Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"title":"DNA damage in foundry workers using non-invasive micronucleus cytome assay","authors":"Hakimeh Nazari Khuniqi ,&nbsp;Yahya Rasoulzadeh ,&nbsp;Yousef Mohammadian","doi":"10.1016/j.mrgentox.2023.503686","DOIUrl":"10.1016/j.mrgentox.2023.503686","url":null,"abstract":"<div><p>Workers in the foundry industry are exposed to hazardous chemical agents such as metal fumes, gases, vapor of molten metal, and respirable dust and hazardous physical agents such as heat, noise, and electromagnetic fields. Co-exposures to hazardous physical and chemical agents in foundry workplaces may cause DNA damage in workers. This study aimed to evaluate DNA damage in foundry workers. Thirty-three exposed foundry workers as a exposure groups and 33 non-exposed individuals as a control groups participated in this study. Buccal micronucleus cytome (BMCyt assay) assay was used to assess DNA damage. Results showed that foundry workers were under exposure to hazardous chemical and physical agents such as metal fumes and noise. The percentage of micronucleus (MN) cells in exposure group (0.59 ± 0.93 %) were statistically higher than control group (0.23 ± 0.23 %) (P &lt; 0.05) %). Also, the percentage of nuclear bud cells and binucleated cells in exposure group were statistically higher than control group (P &lt; 0.05). The percentage of differentiated normal cells were significantly higher in the control group compared to the exposed group (P &lt; 0.05). Foundry workers are at risk of DNA damage; therefore, prevention measures need to be implemented to reduce exposure to air pollutants in foundry workplaces.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503686"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfoquinovosyl acylpropanediol (SQAP): Inhibition of poly(ADP-ribose) metabolism and enhanced cytotoxicity in homologous recombination repair-deficient Chinese hamster-derived cells","authors":"Junko Maeda ,&nbsp;Kaitlyn D. Shellenberger ,&nbsp;Wataru Kurihara ,&nbsp;Tomohiro Haga ,&nbsp;Takamitsu A. Kato","doi":"10.1016/j.mrgentox.2023.503703","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503703","url":null,"abstract":"<div><p>Sulfoquinovosyl acylpropanediol (SQAP; a synthetic derivative of the sulfoglycolipid natural product sulfoquinovosyl acylglycerol, SQAG), has anti-tumor and radiosensitizing activities in tumor xenograft mouse models. Here, we have studied the PARP inhibitory activity of SQAP and synthetic lethality in BRCA2-deficient cells. In initial screening studies with DNA repair-deficient Chinese hamster ovary cells, homologous recombination repair-deficient cell lines showed increased sensitivity to SQAP, compared to wild-type cells or other DNA repair-deficient mutants. Chinese hamster lung V79 cells and the derivative cell lines V-C8 (BRCA2-deficient) and V-C8 + BRCA2 gene corrections were used to test the role of BRCA2 in SQAP cytotoxicity. The findings were confirmed in studies of the human colon cancer cell lines DLD-1 and its BRCA2-knockout derivative. SQAP inhibited the enzymes poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG). SQAP pretreatment decreased H₂O₂induced poly(ADP-ribose) formation in V79 cells. SQAP caused DNA double-strand breaks and chromosome aberrations in V79 BRCA2-mutated cells but did not affect cells in the G2 phase. We have demonstrated that SQAP induces synthetic lethality in BRCA2-deficient Chinese hamster-derived cells via its effects on poly(ADP-ribose) metabolism, motivating further examination of its therapeutic potential, especially against tumors that are deficient in homologous recombination repair due to mutations in BRCA2 or other genes.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503703"},"PeriodicalIF":1.9,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49849067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of genotoxicity, neurotoxicity, and antioxidant imbalance in silver catfish Rhamdia quelen after subchronic exposure to diisopentyl phthalate","authors":"Laís Fernanda Oya-Silva ,&nbsp;Izonete Cristina Guiloski ,&nbsp;Taynah Vicari ,&nbsp;Bruna Deda ,&nbsp;Fellip Rodrigues Marcondes ,&nbsp;Rafael Dias Simeoni ,&nbsp;Maiara Carolina Perussolo ,&nbsp;Anderson Joel Martino-Andrade ,&nbsp;Daniela Morais Leme ,&nbsp;Helena Cristina Silva de Assis ,&nbsp;Marta Margarete Cestari","doi":"10.1016/j.mrgentox.2023.503702","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503702","url":null,"abstract":"<div><p>Diisopentyl phthalate (DiPeP) is a plasticizer with significant offer and application in Brazilian industries. This is attributed to its origin, which is closely linked to the refining process of sugarcane for ethanol production in the country. In this work, we developed a model for trophic exposure to environmentally relevant doses (5, 25, and 125 ng/g of DiPeP) to identify possible target tissues and toxic effects promoted by subchronic exposure to DiPeP in a Neotropical catfish species (<em>Rhamdia quelen)</em>. After thirty days of exposure, blood, liver, kidney, brain, and muscle were collected and studied regarding DNA damage in blood cells and biochemical analyses. The kidney was the most affected organ, as in the head kidney, genotoxicity was evidenced in all groups exposed to DiPeP. Besides, the caudal kidney showed a reduction in the superoxide dismutase and glutathione peroxidase activities as well as a reduced glutathione concentration. In the liver, exposure to 125 ng/g of DiPeP increased glutathione S-transferase activity and reduced glutathione levels. In muscle, acetylcholinesterase (AChE) was reduced. However, in the brain, an increase in AChE activity was observed after the exposure to lowest doses. In contrast, a significant reduction of brain AChE activity after exposure to the highest dose was detected. The pronounced genotoxicity observed in head kidney cells is of concern, as it may compromise different functions performed by this organ (e.g., hematopoiesis, immune and endocrine functions). In our study, DiPeP proved to be a compound of environmental concern since we have evidenced its nephrotoxic and neurotoxic potential even in low doses.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503702"},"PeriodicalIF":1.9,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49849066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The calculation of historical control limits in toxicology: Do's, don'ts and open issues from a statistical perspective","authors":"Max Menssen","doi":"10.1016/j.mrgentox.2023.503695","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503695","url":null,"abstract":"<div><p>For reporting toxicology studies, the presentation of historical control data and the validation of the concurrent control group with respect to historical control limits have become requirements. However, many regulatory guidelines fail to define <em>how</em> such limits should be calculated and what kind of target value(s) they should cover. Hence, this manuscript is aimed to give a brief review on the methods for the calculation of historical control limits that are in use as well as on their theoretical background. Furthermore, this manuscript is aimed to identify open issues for the use of historical control limits that need to be discussed by the community. It seems that, even after 40 years of discussion, more issues remain open than solved, both, with regard to the available methodology as well as its implementation in user-friendly software. Since several of these topics equally apply to several research fields, this manuscript is addressed to all relevant stakeholders who deal with historical control data obtained from toxicological studies, regardless of their background or field of research.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503695"},"PeriodicalIF":1.9,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49849068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paraoxon and glyphosate induce DNA double-strand breaks but are not type II topoisomerase poisons","authors":"Regina Montero-Montoya ,&nbsp;Karen Suárez-Larios,&nbsp;Luis Serrano-García","doi":"10.1016/j.mrgentox.2023.503657","DOIUrl":"10.1016/j.mrgentox.2023.503657","url":null,"abstract":"<div><p>We tested the hypothesis that the pesticides paraoxon and glyphosate cause DNA double-strand breaks (DSB) by poisoning the enzyme Type II topoisomerase (topo II). Peripheral lymphocytes in G0 phase, treated with the pesticides, plus or minus ICRF-187, an inhibitor of Topo II, were stimulated to proliferate; induced cytogenetic damage was measured.</p><p>Micronuclei, chromatin buds, nucleoplasmic bridges, and extranuclear fragments were induced by treatments with the pesticides, irrespective of the pre-treatment with ICRF-187. These results indicate that the pesticides do not act as topo II poisons. The induction of DSB may occur by other mechanisms, such as effects on other proteins involved in recombination repair.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"890 ","pages":"Article 503657"},"PeriodicalIF":1.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9982205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocyte proliferation activity in untreated rats, measured by immunohistochemical detection of Ki-67: The effect of age on the repeated-dose liver micronucleus assay","authors":"Kensuke Satomoto ,&nbsp;Moeko Aoki ,&nbsp;Atsushi Wakita ,&nbsp;Hiroshi Yamagata ,&nbsp;Tatsuya Mitsumoto ,&nbsp;Takezo Okamoto ,&nbsp;Ryoko Harada ,&nbsp;Shuichi Hamada","doi":"10.1016/j.mrgentox.2023.503658","DOIUrl":"10.1016/j.mrgentox.2023.503658","url":null,"abstract":"<div><p>The repeated-dose liver micronucleus (RDLMN) assay is a widely accepted method for detecting genotoxic substances. We investigated the effect of animal age on this assay. Proliferation activity in the liver tissue of untreated rats at age = 3.5, 6, 8, 10, or 12 weeks was measured via immunohistochemical expression of Ki-67 protein. The percentage of Ki-67-positive hepatocytes decreased markedly with age, reaching very low levels after 10 weeks, indicating decline with age of proliferative capacities in the liver. We calculated the area under the curve (AUC) of the approximate curve generated from the percentage of Ki-67-positive cells, to estimate the hepatocyte proliferation activity over the dosing period in the two regimens of the 4-week RDLMN assay: dosing initiated at age = 6 or 8 weeks. Hepatocyte proliferation activity of the former regimen was approximately double that of the latter. We also calculated the AUC for the juvenile-rat method, in which rats are treated for two days at age = 3.5 weeks. The AUC calculated for that method was approximately half of that for the 4-week repeated-dosing regimen initiated at 6 weeks of age. These findings suggest that the 4-week RDLMN assay with dosing initiated at age = 6 weeks could be approximately twice as sensitive as the other two methods.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"890 ","pages":"Article 503658"},"PeriodicalIF":1.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative mutagenic effectiveness and efficiency of chemical mutagens (Caffeine and EMS) and heavy metals [(Pb(NO3)2 and Cd(NO3)2)] in developing chlorophyll and morphological mutants in lentil","authors":"Durre Shahwar ,&nbsp;Zeba Khan ,&nbsp;Mohammad Yunus Khalil Ansari ,&nbsp;Younghoon Park","doi":"10.1016/j.mrgentox.2023.503668","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503668","url":null,"abstract":"<div><p>Mutagenic effectiveness and efficiency are the utmost vital indices to determine the effective and efficient mutagenic concentrations for the generation of high frequency of desirable mutation in mutation breeding. Nevertheless, there are meager study are available for employing effective and efficient concentration of caffeine, EMS, Pb(NO₃)₂ and Cd(NO₃)₂ for the crop improvement. Thus, the current study was performed to assess the mutagenic effectiveness and efficiency of caffeine, EMS and heavy metals [Pb(NO₃)₂ Cd(NO₃)₂] and to determine the genetic variability of M₂ and M₃ lentil mutant lines. The frequency of different chlorophyll and chromophyll mutation was found highest at moderate and higher concentrations of chemical mutagens and heavy metals in M₁ and M₂ generation. The highest effectiveness was in 20 ppm Cd(NO₃)₂, followed by 20 ppm Pb(NO₃)₂, 0.10% EMS, and 0.10% caffeine. The present investigation also showed lower doses of caffeine, EMS, Pb(NO₃)₂, and Cd(NO₃)₂ were more efficient than higher concentrations, and caffeine was found more efficient followed by EMS, Pb(NO₃)₂, and Cd(NO₃)₂. Furthermore, a broad spectrum of viable mutations affecting different morphological characters of the plants viz., leaves, plant height, growth habits, flowers, pods, and seeds in M₂ and M₃ generation were recorded. Ten morphological mutants showing acceptable agronomic and horticultural features were identified, as genetic resources for further breeding.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"890 ","pages":"Article 503668"},"PeriodicalIF":1.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49839480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of quercetin and thymoquinone against genotoxicity and oxidative stress induced by ZnO nanoparticles in the Wistar rat model","authors":"Nuzhat Parveen ,&nbsp;Mohammad Abdulkader Akbarsha ,&nbsp;A.B. Latif Wani ,&nbsp;Mohd Owais Ansari ,&nbsp;Md Fahim Ahmad ,&nbsp;G.G.H.A. Shadab","doi":"10.1016/j.mrgentox.2023.503661","DOIUrl":"10.1016/j.mrgentox.2023.503661","url":null,"abstract":"<div><p>Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in a variety of consumer and other commercial products. Hence, man faces the risk of exposure to ZnO-NPs and the consequent adverse health effects. Mitigation/prevention of such effects using natural products has drawn the attention of scientists. Therefore, the aim of the present study has been to find the toxic effects associated with exposure to ZnO-NPs, and the protective role of the phytochemicals thymoquinone (TQ) and quercetin (QCT) in the rat model. ZnO-NPs were administered to male Wistar rats through oral route; TQ / QCT was concurrently administered through intra-peritoneal route. The response in the animal was analyzed adopting chromosomal aberration test, micronucleus test, and comet assay of bone marrow cells to assess the genotoxicity, and biochemical assays of superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), total extractable protein of liver, and reduced glutathione (GSH) of liver homogenate to monitor the changes in the antioxidant defense mechanism in response to the oxidative stress. Treatment of 300 mg/kg body weight (bw) of ZnO-NPs produced adverse effects on all aspects analyzed viz., structural chromosomal aberrations, micronuclei formation, DNA damage, SOD, catalase, lipid peroxidation, GSH, and extractable total protein of liver. Co-treatment of TQ / QCT offered protection against the toxicity induced by ZnO-NPs. The most optimum doses of TQ and QCT that offered the best protection were 18 mg/kg bw and 500 mg/kg bw, respectively. The study reveals that TQ / QCT supplementation is beneficial in the context of toxic effects of ZnO-NPs.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"890 ","pages":"Article 503661"},"PeriodicalIF":1.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The moderating role of macronutrient intake in relation to body composition and genotoxicity: A study with gym users","authors":"Diene da Silva Schlickmann ,&nbsp;Patrícia Molz ,&nbsp;Gabriela Cristina Uebel ,&nbsp;Caroline Santos ,&nbsp;Caroline Brand ,&nbsp;Renato Alberto Weber Colombelli ,&nbsp;Thalia Gama da Silva ,&nbsp;Juliana Priebe Steffens ,&nbsp;Eduarda da Silva Limberger Castilhos ,&nbsp;Pedro J. Benito ,&nbsp;Alexandre Rieger ,&nbsp;Silvia Isabel Rech Franke","doi":"10.1016/j.mrgentox.2023.503660","DOIUrl":"10.1016/j.mrgentox.2023.503660","url":null,"abstract":"<div><p>In a cross-sectional study of gymnasium users (both sexes, ages = 41.9 ± 14.8 years), we examined the moderating role of macronutrient intake in relation to body composition and genotoxicity. A questionnaire was administered to evaluate characteristics of the participants. To assess macronutrient consumption, we used 24-h food recalls on three non-consecutive days. Body composition (body fat percentage and muscle mass) was evaluated with a bioimpedance scale. Genotoxicity was assessed with the buccal micronucleus cytome assay. Multiple linear regression models were applied, adjusting for age; sex; tobacco and alcohol consumption; and (with regard to exercise habits) frequency, training time, intensity, and types. Micronucleus frequency was directly associated with body fat and inversely associated with muscle mass. Our study shows that carbohydrate and fat intakes affect body fat percentage and micronucleus frequency in gymnasium users.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"890 ","pages":"Article 503660"},"PeriodicalIF":1.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micronuclei and nuclear buds in amniotic tissue of rats treated with cyclophosphamide","authors":"Ramón Guillermo Ortiz-García ,&nbsp;Belinda Claudia Gómez-Meda ,&nbsp;Juan Ernesto Gutiérrez-Sevilla ,&nbsp;Martha Patricia Gallegos-Arreola ,&nbsp;Ana Lourdes Zamora-Perez ,&nbsp;Yveth Marlene Ortiz-García ,&nbsp;Víctor Eduardo García-Arias ,&nbsp;Blanca Miriam Torres-Mendoza ,&nbsp;Guillermo Moisés Zúñiga-González","doi":"10.1016/j.mrgentox.2023.503659","DOIUrl":"10.1016/j.mrgentox.2023.503659","url":null,"abstract":"<div><p>Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14–19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48–120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"890 ","pages":"Article 503659"},"PeriodicalIF":1.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}