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B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While the majority of B-ALL patients (90%) experience successful recovery, early relapse cases of B-ALL continue to exhibit high mortality rates. MZ1, a novel inhibitor of Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective of this study was to examine the role and therapeutic potential of MZ1 in the treatment of B-ALL. In order to ascertain the fundamental mechanism of MZ1, a sequence of in vitro assays was conducted on B-ALL cell lines, encompassing Cell Counting Kit 8 (CCK8) assay, Propidium iodide (PI) staining, and Annexin V/PI staining. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to examine protein and mRNA expression levels. Transcriptomic RNA sequencing (RNA-seq) was utilized to screen the target genes of MZ1, and lentiviral transfection was employed to establish stably-expressing/knockdown cell lines. MZ1 has been observed to induce the degradation of Bromodomain Containing 4 (BRD4), Bromodomain Containing 3 (BRD3), and Bromodomain Containing 2 (BRD2) in B-ALL cell strains, leading to inhibited cell growth and induction of cell apoptosis and cycle arrest in vitro. These findings suggest that MZ1 exhibits cytotoxic effects on two distinct molecular subtypes of B-ALL, namely 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines. Additionally, RNA-sequencing analysis revealed that MZ1 significantly downregulated the expression of Cyclin D3 (CCND3) gene in B-ALL cell lines, which in turn promoted cell apoptosis, blocked cell cycle, and caused cell proliferation inhibition. Our results suggest that MZ1 has potential anti-B-ALL effects and might be a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance and relapse resulting in high mortality. Recently, bromodomains and extra-terminal (BET) protein inhibitors have been extensively researched in hematological tumors as potential anticancer agents. MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML. In this study, we first identified that AML patients with high BRD4 expression had poor overall survival than those with low expression group. MZ1 inhibited AML cell growth and induced apoptosis and cycle arrest in vitro. MZ1 induced degradation of BRD4, BRD3 and BRD2 in AML cell strains. Additionally, MZ1 also initiated the cleavage of poly-ADP-ribose polymerase (PARP), which showed cytotoxic effects on NB4 (PML-RARa), K562 (BCR-ABL), Kasumi-1 (AML1-ETO), and MV4-11 (MLL-AF4) cell lines representing different molecular subtypes of AML. In AML mouse leukemia model, MZ1 significantly decreased leukemia cell growth and increased the mouse survival time. According to the RNA-sequencing analysis, MZ1 led to c-Myc and ANP32B genes significant downregulation in AML cell lines. Knockdown of ANP32B promoted AML cell apoptosis and inhibited cell growth. Overall, our data indicated that MZ1 had broad anti-cancer effects on AML cell lines with different molecular lesions, which might be exploited as a novel therapeutic strategy for AML patients. [ABSTRACT FROM AUTHOR]

In the natural process of bone repair, matricryptic peptides were activated by up-regulated ECM-degrading enzymes and properly released at bone injury sites, which plays critical roles in bone self-healing. Inspired by this natural process, here, matricryptic peptide-inspired (MPI) hydrogels were designed to promote osteogenic differentiation. MPI hydrogels can be degraded by enzymes and during this time, the masked bioactive components were released to promote osteogenic differentiation. These MPI hydrogels which normally serve as structural support for cell proliferation while promote osteogenic differentiation using embedded osteogenic BFP-1 peptides after degradation may provide a novel design for bone regeneration materials. [ABSTRACT FROM AUTHOR]

This article describes the application of the updraft biomass gasifier in the non-ferrous metal smelting system. Solving the severe corrosion problem of graphite-SiC crucibles is the purpose of this study, with special emphasis on influence and control to the crucible corrosion caused by the migration of alkali metals, which are usually richest in the biomass. XRD and SEM-EDX analysis of the crucibles showed that compared with the original, K and O in the crucible increased markedly when using the burning engine as a heat source. However, only O in the crucible increased significantly when the updraft gasifier was used as the heat source. It illustrates that the updraft gasifier with the biomass as fuel has a unique filter retention effect on the volatile alkali metals, which can solve the corrosion issue of graphite-SiC crucibles. [ABSTRACT FROM AUTHOR]

China's diplomacy has undergone a sea of changes under Xi Jinping's rein. But there is no consensus on the nature, scope, essence and direction of these changes. This article aims to explore both the changes and continuities in Chinese foreign affairs under the Xi Jinping leadership through the lens of his recently much-advocated formulation of 'major country diplomacy with distinctive Chinese features'. Tracing the evolution, manifestation and causes of Xi's 'major country diplomacy', it is argued that Xi's diplomacy is a clear departure from Deng Xiaoping's TGYH ([Tao Guang Yang Hui] low profile) strategy and therefore transformative in nature. On the other hand, however, his strong adherence to the core realist assumptions about national security issues makes his idealistic and liberal global vision and his efforts to transcend 'the traditional Western theories of international relations' more difficult to accomplish. In this respect, the glass is still half full and half empty. [ABSTRACT FROM AUTHOR]

Road network maintenance scheduling mainly considers budget limits in the previous studies and largely ignores the capital constraints. This study proposes a bi-objective mixed integer programming model, in which the net present value (NPV) is maximized and the increased total system travel time (ITSTT) due to maintenance activities under the capital constraints is minimized. Since the road network flows cannot reach an equilibrium state overnight due to the variation of network capacity, a link-based day-to-day dynamics model is developed to simulate the transient fluctuation in the traffic flows and calculate the total system travel time of each day. The bi-objective model is solved by the nondominated sorting genetic algorithm-II (NSGA-II) that generates a set of optimal Pareto solutions. The TOPSIS method is then adopted to determine the best compromise solution. Finally, a case study is conducted to demonstrate the effects of key parameters on the values of the two objectives. [ABSTRACT FROM AUTHOR]

Entering the twenty-first century, particularly under the reign of Hu Jintao, China began to pursue an increasingly pro-active diplomacy in Africa. Most analysis on China's offensive diplomacy in Africa focuses on Beijing's thirst for energy and raw materials, and for economic profits and benefits. That is why it is often called ‘energy diplomacy’ or ‘economic diplomacy’ as if China, just like Japan in the 1980s, became another ‘economic animal’. But if one looks at the history of the PRC's foreign policy, Beijing has seldom pursued its diplomacy from purely economic considerations. Is this time any different? This article exams China's diplomacy in Africa from a strategic and political perspective such as its geo-strategic calculations, political and security ties with African countries, peacekeeping and anti-piracy efforts in the region, support for African regionalism, etc. It argues that China's diplomatic expansion in Africa, while partially driven by its need for economic growth, cannot be fully understood without taking into consideration its strategic impulse accompanying its accelerating emergence as a global power. Africa is one of China's diplomatic ‘new frontiers’ as exemplified by new Chinese leader Xi Jinping's maiden foreign trip to Africa in 2013. [ABSTRACT FROM PUBLISHER]

Laboratory fish play an important role in many research fields, and they are also raised and bred in many laboratories around the world. While many studies have suggested suitable feeding densities for various laboratory fish, significant variations exist in the sizes of rearing tanks across different laboratories. Moreover, there is limited research on the effects of different rearing tank sizes. In this study, we set up the same rearing density (one liter of water corresponding to two fishes) and four treatments with different tank sizes (5 L, 10 L, 15 L, 20 L). We found that different sizes of rearing tanks had no significant effect on the growth and shoaling of laboratory rare minnow. However, the rare minnow in 10 L tank had lower cortisol levels, while the rare minnow in 20 L tank had higher levels of dopamine (DA), serotonin (5-HT) and their metabolites (DOPAC and 5-HIAA). These results show that even under the same rearing density, different sizes of rearing tanks will still have a physiological effect on the rare minnow, and the tank size suitable for laboratory fish should be considered. [ABSTRACT FROM AUTHOR]

Animal derived biomaterials have attracted much attentions in treating large size bone defect due to their excellent biocompatibility and potent bioactivities offered by the biomacromolecules and growth factors contained in these materials. Dermis-derived matrix (ADM) has been used as skin grafts and wound dressings for decades, however its application in bone tissue engineering has been largely limited as ADM possesses a dense structure which does not support bone tissue ingrowth. Recently, we have successfully fabricated porous scaffold structure using an ADM with the aid of micronization technique. When integrated with inorganic components such as calcium phosphate, ADM could be transformed to bone graft substitutes with desirable osteogenic properties. While purified and chemically cross-linked collagen has lost its natural structure, our ADM successfully preserved natural tropocollagen structure, as well as other bioactive components. A composite scaffold was fabricated by incorporating dicalcium phosphate (DCP) microparticles into ADM microfibers and freeze-dried to form a highly porous structure. Unlike conventional ADM materials, this scaffold possesses high porosity with interconnected pores. More importantly, our evaluation data demonstrated that it performed much more effective in treating critical bone defects in comparison with best commercial product on the market. In a head-to-head comparison with a commercial bone graft material Bongold®, the ADM/DCP scaffold showed superior osteogenic capacity by filling the defect with well-organized new bone tissue in a rabbit radius segmental defect model. Put together, our results exhibited a novel bone graft substitute was developed by circumventing processing barriers associated with natural ADM, which offers another novel bone graft substitute for bone regeneration. [ABSTRACT FROM AUTHOR]

Microwave lignite drying with assistance of biomass-derived char was addressed and effect of bio-char on drying rate and energy consumption was investigated in this work. Effective diffusion coefficient and activation energy for the drying process were also analyzed. The results indicated the drying process was largely dependent on the variation of sample temperature. Bio-char originated from pine wood was most favorable for lignite drying, considering its better promoting effect and advanced security. There existed an optimal bio-char addition ratio for drying process at different power. The corresponding optimal ratio was 10% at 231 W and 15% at 385 W, at which the biggest drying rate and the least energy consumption were reached. It was compared lignite drying initiated at 385 W was better for energy conservation. Effective diffusivity was improved and activation energy was simultaneously reduced, with the addition of bio-char. The minimum activation energy was 15.54 W · g−1, which was gained at bio-char addition ratio of 10%. The results revealed the effect of bio-char on depressing activation energy could rival that of metal-based additives. The drying process with assistance of microwave and bio-char could present technical and economical benefits on lignite upgrading. [ABSTRACT FROM AUTHOR]

Purpose: The neural bases of fatigue in Parkinson's disease (PD) remain uncertain. We aimed to assess the brain metabolic correlates of fatigue in patients with PD. Patients and methods: Twenty-seven PD patients without clinically relevant depression (17-item Hamilton Depression Rating Scale (HAMD) score ≥ 14), apathy (Apathy Scale (AS) score ≥ 14) and excessive daytime somnolence (Epworth Sleepiness Scale (ESS) score ≥ 10) were evaluated with Fatigue Severity Scale (FSS). Each patient had an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale motor part. Levodopa equivalent daily dose for each patient was also calculated. The PET images were analyzed using statistical parametric mapping software. We introduced the age, educational level, HAMD scores, AS scores and ESS scores as covariates. Results: High FSS scores were associated with brain hypermetabolism in areas including the right middle temporal gyrus (Brodmann area (BA) 37) and left middle occipital gyrus (BA 19). Increased FSS scores correlated with hypometabolism in regions such as the right precuneus (BA 23), left inferior frontal gyrus (BA 45) and left superior frontal gyrus (orbital part, BA 11). Conclusion: This study demonstrates that brain areas including frontal, temporal and parietal regions indicative of emotion, motivation and cognitive functions are involved in fatigue in PD patients. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations are performed to study the growth of carbon dioxide (CO2) hydrate in electrolyte solutions of NaCl and MgCl2. The kinetic behaviour of the hydrate growth is examined in terms of cage content, density profile, and mobility of ions and water molecules, and how these properties are influenced by added NaCl and MgCl2. Our simulation results show that both NaCl and MgCl2inhibit the CO2hydrate growth. With a same mole concentration or ion density, MgCl2exhibits stronger inhibition on the growth of CO2hydrate than NaCl does. The growth rate of the CO2hydrate in NaCl and MgCl2solutions decreases slightly with increasing pressure. During the simulations, the Na+, Mg2+, and Cl−ions are mostly excluded by the growing interface front. We find that these ions decrease the mobility of their surrounding water molecules, and thus reduce the opportunity for these water molecules to form cage-like clusters toward hydrate formation. We also note that during the growth processes, several 51263cages appear at the hydrate/solution interface, although they are finally transformed to tetrakaidecahedral (51262) cages. Structural defects consisting of one water molecule trapped in a cage with its hydrogen atoms being attracted by two Cl−ions have also been observed. [ABSTRACT FROM AUTHOR]