Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

Exploring biomechanical variations in ankle joint injuries among Latin dancers with different stance patterns: utilizing OpenSim musculoskeletal models.

Background: Dancers represent the primary demographic affected by ankle joint injuries. In certain movements, some Latin dancers prefer landing on the Forefoot (FT), while others prefer landing on the Entire foot (ET). Different stance patterns can have varying impacts on dancers' risk of ankle joint injuries. The purpose of this study is to investigate the differences in lower limb biomechanics between Forefoot (FT) dancers and Entire foot (ET) dancers. Method: A group of 21 FT dancers (mean age 23.50 (S.D. 1.12) years) was compared to a group of 21 ET dancers (mean age 23.33 (S.D. 0.94) years), performing the kicking movements of the Jive in response to the corresponding music. We import data collected from Vicon and force plates into OpenSim to establish musculoskeletal models for computing kinematics, dynamics, muscle forces, and muscle co-activation. Result: In the sagittal plane: ankle angle (0%-100%, p < 0.001), In the coronal plane: ankle angle (0%-9.83%, p = 0.001) (44.34%-79.52%, p = 0.003), (88.56%-100%, p = 0.037), ankle velocity (3.73%-11.65%, p = 0.017) (94.72-100%, p = 0.031); SPM analysis revealed that FT dancers exhibited significantly smaller muscle force than ET dancers around the ankle joint during the stance phase. Furthermore, FT dancers displayed reduced co-activation compared to ET dancers around the ankle joint during the descending phase, while demonstrating higher co-activation around the knee joint than ET dancers. Conclusion: This study biomechanically demonstrates that in various stance patterns within Latin dance, a reduction in lower limb stance area leads to weakened muscle strength and reduced co-activation around the ankle joint, and results in increased ankle inversion angles and velocities, thereby heightening the risk of ankle sprains. Nevertheless, the increased co-activation around the knee joint in FT dancers may be a compensatory response for reducing the lower limb stance area in order to maintain stability.

Biomechanical Analysis of Latin Dancers' Lower Limb during Normal Walking.

Latin dance involves fundamental walking steps, integral to the dance process. While resembling daily walking, Latin dance demands higher balance levels, necessitating body adjustments by dancers. These adaptations affect dancers' gait biomechanics, prompting our study on gait differences between Latin dancers (LDs) and non-dancers (NDs). We enlisted 21 female Latin dancers and 21 subjects based on specific criteria. Participants executed walking tasks, with an independent sample t-test for 1-dimensional statistical parameter mapping (SPM 1d) analyzing stance phase variations between LDs and NDs. Notably, significant differences in ankle and hip external rotation were evident during the 16.43-29.47% (p = 0.015) and 86.35-100% (p = 0.014) stance phase. Moreover, pronounced distinctions in rectus Achilles tendon force (ATF) (12.83-13.10%, p = 0.049; 15.89-80.19%, p < 0.001) and Patellofemoral joint contact force (PTF) (15.85-18.31%, p = 0.039; 21.14-24.71%, p = 0.030) during stance were noted between LDs (Latin dancers) and NDs (Non-dancers). The study revealed dancers' enhanced balance attributed to external ankle rotation for dance stability, coupled with augmented Achilles tendon and patellofemoral joint strength from prolonged practice. Moreover, integrating suitable Latin dance into rehabilitation may benefit those with internal rotation gait issues.

Rapid transesterification of cellulose in a novel DBU-derived ionic liquid: Efficient synthesis of highly substituted cellulose acetate.

Cellulose acetate (CA) is one of the most important cellulose plastics that has demonstrated extensive applications in many areas. In search of a more sustainable and efficient way to prepare CA, we synthesized a novel ionic liquid, [DBUC8]Cl, based on the commonly used catalyst DBU (1,8-diazabicyclo[5.4.0]undecyquin-7-ene) in a simple manner. [DBUC8]Cl can dissolve cellulose more efficiently than the same type of imidazolyl ionic liquid, owing to the stronger alkalinity of DBU. It is noteworthy that highly substituted CA (DS = 2.82) was successfully synthesized via transesterification with alkenyl ester under mild conditions (80 °C, 40 min) without the addition of a catalyst in this solvent, which is superior to most of the reported work. Furthermore, we confirmed that the synthesized CA had good thermoplasticity, and a transparent cellulose acetate film (CAF) was obtained by hot pressing with a small amount of glycerol. Therefore, we propose a new DBU-derived ionic liquid, which may serve as a versatile platform system for producing cellulose-derived bioplastics more sustainably and efficiently.

Efficient Cellulose Dissolution and Film Formation Enabled by Superbase Amino Acid Ionic Liquids.

Cellulose is a promising feedstock for the production of sustainable materials. To fully utilize its potential, exploring efficient cellulose solvents is a paramount prerequisite. In this study, ten superbase amino acid ionic liquids (SAAILs) are synthesized using 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with different amino acid anions via a simple neutralization method. The properties of these SAAILs, such as viscosity and glass transition temperature, varied with their cation and anion structures. The ability of the SAAILs to dissolve cellulose is related to their Kamlet-Taft parameters, particularly hydrogen bond basicity (ß). The main driving force for cellulose dissolution in SAAILs is thought to be hydrogen bonding interactions between SAAILs and cellulose hydroxyl groups. Four SAAILs composed of DBN or DBU cations and proline, or aspartic acid anions are identified as promising solvents for preparing regenerated cellulose films (RCFs). The RCF prepared from [DBN]Proline(Pro) showed a favorable combination of high tensile strength (76.9 MPa), high Young's modulus (5201.2 MPa), good transparency (≈70% at 550 nm), and smooth surface morphology. These halogen- and metal-free SAAILs show the potential to provide a new avenue for cellulose processing.

AMLnet, A deep-learning pipeline for the differential diagnosis of acute myeloid leukemia from bone marrow smears.

Acute myeloid leukemia (AML) is a deadly hematological malignancy. Cellular morphology detection of bone marrow smears based on the French-American-British (FAB) classification system remains an essential criterion in the diagnosis of hematological malignancies. However, the diagnosis and discrimination of distinct FAB subtypes of AML obtained from bone marrow smear images are tedious and time-consuming. In addition, there is considerable variation within and among pathologists, particularly in rural areas, where pathologists may not have relevant expertise. Here, we established a comprehensive database encompassing 8245 bone marrow smear images from 651 patients based on a retrospective dual-center study between 2010 and 2021 for the purpose of training and testing. Furthermore, we developed AMLnet, a deep-learning pipeline based on bone marrow smear images, that can discriminate not only between AML patients and healthy individuals but also accurately identify various AML subtypes. AMLnet achieved an AUC of 0.885 at the image level and 0.921 at the patient level in distinguishing nine AML subtypes on the test dataset. Furthermore, AMLnet outperformed junior human experts and was comparable to senior experts on the test dataset at the patient level. Finally, we provided an interactive demo website to visualize the saliency maps and the results of AMLnet for aiding pathologists' diagnosis. Collectively, AMLnet has the potential to serve as a fast prescreening and decision support tool for cytomorphological pathologists, especially in areas where pathologists are overburdened by medical demands as well as in rural areas where medical resources are scarce.

Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells.

Parthenolide (PTL) shows potent anti-inflammatory and anti-cancer activities. In the present study, the molecular mechanisms of PTL's activities were explored in lipopolysaccharide (LPS)-induced human leukemia monocytic THP-1 cells and human primary monocytes. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay was used to analyze the effect of PTL on THP-1 cell viability. Enzyme-linked immunosorbent assay was used to determine the effect of PTL on LPS-induced inflammatory cytokine secretion. Flow cytometry and quantitative real-time polymerase chain reaction were used to assess the effect of PTL on LPS-induced toll-like receptor 4 (TLR4) expression. Phosphorylation levels of signaling molecules were determined by western blot analysis. Results showed that PTL <12.5 µM did not significantly affect THP-1 cells viability. LPS treatment led to a marked up-regulation of interleukin (IL)-6, IL-1ß, IL-8, IL-12p40, tumor necrosis factor-α, IL-18, and NO in THP-1 cells. However, PTL inhibited the expression of these cytokines in a dose-dependent manner, with IC50 values of 1.091-2.620 µM. PTL blocked TLR4 expression with an IC50 value of 1.373 µM as determined by the flow cytometry analysis, and this blocking effect was verified at both protein and mRNA levels. Up-regulation of phosphorylation levels of extracellular signal-regulated kinase 1/2, Jun N-terminal kinase, p38, nuclear factor κB (NF-κB) p65, and IκBα and up-regulation of expressions of other molecules (inducible nitric oxide synthase, TLR4, and TNF receptor-associated factor 6) induced by LPS were abolished by PTL in a dose-dependent manner. The anti-inflammatory mechanisms of PTL operate partly through the TLR4-mediated mitogen-activated protein kinase and NF-κB signaling pathways. Therefore, TLR4 may be a new target for anti-inflammation therapies.

Identification of stage-specific markers during differentiation of hair cells from mouse inner ear stem cells or progenitor cells in vitro.

The induction of inner ear hair cells from stem cells or progenitor cells in the inner ear proceeds through a committed inner ear sensory progenitor cell stage prior to hair cell differentiation. To increase the efficacy of inducing inner ear hair cell differentiation from the stem cells or progenitor cells, it is essential to identify comprehensive markers for the stem cells/progenitor cells from the inner ear, the committed inner ear sensory progenitor cells and the differentiating hair cells to optimize induction conditions. Here, we report that we efficiently isolated and expanded the stem cells or progenitor cells from postnatal mouse cochleae, and induced the generation of inner ear progenitor cells and subsequent differentiation of hair cells. We profiled the gene expression of the stem cells or progenitor cells, the inner ear progenitor cells, and hair cells using aRNA microarray analysis. The pathway and gene ontology (GO) analysis of differentially expressed genes was performed. Analysis of genes exclusively detected in one particular cellular population revealed 30, 38, and 31 genes specific for inner ear stem cells, inner ear progenitor cells, and hair cells, respectively. We further examined the expression of these genes in vivo and determined that Gdf10+Ccdc121, Tmprss9+Orm1, and Chrna9+Espnl are marker genes specific for inner ear stem cells, inner ear progenitor cells, and differentiating hair cells, respectively. The identification of these marker genes will likely help the effort to increase the efficacy of hair cell induction from the stem cells or progenitor cells.

PA2800 plays an important role in both antibiotic susceptibility and virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an important human pathogen which causes a variety of infections. P. aeruginosa infections are often difficult to treat due to the pathogen's resistance to many antibiotics. Previously, it has been reported that a transposon insertion mutant in gene PA2800 of P. aeruginosa PAO1 was more sensitive to tetracycline and ciprofloxacin. Further characterization of this gene, a vacJ homolog, in this study indicated that this gene plays an important role in both antibiotic susceptibility and virulence in P. aeruginosa. The role of PA2800 in antibiotic susceptibility probably signifies its involvement in maintaining outer membrane stability, similar to the role of vacJ in E. coli and Shigella flexneri. However, in contrast to vacJ in other bacteria, PA2800 also affects antibiotic susceptibility by affecting the expression of oprH in P. aeruginosa. As shown by in vivo studies using a Drosophila melanogaster infection model, significantly increased virulence was observed in the PA2800 mutant when compared to the wild type, and such a difference is likely a result of disrupted outer membrane stability and altered expression of znuA in the mutant. The role of PA2800 or vacJ in antibiotic susceptibility and pathogenicity seems to be unique in P. aeruginosa in which it affects both outer membrane stability as well as gene expression.

[Effects of 1,4-benzoquinone on the proliferation activity of human bone marrow stem cells].

OBJECTIVE: To explore the influence of 1,4-benzoquinone (1,4-BQ) on proliferation of human bone marrow haematopoietic stem cells (hBM-HSCs) and human bone marrow mesenchymal stem cells (hBM-MSCs). METHODS: The bone marrow samples were collected from a healthy donor. Methylcellulose semi-solid culture medium was used to culture the mononuclear cells of bone marrow in different culture systems. Colony-forming unit (CFU) assay was utilized to evaluate the proliferation of hBM-HSCs exposed to 1,4-BQ at the doses of 10, 25, 50 and 100 µmol/L and to observe the influence of 1,4-BQ on the Colony-forming unit-erythroid (CFU-E)/Burst-forming unit-erythroid (BFU-E), Colony-forming unit-granulocyte, macrophage (CFU-GM), Colony-forming unit-granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM) in hBM-MSCs. MTT assay was used to detect the proliferation of hBM-MSCs exposed to 1,4-BQ at the doses of 1, 5, 10, 25, 50, 100, 200, 500 and 1000 µmol/L for 24 h, respectively, after hBM-MSCs were isolated, cultured and expanded. RESULTS: The results of CFU assay indicated that numbers of CFU-E/BFU-E, CFU-GM and CFU-GEMM in 25, 50 and 100 µmol/L groups significantly decreased, as compared with control group (P < 0.05). However, no significant difference was found between the 10 µmol/L group and the control group. The results of MTT assay showed that the cellular viability of hBM-MSCs exposed to 1,4-BQ at the doses of 50 ∼ 200 µmol/L for 24 h significantly decreased in a dose-depended manner. When the exposure dose was higher than 200 µmol/L, the cellular viability of hBM-MSCs was lower than 5% which was significantly lower than that of control group (P < 0.05). When the exposure dose was lower than 25 µmol/L, there was no significant difference of cellular viability between exposure group and control group (P > 0.05). CONCLUSION: The results of the present study demonstrated that 1,4-BQ could inhibit the colony forming of hBM-HSCs and the relative viability of hBM-MSCs in vitro. The hematotoxicity induced by 1,4-BQ may be related to inhibiting the proliferation capacity of hBM-HSCs.