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Neoadjuvant chemotherapy (NAC) is the most crucial prognostic factor for osteosarcoma (OS), it significantly prolongs progression-free survival and improves the quality of life. This study aims to develop a deep learning radiomics (DLR) model to accurately predict the response to NAC in patients diagnosed with OS using preoperative MR images. We reviewed axial T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted (T1CE) of 106 patients pathologically confirmed as OS. First, the Auto3DSeg framework was utilized for automated OS segmentation. Second, using three feature extraction methods, nine risk classification models were constructed based on three classifiers. The area under the receiver operating curve (AUC), sensitivity, specificity, accuracy, negative predictive value and positive predictive value were calculated for performance evaluation. Additionally, we developed a deep learning radiomics nomogram with clinical indicators. The model for OS automatic segmentation achieved a Dice coefficient of 0.868 across datasets. To predict the response to NAC, the DLR model achieved the highest prediction performance with an accuracy of 93.8% and an AUC of 0.961 in the test sets. We used calibration curves to assess the predictive ability of the models and performed decision curve analysis to evaluate the clinical net benefit of the DLR model. The DLR model can serve as a pragmatic prediction tool, capable of identifying patients with poor response to NAC, providing information for risk counseling, and assisting in making clinical treatment decisions. Poor responders are better advised to undergo immunotherapy and receive the best supportive care. [ABSTRACT FROM AUTHOR]

• We cloned and produced recombinant Phosphotyrosyl phosphatase activator (PTPA) protein from Haemonchus contortus (rHCPTPA). • The pNPP phosphatase activity of bovine PP2A 1 was increased, due to the existence of rHCPTPA, dose-dependently. • rHCPTPA could be bound by goat PBMCs and exerts its immunomodulatory effects on multiple aspects. Suppression and modulation of the host immune response to parasitic nematodes have been extensively studied. In the present study, we cloned and produced recombinant phosphotyrosyl phosphatase activator protein from Haemonchus contortus (rHCPTPA), a parasitic nematode of small ruminants, and studied the effect of this protein on modulating the immune response of goat peripheral blood mononuclear cells. Enzymatic assays revealed that rHCPTPA enhanced the p-nitrophenylphosphate phosphatase activity of bovine PP2A 1. Immunohistochemical tests verified that the HCPTPA protein was localised mainly in the bowel wall and on the body surface of worms. It was also shown that serum produced by goats artificially infected with H. contortus successfully recognised rHCPTPA, which conjugated with goat peripheral blood mononuclear cells. The rHCPTPA was then co-incubated with goat peripheral blood mononuclear cells to assess its immunomodulatory effects on proliferation, apoptosis, cytokine secretion, migration and nitric oxide production. Our results showed that rHCPTPA suppressed the proliferation of goat peripheral blood mononuclear cells stimulated by concanavalin A and induced apoptosis in goat peripheral blood mononuclear cells. After rHCPTPA exposure, IFN-γ and IL-2 expression was markedly reduced, whereas secretion of IL-10 and IL-4 was significantly elevated, in goat peripheral blood mononuclear cells. Moreover, rHCPTPA down-regulated nitric oxide production and migration of goat peripheral blood mononuclear cells in a dose-dependent manner. These results illuminate the interaction between parasites and hosts at the molecular level, suggest a possible immunomodulatory target and contribute to the search for innovative proteins that might be candidate targets for drugs and vaccines. [ABSTRACT FROM AUTHOR]

• Fusion protein of C. perfringens Cpa247-370, Cpb108-305 and EtxH118P toxin was generated. • B. subtilis expressing C. perfringens recombinant toxin protein rCpa-b-x was constructed. • Immunization with recombinants can elicit cellular and humoral immune responses. • Immunization with recombinants protected mice from C. perfringens toxins. The anaerobic pathogen Clostridium perfringens is the most potent cause of intestinal diseases, such as enterotoxemia, hemorrhagic enteritis, and lamb dysentery, in sheep. Three toxinotypes (B, C, and D) are usually the cause of these diseases and are mainly mediated via three important exotoxins: alpha toxin (CPA), beta toxin (CPB), and epsilon toxin (ETX). We have designed a chimeric protein, rCpa-b-x, that contains the C-terminal binding region of CPA, partial sequence of CPB, and ETX (Cpa247-370, Cpb108-305, and EtxH118P, respectively) according to the principle of structural vaccinology. The rCpa-b-x protein was then expressed by pHT43 plasmid in vivo using Bacillus subtilis as a delivery vector (Bs-pHT43-Cpa-b-x). The immunological activity of the rCpa-b-x protein was verified by western blot and its immunological efficacy was evaluated in a murine model. Oral administration with a recombinant agent caused local mucosal and systemic immune responses, and serum lgG and intestinal mucosal secretory IgA (sIgA) antibody titers were significantly increased. Levels of IL-2, IL-4, and IFN-γ were significantly higher in lymphocytes isolated from the Bs-pHT43-Cpa-b-x group compared with levels from the control groups. The percentages of CD4+ and CD8+ T lymphocytes in the Bs-pHT43-Cpa-b-x and inactivated vaccine (IV) groups were in the normal range. Mice of vaccine groups and control groups were challenged with 1x LD 100 unit filtrate containing alpha, beta, and epsilon toxins. Mice in the Bs-pHT43-Cpa-b-x group were found to have lower rates of morbidity. The active immunization of mice with Bs-pHT43-Cpa-b-x still maintained 85% to 90% survival at the end of the 10-day observation period, whereas mice of control groups died within two to five days. The results of this study demonstrate the effectiveness of Bs-pHT43-Cpa-b-x in preventing C. perfringens infection in mice, and that Bs-pHT43-Cpa-b-x could be considered a potential vaccine against C. perfringens. [ABSTRACT FROM AUTHOR]

Many squeal studies of brake system finite element (FE) model neglected the disc rotation effect. This paper, based on modal theory and FE modal result, presents a novel method to construct a disc brake model that concerns disc rotation and analyzes its dynamic instability. The rotation effect is embodied in velocity-dependent rotating disc equivalent modal parameters, which are derived through time-space and coordinate transformation and proved to be orthogonal with respect to system matrices in state-space. Through modal synthesis with stationary components, system eigenfunction is formulated in modal space. A comprehensive squeal analysis concerning both rotation and friction negative slope effect is then conducted through complex eigenvalue analysis and modal composition analysis. The result shows the dependency of system instability on rotation speed. Under constant friction, disc rotation is a destabilizing factor to the system as it not only raises the squeal propensity and strengthens the split of eigenvalue loci of mode-merging instability, but also gives rise to additional squeal modes that cannot be generated by mode-merging. Velocity-dependent friction model with negative slope character is proved to generate negative damping and destabilize the system at low speed range. Over high speed range, however, the system becomes more stable due to the decline of friction magnitude. Mechanisms responsible for the squeal are discussed, it is demonstrated that mode-merging induced by the friction coupling is the major mechanism for brake squeal. The destabilizing effects on the system which stems from the split of repeated-root modes caused by rotation, as well as the negative damping effect caused by velocity-dependent negative slope friction, are relatively limited. [ABSTRACT FROM AUTHOR]

In our previous proteomics study, we identified Miro domain-containing protein (Miro-1), an excretory and secretory product of the pole worm, Haemonchus contortus , binds to goat peripheral blood mononuclear cells (PBMCs) in vivo . However, our understanding of the role of Miro-1and its potential immune impact on goat PBMCs is limited. The aim of the present study was to evaluate the effects of Miro-1 on functions of goat PBMCs in vitro. Recombinant protein (rMiro-1) was expressed in a prokaryote and incubated with goat PBMCs. Western blot analysis showed that rMiro-1 is successfully recognized by goat sera infected with H. contortus . Immunofluorescence analysis using rat antibodies against rMiro-1 indicated that this protein binds to goat PBMCs in vitro. Treatment of goat PBMCs/monocytes with various concentrations of rMiro-1 resulted in the upregulation of IL-2, IL-4, and IL-17, which in turn promoted cell proliferation, migration, the release of NO in PBMCs, and enhancement of phagocytosis of monocytes. These findings suggested that rMiro-1 stimulates PBMCs activity. [ABSTRACT FROM AUTHOR]

The modification and destruction of the sub-continental lithospheric mantle (SCLM) has been identified in numerous studies. However, what principally controls the susceptibility and extent of destruction of the SCLM and how this leads to the corresponding variation of the overlying crust remain long-standing issues. Here we provide an integrated study of petrology, mineralogy, and geochemistry, including highly siderophile element (HSE) abundances and whole-rock and/or mineral Os-Hf-Sr-Nd isotopic compositions of mantle peridotite xenoliths from Hainan Island, together with a compiled dataset from the eastern South China Craton (SCC) to investigate the mechanism and timing of replacement and destruction of the SCLM. The mantle xenoliths from the eastern SCC are overall more fertile than cratonic lithospheric mantle, and have generally experienced various extents of metasomatic enrichment, including carbonate and silicate melt metasomatism. In addition, the absence of Archean ages and compositional or temporal stratification of the SCLM beneath the eastern SCC indicates that the Archean lithospheric mantle may have been replaced/reworked and has essentially vanished, hence the present underlying lithospheric mantle is a relatively new and young lithospheric mantle. The formation time of the SCLM underneath Hainan Island constrained by both the Re Os and Lu Hf isotopic systems is late Mesoproterozoic (∼1.2 Ga), largely consistent with the Meso- to Neoproterozoic peak of whole-rock T RD ages (0.9–1.3 Ga) of the refractory mantle peridotites in the compiled dataset. This age distribution can be reconciled with the assembly time of the Rodinia supercontinent, indicating a close linkage between the replacement of large-scale lithospheric mantle via mantle convection erosion and regional continental amalgamation. Meanwhile, the relative location to the plate margins influences the preservation of the cratonic mantle. The SCLM located at the plate margin (e.g., eastern SCC compared to western SCC), where destructive processes frequently occur, is susceptible to destruction, whereas that within the plate interior is likely to remain relatively intact. • Hainan Island mantle peridotites are more fertile than cratonic mantle. • Hainan Island lithospheric mantle was stabilized in the late Mesoproterozoic. • Replacement of large-scale lithospheric mantle is related to Rodinia assembly. • Relative location to plate margins controls the destruction of lithospheric mantle. [ABSTRACT FROM AUTHOR]

Coarsening of the basketweave α + β microstructure in Ti-6Al-4V is a common phenomenon that occurs during thermal cycling in both additive manufacturing and cyclic heat treatment. Such a coarsening process is driven by multiple dissolution and precipitation transformations rather than by conventional Ostwald ripening. It is clear that during the first cycle, the complete dissolution of the thinnest α plates at the heating stage provides large spaces for surviving plates to regrow at the cooling stage, which results in coarsening after the first cycle. However, it is still unclear how the α plates continue to vanish and the remaining α plates sustainably coarsen in the repeated thermal cycles. In this study, cyclic heat-treatment experiments and phase-field simulations were conducted to illustrate the mechanism of sustained coarsening during thermal cycling. It was found that in addition to the complete dissolution of the thinnest α plates in the first thermal cycle, α-plate vanishing continued during repeated thermal cycling in two ways, which has not been reported before. The origin of such sustained vanishing of α plates is related to the Gibbs–Thomson effect. Moreover, the influences of cycling frequency and total duration on the transformation coarsening are detected. Both the experimental and simulation results indicate that long cycling duration results in severe coarsening, while for a given duration time, the final coarsening of the α plates is almost independent of the cycling frequency. [Display omitted] • During the repeated thermal cycling,α–plates vanishing can continue in three ways. • The origin of sustained vanishing of α plates is related to Gibbs–Thomson effect. • The transformation coarsening is more sensitive to cycling time than frequency. [ABSTRACT FROM AUTHOR]

Polybrominated biphenyl ethers (PBDEs) are a group of persistent organic pollutants with endocrine-disrupting, neurotoxic, tumorigenic and DNA-damaging activities. They are hydroxylated by human liver microsomal CYP enzymes, however, their mutagenicity remains unknown. In this study, 2,2′,4,4′-tetrabromobiphenyl ether (BDE-47, relatively abundant in human tissues) was investigated for micronuclei induction and DNA damage in mammalian cells. The results indicated that BDE-47 up to 80 μM under a 6 h/18 h (exposure/recovery, covering 2 cell cycles) regime did not induce micronuclei in V79-Mz and V79-derived cell lines expressing human CYP1A1 or 1A2, while it was moderately positive in human CYP2B6-, 2E1-and 3A4-expressing cell lines (V79-hCYP2B6, V79-hCYP2E1-hSULT1A1 and V79-hCYP3A4-hOR, respectively). Following 24 h exposure, BDE-47 induced micronuclei in V79-hCYP2E1-hSULT1A1 and V79-hCYP3A4 cells at increased potencies. In the human hepatoma (HepG2) cells BDE-47 (48 h exposure) was inactive up to 40 μM, however, pretreatment of the cells with ethanol (0.2%, v:v, inducer of CYP2E1) or rifampicin (10 μM, inducer of CYP3A4) led to significant micronuclei formation by BDE-47; pretreatment with bisphenol AF (100 nM) also potentiated BDE-47-induced micronuclei formation (which was blocked by a CYP2E1 inhibitor trans -1,2-dichloroethylene or a CYP3A inhibitor (ketoconazole). Immunofluorescent staining of centromere protein B with the micronuclei formed by BDE-47 in HepG2 cells pretreated with ethanol or rifampicin demonstrated selective formation of centromere-containing micronuclei. The increased phosphorylation of both histones H2AX and H3 in HepG2 by BDE-47 also indicated an aneugenic potential. Therefore, this study suggests that BDE-47 is an aneugen activated by several human CYP enzymes. [Display omitted] • 2,2′,4,4′-Tetrabromobiphenyl ether (BDE-47) is aneugenic in mammalian cells. • The aneugenicity of BDE-47 depends on metabolic activation by human CYP enzymes. • Human CYP3A4 and 2E1 might be the major enzymes activating BDE-47. [ABSTRACT FROM AUTHOR]

Abstract: Natrojarosite is a very important material. In this paper biosynthesis of pure natrojarosite by immobilized Acidithiobacillus ferrooxidans was described. Scanning electron microscopy (SEM), ICP-AES and XRD analysis revealed the character of natrojarosite. The process is principally influenced by extracellular substances. H+ reduction and the oxidation of Fe2+ can accelerate production of the precipitation. Monovalent cation of the precipitation depends on pH value, especially the type and concentration of monovalent cation in solution. This research thus shows a novel application of A. ferrooxidans. [Copyright &y& Elsevier]

• rHCETFα suppressed the proliferation of goat PBMCs stimulated by concanavalin A. • rHCETFα significantly induced apoptosis in goat PBMCs. • rHCETFα modulated the secretion of cytokines in goat PBMCs. • rHCETFα up-regulated NO production in goat PBMCs. • rHCETFα inhibited phagocytosis of goat monocytes. Suppression and modulation of the host immune response to parasitic nematodes have been extensively studied. In the present study, we cloned and produced recombinant electron transfer flavoprotein α subunit (ETFα) protein from Haemonchus contortus (rHCETFα), a parasitic nematode of small ruminants, and studied the effect of this protein on modulating the immune response of goat peripheral blood mononuclear cells (PBMCs) and monocytes. Immunohistochemical tests verified that the HCETFα protein was localized mainly in the intestinal wall and on the body surface of worms. Immunoblot analysis revealed that rHCETFα was recognized by the serum of goats artificially infected with H. contortus. Immunofluorescence analysis indicated that rHCETFα bound to the surface of PBMCs. rHCETFα was co-incubated with goat PBMCs to observe the immunomodulatory effects exerted by HCETFα on proliferation, apoptosis, cytokine secretion and nitric oxide (NO) production. The results showed that rHCETFα suppressed the proliferation of goat PBMCs stimulated by concanavalin A and induced apoptosis in goat PBMCs. After rHCETFα exposure, IL-2, IL-4, IL-17A and TNF-α expression was markedly reduced, whereas secretion of TGF-β1 was significantly elevated, in goat PBMCs. Moreover, rHCETFα up-regulated NO production in a dose-dependent manner. FITC-dextran internalization assays showed that rHCETFα inhibited phagocytosis of goat monocytes. These results elucidate the interaction between parasites and hosts at the molecular level, suggest a possible immunomodulatory target and contribute to the search for innovative proteins that may be candidate targets for drugs and vaccines. [ABSTRACT FROM AUTHOR]

In the theoretical analysis of grain growth kinetics, the roles of curvature and stochastic effects have been an open question for many years. Considering contributions of microstructure entropy and a phenomenological grain topological energy, the present work develops a thermodynamic dissipation-based framework for representing the stochasticity and spatial correlations in grain growth. This framework reveals the correlations between previous mean-field and stochastic theories, whose validities are further assessed by the 3-D Aboav-Weaire relationship. [Display omitted] [ABSTRACT FROM AUTHOR]

Phase coarsening in multiphase materials is a fundamental and crucial process in the study of microstructure evolution, for which a thorough understanding of kinetics can make a significant contribution to material processing and performance design. In this work, a new framework in the dimensionless Lifshitz-Slyozov-Wagner space is developed to study the kinetics of transient coarsening co-controlled by interface and matrix diffusion. The dynamic equations for individual particles are derived from the thermodynamic extremal principle, in consideration of energy dissipations by matrix diffusion, interface migration/reaction, and trans-interface diffusion. The effects of initial particle size distribution and finite volume fractions are clarified. Different from the conventional viewpoints, the time for transient coarsening is found to change non-monotonically with the width and tail length of the initial distribution. The ultralong transient coarsening with 'quasi-steady' distributions can occur for systems initiated from both the 'wide & long tail' and 'narrow & short tail' distributions. Furthermore, this work proves the existence of a unique attractor state for the steady stage and reveals the numerical origin of 'quasi-steady' distributions, which answers Brown's unsolved puzzle for years [LC Brown. Acta Metall 1989;37:71]. Finally, an increase in volume fraction is shown to directly shorten the transient stage dominated by single mechanism (matrix diffusion or interface), but indirectly delay the transition from the interface-dominated state to the diffusion-controlled stage. These findings not only offer new insights into the previous observations in microgravity experiments [VA Snyder, J Alkemper, PW Voorhees, Acta Mater 2001;23:699], but also theoretically describe the limiting coarsening behaviors at ultrahigh volume fractions [H Yan, KG Wang, ME Glicksman. Acta Mater 2022;117964]. [Display omitted] [ABSTRACT FROM AUTHOR]

• Emissions of pollutants (not including CO 2) are monetized in terms of the pollutant discharge fee. • A considerable risk of emission spillovers between CO 2 and other pollutants now exists in China. • More perfect option for future emissions reduction must be implemented without delay. Environmental quality is strongly coupling with the result of emissions reduction in most countries, while emissions reduction is influenced by the diversity of control policies, engineering facilities and development patterns. Further, local in which technical or policy that concern the control of target emissions will impact other pollutants emission. In China, the emissions of both CO 2 and other pollutants increased substantially during the past decades. With the development of emissions reduction, it promoted a considerable risk of emissions spillovers caused by the present mechanism. In this study, we assessed the contributions of emissions spillovers to emission reductions by applying a more comprehensive indicator of pollutants, pollutant discharge fee (PDF), at the national, regional and provincial levels. The results shown positive and significant mutual effect between the PDF and CO 2 emissions. That is, CO 2 emission is significantly related with the process of other pollutants emissions reduction. Additionally, the positive correlation indicated further increases with the Five-Year Plan (FYP) cycle. Emissions spillovers have become an urgent risk for China. With the performance change, emissions reduction and environmental governance should heighten integration. Regional-level and provincial authorities must reconsider the matched emissions sustainability responsibilities and policies to avoid emissions spillovers and achieve meaningful emission controls. The study therefore suggested that a hierarchy of emission reductions, in the hope to promote emission reductions, improve environmental quality and contribute greenhouse gas reductions. [ABSTRACT FROM AUTHOR]

• Assessed emissions reduction during the past years. • Significant performance changes in China's emissions reduction. • Four major recommendations are raised. With the rapid development of industrialization and urbanization, emissions reduction is becoming an urgent mission for China. This work aims to review and analysis the effectiveness of emissions reduction in China based on the pollution discharge fee (PDF) and Five-year plan (FYP). The results show that, the emissions performance appeared significantly temporal performance changes under the current framework. Due to FYP and environment tax (ET) in parallel is an inevitable choice for environment and emission management, the connection and match among the existing emissions reduction policies are suggested to be enhanced. Four significant recommendations are raised: establishing dynamic economic regulation on emissions feedbacks, improving synchronization matching on information and data, increasing the audit on the technical applications and integrating more supporting policy with ET. [ABSTRACT FROM AUTHOR]

• TPPPS inhibits the replication of Fu-J (SDAU1005) in DF-1 cells. • TPPPS significantly inhibits the replication of Fu-J (SDAU1005) and the growth of its associated tumor in vivo. • TPPPS up-regulated immune-related genes activate immune signaling pathways, and down-regulated tumor-associated gene expression inhibits tumor-associated signaling pathways, thereby exerting antiviral and antitumor effects in vivo. Avian leukosis virus subgroup J (ALV-J) has resulted in considerable economic losses in the poultry industry. In recent years, fibrosarcoma induced by ALV-J, which contains the v-fps oncogene, has gained momentum, and this has brought about new challenges to the poultry industry. To study the inhibitory effects of Taishan Pinus Massoniana pollen polysaccharide (TPPPS) on acute ALV-J infection and tumor development, antiviral and antitumor models of the Fu-J (SDAU1005) strain of ALV-J were established in vitro and in vivo. The results of in vitro experiments showed that TPPPS significantly inhibited viral replication in a dose-dependent manner during adsorption and pretreatment stages. The results of in vivo experiments have shown that TPPPS significantly reduced the viral load in the plasma and tumor tissues, as well as inhibited tumor growth. We further examined the difference in transcriptome expression by using RNA-Seq technology. A total of 560 differentially expressed genes were identified that included 329 up-regulated genes and 231 down-regulated genes. The up-regulated genes were mainly immune-related genes, whereas the down-regulated genes were mainly tumor-regulated genes. Gene Ontology (GO) term enrichment included immune system processes, positive regulation of immune system processes, regulation of immune system processes, leukocyte activation, cell activation, and protein binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the main immune and tumor-related pathways included T-cell receptor signaling pathway, cytokine-cytokine receptor interactions, natural killer cell-mediated cytotoxicity, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, NF-κB signaling pathway, and Ras signaling pathway. In summary, our results preliminarily point to the antiviral and antitumor mechanism of TPPPS in vivo and in vitro. [ABSTRACT FROM AUTHOR]