摘要：
Ionizing radiation, as an increasingly serious environmental pollutant, has aroused widespread public concern. Melatonin, as an indole heterocyclic compound, is known to have anti-inflammatory and antioxidant effects. However, few studies have considered the comprehensive impact of melatonin on radiation damage. In this study, we used zebrafish as experimental materials and employed methods such as acridine orange staining, enzyme-linked immunosorbent assay (ELISA), video tracking for automated behavior analysis, microscope imaging, and real-time fluorescence quantitative analysis. Zebrafish embryos at 2 h post-fertilization (hpf) were treated under four different experimental conditions to assess their growth, development, and metabolic consequences. Our findings indicate that 0.10 Gy gamma radiation significantly augments body length, eye area, spine width, and tail fin length in zebrafish, along with a marked increase in oxidative stress (P < 0.05). Moreover, it enhances cumulative swimming distance, time, and average speed, suggesting elevated activity levels. We observed circadian rhythm phase shifts, peak increases, and cycle shortening, accompanied by abnormal expression of genes pivotal to biological rhythms, exercise, melatonin synthesis, apoptosis/anti-apoptosis, and oxidation/antioxidant balance. The inclusion of melatonin (1 × 10-5 mol/L MLT) ameliorated these radiation-induced anomalies, while its independent effect on zebrafish was negligible. Melatonin can regulate oxidative stress responses, hinders apoptosis responses, and reprogramming the expression of rhythm-related genes in zebrafish embryos after reprogramming radiation stimulation. Overall, our research highlights melatonin's critical role in countering the biological damage inflicted by gamma radiation, proposing its potential as a therapeutic agent in radiation protection.
Ionizing radiation, as an increasingly serious environmental pollutant, has aroused widespread public concern. Melatonin, as an indole heterocyclic compound, is known to have anti-inflammatory and antioxidant effects. However, few studies have considered the comprehensive impact of melatonin on radiation damage. In this study, we used zebrafish as experimental materials and employed methods such as acridine orange staining, enzyme-linked immunosorbent assay (ELISA), video tracking for automated behavior analysis, microscope imaging, and real-time fluorescence quantitative analysis. Zebrafish embryos at 2 h post-fertilization (hpf) were treated under four different experimental conditions to assess their growth, development, and metabolic consequences. Our findings indicate that 0.10 Gy gamma radiation significantly augments body length, eye area, spine width, and tail fin length in zebrafish, along with a marked increase in oxidative stress (P < 0.05). Moreover, it enhances cumulative swimming distance, time, and average speed, suggesting elevated activity levels. We observed circadian rhythm phase shifts, peak increases, and cycle shortening, accompanied by abnormal expression of genes pivotal to biological rhythms, exercise, melatonin synthesis, apoptosis/anti-apoptosis, and oxidation/antioxidant balance. The inclusion of melatonin (1 × 10-5 mol/L MLT) ameliorated these radiation-induced anomalies, while its independent effect on zebrafish was negligible. Melatonin can regulate oxidative stress responses, hinders apoptosis responses, and reprogramming the expression of rhythm-related genes in zebrafish embryos after reprogramming radiation stimulation. Overall, our research highlights melatonin's critical role in countering the biological damage inflicted by gamma radiation, proposing its potential as a therapeutic agent in radiation protection.
摘要：
Multiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin. Male Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out. The results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys. In summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.
作者机构：
[Li, Min; Lu, Jia Xi; Shan, Xiao Yun; Yang, Zhen Yu; Mao, De Qian; Jiang, Shan; Yang, Li Chen] Chinese Ctr Dis Control & Prevent, Key Lab Trace Element Nutr Natl Hlth Comm, Natl Inst Nutr & Hlth, Beijing 100050, Peoples R China.;[Shan, Xiao Yun] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Hunan, Peoples R China.;[Zou, Yan; Huang, Li Chun] Zhejiang Prov Ctr Dis Prevent & Control, Hangzhou 310051, Zhejiang, Peoples R China.;[Qiu, Qiu Lan; Zhou, Wei Wen] Guangxi Zhuang Autonomous Reg Ctr Dis Control & Pr, Nanning 530028, Guangxi, Peoples R China.;[Liu, Chang Qing; Luo, Xiao Yan] Hebei Prov Ctr Dis Control & Prevent, Shijiazhuang 050021, Hebei, Peoples R China.
通讯机构：
[Yang, LC ] C;Chinese Ctr Dis Control & Prevent, Key Lab Trace Element Nutr Natl Hlth Comm, Natl Inst Nutr & Hlth, Beijing 100050, Peoples R China.
关键词：
Median urinary iodine concentration;Thyroid-stimulating hormone;Vitamin A;Vitamin D;Postpartum women
摘要：
Objective Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women.
Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women.
Methods A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured.
A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured.
Results The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels.
The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels.
Conclusion The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels.
The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels.
摘要：
Iron metabolism plays a crucial role in cell viability, but its relationship with adult stem cells and cancer stem cells is not fully understood. The ferritin complex, responsible for intracellular iron storage, is important in this process. We report that conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system reduced the number and repopulation capacity of hematopoietic stem cells (HSCs). These effects were associated with a decrease in cellular iron level, leading to impaired mitochondrial function and the initiation of apoptosis. Iron supplementation, antioxidant, and apoptosis inhibitors reversed the reduced cell viability of Fth1-deleted hematopoietic stem and progenitor cells (HSPCs). Importantly, leukemic stem cells (LSCs) derived from MLL-AF9-induced acute myeloid leukemia (AML) mice exhibited reduced Fth1 expression, rendering them more susceptible to apoptosis induced by the iron chelation compared to normal HSPCs. Modulating FTH1 expression using mono-methyl fumarate increased LSCs resistance to iron chelator-induced apoptosis. Additionally, iron supplementation, antioxidant, and apoptosis inhibitors protected LSCs from iron chelator-induced cell death. Fth1 deletion also extended the survival of AML mice. These findings unveil a novel mechanism by which ferritin-mediated iron homeostasis regulates the survival of both HSCs and LSCs, suggesting potential therapeutic strategies for blood cancer with iron dysregulation.
摘要：
Obstructive sleep apnea (OSA) is a serious type of sleep disorder that can lead to cardiometabolic and neurocognitive diseases. We utilized smart device-based photoplethysmography technology to collect sleep data from the Chinese population from 2019 to 2022. Distributed lag nonlinear models combined with a generalized nonlinear model or a linear mixed effects model were used to investigate the shortterm associations between daily temperature and indicators of OSA severity. We included a total of 6,232,056 d of sleep monitoring data from 51,842 participants with moderate to severe risk of OSA from 313 Chinese cities. The relationships between ambient temperature and OSA exacerbation, apneahypopnea index (AHI), and minimum oxygen saturation (MinSpO2) were almost linear and present only on the same day. Higher temperatures were associated with a greater risk of OSA exacerbation, with an 8.4% (95% confidence interval (CI): 7.6%-9.3%) increase per 10 degrees C increase in temperature. A 10 degrees C increase in daily temperature corresponded to an AHI increase of 0.70 events/h (95% CI: 0.65-0.76) and a MinSpO2 decrease of 0.18% (95% CI: 0.16%-0.19%). Exposure to elevated temperatures during the night can also lead to adverse effects. The effects of higher temperatures on OSA severity were stronger among men, participants with a body mass index >= 24 kg/m2, those aged 45 years and older, individuals with a history of hypertension and diabetes, and during the cold season. This large-scale, nationwide, longitudinal study provides robust evidence suggesting that higher ambient temperatures may immediately worsen OSA. (c) 2024 Science China Press. Published by Elsevier B.V. and Science China Press. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
摘要：
Background: Radiotherapy, a primary approach in cancer treatment, damages normal cells while targeting cancer cells. Therefore, it is crucial to identify drugs with minimal side effects, high reliability, and radioprotective effects to develop novel radiotherapy strategies. Hemerocallis citrina extracts (HCE), which are derived from plants with medicinal and culinary applications, possess antioxidative and anticancer properties. Methods: In this study, we investigated the radioprotective effects of HCE on LO2 cells exposed to radiation to determine whether these effects were mediated through the nuclear factor erythroid 2–related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway. Results: Cell proliferation experiments demonstrated the radioprotective effect of HCE on LO2 cells. Western blot analysis revealed that HCE regulated B-cell lymphoma protein 2-associated X, Cleaved-caspase 3, and B-cell lymphoma protein 2, thereby inhibiting radiation-induced apoptosis, which was consistent with the flow cytometry results. Conclusions: Moreover, the detection of ferroptosis-related markers indicated that HCE alleviated radiation-induced ferroptosis in LO2 cells through the nuclear factor erythroid 2–related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway. These findings provide a theoretical basis for the radioprotective effects of HCE on LO2 cells and offer new insights into the development of radioprotective drugs.
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摘要：
Cervical cancer is a prominent cause of cancer-related mortality among women, with recent attention directed toward exploring the involvement of circular RNAs (circRNAs) in this particular cancer. CircRNAs, characterized by a covalently closed loop structure, belong to a class of single-stranded non-coding RNA (ncRNA) molecules that play crucial roles in cancer development and progression through diverse mechanisms. The abnormal expression of circRNAs in vivo is significantly associated with the development of cervical cancer. Notably, circRNAs actively interact with miRNAs in cervical cancer, leading to the regulation of diverse signaling pathways, and they can contribute to cancer hallmarks such as self-sufficiency in growth signals, insensitivity to antigrowth signals, limitless proliferation, evading apoptosis, tissue invasion and metastasis, and sustained angiogenesis. Moreover, the distinctive biomedical attributes exhibited by circRNAs, including their abundance, conservation, and stability in body fluids, position them as promising biomarkers for various cancers. In this review, we elucidate the tremendous potential of circRNAs as diagnostic markers or therapeutic targets in cervical cancer by expounding upon their biogenesis, characteristics, functions, and databases, highlighting the novel advances in the signaling pathways associated with circRNAs in cervical cancer.
Cervical cancer is a prominent cause of cancer-related mortality among women, with recent attention directed toward exploring the involvement of circular RNAs (circRNAs) in this particular cancer. CircRNAs, characterized by a covalently closed loop structure, belong to a class of single-stranded non-coding RNA (ncRNA) molecules that play crucial roles in cancer development and progression through diverse mechanisms. The abnormal expression of circRNAs in vivo is significantly associated with the development of cervical cancer. Notably, circRNAs actively interact with miRNAs in cervical cancer, leading to the regulation of diverse signaling pathways, and they can contribute to cancer hallmarks such as self-sufficiency in growth signals, insensitivity to antigrowth signals, limitless proliferation, evading apoptosis, tissue invasion and metastasis, and sustained angiogenesis. Moreover, the distinctive biomedical attributes exhibited by circRNAs, including their abundance, conservation, and stability in body fluids, position them as promising biomarkers for various cancers. In this review, we elucidate the tremendous potential of circRNAs as diagnostic markers or therapeutic targets in cervical cancer by expounding upon their biogenesis, characteristics, functions, and databases, highlighting the novel advances in the signaling pathways associated with circRNAs in cervical cancer.
摘要：
A bidirectional self-powered biosensor is constructed for the quasi-simultaneous detection of Pb2+ and Hg2+ based on MoS2@CuS heterostructures as an accelerator and hybridization chain reaction (HCR) as a signal amplification strategy. MoS2@CuS heterostructures significantly facilitate electron transfer between glucose and bioelectrodes, thereby greatly improving the detection signal of self-powered biosensors. This novel biosensor employs the unique sequences of DNAzymes to isolate Pb2+ and Hg2+ by the cleavage effect and thymine (T)–Hg2+–thymine (T) structures, respectively. In the process, Pb2+ cuts the sequence of DNAzyme at the bioanode to trigger glucose oxidation to monitor Pb2+. The as-formed T–Hg2+–T structures activate HCR to reduce [Ru(NH3)6]3+ to detect Hg2+ at the biocathode. It is noteworthy that this biosensor not only realizes Pb2+ or Hg2+ detection in a single-electrode, respectively, but also can quasi-simultaneously detect both Pb2+ and Hg2+ in the bioanode and the biocathode. The novel self-powered biosensor identifies Pb2+ in the range of 106 fM to 10 fM with a limit of detection (LOD) of 3.1 fM and Hg2+ in the range of 106 fM to 1 fM with an LOD of 0.33 fM.
A bidirectional self-powered biosensor is constructed for the quasi-simultaneous detection of Pb2+ and Hg2+ based on MoS2@CuS heterostructures as an accelerator and hybridization chain reaction (HCR) as a signal amplification strategy. MoS2@CuS heterostructures significantly facilitate electron transfer between glucose and bioelectrodes, thereby greatly improving the detection signal of self-powered biosensors. This novel biosensor employs the unique sequences of DNAzymes to isolate Pb2+ and Hg2+ by the cleavage effect and thymine (T)–Hg2+–thymine (T) structures, respectively. In the process, Pb2+ cuts the sequence of DNAzyme at the bioanode to trigger glucose oxidation to monitor Pb2+. The as-formed T–Hg2+–T structures activate HCR to reduce [Ru(NH3)6]3+ to detect Hg2+ at the biocathode. It is noteworthy that this biosensor not only realizes Pb2+ or Hg2+ detection in a single-electrode, respectively, but also can quasi-simultaneously detect both Pb2+ and Hg2+ in the bioanode and the biocathode. The novel self-powered biosensor identifies Pb2+ in the range of 106 fM to 10 fM with a limit of detection (LOD) of 3.1 fM and Hg2+ in the range of 106 fM to 1 fM with an LOD of 0.33 fM.
通讯机构：
[Wang, FD ; Min, JX] Z;Zhejiang Univ, Affiliated Hosp 1, Affiliated Hosp 2, Inst Translat Med,Sch Med,Sch Publ Hlth,State Key, Hangzhou, Peoples R China.;Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch,Basic Med Sci, Hengyang, Peoples R China.;Xinxiang Med Univ, Affiliated Hosp 1, Sch Publ Hlth, Sch Basic Med Sci, Xinxiang, Peoples R China.
摘要：
The identification of aging- and longevity-associated genes is important for promoting healthy aging. By analyzing a large cohort of Chinese centenarians, we previously found that single-nucleotide polymorphisms (SNPs) in the SLC39A11 gene (also known as ZIP11) are associated with longevity in males. However, the function of the SLC39A11 protein remains unclear. Here, we found that SLC39A11 expression is significantly reduced in patients with Hutchinson-Gilford progeria syndrome (HGPS). In addition, we found that zebrafish with a mutation in slc39a11 that significantly reduces its expression have an accelerated aging phenotype, including a shortened average lifespan, muscle atrophy and reduced swimming, impaired muscle regeneration, gut damage, and abnormal morphology in the reproductive system. Interestingly, these signs of premature aging were more pronounced in male zebrafish than in females. RNA-sequencing analysis revealed that cellular senescence may serve as a potential mechanism for driving this slc39a11 deficiency-induced phenotype in mutant zebrafish. Moreover, immunofluorescence showed significantly increased DNA damage and reactive oxygen species signaling in slc39a11 mutant zebrafish. Using inductively coupled plasma mass spectrometry (ICP-MS), we found that manganese significantly accumulates in slc39a11 mutant zebrafish, as well as in the serum of both global Slc39a11 knockout and hepatocyte-specific Slc39a11 knockout mice, suggesting that this metal transporter regulates systemic manganese levels. Finally, using cultured human fibroblasts, we found that both knocking down SLC39A11 and exposure to high extracellular manganese increased cellular senescence. These findings provide compelling evidence that SLC39A11 serves to protect against the aging process, at least in part by regulating cellular manganese homeostasis.
摘要：
Background Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated.
Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated.
Objectives This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved.
This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved.
Methods A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses.
A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses.
Results Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0–3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7–12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism.
Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0–3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7–12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism.
Discussion This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.
This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.
摘要：
Indole-3-acetic acid (IAA), as a critical phytohormone, has positive effects on botanic growth and development. Developed herein is a novel liquid crystal (LC) immunosensor based on the indirect competitive assay format for the detection of IAA. In light of the small molecular weight of antigen IAA, immobilising IAA on the surface of APTES/DMOAP self-assembled membranes by covalent binding has little effect on LC molecular orientation. When anti-IAA was added, anti-IAA specifically bound to immobilised-IAA on the substrate surface, forming an antigen–antibody complex with a large molecular weight, which induced the homeotropic-to-tilted transition of LC, resulting in a change of the optical image from uniformly black to bright under the polarised light. However, when the sample contained free-IAA, the free-IAA would competitively bind to limited anti-IAA with immobilised-IAA on the substrate surface. As the concentration of free-IAA increased, the anti-IAA that could bind to immobilised-IAA gradually decreased, thereby weakening the degree of disturbance to LCs and producing few birefringent textures. The LC-based imaging method had a good signal-to-noise ratio. When the concentration of IAA exceeded 10 −8 M, a ‘positive’ response was observed. The proposed sensor exhibited high sensitivity and desirable selectivity, and it was label free and easy to operate.
