The ciliate Euplotes balteatus is resistant to Paralytic Shellfish Toxins from Alexandrium minutum (Dinophyceae).

Research on interactions between grazers and toxigenic algae is fundamental for understanding toxin dynamics within aquatic ecosystems and developing biotic approaches to mitigate harmful algal blooms. The dinoflagellate Alexandrium minutum is a well-known microalga responsible for paralytic shellfish toxins (PSTs) contamination in many coastal regions worldwide. This study investigated the impact of the ciliate Euplotes balteatus on cell density and PSTs transfer in simulated A. minutum blooms under controlled conditions. E. balteatus exhibited resistance to the PSTs produced by A. minutum with a density of up to 10,000 cells/mL, sustaining growth and reproduction while eliminating algal cells within a few days. The cellular PSTs content of A. minutum increased in response to the grazing pressure from E. balteatus. However, due to the substantial reduction in density, the overall toxicity of the algal population decreased to a negligible level. Most PSTs contained within algal cells were temporarily accumulated in E. balteatus before being released into the water column, suggesting unclear mechanisms for PSTs excretion in unicellular grazers. In principle, the grazing of E. balteatus on A. minutum promotes the transfer of the majority of intracellular PSTs into extracellular portions, thereby mitigating the risk of their accumulation and contamination through marine trophic pathways. However, this process also introduces an increase in the potential environmental hazards posed by extracellular PSTs to some extent.

Sex-specific effects of alcohol on neurobehavioral performance and endoplasmic reticulum stress: an analysis using neuron-specific MANF deficient mice.

Excessive alcohol exposure can cause neurobehavioral deficits and structural alterations in the brain. Emerging research evidence suggests that endoplasmic reticulum (ER) stress plays an important role in alcohol-induced neurotoxicity. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein and is responsible to maintain ER homeostasis. MANF is highly expressed in both the developing and mature brain. We have previously shown that MANF deficiency exacerbated alcohol induced neurodegeneration and ER stress in the developing brain. However, little is known regarding the role of MANF in alcohol induced neuronal damage in the adult brain. In this study, we used a neuron-specific MANF knockout (KO) mouse model to investigate the effect of MANF deficiency on acute binge alcohol exposure-induced neurobehavioral deficits and ER stress. Adult male and female MANF KO mice and littermate controls received daily alcohol gavage (5 g/kg) for 10 days and then subjected to a battery of neurobehavioral tests including rotarods, balance beam, DigiGait, open field, elevated plus maze, Barnes maze, and three-chamber sociability task. Female MANF KO animals were more susceptible to alcohol-induced body weight loss. Alcohol exposure did not affect motor function, however female but not male MANF KO mice exhibited an increased locomotor activity in open field test. Learning and memory was not significantly impaired, but it was altered by MANF deficiency in females while it was affected by alcohol treatment in males. Both alcohol-exposed male and female MANF KO mice displayed increased sociability. Alcohol induced the expression of ER chaperones GRP78 and GRP94 and altered the levels of several unfolded protein response (UPR) and neuroinflammation markers in MANF KO mice in a sex-specific manner. The expression of MANF interacting proteins neuroplastin, PDIA1, and PDIA6 was increased in MANF KO mice, and was further induced by alcohol. In conclusion, alcohol exposure and neuronal MANF deficiency interacted to alter neurobehavioral outcomes, ER homeostasis and neuroinflammation in a sex-specific manner.

Ultrasound-Activatable In Situ Vaccine for Enhanced Antigen Self- and Cross-Presentation to Overcome Cancer Immunotherapy Resistance.

Insufficient antigen self-presentation of tumor cells and ineffective antigen cross-presentation by dendritic cells (DCs) contribute to diminished immune recognition and activation, which cause resistance to immunotherapies. Herein, we present an ultrasound-activatable in situ vaccine by utilizing a hybrid nanovesicle composed of a thylakoid (TK)/platelet (PLT) membrane and a liposome encapsulating DNA methyltransferase inhibitor zebularine (Zeb) and sonosensitizer hematoporphyrin monomethyl ether (HMME). Upon local exposure to ultrasound, reactive oxygen species (ROS) are generated and induce the sequential release of the payloads. Zeb can efficiently inhibit tumor DNA hypermethylation, promoting major histocompatibility complex class I (MHC-I) molecules-mediated antigen self-presentation to improve immune recognition. Meanwhile, the catalase on the TK membrane can decompose the tumoral overexpressed H2O2 into O2, which boosts the generation of ROS and the destruction of tumor cells, resulting in the in situ antigen release and cross-presentation of tumor antigens by DCs. This in situ vaccine simultaneously promotes antigen self-presentation and cross-presentation, resulting in heightened antitumor immunity to overcome resistance.

Emulsion-Based Multi-Phase Integrated Microbeads with Inner Multi-Interface Structure Enable Dual-Modal Imaging for Precision Endovascular Embolization.

Microsphere-based embolic agents have gained prominence in transarterial embolization (TAE) treatment, a critical minimally invasive therapy widely applied for a variety of diseases such as hypervascular tumors and acute bleeding. However, the development of microspheres with long-term, real-time, and repeated X-ray imaging as well as ultrasound imaging remains challenging. In this study, emulsion-based dual-modal imaging microbeads with a unique internal multi-interface structure is developed for TAE treatment. The embolic microbeads are fabricated from a solidified oil-in-water (O/W) emulsion composed of crosslinked CaAlg-based aqueous matrix and dispersed radiopaque iodinated oil (IO) droplets through a droplet-based microfluidic fabrication method. The CaAlg-IO microbeads exhibit superior X-ray imaging visibility due to the incorporation of exceptionally high iodine level up to 221 mgI mL-1, excellent ultrasound imaging capability attributed to the multi-interface structure of the O/W emulsion, great microcatheter deliverability thanks to their appropriate biomechanical properties and optimal microbead density, and extended drug release behavior owing to the biodegradation nature of the embolics. Such an embolic agent presents a promising emulsion-based platform to utilize multi-phased structures for improving endovascular embolization performance and assessment capabilities.

Metagenomic insights into microbial variation and carbon cycling function in crop rotation systems.

The decomposition and utilization of plant-derived carbon by microorganisms and carbon fixation are crucial pathways for enhancing soil organic carbon (SOC) storage. However, a gap remains in our understanding of the impact of microorganisms on the decomposition of plant-derived carbon and their capacity for carbon fixation in crop rotation systems. Based on a 12-year experiment with wheat-maize (WM), wheat-cotton (WC), and wheat-soybean (WS) rotations, the microbial communities and carbon cycle function were investigated. The results indicated that WS rotation significantly increased SOC content compared to WM and WC. In addition, a significant increase was observed in microbially available carbon and microbial biomass carbon in the WS soil compared with those in the others. Further analysis of the microbial community factors that influenced SOC content revealed that WS rotation, in contrast to WM rotation, enhanced the diversity and richness of bacteria and fungi. Analysis of microbial carbon decomposition functions revealed an increase in starch, lignin, and hemicellulose decomposition genes in the WS soil compared to the others. The changes in carbon decomposition genes were primarily attributed to six bacterial genera, namely Nocardioides, Agromyces, Microvirga, Skermanella, Anaeromyxobacter, and Arthrobacter, as well as four fungal genera, namely Dendryphion, Staphylotrichum, Apiotrichum, and Abortiporus, which were significantly influenced by the crop rotation systems. In addition, microbial carbon fixation-related genes such as ACAT, IDH1, GAPDH, rpiA, and rbcS were significantly enriched in WS. Species annotation of differential carbon fixation genes identified 18 genera that play a role in soil carbon fixation variation within the crop rotation systems. This study highlights the impact of crop rotation systems on SOC content and alterations in specific microbial communities on carbon cycle function.

Single-cell RNA sequencing reveals special basal cells and fibroblasts in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most predominant type of idiopathic interstitial pneumonia and has an increasing incidence, poor prognosis, and unclear pathogenesis. In order to investigate the molecular mechanisms underlying IPF further, we performed single-cell RNA sequencing analysis on three healthy controls and five IPF lung tissue samples. The results revealed a significant shift in epithelial cells (ECs) phenotypes in IPF, which may be attributed to the differentiation of alveolar type 2 cells to basal cells. In addition, several previously unrecognized basal cell subtypes were preliminarily identified, including extracellular matrix basal cells, which were increased in the IPF group. We identified a special population of fibroblasts that highly expressed extracellular matrix-related genes, POSTN, CTHRC1, COL3A1, COL5A2, and COL12A1. We propose that the close interaction between ECs and fibroblasts through ligand-receptor pairs may have a critical function in IPF development. Collectively, these outcomes provide innovative perspectives on the complexity and diversity of basal cells and fibroblasts in IPF and contribute to the understanding of possible mechanisms in pathological lung fibrosis.

Ultrasound Speckle Decorrelation Analysis-Based Velocimetry for 3D-Velocity-Components Measurement Using a 1D Transducer Array.

Ultrasound velocimetry has been widely used for blood flow imaging. However, the flow measurements are constrained to resolve the in-plane 2D flow components when using a 1D transducer array. In this work, an ultrasound speckle decorrelation analysis-based velocimetry (3C-vUS) is proposed for 3D velocity components measurement using a 1D transducer array. The 3C-vUS theory is first derived and validated with numerical simulations and phantom experiments. The in vivo testing results show that 3C-vUS can accurately measure the blood flow 3D-velocity-components of the human carotid artery at arbitrary probe-to-vessel angles throughout the cardiac cycle. With such capability, the 3C-vUS will alleviate the requirement of operators and promote disease screening for blood flow-related disorders.

Divergent Synthesis of 2-Chromonyl-3-hydrazono-chromones and 2-Alkoxy-3-hydrazono-chromones through Switchable Annulation Reactions of o-Hydroxyphenylenaminones with Aryldiazonium Salts.

An unprecedented selective chromone annulation reaction controlled by solvent for the divergent synthesis of two types of 2,3-disubstituted chromone skeletons has been developed. A variety of 2-chromonyl-3-hydrazono-chromones and 2-alkoxy-3-hydrazono-chromones were constructed efficiently from readily available o-hydroxyphenylenaminones (o-HPEs) and aryldiazonium salts at room temperature. This strategy is highly chemoselective and features mild reaction conditions, broad substrate scope, broad functional group tolerance, easy gram-scale preparation, and simple filtration to obtain the pure products without tedious column chromatography.

Circ-USP9X accelerates deep vein thrombosis after fracture by acting as a miR-148b-3p sponge and upregulates SRC kinase signaling inhibitor 1.

OBJECTIVES: This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities. METHODS: An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl2) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments. RESULTS: The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl2-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl2's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified. CONCLUSION: circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.

Electron repulsion tuned electronic structure of TiO2 by fluorination for efficient and selective photocatalytic ammonia generation.

The photocatalytic conversion of nitrogen into high-value ammonia products holds tremendous potential in the global nitrogen cycle. However, the activation of N2 and competition of hydrogen evolution limit the improvement of nitrogen fixation performance. In this study, we developed a fluorinated TiO2 (F-TiO2) using a hydrothermal-annealing method. The incorporation of F dopants not only enhances the adsorption and activation of N2 through electronic structure regulation, but also facilitates an in situ increase in active sites via the electron repulsion effect between F and Ti atoms. In addition, the presence of F on the surface effectively improved the nitrogen supply problem and optimized the nitrogen fixation selectivity for its hydrophobic modulation. The NH3 yield of the F-TiO2 photocatalyst reached 63.8 µmol h-1 g-1, which was 8.5 times higher than that of pure TiO2. And the selectivity experiment showed that the electronic ratio of NH3 to H2 production reached 0.890. This research offers valuable insights for the design of highly efficient and selective nitrogen-fixing photocatalysts.

Exogenous putrescine plays a switch-like influence on the pH stress adaptability of biofilm-based activated sludge.

Microbial community adaptability to pH stress plays a crucial role in biofilm formation. This study aims to investigate the regulatory mechanisms of exogenous putrescine on pH stress, as well as enhance understanding and application for the technical measures and molecular mechanisms of biofilm regulation. Findings demonstrated that exogenous putrescine acted as a switch-like distributor affecting microorganism pH stress, thus promoting biofilm formation under acid conditions while inhibiting it under alkaline conditions. As pH decreases, the protonation degree of putrescine increases, making putrescine more readily adsorbed. Protonated exogenous putrescine could increase cell membrane permeability, facilitating its entry into the cell. Subsequently, putrescine consumed intracellular H+ by enhancing the glutamate-based acid resistance strategy and the γ-aminobutyric acid metabolic pathway to reduce acid stress on cells. Furthermore, putrescine stimulated ATPase expression, allowing for better utilization of energy in H+ transmembrane transport and enhancing oxidative phosphorylation activity. However, putrescine protonation was limited under alkaline conditions, and the intracellular H+ consumption further exacerbated alkali stress and inhibits cellular metabolic activity. Exogenous putrescine promoted the proportion of fungi and acidophilic bacteria under acidic stress and alkaliphilic bacteria under alkali stress while having a limited impact on fungi in alkaline biofilms. Increasing Bdellovibrio under alkali conditions with putrescine further aggravated the biofilm decomposition. This research shed light on the unclear relationship between exogenous putrescine, environmental pH, and pH stress adaptability of biofilm. By judiciously employing putrescine, biofilm formation could be controlled to meet the needs of engineering applications with different characteristics.IMPORTANCEThe objective of this study is to unravel the regulatory mechanism by which exogenous putrescine influences biofilm pH stress adaptability and understand the role of environmental pH in this intricate process. Our findings revealed that exogenous putrescine functioned as a switch-like distributor affecting the pH stress adaptability of biofilm-based activated sludge, which promoted energy utilization for growth and reproduction processes under acidic conditions while limiting biofilm development to conserve energy under alkaline conditions. This study not only clarified the previously ambiguous relationship between exogenous putrescine, environmental pH, and biofilm pH stress adaptability but also offered fresh insights into enhancing biofilm stability within extreme environments. Through the modulation of energy utilization, exerting control over biofilm growth and achieving more effective engineering goals could be possible.

Discovery and Biosynthesis of Cihanmycins Reveal Cytochrome P450-Catalyzed Intramolecular C-O Phenol Coupling Reactions.

Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of natural products. The enzyme mechanism for the biaryl phenol coupling reaction of the bicyclic CCNPs remains unclear. Herein, we report the discovery of two new arabinofuranosylated bicyclic CCNPs cihanmycins (CHMs) A (1) and B (2) from Amycolatopsis cihanbeyliensis DSM 45679 and the identification of the CHM biosynthetic gene cluster (cih BGC) by heterologous expression in Streptomyces lividans SBT18 to afford CHMs C (3) and D (4). The structure of 1 was confirmed by X-ray diffraction analysis. Three cytochrome P450 enzyme (CYP)-encoding genes cih26, cih32, and cih33 were individually inactivated in the heterologous host to produce CHMs E (5), F (6), and G (7), respectively. The structures of 5 and 6 indicated that Cih26 was responsible for the hydroxylation and epoxidation of the cinnamoyl moiety, and Cih32 should catalyze the ß-hydroxylation of three amino acid residues. Cih33 and its homologues DmlH and EpcH were biochemically verified to convert CHM G (7) with a monocyclic structure to a bicyclic skeleton of CHM C (3) through an intramolecular C-O phenol coupling reaction. The substrate 7-bound crystal structure of DmlH not only established the structure of 7, which was difficult for NMR analysis for displaying anomalous splitting signals, but also provided the binding mode of macrocyclic peptides recognized by these intramolecular C-O coupling CYPs. In addition, computational studies revealed a water-mediated diradical mechanism for the C-O phenol coupling reaction. These findings have shed important mechanistic insights into the CYP-catalyzed phenol coupling reactions.

Stochastic processes shape microbial community assembly in biofilters: Hidden role of rare taxa.

Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation.

Switchable Skeletal Rearrangement of Hexahydro-4H-indol-4-ones: Divergent Synthesis of Dihydroxy-4H-cyclopenta[b]pyridin-4-ones and 8-Alkenyl Oxepane-2,6-diones.

An unprecedented base-controlled selective skeletal rearrangement reaction of hexahydro-4H-indol-4-ones has been developed. In this protocol, highly functionalized dihydroxy-4H-cyclopenta[b]pyridin-4-ones and 8-alkenyl oxepane-2,6-diones were prepared with a broad substrate scope and high chemoselectivity in moderate to excellent yields selectively by modulating LiOH and Et3N. In addition, the newly formed 8-alkenyl oxepane-2,6-dione scaffolds could be easily further derivatized to 5-(pyrrol-2-yl)dihydrofuran-2(3H)-ones through a rare intramolecular rearrangement reaction.

A Photosensitivity-Enhanced Plant Growth Algorithm for UAV Path Planning.

With the rise and development of autonomy and intelligence technologies, UAVs will have increasingly significant applications in the future. It is very important to solve the problem of low-altitude penetration of UAVs to protect national territorial security. Based on an S-57 electronic chart file, the land, island, and threat information for an actual combat environment is parsed, extracted, and rasterized to construct a marine combat environment for UAV flight simulation. To address the problem of path planning for low-altitude penetration in complex environments, a photosensitivity-enhanced plant growth algorithm (PEPG) is proposed. Based on the plant growth path planning algorithm (PGPP), the proposed algorithm improves upon the light intensity preprocessing and light intensity calculation methods. Moreover, the kinematic constraints of the UAV, such as the turning angle, are also considered. The planned path that meets the safety flight requirements of the UAV is smoother than that of the original algorithm, and the length is reduced by at least 8.2%. Finally, simulation tests are carried out with three common path planning algorithms, namely, A*, RRT, and GA. The results show that the PEPG algorithm is superior to the other three algorithms in terms of the path length and path quality, and the feasibility and safety of the path are verified via the autonomous tracking flight of a UAV.

Substrate Conformational Switch Enables the Stereoselective Dimerization in P450 NascB: Insights from Molecular Dynamics Simulations and Quantum Mechanical/Molecular Mechanical Calculations.

P450 NascB catalyzes the coupling of cyclo-(l-tryptophan-l-proline) (1) to generate (-)-naseseazine C (2) through intramolecular C-N bond formation and intermolecular C-C coupling. A thorough understanding of its catalytic mechanism is crucial for the engineering or design of P450-catalyzed C-N dimerization reactions. By employing MD simulations, QM/MM calculations, and enhanced sampling, we assessed various mechanisms from recent works. Our study demonstrates that the most favorable pathway entails the transfer of a hydrogen atom from N7-H to Cpd I. Subsequently, there is a conformational change in the substrate radical, shifting it from the Re-face to the Si-face of N7 in Substrate 1. The Si-face conformation of Substrate 1 is stabilized by the protein environment and the π-π stacking interaction between the indole ring and heme porphyrin. The subsequent intermolecular C3-C6' bond formation between Substrate 1 radical and Substrate 2 occurs via a radical attack mechanism. The conformational switch of the Substrate 1 radical not only lowers the barrier of the intermolecular C3-C6' bond formation but also yields the correct stereoselectivity observed in experiments. In addition, we evaluated the reactivity of the ferric-superoxide species, showing it is not reactive enough to initiate the hydrogen atom abstraction from the indole NH group of the substrate. Our simulation provides a comprehensive mechanistic insight into how the P450 enzyme precisely controls both the intramolecular C-N cyclization and intermolecular C-C coupling. The current findings align with the available experimental data, emphasizing the pivotal role of substrate dynamics in governing P450 catalysis.

Decoding the influence of low temperature on biofilm development: The hidden roles of c-di-GMP.

Biofilms are widely used and play important roles in biological processes. Low temperature of wastewater inhibits the development of biofilms derived from wastewater activated sludge. However, the specific mechanism of temperature on biofilm development is still unclear. This study explored the mechanism of temperature on biofilm development and found a feasible method to enhance biofilm development at low temperature. The amount of biofilm development decreased by approximately 66 % and 55 % at 4 °C and 15 °C, respectively, as compared to 28 °C. The cyclic dimeric guanosine monophosphate (c-di-GMP) concentration also decreased at low temperature and was positively correlated with extracellular polymeric substance (EPS) content, formation, and adhesion strength. Microbial community results showed that low temperature inhibited the normal survival of most microorganisms, but promoted the growth of some psychrophile bacteria like Sporosarcina, Caldilineaceae, Gemmataceae, Anaerolineaceae and Acidobacteriota. Further analysis of functional genes demonstrated that the abundance of functional genes related to the synthesis of c-di-GMP (K18968, K18967 and K13590) decreased at low temperature. Subsequently, the addition of exogenous spermidine increased the level of intracellular c-di-GMP and alleviated the inhibition effect of low temperature on biofilm development. Therefore, the possible mechanism of low temperature on biofilm development could be the inhibition of the microorganism activity and reduction of the communication level between cells, which is the closely related to the EPS content, formation, and adhesion strength. The enhancement of c-di-GMP level through the exogenous addition of spermidine provides an alternative strategy to enhance biofilm development at low temperatures. The results of this study enhance the understanding of the influence of temperature on biofilm development and provide possible strategies for enhancing biofilm development at low temperatures.

Diastereoselective Three-Component 1,3-Dipolar Cycloaddition to Access Functionalized ß-Tetrahydrocarboline- and Tetrahydroisoquinoline-Fused Spirooxindoles.

A chemselective catalyst-free three-component 1,3-dipolar cycloaddition has been described. The unique polycyclic THPI and THIQs were creatively employed as dipolarophiles, which led to the formation of functionalized ß-tetrahydrocarboline- and tetrahydroisoquinoline-fused spirooxindoles in 60-94% of yields with excellent diastereoselectivities (10: 1->99: 1 dr). This reaction not only realizes a concise THPI- or THIQs-based 1,3-dipolar cycloaddition, but also provides a practical strategy for the construction of two distinctive spirooxindole skeletons.

Fabrication-induced even-odd discrepancy of magnetotransport in few-layer MnBi2Te4.

The van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.