Mechanism underlying synergic activation of Tyrosinase promoter by MITF and IRF4

Background: The transcription factor interferon regulatory factor 4 (IRF4) was identified to be involved in human pigmentation by genome-wide association studies (GWASs). The rs12203592-[T/C], which is located in intron 4 of IRF4, shows the strongest link to these pigmentation phenotypes including freckling, sun sensitivity, eye and hair color. Previous studies indicated a functional cooperation of IRF4 with Microphthalmia-associated transcription factor (MITF), a causing gene of Waardenburg syndrome (WS), to synergistically trans-activate Tyrosinase (TYR). However, the underlying mechanism is still unknown. Methods: To investigate the importance of DNA binding in the synergic effect of IRF4. Reporter plasmids with mutant TYR promoters was generated to locate the IRF4 DNA binding sites in the Tyrosinase minimal promoter. By building MITF and IRF4 truncated mutations plasmids, the necessary regions of the synergy functions of these two proteins were also located. Results: The cooperative effect between MITF and IRF4 was specific for TYR promoter. The DNA-binding of IRF4 was critical for the synergic function. IRF4 DNA binding sites in TYR promoter were identified. The Trans-activation domains in IRF4 (aa134-207, aa300-420) were both important for the synergic function, whereas the auto-mask domain (aa207-300) appeared to mask the synergic effect. Mutational analysis in MITF indicated that both DNA-binding and transcriptional activation domains were both required for this synergic effect. Conclusions: Here we showed that IRF4 potently synergized with MITF to activate the TYR promoter, which was dependent on DNA binding of IRF4. The synergic domains in both IRF4 and MITF were identified by mutational analysis. This identification of IRF4 as a partner for MITF in regulation of TYR may provide an important molecular function for IRF4 in the genesis of melanocytes and the pathogenic mechanism in WS

Influence of Metal Fiber Content and Arrangement on Shielding Effectiveness for Blended Electromagnetic Shielding Fabric

More metal fiber content of blended electromagnetic shielding (EMS) fabric results in higher shielding effectiveness (SE) of the fabric. However, there is little information about the influence of the metal fiber content on the SE considering the fabric structure. This study constructs an index of metal fiber content per unit area (MFCPUA), and discusses the influence of the metal fiber content on the SE of the EMS fabric when fabric parameters are changed. Computations for the MFCPUA and the thickness and porosity of the metal fiber arrangement are given, and then experiments are designed to test the SE of different EMS fabric samples. According to the experimental results, the influence of the MFCPUA on the SE is analyzed and influence mechanism is discussed when the fabric weaves, emission frequencies and weft and warp densities are changed. Results show that the MFCPUA and the SE are positive increase relation; the frequency and the SE are the negative increase relation when the metal fiber content is unchanged; the influence of the fabric weave type on the SE depends on the length of the yarn floats; the SE values of fabric with same weave are same when the MFCPUA is same regardless of the fabric density.DOI: http://dx.doi.org/10.5755/j01.ms.21.2.6529</p

Elemental data for Gonghai Lake sediments show significant effects of human activities on weathering processes after 1550 CE

The international Anthropocene Working Group has recognized the mid-20th centrury (ca. 1950 CE) as the onset of the Anthropocene, but human activities in China altered the land cover and influenced weathering processes much earlier. Changes in the elemental composition of sediment since 1000 CE from Gonghai Lake were studied, using X-ray Fluorescence element scanning (average time-resolution 3 years), to investigate the human impacts on weathering over time. We found that aluminum (Al) and calcium (Ca) containing minerals vary in the resistance to chemical weathering, and the concentrations of Al and Ca provide insights into the intensities of mechanical and chemical weathering respectively. The correlations between Al and Ca concentrations in these two periods, 1000–1550 CE and 1550–1950 CE changed from negative to positive, owing to that agricultural activities evidently enhanced both mechanical and chemical weathering during the latter stage. In addition, the Al and Ca concentrations recorded a border reclamation project in the 16th century and two catastrophic population decreases from 1630s to 1640s and 1850s–1870s. After 1950 CE, the concentrations of Al and Ca became uncorrelated, because weathering processes around Gonghai Lake were impacted by the enhanced anthropogenic perturbations in the Anthropocene

Three-Dimensional Stochastic Distribution Characteristics of Void Fraction in Longwall Mining-Disturbed Overburden of Inclined Coal Seam

AbstractFractures in the overburden induced by mining disturbances provide a channel for fluid flow between the surface and the underground. Mining-induced strata movement and fracture distribution are influenced by the gravity and dip angles of rock seams. In this paper, a new three-dimensional theoretical distribution model for void fraction in each partition of overlying rock strata disturbed by inclined coal seam mining was constructed. Based on the theoretical determination model, the three-dimensional random distribution characteristics for void fraction were obtained by combining the random distribution law of void fraction obtained by similar physical simulation experiments and image processing techniques. Theoretical deterministic models, stochastic theoretical models, and similar physical simulations all show that void fraction distribution in the tendency direction of the coal seam shows a bimodal asymmetric distribution with high and low peaks and a symmetric distribution in the strike direction. The void fraction of the overburden in the central part of the mining area is smaller than that of the surrounding area. The results of the theoretically determined model and stochastic model of the void fraction for the strata with different mining lengths and different coal seam inclinations were compared with the results of similar simulation experiments, respectively. The results are in agreement, further verifying the practicality of the model

Intelligent medication manager: developing and implementing a mobile application based on WeChat

Background: Time and space constraints have often hindered the provision of optimal pharmaceutical care, limiting medication therapy management. Social media tools have gained significant popularity in the field of pharmaceutical care. This study aimed to develop a WeChat-based intelligent medication manager platform that facilitates online pharmaceutical care and encourages self-management.Methods: We developed a WeChat-based Internet pharmacy service platform called Xiang Medicine Guidance (XMG). Through the analysis of surveys and user access data, we evaluated the demand and utilization of the XMG platform and assessed patients’ satisfaction with its services. Patients’ adherence before and after the XMG platform intervention was also investigated.Results: The XMG platform was launched in November 2022, offering medication guidance, reminders, and consultation services through the WeChat mini-program. By the end of April 2023, the platform had attracted 141.2 thousand users, accumulating 571.0 thousand visits. Moreover, 1,183 clients sought online medication consultations during this period. Six months after the launch of XMG, an impressive 91.02% of users expressed their satisfaction with the platform. The medication reminders and consultations provided by XMG significantly contributed to medication adherence, with 56.02% of users categorized as having good adherence, better than the previous 47.26%.Conclusion: Through its services and features, XMG empowers patients to better manage their medications, seek professional advice, and adhere to their prescribed treatment plans. XMG has the potential to positively impact public health on a broader scale

The Sensor Proteins BcSho1 and BcSln1 Are Involved in, Though Not Essential to, Vegetative Differentiation, Pathogenicity and Osmotic Stress Tolerance in Botrytis cinerea

High-osmolarity glycerol (HOG) signaling pathway belongs to mitogen-activated protein kinase (MAPK) cascades that regulate responses of organism to diverse extracellular stimuli. The membrane spanning proteins Sho1 and Sln1 serve as biosensors of HOG pathway in Saccharomyces cerevisiae. In this study, we investigated the biological functions of BcSHO1 and BcSLN1 in the gray mold fungus Botrytis cinerea. Target gene deletion demonstrated that both BcSHO1 and BcSLN1 are important for mycelial growth, conidiation and sclerotial formation. The BcSHO1 and BcSLN1 double deletion mutant ΔBcSln1-Sho1 produced much more, but smaller sclerotia than ΔBcSho1 and the wild-type (WT) strain, while ΔBcSln1 failed to develop sclerotia on all tested media, instead, formed a large number of conidia. Infection tests revealed that the virulence of ΔBcSln1-Sho1 decreased significantly, however, ΔBcSho1 or ΔBcSln1 showed no difference with the WT strain. In addition, ΔBcSln1-Sho1 exhibited resistance to osmotic stress by negatively regulating the phosphorylation of BcSak1 (yeast Hog1). All the phenotypic defects of mutants were recovered by target gene complementation. These results suggest that BcSHO1 and BcSLN1 share some functional redundancy in the regulation of fungal development, pathogenesis and osmotic stress response in B. cinerea