Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.

BACKGROUND: Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive. METHODS: KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines. RESULTS: In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients. CONCLUSION: We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

Crosstalk between lipid metabolism and EMT: emerging mechanisms and cancer therapy.

Lipids are the key component of all membranes composed of a variety of molecules that transduce intracellular signaling and provide energy to the cells in the absence of nutrients. Alteration in lipid metabolism is a major factor for cancer heterogeneity and a newly identified cancer hallmark. Reprogramming of lipid metabolism affects the diverse cancer phenotypes, especially epithelial-mesenchymal transition (EMT). EMT activation is considered to be an essential step for tumor metastasis, which exhibits a crucial role in the biological processes including development, wound healing, and stem cell maintenance, and has been widely reported to contribute pathologically to cancer progression. Altered lipid metabolism triggers EMT and activates multiple EMT-associated oncogenic pathways. Although the role of lipid metabolism-induced EMT in tumorigenesis is an attractive field of research, there are still significant gaps in understanding the underlying mechanisms and the precise contributions of this interplay. Further study is needed to clarify the specific molecular mechanisms driving the crosstalk between lipid metabolism and EMT, as well as to determine the potential therapeutic implications. The increased dependency of tumor cells on lipid metabolism represents a novel therapeutic target, and targeting altered lipid metabolism holds promise as a strategy to suppress EMT and ultimately inhibit metastasis.

Spontaneous formation of multilayer refractory carbide coatings in a molten salt media.

Refractory materials hold great promise to develop functional multilayer coating for extreme environments and temperature applications but require high temperature and complex synthesis to overcome their strong atomic bonding and form a multilayer structure. Here, a spontaneous reaction producing sophisticated multilayer refractory carbide coatings on carbon fiber (CF) is reported. This approach utilizes a relatively low-temperature (950 °C) molten-salt process for forming refractory carbides. The reaction of titanium (Ti), chromium (Cr), and CF yields a complex, high-quality multilayer carbide coating composed of 1) Cr carbide (Cr3C2), 2) Ti carbide, and 3) Cr3C2 layers. The layered sequence arises from a difference in metal dissolutions, reactions, and diffusion rates in the salt media. The multilayer-coated CFs act as a permeable oxidation barrier with no crystalline degradation of the CFs after extreme temperature (1,200 °C) and environment (oxyacetylene flame) exposure. The synthesis of high-quality multilayer refractory coating in a fast, efficient, easy, and clean manner may answer the need for industrial applications that develop cheap and reliable extreme environment protection barriers.

Cancer and stress: NextGen strategies.

Chronic stress is well-known to cause physiological distress that leads to body balance perturbations by altering signaling pathways in the neuroendocrine and sympathetic nervous systems. This increases allostatic load, which is the cost of physiological fluctuations that are required to cope with psychological challenges as well as changes in the physical environment. Recent studies have enriched our knowledge about the role of chronic stress in disease development, especially carcinogenesis. Stress stimulates the hypothalamic-pituitaryadrenal (HPA) axis and the sympathetic nervous system (SNS), resulting in an abnormal release of hormones. These activate signaling pathways that elevate expression of downstream oncogenes. This occurs by activation of specific receptors that promote numerous cancer biological processes, including proliferation, genomic instability, angiogenesis, metastasis, immune evasion and metabolic disorders. Moreover, accumulating evidence has revealed that ß-adrenergic receptor (ADRB) antagonists and downstream target inhibitors exhibit remarkable anti-tumor effects. Psychosomatic behavioral interventions (PBI) and traditional Chinese medicine (TCM) also effectively relieve the impact of stress in cancer patients. In this review, we discuss recent advances in the underlying mechanisms that are responsible for stress in promoting malignancies. Collectively, these data provide approaches for NextGen pharmacological therapies, PBI and TCM to reduce the burden of tumorigenesis.

[Study on liver diseases with zebrafish as an important tool].

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.

MicroRNA-29b-3p suppresses oral squamous cell carcinoma cell migration and invasion via IL32/AKT signalling pathway.

Oral squamous cell carcinoma (OSCC) is aggressive accompanied with poor prognosis. We previously isolated the most invasive cells resembling the invasive tumour front by microfluidic technology and explored their differentially expressed microRNAs (miRNAs) in our previous work. Here, we verified the miR-29b-3p as a guarder that suppressed migration and invasion of OSCC cells and was down-regulated in the most invasive cells. Besides that, the invasion suppression role of miR-29b-3p was achieved through the IL32/AKT pathway. Thus, miR-29b-3p and IL32 might serve as therapeutic targets for blocking the progression and improving the outcome of OSCC.

Anisotropic Enhancement of Second-Harmonic Generation in Monolayer and Bilayer MoS2 by Integrating with TiO2 Nanowires.

The ability to design and enhance the nonlinear optical responses in two-dimensional (2D) transition-metal dichalcogenides (TMDCs) is both of fundamental interest and highly desirable for developing TMDC-based nonlinear optical applications, such as nonlinear convertors and optical modulators. Here, we report for the first time a strong anisotropic enhancement of optical second-harmonic generation (SHG) in monolayer molybdenum disulfide (MoS2) by integrating with one-dimensional (1D) titanium dioxide nanowires (NWs). The SHG signal from the MoS2/NW hybrid structures is over 2 orders of magnitude stronger than that in the bare monolayer MoS2. Polarized SHG measurements revealed a giant anisotropy in SHG response of the MoS2/NW hybrid. The pattern of the anisotropic SHG depends highly on the stacking angle between the nanowire direction and the MoS2 crystal orientation, which is attributed to the 1D NW-induced directional strain fields in the layered MoS2. A similar effect has also been observed in bilayer MoS2/NW hybrid structure, further proving the proposed scenario. This work provides an effective approach to selectively and directionally designing the nonlinear optical response of layered TMDCs, paving the way for developing high-performance, anisotropic nonlinear photonic nanodevices.

A Facile Space-Confined Solid-Phase Sulfurization Strategy for Growth of High-Quality Ultrathin Molybdenum Disulfide Single Crystals.

Single-crystal transition metal dichalcogenides (TMDs) and TMD-based heterojunctions have recently attracted significant research and industrial interest owing to their intriguing optical and electrical properties. However, the lack of a simple, low-cost, environmentally friendly, synthetic method and a poor understanding of the growth mechanism post a huge challenge to implementing TMDs in practical applications. In this work, we developed a novel approach for direct formation of high-quality, monolayer and few-layer MoS2 single crystal domains via a single-step rapid thermal processing of a sandwiched reactor with sulfur and molybdenum (Mo) film in a confined reaction space. An all-solid-phase growth mechanism was proposed and experimentally/theoretically evidenced by analyzing the surface potential and morphology mapping. Compared with the conventional chemical vapor deposition approaches, our method involves no complicated gas-phase reactant transfer or reactions and requires very small amount of solid precursors [e.g., Mo (∼3 µg)], no carrier gas, no pretreatment of the precursor, no complex equipment design, thereby facilitating a simple, low-cost, and environmentally friendly growth. Moreover, we examined the symmetry, defects, and stacking phase in as-grown MoS2 samples using simultaneous second-harmonic-/sum-frequency-generation (SHG/SFG) imaging. For the first time, we observed that the SFG (peak intensity/position) polarization can be used as a sensitive probe to identify the orientation of TMDs' crystallographic axes. Furthermore, we fabricated ferroelectric programmable Schottky junction devices via local domain patterning using the as-grown, single-crystal monolayer MoS2, revealing their great potential in logic and optoelectronic applications. Our strategy thus provides a simple, low-cost, and scalable path toward a wide variety of TMD single crystal growth and novel functional device design.

Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer.

BACKGROUND/AIMS: Cancer stem cells (CSCs) are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. METHODS: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. RESULTS: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. CONCLUSION: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.

cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria.

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na(+)-K(+)-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 µmol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 (3.0 µmol/L), an inhibitor for reverse mode of Na(+)-Ca(2+) exchangers (NCX), but did not by L-type Ca(2+) channel blocker nifedipine (1.0 µmol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 µmol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 µmol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 µmol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 µmol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

SOX1 down-regulates ß-catenin and reverses malignant phenotype in nasopharyngeal carcinoma.

BACKGROUND: Aberrant activation of the Wnt/ß-catenin signaling pathway is an important factor in the development of nasopharyngeal carcinoma (NPC). Previous studies have demonstrated that the developmental gene sex-determining region Y (SRY)-box 1 (SOX1) inhibits cervical and liver tumorigenesis by interfering with the Wnt/ß-catenin signaling pathway. However, the role of SOX1 in NPC remains unclear. This study investigates the function of SOX1 in NPC pathogenesis. RESULTS: Down-regulation of SOX1 was detected in NPC cell lines and tissues. Besides, quantitative methylation-specific polymerase chain reaction revealed that SOX1 promoter was hypermethylated in NPC cell lines. Ectopic expression of SOX1 in NPC cells suppressed colony formation, proliferation and migration in vitro and impaired tumor growth in nude mice. Restoration of SOX1 expression significantly reduced epithelial-mesenchymal transition, enhanced cell differentiation and induced cellular senescence. Conversely, transient knockdown of SOX1 by siRNA in these cells partially restored cell proliferation and colony formation. Notably, SOX1 was found to physically interact with ß-catenin and reduce its expression independent of proteasomal activity, leading to inhibition of Wnt/ß-catenin signaling and decreased expression of downstream target genes. CONCLUSIONS: SOX1 decreases the expression of ß-catenin in a proteasome-independent manner and reverses the malignant phenotype in NPC cells.

Synthesis and positive inotropic evaluation of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted piperazine moieties.

Four series of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted piperazine moieties were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume in isolated rabbit-heart preparations. Several compounds were developed and showed favorable activities compared to the standard drug milrinone, with (4-([1,2,4]triazolo[3,4-a]phthalazin-6-yl)piperazin-1-yl)(p-tolyl)methanone (5g) being identified as the most potent with an increased stroke volume of 19.15±0.22% (milrinone: 2.46±0.07%) at a concentration of 3×10(-5) M. A preliminary study of mechanism of action revealed that 5g displayed its positive inotropic effect may be related to the PDE-cAMP-PKA signaling pathway. Compounds exhibiting inotropic effects were also evaluated in terms of the chronotropic effects.

Robot-assisted internal fixation of calcaneal fractures versus conventional open reduction internal fixation: a systematic review and meta-analysis.

The aim of the study was to compare the efficacy and safety of robot-assisted (RA) percutaneous hollow screw fixation with traditional open reduction internal fixation (ORIF) for the treatment of calcaneal fractures through a systematic review and meta-analysis. An extensive search was conducted in the following databases-PubMed, CNKI, Embase, and the Cochrane Library-to gather research on patients with calcaneal fractures published up to July 2024. This search focuses on studies comparing the effectiveness of robot-assisted percutaneous cannulated screw fixation versus ORIF. We will include studies published in both English and Chinese. Our screening process adhered strictly to predefined inclusion and exclusion criteria, emphasizing randomized controlled trials (RCTs) and cohort studies. The ROBINS-I tool was utilized to evaluate the risk of bias in non-randomized studies. Meta-analysis was conducted using Review Manager 5.4.1. The final analysis incorporated six retrospective cohort studies comprising 247 patients-122 treated with robotic-assisted percutaneous cannulated screw fixation and 125 with conventional open reduction and internal fixation. The findings indicated that patients undergoing robotic-assisted percutaneous cannulated screw fixation experienced advantages over those receiving conventional treatment in terms of reduced hospital stay, lower estimated blood loss, and higher AOFAS scores at both 3 and 6 months. No statistically significant differences were observed between the two methods concerning operative time, fracture healing duration, or the frequency of intraoperative fluoroscopies. Robotic-assisted percutaneous cannulated screw fixation is a safe and viable treatment approach for patients with calcaneal fractures. When compared to ORIF methods, this robotic-assisted technique demonstrated significant benefits, including reduced hospital stay, lower estimated blood loss, and improved AOFAS scores at both 3 and 6 months.

The impact of information presentation on self-other risk decision-making.

To explore the impact of social distance and information presentation types on self-other risk preferences in monetary tasks. Risk preferences were examined in decision-making tasks and experiential information tasks within different frameworks when participants made decisions for themselves and others. Experiment 1 employed experiential decision tasks and revealed individual differences in decision-making for oneself and others. In gain situations, participants exhibited more risk aversion when deciding for others compared to themselves. Experiment 2 presented both types of information simultaneously to investigate whether risk decisions for oneself and others are influenced by information types. Results indicated that experiential information led participants to make more conservative choices for others, while descriptive information eliminated this effect. This study discovered the influence of social distance on self-other risk decisions and the role of information presentation types in self and other risk decision-making. Future research could further explore self-other decision-making from the perspectives of decision-makers' traits and culture.

Oncogenic fatty acid oxidation senses circadian disruption in sleep-deficiency-enhanced tumorigenesis.

Circadian disruption predicts poor cancer prognosis, yet how circadian disruption is sensed in sleep-deficiency (SD)-enhanced tumorigenesis remains obscure. Here, we show fatty acid oxidation (FAO) as a circadian sensor relaying from clock disruption to oncogenic metabolic signal in SD-enhanced lung tumorigenesis. Both unbiased transcriptomic and metabolomic analyses reveal that FAO senses SD-induced circadian disruption, as illustrated by continuously increased palmitoyl-coenzyme A (PA-CoA) catalyzed by long-chain fatty acyl-CoA synthetase 1 (ACSL1). Mechanistically, SD-dysregulated CLOCK hypertransactivates ACSL1 to produce PA-CoA, which facilitates CLOCK-Cys194 S-palmitoylation in a ZDHHC5-dependent manner. This positive transcription-palmitoylation feedback loop prevents ubiquitin-proteasomal degradation of CLOCK, causing FAO-sensed circadian disruption to maintain SD-enhanced cancer stemness. Intriguingly, timed ß-endorphin resets rhythmic Clock and Acsl1 expression to alleviate SD-enhanced tumorigenesis. Sleep quality and serum ß-endorphin are negatively associated with both cancer development and CLOCK/ACSL1 expression in patients with cancer, suggesting dawn-supplemented ß-endorphin as a potential chronotherapeutic strategy for SD-related cancer.

MAPK and PI3K pathways regulate hypoxia-induced atrial natriuretic peptide secretion by controlling HIF-1 alpha expression in beating rabbit atria.

Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways are pivotal and intensively studied signaling pathways in hypoxic conditions. However, the roles of MAPK and PI3K in the regulation of hypoxia-induced atrial natriuretic peptide (ANP) secretion are not well understood. The purpose of the present study was to investigate the mechanism by which the MAPK/ERK (extracellular signal-regulated kinase) and PI3K signaling pathways regulate the acute hypoxia-induced ANP secretion in isolated beating rabbit atria. An acute hypoxic perfused beating rabbit atrial model was used. The ANP levels in the atrial perfusates were measured by radioimmunoassay, and the hypoxia-inducible factor-1α (HIF-1α) mRNA and protein levels in the atrial tissue were determined by RT-PCR and Western blot. Acute hypoxia significantly increased ANP secretion and HIF-1α mRNA and protein levels. Hypoxia-induced ANP secretion was markedly attenuated by the HIF-1α inhibitors, rotenone (0.5µmol/L) and CAY10585 (10µmol/L), concomitantly with downregulation of the hypoxia-induced HIF-1α mRNA and protein levels. PD098059 (30µmol/L) and LY294002 (30µmol/L), inhibitors of MAPK and PI3K, markedly abolished the hypoxia-induced ANP secretion and atrial HIF-1α mRNA and protein levels. The hypoxia-suppressed atrial dynamics were significantly attenuated by PD098059 and LY294002. Acute hypoxia in isolated perfused beating rabbit atria, markedly increased ANP secretion through HIF-1α upregulation, which was regulated by the MAPK/ERK and PI3K pathways. ANP appears to be part of the protective program regulated by HIF-1α in the response to acute hypoxic conditions.

Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure.

Central melanocortin 3/4 receptors (MC3/4Rs) are known to regulate energy balance. Activation of MC3/4Rs causes a greater increase in the firing activity of the PVN neurons in obese Zucker rats than in lean Zucker rats. The present study was undertaken to determine the roles of MC3/4Rs in the hypothalamic paraventricular nucleus (PVN) in modulating the sympathetic activity and blood pressure and its downstream pathway. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN increased the RSNA and MAP. The MC3/4R antagonist agouti-related peptide (AgRP) or SHU9119 decreased the RSNA and MAP, but the MC4R antagonist HS024 had no significant effect on the RSNA and MAP. The effects of MTII were abolished by pretreatment of the PVN with AgRP, SHU9119, the adenylate cyclase inhibitor SQ22536 or the protein kinase A inhibitor Rp-cAMP, and substantially attenuated by HS024. Microinjection of SQ22536 alone into the PVN had no significant effect on the RSNA and MAP, but Rp-cAMP caused significant decreases in the RSNA and MAP. Furthermore, MTII increased the cAMP level in the PVN. These results indicate that activation of MC3/4Rs in the PVN increases the sympathetic outflow and blood pressure via the cAMP-protein kinase A pathway. Melanocortin 3 receptors in the PVN may exert a tonic excitatory effect on sympathetic activity.

Co-Ni layered double hydroxides for water oxidation in neutral electrolyte.

The electrochemical properties of Co-Ni layered double hydroxides (LDHs) as efficient electrocatalysts for water oxidation were investigated in potassium phosphate electrolyte under neutral pH condition. The Co-Ni LDHs with a core-shell structure were fabricated using a facile route from a Co-Ni hydroxide precursor with iodine as a topotactic oxidizer. The unique core-shell morphology is likely due to the enrichment of Co(III) hydroxide in the inner core indicated by selected area electron diffraction and energy-dispersive spectroscopy. Through a self-assembling process at the organic/inorganic interface and dip-coating, the Co-Ni LDHs were deposited onto FTO glass substrates to prepare composite electrodes. Low over-potential and high current density was achieved in the oxygen evolution reaction. The excellent electrocatalytic activity of Co-Ni LDHs may be attributed to more accessible Co active sites and rapid movement of interlayer ions within their layered structure.

A mutation in a coproporphyrinogen III oxidase gene confers growth inhibition, enhanced powdery mildew resistance and powdery mildew-induced cell death in Arabidopsis.

KEY MESSAGE: A gene encoding a coproporphyrinogen III oxidase mediates disease resistance in plants by the salicylic acid pathway. A number of genes that regulate powdery mildew resistance have been identified in Arabidopsis, such as ENHANCED DISEASE RESISTANCE 1 to 3 (EDR1 to 3). To further study the molecular interactions between the powdery mildew pathogen and Arabidopsis, we isolated and characterized a mutant that exhibited enhanced resistance to powdery mildew. The mutant also showed dramatic powdery mildew-induced cell death as well as growth defects and early senescence in the absence of pathogens. We identified the affected gene by map-based cloning and found that the gene encodes a coproporphyrinogen III oxidase, a key enzyme in the tetrapyrrole biosynthesis pathway, previously known as LESION INITIATION 2 (LIN2). Therefore, we designated the mutant lin2-2. Further studies revealed that the lin2-2 mutant also displayed enhanced resistance to Hyaloperonospora arabidopsidis (H.a.) Noco2. Genetic analysis showed that the lin2-2-mediated disease resistance and spontaneous cell death were dependent on PHYTOALEXIN DEFICIENT 4 (PAD4), SALICYLIC ACID INDUCTION-DEFICIENT 2 (SID2), and NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), which are all involved in salicylic acid signaling. Furthermore, the relative expression levels of defense-related genes were induced after powdery mildew infection in the lin2-2 mutant. These data indicated that LIN2 plays an important role in cell death control and defense responses in plants.