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Abstract During cardiac development, mechanotransduction from the in vivo microenvironment modulates cardiomyocyte growth in terms of the number, area, and arrangement heterogeneity. However, the response of cells to different degrees of mechanical stimuli is unclear. Organ-on-a-chip, as a platform for investigating mechanical stress stimuli in cellular mimicry of the in vivo microenvironment, is limited by the lack of ability to accurately quantify externally induced stimuli. However, previous technology lacks the integration of external stimuli and feedback sensors in microfluidic platforms to obtain and apply precise amounts of external stimuli. Here, we designed a cell stretching platform with an in-situ sensor. The in-situ liquid metal sensors can accurately measure the mechanical stimulation caused by the deformation of the vacuum cavity exerted on cells. The platform was applied to human cardiomyocytes (AC16) under cyclic strain (5%, 10%, 15%, 20 and 25%), and we found that cyclic strain promoted cell growth induced the arrangement of cells on the membrane to gradually unify, and stabilized the cells at 15% amplitude, which was even more effective after 3 days of culture. The platform’s precise control and measurement of mechanical forces can be used to establish more accurate in vitro microenvironmental models for disease modeling and therapeutic research.

Aqueous zinc-ion batteries (AZIBs) have raised wide concern as a new generation energy storage device due to their high capacity, low cost, and environmental friendliness. It is a crucial step to develop the ideal cathode materials that match well with the Zn anode. In this work, we report polypyrrole-(PPy)-encapsulated MnO2 nanowires as cathode materials for AZIBs. The assembled Zn//MnO2@PPy batteries deliver a reversible capacity of 385.7 mAh g−1 at a current density of 0.1 A g−1. Also, they possess an energy density of 192 Wh kg−1 at a power density of 50 W kg−1. The cells show long-term cycling stability, with a retention rate of 96% after 1000 cycles. The outstanding electrochemical performance indicates their potential applications in large-scale energy storage.

Research on family businesses has focused on the differences between family and non-family firms regarding the top management team (TMT), while this study further explores the difference within family firms from different regional culture based on the perspective of socio-emotional wealth (SEW) and evolutionary psychology. Using a sample comprised of all 625 family firms listed on the Small & Medium Enterprise Board and Growth Enterprise Board in Shenzhen Stock Exchange, this study finds that in regions of strong clan culture, family members are more willing to be involved in a family business and accept lower economic rewards. Particularly, when financial risk is high, these relationships mentioned above become more significant. Based on the results, this study proves that regional culture can affect the characteristics of top management teams in family firms, explains the heterogeneity of family firms’ decision-making from a culture-based perspective and extends existing research on family business from the level of “family firm vs. non-family firm” to that of “family firms affected by different regional cultures”.

Abstract FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Multiple FLT3 inhibitors are in various stages of clinical evaluation. However, resistance to FLT3 inhibitors resulting from acquired point mutations in tyrosine kinase domain (TKD) have limited the sustained efficacy of treatments, and a “gatekeeper” mutation (F691L) is resistant to most available FLT3 inhibitors. Thus, new FLT3 inhibitors against both FLT3 internal tandem duplication (FLT3-ITD) and FLT3-TKD mutations (including F691L) are urgently sought. Herein, we identified KX2-391 as a dual FLT3 and tubulin inhibitor and investigated its efficacy and mechanisms in overcoming drug-resistant FLT3-ITD-TKD mutations in AML. KX2-391 exhibited potent growth inhibitory and apoptosis promoting effects on diverse AML cell lines harboring FLT3-ITD mutations and AC220-resistant mutations at the D835 and F691 residues in TKD and inhibited FLT3 phosphorylation and its downstream signaling targets. Orally administered KX2-391 significantly prolonged the survival of a murine leukemia model induced by FLT3-ITD-F691L. KX2-391 also significantly inhibited the growth of 4 primary AML cells expressing FLT3-ITD and 2 primary AML cells expressing FLT3-ITD-D835Y. Our preclinical data highlight KX2-391 as a promising FLT3 inhibitor for the treatment of AML patients harboring FLT3 mutations, especially refractory/relapsed patients with F691L and other FLT3-TKD mutations.

TMPRSS2 is a transmembrane serine protease and plays a pivotal role in coronavirus disease 2019 (COVID-19). However, the correlation of TMPRSS2 with prognosis and immune infiltration in tumors has not yet been explored. Here, we analyzed the expression of TMPRSS2 in Oncomine and TIMER databases, the correlation between TMPRSS2 and overall survival in the PrognoScan, Kaplan-Meier plotter, and GEPIA databases. The association between TMPRSS2 and immune infiltration levels was investigated in the TIMER database. In addition, the prognosis of TMPRSS2 related to immune cells in cancers was analyzed. Quantitative real-time PCR (qRT-PCR) confirmed that TMPRSS2 was upregulated in lung adenocarcinoma (LUAD) and downregulated in breast invasive carcinoma (BRCA). We demonstrated that high TMPRSS2 expression was associated with favorable prognosis in LUAD, but it was associated with poor prognosis in BRCA. Interestingly, we found that TMPRSS2 expression was significantly correlated with immune infiltration of B cells, CD4+ T cells, macrophages, and dendritic cells in LUAD, and it was positively correlated with the infiltrating levels of CD8+ T cells, CD4+ T cells, neutrophils, and dendric cells in BRCA. Consistent with the prognosis of TMPRSS2 in LUAD and BRCA, the high expression level of TMPRSS2 has a favorable prognosis in enriched immune cells such as B cells, macrophages, and CD4+ T cells in LUAD, and it has a poor prognosis in CD4+ T cells and CD8+ T cells in BRCA. In conclusion, our results indicate that the prognosis of TMPRSS2 in LUAD and BRCA is significantly correlated with immune cells infiltration. Our study comprehensively revealed the relationship between the prognosis of TMPRSS2 in pan-cancers and tumor immunity.

Materials with outstanding mechanical properties and excellent dielectric properties are increasingly favored in the microelectronics industry. The application of polyimide (PI) in the field of microelectronics is limited because of the fact that PI with excellent mechanical properties does not have special features in the dielectric properties. In this work, PI composite films with high dielectric properties and excellent mechanical properties are fabricated by in-situ reduction of fluorinated graphene (FG) in polyamide acid (PAA) composites. The dielectric permittivity of pure PI is 3.47 and the maximum energy storage density is 0.664 J/cm3 at 100 Hz, while the dielectric permittivity of the PI composite films reaches 235.74 under the same conditions, a 68-times increase compared to the pure PI, and the maximum energy storage density is 5.651, a 9-times increase compared to the pure PI films. This method not only solves the problem of the aggregation of the filler particles in the PI matrix and maintains the intrinsic excellent mechanical properties of the PI, but also significantly improves the dielectric properties of the PI.

Abstract IRF8 is a key regulator of innate immunity receptor signaling and plays diverse functions in the development of hematopoietic cells. The effects of IRF8 on hematopoietic stem cells (HSCs) are still unknown. Here, it is demonstrated that IRF8 deficiency results in a decreased number of long‐term HSCs (LT‐HSCs) in mice. However, the repopulation capacity of individual HSCs is significantly increased. Transcriptomic analysis shows that IFN‐γ and IFN‐α signaling is downregulated in IRF8‐deficient HSCs, while their response to proinflammatory cytokines is unchanged ex vivo. Further tests show that Irf8−/− HSCs can not respond to CpG, an agonist of Toll‐like receptor 9 (TLR9) in mice, while long‐term CpG stimulation increases wild‐type HSC abundance and decreases their bone marrow colony‐forming capacity. Mechanistically, as the primary producer of proinflammatory cytokines in response to CpG stimulation, dendritic cells has a blocked TLR9 signaling due to developmental defect in Irf8−/− mice. Macrophages remain functionally intact but severely reduce in Irf8−/− mice. In NK cells, IRF8 directly regulates the expression of Tlr9 and its deficiency leads to no increased IFNγ production upon CpG stimulation. These results indicate that IRF8 regulates HSCs, at least in part, through controlling TLR9 signaling in diverse innate immune cells.

A laser imaging technique has been proposed in this article for measuring vapor distribution of lower and high volatile components in a multicomponent fuel spray, based on the LAS technique. For a two-component fuel spray which contains n-octane (boiling point: 399 K) and n-tridecane (boiling point: 508 K), vapor distribution of the low boiling point (LBP) component, n-octane, has been determined by using p-xylene (boiling point: 411 K) as its substitute, which has the similar physical properties and absorbs the ultraviolet light but not the visible light, according to the requirements of the LAS technique. Likewise, vapor behavior of the higher boiling point (HBP) component, n-tridecane, has been obtained by using α-methylnaphthalene (boiling point: 517 K). It has been found that difference in vaporization rate between the LBP and HBP components is great over the spray plume at 473 K, this difference, however, reduces significantly as the ambient temperature increases to 573 K; The LBP component vaporizes mainly in the outer region, while the HBP mostly in the inner region of the spray. [ABSTRACT FROM AUTHOR]

The ultraviolet-visible laser absorption-scattering (LAS) technique was extended to simultaneous imaging of two-dimensional vapor/liquid mass distributions in a nonaxisymmetric evaporating diesel spray such as that injected into a two-dimensional model combustion chamber of direct-injection diesel engines. The main error for vapor measurement is incurred by the temperature dependence of molar absorption coefficients (TDMAC) of the test fuel. Thus, selecting a test fuel of negligible TDMAC can greatly increase the measurement accuracy. By means of this extended LAS technique, the overall mass, as well as the mass distribution of vapor and liquid phase per projection area perpendicular to the laser beam, was obtained, and then the behavior of split-injection diesel spray in a two-dimensional model combustion chamber in a high-temperature high-pressure constant-volume vessel was observed. Finally, the effects of injection mass ratios on the distributions of vapor and droplets and characteristics of fuel/air mixing were examined. [ABSTRACT FROM AUTHOR]