Sevoflurane causes neurotoxicity and cognitive impairment by regulating Hippo signaling pathway-mediated ferroptosis via upregulating PRKCD.

BACKGROUND: Sevoflurane (SEV) has been found to induce neurotoxicity and cognitive impairment, leading to the development of degenerative diseases. Protein kinase C delta (PRKCD) is upregulated in the hippocampus of SEV-treated mice and may be related to SEV-related neurotoxicity. However, the underlying molecular mechanisms by which SEV mediates neurotoxicity via PRKCD remain unclear. METHODS: Normal mice and PRKCD knockout (KO) mice were exposed to SEV. Hippocampal neurons were isolated from mice hippocampal tissues. H&E staining was used for pathological morphology of hippocampal tissues, and NISSL staining was used to analyze the number of hippocampal neurons. The mRNA and protein levels were determined using quantitative real-time PCR, western blot, immunofluorescence staining and immunohistochemical staining. The mitochondrial microstructure was observed by transmission electron microscopy. Cell viability was detected by cell counting kit 8 assay, and ferroptosis was assessed by detecting related marker levels. The cognitive ability of mice was assessed by morris water maze test. And the protein levels of PRKCD, ferroptosis-related markers and Hippo pathway-related markers were examined by western bolt. RESULTS: SEV increased PRKCD expression and ferroptosis in hippocampal tissues of mice. Also, SEV promoted mouse hippocampal neuron injury by inducing ferroptosis via upregulating PRKCD expression. Knockout of PRKCD alleviated SEV-induced neurotoxicity and cognitive impairment in mice, and relieved SEV-induced ferroptosis in hippocampal neurons. PRKCD could inhibit the activity of Hippo pathway, and its knockdown also overturned SEV-mediated ferroptosis by activating Hippo pathway. CONCLUSION: SEV could induce neurotoxicity and cognitive impairment by promoting ferroptosis via inactivating Hippo pathway through increasing PRKCD expression.

Multi-omics reveal neuroprotection of Acer truncatum Bunge Seed extract on hypoxic-ischemia encephalopathy rats under high-altitude.

Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.

Unlocking the Multifaceted Mechanisms of Bud Outgrowth: Advances in Understanding Shoot Branching.

Shoot branching is a complex and tightly regulated developmental process that is essential for determining plant architecture and crop yields. The outgrowth of tiller buds is a crucial step in shoot branching, and it is influenced by a variety of internal and external cues. This review provides an extensive overview of the genetic, plant hormonal, and environmental factors that regulate shoot branching in several plant species, including rice, Arabidopsis, tomato, and wheat. We especially highlight the central role of TEOSINTE BRANCHED 1 (TB1), a key gene in orchestrating bud outgrowth. In addition, we discuss how the phytohormones cytokinins, strigolactones, and auxin interact to regulate tillering/branching. We also shed light on the involvement of sugar, an integral component of plant development, which can impact bud outgrowth in both trophic and signaling ways. Finally, we emphasize the substantial influence of environmental factors, such as light, temperature, water availability, biotic stresses, and nutrients, on shoot branching. In summary, this review offers a comprehensive evaluation of the multifaced regulatory mechanisms that underpin shoot branching and highlights the adaptable nature of plants to survive and persist in fluctuating environmental conditions.

Lipidomics reveal the cognitive improvement effects of Acer truncatum Bunge seed oil on hypoxic-ischemic encephalopathy rats.

Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of acute neonatal death and chronic neurological damage, and severe HIE can have secondary sequelae such as cognitive impairment and cerebral palsy, for which effective interventions are lacking. In this study, we found that continuous 30-day intake of Acer truncatum Bunge seed oil (ASO) reduced brain damage and improved cognitive ability in HIE rats. Using lipidomic strategies, we observed that HIE rats had decreased unsaturated fatty acids and increased lysophospholipids in the brain. However, after 30 days of ASO treatment, phospholipids, plasmalogens, and unsaturated fatty acids increased, while lysophospholipids and oxidized glycerophospholipids decreased in both serum and the brain. Enrichment analysis showed that ASO intake mainly affected sphingolipid metabolism, fat digestion and absorption, glycerolipid metabolism and glycerophospholipid metabolic pathways in serum and the brain. Cluster, correlation, and confirmatory factor analyses showed that cognitive improvement after ASO administration was attributed to increased essential phospholipids and ω3/6/9 fatty acids, coupled with decreased oxidized glycerophospholipids in HIE rats. Our findings indicate that ASO has the potential to be developed as an effective food supplement for ischemic hypoxic newborns.

Abnormal Metal-Semiconductor-Like Transition and Exceptional Enhanced Superconducting State in Pressurized Restacked TaS2.

Interlayer coupling and stacking order play essential roles in shaping the exotic electronic properties of two-dimensional materials. Here, we employ restacked TaS2─a novel transition metal dichalcogenide (TMD) with weak vdW bonding and twisted angles─to investigate the strain effects of interlayer modulation on the electronic properties. Under pressure, an unexpected transition from metallic to semiconducting-like states occurs. Superconductivity coexists with the semiconducting-like state over a wide pressure range, which has never before been observed in TMDs. Upon further compression, a new superconducting SC-II state emerges without structural evolution and gradually replaces the initial SC-I state. The emerging SC-II state exhibits robust zero-resistance superconductivity and an ultrahigh upper critical field. The abundant electronic state changes in RS-TaS2 are strongly related to band-structure engineering resulting from pressure-induced interlayer stacking angle modulation. Our results reveal the remarkable effect of interlayer rearrangement on electronic properties and provide a special way to explore the unique properties of 2D materials.

Coordination Changes in Densified Aluminate Glass upon Compression up to 65 GPa: A View from Solid-State Nuclear Magnetic Resonance.

Deciphering the structural evolution in irreversibly densified oxide glasses is crucial for fabricating functional glasses with tunable properties and elucidating the nature of pressure-induced anomalous plastic deformation in glasses. High-resolution NMR spectroscopy quantifies atomic-level structural information on densified glasses; however, its application is limited to the low-pressure range due to technical challenges. Here, we report the first high-resolution NMR spectra of oxide glass compressed by diamond anvil cells at room temperature, extending the pressure record of such studies from 24 to 65 GPa. The results constrain the densification path through coordination transformation of Al cations. Based on a statistical thermodynamic model, the stepwise changes in the Al fractions of oxide glasses and the effects of network polymerization on the densification paths are quantified. These results extend the knowledge on densification of the previously unattainable pressure conditions and contribute to understanding the origin of mechanical strengthening of the glasses.

A long chain-induced depletion effect for abnormal grafting in the preparation of bimodal bidisperse polymer-grafted nanoparticles.

One of the challenging problems in the research field of polymer nanocomposites is how to prepare nanocomposites with high grafting density and strong ability of dispersion at the same time. For nanocomposites composed of bimodal bidisperse polymer chains and nanoparticles, the above requirements can be met by rationally adjusting the ratio of long and short polymer chains. In this study, the process of grafting bimodal bidisperse polymer chains onto the surface of nanoparticles in a grafting-to manner was investigated via computer simulation and theoretical methods. Three grafting strategies were designed: first short then long (SL) system, both short and long (Both) system and first long then short (LS) system. An abnormal phenomenon for the Both system was found by analyzing the grafting density of long and short polymer chains on the surface of nanoparticles. We speculate that the reason for this anomalous phenomenon is the "depletion effect" brought about by the long chains in the Both system. We employ the Polymer Reference Interaction Site Model (PRISM) theory to investigate this anomaly in-depth. By comparing the radial distribution function (RDF) predicted by the PRISM theory with the RDF results obtained by the molecular dynamics (MD) simulation, we found that with the increase of the number of long chains in the system, the grafting density of short polymer chains on the nanoparticle surface showed an obvious upward trend. The "depletion effect" brought by long chains was the main reason for higher short chains' grafting density of the Both system compared to the SL system. Our findings provide effective guidance for the design of nanoparticle-grafted bimodal bidisperse polymer chains and provide a theoretical basis for experimentation and production of polymer nanocomposites with better performance.

OsHYPK-mediated protein N-terminal acetylation coordinates plant development and abiotic stress responses in rice.

N-terminal acetylation is one of the most common protein modifications in eukaryotes, and approximately 40% of human and plant proteomes are acetylated by ribosome-associated N-terminal acetyltransferase A (NatA) in a co-translational manner. However, the in vivo regulatory mechanism of NatA and the global impact of NatA-mediated N-terminal acetylation on protein fate remain unclear. Here, we identify Huntingtin Yeast partner K (HYPK), an evolutionarily conserved chaperone-like protein, as a positive regulator of NatA activity in rice. We found that loss of OsHYPK function leads to developmental defects in rice plant architecture but increased resistance to abiotic stresses, attributable to perturbation of the N-terminal acetylome and accelerated global protein turnover. Furthermore, we demonstrated that OsHYPK is also a substrate of NatA and that N-terminal acetylation of OsHYPK promotes its own degradation, probably through the Ac/N-degron pathway, which could be induced by abiotic stresses. Taken together, our findings suggest that the OsHYPK-NatA complex plays a critical role in coordinating plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover, which are essential for maintaining adaptive phenotypic plasticity in rice.

Record-High Superconductivity in Transition Metal Dichalcogenides Emerged in Compressed 2H-TaS2.

Pressure has always been an effective method for uncovering novel phenomena and properties in condensed matter physics. Here, an electrical transport study is carried on 2H-TaS2 up to ≈208 GPa, and an unexpected superconducting state (SC-II) emerging around 86.1 GPa with an initial critical temperature (Tc ) of 9.6 K is found. As pressure increases, the Tc enhances rapidly and reaches a maximum of 16.4 K at 157.4 GPa, which sets a new record for transition metal dichalcogenides (TMDs). The original superconducting state (SC-I) is found to be re-enhanced above 100 GPa after the recession around 10 GPa, and coexists with SC-II to the highest pressure applied in this work. In situ high-pressure X-ray diffraction and Hall effect measurements reveal that the occurrence of SC-II is accompanied by a structural modification and a concurrent enhancement of hole carrier density. The new high-Tc superconducting state in 2H-TaS2 can be attributed to the change of the electronic states near the Fermi surface, owing to pressure-induced interlayer modulation. It is the first time finding this remarkable superconducting state in TMDs, which not only brings a new broad of perspective on layered materials but also expands the field of pressure-modified superconductivity.

GmPIN-dependent polar auxin transport is involved in soybean nodule development.

To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that are fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed the impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that the establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia.

Evolution of Structural and Electronic Properties in NbTe2 under High Pressure.

Transition metal dichalcogenides (TMDs) have attracted wide attention due to their quasi-two-dimensional layered structure and exotic properties. Plenty of efforts have been done to modulate the interlayer stacking manner for novel states. However, as an equally important element in shaping the unique properties of TMDs, the effect of intralayer interaction is rarely revealed. Here, we report a particular case of pressure-tuned re-arrangement of intralayer atoms in distorted 1T-NbTe2, which was demonstrated to be a new type of structural phase transition in TMDs. The structural transition occurs in the pressure range of 16-20 GPa, resulting in a transformation of Nb atomic arrangement from the trimeric to dimeric structure, accompanied by a dramatic collapse of unit cell volume and lattice parameters. Simultaneously, a charge density wave (CDW) was also found to collapse during the phase transition. The strong increase in the critical fluctuations of CDW induces a significant decline in the electronic correlation and a change of charge carrier type from hole to electron in NbTe2. Our finding reveals a new mechanism of structure evolution and expands the field of pressure-induced phase transition.

Tailoring Antifouling Properties of Nanocarriers via Entropic Collision of Polymer Grafting.

Polymer graftings (PGs) are widely employed in antifouling surfaces and drug delivery systems to regulate the interaction with a foreign environment. Through molecular dynamics simulations and scaling theory analysis, we investigate the physical antifouling properties of PGs via their collision behaviors. Compared with mushroom-like PGs with low grafting density, we find brush-like PGs with high grafting density could generate large deformation-induced entropic repulsive force during a collision, revealing a microscopic mechanism for the hop motions of polymer-grafted nanoparticles for drug delivery observed in experiment. In addition, the collision elasticity of PGs is found to decay with the collision velocity by a power law, i.e., a concise dynamic scaling despite the complex process involved, which is beyond expectation. These results elucidate the dynamic interacting mechanism of PGs, which are of immediate interest for a fundamental understanding of the antifouling performance of PGs and the rational design of PG-coated nanoparticles in nanomedicine for drug delivery.

Activation of ACS7 in Arabidopsis affects vascular development and demonstrates a link between ethylene synthesis and cambial activity.

Ethylene is a gaseous hormone that affects many processes of plant growth and development. During vascular development, ethylene positively regulates cambial cell division in parallel with tracheary element differentiation inhibitory factor (TDIF) peptide signaling. In this study, we identified an ethylene overproducing mutant, acs7-d, exhibiting enhanced cambial activity and reduced wall development in fiber cells. Using genetic analysis, we found that ethylene signaling is necessary for the phenotypes of enhanced cambial cell division as well as defects in stem elongation and fiber cell wall development. Further, the cambial cell proliferation phenotype of acs7-d depends on WOX4, indicating that the two parallel pathways, ethylene and TDIF signaling, converge at WOX4 in regulating cambium activity. Gene expression analysis showed that ethylene impedes fiber cell wall biosynthesis through a conserved hierarchical transcriptional regulation. These results advance our understanding of the molecular mechanisms of ethylene in regulating vascular meristem activity.

Synthesis of Polymer Single-Chain Nanoparticle with High Compactness in Cosolvent Condition: A Computer Simulation Study.

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by intramolecular crosslinking of isolated single polymer chains. Syntheses of such SCNPs usually need to be performed in a dilute solution. In such a condition, the bonding probability of the two active crosslinking units at a short contour distance along the chain backbone is much higher than those which are far away from each other. Such a reaction condition often results in local spheroidization and, therefore, the formation of loosely packed structures. How to inhibit the local spheroidization and improve the compactness of SCNPs is thus a major challenge for the syntheses of SCNPs. In this study, computer simulations are performed and the fact that a precollapse of the polymer chain conformation in a cosolvent condition can largely improve the probability of the crosslinking reactions at large contour distances is demonstrated, favoring the formations of closely packed globular structures. As a result, the formed SCNPs can be more spherical and have higher compactness than those fabricated in ultradilute good solvent solution in a conventional way. It is believed this simulation work can provide a insight into the effective syntheses of SCNPs with spherical conformations and high compactness.

A comparative study on the dynamic heterogeneity of supercooled polymers under nanoconfinement.

Dynamic heterogeneity (DH) is a universal property of glass transition phenomena. In this work, we perform a comparative analysis of DH for pure polymer and polymer/nanoparticle composite systems in both film and bulk states via molecular dynamics simulations. We find that the dynamic gradient and the faster average dynamics due to the presence of a free surface are two leading factors, resulting from a nanoconfinement effect, which influence different parts of DH in a film system. The dynamic gradient results from differences in dynamics at different distances from the mobile surface, which induces a large deviation from the Gaussian distribution for the displacement distribution in the film. At the same time, the maximum string size which describes the region size for cooperative motion (dynamic correlation) can also be influenced by the dynamic gradient, although this influence is much weaker than that on the displacement distribution. On the other hand, reflecting temporal fluctuations of dynamics or temporal parts of DH, characteristic peak times of the non-Gaussian parameter and string size, and the ratio between persistent times and exchange times which describe the dynamic exchange properties, are mainly influenced by the faster dynamics on average. Our results demonstrate that measuring different properties (dynamic distribution, dynamic correlation or dynamic exchange) place an emphasis on distinct temporal and spatial parts of DH. It is necessary to use combinational measurements of these properties to give a complete picture of DH in nanoconfinement environments.

Dynamics and reaction kinetics of coarse-grained bulk vitrimers: a molecular dynamics study.

Vitrimers with dynamic covalent bonds make thermosetting materials plastic, recyclable and self-repairing, and have broad application prospects. However, due to the complex composition of vitrimers and the dynamic bond exchange reactions (BERs), the mechanism behind their unique dynamic behavior is not fully understood. We used the hybrid molecular dynamics-Monte Carlo (MD-MC) algorithm to establish a molecular dynamics model that can accurately reflect BERs, and reveal the intrinsic mechanism of the dynamic behavior of the vitrimer system. The simulation results show that BERs change the diffusion mode of the vitrimer's constituent molecules, which in turn affects the BER and other relaxation dynamics. This provides a theoretical basis and a specific method for the rational design of the rheological properties of vitrimers.

A simulation study on the glass transition behavior and relevant segmental dynamics in free-standing polymer nanocomposite films.

In polymer/nanoparticle composite (PNC) thin films, polymer chains experience strong confinement effects not only at the free surface area but also from nanoparticles (NPs). In this work, the influence of NP-polymer interaction and NP distribution on the polymer segmental dynamics and the glass transition behavior of PNC free-standing films are investigated through molecular dynamics simulations. We demonstrate that NPs will migrate to the film surface area and form an NP-concentrated layer when NP-polymer interactions are weak, while NPs are well dispersed in the bulk region when NP-polymer interactions are strong. In both cases, we find increases in the glass transition temperature Tg compared with the pure film without NPs, although with a different degree. The weakly interacting system has the same Tg as the pure bulk system without NPs. The NP layer formed at the surface area reduces both the mobility of the surface polymer beads and the mobility gradient in the film normal direction (MGFND), therefore resulting in an increase in the Tg which highlights the vital role of the mobile surface layer. In contrast, the NPs in the bulk region enlarge the MGFND. NPs have opposite influences on the polymer bead dynamic anisotropy when they interact weakly or strongly with polymers, weakened for the former and enhanced for the latter. These findings offer a clear picture of the segmental dynamics and glass transition behavior in free-standing PNC films with different NP-polymer interaction strengths. We hope these results will be helpful for the property design of related materials.

Pressure-induced structural and electronic transitions of thiospinel Fe3S4.

We report the investigations on the structural and electronic properties of an inverse spinel Fe3S4 at high pressures using synchrotron x-ray diffraction (XRD) and electrical transport measurements. Our XRD measurements at high pressures reveal an irreversible structural phase transformation on compression above ∼3 GPa from a cubic spinel (Fd-3m space group) into a monoclinic Cr3S4-type structure (I2/m space group). Electrical transport measurements suggest that the high pressure monoclinic phase has a semiconducting behavior. This semiconducting behavior is found to persist up to the highest pressure of measurement of ∼23 GPa. These results show that while Fe3S4 possesses similar high pressure structural properties with other thiospinels, the electronic properties under pressure show a rather strong similarity to its oxide counterpart, Fe3O4, at high pressures.

Translational and rotational dynamics of an ultra-thin nanorod probe particle in linear polymer melts.

The dynamics of nanorods (NRs) in complex liquids is important, not only for new material design and for understanding complex phenomena in biological systems, but also for the development of fundamental theories. In this work, the translational and rotational dynamics of a single rigid ultra-thin nanorod probe particle in linear polymer melts are investigated using coarse-grained molecular dynamics (CG-MD) simulations. Our results indicate that the translational motion of an ultra-thin NR, which has a diameter equal to the polymer monomer size, is not affected by the polymer chain length N in entangled polymer melts. This finding verifies de Gennes' theoretical prediction for the first time. However, the rotational dynamics of a NR with rod length L = 21, which is larger than the polymer tube diameter dt, is weakly coupled with polymer entanglement strands, revealing a different N-dependence for translational and rotational dynamics. The results for NRs with different lengths L also show that the size ratio between L and the polymer characteristic size is the dominant factor for NR dynamics, especially for rotational dynamics in entangled melts.

A Core Regulatory Pathway Controlling Rice Tiller Angle Mediated by the LAZY1-Dependent Asymmetric Distribution of Auxin.

Tiller angle in cereals is a key shoot architecture trait that strongly influences grain yield. Studies in rice (Oryza sativa) have implicated shoot gravitropism in the regulation of tiller angle. However, the functional link between shoot gravitropism and tiller angle is unknown. Here, we conducted a large-scale transcriptome analysis of rice shoots in response to gravistimulation and identified two new nodes of a shoot gravitropism regulatory gene network that also controls rice tiller angle. We demonstrate that HEAT STRESS TRANSCRIPTION FACTOR 2D (HSFA2D) is an upstream positive regulator of the LAZY1-mediated asymmetric auxin distribution pathway. We also show that two functionally redundant transcription factor genes, WUSCHEL RELATED HOMEOBOX6 (WOX6) and WOX11, are expressed asymmetrically in response to auxin to connect gravitropism responses with the control of rice tiller angle. These findings define upstream and downstream genetic components that link shoot gravitropism, asymmetric auxin distribution, and rice tiller angle. The results highlight the power of the high-temporal-resolution RNA-seq data set and its use to explore further genetic components controlling tiller angle. Collectively, these approaches will identify genes to improve grain yields by facilitating the optimization of plant architecture.