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As a promising material in the aircraft industry, 2A97 Al−Cu−Li alloy exhibits high corrosion susceptibility that may limit its application. In the present work, to illustrate the influences of precipitate and grain-stored energy on localized corrosion evolution in 2A97 Al−Cu−Li alloy, cold working and artificial aging were carried out to produce 2A97 Al−Cu−Li alloys under different thermomechanical conditions. Quasi-in-situ analysis, traditional immersion test and electrochemical measurement were then conducted to examine the corrosion behavior of 2A97 alloys. It is revealed that precipitate significantly affects Cu enrichment at corrosion fronts, which determines corrosion susceptibility of alloys, whereas grain-stored energy distribution is closely associated with localized corrosion propagation. It is also indicated that quasi-in-situ analysis exhibits a consistent corrosion evolution with traditional immersion tests, which is regarded as a proper method to explore localized corrosion mechanisms by providing local microstructural information with enhanced time and spatial resolutions.

The TRacing Etiology of Non-communicable Diseases (TREND) cohort is a prospective longitudinal cohort and biobank that is mainly based in Ma’anshan, Anhui Province, China. The primary aim of the study is to decipher comprehensive molecular characterization and deep phenotyping for a broad spectrum of chronic non-communicable diseases (NCDs), which focuses on providing mechanistic insights with diagnostic, prognostic and therapeutic implications. The recruitment was initiated in 2023 and is expected to complete in 2025 with 20,000 participants originated from urban and rural area. In the first phase, 3360 participants were recruited. Follow-up visits are scheduled annually and intervally for a total of 30 years. The cohort includes individuals aged over 18 years. Two participants with first-degree linkage were recruited from a household. The age distribution of recruited participants was stratified into four categories: 18–45, 45–55, 55–65, and ≥65 years, aligning with the population proportions of Ma’anshan. Meanwhile, the gender distribution was controlled by pairing men and women from the same household. Data collected at baseline includes socio-economic information, medical history, lifestyle and nutritional habits, anthropometrics, blood oxygen, electrocardiogram (ECG), heart sound, as well as blood, urine and feces tests results. Molecular profiling includes genome, proteome, metabolome, microbiome and extracellular vesicles -omics. Blood, urine and fecal samples are collected and stored at −80 °C in a storage facility for future research.

Objective: The purpose of this study was to investigate the role of the unfolded protein response, specifically the inositol-requiring enzyme 1 (IRE1) signaling pathway, in hypoxia-induced autophagy in human umbilical venous endothelial cells (HUVECs). Methods: The expression of IRE1 and autophagy relative protein in HUVECs with hypoxia was explored by Western blotting, qRT-PCR and confocal microscopy. Further, we evaluated the biological effects of HUVECs by tube formation assay and wound healing assay in vitro. Finally, we examined the function of IRE1 in local blood vessels through animal models. Results: Hypoxia activated the IRE1 signaling pathway and induced autophagy in a time-dependent manner in HUVECs and further influenced the biological effects of HUVECs. Intraperitoneal injection of IRE1 inhibitors inhibited local vascular autophagy levels and lipid accumulation in model animals. Conclusion: Hypoxia can induce autophagy and activate the IRE1 signaling pathway in HUVECs and the IRE1 signaling pathway is involved in autophagy in hypoxic conditions.

In this paper, 25 sampling points of overlying deposits in Tonglushan mining area, Daye City, Hubei Province, China were tested for heavy metal content to explore pollution characteristics, pollution sources and ecological risks of heavy metals in sediments. A geo-accumulation index method was used to evaluate the degree of heavy metal pollution in the sediment. The mean sediment quality guideline quotient was used for evaluating the ecological risk level of heavy metal in the sediment. And a method of correlation analysis, clustering analysis, and principal component analysis was used for preliminary analysis on the source of heavy metal in the sediment. It was indicated that there was extremely heavy metal pollution in the sediment, among which Cd was extremely polluted, Cu strongly contaminated, Zn, As, and Hg moderately contaminated, and Pb, Cr, and Ni were slightly contaminated. It was also indicated by the mean sediment quality guideline-quotient result that there was a high ecological risk of heavy metals in the sediment, and 64% of the sample sites had extremely high hidden biotoxic effects. For distribution, the contamination of branches was worse than that of the main channel of Daye Dagang, and the deposition of each heavy metal was mainly influenced by the distance from this sample site to the sewage draining exit of a tailings pond. The source analysis showed that the heavy metals in the sediment come from pollution discharging of mining and beneficiation companies, tailings ponds, smelting companies, and transport vehicles. In the study area, due to the influence of heavy metal discharging from these sources, the ecotoxicity of heavy metals in the sediment was extremely high, and Cd was the most toxic pollutant. The research figured out the key restoration area and elements for ecological restoration in the sediment of the Tonglüshan mining area, which could be referenced by monitoring and governance of heavy metal pollution in the sediment of the polymetallic mining area.

Lung cancer is one of the leading causes of cancer-related death worldwide. Various therapeutic failed in the effective treatment of the lung cancer due to their limited accumulation and exposure in tumors. In order to promote the chemotherapeutics delivery to lung tumor, we introduced chitosan oligosaccharide (CSO) modification on the liposomes. CSO conjugated Pluronic P123 polymers with different CSO grafting amounts, called as CP50 and CP20, were synthesized and used to prepare CSO modified liposomes (CP50-LSs and CP20-LSs). CP50-LSs and CP20-LSs displayed significantly enhanced cellular uptake in A549 cells in vitro as well as superior tumor accumulation in vivo compared with non-CSO modified liposomes (P-LSs). This phenomenon was related to the increased affinity between CSO modified liposomes and tumor cells following massive adsorption of collagen, which was highly expressed in lung tumors. In the A549 tumor-bearing mouse model, intravenous injection of paclitaxel (PTX)-loaded CP50-LSs every 3 days for 21 days resulted in optimal antitumor therapeutic performance with an inhibition rate of 86.4%. These results reveal that CSO modification provides promising applicability for nanomedicine design in the lung cancer treatment.

Quantitative assessment of the impact of groundwater depletion on phreatophytes in (hyper-) arid regions is key to sustainable groundwater management. However, a parsimonious model for predicting the response of phreatophytes to a decrease of the water table is lacking. A variable saturated flow model, HYDRUS-1D, was used to numerically assess the influences of depth to the water table (DWT) and mean annual precipitation (MAP) on transpiration of groundwater-dependent vegetation in (hyper-) arid regions of northwest China. An exponential relationship is found for the normalized transpiration (a ratio of transpiration at a certain DWT to transpiration at 1 m depth, Ta*) with increasing DWT, while a positive linear relationship is identified between Ta* and annual precipitation. Sensitivity analysis shows that the model is insensitive to parameters, such as saturated soil hydraulic conductivity and water stress parameters, indicated by an insignificant variation (less than 20% in most cases) under ± 50% changes of these parameters. Based on these two relationships, a universal model has been developed to predict the response of phreatophyte transpiration to groundwater drawdown for (hyper-) arid regions using MAP only. The estimated Ta* from the model is reasonable by comparing with published measured values.

Ferulic acid, a hydroxyl derivative extracted from plants, is abundant in free state in seeds and leaves, or covalently linked with cell wall polysaccharides, lignin and different polymers. It has various pharmacological activities, including antioxidant and anti-inflammatory effects, regulates immunity, protects the cardiovascular system, and contributes to the prevention of tumors and diabetes. The protective effect on cardiovascular system is the most valuable one in view of clinical application. Here, we are reviewing the research progress concerning the pharmacological effects of ferulic acid and its derivatives on cardiovascular diseases in the past five years, mainly focusing on mechanisms of action and clinical application. This should provide guidance for clinical applications of ferulic acid and its derivatives in the treatment of cardiovascular diseases.

Mating systems will influence gene spread across the natural distribution of a plant species. Existing theories have not fully explored the role of mating systems on the wave of advance of an advantageous gene. Here, we develop a theory to account for the rate of spread of both advantageous and neutral genes under different mating systems, based on migration-selection processes. We show that a complex relationship exists between selfing rate and the speed of gene spread. The interaction of selfing with gametophytic selection shapes the traveling wave of the advantageous gene. Selfing can impede (or enhance) the spread of an advantageous gene in the presence (or absence) of gametophytic selection. The interaction of selfing with recombination shapes the spread of a neutral gene. Linkage disequilibrium, mainly generated by selfing, enhances the traveling wave of the neutral gene that is tightly linked with the selective gene. Recombination gradually breaks down the genetic hitchhiking effects along the direction of advantageous gene spread, yielding decreasing waves of advance of neutral genes. The stochastic process does not alter the pattern of selfing effects except for increasing the uncertainty of the waves of advance of both advantageous and neutral genes. This theory helps us to explain how mating systems act as a barrier to spread of adaptive and neutral genes, and to interpret species cohesion maintained by a low level of adaptive gene flow.

Background The aim of this study was to evaluate the landscape of gene mutations and the clinical significance of tumor mutation burden (TMB) in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.Methods A total of 68 patients with soft tissue sarcoma were included. Postoperative tumor tissue specimens from the patients were collected for DNA extraction. Targeted next-generation sequencing of cancer-relevant genes was performed for the detection of gene mutations and the analysis of TMB. Univariate analysis between TMB status and prognosis was carried out using the Kaplan–Meier survival analysis, and multivariate analysis was adjusted by the Cox regression model.Results No specific genetic mutations associated with soft tissue sarcoma were found. The mutation frequency of TP53, PIK3C2G, NCOR1, and KRAS of the 68 patients with soft tissue sarcoma were observed in 19 cases (27.94%), 15 cases (22.06%), 14 cases (20.59%), and 14 cases (20.59%), respectively. With regard to the analysis of TMB, the overall TMB of the 68 patients with soft tissue sarcoma was relatively low (median: 2.05 per Mb (range: 0∼15.5 per Mb)). Subsequently, TMB status was divided into TMB-Low and TMB-Middle according to the median TMB. Patients with TMB-Low and TMB-Middle were 37 cases (54.41%) and 31 cases (45.59%), respectively. Overall survival analysis indicated that the median overall survival of patients with TMB-Low and TMB-Middle was not reached, and 4.5 years, respectively (P=0.015).Conclusion This study characterizes the genetic background of patients with STS soft tissue sarcoma. The TMB was of clinical significance for patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.

The microstructure and the filiform corrosion behaviour of machined AA7150 aluminium alloy were investigated using scanning and transmission electron microscopies combined with potentiodynamic polarization and filiform corrosion testing, respectively. It is found that the grain refinement, redistribution of alloying elements, and elements segregation at grain boundaries are evident within the near-surface region on the machined AA7150 aluminium alloy. The corrosion susceptibility of machining introduced near-surface deformed layer is significantly improved caused by the modified microstructure associated with severe deformation. Filiform corrosion resistance on the machined surface is obviously decreased, due to the surface roughness associated with machining tracks and the presence of the electrochemically more active near-surface deformed layer introduced by machining.

Regional aridity is increasing under global climate change, and therefore the sustainable use of water resources has drawn attention from scientists and the public. Land-use changes can have a significant impact on groundwater recharge in arid regions, and quantitative assessment of the impact is key to sustainable groundwater resources management. In this study, the changes of groundwater recharge after the conversion of natural lands to croplands were investigated and compared in inland and arid region, i.e., the northern slope of the Tianshan Mountain. Stable isotopes suggest that soil water in topsoil (< 2 m) has experienced stronger evaporation under natural lands than croplands, and then moves downward as a piston flow. Recharge was estimated by the tracer-based mass balance method, i.e., chloride and sulfate. Recharge rates under natural conditions estimated by the chloride mass balance (CMB) method were estimated to be 0.07 mm/a in deserts and 0.4 mm/a in oases. In contrast, the estimated groundwater recharge ranged from 61.2 mm/a to 44.8 mm/a in croplands, indicating that groundwater recharge would increase significantly after land changes from natural lands to irrigated croplands in arid regions. Recharge estimated by the sulfate mass balance method is consistent with that from the CMB method, indicating that sulfate is also a good tracer capable of estimating groundwater recharge.

Tamoxifen (TMX) is an antiestrogen drug that is used in the treatment and prevention of all stages of estrogen-dependent breast cancer. Adverse effects of TMX include hepatotoxicity. In this study, we investigated the therapeutic effects of osthole, isolated from medicinal plants especially Fructus Cnidii, on TMX-induced acute liver injury in mice. Mice were injected with osthole (100 mg/kg, ip) or vehicle, followed by TMX (90 mg/kg, ip) 24 h later. We showed that a single injection of TMX-induced liver injury and oxidative stress. Pretreatment with osthole attenuated TMX-induced liver injury evidenced by dose-dependent reduction of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Pretreatment with osthole also blunted TMX-induced oxidative stress, evidenced by significant increase of reduced glutathione (GSH) as well as reduction of malondialdehyde (MDA) and hydrogen peroxide (H2O2). Consistently, osthole significantly enhanced the expressions of antioxidant genes (GPX1, SOD2, GCL-c, and G6pdh), but suppressed those of pro-oxidant genes (NOX2 and ACOX). Furthermore, osthole inhibited the production of inflammatory cytokines, reduced the metabolic activation of TMX, and promoted its clearance. We further revealed that osthole elevated hepatic cAMP and cGMP levels, but inhibition of PKA or PKG failed to abolish the hepatoprotective effect of osthole. Meanwhile, prominent phosphorylation of p38 was observed in liver in response to TMX, which was significantly inhibited by osthole. Pretreatment with SB203580, a p38 inhibitor, significantly attenuated TMX-induced increase of ALT and AST activities, reduced oxidative stress, and reversed the alterations of gene expression caused by TMX. Moreover, pretreatment with L-buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, partly reversed the effect of osthole on TMX-induced liver injury. Consistently, pretreatment with N-acetyl-L-cysteine (NAC) significantly attenuated TMX-induced increase in ALT and AST activities. Notably, both BSO and NAC had no detectable effect on the phosphorylation levels of p38. Collectively, our results suggest that osthole prevents TMX hepatotoxicity by suppressing p38 activation and subsequently reducing TMX-induced oxidative damage.

Artesunate is a semi-synthetic derivative of a Chinese herb namedArtemisia annuaL. that is commonly used as an antimalarial agent in the history of traditional Chinese medicine. Many studies have reported artesunate possesses anti-inflammatory and immunoregulation properties. The present study was conducted to explore whether artesunate was effective in experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. Our data showed that artesunate could improve the clinical symptoms and suppress the development of EAMG. Artesunate exerted its immunomodulatory effects by inhibiting lymphocyte proliferation and the expression of costimulatory molecules CD86, modulating Th1/Th2 cytokine expression levels, and enhancing the level of Treg cells. The final result of administration of artesunate was the decreased synthesis of anti-R97-116 IgG, IgG2a, and IgG2b antibodies. The treatment effect of artesunate was more obvious at dose of 10 mg/kg. These date suggest that artesunate might be a potential drug for the treatment of human myasthenia gravis (MG).

Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Osthole, a natural coumarin found in traditional Chinese medicinal herbs, has therapeutic potential in the treatment of various diseases. In this study, we investigated the effects of osthole against APAP-induced hepatotoxicity in mice. Mice were administered osthole (100 mg·kg-1·d-1, ip) for 3 d, then on the fourth day APAP (300 mg/kg, ip) was co-administered with osthole. The mice were euthanized post-APAP, their serum and livers were collected for analysis. Pretreatment with osthole significantly attenuated APAP-induced hepatocyte necrosis and the increases in ALT and AST activities. Compared with the mice treated with APAP alone, osthole pretreatment significantly reduced serum MDA levels and hepatic H2O2levels, and improved liver GSH levels and the GSSG-to-GSH ratio. Meanwhile, osthole pretreatment markedly alleviated the APAP-induced up-regulation of inflammatory cytokines in the livers, and inhibited the expression of hepatic cytochrome P450 enzymes, but it increased the expression of hepatic UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs). Furthermore, osthole pretreatment reversed APAP-induced reduction of hepatic cAMP levels, but pretreatment with H89, a potent selective PKA inhibitor, failed to abolish the beneficial effect of osthole, whereas pretreatment with L-buthionine sulfoximine, a GSH synthesis inhibitor, abrogated the protective effects of osthole on APAP-induced liver injury, and abolished osthole-caused alterations in APAP-metabolizing enzymes. In cultured murine primary hepatocytes and Raw264.7 cells, however, osthole (40 μmol/L) did not alleviate APAP-induced cell death, but it significantly suppressed APAP-caused elevation of inflammatory cytokines. Collectively, we have demonstrated that osthole exerts a preventive effect against APAP-induced hepatotoxicity by inhibiting the metabolic activation of APAP and enhancing its clearance through an antioxidation mechanism.

METTL3 catalyzes the formation of N6-methyl-adenosine (m6A) which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we generated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and spermatogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and m6A profiling analysis revealed that genes functioning in spermatogenesis had altered profiles of expression and alternative splicing. Our findings provide novel insights into the function and regulatory mechanisms of Mettl3-mediated m6A modification in spermatogenesis and reproduction in mammals.

The recent success of derivation of mammalian haploid embryonic stem cells (haESCs) has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage. Diploidization can be suppressed by small-molecule-mediated inhibition of CDK1 and ROCK. Through ROCK inhibition, we can generate haploid somatic cells of all three germ layers from haESCs, including terminally differentiated neurons. Using piggyBac transposon-based insertional mutagenesis, we generated a haploid neural cell library harboring genome-wide mutations for genetic screening. As a proof of concept, we screened for Mn2+-mediated toxicity and identified the Park2 gene. Our findings expand the applications of mouse haploid cell technology to somatic cell types and may also shed light on the mechanisms of ploidy maintenance.

Osthole, a natural coumarin found in traditional Chinese medicinal plants, has shown multiple biological activities. In the present study, we investigated the preventive effects of osthole on inflammatory bowel disease (IBD). Colitis was induced in mice by infusing TNBS into the colonic lumen. Before TNBS treatment, the mice received osthole (100 mg·kg−1·d−1, ip) for 3 d. Pretreatment with osthole significantly ameliorated the clinical scores, colon length shortening, colonic histopathological changes and the expression of inflammatory mediators in TNBS-induced colitis. Pretreatment with osthole elevated serum cAMP levels; but treatment with the PKA inhibitor H89 (10 mg·kg−1·d−1, ip) did not abolish the beneficial effects of osthole on TNBS-induced colitis. In mouse peritoneal macrophages, pretreatment with osthole (50 μmol/L) significantly attenuated the LPS-induced elevation of cytokines at the mRNA level; inhibition of PKA completely reversed the inhibitory effects of osthole on IL-1β, IL-6, COX2, and MCP-1 but not on TNFα. In Raw264.7 cells, the p38 inhibitor SB203580 markedly suppressed LPS-induced upregulation of the cytokines, whereas the PKA inhibitors H89 or KT5720 did not abolish the inhibitory effects of SB203580. Moreover, in LPS-stimulated mouse peritoneal macrophages, SB203580 strongly inhibited the restored expression of IL-1β, IL-6, COX2, and MCP-1, which was achieved by abolishing the suppressive effects of osthole with the PKA inhibitors. Western blot analysis showed that osthole significantly suppressed the phosphorylation of p38, which was induced by TNBS in mice or by LPS in Raw264.7 cells. Inhibition of PKA partially reversed the suppressive effects of osthole on p38 phosphorylation in LPS-stimulated cells. Collectively, our results suggest that osthole is effective in the prevention of TNBS-induced colitis by reducing the expression of inflammatory mediators and attenuating p38 phosphorylation via both cAMP/PKA-dependent and independent pathways, among which the cAMP/PKA-independent pathway plays a major role.

Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40–50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC50=2.94 μmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50values (0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects.

A method of fast and simultaneous determination of N-methyl-N-ethyl piperidinium, N-methyl-N-propyl piperidinium, N-methyl-N-butyl piperidinium and N-methyl-N-ethyl pyrrolidinium, N-methyl-N-propyl pyrrolidinium, N-methyl-N-butyl pyrrolidinium cations by ion-pair chromatography with direct conductivity detection was described.

To investigate the effects of Polygoni Cuspidati Rhizomaet Radix(PCRR) and its ingredient resveratrol (Res) on experimental autoimmune myasthenia gravis (EAMG).

In order to manifest the influence of specific microstructural component on the development of severe localized corrosion in an AA2099 aluminum–lithium alloy, the corrosion behavior of the alloy subjected to solution heat treatment, cold working and artificial ageing was investigated. Immersion testing and potentiodynamic polarization were employed to introduce localized corrosion; scanning electron microscopy and transmission electron microscopy were used to characterize the alloy microstructure and corrosion morphology. It was found that the susceptibility of the alloy to severe localized corrosion was sensitive to thermomechanical treatments. Additionally, the state of alloying elements influenced the mechanism of localized corrosion propagation. Specifically, the alloy in T8 conditions showed higher susceptibility to severe localized corrosion than that in other conditions. During potentiodynamic polarization, the alloy in solution heat-treated and T3 conditions displayed crystallographic corrosion morphology while the alloy in T6 and T8 conditions exhibited selective attack of grain interiors and grain boundaries in local regions.

ZnFe2O4/Bi2O3composites with different molar ratios of ZnFe2O4and Bi2O3were successfully synthesized. The prepared samples have been characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), infrared spectroscopy (IR) and UV-Vis diffuse reflectance spectroscopy (UV-DRS). The result showed that Zn-O-Bi was formed between the interface of ZnFe2O4and Bi2O3without destroying the structures of ZnFe2O4 and Bi2O3. The photocatalytic activity was tested by methyl orange degradation under visible light and the probable reason for the activity enhancement was also investigated compared with pure Bi2O3and ZnFe2O4. The photodegradation rate increased with the increase of the combination amount of ZnFe2O4, and reached peak value of 0.167 when molar ratio of ZnFe2O4:Bi2O3came to 0.067, and then decreased with the further increase of the amount of ZnFe2O4under the same condition. The synergistic effect of the crystal on the photocatalytic activity of ZnFe2O4/Bi2O3composites were proposed. The higher photocatalytic activity of ZnFe2O4/Bi2O3composite can be closely related to photosensitization of ZnFe2O4rooted in the Zn-O-Bi formed between the interface of ZnFe2O4and Bi2O3.

The porous Al–Cu alloy was prepared by the gelcasting process. And the effects of gelcasting conditions, such as monomer, the volume ratio of cross-linker and monomer, dispersant and redox initiating system on the height, gelling time and the quality of green body were investigated. (It was found that the dispersant and monomer played significant roles in the height and quality of green bodies, respectively.) The optimal conditions were 10% monomer, 2% cross-linker, 0.2% initiator (volume fraction), and 1.2 g dispersant, in which the green body exhibited the best quality. The mechanisms of process conditions in eliminating the cracks and forming the pores of in the five stages were proposed. Mercury porosimetry provided a description of pore diameter ranging from 10 to 10000 nm and open porosity of 38.78 %.

ABSTRACTHepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.

A novel PAHs (polycyclic aromatic hydrocarbons)-degrading strain, TAYx3 was isolated from mineral oil and heavy metal contaminated soil. Strain identification and characterization showed that TAYx3 was Yarrowia lipolytica. Tests for Yarrowia lipolytica TAYx3 growth on different substances are also described. The strain could use all PAHs tasted as sole carbon source, and showed synergistic interaction with humic acid (HA). With the existence of HA, the degradation rate of TAYx3 was naphthalene 90.7%, phenanthrene91.0%, fluoranthene74.7%, pyrene 86.9%, benzanthracene 84.7%, benzopyrene 74.7%, respectively.

Background This study aimed to clarify the clinical significance of drug-resistant HBV in nucleoside/nucleotide analogue (NA)-naive Chinese patients with chronic HBV infection in real clinical practice.Methods A total of 845 NA-naive patients who were admitted to Beijing 302 Hospital between July 2007 and March 2012 were included in the study. HBV drug-resistant mutations were examined by direct sequencing of the viral reverse transcriptase gene and verified by clonal sequencing. Phenotypic analysis of viral replication capacity and drug susceptibility were performed by measuring viral replicative intermediate level in 1.1-mer mutant or wild-type HBV amplicon-transfected HepG2 cells in absence or presence of serially diluted drugs.Results Drug-resistant mutations were detected in 2.01% (17/845) of the patients by direct sequencing, including 15 with lamivudine-resistant mutations (rtM204V, rtM204I), one with adefovir-resistant mutation (rtA181V), and one with both lamivudine- and adefovir-resistant mutations (rtA181V, rtM204I). Clonal sequencing identified 13 drug-resistant HBV strains: rtL80I+M204I, rtL80I+M204V, rtL180M+M204I, rtL180M+M204V, rtM204I, rtM204V, rtL80I+L180M+M204I, rtL80I+L180M+M204V, rtA181V, rtA181V+M204I, rtA181T+N236T, rtA181V+N236T and rtN236T. Phenotypic analysis showed that two preexisting lamivudine-resistant strains (rtL80I+M204I, rtL180M+M204V) had >1,000-fold resistance to lamivudine, and one pre-existing adefovir-resistant strain (rtA181V+N236T) had 15.4-fold resistance to adefovir compared with the wild-type strain. A follow-up study showed that the presence of pre-existing rtM204I strain in one patient increased from 20% at baseline to 85% after 13 months of entecavir treatment with corresponding recession of wild-type strain in the viral pool.Conclusions The incidence of drug-resistant HBV mutations was low in NA-naive Chinese HBV-infected patients. Pre-existing mutants had similar resistance characteristics to those from NA refractory patients.

Experimental study was carried out on compressive cube strength, flexural strength and permeability coefficient of color permeable concrete using concrete waste as coarse recycled aggregate. The results show that watercement ratio has significant effect on compressive cube strength, flexural strength and permeability coefficient of color permeable recycled aggregate concrete (RAC).The flexural strength of RAC is improved by polypropylene fiber. The content of pigment from 5% to 10% has no impact on mechanical properties and permeability of RAC.

The paper discusses the disposal of kitchen garbage by means of comprehensive utilization. The method includes four steps: pretreatment of kitchen garbage; preparation of biodiesel from oil-phase by transesterification; Rhizopus oryzae TZY1 and Saccharomyces cerevisiae TZY0 were co-inoculated into water-phase for fuel ethanol production; preparation of protein feed from solid residue of fermentation. Advantage of the method is to make good use of the kitchen garbage, simplify the disposal process, with good prospects for industrial utilization.

ABSTRACTChronic hepatitis B virus (HBV) infection via perinatal transmission is common in the Asia-Pacific region, but related quasispecies (QS) characteristics are not yet defined. To investigate the homologous, full-length HBV QS after perinatal infection and their clinical implications, five pairs of mother-daughter patients with chronic HBV infection (one patient with liver cirrhosis, one with immune tolerance, and eight with chronic hepatitis) were included. Full-length HBV were amplified by PCR from serum samples before antiviral treatment and cloned; an average of 17 clones per sample were sequenced, and the QS complexities, diversities, and evolution patterns were analyzed. Full-length HBV sequence similarities within mother-daughter pairs were 91.3 to 98.3%. The QS complexities of full-length HBV were similar between mothers and daughters (median of 0.9734 compared to 0.9688, P> 0.05), as were the diversities (median of 3.396 × 10-3compared to 4.617 × 10-3substitutions/site, P> 0.05). However, the distribution patterns of QS complexities and diversities within specific genes were different, and QS genetic distances of the mothers were higher than those of daughters, both more evident in pairs with different antiviral responses and different immune phases or stages. The nucleotide substitution rate of full-length HBV was 14.388 × 10-5substitutions/site/year, whereas the preC/C gene rate was the highest. Mutations and indels were more common in clones from the mothers, which decreased the affinity of epitopes by 6- to 89-fold. The various genes from homologous HBV genomes evolved in different patterns despite numerically comparable full-length QS complexities and diversities. The different patterns may correlate with the immune stages of chronic HBV infection, which warrants further study.

The high-temperature tube furnace was applied to simulate the rotary hearth furnace (RHF) for the direct reduction of zinc-bearing dusts from steel plants. The removal mechanism of Zn, Pb and alkalis from cold bonded briquettes made by mixing metallurgical wastes, such as dust from bag house filter, OG sludge, fine converter ash and dust from the third electric field precipitator of the sinter strand, in various proportions was investigated. More than 70% of metallization rate, more than 95% of zinc removal rate, 80% of lead removal as well as more than 80% of K and Na removal rates were achieved for the briquettes kept at 1473–1603 K for 15 min during the direct reduction process respectively. The soot generated in the direct reduction process was studied by chromatography, X-ray difraction (XRD) and scanning electron microscopy (SEM). The results suggested that the main phases of the soot were ZnO, KCl, NaCl and 4ZnO • ZnCl2• 5H2O. Furthermore, the content of Zn reached 64.2%, which could be used as secondary resources for zinc making. It was concluded that KCl and NaCl in secondary dust resulted from the volatilization from the briquettes, whilst ZnO and PbO were produced by the oxidation of Zn or lead vapour from briquettes by direct reduction.

The high-temperature tube furnace was applied to simulate the rotary hearth furnace (RHF) for the direct reduction of zinc-bearing dusts from steel plants. The removal mechanism of Zn, Pb and alkalis from cold bonded briquettes made by mixing metallurgical wastes, such as dust from bag house filter, OG sludge, fine converter ash and dust from the third electric field precipitator of the sinter strand, in various proportions was investigated. More than 70% of metallization rate, more than 95% of zinc removal rate, 80% of lead removal, as well as more than 80% of K and Na removal rates were achieved for the briquettes kept at 1473–1603 K for 15 min during the direct reduction process respectively. The soot generated in the direct reduction process was studied by chromatography, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results suggested that the main phases of the soot were ZnO, KCl, NaCl and 4ZnO · ZnCl2· 5H2O. Furthermore, the content of Zn reached 64.2%, which could be used as secondary resources for zinc making. It was concluded that KCl and NaCl in secondary dust resulted from the volatilization from the briquettes, whilst ZnO and PbO were produced by the oxidation of Zn or lead vapour from briquettes by direct reduction.

This paper studies thermal and electrochemical approaches on micro bubble generation, which have been commonly used in microelectromechanical system. The size and shape effects of micro-bubble actuators are reported in detail.The rate of bubble generation and energy conversion efficiency of the two mapproaches were compared. The micro bubble generation process of the two approaches were analyzed theoretically. By comparing with the experimental results, the micro bubble actuators were optimized.

The flow of an incompressible viscous power-law fluid over an infinite rotating disk with uniform suction or injection is studied. The governing differential equations, which are partial and coupled, are simplified to a set of ordinary differential equations by generalized Karman similarity transformation. Numerical solutions of the non-linear two point boundary value problem are obtained by multi-shooting method. The effects of the power-law index and the porous parameter on the velocity fields are discussed for shear thinning fluids.

Glucocorticoid (GC)-induced avascular osteonecrosis of femoral head (AOFH) is a devastating complication, and no cures are currently available for it. Previous studies have demonstrated that implantation of bone marrow mesenchymal stem cells (BMMSCs) may prevent the progression of pre-collapse AOFH. Based on previous observations, we hypothesized that GCs induce AOFH via the COX-2 (cyclooxygenase-2)–PGE-2 (prostaglandin E2)–HIF-1α (hypoxia-inducible factor-1α) axis, and that modification of BMMSCs may improve the efficacy of their implantation. BMMSCs isolated from wild-type (WT) mice were treated with dexamethasone (Dex) and the results showed that Dex repressed the expression of COX-2. Femoral head samples harvested from both WT and COX-2 knock-out (COX-2−/−) mice were subjected to micro–computed tomography and histological examinations. Compared with their WT littermates, COX-2−/−mice had larger trabecular separations, diminished microvasculature, and reduced HIF-1α expression in their femoral heads. In vitroangiogenesis assays with tube formation and fetal metatarsal sprouting demonstrated that Dex repressed angiogenesis and PGE-2 antagonized its effects. An AOFH model was successfully established in C57BL/6J mice. In vitroexperiment showed that BMMSCs infected with Lentivirus encoding HIF-1α (Lenti-HIF-1α) resulted in a robust increase in the production of HIF-1α protein. Implantation of BMMSCs overexpressing HIF-1α into femoral heads of AOFH mice significantly reduced osteonecrotic areas and enhanced bone repair, thus largely preserving the structural integrity of femoral heads. Our studies provide strong rationales for early intervention with core decompression and implantation of modified BMMSCs for GC-induced AOFH, which may spare patients from expensive and difficult surgical procedures.

ABSTRACTWe previously reported that, based on clone-based sequencing (CBS), hepatitis B virus (HBV) heterogeneity within the reverse transcriptase (RT) region was a predictor of antiviral efficacy. Here, by comparing ultradeep pyrosequencing (UDPS), i.e., next-generation sequencing (NGS), with CBS in characterizing the genetic heterogeneity of HBV quasispecies within the RT region, we evaluated the performance of UDPS in the analysis of HBV viral populations. HBV genomic DNA was extracted from serum samples from 31 antiviral treatment-naive patients with chronic hepatitis B. The RT region quasispecies were analyzed in parallel using CBS and UDPS. Characterization of quasispecies heterogeneity was conducted using bioinformatics analysis. Quasispecies complexity values were calculated with the formula Sn= -Si(pilnpi)/lnN. The number of qualified strains obtained by UDPS was much larger than that obtained by CBS (P< 0.001). Pearson analysis showed that there was a positive correlation of quasispecies complexity values at the nucleotide level for the two methods (P< 0.05), while the complexity value derived from UDPS data was higher than that derived from CBS data (P< 0.001). Study of the prevalences of variations within the RT region showed that CBS detected an average of 9.7 ± 1.1 amino acid substitutions/sample and UDPS detected an average of 16.2 ± 1.4 amino acid substitutions/sample. The phylogenetic analysis based on UDPS data showed more genetic entities than did that based on CBS data. Viral heterogeneity determination by the UDPS technique is more sensitive and efficient in terms of low-abundance variation detection and quasispecies simulation than that by the CBS method, although imperfect, and thus sheds light on the future clinical application of NGS in HBV quasispecies studies.

This article focuses on the effects of pretreatment on sewage sludge with sodium hypochlorite addition. The solubilization of organic matters of sludge was investigated. It was found that the pypocholoride treatment provided a efficient process to release organics from sludge flocs. When the ClO- dose was about 21mg /g SS with a reaction time of 3 hours, the supernatant soluble chemical oxygen demand (SCOD), total nitrogen (TN), total phosphorus (TP), protein and polysaccharide increased by 400%, 67%, 1791%, 635%, 214%, and 556%, respectively. After hypochlorite pretreatment, the sludge extracelluar polymers (EPS) were disintegrated and the cell walls were broken. Then the intracellular organic matters were released into the supernatant, leading to the increase of organic matters in the supernatant.