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Abstract The objective of this study was to investigate the correlation between Rab10 (GTP binding protein RAB10), TLR4 (Toll-like receptor 4), and NF-κB (nuclear factor kappa-B) levels and therapeutic effects in peripheral blood of patients with breast cancer after surgery. The study included 160 patients with stage I-III breast cancer who underwent surgical treatment at our hospital’s Department of Breast Surgery and Oncology between January 2021 and June 2021. ELISA was used to assess Rab10, TLR4, and NF-κB levels in peripheral blood. Based on their levels of Rab10, TLR4, and NF-κB in peripheral blood, participants were categorized into two groups: the low marker expression group (72 participants with relatively low expression of Rab10, TLR4, and NF-κB: Rab10

Abstract Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.

Abstract Background Breast cancer (BC), a common malignant tumor originating from the terminal ductal lobular unit of the breast, poses a substantial health risk to women. Previous studies have associated cytochrome b561 (CYB561) with a poor prognosis in BC; however, its underlying mechanism of this association remains unclear. Methods We investigated the expression of CYB561 mRNA in BC using databases such as The Cancer Genome Atlas, Gene Expression Omnibus, Tumor–Normal–Metastatic plot, and Kaplan–Meier plotter databases. The prognostic value of CYB561 protein in BC was assessed in relation to its expression levels in tumor tissue samples from 158 patients with BC. The effect of CYB561 on BC progression was confirmed using in vivo and in vitro experiments. The biological functions and related signaling pathways of CYB561 in BC were explored using gene microarray, Innovative Pathway, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The correlation between CYB561 and the BC tumor immune microenvironment was evaluated using the CIBERSORT algorithm and single-cell analysis and further validated through immunohistochemistry of serial sections. Results Our study demonstrated that upregulation of CYB561 expression predicted poor prognosis in patients with BC and that CYB561 knockdown inhibited the proliferation, migration, and invasive ability of BC cells in vitro. CYB561 knockdown inhibited BC tumor formation in vivo.CYB561 was observed to modulate downstream tropomyosin 1 expression. Furthermore, CYB561 expression was associated with macrophage M2 polarization in the BC immune microenvironment. Conclusions Elevated CYB561 expression suggests a poor prognosis for patients with BC and is associated with macrophage M2 polarization in the BC microenvironment. Therefore, CYB561 could potentially serve as a therapeutic target for BC treatment.

Balancing mechanical and corrosion performance is a decisive factor in the use of high entropy and medium entropy alloys (H & MEAs) as advanced engineering structural materials. This study investigates the microstructure of Fe77.3-xMnxSi9.1Cr9.8C3.8 (x = 14, 23.2) HEAs by combining experiments and first-principles calculations to elucidate the effects of adjusting Mn content on the mechanical and corrosion properties of FCC and FCC + HCP phases. The results demonstrate that HEAs with low Mn content exhibit a single FCC phase, whereas increasing Mn content not only precipitates the HCP phase but also refines the grain size. The yield strength, compressive fracture strength, work hardening index, and plasticity of Fe77.3-xMnxSi9.1Cr9.8C3.8 (x = 14, 23.2 at.%) HEAs are 1300 and 1526 MPa, 2380 and 2332 MPa, 0.42 and 0.36, 16.7% and 16%, respectively. Both HEAs exhibit superior electrochemical and salt spray corrosion performance compared to 304 stainless steels, with the Fe63.3Mn14Si9.1Cr9.8C3.8 alloy performing the best, exhibiting a self-corrosion potential of −0.523V and a self-corrosion current density of 2.605 × 10−6 A cm−2. The excellent corrosion resistance of Fe63.3Mn14Si9.1Cr9.8C3.8 can be attributed to the moderate grain size, resulting in excellent passivation film characteristics, and the lower Mn content, leading to a higher Cr2O3 content in the passivation film. First-principles calculations reveal that Fe63.3Mn14Si9.1Cr9.8C3.8 has a lower density of states number at the Fermi level (i.e., Fe63.3Mn14Si9.1Cr9.8C3.8 is 214.145eV, Fe54.1Mn23.2Si9.1Cr9.8C3.8 is 337.077eV), a wider pseudogap width, higher work function (5.700ev, 5.189ev), and better stability. Additionally, there exists a strong trade-off between corrosion and mechanical properties due to the influence of the HCP phase and grain size.

Abstract Background Acute myeloid leukaemia (AML) is a haematological malignancy with unfavourable prognosis. Despite the effectiveness of chemotherapy and targeted therapy, relapse or drug resistance remains a major threat to AML patients. N6‐methyladenosine (m6A) RNA methylation and super‐enhancers (SEs) are extensively involved in the leukaemogenesis of AML. However, the potential relationship between m6A and SEs in AML has not been elaborated. Methods Chromatin immunoprecipitation (ChIP) sequencing data from Gene Expression Omnibus (GEO) cohort were analysed to search SE‐related genes. The mechanisms of m6 A‐binding proteins IGF2BP2 and IGF2BP3 on DDX21 were explored via methylated RNA immunoprecipitation (MeRIP) assays, RNA immunoprecipitation (RIP) assays and luciferase reporter assays. Then we elucidated the roles of DDX21 in AML through functional assays in vitro and in vivo. Finally, co‐immunoprecipitation (Co‐IP) assays, RNA sequencing and ChIP assays were performed to investigate the downstream mechanisms of DDX21. Results We identified two SE‐associated transcripts IGF2BP2 and IGF2BP3 in AML. High enrichment of H3K27ac, H3K4me1 and BRD4 was observed in IGF2BP2 and IGF2BP3, whose expression were driven by SE machinery. Then IGF2BP2 and IGF2BP3 enhanced the stability of DDX21 mRNA in an m6A‐dependent manner. DDX21 was highly expressed in AML patients, which indicated a poor survival. Functionally, knockdown of DDX21 inhibited cell proliferation, promoted cell apoptosis and led to cell cycle arrest. Mechanistically, DDX21 recruited transcription factor YBX1 to cooperatively trigger ULK1 expression. Moreover, silencing of ULK1 could reverse the promoting effects of DDX21 overexpression in AML cells. Conclusions Dysregulation of SE‐IGF2BP2/IGF2BP3‐DDX21 axis facilitated the progression of AML. Our findings provide new insights into the link between SEs and m6A modification, elucidate the regulatory mechanisms of IGF2BP2 and IGF2BP3 on DDX21, and reveal the underlying roles of DDX21 in AML.

Vacuum brazing of GH3535 alloy was conducted using Au–18Ni (wt%) filler metal. The effect of brazing temperature on the microstructure and mechanical properties was investigated. Furthermore, the microstructural evolution and fracture mechanisms of brazed joints were discussed. The cross section of brazed joint could be divided into two distinctive reaction zones. The typical microstructure of the joint brazed at 1030 °C/10min was GH3535 substrate/Ni (s.s) + Mo-rich Ni (s.s) + Au-rich phase/Au (s.s) + FeNi3/Au-rich phase + Mo-rich Ni (s.s) + Ni (s.s) + GH3535 substrate. Raising the brazing temperature promoted the diffusion of elements, Ni (s.s) and Au (s.s) gradually increased, and the second phase particles consisting of FeNi3 gradually decreased. With the increase in brazing temperature, the shear strength of brazed joints first increased and then decreased. The maximum room shear strength of 420 MPa was obtained at 960 °C/25min and the high temperature shear strength of 153 MPa was obtained at 600 °C. Fracture analysis indicated that cracks initiated at the interface of Au (s.s) and then propagated along the zone of FeNi3 with dimple and tearing ridges patterns.

Abstract RAB10, a member of the small GTPase family, has complex biological functions, but its role in breast cancer (BC) remains unclear. The aim of this study was to investigate the relationship between RAB10's role in BC, its biological functions, and BC prognosis. An online database was used to analyze the correlation between differential expression of RAB10 in BC and prognosis. The results of immunohistochemical assays in clinical cohorts were combined with the database analysis. The chi-square test and COX regression were employed to analyze the correlation between RAB10 and pathological features of BC. MTT, Transwell, and wound healing assays were conducted to detect BC cell proliferation, invasion, and metastatic ability. Bioinformatics techniques were employed to explore the correlation between RAB10 and BC tumor immune cell infiltration, and to speculate the biological function of RAB10 in BC and related signaling pathways. Our findings suggest that RAB10 expression is elevated in BC and is associated with HER2 status, indicating a poor prognosis for BC patients. RAB10 can promote the proliferation, migration, and invasion ability of BC cells in vitro. RAB10 is also associated with BC immune cell infiltration and interacts with multiple signaling pathways. RAB10 is a potential biomarker or molecular target for BC.

Bromodomain‐containing protein 4 (BRD4) inhibitors have been clinically developed to treat acute myeloid leukemia (AML), but their application is limited by the possibility of drug resistance, which is reportedly associated with the activation of the WNT/β‐catenin pathway. Meanwhile, homoharringtonine (HHT), a classic antileukemia drug, possibly inhibits the WNT/β‐catenin pathway. In this study, we attempted to combine a novel BRD4 inhibitor (ACC010) and HHT to explore their synergistic lethal effects in treating AML. Here, we found that co‐treatment with ACC010 and HHT synergistically inhibited cell proliferation, induced apoptosis, and arrested the cell cycle in FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD)–positive AML cells in vitro, and significantly inhibiting AML progression in vivo. Mechanistically, ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010‐resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3‐inhibitor‐resistant FLT3‐ITD/tyrosine kinase domain mutations and AML cells without FLT3‐ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3‐ITD.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a kind of highly heterogeneous non-Hodgkin lymphoma, both in clinical and genetic terms. DLBCL is admittedly categorized into six subtypes by genetics, which contain MCD, BN2, EZB, N1, ST2, and A53. Dyslipidemia is relevant to a multitude of solid tumors and has recently been reported to be associated with hematologic malignancies. We aim to present a retrospective study investigating dyslipidemia in DLBCL based on the molecular subtypes.ResultsThis study concluded that 259 patients with newly diagnosed DLBCL and their biopsy specimens were available for molecular typing. Results show that the incidence of dyslipidemia (87.0%, p

Micro/nano-structure is one of the important types of multilayer construction, which can make nanocrystalline metals and alloys with excellent comprehensive mechanical properties. By means of Aluminothermic Reaction (AR) and subsequent rolling with deformation of 50% at room temperature (RT) and followed by annealed at 973 K for 1 h, a heterogeneous composite structure of micro/nano-structured 304 stainless steel (SS) is obtained. Such a stainless steel specimen exhibits a tensile strength as high as 1023 MPa and an elongation-to-failure of about 27.3%. In the process, the much elevated strength originates from martensite strengthening, austenite grain refinement and dislocation density increasing, while ductility promotes from the recrystallization of deformed austenite and recovery of strain induced martensite. Superior strength–ductility combination achieves in micro/nano-structured 304 SS, which demonstrates a novel approach for optimizing the mechanical properties in engineering materials.

Abstract Background Screening of breast cancer in asymptomatic women is important to evaluate for early diagnosis. In China ultrasound is a more frequently used method than mammography for the detection of breast cancer. The objectives of the study were to provide evidence and assessment of parenchymal patterns of ultrasonography for breast cancer detection among Chinese women. Methods Breast ultrasound examinations including the parenchymatous pattern of cytopathological confirmed breast cancer (n = 541) and age-matched cytopathological not confirmed breast cancer (n = 849) women were retrospectively reviewed by seven sonographer physicians. According to compositions of ducts, the thickness of the breast, diameter of ducts, fat lobules, and fibro glandular tissues, the breast parenchymatous pattern was categorized into heterogeneous (high percentage of fatty tissues), ductal (the inner diameters of ducts > 50% of the thick mass of the breast), mixed (the inner diameters of ducts was 50% of the thick mass of the breast), and fibrous categories (a dense classification of the breast). Results Heterogeneous (p

Fe-XMn-5Si-10Cr-0.9C (X = 10, 15, 20, and 25 wt%) medium entropy alloys (MEAs) with different Mn contents were prepared by magnetic suspension melting in a water-cooled copper crucible, and casted in a negative pressure suction copper mould. The modified Warren–Averbach equation and the thermodynamic model were used to calculate the alloy dislocation density and stacking faults, respectively. The effects of the Mn content on the phase structure, stacking fault energy (SFE), dislocation density, and mechanical properties of the alloy were investigated. The results indicate that the MEAs possess a low stacking fault energy (∼8.50–14.44 mJ/m2) and a unique high as-cast dislocation density (up to 4.8 × 1015 m−2). The microstructure of the as-cast alloys consisted of austenite phase. As loading, the γ → ε martensite transformation occurs and is accompanied by obvious work-hardening behaviour. A low SFE and high ΔSmix improved the storage capacity of the dislocation density, promoted the formation of ε-martensite, and improve the strength and plasticity. Both the SFE and ΔSmix increased with an increase in the Mn content, and the dislocation density initially increased and then decreased. Optimising the Mn content and coordinating the balance between the SFE and ΔSmix can regulate the optimal dislocation density.

This case report involves a 93-year-old female patient with atrioventricular block and suffered right ventricular free wall perforation during installation of Micra Leadless Pacemaker (MLP). Pericardial tamponade occurred shortly, and we adopted pericardial catheter drainage as the primary emergency treatment. Considering the patient's physical conditions and leveraging the special treatment facilitates of the Intensive Care Unit (ICU), we tried a new emergency treatment approach. After putting the patient under intravenous anesthesia (no cardiac arrest), we made a small intercostal incision and performed bedside minimally invasive repair of right ventricular free wall perforation. It should be noted that ultrasound played a key role in pinpointing the breach and intraoperative guidance. We first used contrast-enhanced ultrasound (CEUS) to locate the breach. Then guided by bedside ultrasound, we accessed the perforation with the minimum incision size (5 cm). Our experience in this case may serve as a good reference in the emergency treatment for right ventricular free wall perforation.

Background: Rab10 is a small GTPase protein belonging to the Ras superfamily. It is expressed and plays a role in a variety of malignant tumours. However, the expression of Rab10 and its role in breast cancer (BC) prognosis remains unclear. The aim of this study was to analyse the differential expression and prognostic value of Rab10 in BC using bioinformatics techniques and immunohistochemistry in a clinical cohort. Methods: The TIMER2, GEPIA2, and UALCAN databases were used to analyse the correlation between the differential expression of Rab10 and BC. Rab10 and BC prognosis were correlated using the Kaplan–Meier Plotter and UALCAN databases. The expression of Rab10 in BC tissues was detected using immunohistochemistry, and its correlation with the BC clinical cohort was analysed using Chi-squared tests and logistic regression analysis. Results: The expression of Rab10 mRNA identified in BC patients using TIMER2, GEPIA2, and UALCAN databases was higher than that in para-cancerous tissues. Kaplan–Meier plotter and the UALCAN database revealed that increased Rab10 expression was associated with poor prognosis in BC patients. Immunohistochemistry showed that Rab10 was expressed on cell membranes and in cytoplasm of BC tissues. In a clinical cohort, Rab10 expression correlated with histological grade, (human epidermal growth factor receptor 2) HER2 status, and molecular typing. Conclusions: Rab10 can be used as an effective clinical prognostic biomarker for BC.

The salp swarm algorithm imitates the swarm behavior of salps during navigation and hunting that has been proven the superiority of search for best solution. However, although it has sufficient global search ability, it is still worth paying attention to problems of falling into local optima and lower convergence accuracy. This paper proposes some improvements to the salp swarm algorithm that are based on a nonlinear dynamic weight and the mapping mutation operation. Firstly, the nonlinear dynamic weight is helpful for further optimizing the transition from exploration to exploitation and alleviating the local optima stagnation phenomena. Secondly, utilizing a mapping mutation operation can increase the diversity of followers in algorithm, to avoid getting trapped into the local optima during the search and provide a better optimal solution. The proposed algorithm is characterized by a stronger global optimization capability and high convergence accuracy. Finally, to confirm the effectiveness of the proposed algorithm, comparative experiments based on other well-known swarm-based algorithms and each improvement for the original algorithm are conducted. The quantitative results and convergence curves among several algorithms demonstrate that the enhanced algorithm with the nonlinear dynamic weight and mapping mutation operation can outperform the original algorithm.

Calcineurin B-like protein-interacting protein kinases (CIPKs) play important roles in plant responses to stress. However, their function in the ornamental woody plant Lagerstroemia indica is remains unclear. In this study, the LiCIPK gene family was analyzed at the whole genome level. A total of 37 LiCIPKs, distributed across 17 chromosomes, were identified. Conserved motif analysis indicated that all LiCIPKs possess a protein kinase motif (S_TKc) and C-terminal regulatory motif (NAF), while seven LiCIPKs lack a protein phosphatase interaction (PPI) motif. 3D structure analysis further revealed that the N-terminal and C-terminal 3D-structure of 27 members are situated near to each other, while 4 members have a looser structure, and 6 members lack intact structures. The intra- and interspecies collinearity analysis, synonymous substitution rate (Ks) peaks of duplicated LiCIPKs, revealed that ∼80% of LiCIPKs were retained by the two whole genome duplication (WGD) events that occurred approximately 56.12–61.16 million year ago (MYA) and 16.24–26.34 MYA ago. The promoter of each LiCIPK contains a number of auxin, abscisic acid, gibberellic acid, salicylic acid, and drought, anaerobic, defense, stress, and wound responsive cis-elements. Of the 21 members that were successfully amplified by qPCR, 18 LiCIPKs exhibited different expression patterns under NaCl, mannitol, PEG8000, and ABA treatments. Given that LiCIPK30, the AtSOS2 ortholog, responded to all four types of stress it was selected for functional verification. LiCIPK30 complements the atsos2 phenotype in vivo. 35S:LiCIPK-overexpressing lines exhibit increased leaf area increment, chlorophyll a and b content, reactive oxygen species scavenging enzyme activity, and expression of ABF3 and RD22, while the degree of membrane lipid oxidation decreases under NaCl treatment compared to WT. The evolutionary history, and potential mechanism by which LiCIPK30 may regulate plant tolerance to salt stress were also discussed. In summary, we identified LiCIPK members involved in abiotic stress and found that LiCIPK30 transgenic Arabidopsis exhibits more salt and osmotic stress tolerance than WT. This research provides a theoretical foundation for further investigation into the function of LiCIPKs, and for mining gene resources to facilitate the cultivation and breeding of new L. indica varieties in coastal saline-alkali soil.

Abstract Background N6-methyladenosine (m6A) modification is an emerging layer of epigenetic regulation which is widely implicated in the tumorigenicity of hepatocellular carcinoma (HCC), offering a novel perspective for investigating molecular pathogenesis of this disease. The role of AlkB homolog 5 (ALKBH5), one of the m6A demethylases, has not been fully explored in HCC. Here we clarify the biological profile and potential mechanisms of ALKBH5 in HCC. Methods Expression of ALKBH5 and its correlation with clinicopathological characteristics of HCC were evaluated using tissue microarrays and online datasets. And biological effects of ALKBH5 in HCC were determined in vitro and in vivo. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq), and following m6A dot blot, MeRIP-qPCR, RIP-qPCR or dual luciferase reporter assays were employed to screen and validate the candidate targets of ALKBH5. Results We demonstrated that ALKBH5 was down-regulated in HCC, and decreased ALKBH5 expression was an independent prognostic factor of worse survival in HCC patients. Functionally, ALKBH5 suppressed the proliferation and invasion capabilities of HCC cells in vitro and in vivo. Mechanistically, ALKBH5-mediated m6A demethylation led to a post-transcriptional inhibition of LY6/PLAUR Domain Containing 1 (LYPD1), which could be recognized and stabilized by the m6A effector IGF2BP1. In addition, we identified that LYPD1 induced oncogenic behaviors of tumors in contrast to ALKBH5. Dysregulation of ALKBH5/LYPD1 axis impelled the progression of HCC. Conclusion Our study reveals that ALKBH5, characterized as a tumor suppressor, attenuates the expression of LYPD1 via an m6A-dependent manner in HCC cells. Our findings enrich the landscape of m6A-modulated tumor malignancy, and provide new insights into potential biomarkers and therapeutic targets of HCC treatment.

Abstract N6-methyladenosine (m6A) is the most abundant form of mRNA modification in eukaryotes. It affects various aspects of RNA metabolism, including nuclear export, translation, decay and alternative splicing. In addition, m6A also participates in a great number of human physiological processes, ranging from spermatogenesis modulation, response to heat shock, the control of T cell homeostasis to stem cell proliferation and differentiation. The dynamic equilibrium of m6A level is regulated by m6A methyltransferases (“writers”), m6A demethylases (“erasers”) as well as m6A-binding proteins (“readers”). Once the balance is broken, numerous diseases will knock on the door. Recently, increasing studies reveal that m6A methylation exerts a profound impact on tumorigenesis and tumor progression. Therefore, in this review, we summarize the functions of m6A modification and its emerging roles in human cancers, and discuss the potential of m6A regulators as biomarkers or therapeutic targets.

Abstract N6-methyladenosine (m6A) is a well-known post-transcriptional modification that is the most common type of methylation in eukaryotic mRNAs. The regulation of m6A is dynamic and reversible, which is erected by m6A methyltransferases (“writers”) and removed by m6A demethylases (“erasers”). Notably, the effects on targeted mRNAs resulted by m6A predominantly depend on the functions of different m6A-binding proteins (“readers”) including YT521-B homology (YTH) domain family, heterogeneous nuclear ribonucleoproteins (HNRNPs), and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs). Indeed, m6A readers not only participate in multiple procedures of RNA metabolism, but also are involved in a variety of biological processes. In this review, we summarized the specific functions and underlying mechanisms of m6A-binding proteins in tumorigenesis, hematopoiesis, virus replication, immune response, and adipogenesis.

Learning density estimation is important in probabilistic modeling and reasoning with uncertainty. Since B-spline basis functions are piecewise polynomials with local support, density estimation with B-splines shows its advantages when intensive numerical computations are involved in the subsequent applications. To obtain an optimal local density estimation with B-splines, we need to select the bandwidth (i.e., the distance of two adjacent knots) for uniform B-splines. However, the selection of bandwidth is challenging, and the computation is costly. On the other hand, nonuniform B-splines can improve on the approximation capability of uniform B-splines. Based on this observation, we perform density estimation with nonuniform B-splines. By introducing the error indicator attached to each interval, we propose an adaptive strategy to generate the nonuniform knot vector. The error indicator is an approximation of the information entropy locally, which is closely related to the number of kernels when we construct the nonuniform estimator. The numerical experiments show that, compared with the uniform B-spline, the local density estimation with nonuniform B-splines not only achieves better estimation results but also effectively alleviates the overfitting phenomenon caused by the uniform B-splines. The comparison with the existing estimation procedures, including the state-of-the-art kernel estimators, demonstrates the accuracy of our new method.

BackgroundExisting research shows that ABT-199, as a first-line drug, have been widely used in hematological malignancies, especially in leukemia, but the clinical efficacy of single drug therapy was limited part of the reason was that BCL-2 inhibitors failure to target other anti-apoptotic BCL-2 family proteins, such as MCL-1. In this case, combination therapy may be a promising way to overcome this obstacle. Here, we investigate the preclinical efficacy of a new strategy combining ABT-199 with homoharringtonine (HHT), a selective inhibitor of MCL-1 may be a promising approach for AML treatment as these two molecules are important in apoptosis.MethodsA Cell Counting Kit-8 (CCK8) assay and flow cytometry were used to determine the half-maximal inhibitory concentration (IC50) value and cell apoptosis rate, respectively. The flow cytometry results showed that combined treatment with HHT and ABT-199 caused apoptosis in AML patient samples (n=5) but had no effect on normal healthy donor samples (n=11). Furthermore, we used a Western blot assay to explore the mechanism underlying the efficacy of HHT combined with ABT-199. Finally, antileukemic activity was further evaluated in vivo xenograft model.ResultsOur results indicated that ABT-199 combined with HHT significantly inhibited cell growth and promoted apoptosis in both AML cell lines and primary AML tumors in a dose- and time-dependent manner. Moreover, HHT combined with ABT-199 suppressed AML cell growth and progression in vivo xenograft model.ConclusionsOur research found that HHT combined with ABT-199 exerted its anti-leukemia effect by inducing apoptosis through the treatment of AML in vitro and in vivo.

Siamese network trackers based on pre-trained depth features have achieved good performance in recent years. However, the pre-trained depth features are trained in advance on large-scale datasets, which contain feature information of a large number of objects. There may be a pair of interference and redundant information for a single tracking target. To learn a more accurate target feature information, this paper proposes a lightweight target-aware attention learning network to learn the most effective channel features of the target online. The lightweight network uses a designed attention learning loss function to learn a series of channel features with weights online with no complex parameters. Compared with the pre-trained features, the channel features with weights can represent the target more accurately. Finally, the lightweight target-aware attention learning network is unified into a Siamese tracking network framework to implement target tracking effectively. Experiments on several datasets demonstrate that the tracker proposed in this paper has good performance.

The effect of Ca on the microstructure and corrosion behavior of a single-phase Mg–Sc alloy was investigated. The microstructure was characterized by optical microscopy and scanning electron microscopy. Corrosion behavior was measured by hydrogen evolution tests and electrochemical measurements. With the addition of microalloyed Ca, the grain size of Mg-0.3Sc alloy is refined and the Mg2Ca phase particle is precipitated. The corrosion test results reveal that the addition of microalloyed Ca is beneficial to the corrosion resistance of Mg-0.3Sc single-phase alloy, which is related to the grain refinement and the protective performance of the corrosion product film. As the content of Ca increases, the corrosion resistance of the alloy first increases and then decreases, which is mainly related to the microstructure of the alloy.

Building a gradient structure inside the Mg alloy structure can be expected to greatly improve its comprehensive mechanical properties. In this study, AZ31/Mg–Sc laminated composites with gradient grain structure were prepared by hot extrusion. The microstructure and mechanical properties of the Mg–1Sc alloy with different extrusion temperatures and surface AZ31 fine-grain layers were investigated. The alloy has a more obvious gradient microstructure when extruded at 350 °C. The nanoscale hardness value of Mg–1Sc alloy was improved through fine-grain strengthening and solution strengthening of the surface AZ31 fine-grain layer. The strength of Mg–1Sc alloy was improved due to the fine-grain strengthening and dislocation strengthening of the surface AZ31 fine-grain layer, and the elongation of Mg–1Sc alloy was increased by improving the distribution of the microstructure.

OBJECTIVES: Radiographic manifestations of synovitis (e.g., erosions) can be observed only in the late stage of rheumatoid arthritis. Ultrasound is a noninvasive, cheap, and widely available technique that enables the evaluation of inflammatory changes in the peripheral joint. In the same way, dynamic contrast-enhanced magnetic resonance imaging (MRI) enables qualitative and quantitative measurements. The objectives of the study were to compare the sensitivity and accuracy of ultrasound in detecting subclinical synovitis and tenosynovitis with those of contrast-enhanced MRI. METHODS: The ultrasonography and contrast-enhanced MRI findings of the wrist, metacarpophalangeal, and proximal interphalangeal joints (n=450) of 75 patients with a history of joint pain and morning stiffness between 6 weeks and 2 years were reviewed. The benefits score was evaluated for each modality. RESULTS: The ultrasonic findings showed inflammation in 346 (77%) joints, while contrast-enhanced MRI found signs of early rheumatoid arthritis in 372 (83%) joints. The sensitivities of ultrasound and contrast-enhanced MRI were 0.795 and 0.855, respectively, and the accuracies were 0.769 and 0.823, respectively. Contrast-enhanced MRI had a likelihood of 0-0.83 and ultrasound had a likelihood of 0-0.77 for detecting synovitis and tenosynovitis at one time. The two imaging modalities were equally competitive for detecting synovitis and tenosynovitis (p=0.055). CONCLUSION: Ultrasound could be as sensitive and specific as contrast-enhanced MRI for the diagnosis of subclinical synovitis and tenosynovitis.

This article studies the inverse kinematics for asymmetric octahedral variable geometry truss manipulator with obstacle avoidance. The inverse kinematics problem is cast as a nonconvex optimization that having quadratic objective function subject to quadratic constraints. This article uses an inexact interior point optimization to solve it, which is developed on the basis of the imprecise algorithm Ipopt. According to the particularity of our actual optimization problem, each iteration undergoes specific modifications so as to minimize the memory consumption as well as computation time. Utilizing the sparse and binary characteristics of the coefficient matrix, respectively, the algorithm allocates the computation to the finite sparse matrix vector multiplication and changes the storage form, which greatly reduces the memory space. Based on the unique rules of inverse kinematics, the iteration direction of the algorithm becomes more clear. With the aid of mechanical constraints inherent in the manipulator, the algorithm omits the feasibility recovery part that embedded in the solver Ipopt. All these make us save the operation time greatly while utilizing Ipopt algorithm. To demonstrate the effectiveness of the proposed approach, the scheme was applied to obstacle avoidance inverse kinematics of variable geometry truss manipulator with three modules.

Novel ultra-strong medium entropy bulk metallic glasses composites (BMGCs) Fe65.4−xCexMn14.3Si9.4Cr10C0.9 and Ti40−xCexNi40Cu20 (x = 0, 1.0), through the martensite transformation induced plasticity (TRIP effect) to enhance both the ductility and work-hardening capability, were fabricated using magnetic levitation melting and copper mold suction via high frequency induction heating. Furthermore, the Ce microalloying effects on microstructure and mechanical behaviors were studied. The Fe-based BMGCs consisted of face-centered cubic (fcc) γ-Fe and body-centered cubic (bcc) α-Fe phase, as well as Ti-based BMGCs containing supercooled B2-Ti (Ni, Cu) and a thermally induced martensite phase B19’-Ti (Ni, Cu). As loading, the TRIP BMGCs exhibited work-hardening behavior, a high fracture strength, and large plasticity, which was attributed to the stress-induced transformation of ε-Fe martensite and B19’-Ti (Ni, Cu) martensite. Ce addition further improved the strengthening and toughening effects of TRIP BMGCs. Adding elemental Ce enhanced the mixing entropy ΔSmix and atomic size difference δ, while reducing the mixing enthalpy ΔHmix, thus improving the glass forming ability and delaying the phase transition process, and hence prolonging the work-hardening period before fracturing. The fracture strength σf and plastic stress εp of Ti39CeNi40Cu20 and Fe64.4CeMn14.3Si9.4Cr10C0.9 alloys were up to 2635 MPa and 13.8%, and 2905 MPa and 30.1%, respectively.

Bearded irises are ornamental plants with distinctive floral fragrance grown worldwide. To identify the floral scent profiles, twenty-seven accessions derived from three bearded iris, including Iris. germanica, I. pumila and I. pallida were used to investigate the composition and relative contents of floral scent components by headspace solid-phase microextraction (HS-SPME) and gas chromatography−mass spectrometry (GC-MS). A total of 219 floral scent components were detected in blooming flowers. The scent profile varied significantly among and within the three investigated species. Principal component analysis (PCA) indicated that terpenes, alcohols and esters contributed the most to the floral scent components and 1-caryophyllene, linalool, citronellol, methyl cinnamate, β-cedrene, thujopsene, methyl myristate, linalyl acetate, isosafrole, nerol, geraniol were identified as the major components. In a hierarchical cluster analysis, twenty-seven accessions could be clustered into six different groups, most of which had representative scent components such as linalool, citronellyl acetate, thujopsene, citronellol, methyl cinnamate and 1-caryophyllene. Our findings provide a theoretical reference for floral scent evaluation and breeding of bearded irises.

This article studies the inverse kinematics problem of the variable geometry truss manipulator. The problem is cast as an optimization process which can be divided into two steps. Firstly, according to the information about the location of the end effector and fixed base, an optimal center curve and the corresponding distribution of the intermediate platforms along this center line are generated. This procedure is implemented by solving a non-convex optimization problem that has a quadratic objective function subject to quadratic constraints. Then, in accordance with the distribution of the intermediate platforms along the optimal center curve, all lengths of the actuators are calculated via the inverse kinematics of each variable geometry truss module. Hence, the approach that we present is an optimization procedure that attempts to generate the optimal intermediate platform distribution along the optimal central curve, while the performance index and kinematic constraints are satisfied. By using the Lagrangian duality theory, a closed-form optimal solution of the original optimization is given. The numerical simulation substantiates the effectiveness of the introduced approach.