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"Luo, Hong"
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System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy
The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis is an iron-mediated form of cell death caused by the accumulation of lipid peroxides. The intracellular imbalance between oxidant and antioxidant due to the abnormal expression of multiple redox active enzymes will promote the produce of reactive oxygen species (ROS). So far, a few pathways and regulators have been discovered to regulate ferroptosis. In particular, the cystine/glutamate antiporter (System X c − ), glutathione peroxidase 4 (GPX4) and glutathione (GSH) (System X c − /GSH/GPX4 axis) plays a key role in preventing lipid peroxidation-mediated ferroptosis, because of which could be inhibited by blocking System X c − /GSH/GPX4 axis. This review aims to present the current understanding of the mechanism of ferroptosis based on the System X c − /GSH/GPX4 axis in the treatment of drug-resistant solid tumors.
Journal Article
PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3β (GSK-3β), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.
Journal Article
Patent Publication and the Market for Ideas
In this paper, we study the effect of invention disclosure through patent publication on the market for ideas. We do so by analyzing the effects of the American Inventor’s Protection Act of 1999 (AIPA)—which required U.S. patent applications to be published 18 months after their filing date rather than at patent grant—on the timing of licensing deals in the biomedical industry. We find that post-AIPA U.S. patent applications are significantly more likely to be licensed before patent grant and shortly after 18-month publication. Licensing delays are reduced by about 10 months, on average, after AIPA’s enactment. These findings suggest a hitherto unexplored benefit of the patent system: by requiring inventions to be published through a credible, standardized, and centralized repository, it mitigates information costs for buyers and sellers, and thus facilitates transactions in the market for ideas.
The online appendix is available at
https://doi.org/10.1287/mnsc.2016.2622
.
This paper was accepted by Bruno Cassiman, business strategy
.
Journal Article
Hydrogen enhances strength and ductility of an equiatomic high-entropy alloy
Metals are key materials for modern manufacturing and infrastructures as well as transpot and energy solutions owing to their strength and formability. These properties can severely deteriorate when they contain hydrogen, leading to unpredictable failure, an effect called hydrogen embrittlement. Here we report that hydrogen in an equiatomic CoCrFeMnNi high-entropy alloy (HEA) leads not to catastrophic weakening, but instead increases both, its strength and ductility. While HEAs originally aimed at entropy-driven phase stabilization, hydrogen blending acts opposite as it reduces phase stability. This effect, quantified by the alloy’s stacking fault energy, enables nanotwinning which increases the material’s work-hardening. These results turn a bane into a boon: hydrogen does not generally act as a harmful impurity, but can be utilized for tuning beneficial hardening mechanisms. This opens new pathways for the design of strong, ductile, and hydrogen tolerant materials.
Journal Article
Triple-meron crystal in high-spin Kitaev magnets
Skyrmions hold great promise in future spintronics applications since they are robust against local deformations. The meron, due to its topological equivalence to a half skyrmion, has been widely found to appear in pairs. Motivated by recent progresses in high-spin Kitaev magnets, here we investigate numerically a classical Kitaev-Γ model with a single-ion anisotropy. An exotic spin texture consisting of three merons is discovered. Such a state features a peculiar property with an odd number of merons in one magnetic unit cell. Therefore, these merons cannot be dissociated from skyrmions as reported in the literature and their origin is briefly discussed. Moreover, we find that these three merons contribute a finite topological number and thus it can induce the topological Hall effect (THE). Experimentally this spin texture can be observed by the Lorentz transmission electron microscopy and the THE can be used to identify the finite topological number. Our work demonstrates that high-spin Kitaev magnets can host robust unconventional spin textures and thus they offer a versatile platform for exploring exotic spin textures as well as their applications in spintronics.
Journal Article
Metasurface interferometry toward quantum sensors
Optical metasurfaces open new avenues for the precise wavefront control of light for integrated quantum technology. Here, we demonstrate a hybrid integrated quantum photonic system that is capable of entangling and disentangling two-photon spin states at a dielectric metasurface. Via the interference of single-photon pairs at a nanostructured dielectric metasurface, a path-entangled two-photon NOON state with circular polarization that exhibits a quantum HOM interference visibility of 86 ± 4% is generated. Furthermore, we demonstrate nonclassicality andphase sensitivity in a metasurface-based interferometer with a fringe visibility of 86.8 ± 1.1% in the coincidence counts. This high visibility proves the metasurface-induced path entanglement inside the interferometer. Our findings provide a promising way to develop hybrid-integrated quantum technology operating in the high-dimensional mode space in various applications, such as imaging, sensing, and computing.
Journal Article
Shubnikov–de Haas effect in the Falicov–Kimball model: strong correlation meets quantum oscillation
We present a comprehensive investigation of quantum oscillations (QOs) in the strongly-correlated Falicov-Kimball model (FKM). The FKM is a particularly suitable platform for probing the non-Fermi liquid (NFL) state devoid of quasiparticles, affording exact Monte Carlo simulation across all parameter spaces. In the high-correlation regime, we report the presence of prominent QOs in magnetoresistance and electron density at low temperatures within the phase separation state. The frequency behavior of these oscillations uncovers a transition in the Fermi surface as electron density diminishes, switching from hole-like to electron-like. Both types of Fermi surfaces are found to conform to the Onsager relation, establishing a connection between QOs frequency and Fermi surface area. Upon exploring the temperature dependence of QOs amplitude, we discern a strong alignment with the Lifshitz-Kosevich (LK) theory, provided the effective mass is suitably renormalized. Notwithstanding, the substantial enhancement of the overall effective mass results in a notable suppression of the QOs amplitude within the examined temperature scope, a finding inconsistent with Fermi liquid predictions. For the most part, the effective mass diminishes as the temperature increases, but an unusual increase is observed at the proximity of the second-order phase transition instigated by thermal effects. As the transition ensues, the regular QOs disappear, replaced by irregular ones in the NFL state under a high magnetic field. We also uncover significant QOs in the insulating charge density wave state under weak interactions ( 0 < U < 1 ), a phenomenon we elucidate through analytical calculations. Our findings shed light on the critical role of quasiparticles in the manifestation of QOs, enabling further understanding of their function in this context.
Journal Article
Characterization of defensive cadinenes and a novel sesquiterpene synthase responsible for their biosynthesis from the invasive Eupatorium adenophorum
• Eupatorium adenophorum is a malignant invasive plant possessing extraordinary defense potency, but its chemical weaponry and formation mechanism have not yet been extensively investigated.
• We identified six cadinene sesquiterpenes, including two volatiles (amorpha-4,7(11)-diene and (–)-amorph-4-en-7-ol) and four nonvolatiles (9-oxo-10,11-dehydroageraphorone, muurol-4-en-3,8-dione, 9-oxo-ageraphorone and 9β-hydroxy-ageraphorone), as the major constitutive and inducible chemicals of E. adenophorum. All cadinenes showed potent antifeedant activity against a generalist insect Spodoptera exigua, indicating that they have significant defensive roles.
• We cloned and functionally characterized a sesquiterpene synthase from E. adenophorum (EaTPS1), catalyzing the conversion of farnesyl diphosphate to amorpha-4,7(11)-diene and (–)-amorph-4-en-7-ol, which were purified from engineered Escherichia coli and identified by extensive nuclear magnetic resonance (NMR) spectroscopy. EaTPS1 was highly expressed in the aboveground organs, which was congruent with the dominant distribution of cadinenes, suggesting that EaTPS1 is likely involved in cadinene biosynthesis. Mechanical wounding and methyl jasmonate negatively regulated EaTPS1 expression but caused the release of amorpha-4,7(11)-diene and (–)-amorph-4-en-7-ol. Nicotiana benthamiana transiently expressing EaTPS1 also produced amorpha-4,7(11)-diene and (–)-amorph-4-en-7-ol, and showed enhanced defense function.
• The findings presented here uncover the role and formation of the chemical defense mechanism of E. adenophorum – which probably contributes to the invasive success of this plant – and provide a tool for manipulating the biosynthesis of biologically active cadinene natural products.
Journal Article
Even Nāgārjuna Accepts: Remapping the Middle Way in the Light of Ratnākaraśānti’s Interpretation of Mūlamadhyamakakārikā Verse 24.18
Starting with Ratnākaraśānti’s (c. 970–1045 CE) interpretation of Nāgārjuna’s (2nd/3rd CE) Mūlamadhyamakakārikā (MMK) verse 24.18 (24.18), the heart of the Middle Way doctrine, we shall revisit the different explanations of this verse transmitted in classical Chinese, Sanskrit, and classical Tibetan and highlight two hermeneutical trends under which all interpretations of 24.18 in the commentarial literature of the MMK may arguably be subsumed. On the one hand, the treble-schema school, which is best exemplified in Kumārajīva’s (鳩摩羅什, 343–413 CE) Chinese translation of 24.18, the earliest textual witness to 24.18, takes 24.18 as a quotation of the Buddha’s own words, as Jízàng (吉藏, 549–623 CE) specified, from the Fóshuō huāshǒu jīng (佛說華手經, T16 657, HSJ), an underappreciated tathāgatagarbhic scripture. On the other hand, the even-schema school, the most renowned advocate of which is Candrakīrti (600–650 CE), attributes emphatically 24.18 to Nāgārjuna. The exegetical ramification on the origin of 24.18 may have been the hidden drive of the doctrinal disputes and sectarian dislikes in the history of Madhyamaka, and its significance for Buddhist Studies merits and awaits further explorations.
Journal Article