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circDENND4c, a novel serum marker for epithelial ovarian cancer, acts as a tumor suppressor by downregulating miR-200b/c

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ANNALS OF MEDIcINE 2023年第1期55卷 908-919页

作者： Liu, Shuang Yuan, Limei Li, Jinzhu Liu, Yurong Wang, Haibo Ren, Xingye Fourth Peoples Hosp Jinan Dept Gynecol 50 Shifan Rd Jinan 250000 Shandong Peoples R China Fifth Peoples Hosp Jinan Dept Obstet Jinan Peoples R China

Research objective To explore the diagnostic value of circ-DENN domain containing 4 c (circDENND4c) in epithelial ovarian cancer (EOc) and the corresponding mechanism. Methods We determined the expression of circDENND4c and miR-200b/c in tissues and serum specimens as well as EOc cell lines using qRT-PcR. Basic clinical data, and serum HE4 and cAl25 levels were acquired from patients' clinical records. Expression-related correlations and the diagnostic value of serum circDENND4c in EOc were also estimated. ccK-8 and flow cytometry were performed to detect the effect of circDENND4c on cell proliferation and apoptosis. Results circDENND4c level was lowest while miR-200b/c was highest in EOc tissues, followed by benign and normal tissues. Similarly, serum circDENND4c was lowest while miR-200b/c was highest in EOc patients. Moreover, serum circDENND4c was lower in patients with benign ovarian tumors than in healthy women, while miR-200b/c expression was higher. circDENND4c was negatively associated with miR-200b/c in EOc tissues and serum specimens, and serum circDENND4c was also negatively correlated with serum HE4 and cAl25 in EOc patients. circDENND4c expression in both tissue and serum was negatively related to FIGO and TNM stage, and tumor size in EOc. Serum circDENND4c could distinguish healthy persons from patients with benign ovarian tumors and EOc, and they showed a higher specificity and accuracy than serum cA125 or HE4 in EOc diagnosis. circDENND4c upregulation significantly suppressed EOc cell proliferation and facilitated apoptosis by downregulating miR-200b/c in vitro. conclusions Summarily, circDENND4c acts as a tumor inhibitor by downregulating miR-200b/c in EOc and could be a possible tumor marker for EOc diagnosis. KEY MESSAGES circDENND4c expression was lowest while miR-200b/c was highest in EOc tissues or serums, followed by benign and normal tissues or serums. circDENND4c was involved in malignant progression of EOc, concretely, overexpression of ci

关键词： Apoptosis circDENND4c miR-200b c diagnosis epithelial ovarian cancer proliferation

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Temperature acclimation: Temperature shift induces system conversion to cold tolerance in c. elegans

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NEUROScIENcE RESEARcH 2023年第1期194卷 1-6页

作者： Ohta, Akane Yamashiro, Serina Kuhara, Atsushi Konan Univ Grad Sch Nat Sci Kobe 6588501 Japan Konan Univ Fac Sci & Engn Kobe 6588501 Japan Konan Univ Inst Integrat Neurobiol Kobe 6588501 Japan Japan Agcy Med Res & Dev AMED PRIME Tokyo 1000004 Japan

Acclimation to temperature is one of the survival strategies used by organisms to adapt to changing environ-mental temperatures. caenorhabditis elegans' cold tolerance is altered by previous cultivation temperature, and similarly, past low-temperature induces a longer lifespan. Temperature is thought to cause a large shift in ho-meostasis, lipid metabolism, and reproduction in the organism because it is a direct physiological factor during chemical events. This paper will share and discuss what we know so far about the neural and molecular mechanisms that control cold tolerance and lifespan by altering lipid metabolism and physiological character-istics. We hope that this will contribute to a better understanding of how organisms respond to temperature changes.

关键词： c elegans Temperature acclimation cold tolerance Neuroendocrine signaling Lipid metabolism

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Neural mechanism of experience-dependent sensory gain control in c. elegans

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NEUROScIENcE RESEARcH 2023年 191卷 77-90页

作者： Ikejiri, Yosuke Tanimoto, Yuki Fujita, Kosuke Hiramatsu, Fumie Yamazaki, Shuhei J. Endo, Yuto Iwatani, Yasushi Fujimoto, Koichi Kimura, Koutarou D. Nagoya City Univ Grad Sch Sci Dept Informat & Basic Sci Nagoya Aichi 4678501 Japan Osaka Univ Grad Sch Sci Dept Biol Sci Toyonaka Osaka 5600043 Japan Hirosaki Univ Grad Sch Sci & Technol Dept Sci & Technol Hirosaki Aomori 0368561 Japan Nagoya City Univ Grad Sch Sci Nagoya 4678501 Japan RIKEN Ctr Brain Sci Wako Saitama 3510106 Japan Nagoya Univ Dept Ophthalmol Grad Sch Med Nagoya Aichi 4668550 Japan Max Planck Inst Neurobiol Behav Caesar D-53175 Bonn Germany

Animals' sensory systems adjust their responsiveness to environmental stimuli that vary greatly in their intensity. Here we report the neural mechanism of experience-dependent sensory adjustment, especially gain control, in the ASH nociceptive neurons in caenorhabditis elegans. Using calcium imaging under gradual changes in stimulus intensity, we find that the ASH neurons of naive animals respond to concentration increases in a repulsive odor 2nonanone regardless of the magnitude of the concentration increase. However, after preexposure to the odor, the ASH neurons exhibit significantly weak responses to a small gradual increase in odor concentration while their responses to a large gradual increase remain strong. Thus, preexposure changes the slope of stimulus-response relationships (i.e., gain control). Behavioral analysis suggests that this gain control contributes to the preexposure-dependent enhancement of odor avoidance behavior. Mathematical analysis reveals that the ASH response consists of fast and slow components, and that the fast component is specifically suppressed by preexposure for the gain control. In addition, genetic analysis suggests that G protein signaling may be required for the regulation of fast component. We propose how prior experience dynamically and specifically modulates stimulus-response relationships in sensory neurons, eventually leading to adaptive modulation of behavior.

关键词： Gain control Mathematical model Sensory signaling calcium imaging c elegans

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Genetic characterization of c. elegans TMED genes

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DEVELOPMENTAL DYNAMIcS 2023年第9期252卷 1149-1161页

作者： Navarro, Kristen G. G. chamberlin, Helen M. M. Ohio State Univ Dept Mol Genet 484 W 12th Ave Columbus OH 43210 USA

Backgroundp24/transmembrane Emp24 domain (TMED) proteins are a set of evolutionarily conserved, single pass transmembrane proteins that have been shown to facilitate protein secretion and selection of cargo proteins to transport vesicles in the cellular secretion pathway. However, their functions in animal development are incompletely understood. ResultsThe c. elegans genome encodes eight identified TMED genes, with at least one member from each defined subfamily (alpha, beta, gamma, delta). TMED gene mutants exhibit a shared set of defects in embryonic viability, animal movement, and vulval morphology. Two gamma subfamily genes, tmed-1 and tmed-3, exhibit the ability to compensate for each other, as defects in movement and vulva morphology are only apparent in double mutants. TMED mutants also exhibit a delay in breakdown of basement membrane during vulva development. conclusionsThe results establish a genetic and experimental framework for the study of TMED gene function in c. elegans, and argue that a functional protein from each subfamily is important for a shared set of developmental processes. A specific function for TMED genes is to facilitate breakdown of the basement membrane between the somatic gonad and vulval epithelial cells, suggesting a role for TMED proteins in tissue reorganization during animal development.

关键词： basement membrane breakdown c elegans ER Golgi protein transport p24 complex transmembrane Emp24 domain proteins

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Effect of MnO content on the Oxygen Reduction Activity of MnO/c Nanostructures

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ELEcTROcATALYSIS 2023年第5期14卷 788-799页

作者： Mishra, Vineet Mohapatra, Biswaranjan D. Ghosh, Tapan Kumar Rao, G. Ranga Indian Inst Technol Madras Dept Chem Chennai 600036 India Indian Inst Technol Madras DST Solar Energy Harnessing Ctr Chennai 600036 India

Manganese oxide based materials are considered as alternate non-noble metal electrocatalysts for oxygen reduction reaction (ORR). These materials possess rich redox chemistry and can decompose hydrogen peroxide disproportionately to drive the oxygen reduction towards efficient 4-electron pathway. In this work, a set of MnO nanostructures supported on activated charcoal (MnO/c) with varying MnO loadings are prepared by ball milling followed by in-situ pyrolysis. The MnO/c composites are tested for ORR activity by employing cyclic voltammetry and linear sweep voltammetry using rotating-ring disk electrode (RRDE) in 0.1 M KOH. The results indicate that the ORR activity as well as catalytic pathways are sensitive to MnO loading. The ORR activities of the composites follow volcano type relationship with the quantity of MnO loadings. The role of MnO loading on surface morphology, hydrophilicity, electrochemical double layer capacitance (c-dl) and electrochemical active surface area (EcSA) of the composites has been investigated and correlated with ORR activity. Among the MnO electroctalysts studied, 18 wt% MnO loaded sample showed the highest activity, close to that of standard Pt/c, with onset potential of 1.02 V vs. RHE and 3.48 mA cm(-2) limiting disk current in RRDE at 0.2 V. This electrocatalyst also preferred 4-electron reduction pathway in ORR and produced least amount of hydrogen peroxide. No hydrophilicity effect is found on the ORR activity of MnO/c electrocatalysts.

关键词： MnO nanostructure Electrocatalyst ORR MnO c Activated charcoal

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Transient inhibition of mitochondrial function by chrysin and apigenin prolong longevity via mitohormesis in c. elegans

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FREE RADIcAL BIOLOGY AND MEDIcINE 2023年第1期203卷 24-33页

作者： cheng, Yu Hou, Bing-Hao Xie, Gui-Lin Shao, Ya-Ting Yang, Jie Xu, chen Nanjing Univ Sch Life Sci State Key Lab Pharmaceut Biotechnol Nanjing 210023 Peoples R China

Mild inhibition of mitochondrial function leads to longevity. Genetic disruption of mitochondrial respiratory components either by mutation or RNAi greatly extends the lifespan in yeast, worms, and drosophila. This has given rise to the idea that pharmacologically inhibiting mitochondrial function would be a workable strategy for postponing aging. Toward this end, we used a transgenic worm strain that expresses the firefly luciferase enzyme widely to evaluate compounds by tracking real-time ATP levels. We identified chrysin and apigenin, which reduced ATP production and increased the lifespan of worms. Mechanistically, we discovered that chrysin and apigenin transiently inhibit mitochondrial respiration and induce an early ROS, and the lifespan-extending effect is dependent on transient ROS formation. We also show that AAK-2/AMPK, DAF-16/FOXO, and SKN-1/NRF-2 are required for chrysin or apigenin-mediated lifespan extension. Temporary increases in ROS levels trigger an adaptive response in a mitohormetic way, thereby increasing oxidative stress capacity and cellular metabolic adaptation, finally leading to longevity. Thus, chrysin and apigenin represent a class of compounds isolated from natural products that delay senescence and improve age-related diseases by inhibiting mitochondrial function and shed new light on the function of additional plant-derived polyphenols in enhancing health and delaying aging. collectively, this work provides an avenue for pharmacological inhibition of mitochondrial function and the mechanism underlining their lifespan-extending properties.

关键词： Aging c elegans ROS Mitohormesis chrysin Apigenin

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Hollow Ni/NiO/c composite derived from metal-organic frameworks as a high-efficiency electrocatalyst for the hydrogen evolution reaction

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NANO cONVERGENcE 2023年第1期10卷 6页

作者： Do, Ha Huu Tekalgne, Mahider Asmare Le, Quyet Van cho, Jin Hyuk Ahn, Sang Hyun Kim, Soo Young Chung Ang Univ Sch Chem Engn & Mat Sci 84 Heukseok Ro Seoul 06974 South Korea Korea Univ Inst Green Mfg Technol Dept Mat Sci & Engn 145 Anam Ro Seoul 02841 South Korea

Metal-organic frameworks (MOFs) constitute a class of crystalline porous materials employed in storage and energy conversion applications. MOFs possess characteristics that render them ideal in the preparation of electrocatalysts, and exhibit excellent performance for the hydrogen evolution reaction (HER). Herein, H-Ni/NiO/c catalysts were synthesized from a Ni-based MOF hollow structure via a two-step process involving carbonization and oxidation. Interestingly, the performance of the H-Ni/NiO/c catalyst was superior to those of H-Ni/c, H-NiO/c, and NH-Ni/NiO/c catalysts for the HER. Notably, H-Ni/NiO/c exhibited the best electrocatalytic activity for the HER, with a low overpotential of 87 mV for 10 mA cm(-2) and a Tafel slope of 91.7 mV dec(-1). The high performance is ascribed to the synergistic effect of the metal/metal oxide and hollow architecture, which is favorable for breaking the H-OH bond, forming hydrogen atoms, and enabling charge transport. These results indicate that the employed approach is promising for fabricating cost-effective catalysts for hydrogen production in alkaline media.

关键词： MOFs Ni NiO c Hollow structure Electrocatalyst HER

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Adaptive diversity in structure and function of c4 photosynthetic components

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BIOcHEMIcAL SOcIETY TRANSAcTIONS 2023年第3期51卷 1157-1168页

作者： Alvarez, clarisa E. Maurino, Veronica G. Univ Rosario Fac Ciencias Bioquim & Farmaceut Ctr Estudios Fotosintet & Bioquim CEFOBI CONICET Suipacha 570 RA-2000 Rosario Argentina Univ Bonn Inst Cellular Mol Bot IZMB Mol Plant Physiol Kirschallee 1 D-53115 Bonn Germany

Many tropical and subtropical plant lineages have independently evolved c4 photosynthesis. The convergent evolution of this complex functional trait from different ancestors is reflected in variations in the structural and biochemical characteristics of c4 components such as enzymes and cellular specializations. The mechanism of c4 carbon concentration mostly involves coordinated function of mesophyll and bundle sheath cells. Important adaptations of the c4 syndrome include increased vein density and the development of photosynthetic bundle sheath cells with low gas conductance. In addition, the enzymes and transporters of the c4 pathway evolved via the co-option of multiple genes, each derived from a specific lineage of isoforms present in nonc4-ancestors. In particular, the adaptation of c4 enzymes resulted in a variety of structural and biochemical modifications, generally leading to increased catalytic efficiency and regulation by metabolites and post-translational modifications. Differences in these adaptations are particularly evident in the c4-acid decarboxylation step, which can be catalyzed by three decarboxylases that define the c4 subtypes. Associated with the biochemical subtypes, there are also differences in the extend of grana staking and localization of bundle sheath cells chloroplasts. The presence of a suberin layer and symplastic connections also likely vary among the different c4-subtypes. This review examines the current understanding of the diversity of structural and functional changes in key components of the c4 carbon concentration mechanism. This knowledge is necessary not only to identify divergent solutions for convergent optimization of c4 components in different c4 lineages, but also to guide their creation for rational synthetic biology approaches.

关键词： c 4 photosynthesis convergent evolution gene co-option

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Overexpression of Homer1b/c induces valproic acid resistance in epilepsy

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cNS NEUROScIENcE & THERAPEUTIcS 2023年第1期29卷 331-343页

作者： Wang, Yan Li, Youbin Wang, Guangfei Lu, Jinmiao Li, Zhiping Hainan Med Univ Haikou China Haikou Key Lab Li Nationality Med Sch Pharm Key Lab Trop Translat MedMinist Educ Hainan Key Lab Res & Dev Trop Herbs Haikou Hainan Peoples R China Fudan Univ Dept Pharm Childrens Hosp 399 Wanyuan Rd Shanghai 201102 Peoples R China

Aims Resistance to valproic acid (VPA) is a major challenge for epilepsy treatment. We aimed to explore the mechanism underlying this resistance. Methods Pentylenetetrazol-induced chronic epileptic rats were administered VPA (250 mg/Kg) for 14 days;rats with controlled seizure stages (seizure score(14th-before) <= 0) and latent time (latent time(14th-before) >= 0) were considered VPA-responsive, while the others were considered nonresponsive. Differentially expressed genes (DEGs) between the VPA-responsive and nonresponsive rat hippocampus transcriptomes were identified, and their functions were evaluated. The roles of postsynaptic density (PSD) and Homer1 were also determined. Furthermore, a subtype of Homer1 (Homer1b/c) was overexpressed or silenced in HT22 cells to determine its effect on VPA efficacy. Moreover, the membrane levels of mGluR1/5 directly bound to Homer1b/c were assessed. Results Overall, 264 DEGs commonly enriched in the PSD between VPA-responsive and nonresponsive rats. Among them, Homer1 was more highly expressed in the hippocampus of nonresponses compared to that of responses. Overexpression of Homer1b/c interrupted VPA efficacy by increasing reactive oxygen species production, lactate dehydrogenase release, and calcium content. Furthermore, it induced the overexpression of mGluR1 and mGluR5. conclusion Overexpression of Homer1b/c influenced VPA efficacy, revealing it could be a target to improve the efficacy of this treatment.

关键词： efficacy Homer1b c HT22 pentylenetetrazol VPA

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Mapping of centriolar proteins onto the post-embryonic lineage of c. elegans

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DEVELOPMENTAL BIOLOGY 2023年第1期502卷 68-76页

作者： Kalbfuss, Nils Berger, Antonin Gonczy, Pierre Swiss Fed Inst Technol Lausanne EPFL Swiss Inst Expt Canc Res ISREC Sch Life Sci CH-1015 Lausanne Switzerland

centrioles, together with the surrounding peri-centriolar material (PcM), constitute the centrosome, a major microtubule-organizing center of animal cells. Despite being critical in many cells for signaling, motility and division, centrioles can be eliminated in some systems, including in the vast majority of differentiating cells during embryogenesis in caenorhabditis elegans. Whether the cells retaining centrioles in the resulting L1 larvae do so because they lack an activity that eliminates centrioles in the other cells is not known. Moreover, the extent to which centrioles and PcM remain present in later stages of worm development, when all cells but those of the germ line are terminally differentiated, is not known. Here, by fusing cells that lack centrioles with cells that retain them, we established that L1 larvae do not possess a diffusible elimination activity sufficient to remove centrioles. Moreover, analyzing PcM core proteins in L1 larval cells that retain centrioles, we found that some such proteins, but not all, are present as well. Furthermore, we uncovered that foci of centriolar proteins remain present in specific terminally differentiated cells of adult hermaphrodites and males, in particular in the somatic gonad. correlating the time at which cells were born with the fate of their centrioles revealed that it is not cell age, but instead cell fate, that determines whether and when centrioles are eliminated. Overall, our work maps the localization of centriolar and PcM core proteins in the post-embryonic c. elegans lineage, thereby providing an essential blueprint for uncovering mechanisms modulating their presence and function.

关键词： c elegans centriole Peri-centriolar material (PcM) cell fusion Lineage

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