Publications by authors named "Zhiqing Li"

139 Publications

Modified Atmosphere Packaging Maintains the Sensory and Nutritional Qualities of Post-harvest Baby Mustard During Low-Temperature Storage.

Front Nutr 2021 6;8:730253. Epub 2021 Sep 6.

College of Horticulture, Sichuan Agricultural University, Chengdu, China.

Baby mustard is a popular, yet highly perishable, vegetable. There is a need to develop effective methods for maintaining post-harvest qualities of baby mustard. Here, the lateral buds of baby mustard were packed in transparent polyethylene bags with no holes (M0), 6 mm in diameter holes (M1), or 12 mm in diameter holes (M2) and stored at 4°C. The effect of different modified atmosphere packaging (MAP) treatments on the sensory quality, health-promoting compounds, and antioxidant capacity was investigated by comparison with non-wrapped baby mustard. M1 and M2 delayed sensory quality deterioration and slowed declines in the content of ascorbic acid, total phenolics, and glucosinolates and antioxidant capacity during storage. M1 was most effective in prolonging the shelf life (three additional days compared with control lateral buds) and maintaining the content of glucosinolates. However, M0 accelerated the decline in the odor score, acceptability score, and ascorbic acid content and shortened the shelf life of baby mustard by more than 5 d compared with the control. These findings indicate that the effect of MAP treatment depends on the size of the holes in the bag. Based on these results, M1 was an alternative method for prolonging the shelf life and maintaining post-harvest qualities of baby mustard stored at 4°C.
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http://dx.doi.org/10.3389/fnut.2021.730253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450372PMC
September 2021

Fermented Cottonseed Meal as a Partial Replacement for Soybean Meal Could Improve the Growth Performance, Immunity and Antioxidant Properties, and Nutrient Digestibility by Altering the Gut Microbiota Profile of Weaned Piglets.

Front Microbiol 2021 1;12:734389. Epub 2021 Sep 1.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

The study investigated the impact of fermented cottonseed meal (FCSM) on growth performance, immunity and antioxidant properties, nutrient digestibility, and gut microbiota of weaned piglets by replacing soybean meal with FCSM in the diet. The experimental piglets were fed with either the soybean meal diet (SBM group) or fermented cottonseed meal diet (FCSM group) for 14days after weaning. The digestibility of dry matter (DM), organic matter (OM), crude protein (CP), gross energy (GE), amino acids and nitrogen was higher in the FCSM diet than those in the SBM diet (<0.05). The piglets in the FCSM group showed greater growth performance and lower diarrhea rate than those in the SBM group (<0.05). The concentration of serum immunoglobulin G (IgG) and antioxidase, intestinal and hepatic antioxidase were increased and the concentration of malondialdehyde (MDA) in the serum was decreased in those piglets in the FCSM group compared to those piglets in the SBM group (<0.05). The piglets in the FCSM group had a higher concentration of volatile fatty acids (VFAs) in their ileum and cecum and a higher Simpson index of ileum than piglets in the SBM group (<0.05). The relative abundance of and in ileum and , , and in cecum were enhanced in piglets fed with the FCSM diet, whereas the relative abundance of and were increased in piglets fed with the SBM diet. Overall, FCSM replacing SBM improved the growth performance, immunity and antioxidant properties, and nutrient digestibility; possibly the alterant gut microbiota and its metabolism of weaned piglets. Graphical AbstractFermented cottonseed meal as a partial replacement for soybean meal could improve the growth performance, immunity and antioxidant properties, and nutrient digestibility by altering the gut microbiota profile of weaned piglets. SBM, soybean meal; FCSM, fermented cottonseed meal.
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http://dx.doi.org/10.3389/fmicb.2021.734389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440953PMC
September 2021

Pan-HDAC (Histone Deacetylase) Inhibitors Increase Susceptibility of Thoracic Aortic Aneurysm and Dissection in Mice.

Arterioscler Thromb Vasc Biol 2021 Sep 16:ATVBAHA121316808. Epub 2021 Sep 16.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China. (S.Z., Z. Liu, N.X., Z. Li, F.Y., Y.F., W.K.).

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http://dx.doi.org/10.1161/ATVBAHA.121.316808DOI Listing
September 2021

AAV-Containing Exosomes as a Novel Vector for Improved Gene Delivery to Lung Cancer Cells.

Front Cell Dev Biol 2021 13;9:707607. Epub 2021 Aug 13.

Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University at Zhuhai, Zhuhai, China.

Lung carcinoma is the most common type of cancer and the leading cause of cancer-related death worldwide. Among the numerous therapeutic strategies for the treatment of lung cancer, adeno-associated virus (AAV)-mediated gene transfer has been demonstrated to have the potential to effectively suppress tumor growth or reverse the progression of the disease in a number of preclinical studies. AAV vector has a safety profile; however, the relatively low delivery efficacy to particular subtypes of lung carcinoma has limited its prospective clinical translation. Exosomes are nanosized extracellular vesicles secreted from nearly all known cell types. Exosomes have a membrane-enclosed structure carrying a range of cargo molecules for efficient intercellular transfer of functional entities, thus are considered as a superior vector for drug delivery. In the present study, we developed a novel strategy to produce and purify AAV-containing exosomes (AAVExo) from AAV-packaging HEK 293T cells. The cellular uptake capacity of exosomes assisted and enhanced AAV entry into cells and protected AAV from antibody neutralization, which was a serious challenge for AAV application. We tested a list of lung cancer cell lines representing non-small-cell lung cancer and small-cell lung cancer and found that AAVExo apparently improved the gene transfer efficiency compared to conventional AAV vector. Our results were supported in a lung cancer xenograft rodent model. Additionally, we evaluated the gene delivery efficiency in the presence of neutralizing antibody on lung cancer cells. The results demonstrated that AAVExo-mediated gene transfer was not impacted, while the AAV vectors were significantly blocked by the neutralizing antibody. Taken together, we established an efficient methodology for AAVExo purification, and the purified AAVExo largely enhanced gene delivery to lung cancer cells with remarkable resistance to antibody neutralization.
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http://dx.doi.org/10.3389/fcell.2021.707607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414974PMC
August 2021

Characterization of the Role of the Neoxanthin Synthase Gene in Carotenoid Biosynthesis in Chinese Kale.

Genes (Basel) 2021 Jul 24;12(8). Epub 2021 Jul 24.

College of Horticulture, Sichuan Agricultural University, Chengdu 611130, China.

Chinese kale ( var. ) is rich in carotenoids, and neoxanthin is one of the most important carotenoids in Chinese kale. In this study, the function of the neoxanthin synthase gene () in Chinese kale was investigated. , which had a 699-bp coding sequence, was cloned from the white flower cultivar of Chinese kale and was expressed in all developmental stages and organs of Chinese kale; its expression was highest in young seeds. The subcellular localization indicated that BoaNXS was localized in the chloroplast. -overexpressed plants were obtained via -mediated transient overexpression methodology, and the gene overexpression efficiencies ranged from 2.10- to 4.24-fold. The color in the leaves of -overexpressed plants changed from green to yellow-green; the content of total and individual carotenoids, such as neoxanthin, violaxanthin, and lutein, was significantly increased, and the expression levels of most carotenoid biosynthetic genes were notably increased. These findings indicated that is of vital importance in carotenoid biosynthesis in Chinese kale and could be used as a candidate gene for enriching the carotenoid accumulation and color of Chinese kale and other vegetables.
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http://dx.doi.org/10.3390/genes12081122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393425PMC
July 2021

Dietary Inulin Regulated Gut Microbiota and Improved Neonatal Health in a Pregnant Sow Model.

Front Nutr 2021 9;8:716723. Epub 2021 Aug 9.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

This study aimed to investigate the relationship between maternal dietary fiber intake and piglet health. Multiparous sows were randomly assigned to two groups and fed diets without inulin (control group, = 20) or 1.6% inulin (1.6IN group, = 20). The results indicate that 1.6IN prevented the prolonged farrowing duration of sows ( < 0.05) and shortened the average piglet birth interval ( < 0.1). In addition, 1.6IN decreased the percentage of the piglet born weak and the percentage of the piglet with hyperthermia after birth ( < 0.01). Compared with the control group, the 1.6IN group had a lower concentration of urea nitrogen in the colostrum, and also prevented diarrhea, increased litter gain, survival rate, and average daily gain for suckling piglets ( < 0.05). Furthermore, 1.6IN decreased the relative abundance of Firmicutes, , and ; increased the relative abundance of Bacteroidetes, , and . Overall, this study showed that maternal fiber nutrition during pregnancy regulated the health of offspring, and the response of the maternal intestinal microbes played an important role in intervening in the phenotype of sows and neonatal piglets.
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http://dx.doi.org/10.3389/fnut.2021.716723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380823PMC
August 2021

Function of Polyamines in Regulating Cell Cycle Progression of Cultured Silkworm Cells.

Insects 2021 Jul 8;12(7). Epub 2021 Jul 8.

State Key Laboratory of Silkworm Genome Biology, Biological Science Research Center, Southwest University, Chongqing 400715, China.

Background: Putrescine, spermidine, and spermine are polyamines that are ubiquitously distributed in prokaryotic and eukaryotic cells, which play important roles in cell proliferation and differentiation.

Methods: We investigated the expression profiles of polyamine pathway genes by qRT-PCR in different tissues of the lepidopteran silkworm. The polyamine levels in cultured silkworm cells were measured by HPLC. Spermidine and polyamine biosynthetic inhibitors were used for treating the cultured silkworm cells in order to clarify their effects on cell cycle progression.

Results: We identified the anabolic and catabolic enzymes that are involved in the polyamine biosynthetic pathway in silkworm. Transcriptional expression showed at least seven genes that were expressed in different silkworm tissues. Treatments of the cultured silkworm cells with spermidine or inhibitor mixtures of DFMO and MGBG induced or inhibited the expression of cell cycle-related genes, respectively, and thus led to changed progression of the cell cycle.

Conclusions: The present study is the first to identify the polyamine pathway genes and to demonstrate the roles of polyamines on cell cycle progression via regulation of the expression of cell cycle genes in silkworm.
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http://dx.doi.org/10.3390/insects12070624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306941PMC
July 2021

Two-way comparison of brain perfusion image processing software for patients with acute ischemic strokes in real-world.

Neuroradiology 2021 Jul 31. Epub 2021 Jul 31.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.

Purpose: Perfusion imaging generates multimaps of ischemic tissues and is a proven decision-making tool in patients with acute ischemic stroke. However, the reliability of perfusion post-processing outcomes has been debated, given disparate results of various software applications, especially for patients with small ischemic core volume. This study was undertaken to compare ischemic volume estimates determined by imSTROKE (a software with new imaging protocol) and RAPID computer applications, respectively.

Methods: A total of 611 patients qualified for study, each having met inclusion and exclusion criteria of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN trial). Subjects were examined by computed tomography perfusion (CTP) imaging (n = 349) or perfusion-weighted (PWI) and diffusion-weighted (DWI) imaging (n = 262). Ischemic volumes estimated by imSTROKE and RAPID applications were then compared. We used Bland-Altman analysis and intraclass correlation coefficients (ICCs) to ascertain agreement between applications. Accuracies of estimated core infarct and penumbra volumes were tested at specific thresholds (core: 25 mL, 50 mL, and 70 mL; penumbra: 45 mL, 90 mL, and 125 mL).

Results: Median core infarct volumes by imSTROKE and RAPID were 29.18 mL and 29.53 mL, respectively (ICC = 0.9880, 95% confidence interval [CI]: 0.9860-0.9898). Median penumbra volumes by imSTROKE and RAPID were 68.20 mL and 68.55 mL, respectively (ICC = 0.9885, 95% CI: 0.9865-0.9902).

Conclusion: In estimating core infarct and penumbra volumes, imSTROKE and RAPID applications showed high-level agreement. For patients with small ischemic core volume, compared with RAPID, imSTROKE may have better sensitivity.
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http://dx.doi.org/10.1007/s00234-021-02771-2DOI Listing
July 2021

Physiological function and application of dietary fiber in pig nutrition: A review.

Anim Nutr 2021 Jun 17;7(2):259-267. Epub 2021 Apr 17.

College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China.

Dietary fiber (DF), divided into soluble dietary fiber (SDF) and insoluble dietary fiber (IDF), has attracted increasing attention in the field of pig nutrition. Although DF reduces nutrient digestibility and inhibits energy deposition in most cases, fiber-rich feeds have been widely used in pig diets. This is not only because of lower feed costs, but also from the continuous discovery about the nutritional value of DF, mainly including the improvement of piglet intestinal health and sow reproductive performance. The addition timing has also been further considered, which potentially enables the nutritional value of DF to be accurately used in applicable pig models. Furthermore, fiber degrading enzymes have been shown to alleviate the anti-nutritional effects of DF and have ensured the improvement effect of fiber on intestinal health in young piglet models. However, the regulatory effect of fiber on pork quality is still unclear, which requires consideration of the wide range of fiber sources and the complexity of the basic diet composition, as well as the impact of pig breeds. Taken together, future research needs to gain more insight into the combined effects of SDF and IDF, processing methods, and addition timing to improve the nutritional value of DF, and further explore the physiological functions and regulatory mechanisms of DF fermentation products short-chain fatty acids in pigs.
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http://dx.doi.org/10.1016/j.aninu.2020.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245790PMC
June 2021

Enzyme-Treated Soybean Meal Replacing Extruded Full-Fat Soybean Affects Nitrogen Digestibility, Cecal Fermentation Characteristics and Bacterial Community of Newly Weaned Piglets.

Front Vet Sci 2021 20;8:639039. Epub 2021 May 20.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

The study investigated the impact of soybean protein from different processing on the performance, dietary nitrogen digestibility, cecal fermentation characteristics, and bacterial community in newly weaned piglets. The piglets were allocated to two dietary treatment and fed with the extruded full-fat soybean diet (EFS group) and enzyme-treated soybean meal diet (ESBM group), respectively. The piglets in ESBM group showed greater nitrogen digestibility and feed efficiency, and lower diarrhea rate in comparison to piglets in EFS group ( < 0.05). Cecal samples from piglets in ESBM group contained greater concentration of acetate, propionate and total SCFAs ( < 0.05), and lower contents of isobutyrate, isovalerate, total BCFAs, NH-N and putrescine ( < 0.05) than cecal samples from piglets in the EFS group. The cecal samples from piglets in ESBM group contained greater abundances of g_, g_, g_, and g_ than the cecal sample from piglets in the EFS group, which could promote to protect intestinal health. In summary, enzyme-treated soybean meal may enhance the growth performance of weaned piglets increasing the dietary nitrogen digestibility, preventing protein fermentation in the hindgut, which shed light on the mechanism in regulating gut health of dietary protein.
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http://dx.doi.org/10.3389/fvets.2021.639039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173081PMC
May 2021

Selective intra-arterial brain cooling induces cerebral protection against ischemia/reperfusion injury through SENP1-Sirt3 signaling.

Free Radic Biol Med 2021 08 18;171:272-283. Epub 2021 May 18.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, 110004, China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China. Electronic address:

Background: Although it is well known that selective intra-arterial cooling (SI-AC) elicits cerebral protection against ischemia/reperfusion (I/R) injury, the underlying mechanism remains unclear. This study aimed to determine whether SI-AC can protect against cerebral I/R injury by inhibiting oxidative stress and mitochondrial dysfunction through regulation of Sirt3 deSUMOylation via SENP1.

Methods: All mice were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion. SI-AC treatment was performed by infusion with cold saline (10 °C, 20 mL/kg) for 15 min through a microcatheter placed in the internal carotid artery immediately before reperfusion. The infarct volume, survival rate, neurological deficit scores, behavioral parameters, histopathology findings, and apoptosis were assessed. HT22 cells were subjected to 2 h of oxygen and sugar deprivation (OGD) and 22 h of reoxygenation. HA-SUMO1, Flag-Sirt3, a Sirt3 mutation plasmid (Flag-Sirt3 K288R), His-SENP1, and SENP1 small interfering RNA were transfected into HT22 cells 48 h before OGD. Apoptosis-related proteins were analyzed by western blotting. SUMOylation of Sirt3, acetylation of cyclooxygenase 1 (COX1), superoxide dismutase 2 (SOD2), and isocitrate dehydrogenase 2 (IDH2), the activities of COX1, SOD2, and IDH2, oxidative stress, and mitochondrial dysfunction were evaluated.

Results: Compared with the I/R group, SI-AC decreased cerebral infarct volume and neurological deficit scores and increased motor coordination, exploratory behavior, and memory. Hematoxylin and eosin and Nissl staining showed that SI-CA decreased karyopyknosis, nuclear fragmentation, and nucleolysis, increased neuron density, and decreased the cell apoptosis rate. In addition, Sirt3 was revealed as a target protein of SUMO1. SI-AC attenuated cerebral I/R injury through Sirt3 deSUMOylation via SENP1.

Conclusions: SENP1-mediated deSUMOylation of Sirt3 plays an essential role in SI-AC-induced cerebral protection against I/R injury. Our findings provide a promising therapeutic approach for treatment of acute cerebral I/R injury.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.05.026DOI Listing
August 2021

Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study.

Br J Ophthalmol 2021 May 17. Epub 2021 May 17.

Department of Ophthalmology (aka National Clinical Research Center for Eye Diseases), Shanghai General Hospital, Shanghai, China

Background: To demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME).

Methods: A 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline.

Results: A total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study.

Conclusion: The use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept.

Trial Registration Number: NCT02194634.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318690DOI Listing
May 2021

Artificial Intelligence-Based Diagnosis of Diabetes Mellitus: Combining Fundus Photography with Traditional Chinese Medicine Diagnostic Methodology.

Biomed Res Int 2021 20;2021:5556057. Epub 2021 Apr 20.

Tianjin Medical University, 300384, China.

In this study, we propose a technique for diagnosing both type 1 and type 2 diabetes in a quick, noninvasive way by using equipment that is easy to transport. Diabetes mellitus is a chronic disease that affects public health globally. Although diabetes mellitus can be accurately diagnosed using conventional methods, these methods require the collection of data in a clinical setting and are unlikely to be feasible in areas with few medical resources. This technique combines an analysis of fundus photography of the physical and physiological features of the patient, namely, the tongue and the pulse, which are used in Traditional Chinese Medicine. A random forest algorithm was used to analyze the data, and the accuracy, precision, recall, and F1 scores for the correct classification of diabetes were 0.85, 0.89, 0.67, and 0.76, respectively. The proposed technique for diabetes diagnosis offers a new approach to the diagnosis of diabetes, in that it may be convenient in regions that lack medical resources, where the early detection of diabetes is difficult to achieve.
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http://dx.doi.org/10.1155/2021/5556057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081616PMC
May 2021

Effect of Long-Term Frozen Storage on Health-Promoting Compounds and Antioxidant Capacity in Baby Mustard.

Front Nutr 2021 6;8:665482. Epub 2021 Apr 6.

College of Horticulture, Sichuan Agricultural University, Chengdu, China.

This study investigated the effects of blanching and subsequent long-term frozen storage on the retention of health-promoting compounds and antioxidant capacity in frozen lateral buds of baby mustard. Results showed that all glucosinolates were well preserved during frozen storage, and 72.48% of total glucosinolate content was retained in the unblanched treatment group after 8 months, as were chlorophylls, carotenoids, ascorbic acid, total phenolics, soluble sugars, soluble proteins, and antioxidant capacity. The loss of nutritional qualities mainly occurred in the 1st month of frozen storage, and nutritional qualities in the unblanched treatment group were significantly better than those in the blanched treatment group during frozen storage. Blanching before freezing reduced contents of high-content glucosinolates and ascorbic acid, as well as antioxidant capacity levels. Therefore, we recommend using long-term frozen storage to preserve the quality of baby mustard to achieve annual supply, and freezing without blanching.
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http://dx.doi.org/10.3389/fnut.2021.665482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055821PMC
April 2021

Evolution of the Gut Microbiota and Its Fermentation Characteristics of Ningxiang Pigs at the Young Stage.

Animals (Basel) 2021 Feb 27;11(3). Epub 2021 Feb 27.

College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China.

The current study aimed to investigate the evolution of gut microbiota and its influencing factors for NXP in youth. The results showed that Shannon index increased from d 21 to d 28 whereas the ACE index increased from d 21 until d 60. Firmicutes, mainly Lactobacillus dominated on d 21. The Bacteroides and Spirochetes showed highest relative abundance on d 28. Fiber-degrading bacteria, mainly , , , , and , dominated the microbial communities at d 28 and d 35. The microbial communities at d 60 and d 75 contained more , and than other ages, which had significantly positive correlations with acetate and total SCFAs concentration. In conclusion, the evolution of gut microbiota was mainly adapted to the change of dietary factors during NXP growth. The response of fiber-degrading bacteria at different stages may help NXP better adapt to plant-derived feeds.
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http://dx.doi.org/10.3390/ani11030638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997423PMC
February 2021

Corrigendum to 'The antiinflammatory effects of Xuefu Zhuyu decoction on C3H/HeJ mice with alopecia areata' [Phytomedicine vol. 81 (2021), 1-14 / 153423].

Phytomedicine 2021 Mar 21;83:153510. Epub 2021 Feb 21.

Department of dermatology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu 610071, China. Electronic address:

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http://dx.doi.org/10.1016/j.phymed.2021.153510DOI Listing
March 2021

Cartilage oligomeric matrix protein is an endogenous β-arrestin-2-selective allosteric modulator of AT1 receptor counteracting vascular injury.

Cell Res 2021 Jul 28;31(7):773-790. Epub 2021 Jan 28.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.

Compelling evidence has revealed that biased activation of G protein-coupled receptor (GPCR) signaling, including angiotensin II (AngII) receptor type 1 (AT1) signaling, plays pivotal roles in vascular homeostasis and injury, but whether a clinically relevant endogenous biased antagonism of AT1 signaling exists under physiological and pathophysiological conditions has not been clearly elucidated. Here, we show that an extracellular matrix protein, cartilage oligomeric matrix protein (COMP), acts as an endogenous allosteric biased modulator of the AT1 receptor and its deficiency is clinically associated with abdominal aortic aneurysm (AAA) development. COMP directly interacts with the extracellular N-terminus of the AT1 via its EGF domain and inhibits AT1-β-arrestin-2 signaling, but not Gq or Gi signaling, in a selective manner through allosteric regulation of AT1 intracellular conformational states. COMP deficiency results in activation of AT1a-β-arrestin-2 signaling and subsequent exclusive AAA formation in response to AngII infusion. AAAs in COMP or ApoE mice are rescued by AT1a or β-arrestin-2 deficiency, or the application of a peptidomimetic mimicking the AT1-binding motif of COMP. Explorations of the endogenous biased antagonism of AT1 receptor or other GPCRs may reveal novel therapeutic strategies for cardiovascular diseases.
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http://dx.doi.org/10.1038/s41422-020-00464-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249609PMC
July 2021

Quantum defect-assisted multiphonon Raman scattering in metal halide perovskites.

J Phys Condens Matter 2021 Jan 25. Epub 2021 Jan 25.

Department of Applied Physics, Tianjin University, Tianjin 300354, PEOPLES REPUBLIC OF CHINA, Tianjin, 300354, CHINA.

Quantum defects are essential to understand the non-radiative recombination processes in metal halide perovskites-based photovoltaic devices, in which Huang-Rhys factor, reflecting the coupling strength between the charge carrier and optical phonons, plays a key role in determining the nonradiative recombination via multiphonon processes. Herein, we theoretically present multiphonon Raman scattering intermediated by defects arising from the charge carrier of defect coupled with the longitudinal optical (LO) phonon in the deformation potential and Fr¨ohlich mechanisms, respectively. We find that the Raman scattering shows multiple LO phonon overtones at equal interval LO phonons, where Huang-Rhys factor could be evaluated by the order of the strongest overtone. Meanwhile, we give the combinational multiphonon scattering between two mechanisms. Different types of the combinational modes with the weak scattering intensities provide a possible explanation for the long non-radiative charges-carrier lifetimes in metal halide perovskites.
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http://dx.doi.org/10.1088/1361-648X/abdf92DOI Listing
January 2021

Long-term efficacy and safety of curative embolization of brain arteriovenous malformations using the dual microcatheter technique: A single-institution case series and literature review.

Clin Neurol Neurosurg 2021 02 13;201:106417. Epub 2020 Dec 13.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People's Republic of China. Electronic address:

Objective: Brain arteriovenous malformations (bAVMs) are among the most common causes of cerebral hemorrhage in adolescents. For multiple-feeder bAVMs, complete exclusion of the nidus by endovascular embolization is challenging. This case series and literature review examined the long-term efficacy and safety of bAVM embolization using the dual microcatheter technique (DMCT).

Methods: A total of 38 consecutive patients who underwent endovascular treatment for bAVMs with the DMCT along with all cases reported in the literature were retrospectively reviewed. Patient demographics, clinical presentation, bAVM angioarchitecture, treatment, complications, and long-term outcome were independently assessed.

Results: Patients with bAVM (24 male and 14 female, mean age: 33.87 ± 13.70 years) treated at our institution were followed up for 97.76 ± 14.51 months. Angiographic obliteration was achieved in a single embolization session in 27/38 (71.05 %) cases; 4/38 (10.53 %) required multiple sessions, and 7/38 (18.42 %) underwent embolization combined with microsurgery or radiotherapy. Neurologic improvement at 90 days was observed in 29/38 patients (76.32 %). At the final follow-up, 34/38 patients (89.47 %) had a favorable clinical outcome. Two patients experienced recurrence during the follow-up period. In total, 55 patients were ultimately analyzed in our literature review. Complete exclusion of bAVMs was achieved in 35 patients (63.63 %), including in 54.54 % after a single endovascular treatment session. One patient died of hemorrhagic complication after endovascular treatment for an overall mortality rate of 1.82 %.

Conclusions: DMCT is safe for bAVM embolization and shows long-term efficacy, especially for multiple-feeder bAVMs.
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http://dx.doi.org/10.1016/j.clineuro.2020.106417DOI Listing
February 2021

Decreased Expression of the Host Long-Noncoding RNA-GM Facilitates Viral Escape by Inhibiting the Kinase activity TBK1 via S-glutathionylation.

Immunity 2020 12;53(6):1168-1181.e7

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Medical Immunology, Institute of Immunology, Navy Medical University, Shanghai 200433, China; Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address:

Viruses have evolved multiple strategies to evade elimination by the immune system. Here we examined the contribution of host long noncoding RNAs (lncRNAs) in viral immune evasion. By functional screening of lncRNAs whose expression decreased upon viral infection of macrophages, we identified a lncRNA (lncRNA-GM, Gene Symbol: AK189470.1) that promoted type I interferon (IFN-I) production and inhibited viral replication. Deficiency of lncRNA-GM in mice increased susceptibility to viral infection and impaired IFN-I production. Mechanistically, lncRNA-GM bound to glutathione S-transferase M1 (GSTM1) and blocked GSTM1 interaction with the kinase TBK1, reducing GSTM1-mediated S-glutathionylation of TBK1. Decreased S-glutathionylation enhanced TBK1 activity and downstream production of antiviral mediators. Viral infection reprogrammed intracellular glutathione metabolism and furthermore, an oxidized glutathione mimetic could inhibit TBK1 activity and promote viral replication. Our findings reveal regulation of TBK1 by S-glutathionylation and provide insight into the viral mediated metabolic changes that impact innate immunity and viral evasion.
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http://dx.doi.org/10.1016/j.immuni.2020.11.010DOI Listing
December 2020

The antiinflammatory effects of Xuefu Zhuyu decoction on C3H/HeJ mice with alopecia areata.

Phytomedicine 2021 Jan 22;81:153423. Epub 2020 Nov 22.

Department of dermatology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu 610071, China. Electronic address:

Background: As a traditional and typical prescription of prominently activating blood circulation to remove blood stasis, Xuefu Zhuyu decoction (XZD) consists of 15 kinds of herbal medicine. Clinical investigations have showed that XZD could significantly promote the new hair generation of alopecia areata (AA) patients characterized by Qi stagnation and blood stasis.

Purpose: The purpose of this study was executed to determine whether the mechanisms by which XZD stimulated newborn hair were related to its anti-inflammatory effects.

Methods: Clinical AA individuals were recruited to confirm the efficies of XZD. High performance liquid chromatography (HPLC) analysis was performed to qualitatively and quantitatively determine the contents of 15 compounds in XZD. Schrodinger molecular docking and in vivo surface plasmon resonance (SPR) techniques were used to evaluate the potential binding properties of compounds to target proteins. C3H/HeJ mice were randomly assigned to groups control, AA, and the XZD administration (6.5, 13.0 and 26.0 g/kg/d). Except for mice in control group, all the mice in the other groups were treated with a 21-day chronic unpredictable mild stress (CUMS) induced AA. Hematoxylin-eosin (H&E) staining was performed to determine the degree of pathological damage to the skin. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) and in serum and skin tissues. Western blot, immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to examine the expression levels of IL-6, IL-1β, TNF-α and osteopontin proteins and genes in skin tissues.

Results: XZD could visibly promote hair regeneration of AA patients. The potential active ingredients in XZD prescription included at least amygdalin, hydroxysafflor yellow A, kaempferide, ferulic acid, catalpol, verbascoside, β-ecdysone, platycodin D, paeoniflorin, naringin, neohesperidin, liquiritin, glycyrrhizic acid, saikosaponin A and saikosaponin D. The results of molecular docking and SPR analysis showed that verbascoside, liquiritin, kaempferide and amygdalin showed the best potential binding properties with IL-6, IL-1β, TNF-α and osteopontin, respectively. Pathological evaluation showed that compared with the CUMS group, the administration of XZD significantly promoted hair regeneration, evidenced by increased number of skin hair follicles in C3H/HeJ AA mice. Compared with control group, ELISA data showed that the levels of IL-6, IL-1β and TNF-α in serum and skin tissues of CUMS induced AA mice were significantly increased, while XZD administration dramatically restrained the contents of the three pro-inflammatory factors. Western blot, immunohistochemistry, and qRT-PCR results further demonstrated that XZD administration notably down-regulated the protein and gene expression levels of osteopontin, IL-6, IL-1β and TNF-α in comparation with CUMS group.

Conclusion: XZD could dramatically ameliorate CUMS-induced AA damage in the skin of C3H/HeJ mice, possibly by suppressing the levels of IL-6, IL-1β, TNF-α and osteopontin.
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http://dx.doi.org/10.1016/j.phymed.2020.153423DOI Listing
January 2021

Targeted exome sequencing identified a novel USH2A mutation in a Chinese usher syndrome family: a case report.

BMC Ophthalmol 2020 Dec 10;20(1):485. Epub 2020 Dec 10.

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Tianjin, 300384, China.

Background: Usher syndrome is a disease with a heterogeneous phenotype and genotype. Our purpose was to identify the gene mutation in a Chinese family with Usher syndrome type 2 and describe the clinical features.

Case Presentation: A 23-year-old man complained of a 10-year duration of nyctalopia and a 3-year decline in visual acuity of both eyes accompanied by congenital dysaudia. To clarify the diagnosis, the clinical symptoms were observed and analysed in combination with comprehensive ophthalmologic examinations as well as genetic analysis (targeted exome sequencing, TES). A typical clinical presentation of Usher syndrome of the fundus was found, including a waxy yellow-like disc, bone-spicule formations and retinal vessel stenosis. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) showed loss of the ellipsoid zone and a reduction in paracaval vessel density in both eyes. Genetic analysis identified a novel homozygous c.8483_8486del (p.Ser2828*) mutation in USH2A. The mutation resulted in premature termination of translation and caused the deletion of 19 fibronectin type 3 domains (FN3), transmembrane (TM) region and PDZ-binding motif domain, which play an important role in protein binding. After combining the clinical manifestations and genetic results, the patient was diagnosed with Usher syndrome type 2.

Conclusion: We found a novel c.8483_8486del mutation in the USH2A gene through TES techniques. The results broaden the spectrum of mutations in Usher syndrome type 2 and suggest that a combination of clinical information and molecular diagnosis via TES could help Usher syndrome patients obtain a better diagnosis.
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http://dx.doi.org/10.1186/s12886-020-01711-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727220PMC
December 2020

Long-term follow-up of transarterial balloon-assisted Onyx embolization for endovascular treatment of dural arteriovenous fistulas: A single-institution case series and literature review.

Clin Neurol Neurosurg 2020 12 1;199:106256. Epub 2020 Oct 1.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, 110004, People's Republic of China. Electronic address:

Objective: Dural arteriovenous fistulas (DAVFs)-specifically, symptomatic DAVFs with cortical venous reflux-are aggressive lesions with a poor prognosis. Intra-arterial endovascular closure is considered the optional treatment for DAVFs and is currently performed at several international centers. However, long-term outcomes remain unknown. This study investigated the long-term efficacy and safety of transarterial balloon-assisted Onyx embolization in the treatment of DAVFs.

Methods: A total of 14 consecutive patients who underwent endovascular treatment for DAVFs were treated by balloon-assisted Onyx embolization. Additionally, we retrospectively reviewed all cases reported in the literature and compared the outcomes of patients treated with single- vs dual-lumen microcatheters.

Results: The patients at our institution were followed-up for 114.57 ± 33.52 months. Embolization was performed by balloon-assisted Onyx injection via a single feeding artery. Complete occlusion was achieved in 13 cases and partial occlusion in 1 case. At the final follow-up, all patients were functionally independent (Modified Rankin Scale score of 0-2), with no recurrence. In our review of 70 published cases of DAVFs that underwent endovascular treatment by balloon-assisted Onyx embolization, single- and dual-lumen balloon catheters were used in 33 and 37 patients, respectively. In the former group, there was complete or near-complete occlusion in 32 cases and partial occlusion in 1 case; and in the latter, there was complete or near-complete occlusion in 35 cases and partial occlusion in 2 cases. There were no deaths following endovascular treatment.

Conclusion: Measurable and durable outcomes can be achieved by endovascular treatment of DAVFs with the transarterial balloon-assisted Onyx embolization technique, especially in cases with small, distal, and circuitous feeding arteries.
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http://dx.doi.org/10.1016/j.clineuro.2020.106256DOI Listing
December 2020

How mammalian piRNAs instruct de novo DNA methylation of transposons.

Signal Transduct Target Ther 2020 09 7;5(1):190. Epub 2020 Sep 7.

Key Laboratory of Growth Control and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.

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http://dx.doi.org/10.1038/s41392-020-00294-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477131PMC
September 2020

Erratum to: Herbal decoctosome is a novel form of medicine.

Sci China Life Sci 2020 Sep 8;63(9):1428. Epub 2020 Jul 8.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Beijing, 100005, China.

Following the published article, we noticed an error duplication in Figure 5G "control" and "PGY-6" that was introduced during the revised process, with an attempt to replace it with higher-resolution images. Here we provide the original data in the first submitted manuscript (Figure 5G).
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http://dx.doi.org/10.1007/s11427-020-1760-4DOI Listing
September 2020

Advances and Prospects of Vasculogenic Mimicry in Glioma: A Potential New Therapeutic Target?

Onco Targets Ther 2020 21;13:4473-4483. Epub 2020 May 21.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.

Vasculogenic mimicry (VM) is the formation of a "vessel-like" structure without endothelial cells. VM exists in vascular-dependent solid tumors and is a special blood supply source involved in the highly invasive tumor progression. VM is observed in a variety of human malignant tumors and is closely related to tumor proliferation, invasion, and recurrence. Here, we review the mechanism, related signaling pathways, and molecular regulation of VM in glioma and discuss current research problems and the potential future applications of VM in glioma treatment. This review may provide a new viewpoint for glioma therapy.
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http://dx.doi.org/10.2147/OTT.S247855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247597PMC
May 2020

Vascular Extracellular Matrix Remodeling and Hypertension.

Antioxid Redox Signal 2021 04 27;34(10):765-783. Epub 2020 May 27.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.

The vascular extracellular matrix (ECM) not only provides mechanical stability but also manipulates vascular cell behaviors, which are crucial for vascular function and homeostasis. ECM remodeling, which alters vascular wall mechanical properties and exposes vascular cells to bioactive molecules, is involved in the development and progression of hypertension. This brief review summarized the dynamic changes in ECM components and their modification and degradation during hypertension and after antihypertensive treatment. We also discussed how alterations in the ECM amount, assembly, mechanical properties, and degradation fragment generation provide input into the pathological process of hypertension. Although the relevance between ECM remodeling and hypertension has been recognized, the underlying mechanism by which ECM remodeling initiates the development of hypertension remains unclear. Therefore, the modulation of ECM remodeling on arterial stiffness and hypertension in genetically modified rodent models is summarized in this review. The circulating biomarkers based on ECM metabolism and therapeutic strategies targeting ECM disorders in hypertension are also introduced. Further research will provide more comprehensive understanding of ECM remodeling in hypertension by the application of matridomic and degradomic approaches. The better understanding of mechanisms underlying vascular ECM remodeling may provide novel potential therapeutic strategies for preventing and treating hypertension. . 34, 765-783.
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http://dx.doi.org/10.1089/ars.2020.8110DOI Listing
April 2021

Three-dimensional pore characterization of intact loess and compacted loess with micron scale computed tomography and mercury intrusion porosimetry.

Sci Rep 2020 05 22;10(1):8511. Epub 2020 May 22.

Key Laboratory of Shale Gas and Geoengineering, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing, China.

The pore structure is one of the most important properties of soil, which can directly affect the other properties such as water content, permeability and strength. It is of great significance to study the soil pore structure for agricultural cultivation, water and soil conservation and engineering construction. This paper investigates the 3D pore characterization of intact loess and four kinds of compacted loess (with different dry density) in northwest China. Micro scale computed tomography and mercury intrusion porosimetry tests were performed to get the porosity, specific surface area, pore size distribution, connected pores content and isolated pores content of different samples. Results show that the intact loess has more connected pores than the compacted loess, and the compacted loess whose dry density appears to be modelled well still have different pore structure with the intact loess. In addition, as the compactness increasing, the large pores (>13 μm) were firstly broken into medium pores (8~13 μm) and some small pores (<8 μm) until the pore structure was close to the natural structure of the intact loess, after that medium pores began to be broken into small pores.
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http://dx.doi.org/10.1038/s41598-020-65302-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244767PMC
May 2020

The fellow eye effect of unilateral intravitreal conbercept injections in eyes with diabetic macular edema.

Acta Diabetol 2020 Aug 25;57(8):1001-1007. Epub 2020 Mar 25.

Tianjin Medical University Eye Hospital, Tianjin, 300384, China.

Aims: To investigate whether intravitreal conbercept injection affects contralateral untreated eyes in bilateral diabetic macular edema (DME) patients.

Methods: In this retrospective study, 15 patients (30 eyes) with type 2 diabetes were followed after bilateral DME diagnosis in the Department of Ophthalmology, Peking Union Medical College Hospital from 2015 to 2018. Patients underwent examinations including best corrected visual acuity (BCVA), slit-lamp microscopy, indirect ophthalmoscope, color fundus photography, fundus fluorescein angiography, optical coherence tomography, and glycated hemoglobin (HbA1c). Each patient received conbercept (0.5 mg) intravitreally in the severe eye. Nonparametric Wilcoxon signed-rank tests and Pearson's correlation coefficient were used to assess changes in BCVA and central retinal thickness (CRT) and relations between BCVA changes in treated and untreated eyes, respectively.

Results: The mean follow-up time was 10.60 ± 2.29 months, and the mean injection number of 15 treated eyes was 9.13 ± 0.68. HbA1c remained below 10% during treatment with no significant changes between the initial and final visits (7.81 ± 1.17 vs 7.62 ± 1.19%) (P = 0.576). In untreated eyes, CRT significantly decreased from the initial to final visits (368.93 ± 125.45 vs 306.27 ± 89.70 μm) (P = 0.028). In untreated eyes, BCVA showed no significant difference between the initial and final visits (0.38 ± 0.30 vs 0.40 ± 0.30 logMAR) (P = 0.937), but BCVA changes in treated and untreated eyes were positively correlated (r = 0.527, P = 0.044).

Conclusions: Intravitreal conbercept injection results in decreased CRT and increased BCVA in untreated eyes, which is consistent with the changes in treated eyes for patients with bilateral DME.
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http://dx.doi.org/10.1007/s00592-020-01511-xDOI Listing
August 2020

Runx2 (Runt-Related Transcription Factor 2)-Mediated Microcalcification Is a Novel Pathological Characteristic and Potential Mediator of Abdominal Aortic Aneurysm.

Arterioscler Thromb Vasc Biol 2020 05 26;40(5):1352-1369. Epub 2020 Mar 26.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China (Z.L., Z.C., L.Y., Y.F., W.K.).

Objective: Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification, as detected by fluorine-18-sodium fluoride, has recently been recognized as a valuable indicator in predicting atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification involved in the pathogenesis of AAA remains elusive. Approach and Results: Microcalcification was analyzed in human aneurysmal aortas histologically and in AngII (angiotensin II)-infused mouse aortas by fluorine-18-sodium fluoride positron emission tomography and X-ray computed tomography scanning in chronological order in live animals. AAA patients' aortic tissue showed markedly enhanced microcalcification in the aortic media within the area proximal to elastic fiber degradation, compared with non-AAA patients. Enhanced fluorine-18-sodium fluoride uptake preceded significant aortic expansion in mice. Microcalcification-positive mice on day 7 of AngII infusion showed dramatic aortic expansion on subsequent days 14 to 28, whereas microcalcification-negative AngII-infused mice and saline-induced mice did not develop AAA. The application of hydroxyapatite, the main component of microcalcification, aggravated AngII-induced AAA formation in vivo. RNA-sequencing analysis of the suprarenal aortas of 4-day-AngII-infused mice and bioinformatics analysis with ChIP-Atlas database identified the potential involvement of the osteogenic transcriptional factor Runx2 (runt-related transcription factor 2) in AAA. Consistently, vascular smooth muscle cell-specific Runx2 deficiency markedly repressed AngII-induced AAA formation in the mice compared with the control littermates.

Conclusions: Our studies have revealed microcalcification as a novel pathological characteristic and potential mediator of AAA, and targeting microcalcification may represent a promising strategy for AAA prevention and treatment.
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http://dx.doi.org/10.1161/ATVBAHA.119.314113DOI Listing
May 2020
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