Unconventional Mechanism Research Articles

Environmentally Induced Photon Blockade via Two-Photon Absorption

We propose that photon blockade can be enabled by a two-photon absorption environment. The validity of this conclusion is confirmed by studying the blockade in a driven single-mode cavity. The feature of this environmentally induced photon blockade is that the nonlinear interaction in the system is not needed, which is entirely different from the conventional and the unconventional blockade mechanisms. We clearly give the physics behind this blockade mechanism. And the advantages of this environmentally induced photon blockade are discovered by comparing it with the conventional mechanism in a weakly driven region. In addition, we show that the proposal can be generalized straightforwardly to realize environmentally induced photon blockade in two coupled single-mode cavities.

Reversible Drug Resistance Mechanisms in Non-small Cell Lung Cancer

Although molecular targeted drugs are significantly effective in many types of cancer treatment, almost all patients suffer from drug resistance. For instance, non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation invariably develop resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and melanoma patients with BRAF mutation develop resistance to BRAF inhibitors. Mechanistically, genetic and irreversible resistance mechanisms have been studied for more than a decade, while non-mutational and reversible resistance mechanisms are yet to be clearly understood. Since drug tolerant persisters (DTPs), which emerge at the beginning of the drug treatment, have been reported in 2010, several non-mutational tolerance mechanisms have been reported by various researchers. Furthermore, with the advancement in single cell sequencing technology, increasing attention has been drawn towards the investigation of the heterogeneous characteristics of drug tolerant cell populations. Here, we describe the recent advances in non-mutational drug tolerant mechanisms toward the molecular targeted drugs. In our study, we tried to elucidate the unconventional resistance mechanisms by utilizing newly approved EGFR-TKI, dacomitinib. Our established drug resistant cells did not gain new mutation in EGFR even after long time exposure to the drug. In addition, the drug resistance vanished when resistant cells were implanted in mice, which indicates that mechanisms conferring drug sensitivity might be host-dependent. Thus, our study may provide a new insight into non-mutational drug tolerant mechanisms.

O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation.

In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms.

Multiferroic nitride perovskites with giant polarizations and large magnetic moments

Multiferroics with coupling between ferroelectricity and magnetism have been pursued for decades. However, their magnetoelectric performances remain limited due to the common trade-off between ferroelectricity and magnetism. Here, a family of nitride perovskites is proposed as multiferroics with prominent physical properties and nontrivial mechanisms. Taking GdWN$_3$ as a prototype, our first-principles calculations found that its perovskite phases own large polarizations (e.g. $111.3$ $\mu$C/cm$^2$ for the $R3c$ phase) and a magnetic moment $7$ $\mu_{\rm B}$/Gd$^{3+}$. More interestingly, its ferroelectric origin is multiple, with significant contributions from both Gd$^{3+}$ and W$^{6+}$ ions, different from its sister member LaWN$_3$ in which the ferroelectricity almost arises from W$^{6+}$ ions only. With decreasing size of rare earth ions, the A site ions would contribute more and more to the ferroelectric instability. Considering that small rare earth ions can be primary origins of both proper ferroelectricity and magnetism in nitride perovskites, our work provides a route to pursuit more multiferroics with unconventional mechanisms and optimal performances.

Review on Developments and Progress in Nickelate‐Based Heterostructure Composites and Superconducting Thin Films

AbstractIn the past decade, the rapid development of modern heterointerface growth and characterization techniques has stimulated great effort to research and design the extraordinary physical properties of transition metal heterostructure composite materials. Here, new physics originates from the rearrangement of orbital, charge, spin, and lattice and the resulting rebalancing of their mutual interactions. In this paper, recent experimental and theoretical progress in the design, preparation, characterization, and physical property measurement of LaNiO3‐based heterostructure composites and the infinite‐layer Ni1 + nickelate superconducting thin films on (001) SrTiO3 substrate is reviewed, mainly by the methods of various X‐ray spectroscopy measurements, scanning transmission electron microscopy, and magneto‐transport measurements. In these materials, the electronic structure and orbital occupation around the Fermi level are modified, enabling nickelate‐based composite materials to exhibit new states of matter and physical phenomena, which are absent in the bulk constituents. Their confined structures, superconductivity, orbital polarization, charge transfer, electronic structures, magnetic properties, and X‐ray spectroscopic analysis, are therefore highlighted, aiming at understanding unconventional superconducting mechanisms and designing new high‐Tc superconducting low‐dimensional materials for device applications.

Multistimuli-responsive microrobots: A comprehensive review.

Untethered robots of the size of a few microns have attracted increasing attention for the potential to transform many aspects of manufacturing, medicine, health care, and bioengineering. Previously impenetrable environments have become available for high-resolution in situ and in vivo manipulations as the size of the untethered robots goes down to the microscale. Nevertheless, the independent navigation of several robots at the microscale is challenging as they cannot have onboard transducers, batteries, and control like other multi-agent systems, due to the size limitations. Therefore, various unconventional propulsion mechanisms have been explored to power motion at the nanoscale. Moreover, a variety of combinations of actuation methods has also been extensively studied to tackle different issues. In this survey, we present a thorough review of the recent developments of various dedicated ways to actuate and control multistimuli-enabled microrobots. We have also discussed existing challenges and evolving concepts associated with each technique.

Solute clustering governed elastic properties in aluminum

Here, we report an extensive screening of homoatomic solute-solute binding energies and calculate the resulting elastic moduli in aluminum using density functional theory. Following a full-configuration strategy, a robust solute clustering map made up of 65 elements is established. Deriving from elemental and DFT-calculated properties, a total of 20 atomistic descriptors are used to evaluate the contributions of cluster bindings. A volume-effect dominated solute atomic binding mechanism is proposed. It suggests that not only the central zone but also the outer Al shell responds to solute bindings. The impact of stable solute clusters on the elastic properties of Al alloys is calculated. An unconventional enhancement mechanism of Young's modulus in these Al-based alloys is proposed. Based on the interatomic interaction forces derived elastic response theory, modified ‘atomic distance-electron density-Young's modulus' models applying to different element groups are proposed. Our work is expected to provide insight into the design of high strength, and high stiffness Al alloys.

Antigen-presenting Tcells provide critical B7 co-stimulation for thymic iNKT cell development via CD28-dependent trogocytosis.

Invariant natural killer T (iNKT) cell development in the thymus depends on Tcell receptor recognition of CD1dligand on CD4/CD8 double-positive thymocytes. We previously reported that B7-CD28 co-stimulation is required for thymic iNKT cell development, but the cellular and molecular mechanisms underlying this co-stimulatory requirement are not understood. Here we report that CD28 expression on CD1d-expressing antigen-presenting Tcells is required for thymic iNKT cell development. Mechanistically, antigen-presenting T cells provide co-stimulation through an unconventional mechanism, acquiring B7molecules via CD28-dependent trogocytosis from B7-expressing thymic epithelial cells, dendritic cells,and B cells and providing critical B7 co-stimulation to developing iNKT cells. Thus, the present study demonstrates a mechanism of B7 co-stimulation in thymic Tcell development by antigen-presenting Tcells.

IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport.

Initially discovered as the smallest component of the intraflagellar transport (IFT) system, the IFT20 protein has been found to be implicated in several unconventional mechanisms beyond its essential role in the assembly and maintenance of the primary cilium. IFT20 is now considered a key player not only in ciliogenesis but also in vesicular trafficking of membrane receptors and signaling proteins. Moreover, its ability to associate with a wide array of interacting partners in a cell-type specific manner has expanded the function of IFT20 to the regulation of intracellular degradative and secretory pathways. In this review, we will present an overview of the multifaceted role of IFT20 in both ciliated and non-ciliated cells.

Integrated stress response is involved in the 24(S)-hydroxycholesterol-induced unconventional cell death mechanism

Perturbation of proteostasis triggers the adaptive responses that contribute to the homeostatic pro-survival response, whereas disruption of proteostasis can ultimately lead to cell death. Brain-specific oxysterol—i.e., 24(S)-hydroxycholesterol (24S-OHC)—has been shown to cause cytotoxicity when esterified by acyl-CoA:cholesterol acyltransferase 1 (ACAT1) in the endoplasmic reticulum (ER). Here, we show that the accumulation of 24S-OHC esters caused phosphorylation of eukaryotic translation initiator factor 2α (eIF2α), dissociation of polysomes, and formation of stress granules (SG), resulting in robust downregulation of global protein de novo synthesis in human neuroblastoma SH-SY5Y cells. We also found that integrated stress response (ISR) activation through PERK and GCN2 activation induced by 24S-OHC treatment caused eIF2α phosphorylation. 24S-OHC-inducible SG formation and cell death were suppressed by inhibition of ISR. These results show that ACAT1-mediated 24S-OHC esterification induced ISR and formation of SG, which play crucial roles in 24S-OHC-inducible protein synthesis inhibition and unconventional cell death.

Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism.

The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defenses against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identifies etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step 2 activators. High concentrations of these metabolites fully and rapidly activate pyrin, in a human specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) and familial Mediterranean fever (FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, display increased responses to these metabolites. This study identifies an unconventional pyrin activation mechanism, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and explains the "steroid fever" described in the late 1950s upon steroid injection in humans.

Принципы построения геометрических моделей нанокластеров по тетраэдрической линии

In connection with the development of new methods of nanotechnology, the article discusses the features of the morphology of nanoobjects that determine the relevance of the modernization of the training of undergraduates in the study of the disciplines «Nanomaterial Science», «Nanotechnology», «Descriptive geometry, engineering and computer graphics» and «Computer modeling».
 Recently, the concept of «cluster» has become relevant due to the trend in the development of nanomaterials. Such nanomaterials obtained using unconventional growth mechanisms (including oriented attachment) are extremely interesting in the field of electronics, photonics and are of great interest for catalysis.
 The article considers homoatomic clusters constructed from identical structural units. The desire to minimize energy is expressed in the tendency to the densest arrangement of structural units in the cluster. This allows us to assert that cluster structures with the maximum number of connections per structural unit will be the most stable; that clusters tend to a quasi-spherical shape (i.e., cluster sizes along three Cartesian axes should be close if possible, while dense structures are formed, the surface of which is minimal, and the number of connections is maximum); that clusters with higher symmetry are preferable (identical structural units composing the cluster framework should strive to stay in an indistinguishable state and position from each other).
 The work applies the knowledge and skills laid down by students in the course of engineering and computer graphics to the study of the patterns of processes in the nanowire on the example of the principles of building nanoclusters along a tetrahedral line using three-dimensional modeling in the Autodesk 3ds Max environment. Visualization and visual representation of geometric images of nanoclusters will allow students to avoid a primitive geometric representation of nanoobjects and will serve as motivation to study other natural science subjects.
 The content of the article is intended for specialists working in the fields of nanotechnology, solid-state electronics, micro- and nanoelectronics, micro- and nanosystem technology, thin-film sensors.

A Unique NiOOH@FeOOH Heteroarchitecture for Enhanced Oxygen Evolution in Saline Water.

The development of highly efficient non-precious metal electrocatalysts for the oxygen evolution reaction (OER) in low-grade or saline water is currently of great importance for the large-scale production of hydrogen. In this study, by using an electrochemical activation pretreatment, metal oxy(hydroxide) nanosheet structures derived from self-supported nickel-iron phosphide and nitride nanoarrays grown on Ni foam are successfully fabricated for OER catalysis in saline water. It is demonstrated that the different NiOOH and NiOOH@FeOOH (NiOOH grown on FeOOH) structures are generated from nickel-iron nitride and phosphide, respectively, after electrochemical activation. In particular, the NiOOH@FeOOH heteroarchitecture shows outstanding electrocatalytic performance with an ultralow overpotential of 292mV to drive the current density of 500mAcm-2 . An unconventional dual-sites mechanism (UDSM) is proposed to address the OER process on NiOOH@FeOOH and show that the FeOOH underlayer plays a critical role regarding the enhanced OER activity of NiOOH. The new possible UDSM involving two reaction sites presents a different understanding of the OER process on multi-OH layer complexes, which is expected to guide the design of heteroarchitecture electrocatalysts.

Record high Tc element superconductivity achieved in titanium

It is challenging to search for high Tc superconductivity (SC) in transition metal elements wherein d electrons are usually not favored by conventional BCS theory. Here we report experimental discovery of surprising SC up to 310 GPa with Tc above 20 K in wide pressure range from 108 GPa to 240 GPa in titanium. The maximum Tconset above 26.2 K and zero resistance Tczero of 21 K are record high values hitherto achieved among element superconductors. The Hc2(0) is estimated to be ∼32 Tesla with coherence length 32 Å. The results show strong s-d transfer and d band dominance, indicating correlation driven contributions to high Tc SC in dense titanium. This finding is in sharp contrast to the theoretical predications based on pristine electron-phonon coupling scenario. The study opens a fresh promising avenue for rational design and discovery of high Tc superconductors among simple materials via pressure tuned unconventional mechanism.

Unveiling unconventional ferroelectric switching in multiferroic Ga0.6 Fe1.4O3 thin films through multiscale electron microscopy investigations

Understanding the polarization switching mechanisms at play in ferroelectric materials is crucial for their exploitation in electronic devices. The conventional centrosymmetric reference structure-based mechanism which accounts for ferroelectricity in most of the usual displacive ferroelectric materials is too energy-demanding for some newly diagnosed ferroelectric materials such as the Ga2-xFexO3 (0.8 ≤ x ≤ 1.4) compounds. Some alternative theoretical propositions have been made and need experimental confirmation. A dual-scale electron microscopy study is performed on thin films of the Ga0.6Fe1.4O3 multiferroic compound. A wide scale precession-assisted electron diffraction tomography study first allows the determination of the structure the compound adopts in thin films, and even permits the refinement of the atomic positions within this structure. Cationic mobility is suggested for two of the atomic positions through the existence of extra electronic density. A local in situ high resolution scanning transmission electron microscopy study then allows confirming these mobilities by directly spotting the cationic displacements on successively acquired images. The whole study confirms an unconventional switching mechanism via local domain wall motion in this compound.

Epstein-Barr virus protein BKRF4 restricts nucleosome assembly to suppress host antiviral responses

Inhibition of host DNA damage response (DDR) is a common mechanism used by viruses to manipulate host cellular machinery and orchestrate viral life cycles. Epstein-Barr virus tegument protein BKRF4 associates with cellular chromatin to suppress host DDR signaling, but the underlying mechanism remains elusive. Here, we identify a BKRF4 histone binding domain (residues 15-102, termed BKRF4-HBD) that can accumulate at the DNA damage sites to disrupt 53BP1 foci formation. The high-resolution structure of the BKRF4-HBD in complex with a human H2A-H2B dimer shows that BKRF4-HBD interacts with the H2A-H2B dimer via the N-terminal region (NTR), the DWP motif (residues 80-86 containing D81, W84, P86), and the C-terminal region (CTR). The "triple-anchor" binding mode confers BKRF4-HBD the ability to associate with the partially unfolded nucleosomes, promoting the nucleosome disassembly. Importantly, disrupting the BKRF4-H2A-H2B interaction impairs the binding between BKRF4-HBD and nucleosome invitro and inhibits the recruitment of BKRF4-HBD to DNA breaks invivo. Together, our study reveals the structural basis of BKRF4 bindings to the partially unfolded nucleosome and elucidates an unconventional mechanism of host DDR signal attenuation.

Unconventional Stereoerror Formation Mechanisms in Nonmetallocene Propene Polymerization Systems Revealed by DFT Calculations.

An unconventional mechanism for the stereoerror formation in propene polymerization catalyzed by C1-symmetric salalen-M systems (M = Zr, Hf) is suggested by DFT calculations. While propagation happens with the ligand in its fac-mer conformation, a change of ligand wrapping mode from fac-mer to fac-fac is the main source of the lower stereoselectivities obtained with Zr and Hf. This is different for the Ti analogues, where the ligand fac-mer wrapping mode does not play a role. Activation strain analysis indicates that the preference for a chain stationary mechanism of the Zr/Hf species is due to the energy required to distort the reactants (ΔEStrain) rather than to their mutual interaction (ΔEInt).

Inaccessible Polarization-Induced Phase Transitions in a Block Copolymer Electrolyte: An Unconventional Mechanism for the Limiting Current

Inaccessible Polarization-Induced Phase Transitions in a Block Copolymer Electrolyte: An Unconventional Mechanism for the Limiting Current

QM/MM Well-Tempered Metadynamics Study of the Mechanism of XBP1 mRNA Cleavage by Inositol Requiring Enzyme 1α RNase.

A range of in silico methodologies were herein employed to study the unconventional XBP1 mRNA cleavage mechanism performed by the unfolded protein response (UPR) mediator Inositol Requiring Enzyme 1α (IRE1). Using Protein–RNA molecular docking along with a series of extensive restrained/unrestrained atomistic molecular dynamics (MD) simulations, the dynamical behavior of the system was evaluated and a reliable model of the IRE1/XBP1 mRNA complex was constructed. From a series of well-converged quantum mechanics molecular mechanics well-tempered metadynamics (QM/MM WT-MetaD) simulations using the Grimme dispersion interaction corrected semiempirical parametrization method 6 level of theory (PM6-D3) and the AMBER14SB-OL3 force field, the free energy profile of the cleavage mechanism was determined, along with intermediates and transition state structures. The results show two distinct reaction paths based on general acid–general base type mechanisms, with different activation energies that perfectly match observations from experimental mutagenesis data. The study brings unique atomistic insights into the cleavage mechanism of XBP1 mRNA by IRE1 and clarifies the roles of the catalytic residues H910 and Y892. Increased understanding of the details in UPR signaling can assist in the development of new therapeutic agents for its modulation.

The mechanism of RNA capping by SARS-CoV-2

The RNA genome of SARS-CoV-2 contains a 5′ cap that facilitates the translation of viral proteins, protection from exonucleases and evasion of the host immune response1–4. How this cap is made in SARS-CoV-2 is not completely understood. Here we reconstitute the N7- and 2′-O-methylated SARS-CoV-2 RNA cap (7MeGpppA2′-O-Me) using virally encoded non-structural proteins (nsps). We show that the kinase-like nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain5 of nsp12 transfers the RNA to the amino terminus of nsp9, forming a covalent RNA–protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers the RNA to GDP, forming the core cap structure GpppA-RNA. The nsp146 and nsp167 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication–transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system8 that the N terminus of nsp9 and the kinase-like active-site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19.