The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural p...
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The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.
In recent years, the construction of subway projects has flourished, and the flow of personnel in underground structures such as subway stations has also increased. Once earthquakes occur, they will bring a series of ...
In recent years, the construction of subway projects has flourished, and the flow of personnel in underground structures such as subway stations has also increased. Once earthquakes occur, they will bring a series of unpredictable and malignant effects to the country. Therefore, it is necessary to strengthen the subway stations, etc. Research on earthquake resistance of underground structures. According to the research on the earthquake damage that has occurred, it is found that the underground structure damage such as the subway station is caused by the liquefaction caused by the earthquake. Based on the powerful functions of ABAQUS in solving nonlinear problems, this project establishes a two-dimensional liquefiable field-metro station finite element analysis model. The subway station form mainly adopts the commonly used two-story double-span island metro station structure. Based on the open secondary development port of ABAQUS embeds a sand constitutive subroutine that can describe the nonlinear characteristics of sand liquefaction dynamics, which provides a reference for a certain degree of reference for the difference of seismic response of metro stations in the future.
The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau...
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The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau phosphorylation, aggregation, and a translational stress response that includes stress granules and reduced protein synthesis. Proteomic analysis identifies HNRNPA2B1 as a principle target of oTau-c. The association of HNRNPA2B1 with endogenous oTau was verified in neurons, animal models, and human Alzheimer brain tissues. Mechanistic studies demonstrate that HNRNPA2B1 functions as a linker, connecting oTau with N6-methyladenosine (m6A) modified RNA transcripts. Knockdown of HNRNPA2B1 prevents oTau or oTau-c from associating with m6A or from reducing protein synthesis and reduces oTau-induced neurodegeneration. Levels of m6A and the m6A-oTau-HNRNPA2B1 complex are increased up to 5-fold in the brains of Alzheimer subjects and P301S tau mice. These results reveal a complex containing oTau,
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