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Singapore grouper iridovirus infection counteracts poly I:c induced antiviral immune response in vitro

FISH & SHELLFISH IMMUNOLOGY 2023年 135卷 108685页

作者： Wang, Wenji Zhang, Ya Guo, Xixi Xu, Weihua Qin, Qiwei Huang, Youhua Huang, Xiaohong South China Agr Univ Coll Marine Sci Lingnan Guangdong Lab Modern Agr Guangzhou 510642 Peoples R China Southern Marine Sci & Engn Guangdong Lab Zhuhai 519082 Peoples R China Lab Marine Biol & Biotechnol Qingdao Natl Lab Marine Sci & Technol Qingdao 266000 Peoples R China South China Agr Univ Coll Marine Sci Guangzhou 510642 Peoples R China

Groupers are important mariculture fish in South china and Southeast Asian countries. However, the increasing frequency of infectious disease outbreaks has caused great economic losses in the grouper industry. Among these pathogens, Singapore grouper iridovirus (SGIV) infection causes high mortality in larval and juvenile stages of grouper. However, the mechanism underlying the action of viral manipulation on cellular immune response still remained largely uncertain. Here, using RNA-seq technology, we investigated the regulatory roles of SGIV infection on synthetic RNA duplex poly I:c induced immune response in vitro. Using reporter gene assays, we found that SGIV infection decreased poly I:c induced interferon promoter activation. Transcriptomic analysis showed that the mRNA expression levels of 2238 genes were up-regulated, while 1247 genes were down -regulated in poly I:c transfected grouper spleen (GS) cells. Interestingly, SGIV infection decreased the expres-sion of 1479 up-regulated genes and increased the expression of 297 down-regulated genes in poly I:c transfected cells. The differentially expressed genes (DEGs) down-regulated by SGIV were directly related to immune, inflammation and viral infection, and JUN, STAT1, NFKB1, MAPK14A, TGFB1 and MX were the 6 top hub genes in the down-regulated DEGs' protein-protein interaction (PPI) network. Furthermore, quantitative real-time PcR (qPcR) analysis confirmed that the interferon signaling and inflammatory-related genes, including cGAS, STING, TBK1, MAVS, TNF, IRAK4 and NOD2 were up-regulated by poly I:c stimulation, but all significantly down -regulated after SGIV infection. Thus, we speculated that SGIV infection counteracted poly I:c induced anti-viral immune response and this ability helped itself to escape host immune surveillance. Together, our data will contribute greatly to understanding the potential immune evasion mechanism of iridovirus infection in vitro.

关键词： SGIV Poly I c Immune response Inflammatory response Immune evasion

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Ultra-high temperature ablation behavior of cVD-Hf5Tac6 solid solution ceramic coating for c/c composites: Experiment and first-principle calculation

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JOURNAL OF ALLOYS AND cOMPOUNDS 2023年第1期965卷

作者： chen, Hui Zhang, Yulei Li, Zhenglong Shuai, Kang Fu, Yanqin Meng, Jiachen Liu, Kun Zhang, Jian Li, Tao Northwestern Polytech Univ Shaanxi Key Lab Fiber Reinforced Light Composite M Xian 710072 Peoples R China Henan Acad Sci Inst Carbon Matrix Composites Henan Key Lab High Performance Carbon Fiber Reinfo Zhengzhou 450046 Peoples R China

To address the problem that the oxidized layer of Hfc coating was loose and porous, HfxTaycx+y solid solution with good thermal stability and ablation resistance was proposed as coating for carbon/carbon (c/c) composites. In present work, Hfc, Tac and the novel Hf5Tac6 solid solution coatings were synthesized on c/c composites by chemical vapor deposition. combing with the ablation test and density functional theory calculations about oxygen-adsorption energies, the ablation mechanism of Hfc, Tac and Hf5Tac6 solid solution coatings were investigated. The Hf5Tac6 solid solution coating showed superior ablation resistance than that of Hfc and Tac coatings, benefitting from the solid-liquid composite oxide layer with HfO2 and Hf6Ta2O17 as solid structure to further stabilize the oxides and resist mechanical erosion, Ta2O5 as the liquid filler to heal cracks to inhibit the oxygen infiltration.

关键词： c c composites Hf 5 Tac 6 solid solution coating Density functional theory Oxygen adsorption Ablation resistance

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Photoinduced electron transfer in cytochrome bc1: Dynamics of rotation of the Iron-sulfur protein during bifurcated electron transfer from ubiquinol to cytochrome c1 and cytochrome bL

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BIOcHIMIcA ET BIOPHYSIcA AcTA-BIOENERGETIcS 2023年第2期1864卷

作者： Havens, Jeffrey Su, Ting Wang, Qiyu Yu, chang-An Yu, Linda Durham, Bill Millett, Francis Univ Arkansas Dept Chem & Biochem Fayetteville AR 72701 USA Oklahoma State Univ Dept Biochem & Mol Biol Stillwater OK 74078 USA Vaccines & Therapeut Div Def Threat Reduct Agcy Chem & Biol Technol Ft Belvoir VA 22060 USA ABclonal Technol Woburn MA 01801 USA Vesigen Therapeut Cambridge MA 02139 USA

The electron transfer reactions within wild-type Rhodobacter sphaeroides cytochrome bc1 (cyt bc1) were studied using a binuclear ruthenium complex to rapidly photooxidize cyt c1. When cyt c1, the iron-sulfur center Fe2S2, and cyt bH were reduced before the reaction, photooxidation of cyt c1 led to electron transfer from Fe2S2 to cyt c1 with a rate constant of ka = 80,000 s- 1, followed by bifurcated reduction of both Fe2S2 and cyt bL by QH2 in the Qo site with a rate constant of k2 = 3000 s- 1. The resulting Q then traveled from the Qo site to the Qi site and oxidized one equivalent each of cyt bL and cyt bH with a rate constant of k3 = 340 s- 1. The rate constant ka was decreased in a nonlinear fashion by a factor of 53 as the viscosity was increased to 13.7. A mechanism that is consistent with the effect of viscosity involves rotational diffusion of the iron-sulfur protein from the b state with reduced Fe2S2 close to cyt bL to one or more intermediate states, followed by rotation to the final c1 state with Fe2S2 close to cyt c1, and rapid electron transfer to cyt c1.

关键词： cyt cytochrome ISP Rieske iron‑sulfur protein ISP-ED extrinsic domain of ISP Fe 2 S 2 Rieske iron‑sulfur center Ru 2 D [Ru(bpy) 2 ] 2 (qpy)(PF 6 ) 4 qpy 2,2′:4′,4″:2″,2‴–quaterpyridine Q 0 c 10 BrH 2 2,3-dimethoxy-5-methyl-6-(10-bromodecyl)-1,4-benzoquinol ScR succinate cytochrome c reductase EPR electron paramagnetic resonance

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contrasting dose response relationships of neuroactive antidepressants on the behavior of c. elegans

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EcOTOXIcOLOGY AND ENVIRONMENTAL SAFETY 2023年第1期250卷 114493页

作者： van der Most, Merel A. Estruch, Ignacio Miro van den Brink, Nico W. Wageningen Univ & Res Div Toxicol NL-6708 WE Wageningen Netherlands

Antidepressant prescriptions are on a rise worldwide and this increases the concerns for the impacts of these pharmaceuticals on nontarget organisms. Antidepressants are neuroactive compounds that can affect organism's behavior. Behavior is a sensitive endpoint that may also propagate effects at a population level. Another interesting aspect of antidepressants is that they have shown to induce non-monotonic dose-response (NMDR) curves. While such NMDR relationships may have clear implications for the environmental risk, the resolution of current studies is often too coarse to be able to detect relevant NMDR. Therefore, the current study was per-formed into the behavioral effects (activity, feeding and chemotaxis) in caenorhabditis elegans as the model or-ganism of the selective serotonin reuptake inhibitors fluoxetine and sertraline and the acetylcholinesterase inhibiting pesticide chlorpyrifos, using a wide range of concentrations (ng/l to mg/l). In order to statistically examine the non-monotonicity, nonlinear regression models were applied to the results. The results showed a triphasic dose-response relationship for activity and chemotaxis after exposure to fluoxetine, but not to sertraline or chlorpyrifos. Effects of fluoxetine already occurred at low concentrations in the range of ng/l while sertraline only showed effects at concentrations in the mu g/l range, similar to chlorpyrifos. The different responses between fluoxetine and sertraline, both SSRIs, indicate that response patterns may not always be extrapolated from chemicals with the same primary mode of action. The effects of fluoxetine at low concentrations, in a non-monotonic manner, confirm the relevance of examining such responses at low concentrations.

关键词： Antidepressants Behavior Non-monotonic dose-response curves c elegans

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The clinical significance of circulating glucose-regulated protein 78, caspase-3, and c/EBP homologous protein levels in patients with heart failure

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HELIYON 2023年第2期9卷 e13436页

作者： Zhao, Xuecheng Zhang, Da-Qi Song, Rongjing Wang, Rong Zhang, Guoqiang China Japan Friendship Hosp Dept Emergency Med Beijing Peoples R China Hainan Med Univ Dept Neurol Affiliated Hosp 1 Haikou Peoples R China Peking Univ Peoples Hosp Dept Pharm Beijing Peoples R China Hainan Univ Sch Pharmaceut Sci Haikou Peoples R China Hainan Med Univ Dept Neurol Affiliated Hosp 1 Longhua Rd Haikou 570102 Hainan Peoples R China China Japan Friendship Hosp Dept Emergency Med 2 Yinghua Dongjie Beijing 100029 Peoples R China

Background and aims: The destruction of endoplasmic reticulum (ER) homeostasis leads to heart failure (HF), which further aggravates ER stress. Limited data are available on the levels of ER stress markers in HF patients in clinical practice. This study aimed to determine the clinical significance of the ER stress markers, glucose-regulated protein 78 (GRP78), caspase-3, and c/ EBP homologous protein (cHOP), in predicting HF and its severity. Materials and methods: A total of 62 patients with HF and 44 healthy controls were enrolled in the study, and all participants were followed-up for 2 years. Results: Serum GRP78, caspase-3, and cHOP levels were significantly higher in patients with HF than those in healthy controls. The level of GRP78 increased with the severity of HF. GRP78 levels were negatively correlated with left ventricular ejection fraction, and positively correlated with N-terminal B-type natriuretic peptide, D-dimer, and lactic acid. Serum GRP78 and caspase-3 levels showed moderate predictive values for HF patients. conclusion: ER stress markers, GRP78 and caspase-3, had a certain predictive value in HF and can be used as serum biomarkers for the diagnosis of HF. Additionally, GRP78 showed a certain predictive value in HF severity.

关键词： Glucose-regulated protein 78 caspase-3 c EBP homologous Protein Heart failure

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Soil fungal mycelia have unexpectedly flexible stoichiometric c:N and c:P ratios

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EcOLOGY LETTERS 2021年第2期24卷 208-218页

作者： camenzind, Tessa Philipp Grenz, Kay Lehmann, Johannes Rillig, Matthias c. Free Univ Berlin Inst Biol Altensteinstr 6 D-14195 Berlin Germany Berlin Brandenburg Inst Adv Biodivers Res BBIB D-14195 Berlin Germany Cornell Univ Sch Integrat Plant Sci Soil & Crop Sci Ithaca NY 14853 USA

Soil ecological stoichiometry provides powerful theories to integrate the complex interplay of element cycling and microbial communities into biogeochemical models. One essential assumption is that microbes maintain stable c:N:P (carbon:nitrogen:phosphorus) ratios independent of resource supply, although such homeostatic regulations have rarely been assessed in individual microorganisms. Here, we report an unexpected high flexibility in c:N and c:P values of saprobic fungi along nutrient supply gradients, overall ranging between 7-126 and 20-1488, respectively, questioning microbial homeostasis. Fungal N:P varied comparatively less due to simultaneous reductions in mycelial N and P contents. As a mechanism, internal recycling processes during mycelial growth and an overall reduced N and P uptake appear more relevant than element storage. The relationships among fungal stoichiometry and growth disappeared in more complex media. These findings affect our interpretation of stoichiometric imbalances among microbes and soils and are highly relevant for developing microbial soil organic carbon and nitrogen models.

关键词： c N P ratios element homeostasis fungal nutrient retranslocation microbial carbon sequestration mycelial growth nutrient limitations saprobic fungi soil ecological stoichiometry soil nutrient cycling

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composting and vermicomposting of sewage sludge at various c/N ratios: Technological feasibility and end-product quality

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EcOTOXIcOLOGY AND ENVIRONMENTAL SAFETY 2023年第1期263卷 115255页

作者： Dume, Bayu Hanc, Ales Svehla, Pavel Michal, Pavel chane, Abraham Demelash Nigussie, Abebe Czech Univ Life Sci Fac Agrobiol Food & Nat Resources Dept Agroenvironm Chem & Plant Nutr Kamycka 129 Prague 16500 Czech Republic Jimma Univ Coll Agr Jimma 307 Ethiopia

Even though sewage sludge (SS) contains a high level of pollutants, it is rich in essential plant nutrients and has the potential to enhance soil fertility. However, the SS must be further treated through pre-composting plus vermicomposting to make it safe for use on food crops. More research and data are needed to determine how different carbon-to-nitrogen ratios (c/N) affect the feasibility and quality of composting vs vermicomposting of SS. Therefore, in this study we comprehensively evaluated the feasibility and end-product quality of compost and vermicompost produced from SS under different c/N ratios. SS was mixed with pelletized wheat straw (PWS) at various proportions to produce c/N ratios of 6:1, 18:1, 28:1, and 38:1, then pre-composted for 14 days followed by vermicomposting using the earthworm Eisenia andrei for 120 days. Agrochemical properties were measured at 0, 30, 60, 90, and 120 days. Results revealed significantly higher levels of agrochemicals in vermicompost compared to compost, including total potassium (37-88%) and magnesium (4.3-12%), nitrate nitrogen (71-98%), available potassium (53-88%), available phosphorus (79%), available magnesium (54-453%), available boron (48-303%), and available copper (2.5-82%). However, lower levels of ammonium nitrogen by (59-85%), available iron (2.3-51.3%), available manganese (29.7-52.2%), available zinc (10.5-29.8%), total carbon (0.75-4.5%), and total nitrogen (1.6-22.2%) were measured. comparison of the various c/N ratios, showed that vermicompost with an 18:1 c/N ratio outperformed compost and demonstrated the highest earthworm population (165 pieces/kg). Thus, vermicomposting SS at an 18:1 c/N ratio is strongly recommended as a sustainable technology for producing high-quality vermicompost from SS.

关键词： Sewage sludge Vermicomposting Eisenia andrei composting c N ratio

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characterization of a germline variant MSH6 c.4001G >c in a Lynch syndrome family

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MOLEcULAR GENETIcS & GENOMIc MEDIcINE 2023年第2期11卷 e2104页

作者： Yang, ciyu Misyura, Maksym Kane, Sarah Rai, Vikas Latham, Alicia Zhang, Liying Mem Sloan Kettering Canc Ctr Dept Pathol New York NY USA Mem Sloan Kettering Canc Ctr Dept Med New York NY USA Univ Calif Los Angeles UCLA David Geffen Sch Med Dept Pathol & Lab Med Los Angeles CA USA UCLA Dept Pathol & Lab Med David Geffen Sch Med 10833 Conte Ave Los Angeles CA 90095 USA

BackgroundGermline variants in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) cause Lynch syndrome, an autosomal dominant hereditary cancer susceptibility syndrome. The risk for endometrial cancer is significantly higher in women with MSH6 pathogenic/likely pathogenic (P/LP) variants compared with that for MLH1 or MSH2 variants. MethodsThe proband was tested via a clinical testing, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable cancer Targets (MSK-IMPAcT). RT-PcR was performed using patient's blood DNA and cDNA was analyzed by DNA sequencing and a cloning approach. ResultsWe report a 56-year-old female with endometrial cancer who carries a germline variant, MSH6 c.4001G > c, located at the last nucleotide of exon 9. While the pathogenicity of this variant was previously unknown, functional studies demonstrated that this variant completely abolished normal splicing and caused exon 9 skipping, which is expected to lead to a prematurely truncated or abnormal protein. conclusionOur results indicate that this variant likely contributes to cancer predisposition through disruption of normal splicing, and is classified as likely pathogenic.

关键词： c 4001G > c germline Lynch syndrome MSH6 splice site variant

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Targeting unfolded protein response reverts ER stress and ER ca²⁺ homeostasis in cardiomyocytes expressing the pathogenic variant of Lamin A/c R321X

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JOURNAL OF TRANSLATIONAL MEDIcINE 2023年第1期21卷 340-340页

作者： Pietrafesa, Giusy De Zio, Roberta Scorza, Simona Ida Armentano, Maria Francesca Pepe, Martino Forleo, cinzia Procino, Giuseppe Gerbino, Andrea Svelto, Maria carmosino, Monica Univ Basilicata Dept Sci Potenza Italy Univ Bari Aldo Moro Dept Biosci Biotechnol & Environm Bari Italy Univ Bari Aldo Moro Dept Emergency & Organ Transplantat Cardiol Unit Bari Italy

BackgroundWe previously demonstrated that an Italian family affected by a severe dilated cardiomyopathy (DcM) with history of sudden deaths at young age, carried a mutation in the Lmna gene encoding for a truncated variant of the Lamin A/c protein (LMNA), R321X. When expressed in heterologous systems, such variant accumulates into the endoplasmic reticulum (ER), inducing the activation of the PERK-cHOP pathway of the unfolded protein response (UPR), ER dysfunction and increased rate of apoptosis. The aim of this work was to analyze whether targeting the UPR can be used to revert the ER dysfunction associated with LMNA R321X expression in HL-1 cardiac ***-1 cardiomyocytes stably expressing LMNA R321X were used to assess the ability of 3 different drugs targeting the UPR, salubrinal, guanabenz and empagliflozin to rescue ER stress and dysfunction. In these cells, the state of activation of both the UPR and the pro-apoptotic pathway were analyzed monitoring the expression levels of phospho-PERK, phospho-eIF2 alpha, ATF4, cHOP and PARP-cL. In addition, we measured ER-dependent intracellular ca2+ dynamics as indicator of proper ER *** found that salubrinal and guanabenz increased the expression levels of phospho-eIF2 alpha and downregulated the apoptosis markers cHOP and PARP-cL in LMNA R321X-cardiomyocytes, maintaining the so-called adaptive UPR. These drugs also restored ER ability to handle ca2+ in these cardiomyocytes. Interestingly, we found that empagliflozin downregulated the apoptosis markers cHOP and PARP-cL shutting down the UPR itself through the inhibition of PERK phosphorylation in LMNA R321X-cardiomyocytes. Furthermore, upon empagliflozin treatment, ER homeostasis, in terms of ER ability to store and release intracellular ca2+ was also restored in these *** provided evidence that the different drugs, although interfering with different steps of the UPR, were able to counteract pro-apoptotic processes

关键词： cardiomyocytes ER stress Lamin A c cardiomyopathy Guanabenz Empagliflozin

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Photo-and thermo-regulation by photonic crystals for extended longevity of c. elegans

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MEcHANISMS OF AGEING AND DEVELOPMENT 2023年第1期212卷 111819页

作者： Yu, Shuzhen Shao, Yating Qiu, Qineng cheng, Yu Qing, Renkun Wang, cai-Feng chen, Su Xu, chen Nanjing Univ Sch Life Sci State Key Lab Pharmaceut Biotechnol Nanjing 210023 Peoples R China Nanjing Tech Univ Coll Chem Engn State Key Lab Mat Oriented Chem Engn Nanjing 210009 Peoples R China

Methods allowing light energy to be modulated in a controllable fashion are potentially important for finding the correlation between light-related environmental factors and aging-related lifespan. Here, we report photo- and thermo-regulation based on photonic crystals (Pcs) for extended longevity of c. elegans. We show that Pcs can function as a regulator of visible spectrum to tune photonic energy received by ***. We provide direct evidence that lifespan depends on photonic energy, and the use of Pcs reflecting blue light (440-537 nm) gives 8.3 % increasement in lifespan. We demonstrate that the exposure to modulated light alleviates photo-oxidative stress and unfolded-protein response. We realize reflective passive cooling temperature using Pcs, and favorable low temperature could be created for worms to extend lifespan. This work offers a new path based on Pcs to resist negative effects light and temperature for longevity, provides an available platform for studying the role of light in aging.

关键词： Photo effect Thermal effect Photonic crystal Light energy Longevity c elegans

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