Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells.

Cancer cells within individual tumors often exist in distinct phenotypic states that differ in functional attributes. While cancer cell populations typically display distinctive equilibria in the proportion of cells in various states, the mechanisms by which this occurs are poorly understood. Here, we study the dynamics of phenotypic proportions in human breast cancer cell lines. We show that subpopulations of cells purified for a given phenotypic state return towards equilibrium proportions over time. These observations can be explained by a Markov model in which cells transition stochastically between states. A prediction of this model is that, given certain conditions, any subpopulation of cells will return to equilibrium phenotypic proportions over time. A second prediction is that breast cancer stem-like cells arise de novo from non-stem-like cells. These findings contribute to our understanding of cancer heterogeneity and reveal how stochasticity in single-cell behaviors promotes phenotypic equilibrium in populations of cancer cells.

Ligand-induced monoubiquitination of BIK1 regulates plant immunity.

Recognition of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) triggers the first line of inducible defence against invading pathogens1-3. Receptor-like cytoplasmic kinases (RLCKs) are convergent regulators that associate with multiple PRRs in plants4. The mechanisms that underlie the activation of RLCKs are unclear. Here we show that when MAMPs are detected, the RLCK BOTRYTIS-INDUCED KINASE 1 (BIK1) is monoubiquitinated following phosphorylation, then released from the flagellin receptor FLAGELLIN SENSING 2 (FLS2)-BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) complex, and internalized dynamically into endocytic compartments. The Arabidopsis E3 ubiquitin ligases RING-H2 FINGER A3A (RHA3A) and RHA3B mediate the monoubiquitination of BIK1, which is essential for the subsequent release of BIK1 from the FLS2-BAK1 complex and activation of immune signalling. Ligand-induced monoubiquitination and endosomal puncta of BIK1 exhibit spatial and temporal dynamics that are distinct from those of the PRR FLS2. Our study reveals the intertwined regulation of PRR-RLCK complex activation by protein phosphorylation and ubiquitination, and shows that ligand-induced monoubiquitination contributes to the release of BIK1 family RLCKs from the PRR complex and activation of PRR signalling.

10†µm-Level TiNb2 O7 Secondary Particles for Fast-Charging Lithium-Ion Batteries.

TiNb2 O7 with Wadsley-Roth phase delivers double theoretical specific capacity and similar working potential in comparison to spinel Li4 Ti5 O12 , the commercial high-rate anode material, and thus can enable much higher energy density of lithium-ion batteries. However, the inter-particle resistance within the high-mass-loading TiNb2 O7 electrode would impede the capacity release for practical application, especially under fast-charging conditions. Herein, 10-20 µm-size carbon-coated TiNb2 O7 secondary particle (SP-TiNb2 O7 ) consisting of initial micro-scale TiNb2 O7 particles (MP-TiNb2 O7 ) was fabricated. The high crystallinity of active material could enable fast-charge diffusion and electrochemical reaction rate within particles, and the small number of stacking layers of SP-TiNb2 O7 could reduce the large inter-particle resistance that regular particle electrode often possess and achieve high compaction density of electrodes with high mass loading. The investigation on materials structure and electrochemical reaction kinetics verified the advances of the as-fabricated SP-TiNb2 O7 in achieving superior electrochemical performance. The SP-TiNb2 O7 exhibited high reversible capacity of 292.7 mAh g-1 in the potential range of 1-3 V (Li+ /Li) at 0.1 C, delivering high-capacity release of 94.3 %, and high capacity retention of 86 % at 0.5 C for 250 cycles in half cell configuration. Particularly, the advances of such an anode were verified in practical 5 Ah-level laminated full pouch cell. The as-assembled LiFePO4 ||TiNb2 O7 full cell exhibited a high capacity of 5.08 Ah at high charging rate of 6 C (77.9 % of that at 0.2 C of 6.52 Ah), as well as an ultralow capacity decay rate of 0.0352 % for 250 cycles at 1 C, suggesting the great potential for practical fast-charging lithium-ion batteries.

Ferroptosis is a protective factor for the prognosis of cancer patients: a systematic review and meta-analysis.

BACKGROUND: Cancer is a leading global cause of death. Conventional cancer treatments like surgery, radiation, and chemotherapy have associated side effects. Ferroptosis, a nonapoptotic and iron-dependent cell death, has been identified and differs from other cell death types. Research has shown that ferroptosis can promote and inhibit tumor growth, which may have prognostic value. Given the unclear role of ferroptosis in cancer biology, this meta-analysis aims to investigate its impact on cancer prognosis. METHODS: This systematic review and meta-analysis conducted searches on PubMed, Embase, and the Cochrane Library databases. Eight retrospective studies were included to compare the impact of ferroptosis inhibition and promotion on cancer patient prognosis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Studies lacking clear descriptions of hazard ratios (HR) and 95% confidence intervals for OS and PFS were excluded. Random-effects meta-analysis and meta-regression were performed on the included study data to assess prognosis differences between the experimental and control groups. Meta-analysis results included HR and 95% confidence intervals. This study has been registered with PROSPERO, CRD 42023463720 on September 27, 2023. RESULTS: A total of 2,446 articles were screened, resulting in the inclusion of 5 articles with 938 eligible subjects. Eight studies were included in the meta-analysis after bias exclusion. The meta-analysis, after bias exclusion, demonstrated that promoting ferroptosis could increase cancer patients' overall survival (HR 0.31, 95% CI 0.21-0.44) and progression-free survival (HR 0.26, 95% CI 0.16-0.44) compared to ferroptosis inhibition. The results showed moderate heterogeneity, suggesting that biological activities promoting cancer cell ferroptosis are beneficial for cancer patient's prognosis. CONCLUSIONS: This systematic review and meta-analysis demonstrated that the promotion of ferroptosis yields substantial benefits for cancer prognosis. These findings underscore the untapped potential of ferroptosis as an innovative anti-tumor therapeutic strategy, capable of addressing challenges related to drug resistance, limited therapeutic efficacy, and unfavorable prognosis in cancer treatment. REGISTRATION: CRD42023463720.

Identification of selective inhibitors of cancer stem cells by high-throughput screening.

Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs.

The Role of MicroRNA-206 in the Regulation of Diabetic Wound Healing via Hypoxia-Inducible Factor 1-Alpha.

Successful wound healing in diabetic patients is hindered by dysregulated miRNA expression. This study aimed to investigate the abnormal expression of miRNAs in diabetic wound healing and the potential therapeutic role of modulating the miR-206/HIF-1α pathway. MicroRNA assays were used to identify differentially expressed miRNAs in diabetic wound sites and adjacent areas. In vitro models and a rat diabetic model were established to evaluate the effects of miR-206 on HIF-1α regulation and wound healing. The study revealed differential expression of miR-206 in diabetic wound tissues, its interaction with HIF-1α, and the inhibitory effect of miR-206 on cell growth under high glucose conditions. Modulating the miR-206/HIF-1α pathway using miR-206 antagomir promoted HIF-1α, CD34, and VEGF expression, ultimately enhancing diabetic wound healing.

Track Irregularity Identification Method of High-Speed Railway Based on CNN-Bi-LSTM.

Track smoothness has become an important factor in the safe operation of high-speed trains. In order to ensure the safety of high-speed operations, studies on track smoothness detection methods are constantly improving. This paper presents a track irregularity identification method based on CNN-Bi-LSTM and predicts track irregularity through car body acceleration detection, which is easy to collect and can be obtained by passenger trains, so the model proposed in this paper provides an idea for the development of track irregularity identification method based on conventional vehicles. The first step is construction of the data set required for model training. The model input is the car body acceleration detection sequence, and the output is the irregularity sequence of the same length. The fluctuation trend of the irregularity data is extracted by the HP filtering (Hodrick Prescott Filter) algorithm as the prediction target. The second is a prediction model based on the CNN-Bi-LSTM network, extracting features from the car body acceleration data and realizing the point-by-point prediction of irregularities. Meanwhile, this paper proposes an exponential weighted mean square error with priority inner fitting (EIF-MSE) as the loss function, improving the accuracy of big value data prediction, and reducing the risk of false alarms. In conclusion, the model is verified based on the simulation data and the real data measured by the high-speed railway comprehensive inspection train.

Assessing biomarkers for post-surgical wound healing: A meta-analysis of exosome-based CircRNA in breast cancer recovery.

To evaluate the diagnostic potential of exosome-based circular RNAs (circRNAs) as biomarkers for wound healing in patients after breast cancer surgery, we conducted a comprehensive meta-analysis of studies that measured exosome-based circRNA levels in breast cancer patients post-surgery. Data sources included several biomedical databases up to April 2023. Two independent reviewers extracted the data and assessed study quality. Sensitivity, specificity and diagnostic odds ratios were synthesized using random-effects model with subgroup analyses performed based on study characteristics. Seventeen studies met the inclusion criteria, encompassing a total of 1234 patients. The pooled sensitivity and specificity of exosome-based circRNA for detecting wound healing complications were 0.85 (95% CI: 0.77-0.91) and 0.83 (95% CI: 0.78-0.88), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.90, indicating high diagnostic accuracy. Subgroup analyses revealed that diagnostic performance was consistent across studies of different geographic regions and sample types but indicated potential variability related to patient age and study design. Exosome-based circRNA profiles exhibited the high diagnostic accuracy for monitoring wound healing in breast cancer post-operative care. These findings supported the potential utility of circRNA as non-invasive biomarkers for post-surgical recovery. However, variability among studies suggested the need for standardized protocols in biomarker measurement. Future research should focus on longitudinal studies to validate the prognostic value of these biomarkers and investigate their role in personalized patient management.

MOF-derived NiCo-LDH Nanocages on CuO Nanorod Arrays for Robust and High Energy Density Asymmetric Supercapacitors.

Layered double hydroxide (LDH) is widely explored in supercapacitors on account of its high capacity, adjustable composition and easy synthesis process. Unfortunately, solitary LDH still has great limitations as an electrode material due to its shortcomings, such as poor conductivity and easy agglomeration. Herein, nanoflakes assembled NiCo-LDH hollow nanocages derived from a metal-organic framework (MOF) precursor are strung by CuO nanorods formed from etching and oxidation of copper foam (CF), forming hierarchical CuO@NiCo-LDH heterostructures. The as-synthesized CuO@NiCo-LDH/CF shows a large capacitance (5607 mF cm-2 at 1 mA cm-2 ), superior rate performance (88.3 % retention at 10 mA cm-2 ) and impressive cycling durability (93.1 % capacitance is retained after 5000 cycles), which is significantly superior to control CuO/CF, CuO@ZIF-67/CF, NiCo-LDH/CF and Cu(OH)2 @NiCo-LDH/CF electrodes. Besides, an asymmetrical supercapacitor consists of CuO@NiCo-LDH/CF and activated carbon displays a maximum energy density of 47.3 Wh kg-1 , and its capacitance only declines by 6.8 % after 10000 cycles, demonstrating remarkable cycling durability. The advantages of highly conductive and robust CuO nanorods, MOF-derived hollow structure and the core-shell heterostructure contribute to the outstanding electrochemical performance. This synthesis strategy can be extended to design various core-shell heterostructures adopted in versatile electrochemical energy storage applications.

OTUB2 promotes the progression of endometrial cancer by regulating the PKM2-mediated PI3K/AKT signaling pathway.

Endometrial carcinoma (EC) morbidity and mortality have been increasing in recent years. Otubain 2 (OTUB2) was shown to be upregulated in EC patients, so the aim of this study was to explore the role of OTUB2 in EC. Cell Counting Kit-8 (CCK-8), colony formation, enzyme-linked immunosorbent assay, the wound healing assay, and Transwell invasion assays were used to investigate the specific role of OTUB2 in EC tumorigenesis. Real-time polymerase chain reaction and western blot analysis were used to detect the expression of OTUB2 in EC tissues and cells. OTUB2 is upregulated in EC patients and cell lines and is associated with a poor prognosis. The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells. The silencing of OTUB2 had the opposite effect. In addition, the silencing of OTUB2 significantly suppressed the expression levels of PKM2. Importantly, inhibition of the PKM2/PI3K/AKT signaling pathway significantly reversed the promoting effect of OTUB2 overexpression on EC. OTUB2 regulated the proliferation and invasion of EC cells by regulating the PKM2/PI3K/AKT signaling pathway. OTUB2 may serve as a potential prognostic and therapeutic target in EC.

Sulfur Vacancy-Engineered Co3S4/MoS2-Interfaced Nanosheet Array for Enhanced Alkaline Overall Water Splitting.

Electrochemical water splitting, a crucial reaction for renewable energy storage, demands highly efficient and stable catalysts. Defect and interface engineering has been widely acknowledged to play a pivotal role in improving electrocatalytic performance. Herein, we demonstrate a facile strategy to construct sulfur vacancy (Sv)-engineered Co3S4/MoS2-interfaced nanosheet arrays to modulate the interface electronic structure in situ reduction with NaBH4. The abundant sulfur vacancies and well-arranged nanosheet arrays in Sv-Co3S4/MoS2 lead to pronounced electrocatalytic properties for hydrogen and oxygen evolution reactions (HER/OER) in an alkaline medium, with observed overpotentials of 156 and 209 mV at 10 mA cm-2, respectively. Additionally, as a bifunctional electrocatalyst, Sv-Co3S4/MoS2 requires a cell voltage of 1.67 V at 10 mA cm-2 for overall water splitting and exhibits long-term stability with activity sustained for more than 20 h. This study provides a novel approach to producing transition metal compound-interfaced electrocatalysts with rich vacancies under mild conditions, showcasing their potential for efficient water splitting applications.

Rapid Amorphization in MOF/Metal Selenite Nanocomposites for Enhanced Capacity in Supercapacitors.

MOF/inorganic nanocomposites combine the advantages of each component. Herein, two MOF/metal selenite nanocomposites, Co-NH2-BDC/CoSeO3·H2O and Co-BDC/CoSeO3·H2O, are prepared on nickel foam through a facile two-step hydrothermal method, which inherit the 2D morphology and porosity properties of their MOF precursors. Furthermore, during the electrochemical activation process, the crystallized nanocomposites can easily transform into amorphous structures in a short time of 20 min in the presence of an electric field, similar to CoSeO3·H2O. Due to amorphization, the electrochemical performance of the two nanocomposites is much enhanced relative to that of their MOF precursors. Specifically, the areal capacitances of Co-NH2-BDC/CoSeO3·H2O and Co-BDC/CoSeO3·H2O are 5.35 and 10.65 F·cm-2 at 2 mA·cm-2, respectively. The assembled asymmetric supercapacitor (ASC) using Co-NH2-BDC/CoSeO3·H2O as positive electrodes delivers an energy density of 0.207 mWh·cm-2 at a power density of 0.799 mW·cm-2 with outstanding cycling stability (93% capacity retention after 5000 cycles). Using Co-BDC/CoSeO3·H2O as positive electrodes, the ASC can reach a high energy density of 0.483 mWh·cm-2 at a power density of 0.741 mW·cm-2 and 84% capacity retention after 5000 cycles. This work provides an efficient strategy for constructing MOF/metal selenite nanocomposites for energy storage and conversion.

Zeolitic Imidazolate Framework-Derived Zn/Co-S@Ni(OH)2 Nanoarrays with Excellent Energy Storage and Electrocatalytic Performance.

The design and development of high-performance electrochemical electrode materials are crucial for energy storage and conversion systems. This work reports a facile preparation of a self-supported Zn/Co-S@Ni(OH)2 array electrode in which a Zn/Co-S nanosheet is derived from a leaf-like zeolitic imidazolate framework (Zn/Co-ZIF-L). The core-shell structure provides multiple benefits such as enhanced electrical conductivity, an abundance of exposed active sites, and strong electronic interactions between Zn/Co-S and ultra-thin Ni(OH)2 nanosheets, facilitating faster charge transfer. Consequently, Zn/Co-S@Ni(OH)2 demonstrates remarkable electrochemical characteristics as an electrode material for supercapacitors with an area capacitance of 12.9 F cm-2 at a current density of 2 mA cm-2 in 2 M KOH. The assembled asymmetric supercapacitor device achieves a high energy density of 0.95 mW h cm-2, while showing excellent longevity with a retention of 90.9% over 5000 cycles. Additionally, the Zn/Co-S@Ni(OH)2 arrays demonstrate significant oxygen evolution reaction activity with an overpotential of 242 mV at 10 mA cm-2 in 1 M KOH and significant stability for more than 100 h. This work provides a valuable approach for synthesizing bifunctional electrode materials for both energy storage and electrocatalysis applications.

Electron-Redistributed NiCo@NiFe-LDH Core-Shell Heterostructure for Significantly Enhancing Electrochemical Water Splitting.

Layered double hydroxides (LDHs) are some of the most promising precursors for the development of economically stable and efficient electrocatalysts for water splitting. An effective strategy for designing excellent performance electrocatalysts is to assemble core-shell heterostructures with a tunable electronic structure. In this work, three core-shell heterostructure electrocatalysts (NiCo@NiFe-LDH100/150/200) are developed by a simple hydrothermal and subsequent electrodeposition method on Ni foam. Among them, NiCo@NiFe-LDH150/NF exhibits the best oxygen evolution reaction electrocatalytic activity and long-term stability with a low overpotential of 197 mV to deliver a current density of 10 mA cm-2. In addition, an efficient and stable alkaline electrolytic cell with NiCo@NiFe-LDH150/NF both as the cathode and anode achieves a voltage of 1.66 V at a current density of 10 mA cm-2 and realization of ultralong stability at current densities of 20 and 200 mA cm-2 for 200 h. Density functional theory calculations reveal the strong electron interaction at the heterogeneous interface of the NiCo@NiFe-LDH150/NF core-shell structure, which effectively improves the intrinsic electron conductivity and ion diffusion kinetics and makes an important contribution to the electrocatalytic performance of the material. This work provides a new idea for the selection of materials for electrochemical water splitting by the construction of heterojunction interfaces.

Microfabrication of peptide self-assemblies: inspired by nature towards applications.

Peptide self-assemblies show intriguing and tunable physicochemical properties, and thus have been attracting increasing interest over the last two decades. However, the micro/nano-scale dimensions of the self-assemblies severely restrict their extensive applications. Inspired by nature, to genuinely realize the practical utilization of the bio-organic super-architectures, it is beneficial to further organize the peptide self-assemblies to integrate the properties of the individual supermolecules and fabricate higher-level organizations for smart functional devices. Therefore, cumulative studies have been reported on peptide microfabrication giving rise to diverse properties. This review summarizes the recent development of the microfabrication of peptide self-assemblies, discussing each methodology along with the diverse properties and practical applications of the engineered peptide large-scale, highly-ordered organizations. Finally, the current limitations of the state-of-the-art microfabrication strategies are critically assessed and alternative solutions are suggested.

MOF-Derived Iron-Cobalt Bimetallic Selenides for Water Electrolysis with High-Efficiency Oxygen Evolution Reaction.

Highly active and stable oxygen evolution reaction (OER) electrocatalysts for water electrolysis are currently in high demand. Herein, a rationally designed three-dimensional (3D) CoFe selenide porous array (Fe-CoSe PA) is synthesized through ion exchange from zeolitic imidazolate framework-L (ZIF-L) nanoarray, followed by a facile selenization under hydrothermal conditions for OER electrocatalysis. During the OER process, the surface of Fe-CoSe PA is rapidly oxidized to CoFe oxides/hydroxides, which prevents the inner layer from being oxidized. Benefiting from the high porosity, abundant active sites, and the high conductivity of inner Fe-CoSe, Fe-CoSe PA exhibits excellent OER performance, with an overpotential of 285 mV at a current density of 10 mA cm-2, and a small Tafel slope of 68 mV dec-1, as well as high stability under 50 h of continuous testing. The present work could provide a facile route for fabricating 3D porous selenides for highly efficient OER catalysis.

Assembly of Metal-Organic Frameworks on Transition Metal Phosphides as Self-Supported Electrodes for High-Performance Hybrid Supercapacitors.

In this work, the composite electrode composed of metal-organic frameworks and transition metal phosphides is first assembled on the nickel foam substrate. The as-prepared NiCo-MOF-74@Ni12P5/NF exhibits excellent performances with ultrahigh specific capacitance (12.8 F/cm2 at 1 mA/cm2), stable charge-discharge rate (82.8%), and excellent cycling stability (reserve 73.90% after 5000 charge and discharge cycles at 30 mA/cm2), which are better than those of NiCo-MOF-74@NF without phosphating treatment of nickel foam. The corresponding hybrid supercapacitor (SC) device (NiCo-MOF-74@Ni12P5/NF//AC) delivers high storage capability (44.33 W·h/kg at 800 W/kg) and distinguished operating durability (83.04% after 5000 cycles). In addition, an all-solid-state hybrid SC successfully lit the LED for more than 2 min, which means that there is viable potential for practical applications in energy storage. The improved electrical properties are mainly due to the 3D heterostructure, the positive cooperative binding of nickel and cobalt elements, and the excellent electrical conductivity of the phosphide. As a result, this study proves the possibility of practical applications of NiCo-MOF-74@Ni12P5/NF electrodes for energy storage in hybrid SCs.

Controllable In Situ Transformation of Layered Double Hydroxides into Ultrathin Metal-Organic Framework Nanosheet Arrays for Energy Storage.

Ultrathin two-dimensional metal-organic frameworks (MOFs) have convincing performances in energy storage, which can be put down to their accessible active sites with rapid charge transfer. Herein, NiCo-layered double hydroxide (LDH) nanosheet arrays are used as self-sacrificial templates to in situ fabricate ultrathin NiCo-MOF nanosheet arrays on Ni foam (NS/NF) by using organic ligands without adding metal sources. Two ultrathin MOF nanosheets with different ligands, terephthalate (BDC) and 2-aminoterephthalate (NH2-BDC), are synthesized, characterized, and discussed in detail. Specifically, NiCo-NH2-BDC-MOF NS/NF exhibits the best electrochemical performance as a battery-type electrode for supercapacitors, achieves an areal capacitance of 12.13 F cm-2 at a current density of 2 mA cm-2, and retains the original capacitance of 73.08 % after 5000 cycles at a current density of 50 mA cm-2. Furthermore, when NiCo-NH2-BDC-MOF NS/NF is assembled with activated carbon (AC) to form an asymmetric supercapacitor (ASC), an energy density of 0.81 mWh cm-2 can be provided at a power density of 1.60 mW cm-2. These results offer an effective and controllable synthetic strategy to in situ prepare ultrathin MOF nanosheet arrays with different ligands and metal ions from LDH precursors.

Controllable Transformation of Metal-Organic Framework Nanosheets into Oxygen Vacancy NixCo3-xO4 Arrays for Ultrahigh-Capacitance Supercapacitors with Long Lifespan.

The amino-functionalized bimetal NH2-NiCo-MOF nanosheet array is first fabricated on Ni foam substrates and then controllably transformed into oxygen vacancy bimetal oxide arrays by simply thermal annealing in air. This NiCo-based oxide array (NixCo3-xO4/NF) achieves high capacitance (2484 F g-1 at 1 A g-1), excellent rate performance (91.4%), and long cycling life when assessed as promising electrode material for supercapacitors. Notably, the existing oxygen vacancy in NixCo3-xO4 promotes the electrochemical performance of NixCo3-xO4/NF due to the enhancement of electrical conductivity and capture capability for OH-. In addition, the assembled asymmetric supercapacitor (ASC) device exhibits an excellent energy density of 39.3 W h kg-1 at a power density of 800.2 W kg-1, which still remains 32.2 W h kg-1 even at a high power density of 7994.5 W kg-1. Furthermore, a light-emitting diode can be lightened for more than 6 min, demonstrating a great potential for practical application of ASC devices. This work knocks on the door of a feasible strategy for designing and synthesizing 2D metal oxide nanosheet arrays with excellent electrochemical properties.

Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression.

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.