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Summary: Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity phosphatases (DUSPs), the activities of which are tightly regulated during cell differentiation. Using knockdown screening and single-cell transcriptional analysis, we demonstrate that DUSP4 is the phosphatase that specifically inactivates p38 kinase to promote megakaryocyte (Mk) differentiation. Mechanistically, PRMT1-mediated methylation of DUSP4 triggers its ubiquitinylation by an E3 ligase HUWE1. Interestingly, the mechanistic axis of the DUSP4 degradation and p38 activation is also associated with a transcriptional signature of immune activation in Mk cells. In the context of thrombocytopenia observed in myelodysplastic syndrome (MDS), we demonstrate that high levels of p38 MAPK and PRMT1 are associated with low platelet counts and adverse prognosis, while pharmacological inhibition of p38 MAPK or PRMT1 stimulates megakaryopoiesis. These findings provide mechanistic insights into the role of the PRMT1-DUSP4-p38 axis on Mk differentiation and present a strategy for treatment of thrombocytopenia associated with MDS.

Objective: To explore the relationship between the expressions of P21, P27 and proliferating cell nuclear antigen (PCNA) in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A (IgA) nephropathy. Methods: A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object. The expressions of P21, P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry. All patients were followed up for 24 months, and the prognosis were counted. The expressions of P21, P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis. Results: The expression rates of P21, P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were (38.69±6.83)%, (55.94±8.08)%, (33.47±5.72)%, respectively. The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%, and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group (P<0.05), while the expression rate of P27 positive cells was lower than that in good prognosis group (P<0.05). Logistic multiple regression analysis showed that elevated diastolic blood pressure, increased 24 h proteinuria, mesangial cell proliferation, segmental glomerulosclerosis, renal tubular atrophy/interstitial fibrosis, crescentic body, increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy (P<0.05). Conclusion: There are positive expressions of P21, P27 and PCNA in glomerular mesangial tissue of IgA nephropathy. The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis, while the expression rate of P27 protein positive cells is lower than those with good prognosis, which are risk factors for poor prognosis of patients with IgA nephropathy. [ABSTRACT FROM AUTHOR]

Hydrothermal humification technology for the preparation of artificial humic matters provides a new strategy, greatly promoting the natural maturation process. Iron, as a common metal, is widely used in the conversion of waste biomass; however, the influence of Fe3+ on hydrothermal humification remains unknown. In this study, FeCl3 is used to catalyze the hydrothermal humification of corn straw, and the influence of Fe3+ on the hydrothermal humification is explored by a series of characterization techniques. Results show that Fe3+ as the catalyst can promote the decomposition of corn straw, shorten the reaction time from 24 h to 6 h, and increase the yield from 6.77 % to 14.08 %. However, artificial humic acid (A‐HA) obtained from Fe3+‐catalysis hydrothermal humification contains more unstable carbon and low amount of aromatics, resulting in a significantly decreased stability of the artificial humic acid. These results provide theoretical guidance for regulating the structure and properties of artificial humic acid to meet various maintenance needs. [ABSTRACT FROM AUTHOR]

The study of quasi-periodic oscillations (QPOs) and power density spectra (PDSs) continuum properties can help shed light on the still elusive emission physics of magnetars and as a window into the interiors of neutron stars using asteroseismology. In this work, we employ a PDS method to search for the QPOs in the hundreds of X-ray bursts from SGR J1935+2154 observed by Insight - HXMT, GECAM , and Fermi/ GBM from 2014 July to 2022 January. Although no definitive QPO signal (significance >3 σ) is detected in individual bursts or the averaged periodogram of the bursts grouped by duration, we identify several bursts exhibiting features at ∼40 Hz, attributed to the the proximity intervals between adjacent pulses and consistent with that reported in the X-ray burst associated with FRB 200428. We investigate the PDS continuum properties and find that the distribution of the PDS slope in the simple power-law model peaks at ∼2.5, which is consistent with other magnetars but higher than 5/3 commonly seen in gamma-ray bursts. Besides, the distribution of the break frequency in the broken power-law model peaks at ∼60 Hz. Finally, we report that the power-law index of PDS has an anti-correlation and power-law dependence on the burst duration as well as the minimum variation time-scale. [ABSTRACT FROM AUTHOR]

Electroactive biomaterials can influence the microenvironment between cells and a material's surface by controlling surface electrical signals, thereby affecting cellular physiological activities. As the most commonly used ferroelectric polymer, Poly(vinylidene fluoride-trifluoroethylene) (PVTF) has attracted widespread attention due to its good stability, biocompatibility and mechanical properties. However, it has limitations such as non-degradability. In this study, PVTF nanoparticles (PVTF NPs), prepared using a phase separation method, were compounded with polylactide (PLA) to prepare PVTF NPs/PLA composite membrane (PN/PLA), which simultaneously achieved electroactivity and degradability. PVTF NPs containing ferroelectric β phase were evenly distributed on the PLA substrate, forming negative potential spots through corona polarization. The PLA substrate gradually degraded in a simulated body fluid environment. The negative surface potential provided by PVTF NPs in PN/PLA enhanced the adhesion, proliferation, and early-stage osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The electrical bioactivity and degradability could be joined together in this study, which is promising for tissue regeneration biomaterials, such as guided bone regeneration membrane. [ABSTRACT FROM AUTHOR]