Multiferroic Magnon Spin-Torque Based Reconfigurable Logic-In-Memory

Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we present a magnon logic-in-memory device in a spin-source/multiferroic/ferromagnet structure, where multiferroic magnon modes can be electrically excited and controlled. In this device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. We show that the ferroelectric polarization can electrically modulate the magnon spin-torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. By manipulating the two coupled non-volatile state variables (ferroelectric polarization and magnetization), we further demonstrate reconfigurable logic-in-memory operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing

Triptolide Inhibits the Proliferation of Prostate Cancer Cells and Down-Regulates SUMO-Specific Protease 1 Expression

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs

Acoustic-driven magnetic skyrmion motion

Abstract Magnetic skyrmions have great potential for developing novel spintronic devices. The electrical manipulation of skyrmions has mainly relied on current-induced spin-orbit torques. Recently, it was suggested that the skyrmions could be more efficiently manipulated by surface acoustic waves (SAWs), an elastic wave that can couple with magnetic moment via the magnetoelastic effect. Here, by designing on-chip piezoelectric transducers that produce propagating SAW pulses, we experimentally demonstrate the directional motion of Néel-type skyrmions in Ta/CoFeB/MgO/Ta multilayers. We find that the shear horizontal wave effectively drives the motion of skyrmions, whereas the elastic wave with longitudinal and shear vertical displacements (Rayleigh wave) cannot produce the motion of skyrmions. A longitudinal motion along the SAW propagation direction and a transverse motion due to topological charge are simultaneously observed and further confirmed by our micromagnetic simulations. This work demonstrates that acoustic waves could be another promising approach for manipulating skyrmions, which could offer new opportunities for ultra-low power skyrmionics

IC₅₀ values.

<p>IC₅₀ values.</p

Triptolide and Celastrol induce apoptosis in PCa cells <i>in vitro</i>.

<p>(A) and (B) Fluorescence microscopy observation of Triptolide- and Celastrol- induced apoptosis in LNCaP (A) and PC-3 (B) cells. After treatment with 1 µM Celastrol or Triptolide for 24 h, LNCaP and PC-3 cells were incubated with AV-FITC (green) and PI (red). Representative bright field and fluorescent images are shown. (C) Flow cytometric detection of apoptosis in LNCaP and PC-3 cells treated as above. Percentage of intact cells (AV−/PI−), early apoptotic cells (AV+/PI−), late apoptotic/necrotic cells (AV+/PI+) and necrotic cells (AV−/PI+) are presented. (D) and (E) Western blot analysis of caspase-3 protein in Triptolide- or Celastrol-treated LNCaP (D) and PC-3 (E) cells. Cells were treated with indicated concentrations of Triptolide or Celastrol for 24 h and subjected to analysis. Uncleaved caspase-3 and cleaved products are indicated. α-tubulin was used as a loading control. (F) and (G) Western blot analysis of PARP and caspase-3 proteins in Triptolide- or Celastrol-treated LNCaP (F) and PC-3 (G) cells. Cells were treated with 1 µM Triptolide or Celastrol for desired times. Uncleaved PARP and caspase-3 and their cleaved products are indicated. α-tubulin was used as a loading control.</p

Triptolide down-regulated c-Jun expression in PCa cells.

<p>(A) Triptolide decreased c-Jun mRNA level in LNCaP and PC-3 cells in a dose-dependent manner. Cells were treated with indicated dose of Triptolide for 24 h before RNA extraction and qRT-PCR using the specific primers for c-Jun and β-actin. (B) Triptolide decreased c-Jun mRNA level in LNCaP and PC-3 cells in a time-dependent manner. Cells were treated with 0.1 µM Triptolide for indicated time before RNA extraction and qRT-PCR. (C) and (D) Triptolide decreased c-Jun protein level in LNCaP (C) and PC-3 (D) cells in a dose-dependent manner. Cells were treated with indicated dose of Triptolide or Celastrol for 24 h before Western blot analysis. α-tubulin was used as a loading control. (E) Triptolide decreased c-Jun protein level in LNCaP cells in a time-dependent manner. LNCaP cells were treated with 0.1 µM Triptolide for indicated time before Western blot analysis. α-tubulin was used as a loading control. (F) Triptolide inhibited c-Jun target genes expression in LNCaP cells. LNCaP cells were treated with indicated concentration of Triptolide for 24 h before qRT-PCR analysis of c-Jun target genes using respective specific primers.</p

Triptolide down-regulated SENP1 expression in PCa cells.

<p>(A) Triptolide decreased SENP1 mRNA level in both LNCaP and PC-3 cells in a dose-dependent manner. Cells were treated with indicated doses of Triptolide or Celastrol for 24 h before analysis. qRT-PCR were performed using the specific primers for SENP1 and β-actin (used as an internal control). (B) Triptolide decreased SENP1 mRNA level in both LNCaP and PC-3 cells in a time-dependent manner. Cells were treated with 0.1 µM Triptolide or Celastrol for indicated times, SENP1 and β-actin mRNA levels were determined by qRT-PCR. (C) Effect of Triptolide on SENP1 mRNA level in PCa cells. IC₅₀ was shown as calculated by Prism 5.04. (D) and (E) Triptolide decreased SENP1 protein level in LNCaP (D) and PC-3 (E) in a dose-dependent manner. Cells were treated with indicated doses of Triptolide or Celastrol for 24 h before Western blot analysis. α-tubulin was used as a loading control. (F) Triptolide decreased SENP1 protein level in PCa cells in a time-dependent manner. PC-3 cells were treated with 1 µM Triptolide for indicated time before Western blot analysis. β-actin was used as a loading control. (G) Triptolide enhanced cellular SUMOylation in PC-3 cells. PC-3 cells were treated with 1 µM Triptolide or Celastrol for 24 h before Western blot analysis using SUMO-1 antibody. NEM was used as a positive control for a SUMO protease inhibitor.</p

Hypothetic mechanisms of anti-PCa effects of Triptolide.

<p>Triptolide suppresses SENP1, AR and c-Jun expression, induces restoration of SUMOylation/deSUMOyaltion balance, inhibitions of the AR and c-Jun mediated transcription, which may all contribute to the anti-PCa effect of Triptolide. Other genes or proteins may involve in mechanism of Triptolide effect (see Discussion for detail).</p

Down-regulation or over-expression of SENP1, c-Jun or AR inhibited Triptolide anti-PCa efficacy.

<p>(A) and (B) Down-regulation of SENP1, c-Jun or AR expression increased cell viability upon Triptolide treatment. LNCaP and PC-3 cells were transfected with specific siRNA against SENP1, c-Jun and AR. 24 h after transfection, the transfected cells were treated with 100 nM triptolide or vehicle control for 48 h, then the viable cell number was counted in each treatment. (A) Effect of knockdown SENP1, c-Jun and AR on Triptolide efficacy in LNCaP cell. Left chart shows the viable cell number in each treatment. Right chart shows the viability ratio. (B) Effect of knockdown SENP1 and c-Jun on Triptolide efficacy in PC-3 cell. * indicates P<0.05 (compared to control). (C) Down-regulation of SENP1, c-Jun and AR protein levels by siRNA in (A) and (B). (D) and (E) Over-expression of SENP1, c-Jun and AR rescued cell viability upon Triptolide treatment. PCa cells were transfected or cotransfected with 800 ng SENP1, c-Jun and AR expression plasmids DNA as indicated. EGFP protein was used as a negative control and the Triptolide binding protein XPB was used as a positive control. Empty vector was used as blank control and to keep the total amount of plasmids DNA equal in each well. 48 h after transfection, cells were treated with Triptolide for another 48 h and viable cell number were counted. (D) Effect of ectopic expression or coexpression of SENP1, c-Jun and AR on Triptolide efficacy in LNCaP cells. (E) Effect of ectopic expression or coexpression of SENP1 and c-Jun on Triptolide efficacy in PC-3 cells. * indicates P<0.05 (compared to control). (F) Ectopic expression or coexpression of SENP1, c-Jun and AR in PCa cells evaluated by Western blot using anti-Flag and anti-HA antibodies.</p