Publications by authors named "Le Zhang"

975 Publications

Natural copper isotopic abnormity in maternal serum at early pregnancy associated to risk of spontaneous preterm birth.

Sci Total Environ 2022 Aug 5:157872. Epub 2022 Aug 5.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Spontaneous preterm birth (SPB) has drawn public attention due to its increasing incidence and adverse effects on fetal growth. Effect of copper (Cu) imbalance in maternal bodies on the risk of SPB remains a subject of debate, and the related mechanisms are still unraveled. Here we applied natural stable copper isotopes to explore the underlying association and mechanism of copper imbalance with SPB using a nested case-control study. We collected maternal sera at the early pregnancy stage and then measured their copper isotopic ratio (Cu/Cu, expressed as δCu) as well as physiological and biochemical indexes from women with and without delivering SPB. We found that SPB cases had no significant difference in serum copper level from their controls, but their serum copper was significantly isotopically heavier than the controls (δCu value = 0.15 ± 0.34 ‰ versus -0.15 ± 0.17 ‰, P = 0.0149). Compared with the controls with lower δCu values, the crude odds ratio (OR) associated with SPB risk increased to 4.00 (95 % confidence interval (CI): 1.37-11.70) and the adjusted OR reached up to 11.35 (95 % CI: 1.35-95.60). Furthermore, via the copper isotopic fractionation, we revealed that dietary intake and blood ceruloplasmin may play more important roles than blood lipids and mother-to-child transmission in the copper imbalance associated with SPB. Further studies will be needed to understand the mechanisms of isotope fractionation related to reproductive health.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157872DOI Listing
August 2022

The Upregulation of HAS2-AS1 Relates to the Granulosa Cell Dysfunction by Repressing TGF-β Signaling and Upregulating HAS2.

Mol Cell Biol 2022 Aug 8:e0010722. Epub 2022 Aug 8.

Department of Reproductive Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

HAS2 antisense RNA 1 (HAS2-AS1) is a long noncoding RNA that has increased expression in mature granulosa cells (GCs) and contributes to cumulus expansion by regulating HAS2 expression. However, the roles of HAS2-AS1 during the pathological process of polycystic ovary syndrome (PCOS) are still unclear. This study investigated the roles of HAS2-AS1 in patients with PCOS. Here, a significant upregulation of HAS2-AS1 was found in the primary GCs from patients with PCOS, which was positively correlated with the level of the protein HAS2. The knockdown of HAS2 restored the upregulation of HAS2-AS1 in promoting migration but could not restore the effects of HAS2-AS1 overexpression in promoting proliferation and repressing apoptosis. Transforming growth factor β (TGF-β) upregulated HAS2-AS1 levels, while HAS2-AS1 functioned as a feedback inhibition factor repressing TGF-β signaling by inhibiting TGF-β receptor type 2 (TGFBR2) expression. HAS2-AS1 bonded with EZH2 and guided the polycomb complex 2 to the TGFBR2 promoter region. HAS2-AS1 overexpression induced H3K27 hypermethylation in the TGFBR2 promoter region and then repressed TGFBR2 transcription in KGN cells and primary GCs. In conclusion, we identified for the first time that HAS2-AS1 is upregulated in patients with PCOS and represses TGF-β signaling via inducing TGFBR2 promoter region hypermethylation, which allowed us to explore the pathological processes of PCOS.
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http://dx.doi.org/10.1128/mcb.00107-22DOI Listing
August 2022

A Review on Enhancing Fermentation for Poly(3-hydroxybutyrate) (PHB) Production From Low-Cost Carbon Sources.

Front Bioeng Biotechnol 2022 19;10:946085. Epub 2022 Jul 19.

NUS Environmental Research Institute, National University of Singapore, Singapore, Singapore.

In the context of a circular economy, bioplastic production using biodegradable materials such as poly(3-hydroxybutyrate) (PHB) has been proposed as a promising solution to fundamentally solve the disposal issue of plastic waste. PHB production techniques through fermentation of PHB-accumulating microbes such as have been revolutionized over the past several years with the development of new strategies such as metabolic engineering. This review comprehensively summarizes the latest PHB production technologies fermentation. The mechanism of the biosynthesis pathway for PHB production was first assessed. PHB production efficiencies of common carbon sources, including food waste, lignocellulosic materials, glycerol, and carbon dioxide, were then summarized and critically analyzed. The key findings in enhancing strategies for PHB production in recent years, including pre-treatment methods, nutrient limitations, feeding optimization strategies, and metabolism engineering strategies, were summarized. Furthermore, technical challenges and future prospects of strategies for enhanced production efficiencies of PHB were also highlighted. Based on the overview of the current enhancing technologies, more pilot-scale and larger-scale tests are essential for future implementation of enhancing strategies in full-scale biogas plants. Critical analyses of various enhancing strategies would facilitate the establishment of more sustainable microbial fermentation systems for better waste management and greater efficiency of PHB production.
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http://dx.doi.org/10.3389/fbioe.2022.946085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343952PMC
July 2022

Acute kidney injury and its association with mortality in Asian COVID-19 patients: A meta-analysis.

Clin Nephrol 2022 Aug 4. Epub 2022 Aug 4.

Background: Previous evidence suggests that acute kidney injury (AKI) is common in patients with COVID-19 and associated with adverse outcomes. Moreover, the incidence and mortality of AKI in Asia are ambiguous.

Objective: Evaluating the risk factors and risk of death from AKI in COVID-19 patients in Asia.

Materials And Methods: We conducted a meta-analysis of clinical observational studies of COVID-19 patients in Asia. Outcome measures included: AKI in COVID-19 patients, overall mortality in COVID-19 patients, and mortality assessment in patients with AKI. The random-effects model was adopted, with heterogeneity and sensitivity analysis.

Results: 27 clinical studies (18,216 Asian patients with COVID-19) have been included in the study. The pooled incidence of AKI was 0.19 (95% CI 16 - 23%; I2 = 98.9%, p < 0.001); the pooled incidence of total mortality was 0.19 (95% CI 17 - 22%; I2 = 98.9%, p < 0.001). No publication bias was found (Egger's test, p = 0.396, 0.213). The pooled mortality in AKI patients with COVID-19 was 50% (95% CI 33 - 67%; I2 by random-effects model = 98.4%, p < 0.001). AKI was found to be a risk factor for death in stepwise regression analysis; age, diabetes, and hypertension were influencing factors for AKI risk in COVID-19 patients.

Conclusion: AKI is a common complication in Asian COVID-19 patients, and it is associated with an increase in mortality of Asian COVID-19 patients. Any treatment that protects the kidney may be a practical intervention to reduce the mortality of COVID-19 patients in Asia.
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http://dx.doi.org/10.5414/CN110899DOI Listing
August 2022

Prevalence of Metabolic Syndrome and Risk Factors Among Chinese Adults: Results from a Population-Based Study - Beijing, China, 2017-2018.

China CDC Wkly 2022 Jul;4(29):640-645

Institute of Reproductive and Child Health / Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.

What Is Already Known About This Topic?: Metabolic syndrome (MetS) is one of the most easily available health indicative markers for cardiovascular diseases, and it has become a major public health problem worldwide due to increasing urbanization and aging populations. The prevalence of MetS increased dramatically in China, however, there are no records of MetS defined by the 2017 Chinese Diabetes Society for Beijing by far.

What Is Added By This Report?: In this study, the data of 24,412 participants aged 18-74 years from a large population-based study in Beijing was collected. The overall prevalence of MetS among Beijing residents was 24.5%. The prevalence was 35.2% in males and 15.4% in females.

What Are The Implications For Public Health Practice?: Effective public health strategies should target males, people with older age, lower education, higher body mass index, smokers, those who drink alcohol, those who are unemployed or retired, and those who live in rural areas on MetS prevention and control.
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http://dx.doi.org/10.46234/ccdcw2022.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339350PMC
July 2022

First Report of leaf spot disease caused by Enterobacter mori on Canna indica in China.

Plant Dis 2022 Aug 1. Epub 2022 Aug 1.

College of Coastal Agricultural Sciences of Guangdong Ocean University, Department of Biotechnology, Zhanjiang, China;

Canna indica L. is a popular landscape ornamental herb of family Cannaceae throughout China. This plant has been extensively cultivated for decoration and as an ornamental in China. C. indica was seriously affected by a disease in the garden in spring of 2021 with an incidence of 21.2 to 45.6%, and it caused economic loss to control plant diseases with chemicals. Both young and older leaves developed necrotic lesions with small water-soaked spots on leaves, which then enlarged and were bordered by chlorosis. Symptomatic tissues were collected from Zhanjiang city (21.2N110.3E) and Wuchuan city (21.4N110.7E) in Guangdong province. Three symptomatic leaves from each city were surface disinfected in a 1% hypochlorite solution for 3 mins followed by being rinsed in sterile distilled water for 3 times. Six bacterial isolates originated from six single colonies were recovered from the samples. Colonies were raised and opaque with smooth margins. The bacteria were gram-negative, rod-shaped with sizes ranged from 0.4-0.7 μm wide and 1.2-2.0 μm long, without endospore, and were facultative anaerobes. For molecular identification, the direct colony PCR method (Lu et al. 2012) was used to amplify the 16S rDNA (Moreno et al., 2002), gyrB, leuS and rpoB of 2 selected strains, EM21ZJ1 and EM21WC1 using the primer pairs 27F/1492R, gyrB3/gyrB4, leuS3 /leuS4 and rpoBjt112/ rpoBjt748 respectively (Deletoile et al., 2009). The resulting sequences were deposited in GenBank (ON600470 and ON600471 for 16S rDNA; ON600472 and ON600473 for gyrB; ON600474 and ON600475 for LeuS; ON600476 and ON600477 for rpoB). BLAST searches with the four gene sequences revealed the greatest similarity with the sequences of Enterobacter mori (Zhu et al. 2011). The available complete genome sequences of Enterobacter species, especially type strains, were downloaded and the sequences of the corresponding 4 genes of each genome was extracted by Bioedit software. The concatenated sequences were aligned by Mega 11.0 with the neighbor-joining method. Multilocus sequence typing analysis showed that the concatenated sequences of the 2 isolates were clustered with E. mori with 100% bootstrap value. The 2 isolates were selected for pathogenicity tests to fulfill Koch's postulates. Six plants at three- to five-leaf stage were inoculated with each isolate separately, 2 sites of each leaf were inoculated, one site was wounded with a sterile needle and the other was not. The 2 sites of each leaf were covered with a piece of cotton drenched with 200 µl bacteria suspension (108 CFU/ml) from 2 isolates separately. Control plants were inoculated identically except Luria-Bertani (LB) medium was used to drench the cotton. Inoculated plants were placed in an incubator at 25°C, and 80% humidity under a 12-h light/dark cycle for 7 days. After 3 days of incubation, water-soaked yellow spots were observed in all the inoculated plants in both wounded and unwounded sites, except the negative control. The water-soaked yellow spots enlarged and became necrotic that matched those seen in garden. The pathogenicity tests were conducted three times with similar results. The bacteria were then reisolated from the lesions and found to have the same colony morphology and 99.9% identity of 16S rDNA sequences as those of the inoculum. According to morphological and sequence analysis, the pathogen was identified as E. mori. To our knowledge, this is the first report of disease of C. indica caused by E. mori.
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http://dx.doi.org/10.1094/PDIS-05-22-1223-PDNDOI Listing
August 2022

Reduced HGF/MET Signaling May Contribute to the Synaptic Pathology in an Alzheimer's Disease Mouse Model.

Front Aging Neurosci 2022 12;14:954266. Epub 2022 Jul 12.

Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United States.

Alzheimer's disease (AD) is a neurodegenerative disorder strongly associates with aging. While amyloid plagues and neurofibrillary tangles are pathological hallmarks of AD, recent evidence suggests synaptic dysfunction and physical loss may be the key mechanisms that determine the clinical syndrome and dementia onset. Currently, no effective therapy prevents neuropathological changes and cognitive decline. Neurotrophic factors and their receptors represent novel therapeutic targets to treat AD and dementia. Recent clinical literature revealed that MET receptor tyrosine kinase protein is reduced in AD patient's brain. Activation of MET by its ligand hepatocyte growth factor (HGF) initiates pleiotropic signaling in the developing brain that promotes neurogenesis, survival, synaptogenesis, and plasticity. We hypothesize that if reduced MET signaling plays a role in AD pathogenesis, this might be reflected in the AD mouse models and as such provides opportunities for mechanistic studies on the role of HGF/MET in AD. Examining the 5XFAD mouse model revealed that MET protein exhibits age-dependent progressive reduction prior to overt neuronal pathology, which cannot be explained by indiscriminate loss of total synaptic proteins. In addition, genetic ablation of MET protein in cortical excitatory neurons exacerbates amyloid-related neuropathology in 5XFAD mice. We further found that HGF enhances prefrontal layer 5 neuron synaptic plasticity measured by long-term potentiation (LTP). However, the degree of LTP enhancement is significantly reduced in 5XFAD mice brain slices. Taken together, our study revealed that early reduction of HGF/MET signaling may contribute to the synaptic pathology observed in AD.
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http://dx.doi.org/10.3389/fnagi.2022.954266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314739PMC
July 2022

Berberine Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis and Inhibits the Secretion of Gut Lysozyme via Promoting Autophagy.

Metabolites 2022 Jul 23;12(8). Epub 2022 Jul 23.

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease, the occurrence of which has been increasing worldwide. Research in recent years has found that the level of lysozyme in the feces and blood of UC patients is abnormally elevated, and the bacterial product after the action of lysozyme can be used as an agonist to recognize different cell pattern receptors, thus regulating the process of intestinal inflammation. Berberine (BBR), as a clinical anti-diarrhea and anti-inflammatory drug, has been used in China for hundreds of years. In this study, results showed that BBR can significantly inhibit the expression and secretion of lysozyme in mice. Therefore, we try to investigate the mechanism behind it and elucidate the new anti-inflammatory mechanism of BBR. In vitro, lipopolysaccharide (LPS) was used to establish an inflammatory cell model, and transcriptomic was used to analyze the differentially expressed genes (DEGs) between the LPS group and the LPS + BBR treatment group. In vivo, dextran sulfate sodium salt (DSS) was used to establish a UC mice model, and histologic section and immunofluorescence trails were used to estimate the effect of BBR on UC mice and the expression of lysozyme in Paneth cells. Research results showed that BBR can inhibit the expression and secretion of lysozyme by promoting autophagy via the AMPK/MTOR/ULK1 pathway, and BBR promotes the maturation and expression of lysosomes. Accordingly, we conclude that inhibiting the expression and secretion of intestinal lysozyme is a new anti-inflammatory mechanism of BBR.
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http://dx.doi.org/10.3390/metabo12080676DOI Listing
July 2022

Fatty Acid Signaling Impacts Prostate Cancer Lineage Plasticity in an Autocrine and Paracrine Manner.

Cancers (Basel) 2022 Jul 15;14(14). Epub 2022 Jul 15.

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Prostate cancer (PCa) affects an estimated 250,000 men every year and causes 34,000 deaths annually. A high-fat diet and obesity are associated with PCa progression and mortality. This study's premise was the novel observation of crosstalk between PCa epithelia and cancer-associated fibroblasts (CAF) in response to palmitate-mediated lineage plasticity. We found that cholesterol activated canonical Hedgehog (Hh) signaling by increasing cilium Gli activity in PCa cells, while palmitate activated Hh independent of Gli. Exogenous palmitate activated SOX2, a known mediator of lineage plasticity, in PCa cells cocultured with CAF. Stroma-derived Wnt5a was upregulated in CAF while cocultured with PCa cells and treated with palmitate. Wnt5a knockdown in CAF inhibited Hh and SOX2 expression in PCa cells from cocultures. These findings supported our proposed mechanism of a high-fat diet promoting Hh signaling-mediated transformation within the tumor microenvironment. SOX2 and Wnt5a expression were limited by the CD36 neutralizing antibody. Mice xenografted with PCa epithelia and CAF tumors were fed a high-fat diet, leading to elevated SOX2 expression and lineage plasticity reprogramming compared to mice fed an isocaloric rodent diet. CD36 inhibition with enzalutamide elevated apoptosis by TUNEL, but limited proliferation and SOX2 expression compared to enzalutamide alone. This study revealed a mechanism for a high-fat diet to affect prostate cancer progression. We found that saturated fat induced lineage plasticity reprogramming of PCa by interaction with CAF through Wnt5a and Hh signaling.
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http://dx.doi.org/10.3390/cancers14143449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318639PMC
July 2022

Association Between Plasma Fibulin-1 and Brachial-Ankle Pulse Wave Velocity in Arterial Stiffness.

Front Cardiovasc Med 2022 7;9:837490. Epub 2022 Jul 7.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Arterial stiffness forms the basis of cardiovascular diseases (CVD) and is also an independent predictor of CVD risk. Early detection and intervention of arterial stiffness are important for improving the global burden of CVD. Pulse wave velocity (PWV) is the gold standard for assessing arterial stiffness and the molecular mechanism of arterial stiffness remains to be studied. Extracellular matrix (ECM) remodeling is one of the major mechanisms of arterial stiffness. Partial quantitative changes of ECM proteins can be detected in plasma. Therefore, we examined the hypothesis that a discovery proteomic comparison of plasma proteins between high arterial stiffness (baPWV ≥ 1,400 cm/s) and normal arterial stiffness (baPWV < 1,400 cm/s) populations might identify relevant changed ECM proteins for arterial stiffness. Plasma samples were randomly selected from normal arterial stiffness ( = 6) and high arterial stiffness ( = 6) people. Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomics technique was performed to find a total of 169 differentially expressed proteins (DEPs). Nine ECM proteins were included in all DEPs and were all up-regulated proteins. Fibulin-1 had the highest statistically fold-change (FC = 3.7, < 0.0001) in the high arterial stiffness population compared with the control group during the nine ECM proteins. The expression of plasma fibulin-1 in normal arterial stiffness ( = 112) and high arterial stiffness ( = 72) populations was confirmed through enzyme-linked immunosorbent assay (ELISA). Similarly, ELISA results showed that plasma concentrations of fibulin-1 in the high arterial stiffness group were higher than those in the normal arterial stiffness group (12.69 ± 0.89 vs. 9.84 ± 0.71 μg/ml, < 0.05). Univariate analysis of fibulin-1 with brachial-ankle pulse wave velocity (baPWV) indicated that fibulin-1 was positively correlated with baPWV in all participants ( = 0.32, < 0.01) and a stronger positive correlation between baPWV and fibulin-1 in high arterial stiffness group ( = 0.64, < 0.0001) was found. Multiple regression analysis of factors affecting baPWV showed that fibulin-1 was also a significant determinant of the increased ba-PWV ( = 0.635, = 0.001). Partial correlation analysis showed that baPWV increased with the growth of plasma fibulin-1( = 0.267, < 0.001). In conclusion, our results demonstrated that fibulin-1 is positively correlated with ba-PWV and an independent risk factor for arterial stiffness.
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http://dx.doi.org/10.3389/fcvm.2022.837490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302601PMC
July 2022

Sudden Cardiac Death in Schizophrenia During Hospitalization: An Autopsy-Based Study.

Front Psychiatry 2022 1;13:933025. Epub 2022 Jul 1.

Department of Forensic Medicine, School of Basic Medical Sciences, Gannan Medical University, Ganzhou, China.

Schizophrenia is a severe mental disorder that is often comorbid with heart dysfunction and even sudden cardiac death (SCD). Clinical studies of SCD in schizophrenia have been largely reported, while there are limited autopsy studies that directly showed whole-scale information of such events. In this study, we present nine autopsy-based SCD cases in schizophrenia patients who died suddenly during hospitalization. Their medical records before and during hospitalization, and postmortem autopsy findings were summarized. These decedents had an average duration of schizophrenia for 6.83 ± 3.75 years with a male/female ratio of 4:5. They were all on intermittent antipsychotics medication before hospitalization and died within 15 days after hospitalization. Seven of the nine cases (77.8%) died of organic heart diseases such as severe coronary artery atherosclerosis ( = 4), myocarditis ( = 1), cardiomyopathy ( = 1), and pulmonary thromboembolism ( = 1). Two cases remained unexplained after systemic autopsy and toxicological examinations. Postmortem autopsy identified hepatic steatosis ( = 6) and respiratory inflammation ( = 3) as the most common associate extra-cardiac lesions. Our data provided autopsy-based data of SCD cases in schizophrenia and highlighted an intensive care of such patients during hospitalization.
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http://dx.doi.org/10.3389/fpsyt.2022.933025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283754PMC
July 2022

Access to Phosphine-Containing Quinazolinones Enabled by Photo-Induced Radical Phosphorylation/Cyclization of Unactivated Alkenes.

J Org Chem 2022 Aug 13;87(15):10146-10157. Epub 2022 Jul 13.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

A mild and facile photo-induced cascade radical addition/cyclization of unactivated alkenes has been reported, through which a variety of biologically valuable phosphine-containing quinazolinones could be obtained in moderate to good yields. The protocol was characterized by mild conditions, broad substrate scope, and high atomic economy.
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http://dx.doi.org/10.1021/acs.joc.2c01092DOI Listing
August 2022

Combined with Galactooligosaccharides Supplement: A Neuroprotective Regimen Against Neurodegeneration and Memory Impairment by Regulating Short-Chain Fatty Acids and the c-Jun N-Terminal Kinase Signaling Pathway in Mice.

J Agric Food Chem 2022 Jul 11;70(28):8619-8630. Epub 2022 Jul 11.

College of Food Science, Northeast Agricultural University, Harbin, 150030, China.

Probiotics and prebiotics have received attention in alleviating neurodegenerative diseases. () 69-2 was combined with galactooligosaccharides (GOS) and supplemented in a d-galactose (d-gal)-induced neurodegeneration and memory impairment mice model to explore its effects on the brain and the regulation of short-chain fatty acids. The results showed that the -GOS supplementation inhibited d-gal-induced oxidative stress and increased the brain's nuclear factor erythroid 2-related factor 2 (Nrf2) levels. Butyrate, a metabolite of the gut microbiota regulated by combined with GOS, inhibits p-JNK expression, downregulates pro-apoptotic proteins expression and the activation of inflammatory mediators, and upregulates synaptic protein expression. This might be a potential mechanism for 69-2 combined with GOS supplementation to alleviate d-gal-induced neurodegeneration and memory impairment. This study sheds new light on the development of aging-related neuroprotective dietary supplements based on the gut-brain axis.
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http://dx.doi.org/10.1021/acs.jafc.2c01950DOI Listing
July 2022

Bioaugmentation of Methanosarcina thermophila grown on biochar particles during semi-continuous thermophilic food waste anaerobic digestion under two different bioaugmentation regimes.

Bioresour Technol 2022 Jul 7;360:127590. Epub 2022 Jul 7.

Energy and Environmental Sustainability for Megacities (E2S2) Phase II, Campus for Research Excellence and Technological Enterprise (CREATE), 1 Create Way, Singapore 138602, Singapore; Department of Chemical & Biomolecular Engineering, NUS, Singapore. Electronic address:

This study presents the effect of bioaugmentation of thermophilic anaerobic digestion of food waste with Methanosarcina thermophila grown on a wood-derived biochar. Two different supplementation regimes were tested, namely a single bioaugmentation (SBABC) in which 10% v/v of the microbes grown on biochar (1 g/L) is added at setup of the reactors, versus a routine bioaugmentation (RBABC) wherein the same amount of supplements were added over 10 feeding cycles. The optimally performing 'R' and 'S' reactors had increased methane yields by 37% and 32% over their respective controls while reactors SBABC 2 and 3 produced 21.89% and 56.09% higher average methane yield than RBABC 2 and 3, respectively. It appears that a single dose bioaugmentation is advantageous for improving AD as analysed in terms of average methane yield and VFA production. This study provides the basis for understanding how biochar and bioaugmentation can be used for engineering sustainable pilot-scale AD processes.
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http://dx.doi.org/10.1016/j.biortech.2022.127590DOI Listing
July 2022

Probing interlayer shear thermal deformation in atomically-thin van der Waals layered materials.

Nat Commun 2022 Jul 9;13(1):3996. Epub 2022 Jul 9.

Department of Electrical and Electronic Engineering, Southern University of Science and Technology, 1088 Xueyuan Avenue, 518055, Shenzhen, P.R. China.

Atomically-thin van der Waals layered materials, with both high in-plane stiffness and bending flexibility, offer a unique platform for thermomechanical engineering. However, the lack of effective characterization techniques hinders the development of this research topic. Here, we develop a direct experimental method and effective theoretical model to study the mechanical, thermal, and interlayer properties of van der Waals materials. This is accomplished by using a carefully designed WSe-based heterostructure, where monolayer WSe serves as an in-situ strain meter. Combining experimental results and theoretical modelling, we are able to resolve the shear deformation and interlayer shear thermal deformation of each individual layer quantitatively in van der Waals materials. Our approach also provides important interlayer coupling information as well as key thermal parameters. The model can be applied to van der Waals materials with different layer numbers and various boundary conditions for both thermally-induced and mechanically-induced deformations.
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http://dx.doi.org/10.1038/s41467-022-31682-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271035PMC
July 2022

Association of Preconception Blood Pressure with the Risk of Anemia in Children under Five Years of Age: A Large Longitudinal Chinese Birth Cohort.

Nutrients 2022 Jun 26;14(13). Epub 2022 Jun 26.

Ministry of Health Key Laboratory of Reproductive Health, Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing 100191, China.

Hypertension during pregnancy may increase the risk of anemia in the offspring. However, few studies have investigated the effects of elevated blood pressure during the preconception period on childhood anemia. This large population-based birth cohort study was performed to determine whether abnormal preconception blood pressure has long-term consequences for childhood health. Data were obtained from the China-US Collaborative Project for Neural Tube Defect Prevention. The study consisted of 40,638 women with singleton live births who were registered in a monitoring system before pregnancy in southern China during the period 1993-1996. Children were assessed by hemoglobin measurement at approximately 53 months of age. The incidences of childhood anemia were 19.80% in the hypertension group and 16.07% in the non-hypertension group. Compared with the non-hypertension group, the hypertension group had an increased risk of childhood anemia (adjusted risk ratio (RR): 1.25; 95% confidence interval (CI): 1.11-1.41). After categorization according to blood pressure, combined systolic and diastolic hypertension was associated with a significantly increased risk of childhood anemia, compared with normotension (adjusted RR: 1.37; 95% CI: 1.16-1.63). Compared with women who had normal blood pressure, the adjusted RRs for childhood anemia were 1.20 (95% CI: 1.13-1.28), 1.26 (95% CI: 1.08-1.47), and 1.38 (95% CI: 1.14-1.67) among women with prehypertension, stage-1 hypertension, and stage-2 hypertension, respectively. Our results suggest a linear association between prepregnancy hypertension and the risk of childhood anemia in the Chinese population. Interventions targeting preconception blood pressure may have a positive effect on childhood health.
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http://dx.doi.org/10.3390/nu14132640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268260PMC
June 2022

A Molecular "A-Type" Tangled Metallocube.

Angew Chem Int Ed Engl 2022 Jul 7:e202208376. Epub 2022 Jul 7.

Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710127, P. R. China.

Tangled cubes feature the topology of typical Platonic cubes, with their "faces" traversed by edges in different ways. This study generates an "A-type" tangled metallocube from the reaction of binuclear gold-NHC complex and H S. The tangled cube topology was validated by multinuclear nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray-ionization (HR-ESI) mass spectrometry, and single-crystal X-ray diffraction analysis. This study offers a simple and effective approach to designing and fabricating new, topologically unique molecular structures.
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http://dx.doi.org/10.1002/anie.202208376DOI Listing
July 2022

High prevalence of taurodontism in North China and its relevant factors: a retrospective cohort study.

Oral Radiol 2022 Jun 30. Epub 2022 Jun 30.

Department of Stomatology, Third Medical Center of Chinese PLA General Hospital, Yongding road No:69, Haidian, Beijing, China.

Objective: The purpose of this study was to investigate the prevalence and relevant factors of taurodontism in North China.

Methods: We retrospectively analysed the cone beam computed tomography (CBCT) of 1025 patients (496 male and 529 female) aged between 10 and 59 years. The crown-body/root (CB/R) ratios of the maxillary and mandibular molars were measured. The prevalence of hypotaurodontism, mesotaurodontism, and hypertaurodontism was then calculated and the incidence of taurodontism along with its relevant factors, was evaluated.

Results: The overall rate of taurodontism in North China was as high as 78.9%. If the third molars (opsigenes) were excluded, which have a big morphological variation from each other, the rate was 52.4%. The mean CB/R ratio of taurodontism differs from tooth position: maxillary mandibular third molars > maxillary third molars > maxillary second molars > maxillary first molars > mandibular second molars > mandibular first molars (P < 0.05). In addition, the 1025 patients were divided into different age groups, and it was found that the mean CB/R ratio decreased with age (P < 0.05). Moreover, the CB/R ratio of the mandibular first and second molars in female patients was higher than males (P < 0.05).

Conclusion: This study revealed that taurodontism is widely prevalent in North China. The incidence of taurodontism increases the closer the tooth is to the back end of the dental arch, and quite a few of the maxillary and mandibular third molars teeth have tapered roots. And the taurodontism is decreased by age, as there were more affected female than male patients.
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http://dx.doi.org/10.1007/s11282-022-00630-1DOI Listing
June 2022

Plastid RNA editing reduction accompanied with genetic variations in , a genus with diverse lifestyle modes.

Plant Divers 2022 May 12;44(3):316-321. Epub 2021 Jul 12.

Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.

Recent sequencing efforts have broadly uncovered the evolutionary trajectory of plastid genomes (plastomes) of flowering plants in diverse habitats, yet our knowledge of the evolution of plastid posttranscriptional modifications is limited. In this study, we generated 11 complete plastomes and performed ultra-deep transcriptome sequencing to investigate the co-evolution of plastid RNA editing and genetic variation in , a genus with diverse trophic lifestyles. Genome size and gene content is reduced in terrestrial and green mycoheterotrophic orchids relative to their epiphytic relatives. This could be partly due to extensive losses and pseudogenization of genes for the plastid NADH dehydrogenase-like complex, but independent pseudogenization of genes has also occurred in the epiphyte , which was reported to use strong crassulacean acid metabolism photosynthesis. RNA editing sites are abundant but variable in number among plastomes. The nearly twofold variation in editing abundance is mainly due to extensive reduction of ancestral editing sites in transcripts of terrestrial, mycoheterotrophic, and plastomes. The co-occurrence of editing reduction and pseudogenization in genes suggests functional constraints on editing machinery may be relaxed, leading to nonrandom loss of ancestral edited sites via reduced editing efficiency. This study represents the first systematic examination of RNA editing evolution linked to plastid genome variation in a single genus. We also propose an explanation for how genomic and posttranscriptional variations might be affected by lifestyle-associated ecological adaptation strategies in .
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http://dx.doi.org/10.1016/j.pld.2021.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209865PMC
May 2022

Methanosarcina thermophila bioaugmentation and its synergy with biochar growth support particles versus polypropylene microplastics in thermophilic food waste anaerobic digestion.

Bioresour Technol 2022 Jun 25;360:127531. Epub 2022 Jun 25.

Energy and Environmental Sustainability for Megacities (E2S2) Phase II, Campus for Research Excellence and Technological Enterprise (CREATE), 1 Create Way, Singapore 138602, Singapore; Department of Chemical & Biomolecular Engineering, NUS, Singapore. Electronic address:

Both biochar supplementation as well as bioaugmentation have been shown in literature to improve the methane yield of anaerobic digestion. In this study, the combination of both are evaluated by growing Methanosarcina thermophila on biochar support particles prior to augmentation of thermophilic food waste anaerobic digestion. Biochar stand alone, bioaugmentation solely, a combination of both added separately or grown together, and utilizing polypropylene (PP) microplastics as growth support instead were all tested when starting up a thermophilic process from mesophilic inoculum. Methanosarcina thermophila and biochar supplementation displayed synergy, with 5% M. thermophila on 1 g/L biochar presenting a 32% increase in specific methane yield over the control. Double the bioaugmentation dosage/concentration was also trialled with a thermophilic inoculum, and 10% M. thermophila grown on 2 g/L biochar displayed the best results with a 20% increase specific methane yield from its control standard.
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http://dx.doi.org/10.1016/j.biortech.2022.127531DOI Listing
June 2022

Association of gestational hypertension and preeclampsia with nonsyndromic orofacial clefts in China: a large prospective cohort study.

J Hypertens 2022 Jul;40(7):1352-1358

Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health.

Background: The associations between hypertensive disorders of pregnancy and nonsyndromic orofacial clefts (NSOFCs) are not consistent or based on case-control study design. We hypothesize that OFCs and NSOFCs are associated with hypertensive disease in pregnancy.

Methods: Data were collected from the Project for Neural Tube Defects Prevention (1993-1996), a large population-based cohort study conducted in two southern provinces of China. We used a system to record all births after 20 complete gestational weeks, including live births and stillbirths, and all structural congenital anomalies regardless of gestational week. A total of 200 215 singleton live births without other external birth defects were finally included.

Results: The incidence of NSOFCs was 20.2 per 10 000 for the whole population, and 20.5 and 39.2 per 10 000 for women with gestational hypertension and preeclampsia, respectively. Compared with the nonpreeclampsia group, preeclampsia was associated with an increased risk of NSOFCs [adjusted risk ratio (RR) = 2.02, 95% confidence interval (CI): 1.27-3.20], cleft lip with or without cleft palate (CL/P) [adjusted RR = 2.24, 95% CI 1.37-3.65], and cleft lip and palate (CLP) [adjusted RR = 2.60, 95% CI 1.45-4.67] but not cleft lip only (CLO) [adjusted RR = 1.66, 95% CI 0.68-4.07] or cleft palate only (CPO) [adjusted RR = 1.09, 95% CI 0.27-4.45]. No associations were observed between gestational hypertension and any types of NSOFCs.

Conclusion: Our study supported that among hypertensive disorders of pregnancy, only preeclampsia increased the risk of NSOFCs and its subtypes (CL/P and CLP).
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http://dx.doi.org/10.1097/HJH.0000000000003150DOI Listing
July 2022

Region-Based Convolutional Neural Network-Based Spine Model Positioning of X-Ray Images.

Biomed Res Int 2022 17;2022:7512445. Epub 2022 Jun 17.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Idiopathic scoliosis accounts for over 80% of all cases of scoliosis but has an unclear pathogenic mechanism. Many studies have introduced conventional image processing methods, but the results often fail to meet expectations. With the improvement and evolution of research in neural networks in the field of deep learning, many research efforts related to spinal reconstruction using the convolutional neural network (CNN) architecture of deep learning have shown promise.

Purpose: To investigate the use of CNN for spine modeling.

Methods: The primary technique used in this study involves Mask Region-based CNN (R-CNN) image segmentation and object detection methods as applied to spine model positioning of radiographs. The methods were evaluated based on common evaluation criteria for vertebral segmentation and object detection. Evaluations were performed using the loss function, mask loss function, classification loss function, target box loss function, average accuracy, and average recall.

Results: Many bony structures were directly identified in one step, including the lumbar spine (L1-L5) and thoracic spine (T1-T12) in frontal and lateral radiographs, thereby achieving initial positioning of the statistical spine model to provide spine model positioning for future reconstruction and classification prediction. An average detection box accuracy of 97.4% and an average segmentation accuracy of 96.8% were achieved for the prediction efficacy of frontal images, with good image visualization. Moreover, the results for lateral images were satisfactory considering the evaluation parameters and image visualization.

Conclusion: Mask R-CNN can be used for effective positioning in spine model studies for future reconstruction and classification prediction.
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http://dx.doi.org/10.1155/2022/7512445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232328PMC
June 2022

A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources.

Cancers (Basel) 2022 Jun 19;14(12). Epub 2022 Jun 19.

BGI-Shenzhen, Shenzhen 518103, China.

Tumor-specific antigens can activate T cell-based antitumor immune responses and are ideal targets for cancer immunotherapy. However, their identification is still challenging. Although mass spectrometry can directly identify human leukocyte antigen (HLA) binding peptides in tumor cells, it focuses on tumor-specific antigens derived from annotated protein-coding regions constituting only 1.5% of the genome. We developed a novel proteogenomic integration strategy to expand the breadth of tumor-specific epitopes derived from all genomic regions. Using the colorectal cancer cell line HCT116 as a model, we accurately identified 10,737 HLA-presented peptides, 1293 of which were non-canonical peptides that traditional database searches could not identify. Moreover, we found eight tumor neo-epitopes derived from somatic mutations, four of which were not previously reported. Our findings suggest that this new proteogenomic approach holds great promise for increasing the number of tumor-specific antigen candidates, potentially enlarging the tumor target pool and improving cancer immunotherapy.
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http://dx.doi.org/10.3390/cancers14123016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220843PMC
June 2022

Recent Advances in the Recognition Elements of Sensors to Detect Pyrethroids in Food: A Review.

Biosensors (Basel) 2022 Jun 10;12(6). Epub 2022 Jun 10.

Institute of Quality Standards & Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

The presence of pyrethroids in food and the environment due to their excessive use and extensive application in the agriculture industry represents a significant threat to public health. Therefore, the determination of the presence of pyrethroids in foods by simple, rapid, and sensitive methods is warranted. Herein, recognition methods for pyrethroids based on electrochemical and optical biosensors from the last five years are reviewed, including surface-enhanced Raman scattering (SERS), surface plasmon resonance (SPR), chemiluminescence, biochemical, fluorescence, and colorimetric methods. In addition, recognition elements used for pyrethroid detection, including enzymes, antigens/antibodies, aptamers, and molecular-imprinted polymers, are classified and discussed based on the bioreceptor types. The current research status, the advantages and disadvantages of existing methods, and future development trends are discussed. The research progress of rapid pyrethroid detection in our laboratory is also presented.
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http://dx.doi.org/10.3390/bios12060402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220870PMC
June 2022

Unveiling the risks and critical mechanisms of polyhexamethylene guanidine on the antibiotic resistance genes propagation during sludge fermentation process.

Bioresour Technol 2022 Sep 17;359:127488. Epub 2022 Jun 17.

Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes, Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China; Anhui Provincial Key Laboratory of Environmental Pollution Control and Resource Reuse, China. Electronic address:

This study mainly investigated the environmental risks of polyhexamethylene guanidine (PHMG) occurred in waste activated sludge (WAS) on the antibiotic resistance genes (ARGs) spread during anaerobic fermentation, and disclosed the critical mechanisms. The total ARGs abundance was increased by 32.2-46.4% at different stressing levels of PHMG. The main resistance mechanism categories of ARGs shifted to the target alternation and efflux pump. PHMG disintegrated WAS structure and increased the cell permeability, which benefitted the mobile genetic elements (MGEs) release and horizontal transfer of ARGs. Besides, PHMG induced the enrichment of potential ARGs hosts (i.e., Burkholderia, Bradyrhizobium and Aeromonas). Moreover, PHMG upregulated the metabolic pathways (i.e., two-component system, quorum sensing, and ATP-binding cassette transporters) and critical genes expression (i.e., metN, metQ, rpfF, rstA and rstB) related with ARGs generation and dissemination. Structural equation model analysis revealed that microbial community structure was the predominant contributor to the ARGs propagation.
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http://dx.doi.org/10.1016/j.biortech.2022.127488DOI Listing
September 2022

Chromosome-scale genomes reveal genomic consequences of inbreeding in the South China tiger: A comparative study with the Amur tiger.

Mol Ecol Resour 2022 Jun 20. Epub 2022 Jun 20.

College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.

The South China tiger (Panthera tigris amoyensis, SCT) is the most critically endangered subspecies of tiger due to functional extinction in the wild. Inbreeding depression is observed among the captive population descended from six wild ancestors, resulting in high juvenile mortality and low reproduction. We assembled and characterized the first SCT genome and an improved Amur tiger (P. t. altaica, AT) genome named AmyTig1.0 and PanTig2.0. The two genomes are the most continuous and comprehensive among any tiger genomes yet reported at the chromosomal level. By using the two genomes and resequencing data of 15 SCT and 13 AT individuals, we investigated the genomic signature of inbreeding depression of the SCT. The results indicated that the effective population size of SCT experienced three phases of decline, ~5.0-1.0 thousand years ago, 100 years ago, and since captive breeding in 1963. We found 43 long runs of homozygosity fragments that were shared by all individuals in the SCT population and covered a total length of 20.63% in the SCT genome. We also detected a large proportion of identical-by-descent segments across the genome in the SCT population, especially on ChrB4. Deleterious nonsynonymous single nucleotide polymorphic sites and loss-of-function mutations were found across genomes with extensive potential influences, despite a proportion of these loads having been purged by inbreeding depression. Our research provides an invaluable resource for the formulation of genetic management policies for the South China tiger such as developing genome-based breeding and genetic rescue strategy.
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http://dx.doi.org/10.1111/1755-0998.13669DOI Listing
June 2022

Nanoplastics cause transgenerational toxicity through inhibiting germline microRNA mir-38 in C. elegans.

J Hazard Mater 2022 09 6;437:129302. Epub 2022 Jun 6.

Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing 210009, China; Shenzhen Ruipuxun Academy for Stem Cell & Regenerative Medicine, Shenzhen 518122, China. Electronic address:

Nanoplastic exposure potentially caused the induction of transgenerational toxicity. Nevertheless, the molecular basis for nanoplastic exposure-induced transgenerational toxicity remains largely unclear. Using Caenorhabditis elegans as an animal model, we examined the role of germline microRNA (miRNA) mir-38 in regulating the transgenerational toxicity of polystyrene nanoparticles (PS-NPs). After the exposure, 1-100 μg/L PS-NP decreased expression of germline mir-38. Meanwhile, germline mir-38 overexpression conferred a resistance to transgenerational PS-NP toxicity, which suggested that the decrease in germline mir-38 mediated the induction of transgenerational PS-NP toxicity. In the germline, mir-38 regulated transgenerational PS-NP toxicity by inhibiting activity of downstream targets (NDK-1, NHL-2, and WRT-3). Among these three downstream targets, germline NDK-1 further controlled transgenerational PS-NP toxicity by suppressing the function of KSR-1/2, two kinase suppressors of Ras. Therefore, in the germline, the decrease in mir-38 mediated induction of transgenerational PS-NP toxicity by at least inhibiting signaling cascade of NDK-1-KSR-1/2 in nematodes. The findings in this study are helpful for providing relevantly molecular endpoints to assess potential transgenerational toxicity of nanoplastics.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129302DOI Listing
September 2022

Post-Translational Modifications of p53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy.

Front Pharmacol 2022 24;13:908772. Epub 2022 May 24.

Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China.

The tumor suppressor p53 is a well-known cellular guardian of genomic integrity that blocks cell cycle progression or induces apoptosis upon exposure to cellular stresses. However, it is unclear how the remaining activities of p53 are regulated after the abrogation of these routine activities. Ferroptosis is a form of iron- and lipid-peroxide-mediated cell death; it is particularly important in p53-mediated carcinogenesis and corresponding cancer prevention. Post-translational modifications have clear impacts on the tumor suppressor function of p53. Here, we review the roles of post-translational modifications in p53-mediated ferroptosis, which promotes the elimination of tumor cells. A thorough understanding of the p53 functional network will be extremely useful in future strategies to identify pharmacological targets for cancer therapy.
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http://dx.doi.org/10.3389/fphar.2022.908772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171069PMC
May 2022

Novel Fluorescent Probe Based on Rare-Earth Doped Upconversion Nanomaterials and Its Applications in Early Cancer Detection.

Nanomaterials (Basel) 2022 May 24;12(11). Epub 2022 May 24.

Jiangsu Key Laboratory of Advanced Laser Materials and Devices, School of Physics and Electronic Engineering, Jiangsu Normal University, Xuzhou 221116, China.

In this paper, a novel rare-earth-doped upconverted nanomaterial NaYF:Yb,Tm fluorescent probe is reported, which can detect cancer-related specific miRNAs in low abundance. The detection is based on an upconversion of nanomaterials NaYF:Yb,Tm, with emissions at 345, 362, 450, 477, 646, and 802 nm, upon excitation at 980 nm. The optimal Yb:Tm doping ratio is 40:1, in which the NaYF:Yb,Tm nanomaterials have the strongest fluorescence. The NaYF:Yb, Tm nanoparticles were coated with carboxylation or carboxylated protein, in order to improve their water solubility and biocompatibility. The two commonly expressed proteins, miRNA-155 and miRNA-150, were detected by the designed fluorescent probe. The results showed that the probes can distinguish miRNA-155 well from partial and complete base mismatch miRNA-155, and can effectively distinguish miRNA-155 and miRNA-150. The preliminary results indicate that these upconverted nanomaterials have good potential for protein detection in disease diagnosis, including early cancer detection.
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http://dx.doi.org/10.3390/nano12111787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181853PMC
May 2022
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