OR, 29.27; 95% CI, 1.79-478.22). Conclusions and Relevance: The findings of this cross-sectional study suggest that mandatory mask-wearing policies were associated with increased mask wearing during the COVID-19 pandemic. Mask wearing was associated with reduced face-touching behavior, especially touching of the eyes, nose, and mouth, which may prevent contact transmission of COVID-19 among the general population in public areas.

How biofilms affect the uptake and fate of hydrophobic organic compounds (HOCs) in microplastic: Insights from an In situ study of Xiangshan Bay, China.

Microplastic (MP) has been identified as an emerging vector that transports hydrophobic organic compounds (HOCs) across aquatic environments due to its hydrophobic surfaces and small size. However, it is also recognized that environmental factors affect MP's chemical vector effects and that attached biofilms could play a major role, although the specific mechanisms remain unclear. To explore this issue, an in situ experiment was conducted at Xiangshan Bay of southeastern China, and dynamics of HOCs (i.e., polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs)) and bacterial communities related to the model MP (i.e., PE fibers) were analyzed and compared. Through bacterial characterizations including the 16S rRNA approach, higher summer temperatures (31.4 ± 1.07 °C) were found to promote colonizing bacterial assemblages with larger biomasses, higher activity and more degrading bacteria than winter temperatures (13.3 ± 2.49 °C). Consequently, some sorbed pollutants underwent significant decline in the summer, and this decline was particularly the case for PAHs with low (2-3 rings) and median (4 rings) molecular weights such as phenanthrene (59.4 ± 1.6%), chrysene (70.6 ± 4.2%), fluoranthene (77.1 ± 13.3%) and benz[a]anthracene (71.5 ± 11.0%). In our winter test, however, most pollutants underwent a consistent increase throughout the 8-week exposure period. Moreover, more biorefractory pollutants including PCBs and high molecular weight (5-6 rings) PAHs accumulated regardless of bacterial characteristics. Two putative PAH-degrading bacteria appeared with high relative abundances during the summer test, i.e., family Rhodobacteraceae (18.6 ± 0.5%) and genus Sphingomicrobium (22.4 ± 3.6%), associated with drastic decreases in low (45.2 ± 0.4%) and median (66.0 ± 2.5%) molecular weight PAHs, respectively. Bacterial degradation effects of biofilms on PAHs are also supported by the correlative dynamics of salicylic acid, an important degradation intermediate of PAHs. The results of this study indicate that MP's HOC vector effects are essentially determined by interactions between attached pollutants and microbial assemblages, which are further related to bacterial activity and pollutant features. Further studies of biofilm effects on MP toxicity and on the metabolic pathways of MP-attached HOCs are required.

Occurrence and mass loads of biocides in plastic debris from the Pearl River system, South China.

Chemical pollution in the plastic debris is an increasing global concern as most pollutants might transfer from the environment to living organisms via plastic debris. In this study, biocides in the plastic debris floating on the surface water of the Pearl River system were investigated. The abundances of large plastic debris and microplastics in the surface water were 0.07 ± 0.13 and 0.94 ± 1.87 items/m3, respectively. Totally, 15 and 16 out of 19 biocides were detected in the large plastic debris and microplastics, with the concentration of each biocide in the ranges of 22.6-2460 ng/g and 16.9-2890 ng/g, respectively. Meanwhile, the concentration ranges of the detected biocides were 0.01-215 ng/L in surface water. Triclosan, triclocarban, methylparaben, and N,N-diethyl-3-methylbenzamide (DEET) were the frequently detected compounds in the plastic samples and surface water. The partition coefficients (Kd) of biocides between the plastic debris and surface water showed a weak positive correlation with Kow values. Biocides were also detected on the natural floats (tree leaves and branches) at concentrations of 13.7-786 ng/g. The annual mass load of biocides in plastic debris at each site was up to 265 g/y, thereby suggesting that plastic debris might be an important carrier for the emerging contaminants, such as biocides.

Effect of High Positive Acceleration (+Gz) Environment on Dental Implant Osseointegration:A Preliminary Animal Study.

OBJECTIVE: To observe the effect of high positive acceleration (+Gz) environment on dental implant osseointegration in a rabbit model and to investigate its mechanism. METHODS: Forty-eight New Zealand white rabbits were randomly divided into 6 groups. The rabbit's mandibular incisors were extracted and 1 implant was placed in each socket immediately. After 1 week of rest, the rabbits were exposed to a high +Gz environment, 3 times a week. The rabbits were sacrificed at 3 weeks (2 weeks +Gz exposure), 5 weeks (4 weeks +Gz exposure), and 12 weeks (4 weeks +Gz exposure and 7 weeks normal environment) after surgery, respectively. Specimens were harvested for micro-CT scanning, histological analysis, and real-time polymerase chain reaction examination. RESULTS: Compared with those in the control group, the mRNA expression levels of bone morphogenetic protein-2 (BMP-2), osteopontin (OPN), and transforming growth factor-ß1 (TGF-ß1) were significantly lower (P < 0.05), while the mRNA expression level of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL/osteoprotegerin (OPG) ratio were significantly higher (P < 0.05) at 3 weeks; values of bone volume fraction, trabecular number, bone-implant contact (BIC), and TGF-ß1 and OPG mRNA expression levels were significantly lower (P < 0.05), and the value of trabecular separation, RANKL mRNA expression level and RANKL/OPG ratio were significantly higher (P < 0.05) at 5 weeks; and the value of BIC was still significantly lower (P < 0.05) at 12 weeks in the experimental group. CONCLUSION: Early exposure to the high +Gz environment after implant surgery might have an adverse effect on osseointegration, and its mechanism could be related to the inhibition of osteoblast activity and promotion of osteoclast activity.

The current strategy of repair of tetralogy of Fallot in children and adults.

OBJECTIVES: The strategies of repair of tetralogy of Fallot change with the age of patients. In children older than 4 years and adults, the optimal strategy may be to use different method of reconstruction of the right ventricular outflow tract from those followed in younger children, so as to avoid, or reduce, the pulmonary insufficiency that is increasingly known to compromise right ventricular function. METHODS: From April, 2001, through May, 2008, we undertook complete repair in 312 patients, 180 male and 132 female, with a mean age of 11.3 years +/-0.4 years, and a range from 4 to 48 years, with typical clinical and morphological features of tetralogy of Fallot, including 42 patients with the ventriculo-arterial connection of double outlet right ventricle. The operation was performed under moderate hypothermia using blood cardioplegia. The ventricular septal defect was closed with a Dacron patch. When it was considered necessary to resect the musculature within the right ventricular outflow tract, or perform pulmonary valvotomy, we sought to preserve the function of the pulmonary valve by protecting as far as possible the native leaflets, or creating a folded monocusp of autologous pericardium. RESULTS: The repair was achieved completely through right atrium in 192, through the right ventricular outflow tract in 83, and through the right atrium, the outflow tract, and the pulmonary trunk in 36 patients. A transjunctional patch was inserted in 169 patients, non-valved in all but 9. There were no differences regarding the periods of aortic cross-clamping or cardiopulmonary bypass. Of the patients, 5 died (1.6%), with no influence noted for the transjunctional patch. Of those having a non-valved patch inserted, three-tenths had pulmonary regurgitation of various degree, while those having a valved patch had minimal pulmonary insufficiency and good right ventricular function postoperatively, this being maintained after follow-up of 8 to 24-months. CONCLUSIONS: Based on our experience, we suggest that the current strategy of repair of tetralogy of Fallot in older children and adults should be based on minimizing the insertion of transjunctional patches, this being indicated only in those with very small ventriculo-pulmonary junctions. If such a patch is necessary, then steps should be taken to preserve the function of the pulmonary valve.

Development of a New RT-PCR with Multiple Primers for Detecting Southern African Territories Foot-and-mouth Disease Viruses.

INTRODUCTION: The extremely high genetic variation and the continuously emerging variants of foot-and-mouth disease virus (FMDV) of Southern African Territory (SAT) serotypes including SAT1, SAT2, and SAT3 make it necessary to develop a new RT-PCR for general use for monitoring viruses based on the updated genome information. MATERIAL AND METHODS: A FMDV SAT-D8 one-step RT-PCR was established based on the 1D2A2B genes of the SAT serotype viruses with a multiplex primer set. FMDV A, O, C, and Asia 1 serotypes, other vesicular disease viruses, inactivated SAT viruses, and 125 bovine, ovine, caprine and porcine tissue samples collected from the Chinese mainland were included for evaluating the assay. RESULTS: The new RT-PCR was proven to be specific without cross-reactions with Eurasian FMDV, swine vesicular disease virus (SVDV), Seneca valley virus (SVV), or other common viral pathogens of cattle, sheep, goat, and pig. An around 257 bp-sized amplicon clearly appeared when the inactivated SAT viruses were detected. However, all 125 samples collected from FMDV-susceptible animals from the Chinese mainland which has not known SAT epidemics showed negative results. CONCLUSIONS: A FMDV SAT-D8 one-step RT-PCR is a promising method for primary screening for FMDV SAT serotypes.

Effect of fluoride treatment on gene expression in tea plant (Camellia sinensis).

Tea plant is a typical fluorine (F) accumulator. F concentration in mature tea leaves is several hundred times higher than that in normal field crops. Long-term consumption of teas with high level F will increase the risks of dental and skeletal fluorosis. The mechanism of F accumulation in tea stands unclear. RNA-Seq and digital gene expression (DGE) techniques were used to investigate the effect of F on the differential expressions of transcriptome in tea plant. The results showed that F content in mature tea leaves was increased with increase in F concentration of cultural solution and duration of F treatment time. Based on comparison with data of GO, COG, KEGG and Nr databases, 144 differentially expressed unigenes with definite annotation were identified. Real-time reverse transcription PCR (qRT-PCR) was used to validate the effect of F on expression of 5 unigenes screened from the 144 unigenes. F treatment induced the expression of defense genes such as receptor-like kinases (RLKs) and U-box domain-containing protein. Based on the present study, F uptake is considered to be related to calcium-transporting ATPase, especially autoinhibited Ca2+ ATPase (ACAs) which was activated by the RLKs and worked as a carrier in uptake of F by tea plant.

[Histopathological and ultrastructural characteristics of oil-associated complications in silicone oil-filled human eyes].

OBJECTIVE: To observe morphological changes of oil-associated complications in silicone oil-filled human eyes, and to further explore their pathogenesis. METHODS: The morphology analysis and immunohistochemistrical study were performed in 25 specimens including 8 eyeballs, 1 ocular content, 4 preretinal membranes, 4 corneal buttons and 8 lens from human eyes with silicone oil tamponade. Two of preretinal membranes acquired freshly were also evaluated by transmission electron microscopy (TEM). RESULTS: Endothelium cell loss (90%) and band keratopathy (83%) were the most typical changes in silicone oil-associated keratopathy;while epithelial cell fibrosis was the most frequent histopathological features in silicone oil-associated cataract. In 8 eyeballs and 1 ocular content, it was found that damages to normal retinal layers and formation of preretinal or subretinal membrane with extensive silicone bubbles were obvious in the cases of silicone oil-associated retinopathy, which included loss and degeneration of neuron cells. Moreover, in 3 eyeballs with silicone oil for more than 60 months, retinas were completely replaced by fibril membranes, and the oil vacuoles were also found in sclerocorneal scar, trabecula, iris, ciliary body, choroid, optic nerve and its tunica vaginalis. These finding demonstrated that the longer the silicone oil was retained in eyeballs, the more severe its complications were. Different sizes of silicone bubbles in 2 preretinal membranes were noted easier by TEM than light microscopy. There were some macrophages marker (CD68) positive staining cells in the tissues filled with silicone bubbles, such as preretinal or subretinal membrane and optic nerve. Partial of the membranes surrounding the oil bubbles was positive for GFAP staining, and other part was positive stained for Vimentin. CONCLUSIONS: Intraocular silicone oil can damage the normal tissue structures and function if it is retained in eyeballs too long. This results suggest that silicone oil should be removed timely after the retinal reattachment stabilized and can not be used as a kind of long term intraocular tamponade.