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Fully plastic J-integral and c* equations for small punch test specimen with a surface crack

INTERNATIONAL JOURNAL OF PRESSURE VESSELS AND PIPING 2020年 188卷 104214-104214页

作者： Thanh Tuan Nguyen Yoon, Kee Bong Korean Res Inst Stand & Sci KRISS Ctr Mat & Energy Measurement Daejeon South Korea Chung Ang Univ Dept Mech Engn 84 Heukseok Ro Seoul 06974 South Korea

Small punch (SP) creep test specimen with an elliptical surface crack was suggested for use with creep crack growth testing. Estimation equations for fracture parameters are needed. K-equation was derived previously for the crack in the SP specimen. In this study, estimation equations for J and c* were derived. 3D elastic-plastic finite element analyses were carried out to determine J value along the front of the surface cracks of the same geometries as were employed for the K-estimation. The dimensionless function, h(1) was determined for various crack locations according to the EPRI scheme. The plastic limit load solution was also determined. The c*-equation of the cracked SP specimen was derived based on the J(p) solution using the analogy between the secondary creep constitutive law and the Ramberg-Osgood plasticity law. The c*-equation may be able to be used to characterize the creep crack growth behavior under the extensive creep condition of the cracked SP specimen.

关键词： J-integral c Plastic limit load h(1)-function Small punch creep creep crack growth

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Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross

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MOLEcULAR PAIN 2022年 18卷 17448069221079540页

作者： Beierle, Jacob A. Yao, Emily J. Goldstein, Stanley, I Scotellaro, Julia L. Sena, Katherine D. Linnertz, colton A. Willits, Adam B. Kader, Leena Young, Erin E. Peltz, Gary Emili, Andrew Ferris, Martin T. Bryant, camron D. Boston Univ Sch Med Program Biomol Pharmacol Boston MA 02118 USA Boston Univ Dept Pharmacol & Expt Therapeut & Psychiat Lab Addict Genet Sch Med Boston MA 02118 USA Boston Univ Ctr Network Syst Biol Dept Biol & Biochem Sch Med Boston MA 02118 USA Boston Univ Undergrad Res Opportun Program Boston MA 02118 USA Univ N Carolina Dept Genet Chapel Hill NC 27515 USA Univ Kansas Med Ctr Neurosci Program Kansas City KS 66103 USA Univ Kansas Med Ctr Dept Anesthesiol Kansas City KS 66103 USA Stanford Univ Sch Med Dept Anesthesiol Pain & Preoperat Med Stanford CA 94305 USA

Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the cNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants. We found BALB/cByJ mice showed enhanced sensitivity on the 53.5 degrees c hot plate and mechanical stimulation in the von Frey test compared to BALB/cJ mice and replicated decreased gross brain weight in BALB/cByJ versus BALB/cJ. We then identified a quantitative trait locus (QTL) on chromosome 13 for hot plate sensitivity (LOD = 10.7;p < 0.001;peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7;p < 0.001). Expression QTL mapping of brain tissues identified H2afy (56.07 Mb) as the top transcript with the strongest association at the hot plate locus (FDR = 0.0002) and spliceome analysis identified differential exon usage within H2afy associated with the same locus. Whole brain proteomics further supported decreased H2AFY expression could underlie enhanced hot plate sensitivity, and identified AcADS as a candidate for reduced brain weight. To summarize, a BALB/c reduced complexity cross combined with multiple-omics approaches facilitated identification of candidate genes underlying thermal nociception and brain weight. These substrains provide a powerful, reciprocal platform for future validation of candidate variants.

关键词： Thermal nociception hot plate von frey genetics BALB c reduced complexity cross brain weight H2afy

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Escaping social rejection, gaining total capital: the complex psychological experience of female genital mutilation/cutting (FGM/c) among the Izzi in Southeast Nigeria

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REPRODUcTIVE HEALTH 2022年第1期19卷 41-41页

作者： Omigbodun, Olayinka Bella-Awusah, Tolulope Emma-Echiegu, Nkechi Abdulmalik, Jibril Omigbodun, Akinyinka Doucet, Marie-Helene Groleau, Danielle Univ Ibadan Coll Med Ctr Child & Adolescent Mental Hlth Ibadan Nigeria Univ Ibadan Coll Med Dept Psychiat Ibadan Nigeria Ebonyi State Univ Dept Psychol & Sociol Studies Abakaliki Nigeria McGill Univ Div Social & Transcultural Psychiat Montreal PQ Canada Jewish Gen Hosp Lady Davis Med Inst Culture & Mental Hlth Res Unit Montreal PQ Canada Univ Ibadan Nigeria Coll Med Dept Obstet & Gynaecol Ibadan Nigeria

Background While the deleterious effects of FGM/c on physical health are well documented, the psychological experience of this harmful practice is a neglected area of research, which limits global mental health actions. As FGM/c was a traditional practice in some areas of Nigeria, the study aimed to understand the psychological experience of FGM/c in context. Methods This qualitative study was completed in urban and rural Izzi communities in Southeast Nigeria where FGM/c was widely practiced. In-depth interviews were completed with 38 women of the same ethnicity using the McGill Illness Narrative Interview (MINI) to explore the collective psychological experience of FGM/c before, during and after the procedure. The MINI was successfully adapted to explore the meaning and experience of FGM/c. We completed thematic content analysis and used the concepts of total capital and habitus by Bourdieu to interpret the data. Results During the period of adolescence, Izzi young women who had not yet undergone FGM/c reported retrospectively being subjected to intense stigma, humiliation and rejection by their cut peers. Alongside the social benefits from FGM/c the ongoing psychological suffering led many to accept or request to be cut, to end their psychological torture. Virtually all women reported symptoms of severe distress before, during and after the procedure. Some expressed the emotion of relief from knowing their psychological torture would end and that they would gain social acceptance and total capital from being cut. Newly cut young women also expressed that they looked forward to harassing and stigmatizing uncut ones, therein engaging in a complex habitus that underscores their severe trauma as well as their newly acquired enhanced social status. conclusion FGM/c is profoundly embedded in the local culture, prevention strategies need to involve the whole community to develop preventive pathways in a participatory way that empowers girls and women while preventing the

关键词： FGM c Psychological experience Nigeria Global mental health Power capital Habitus Adolescents McGill Illness Narrative Interview Schedule (MINI)

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Identifying the Types and characterization of the Active Sites on M-X-c Single-Atom catalysts

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cHEMPHYScHEM 2020年第23期21卷 2486-2496页

作者： Yang, Jiarui Wang, Dingsheng Li, Yadong Tsinghua Univ Dept Chem Beijing 100084 Peoples R China

Single atom catalysts (SAcs) have attracted much attention in recent years. As an essential group in SAcs, M-X-c (X=nonmetallic element) materials have been demonstrated to be efficient in many reactions. However, identifying the active sites on M-X-c, especially under working conditions, is still challenging, which is crucial for chemists to further understand the mechanism underlying the reaction and better design proper SAcs for specific reactions. Herein, the types and characterization of M-X-c are comprehensively summarized and discussed in this review. In addition to the basic information above, the challenges and opportunities remaining in this field will be also proposed to present a perspective to the research on the next step.

关键词： active sites characterization M− X− c nanomaterials single-atom catalysts

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Mutant c. elegans mitofusin leads to selective removal of mtDNA heteroplasmic deletions across generations to maintain fitness

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BMc BIOLOGY 2022年第1期20卷 40-40页

作者： Meshnik, Lana Bar-Yaacov, Dan Kasztan, Dana Neiger, Tali cohen, Tal Kishner, Mor Valenci, Itay Dadon, Sara Klein, christopher J. Vance, Jeffery M. Nevo, Yoram Zuchner, Stephan Ovadia, Ofer Mishmar, Dan Ben-Zvi, Anat Ben Gurion Univ Negev Dept Life Sci Beer Sheva Israel Ben Gurion Univ Negev Dept Microbiol Immunol & Genet Beer Sheva Israel Mayo Clin Dept Neurol Dept Lab Med & Pathol Rochester MN USA Univ Miami Miller Sch Med Dept Human Genet Dr John T Macdonald Fdn Miami FL 33136 USA Univ Miami Miller Sch Med Hussman Inst Human Genom Miami FL 33136 USA Tel Aviv Univ Schneider Childrens Med Ctr Israel Inst Neurol Petah Tiqwa Israel

Background Mitochondrial DNA (mtDNA) is present at high copy numbers in animal cells, and though characterized by a single haplotype in each individual due to maternal germline inheritance, deleterious mutations and intact mtDNA molecules frequently co-exist (heteroplasmy). A number of factors, such as replicative segregation, mitochondrial bottlenecks, and selection, may modulate the exitance of heteroplasmic mutations. Since such mutations may have pathological consequences, they likely survive and are inherited due to functional complementation via the intracellular mitochondrial network. Here, we hypothesized that compromised mitochondrial fusion would hamper such complementation, thereby affecting heteroplasmy inheritance. Results We assessed heteroplasmy levels in three caenorhabditis elegans strains carrying different heteroplasmic mtDNA deletions (Delta mtDNA) in the background of mutant mitofusin (fzo-1). Animals displayed severe embryonic lethality and developmental delay. Strikingly, observed phenotypes were relieved during subsequent generations in association with complete loss of Delta mtDNA molecules. Moreover, deletion loss rates were negatively correlated with the size of mtDNA deletions, suggesting that mitochondrial fusion is essential and sensitive to the nature of the heteroplasmic mtDNA mutations. Introducing the Delta mtDNA into a fzo-1;pdr-1;+/Delta mtDNA (PARKIN ortholog) double mutant resulted in a skewed Mendelian progeny distribution, in contrast to the normal distribution in the fzo-1;+/Delta mtDNA mutant, and severely reduced brood size. Notably, the Delta mtDNA was lost across generations in association with improved phenotypes. conclusions Taken together, our findings show that when mitochondrial fusion is compromised, deleterious heteroplasmic mutations cannot evade natural selection while inherited through generations. Moreover, our findings underline the importance of cross-talk between mitochondrial fusion and mitophagy in modulat

关键词： c elegans fzo-1 Heteroplasmy inheritance Mitofusin mtDNA PARKIN pdr-1

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Imaging of lipid droplets using coumarin fluorophores in live cells and c. elegans

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JOURNAL OF PHOTOcHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2022年第0期237卷 000-000页

作者： Singh, Deepmala Regar, Ramprasad Soppina, Pushpanjali Soppina, Virupakshi Kanvah, Sriram Indian Inst Technol Gandhinagar Dept Chem Gandhinagar 382055 Gujarat India Indian Inst Technol Gandhinagar Dept Biol Engn Gandhinagar 382055 Gujarat India Sambalpur Univ Dept Biotechnol & Bioinformat Sambalpur 768019 Orissa India

Fluorescent probes offer incredibly effective tools for visualizing the dynamic morphology of lipid droplets (LDs) and investigating their physiological interactions. In this work, we have utilized solvatochromic coumarin probes bearing nitrile and ester substituents for live-cell imaging. The fluorescence probes are characterized by a donor (diethylamino) and acceptor (nitrile and/or ester) substituents and a rotatable double bond. The designed ar-chitecture allows investigation of environmental sensitivity apart from providing excellent ability to target sub -cellular organelles. The synthesized fluorophores showed low cytotoxicity and excellent localization within the lipid droplets. Further, the fluorophores were also utilized to study viscosity changes within the LDs induced by Nystatin. More importantly, we also demonstrate imaging of LDs in multi-cellular animal models such as c. elegans.

关键词： Viscosity sensing Visualization Fluorescence Sub-cellular organelles Lipid droplets c elegans coumarin-fluorophores

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seco-Prezizanne Sesquiterpenes and Prenylated c6-c3 compounds from the Fruits of Illicium lanceolatum A. c. Smith

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cHEMISTRY & BIODIVERSITY 2022年第1期19卷 e202100868-e202100868页

作者： Nie, Wei Ding, Lin-Fen Tie-Lei Zhou, Hao-Feng Bao, Yi Song, Liu-Dong Pan, Zheng-Hong Wu, Xing-De Zhao, Qin-Shi Chinese Acad Sci Kunming Inst Bot State Key Lab Phytochem & Plant Resources West Ch Kunming 650201 Yunnan Peoples R China Yunnan Minzu Univ State Ethn Affairs Commiss Key Lab Ethn Med Resource Chem Kunming 650500 Yunnan Peoples R China Yunnan Minzu Univ Minist Educ Kunming 650500 Yunnan Peoples R China Kunming Med Univ Sch Pharmaceut Sci Kunming 650500 Yunnan Peoples R China Kunming Med Univ Yunnan Key Lab Pharmacol Nat Prod Kunming 650500 Yunnan Peoples R China Chinese Acad Sci Guangxi Inst Bot Guangxi Key Lab Funct Phytochem Res & Utilizat Guilin 541006 Peoples R China

Two new seco-prezizaane-type sesquiterpenes, 2 beta-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1 alpha-hydroxy-6-deoxyneoanisatin (2), and two new prenylated c-6-c-3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated c-6-c-3 compounds (5-8). Their structures were proposed through HR-ESI-MS, H-1, c-13, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (EcD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+-induced Pc12 cell damage in a dose-dependent manner.

关键词： Illicium lanceolatum A c Smith seco-prezizanne sesquiterpene prenylated c6-c3 compound neuroprotective activity

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PITX2c increases the stemness features of hepatocellular carcinoma cells by up-regulating key developmental factors in liver progenitor

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JOURNAL OF EXPERIMENTAL & cLINIcAL cANcER RESEARcH 2022年第1期41卷 211-211页

作者： Jiang, Lingxi Wang, Xia Ma, Fangfang Wang, Xuelong Shi, Minmin Yan, Qian Liu, Ming chen, Juan Shi, chaoran Guan, Xin-yuan Shanghai Jiao Tong Univ Ruijin Hosp Dept Gen Surg Sch Med Shanghai 200025 Peoples R China Univ Hong Kong Li Ka Shing Fac Med Dept Clin Oncol Pokfulam Room L10-56Lab Block21 Sassoon Rd Hong Kong Peoples R China Shanghai Jiao Tong Univ Res Inst Pancreat Dis Sch Med Shanghai Peoples R China Univ Hong Kong State Key Lab Liver Res Hong Kong Peoples R China Sun Yat Sen Univ Guangdong Inst Gastroenterol Affiliated Hosp 6 Dept Colorectal SurgGuangdong Prov Key Lab Color Guangzhou Peoples R China Guangzhou Med Univ Sch Basic Med Sci Affiliated Canc Hosp & Inst Guangzhou Municipal & Guangdong Prov Key Lab Prot Guangzhou Peoples R China

Background Tumor cells exhibited phenotypic and molecular characteristics similar to their lineage progenitor cells. Liver developmental signaling pathways are showed to be associated with Hcc development and oncogenesis. The similarities of expression profiling between liver progenitors (LPs) and Hcc suggest that understanding the molecular mechanism during liver development could provide insights into Hcc. Methods To profile the dynamic gene expression during liver development, cells from an in vitro liver differentiation model and two paired hepatocellular carcinoma (Hcc) samples were analyzed using deep RNA sequencing. The expression levels of selected genes were analyzed by qRT-PcR. Moreover, the role of a key transcription factor, pituitary homeobox 2 (PITX2), was characterized via in vitro and vivo functional assays. Furthermore, molecular mechanism studies were performed to unveil how PITX2c regulate the key developmental factors in LPs, thereby increasing the stemness of Hcc. Results PITX2 was found to exhibit a similar expression pattern to specific markers of LPs. PITX2 consists of three isoforms (PITX2A/B/c). The expression of PITX2 is associated with tumor size and overall survival rate, whereas only PITX2c expression is associated with AFP and differentiation in clinical patients. PITX2A/B/c has distinct functions in Hcc tumorigenicity. PITX2c promotes Hcc metastasis, self-renewal and chemoresistance. Molecular mechanism studies showed that PITX2c could up-regulate RALYL which could enhance Hcc stemness via the TGF-beta pathway. Furthermore, chIP assays confirmed the role of PITX2c in regulating key developmental factors in LP. conclusion PITX2c is a newly discovered transcription factor involved in hepatic differentiation and could increase Hcc stemness by upregulating key transcriptional factors related to liver development.

关键词： PITX2A B c Hcc Tumorigenicity Stemness Developmental factors in liver progenitor

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Sperm associated antigen 4 promotes SREBP1-mediated de novo lipogenesis via interaction with lamin A/c and contributes to tumor progression in hepatocellular carcinoma

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cANcER LETTERS 2022年 536卷 215642-215642页

作者： Liu, Tengfei Yu, Junming Ge, chao Zhao, Fangyu chen, Jing Miao, chunxiao Jin, Wenjiao Zhou, Qingqing Geng, Qin Lin, Hechun Tian, Hua chen, Taoyang Xie, Haiyang cui, Ying Yao, Ming Xiao, Xiuying Li, Jinjun Li, Hong Shanghai Jiao Tong Univ Renji Hosp Shanghai Canc Inst State Key Lab Oncogenes & Related GenesSch Med Shanghai 200032 Peoples R China Shanghai Jiao Tong Univ Rui jin Hosp Sch Med Dept Oncol Shanghai 200020 Peoples R China Qi Dong Liver Canc Inst Qi Dong 226200 Peoples R China Zhejiang Univ Affiliated Hosp 1 Sch Med Dept Gen Surg Hangzhou 310000 Peoples R China Canc Inst Guangxi Nanning 530027 Peoples R China Shanghai Jiao Tong Univ Ren ji Hosp Sch Med Dept Oncol Shanghai 200127 Peoples R China

Hepatocellular carcinoma (Hcc) is a highly malignant tumor and its progression is associated with altered lipid metabolism in precancerous lesions, such as non-alcoholic fatty liver disease. Here, we identified sperm associated antigen 4 (SPAG4), and explored its oncogenic role in Hcc progression. Database analysis and immunohistochemistry indicated increased level of SPAG4 in Hcc tissues which was of prognostic value. Gain/loss-offunction experiments showed that SPAG4 exerted oncogenic roles in Hcc growth both in vitro and in vivo. RNA sequencing revealed activation of a lipogenic state and SREBP1-mediated pathway following SPAG4 overexpression. Mechanistically, the N-terminal region of SPAG4 bound to lamin A/c, which increased SREBP1 expression, nuclear translocation, and transcriptional activity. Treatment with orlistat, a lipid synthesis inhibitor, reversed SPAG4-mediated oncogenic effects, and its efficacy varied with SPAG4 level. The effect of orlistat was further amplified when combined with sorafenib in tumor xenograft mouse models. Our study provides evidence that SPAG4 mediates Hcc progression by affecting lipid metabolism. Administration of orlistat combined with sorafenib reverses SPAG4-mediated oncogenesis in Hcc cells and ectopic xenograft tumors in mice, suggesting that this pathway represents a potential target for Hcc treatment.

关键词： Hepatocellular carcinoma SPAG4 Lipogenesis SREBP1 Lamin A c

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Identification and analysis of differentially expressed microRNAs in gibel carp carassius auratus gibelio responding to polyinosinic-polycytidylic acid (poly I:c) stimulation

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FISH AND SHELLFISH IMMUNOLOGY REPORTS 2023年 4卷

作者： Zhang, Jialin Sun, Shanling Mao, Yiyang Qiao, Guo Li, Qiang Yancheng Inst Technol Coll Marine & Bioengn Yancheng 224051 Peoples R China

Polyinosinic-polycytidylic acid (poly I:c) is a synthesized analogue of viral double-strand RNA and considered as a potential immunostimulant in aquaculture. MicroRNAs (miRNAs) have been reported to play important roles in the development of the immune system and in regulation of host antiviral responses. In our earlier study, it was found that poly I:c pre-treatment could stimulate the resistance against cyprinid herpesvirus 2 (cyHV-2) infection and enhance the antiviral immune response in gibel carp. To understand the role of miRNAs in regulating the host response to poly I:c treatment, we investigated the expression profiles of miRNAs in the head kidney of poly I:c-treated gibel carp with small RNA sequencing technology. When compared with the untreated group, a total of 24 differentially expressed miRNAs were identified in the poly I:c-stimulated fish, among which, 7 and 17 miRNAs were upregulated and downregulated, respectively. Analysis of target genes of these differentially expressed miRNAs found that most targeted mRNAs were involved in catalytic activity, peptidase activity and endopeptidase activity, and were enriched in the metabolic, protein processing in endoplasmic reticulum and oxidative phosphorylation signaling pathways, suggesting that poly I:c could alter the expression of metabolism-related miRNAs in the kidney of gibel carp. Besides, it was noted that some immune-related miRNAs, including inflammation-related miRNAs (miR-192 and miR-731) and interferon-related miRNAs (miR-194a and miR-122), were downregulated after poly I:c treatment. In summary, it was found that poly I:c could regulate the cellular levels of specific miRNAs involved in metabolism and immune responses in the head kidney of gibel carp, which may increase the capacity of the immune cells to fight against pathogens infection.

关键词： Gibel carp Poly I c MicroRNA Transcriptome Immune response

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