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Several canonical translocations produce oncofusion genes that can initiate acute myeloid leukemia (AML). Although each translocation is associated with unique features, the mechanisms responsible remain unclear. While proteins interacting with each oncofusion are known to be relevant for how they act, these interactions have not yet been systematically defined. To address this issue in an unbiased fashion, we fused a promiscuous biotin ligase (TurboID) in-frame with 3 favorablerisk AML oncofusion cDNAs (PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11) and identified their interacting proteins in primary murine hematopoietic cells. The PML::RARA- and RUNX1::RUNX1T1-TurboID fusion proteins labeled common and unique nuclear repressor complexes, implying their nuclear localization. However, CBFB::MYH11-TurboID-interacting proteins were largely cytoplasmic, probably because of an interaction of the MYH11 domain with several cytoplasmic myosin- related proteins. Using a variety of methods, we showed that the CBFB domain of CBFB::MYH11 sequesters RUNX1 in cytoplasmic aggregates; these findings were confirmed in primary human AML cells. Paradoxically, CBFB::MYH11 expression was associated with increased RUNX1/2 expression, suggesting the presence of a sensor for reduced functional RUNX1 protein, and a feedback loop that may attempt to compensate by increasing RUNX1/2 transcription. These findings may have broad implications for AML pathogenesis., Introduction Oncofusion genes exist in a variety of solid tumors and hematopoietic malignancies, and are often predictive of outcomes. Elucidating the mechanism of action of an oncofusion protein presents unique [...]

A comprehensive investigation was conducted on the relationships between molecular structure, morphology and thermoelectric properties of HCl-doped polyaniline (PANi) nanorods subjected to 10MeV electron beam irradiation. Morphological and structural characterization revealed that the crystallinity of irradiated PANi nanorods remained almost unchanged, and minimal oxygen content was detected. This resulted in minimal alterations to the thermo-stability. In addition, the thermoelectric properties of PANi were enhanced. A maximum conductivity of 22.85S/cm was obtained at 50kGy, which was 1.46 times that of pristine PANi. Interestingly, the Seebeck coefficient reached a maximum of −3.56μV/K at 100kGy, indicating n-type organic semiconductor properties. However, a peak power factor of 0.024μWm−1 K−2 was achieved with 60kGy irradiation, which was slightly enhanced compared to 0.018μWm−1K−2 for pristine PANi. These results demonstrate that PANi exhibits good irradiation resistance after irradiated with a dose of 100kGy. Thus, PANi could be used in high-β ray (electron) environments, such as radioisotope thermoelectric generators (RTGs). [ABSTRACT FROM AUTHOR]

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5- tagged PML::RARA, using anti- V5- PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin- accessible (defined by ATAC- seq) in unmanipulated, wild- type promyelocytes, suggesting that these regions are -open- prior to PML::RARA expression. We found that GATA binding motifs, and the direct binding of the chromatin -pioneering factor- GATA2, were significantly enriched near PML::RARA binding sites. Proximity labeling studies revealed that PML::RARA interacts with -250 proteins in primary mouse hematopoietic cells; GATA2 and 33 others require PML::RARA binding to DNA for the interaction to occur, suggesting that binding to their cognate DNA target motifs may stabilize their interactions. In the absence of PML::RARA, Gata2 overexpression induces many of the same epigenetic and transcriptional changes as PML::RARA. These findings suggested that PML::RARA may indirectly initiate its transcriptional program by activating Gata2 expression: Indeed, we demonstrated that inactivation of Gata2 prior to PML::RARA expression prevented its ability to induce self- renewal. These data suggested that GATA2 binding creates accessible chromatin regions enriched for both GATA and Retinoic Acid Receptor Element motifs, where GATA2 and PML::RARA can potentially bind and interact with each other. In turn, PML::RARA binding to DNA promotes a feed- forward transcriptional program by positively regulating Gata2 expression. Gata2 may therefore be required for PML::RARA to establish its transcriptional program. [ABSTRACT FROM AUTHOR]

Oral administration is a convenient drug delivery method in our daily lives. However, it remains a challenge to achieve precise target delivery and ensure the efficacy of medications in extreme environments within the digestive system with complex environments. This paper proposes an oral multilayer magnetic hydrogel microrobot for targeted delivery and on-demand release driven by a gradient magnetic field. The inner hydrogel shells enclose designated drugs and magnetic microparticles. The outer hydrogel shells enclose the inner hydrogel shells, magnetic microparticles, and pH neutralizers. The drug release procedure is remotely implemented layer-by-layer. When the required gradient magnetic field is applied, the outer hydrogel shells are destroyed to release their inclusions. The enclosed pH neutralizers scour the surrounding environment to avoid damaging drugs by the pH environment. Subsequently, the inner hydrogel shells are destroyed to release the drugs. A set of experiments are conducted to demonstrate the wirelessly controllable target delivery and release in a Petri dish and biological tissues. The results demonstrated attractive advantages of the reported microrobot in microcargo delivery with almost no loss, remote controllable release, and drug protection by the pH neutralizers. It is a promising approach to advance next-generation precision oral therapies in the digestive system. [ABSTRACT FROM AUTHOR]

The microenvironment and stem cell fate guidance of post‐traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular cartilage, stem cells are characterized by overlapping lineages and uneven effectiveness. Within the first 12 weeks after trauma, the articular inflammatory microenvironment (AIME) plays a decisive role in determining the fate of stem cells and cartilage. The development of fibrocartilage and osteophyte hyperplasia is an adverse outcome of chronic inflammation, which results from an imbalance in the AIME during the cartilage tissue repair process. In this review, the sources for the different types of stem cells and their fate are summarized. The main pathophysiological events that occur within the AIME as well as their protagonists are also discussed. Additionally, regulatory strategies that may guide the fate of stem cells within the AIME are proposed. Finally, strategies that provide insight into AIME pathophysiology are discussed and the design of new materials that match the post‐traumatic progress of AIME pathophysiology in a spatial and temporal manner is guided. Thus, by regulating an appropriately modified inflammatory microenvironment, efficient stem cell‐mediated tissue repair may be achieved. [ABSTRACT FROM AUTHOR]

With the development of green logistics, logistics companies gradually are paying attention to the application of hybrid electric vehicles (HEVs). HEVs have the advantages of low energy consumption and pollution, while their disadvantage mainly lies in their limited continuous driving range. Therefore, it is necessary to optimize the use of fuel during the distribution process. We study the mode selection system in HEVs based on the background of green logistics and the above characteristics of HEVs. The mode selection system can adjust the driving mode of the HEV according to different road conditions to obtain the optimal use of fuel. In this paper, we propose a new study of a hybrid electric vehicle routing problem with mode selection. This problem is formulated as a mixed integer linear programming model. An improved particle swarm optimization algorithm (IPSO) is developed to solve this problem. Extensive numerical experiments are conducted to validate the effectiveness of the proposed model and the efficiency of the proposed solution method. The experimental results show that our proposed algorithm not only obtains the optimal solution for some small-scale problem instances and some medium-scale problems but also solves some large-scale situations (one hundred customers, eleven vehicles, eleven charging stations, eleven gas stations and four modes) within an hour. [ABSTRACT FROM AUTHOR]

Pyrolysis of mussel‐inspired polydopamine (PDA) can yield carbon material with high electrical conductivity and n‐type semiconductor performance. Investigating the relationship between the structure and the thermoelectric properties of carbonized PDA (cPDA) is therefore highly desired. In this work, a series of cPDA annealed at 800°C has been successfully prepared by adjusting the concentration of dopamine (DA) monomers, which had a significant effect on the shape and size of cPDA nanoparticles and their thermoelectric properties. Structural analyses indicate that cPDA are mainly amorphous with some graphite like structure and short‐range ordering. The electrical conductivity and Seebeck coefficient show different trends with the concentration of DA monomers. The largest room‐temperature power factor of 26.15 μW m−1 K−2 was obtained on cPDA when the concentration of DA was 13.12 mM with a conductivity of 28,493 S m−1 and a Seebeck coefficient of −9.58 μV K−1. [ABSTRACT FROM AUTHOR]

Featured Application: The results of this paper can be used in all the fields related to encrypted traffic analysis, especially in the field of encrypted traffic classification and encrypted traffic identification which depend on a large number of labeled samples. Encrypted traffic classification can essentially support network QoS (Quality of Service) and user QoE (Quality of Experience). However, as a typical supervised learning problem, it requires sufficiently labeled samples, which should be frequently updated. The current gateway-based labeled sample acquisition methods can only be carried out under TLS traffic. It relies on the Server Name Indication, a confused optional field that can be tampered with. The current end-based methods carried out manually or automatically have low efficiency and lack sample integrity, category purity, and label authenticity. In addition, they may have colossal packet loss and violate device security and user privacy. To solve these problems, we propose a one-stop automated encrypted traffic labeled sample collection, construction, and correlation system, A3C. First, we carry out the automated process-isolated traffic collection and labeled sample construction in the mixed application scenario, which can be used on Windows, Linux, and Android systems. Then, we propose the Segmented Entropy Distribution Capsule Neural Network (SED-CapsNet) to validate the encryption of the collected samples. We also propose optional authenticity validation and context flow correlation methods. Experimental results show that the system can effectively achieve one-stop encrypted traffic labeled dataset acquisition. It is superior to the existing methods. [ABSTRACT FROM AUTHOR]

Salmonella is capable of harming human and animal health, and its multidrug resistance (MDR) has always been a public health problem. In addition, antibiotic-free or antibiotic-reduced policies have been implemented in poultry production. Therefore, the search for antibiotic alternatives is more urgent than ever before. The aim of this study was to assess the antibacterial activity of star anise-cinnamon essential oil (SCEO) in vitro and its prophylactic effect against the infections of Salmonella pullorum, Salmonella give, and Salmonella kentucky in vivo. The results demonstrated that SCEO is effective against Salmonella pullorum, Salmonella give, and Salmonella kentucky in vitro. Supplementation with SCEO could significantly decrease the infections of Salmonella pullorum and Salmonella give, whereas it could slightly but not significantly decrease the infection of Salmonella kentucky, while also significantly alleviating the body weight (BW) loss caused by the infections of Salmonella pullorum, Salmonella give, and Salmonella kentucky in Yellow chickens. The SCEO had the best prophylactic effect against the infection of Salmonella give in Yellow chickens, followed by the infection of Salmonella pullorum and the infection of Salmonella kentucky. The SCEO, used as an antibiotic alternative, could be an effective prevention strategy against the infections of Salmonella pullorum, Salmonella give, and Salmonella kentucky in Yellow chickens. [ABSTRACT FROM AUTHOR]

Meadow soil is a vital ecosystem component and can be influenced by meadow vegetation. Evaluating soil quality in mountain meadows subjected to different levels of tourism disturbance is essential for scientific research, ecological restoration, and sustainable management. This study aimed to evaluate meadow soil quality at different tourism-disturbance levels and attempted to establish a minimum data set (MDS) with compatible indicators for soil quality assessment of subtropical mountain meadows. We analyzed fifteen soil physical, chemical, and biological indicators in control check (CK), light disturbance (LD), medium disturbance (MD), and severe disturbance (SD) meadow areas in Wugong Mountain, west of Jiangxi, China. In addition, a soil quality index (SQI) was determined using the established MDS based on the integrated soil quality index. Average soil permeability, soil pH, available nitrogen (AN), available phosphorus (AP), and number of fungal OTUs were finally introduced into the MDS to evaluate meadow soil quality at different tourism-disturbance levels. The study found that the soil of the Wugong Mountain meadow was acidic, the bulk density was loose, and the nutrient content was rich. Additionally, SQI decreased with increase in tourism-disturbance level. The mean SQI values of the Wugong Mountain meadow areas were: CK, 0.612; LD, 0.493; MD, 0.448; and SD, 0.416. Our results demonstrate that the SQI based on the MDS method could be a valuable tool with which to indicate the soil quality of mountain meadow areas, and the SQI can be regarded as a primary indicator of ecological restoration and sustainable management. [ABSTRACT FROM AUTHOR]

We report a child with persistently low oxygen saturations (SpO2 90%–92%) [normal SpO2 > 98%], with delayed diagnosis due to the co‐existing congenital pulmonary airway malformation with possible arterio‐venous malformation. The diagnosis was only achieved after low oxygen saturations incidentally discovered from the child's father. The eventual cause was Hemoglobin I‐Toulouse, making both patients the first reported cases with low oxygen saturations. [ABSTRACT FROM AUTHOR]

Environmental pollution is currently a major concern globally owing to increase in the world population and advances in industrialization. An automatic waste separation and sorting equipment for small-scale waste sorting systems was constructed in this paper. A two-DoF (two-degree-of-freedom) parallel sorting mechanism as well as a belt waste separation and feeding mechanism were designed, and 3D models of the mechanism were established. Finite element analysis (FEA) was conducted for the sorting mechanism, and kinematic and dynamic analysis and numerical simulation were performed for the waste and sorting mechanism. The simulation results demonstrated that the spherical waste did not roll out of the platform after leaving the slideway. The waste was stabilized at the center of the platform within a short duration with movement of the collecting mechanism of the platform. The system was optimized to reduce waste separation and sorting time. Stability of the waste motion in the equipment as well as efficiency of the system were significantly improved after optimization. The results showed that the designed equipment can complete separation and sorting of waste materials at lower output power. [ABSTRACT FROM AUTHOR]

This paper presents the design and optimization of a new alternating electromagnetic-field-generation system, which is dedicated to actuating untethered magnetic microrobots under an inverted microscope. Its uniqueness is that the system parameters are optimally designed by considering both electric and geometry constraints for the target-driving application. The dominant parameters of the system are first determined by establishing analytical models. According to the requirements of targeted application, the optimization problem with certain constraints is formulated, which is solved via the multiobjective genetic algorithm method. A prototype system with the optimal parameters is developed for experimental testing. Experimental studies are carried out to characterize actual performance of the developed actuation system. For demonstration, a magnetic microball has been actuated for navigation by surface rolling in a petri dish filled with pure water. Results indicate that the reported electromagnetic-field-generation system meets the actuation requirements for potential applications. [ABSTRACT FROM AUTHOR]

Salmonella is one of the major pathogenic bacteria causing foodborne diseases. The rapid detection of Salmonella in food is of great significance to food safety. In this study, the loop-mediated isothermal amplification (LAMP) method was developed, and primers were designed targeting the invA gene of Salmonella. Standard samples of recombinant invA-plasmid and 100 retail meat samples were tested by LAMP and compared with the results tested by conventional PCR and the routine Chinese National Food Safety Standard–Microbiological Examination of Food–Examination of Salmonella, respectively. The results showed that Salmonella strains of eight different serotypes were amplified successfully by the developed LAMP assay, and it was 1,000-fold more sensitive than conventional PCR, with the analytical sensitivity of 8 × 102 copies per μL of the standard sample of invA-plasmid. The results were visualized directly by adding calcein and MnCl2 in the LAMP reaction tube, and the positively amplified products turned green after an incubation of 2 min. In parallel detection, the positive rate of Salmonella by the LAMP assay was highly correlated with the routine Chinese national standard method. The results of the study demonstrated that the developed LAMP assay is a simple, rapid, strongly specific, highly sensitive, and visual detection method for Salmonella. The LAMP assay was rapid, strongly specific, highly sensitive, and visual for Salmonella detection. The developed LAMP assay was 1,000-fold more sensitive than the conventional PCR method. Positive rate of Salmonella with the LAMP assay was highly correlated with Chinese national standard. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) biofilm plays an important role in the persistence of chronic infection due to its resistance to antibiotics. Because of their functional diversity, active polysaccharide is increasingly being applied as a biocontrol agent to inhibit the formation of biofilm by pathogens. In this study, a new polysaccharide, GBSPII-1, isolated from the fresh sarcotesta of Ginkgo biloba L. (G. biloba) was characterized and its effect on antibiofilm formation of S. aureus was examined in vitro. High-Performance Liquid Chromatography (HPLC) analysis showed that GBSPII-1 is an acidic heteropolysaccharide composed of mannose, rhamnose, glucose, glucuronic acid, and galacturonic acid. GBSPII-1 demonstrated a molecular weight of 34 kDa and may affect the accumulation of polysaccharide intercellular adhesion (PIA) by inhibiting icaA, icaB, icaC, and icaD gene expression at subinhibitory concentrations. Under 10 g/L, GBSPII-1 showed an antioxidant effect on the inhibition rate of H2O2-induced erythrocyte hemolysis and the scavenging rate of DPPH radicals was 76.5 ± 0.5% and 89.2 ± 0.26%, respectively. The findings obtained in this study indicate that GBSPII-1 has antibacterial effect, is a possible source of natural antioxidants, and may be a potential biocontrol agent for the design of new therapeutic strategies for biofilm-related S. aureus infections. [ABSTRACT FROM AUTHOR]

To improve customer service in the reverse logistics, this article defines a new variant of the vehicle routing problem (VRP) by combining the consistent VRP (ConVRP) and the VRP with simultaneous distribution and collection (VRPSDC). This new variant is called the consistent vehicle routing problem with simultaneous distribution and collection, for which a mixed-integer programming model is formulated. To solve this problem, three heuristics are proposed on the basis of the record-to-record (RTR) travel algorithm, the local search with variable neighbourhood search (LSVNS), and the tabu search-based method. Numerical experiments are performed to validate the efficiency of our proposed solution methods and the effectiveness of the proposed model. The results show that the RTR-based heuristic has an advantage in small-scale instances. However, for medium-scale instances, the best option is the LSVNS-based heuristic, which can solve instances with 40 customers and 5 days within 10 s. Moreover, the LSVNS-based heuristic can solve large-scale instances with 200 customers and 5 days 3 hours. [ABSTRACT FROM AUTHOR]

Introduction: Sorafenib is a multitargeted tyrosine kinase inhibitor, which has been mainly used in the treatment of advanced hepatocellular carcinoma and renal cancer. However, hand-foot skin reaction (HFSR), as one of the most common adverse reactions, have hindered its long-term clinical application. At present, the mechanism of its occurrence has not been clearly studied and it leads to the lack of effective means of intervention. This article reviews known mechanism and management methods of HFSR caused by sorafenib. Areas covered: The author reviews HFSR caused by the treatment of sorafenib including the mechanism and management. English language reports located through PubMed are reviewed. Expert opinion: There are some conjectures about the mechanism of HFSR. However, the mechanism of HFSR induced by sorafenib is still unclear at present. In the absence of understanding the mechanism of HFSR, the most common method for clinical treatment of sorafenib-induced HFSR is dose down-regulation or discontinuation of treatment, which affects efficacy and even survival. Future research should focus on the mechanism of HFSR to find out new ways for prevention. Precautionary measures before the occurrence of HFSR can also be studied in the future. [ABSTRACT FROM AUTHOR]

Response surface methodology and central composite design based on single-factor experiments were used to optimize the extraction parameters (i.e., extraction time, extraction temperature, and solid-liquid ratio) of polysaccharides from the testa of Salicornia herbacea (STP). The optimal conditions included a liquid-solid ratio of 57:1 (volume/mass), an extraction time of 300 min and an extraction temperature of 87 °C. Under these conditions, the maximal yield of crude STP was 1.30 ± 0.06%, which agreed with model predictions. Preliminary characterization of the purified acidic polysaccharide (STP II-1) by high performance liquid chromatography indicated that it was composed mainly of d -mannose, d -rhamnose, d -glucose, d -galactose, d -arabinose, glucuronic acid and galacturonic acid. The antioxidant capacity of STP II-1 was analyzed by monitoring both the scavenging rate of the 2,2-diphenyl - 1-picrylhydrazyl free radical and inhibition rate of H 2 O 2 -induced erythrocyte hemolysis. [ABSTRACT FROM AUTHOR]