Publications by authors named "Ning Zhang"

2,769 Publications

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Differences in epidemiology of patients with preeclampsia between China and the US (Review).

Exp Ther Med 2021 Sep 15;22(3):1012. Epub 2021 Jul 15.

Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.

Preeclampsia (PE) is a complex complication that occurs during pregnancy. Studies indicated that morbidity from PE exhibits marked variations among geographical areas. Disparities in the incidence of PE between China and the US may be due to differences in ethnicity and genetic susceptibility, maternal age, sexual culture, body mass index, diet, exercise, multiple pregnancies and educational background. These epidemiological differences may give rise to differences between the two countries in terms of diagnostic and therapeutic criteria for PE. PE may be largely attributed to susceptibility genes and lifestyles, such as diet, body mass index and cultural norms regarding sexual relationships. The epidemiologic differences of patients with PE between the two countries indicated that appropriate prevention plans for PE require to be developed according to local conditions.
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http://dx.doi.org/10.3892/etm.2021.10435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311229PMC
September 2021

A time-resolved transcriptome landscape of the developing mouse ovary.

Biochem Biophys Res Commun 2021 Jul 31;572:57-64. Epub 2021 Jul 31.

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China. Electronic address:

The ovarian structure is complex and diverse, including egg cells, granulosa cells and other cell types. Its organ function depends heavily on normal development. Numerous studies have focused on certain gene function changes during ovarian development, but systematic analyses of its molecular changes are extremely rare. Here, we present a comprehensive transcriptional profile of the mouse ovary from 11 time points across multiple developmental stages, which enables us to explore the dynamics of ovarian development. By performing coexpression analysis, we identified gene modules with similar expression trends and determined 159 functional gene interaction networks based on machine learning. Most of these gene interaction networks are related to biological processes involved in the development of the ovary, which provides functional predictions for some genes with unknown functions and a reference for subsequent functional research. In general, our study provides a resource for understanding ovarian development.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.083DOI Listing
July 2021

The Effect of Computerized Cognitive Behavioral Therapy on People's Anxiety and Depression During the 6 Months of Wuhan's Lockdown of COVID-19 Epidemic: A Pilot Study.

Front Psychol 2021 14;12:687165. Epub 2021 Jul 14.

Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.

The effectiveness of computerized cognitive behavioral therapy (CCBT) has been proven for mild and moderate anxiety and depression. In 2016, the first official Chinese CCBT system was launched by Chinese Cognitive Behavior Therapy Professional Organizations and included four items: getting out of depression, overcoming anxiety, staying away from insomnia and facing Obsessive-compulsive disorder. During the COVID-19 epidemic, Chinese CCBT system served the public for free. This study explored the effects of CCBT on anxiety and depression by comparing the use of the platform during the epidemic and during the same period in 2019. Users were divided into a depression group or an anxiety group according to their own discretion. The subjects used the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) before each training. Each training group completed the corresponding CCBT training project, which had 5-6 training sessions, an average of once every 5 days. The training content in 2019 and 2020 was identical. This study compared the demographic characteristics, depression, and anxiety levels of CCBT platform users during the lockdown period in Wuhan (LP2020), where the outbreak was concentrated in China, from January 23 to July 23, 2020 and the same period in 2019 (SP2019). (1) There were significant differences in gender (χ = 7.215, = 0.007), region (χ = 4.225, = 0.040) and duration of illness (χ = 7.867, = 0.049) between the two periods. (2) There was a positive Pearson correlation between the number of users of CCBT platform during LP2020 and number of confirmed cases of COVID-19 in each province ( = 0.9429, < 0.001). (3) In LP2020, the SAS ( = 2.579, = 0.011) and SDS ( = 2.894, = 0.004) scores at T0 in Hubei were significantly higher than those in other regions. (4) The CCBT platform has an obvious effect on anxiety ( = 4.74, = 0.009) and depression on users ( = 4.44, = 0.009). This study showed women, students and people who are more seriously affected by the epidemic were more likely to accept the CCBT training. The CCBT platform made a significant contribution toward alleviating the anxiety and depression symptoms of users during the epidemic. When face-to-face psychotherapy is not available during the epidemic, CCBT can be used as an effective alternative.
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http://dx.doi.org/10.3389/fpsyg.2021.687165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316618PMC
July 2021

Isorhapontigenin (ISO) inhibits EMT through FOXO3A/METTL14/VIMENTIN pathway in bladder cancer cells.

Cancer Lett 2021 Jul 28. Epub 2021 Jul 28.

Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25th Street, New York, NY, 10010, USA. Electronic address:

Epithelial mesenchymal transition (EMT) is highly correlated with metastasis during cancer development. Although previous studies have revealed that ISO is able to inhibit cancer cell invasion and stem-cell properties, little is known about the effects of ISO on EMT markers. The present study explores the potential regulation of ISO on EMT, leading to the inhibition of migration and invasion of bladder cancer cells. We found that ISO inhibited Vimentin, one of the EMT markers, in the invasive bladder cancer cell lines U5637 and T24T. ISO reduced Vimentin protein level by increasing the expression of METTL14. On the other hand, ISO upregulated the METTL14 mRNA by activating the transcription factor FOXO3a. The results demonstrate that ISO inhibits invasion by affecting the EMT marker and offers a novel insight into understanding the upregulation of METTL14 by ISO.
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http://dx.doi.org/10.1016/j.canlet.2021.07.041DOI Listing
July 2021

A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection.

Nat Commun 2021 07 30;12(1):4635. Epub 2021 Jul 30.

University of CAS, Beijing, China.

SARS-CoV-2, the causative agent of COVID-19, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein. Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (K = 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC = 0.42 μg mL). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log. Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak.
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http://dx.doi.org/10.1038/s41467-021-24905-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324831PMC
July 2021

The ubiquitin-interacting motif-type ubiquitin receptor HDR3 interacts with and stabilizes the histone acetyltransferase GW6a to control grain size in rice.

Plant Cell 2021 Jul 29. Epub 2021 Jul 29.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, the Chinese Academy of Sciences, No.20 Nanxincun, Xiangshan, Beijing 100093, China.

For grain crops such as rice (Oryza sativa), grain size substantially affects yield. The histone acetyltransferase GRAIN WEIGHT 6a (GW6a) determines grain size and yield in rice. However, the gene regulatory network underlying GW6a-mediated regulation of grain size has remained elusive. In this study, we show that GW6a interacts with HOMOLOGUE OF DA1 ON RICE CHROMOSOME 3 (HDR3), a ubiquitin-interacting motif-containing ubiquitin receptor. Transgenic rice plants over-expressing HDR3 produced larger grains, whereas HDR3 knockout lines produce smaller grains compared to the control. Cytological data suggest that HDR3 modulates grain size in a similar manner to GW6a, by altering cell proliferation in spikelet hulls. Mechanistically, HDR3 physically interacts with and stabilizes GW6a in a ubiquitin-dependent manner, delaying protein degradation by the 26S proteasome. The delay in GW6a degradation results in dramatic enhancement of the local acetylation of H3 and H4 histones. Furthermore, RNA sequencing analysis and chromatin immunoprecipitation assays reveal that HDR3 and GW6a bind to the promoters of and modulate a common set of downstream genes. In addition, genetic analysis demonstrates that HDR3 functions in the same genetic pathway as GW6a to regulate grain size. Therefore, we identified the grain-size regulatory module HDR3-GW6a as a potential target for crop yield improvement.
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http://dx.doi.org/10.1093/plcell/koab194DOI Listing
July 2021

Single-cell DNA methylome analysis of circulating tumor cells.

Chin J Cancer Res 2021 Jun;33(3):391-404

Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.

Objective: Previous investigations of circulating tumor cells (CTCs) have mainly focused on their genomic or transcriptomic features, leaving their epigenetic landscape relatively uncharacterized. Here, we investigated the genome-wide DNA methylome of CTCs with a view to understanding the epigenetic regulatory mechanisms underlying cancer metastasis.

Methods: We evaluated single-cell DNA methylome and copy number alteration (CNA) in 196 single cells, including 107 CTCs collected from 17 cancer patients covering six different cancer types. Our single-cell bisulfite sequencing (scBS-seq) covered on average 11.78% of all CpG dinucleotides and accurately deduced the CNA patterns at 500 kb resolution.

Results: We report distinct subclonal structures and different evolutionary histories of CTCs inferred from CNA and DNA methylation profiles. Furthermore, we demonstrate potential tumor origin classification based on the tissue-specific DNA methylation profiles of CTCs.

Conclusions: Our work provides a comprehensive survey of genome-wide DNA methylome in single CTCs and reveals 5-methylcytosine (5-mC) heterogeneity in CTCs, addressing the potential epigenetic regulatory mechanisms underlying cancer metastasis and facilitating the future clinical application of CTCs.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.03.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286897PMC
June 2021

Epidemiology of Idiopathic Pulmonary Fibrosis Among U.S. Veterans, 2010 - 2019.

Ann Am Thorac Soc 2021 Jul 27. Epub 2021 Jul 27.

San Francisco VA Medical Center, 19980, San Francisco, California, United States.

Rationale: The development of novel therapies for idiopathic pulmonary fibrosis (IPF) has brought increased attention to the population burden of disease. However, little is known about the epidemiology of IPF among United States Veterans.

Objectives: This study examines temporal trends in incidence and prevalence, patient characteristics, and risk factors associated with IPF among a national cohort of United States Veterans.

Methods: We used data from Veterans Health Administration (VHA) electronic health record system to describe the incidence, prevalence, and geographic distribution of IPF between January 2010 and December 2019. We evaluated patient characteristics associated with IPF using multivariate logistic regression.

Results: Among 10.7 million Veterans who received care from the VHA between 2010 and 2019, 139,116 (1.26%) were diagnosed with IPF. Using a narrow case definition of IPF, the prevalence increased from 276 cases per 100,000 in 2010 to 725 cases per 100,000 in 2019. The annual incidence increased from 73 cases per 100,000 person-years in 2010 to 210 cases per 100,000 person-years in 2019. Higher absolute incidence and prevalence rates were noted when a broader case definition of IPF was used. Risk factors associated with IPF among Veterans included older age, White race, tobacco use, and rural residence. After accounting for interactions, the average marginal difference in IPF prevalence between males and female sex was small. There was significant geographic heterogeneity of disease across the U.S.

Conclusions: This study is the first comprehensive epidemiologic analysis of IPF among the U.S. Veteran population. The incidence and prevalence of IPF among Veterans has increased over the past decade. The effect of sex on risk of IPF was attenuated once accounting for other risk factors. The geographic distribution of disease is heterogenous across the U.S with rural residence associated with a higher odds of IPF. The reason for these trends deserves further study.
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http://dx.doi.org/10.1513/AnnalsATS.202103-295OCDOI Listing
July 2021

Stability of Zika Virus Antibodies in Specimens from a Retrospective Serological Study.

Am J Trop Med Hyg 2021 Jul 26. Epub 2021 Jul 26.

Jilin Dabeinong Agriculture and Animal Husbandry Technology Co., Ltd. Changchun 130102, China.

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http://dx.doi.org/10.4269/ajtmh.21-0564aDOI Listing
July 2021

Bimetallic Metal-Organic Frameworks: Enhanced Peroxidase-like Activities for the Self-Activated Cascade Reaction.

ACS Appl Mater Interfaces 2021 Jul 27. Epub 2021 Jul 27.

School of Chemistry, Xi'an Key Laboratory of Sustainable Energy Material Chemistry, Xi'an Jiaotong University, Xi'an 710049, P. R. China.

Metal-organic frameworks (MOFs) are significant useful molecular materials as a result of their high surface area and flexible catalytic activities by tuning the metal centers and ligands. MOFs have attracted great attention as efficient nanozymes recently; however, it is still difficult to understand polymetallic MOFs for enzymatic catalysis because of their complicated structure and interactions. Herein, bimetallic NiFe MOF octahedra were well prepared and exhibited enhanced peroxidase-like activities. The synergistic effect of Fe and Ni atoms was systematically investigated by electrochemistry, X-ray photoelectron spectrometry, (XPS) and Raman techniques. The electrons tend to transfer from Ni to Fe in NiFe MOFs, and the resulting Fe is ready to decompose HO and generate OH by a Fenton-like reaction. After integration with glucose oxidase (GOx), which can downgrade the pH value and generate HO by oxidation of glucose, a self-activated cascade reagent is therefore established for efficiently inducing cell death. The changes of cell morphology, DNA, and protein are also successfully recorded during the cell death process by Raman spectroscopy and fluorescence imaging.
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http://dx.doi.org/10.1021/acsami.1c05615DOI Listing
July 2021

Pulmonary Functional Imaging for Lung Adenocarcinoma: Combined MRI Assessment Based on IVIM-DWI and OE-UTE-MRI.

Front Oncol 2021 6;11:677942. Epub 2021 Jul 6.

MR Collaboration, Central Research Institute, United Imaging Healthcare, Shanghai, China.

Purpose: The goal of current study was to introduce noninvasive and reproducible MRI methods for functional assessment of lung adenocarcinoma (LUAD).

Methods: Forty-four patients with pathologically confirmed LUAD were included in this study. All the lesions were classified as adenocarcinoma (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA). The IA lesions were further divided into five subtype patterns, including acinar, lepidic, papillary, micropapillary and solid. Tumors were grouped depending on predominant subtype: low grade (AIS, MIA or lepidic predominant), intermediate grade (papillary or acinar predominant) and high grade (micropapillary, or solid predominant). Spirometry was performed according to American Thoracic Society guidelines. For each patient, Intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) analysis and oxygen-enhanced MRI (OE-MRI) analysis were performed. Spearman's test was used to assess the relationship between a) whole lung mean percent signal enhancement (PSE) and pulmonary function tests (PFTs) parameters; b) IVIM-derived parameters and PFTs parameters; c) tumor mean PSE and IVIM-derived parameters. Kruskal -Wallis tests were applied to test the difference of tumor mean PSE and IVIM-derived parameters between different histological tumor grades. Receiver operating characteristics (ROC) analysis was used to evaluate the diagnostic performance.

Results: Whole lung mean PSE was significantly positively correlated with PFTs parameters (r = 0.40 ~ 0.44, < 0.05). f value derived from IVIM-DWI was significantly negatively correlated with PFTs parameters (r = -0.38 ~ -0.47, < 0.05). Both tumor mean PSE ( = 0.030 < 0.05) and f ( = 0.022 < 0.05) could differentiate different histological grades. f was negatively correlated with tumor mean PSE (r = -0.61, < 0.001). For the diagnostic performance, the combination of tumor mean PSE and f outperformed than using tumor mean PSE or f alone in both sensitivity and area under the ROC curve.

Conclusions: The combined measurement of OE-MRI and IVIM-DWI may serve as a promising method for the noninvasive and non-radiation evaluation of pulmonary function. Quantitative analyses achieved by OE-MRI and IVIM-DWI offer an approach of the classification of LUAD subtypes.
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http://dx.doi.org/10.3389/fonc.2021.677942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292137PMC
July 2021

Corrigendum: A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats.

Front Pharmacol 2021 9;12:724416. Epub 2021 Jul 9.

Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

[This corrects the article DOI: 10.3389/fphar.2020.599577.].
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http://dx.doi.org/10.3389/fphar.2021.724416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299940PMC
July 2021

Clinical Significance of Infection and Enrichment in Esophageal Squamous Cell Carcinoma.

Pathol Oncol Res 2021 9;27:1609846. Epub 2021 Jul 9.

Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, China.

A variety of pathogenic microorganisms promote tumor occurrence and development through long-term colonization in the body. () is abundant in precancerous esophageal lesions and is closely related to the malignant progression of esophageal squamous cell carcinoma (ESCC). The invasion of exogenous microorganisms can reshape the immune microenvironment, make the immune system incapacitated, and assist tumor cells in immune escape. A variety of pathogenic microorganisms induce the recruitment of () to allow tumor cells to escape immune surveillance and provide favorable conditions for their own long-term colonization. are one of the major obstacles to tumor immunotherapy and have a significant positive correlation with the occurrence and development of many kinds of tumors. Because can instantly enter cells and colonize for a long time, we speculated that F. nucleatum infection could facilitate the immune escape of tumor cells through enrichment of Tregs and promote the malignant progression of ESCC. In this study, we found a significant concordance between infection and infiltration. Therefore, we propose the view that chronic infection of may provide favorable conditions for long-term colonization of itself by recruiting and suppressing the immune response. At the same time, the massive enrichment of may also weaken the immune response and assist in the long-term colonization of . We analyzed the correlation between infection with the clinicopathological characteristics and survival prognosis of the patients. infection was found to be closely related to sex, smoking, drinking, degree of differentiation, depth of invasion, lymph node metastasis, and clinical stage. The degree of differentiation, depth of infiltration, lymph node metastasis, clinical stage, and infection are independent risk factors affecting ESCC prognosis. Additionally, the survival rate and median survival time were significantly shortened in the infection positive group. Therefore, we propose that long-term smoking and alcohol consumption cause poor oral and esophageal environments, thereby significantly increasing the risk of infection. In turn, infection and colonization may weaken the antitumor immune response through enrichment and further assist in self-colonization, promoting the malignant progression of ESCC.
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http://dx.doi.org/10.3389/pore.2021.1609846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300010PMC
July 2021

Effects of home-based walking on cancer-related fatigue in patients with breast cancer: a meta-analysis of randomized controlled trials.

Arch Phys Med Rehabil 2021 Jul 21. Epub 2021 Jul 21.

The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China; School of Nursing, Medical College of Soochow University, Suzhou 215006, People's Republic of China. Electronic address:

Objective: This study was designed to critically evaluate the effect of home-based walking on cancer-related fatigue (CRF) in patients with breast cancer receiving anti-cancer treatment.

Data Sources: Eight databases were systematically searched from inception to March 2021 for randomized controlled trials (RCTs) without language restrictions.

Study Selection: Two reviewers scanned the titles and abstracts, and then read the full texts of potentially eligible trials to screen the literature. Inclusion criteria were studies of home-based walking (HBW) intervention in adult breast cancer patients, and used fatigue as a primary or secondary outcome and containing extractable fatigue scores.

Data Extraction: Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed extraction form. The standardized mean difference (SMD) was used when the outcome assessment tools were different. All of the analyses were performed using Review Manager 5.3.

Data Synthesis: Eight RCTs, including 764 patients (HBW: 377, control: 387) meeting the inclusion criteria for the meta-analysis were identified. HBW had a significant effect on CRF in breast cancer (BC) patients receiving multiple anti-cancer treatments [SMD = -0.61, 95% CI (-0.86, -0.36), p<0.001]. HBW without other exercises [SMD = -0.83, 95% CI (-1.39, -0.27), p = 0.003], walking for a gradually increased duration [SMD = -1.24, 95% CI (-2.20, -0.28), p = 0.010] and no restrictions on walking intensity [SMD = -1.03, 95% CI (-1.75, -0.31), p = 0.005] demonstrated substantial effects on CRF. Of the eight included studies, only three reported adverse events.

Conclusions: HBW can be considered as an alternative therapy for relieving CRF in breast cancer patients undergoing anti-cancer treatment.
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http://dx.doi.org/10.1016/j.apmr.2021.06.020DOI Listing
July 2021

Assessment of Water Resources Carrying Risk and the Coping Behaviors of the Government and the Public.

Int J Environ Res Public Health 2021 07 20;18(14). Epub 2021 Jul 20.

School of Management, Hangzhou Dianzi University, Hangzhou 310018, China.

The carrying capacity of water resources is of great significance to economic and social development, eco-environmental protection, and public health. The per capita water resources in Zhejiang Province is only 2280.8 m, which is more likely to cause the risk of water resources carrying capacity in the case of water shortage. Therefore, this paper applies Analytic Hierarchy Process-Fuzzy Comprehensive Evaluation and Entropy-Principal Component Analysis to evaluate the vulnerability of disaster-bearers and the risk of disaster-causing factors; it comprehensively evaluates the risk of water resources carrying capacity in Zhejiang Province by constructing risk matrix and ranking scores. The specific results are as follows: According to the comprehensive evaluation of the vulnerability of disaster-bearers in Zhejiang Province from the three aspects of supporting force, regulating force, and pressure, the overall performance was good. In particular, the role of supporting force is the most obvious. In the risk of disaster factors, it was found that industrial structure, climate change, water use efficiency, and population structure have great influence, showing that southern Zhejiang is at a greater risk than northern Zhejiang, and western Zhejiang is at a greater risk than eastern Zhejiang, but the overall score gap is not large. Combining the two results, the order of water resources carrying risk in Zhejiang Province from low to high was Hangzhou, Ningbo, Shaoxing, Jiaxing, Huzhou, Jinhua, Quzhou, Wenzhou, Lishui, Taizhou, and Zhoushan. Finally, according to the development planning of different cities, the coping behaviors of the government and the public regarding water resources carrying risk are put forward.
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http://dx.doi.org/10.3390/ijerph18147693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306389PMC
July 2021

Novel Perbutyrylated Glucose Derivatives of (-)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis, Cytotoxicity, and Molecular Docking.

Molecules 2021 Jul 19;26(14). Epub 2021 Jul 19.

Key Laboratory of Pu-er Tea Science, Ministry of Education, College of Science, Yunnan Agricultural University, Kunming 650201, China.

Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (-) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property-activity relationship of EGCG derivatives. Compounds and showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC values in the range of 22.90-37.87 μM. Compounds and decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds and , both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.
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http://dx.doi.org/10.3390/molecules26144361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306927PMC
July 2021

Biogas energy generated from livestock manure in China: Current situation and future trends.

J Environ Manage 2021 Jul 21;297:113324. Epub 2021 Jul 21.

State Key Laboratory of Marine Environmental Science, College of Environment and Ecology, Xiamen University, Xiamen, Fujian, 361102, China.

This article investigates the current status of the livestock industry (cattle, pigs, sheep, and poultry) in China and assesses the potential for biogas production from anaerobically digested livestock manure. According to calculation results based on the latest data of livestock released by the National Bureau of Statistics of China in 2018, China produced 2 × 10 kg of manure pollution in 2017, with pig waste representing the largest single manure source. Biogas that can be converted from high organic containing manure is a kind of clean bioenergy with low carbon footprint. In 2017, the energy potential from manure-produced biogas was about 5.74 × 10-6.73 × 10 MJ, which corresponds to 4-5% of China's total energy demand. Correlation analysis between biogas production and the livestock industry showed that crop production had significant effects on manure-generated biogas production. However, it is necessary to address the challenges when applying AD technology. Bioenergy potential from manure will be lost during material collection and transportation. Although large-scale livestock farming remains controversial, this type of farming can improve the energy recovery rate of livestock manure. How to gain benefits and maintain sustainable development is also a bottleneck for AD promotion. Reducing energy input in AD projects as well as enhancing the efficiency of methanogenesis of livestock manure are key factors for achieving a high net output of biogas projects. More inclusive strategies and a broader vision should be adopted to allow stakeholders to benefit from manure-generated biogas projects.
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http://dx.doi.org/10.1016/j.jenvman.2021.113324DOI Listing
July 2021

Corrigendum: Polysaccharide Biosynthesis: Glycosyltransferases and Their Complexes.

Front Plant Sci 2021 6;12:720709. Epub 2021 Jul 6.

Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, United States.

[This corrects the article DOI: 10.3389/fpls.2021.625307.].
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http://dx.doi.org/10.3389/fpls.2021.720709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290870PMC
July 2021

Direct in vivo reprogramming with non-viral sequential targeting nanoparticles promotes cardiac regeneration.

Biomaterials 2021 Jul 15;276:121028. Epub 2021 Jul 15.

Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Shanghai, 20032, China; Institute of Biomedical Sciences, Fudan University, Shanghai, 20032, China. Electronic address:

microRNA-mediated direct cardiac reprogramming, directly converts fibroblasts into induced cardiomyocyte-like cells (iCMs), which holds great promise in cardiac regeneration therapy. However, effective approaches to deliver therapeutic microRNA into cardiac fibroblasts (CFs) to induce in vivo cardiac reprogramming remain to be explored. Herein, a non-viral biomimetic system to directly reprogram CFs for cardiac regeneration after myocardial injury was developed by coating FH peptide-modified neutrophil-mimicking membranes on mesoporous silicon nanoparticles (MSNs) loaded with microRNA1, 133, 208, and 499 (miR Combo). Through utilizing the natural inflammation-homing ability of neutrophil membrane protein and FH peptide's high affinity to tenascin-C (TN-C) produced by CFs, this nanoparticle could realize sequential targeting to CFs in the injured heart and precise intracellular delivery of miRCombo, which induced reprogramming resident CFs into iCMs. In a mouse model of myocardial ischemia/reperfusion injury, intravenous injection of the nanoparticles successfully delivered miRCombo into fibroblasts and led to efficient reprogramming, resulting in improved cardiac function and attenuated fibrosis. This delivery system is minimally invasive and bio-safe, providing a proof-of-concept for biomimetic and sequential targeting nanomedicine delivery system for microRNA-mediated reprogramming therapy in multiple diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121028DOI Listing
July 2021

Energy, environment and economy assessment of medical waste disposal technologies in China.

Sci Total Environ 2021 Jul 9;796:148964. Epub 2021 Jul 9.

College of Energy and Safety Engineering, Tianjin Chengjian University, Tianjin 300384, China; Tianjin Key Laboratory of Building Green Functional Materials, Tianjin 300384, China.

Medical waste (MW) has exploded since the COVID-19 pandemic and aroused great concern to MW disposal. Meanwhile, the energy recovery for MW disposal is necessary due to high heat value of MW. Harmless disposal of MW with economically and environmentally sustainable technologies along with higher energy recovery is urgently required, and their energy recovery efficiencies and environmental impacts reduction due to energy recovery are key issues. In this study, five MW disposal technologies, i.e. rotary kiln incineration, pyrolysis incineration, plasma melting, steam sterilization and microwave sterilization, were evaluated and compared via energy recovery analysis (ERA), life cycle assessment (LCA), and life cycle costing (LCC) methods. Furthermore, three MW incineration technologies with further energy recovery and two sterilization followed by co-incineration technologies were analyzed to explore their improvement potential of energy recovery and environment benefits via scenario analysis. ERA results reveal that the energy recovery efficiencies of "steam and microwave sterilization + incineration" are the highest (≥83.4%), while that of the plasma melting is the lowest (19.2%). LCA results show that "microwave sterilization + landfill" outperforms others while the plasma melting exhibits the worst, electricity is the most significant contributor to the environmental impacts of five technologies. Scenario analysis shows that the overall environmental impact of all technologies reduced by at least 45% after further heat utilization. LCC results demonstrate that pyrolysis incineration delivers the lowest economic cost, while plasma melting is the highest. Co-incineration of sterilized MW and municipal solid waste could be recommended.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148964DOI Listing
July 2021

Crystal Engineering of Angular-Shaped Heteroarenes Based on Cyclopenta[]thiopyran for Controlling the Charge Carrier Mobility.

J Am Chem Soc 2021 Jul 16;143(29):11088-11101. Epub 2021 Jul 16.

Department of Materials Science, Fudan University, Shanghai 200433, China.

Cyclopenta[]thiopyran, isomeric to benzo[]thiophene while isoelectronic to azulene, is involved as a building block to construct soluble organic semiconductors for field-effect transistors. Two series of angular-shaped heteroarenes based on cyclopenta[]thiopyran, that is, ( = 4, 6, 8, 10) with different linear alkyl groups and ( = 2, 3, 4) with chlorides substituted at different positions, have been straightforward synthesized. The obtained seven S-heteroarenes exhibit intriguing and similar photophysical and electrochemical properties, such as near-infrared absorption and high-energy levels of the highest occupied molecular orbitals. Nevertheless, the S-heteroarenes with identical π-conjugated skeletons demonstrate completely different molecular packing structures, which is proofed to be the key determinate factor for the charge carrier mobilities. Upon the engineering of the pendant alkyl lengths, the highest hole mobility in the series is achieved for (1.1 cm V s) with moderate alkyl length. The further incorporation of chlorides on results in the shortened intermolecular H···S contacts and the interplane distances. Most interestingly, when chlorine-containing chloroform and chlorobenzene are used as crystallization solvents, single crystals of with different packing structures are produced owing to the intermolecular interactions among the solute and solvent molecules. Upon further engineering of the chlorination position and the crystallization solvent, the maximum hole mobility in the ambient air improves to 2.7 cm V s for crystallized from chlorobenzene, suggesting that the introduction of the accessible chlorides is a feasible pathway to engineering the crystal structures and controlling the charge transport characteristics.
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http://dx.doi.org/10.1021/jacs.1c04576DOI Listing
July 2021

Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats.

Sci Rep 2021 Jul 15;11(1):14511. Epub 2021 Jul 15.

Department of Critical Care Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China.

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.
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http://dx.doi.org/10.1038/s41598-021-93861-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282649PMC
July 2021

Size-Dependent Absorption through Stratum Corneum by Drug-Loaded Liposomes.

Pharm Res 2021 Jul 12. Epub 2021 Jul 12.

Center for drug evaluation, NMPA, Beijing, China.

Purpose: Topical treatment of various skin disorders requires drug absorption and penetration through the stratum corneum (SC) into the epidermis and dermis tissues. The use of nano-drug delivery systems including liposomes and lipid nanoparticles (SLNs) have been shown to facilitate SC penetration. The goal of this work was to study the impact of liposome sizes and the resulted drug distribution inside various skin tissue.

Methods: All trans retinoic acid (ATRA) was used as the model drug and loaded into gel phase HSPC/CHOL/DSPE-PEG liposomes (lipo-ATRA) with sizes ranging from 80 nm to more than 300 nm. The percutaneous drug absorption process was monitored and analyzed.

Results: There were significant differences in percutaneous absorption and tissue distribution resulted from liposomes smaller than 100 nm and those bigger than 200 nm. Lipo-ATRA with a mean diameter of 83 nm can deliver the content to epidermis and dermis. But for 200 nm - 300 nm liposomes, the resulted epidermis and dermis ATRA levels were less than about one third, suggesting bigger liposomes had poor penetration through the brick and mortar structure of SC.

Conclusions: Gel phase liposomes with sizes under 100 nm improved encapsulated drug absorption and distribution into the epidermis and dermis tissues. A size dependent mechanism for liposome penetration of the stratum corneum was proposed.
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http://dx.doi.org/10.1007/s11095-021-03079-9DOI Listing
July 2021

IDH Mutation Subgroup Status Associates with Intratumor Heterogeneity and the Tumor Microenvironment in Intrahepatic Cholangiocarcinoma.

Adv Sci (Weinh) 2021 Jul 11:e2101230. Epub 2021 Jul 11.

Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China.

Intrahepatic cholangiocarcinoma (ICC) is highly heterogeneous. Here, the authors perform exome sequencing and bulk RNA sequencing on 73 tumor regions from 14 ICC patients to portray the multi-faceted intratumor heterogeneity (ITH) landscape of ICC. The authors show that ITH is highly concordant across genomic, transcriptomic, and immune levels. Comparison of these data to 8 published datasets reveals significantly higher degrees of ITH in ICC than hepatocellular carcinoma. Remarkably, the authors find that high-ITH tumors highly overlap with the IDH (isocitrate dehydrogenase)-mutant subgroup (IDH-SG), comprising of IDH-mutated tumors and IDH-like tumors, that is, those IDH-wildtype tumors that exhibit similar molecular profiles to the IDH-mutated ones. Furthermore, IDH-SG exhibits less T cell infiltration and lower T cell cytotoxicity, indicating a colder tumor microenvironment (TME). The higher ITH and colder TME of IDH-SG are successfully validated by single-cell RNA sequencing on 17 503 cells from 4 patients. Collectively, the study shows that IDH mutant subgroup status, rather than IDH mutation alone, is associated with ITH and the TME of ICC tumors. The results highlight that IDH-like patients may also benefit from IDH targeted therapies and provide important implications for the diagnosis and treatment of ICC.
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http://dx.doi.org/10.1002/advs.202101230DOI Listing
July 2021

A Novel Medial Malleolar Osteotomy Technique for the Treatment of Osteochondral Lesions of the Talus.

Orthop J Sports Med 2021 Mar 23;9(3):2325967121989988. Epub 2021 Mar 23.

Department of Foot and Ankle Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: The current techniques for medial malleolar osteotomy may lead to posterior tibial tendon injury and have a high rate of malunion.

Purpose: To describe a novel partial step-cut medial malleolar osteotomy technique and evaluate its technical feasibility and its advantages compared with traditional methods.

Study Design: Case series; Level of evidence, 4.

Methods: The novel technique consisted of osteotomy of the anterior one-third to two-thirds of the medial malleolus. A total of 19 ankles (18 patients) with osteochondral lesions of the talus underwent the novel osteotomy technique before osteochondral reconstruction. All patients were evaluated for more than 2 years. Radiographs were analyzed for postoperative displacement and malunion, and postoperative ankle function was evaluated according to the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale and the visual analog scale (VAS) for pain.

Results: The partial step-cut osteotomy technique was able to provide adequate intra-articular exposure without disturbing the posterior tibial tendon. The 19 ankles healed at a mean of 7.3 ± 1.5 weeks (range, 6-12 weeks). There was slight incongruence in 4 ankles, with a displacement of 1.0 ± 0.1 mm proximally and 0.3 ± 0.1 mm medially. The mean postoperative AOFAS and VAS scores improved compared with preoperatively, from 54.2 ± 12.1 to 84.6 ± 6.6 and from 6.4 ± 1.0 to 1.8 ± 1.3, respectively ( < .001 for both). No intraoperative tendon injuries were observed.

Conclusion: Results indicated that partial step-cut osteotomy is a reliable and effective method for providing enough exposure, avoiding displacement after reduction, and not disturbing the anatomic structures behind the medial malleolus.
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http://dx.doi.org/10.1177/2325967121989988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237210PMC
March 2021

The effect of thyroid autoantibody on assisted reproduction technology outcome in euthyroid women: One center experience.

Pak J Pharm Sci 2021 Jan;34(1):15-19

Reproductive Medicine Centre, Yuhuangding Hospital of Yantai, Affiliated Hospital of Qingdao University, Yantai, Shandong, China.

Thyroid dysfunction is an important factor to cause failure in assisted reproduction technology (ART) procedures. In this study, we recorded the serum level of thyroid autoantibody to fig. out its relationship with the ART outcome. The results showed that the serum concentrations of TSH had a statistically significant increase between the basal level and the levels at time of serum pregnancy test both in women with and without thyroid autoantibody (p= 0.002 and p=0.019, respectively). Additionally, the TSH level increased significantly in thyroid autoantibody-positive group than those in thyroid autoantibody-negative group during controlled ovarian hyper stimulation (COH) process(p = 0.006). The risk of preterm delivery was lower in thyroid autoantibody-negative group. In sum, the present study provided evidence of an association between thyroid autoantibody and preterm delivery in euthyroid women.
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January 2021

Knockdown of MicroRNA160a/b by STTM leads to root architecture changes via auxin signaling in Solanum tuberosum.

Plant Physiol Biochem 2021 Jun 29;166:939-949. Epub 2021 Jun 29.

Gansu Provincial Key Laboratory of Aridland Crop Science, Gansu Agricultural University, Lanzhou, 730070, China; College of Life Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China.

The root phenotype is an important aspect of plant architecture and plays a critical role in plant facilitation of the extraction of water and nutrition from the soil. MicroRNAs (miRNAs) are classes of small RNAs with important roles in regulating endogenous gene expression at the post-transcriptional level that function in a range of plant development processes and in the response to abiotic stresses. However, little is known concerning the molecular mechanism of miRNAs in regulating the generation and development of plant root architecture. Herein, we demonstrated that potato miR160a/b acted as a critical regulator and affected plant root architecture by targeting the mRNA of StARF10 and StARF16 for cleavage. The miR160a/b precursor was cloned from potato. Quantitative PCR assays showed that the expression levels of miR160 and its targets were down- or up-regulated with the development of potato roots, respectively. Moreover, transgenic lines with suppressed stu-miR160 expression were established with the short tandem targets mimic (STTM), and the results showed that the ectopic expression of miR160a/b altered the levels of auxin and the expression of auxin signaling-related genes and caused drastic change in root architecture compared with that in control plants. Suppressing the expression of miR160 led to a severe reduction in root length, an increase in the number of lateral roots, and a decrease in fresh root weight in potato. Collectively, our data established a key role of miR160 in modulating plant root architecture in potato.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.051DOI Listing
June 2021

Structural characteristics of small-molecule inhibitors targeting demethylase.

Future Med Chem 2021 Jul 9. Epub 2021 Jul 9.

Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, China.

Studies have shown that the gene is closely related to obesity and weight gain in humans. is an N-methyladenosine demethylase and is linked to an increased risk of obesity and a variety of diseases, such as acute myeloid leukemia, type 2 diabetes, breast cancer, glioblastoma and cervical squamous cell carcinoma. In light of the significant role of , the development of small-molecule inhibitors targeting the protein provides not only a powerful tool for grasping the active site of but also a theoretical basis for the design and synthesis of drugs targeting the protein. This review focuses on the structural characteristics of inhibitors and discusses the occurrence of obesity and cancer caused by gene overexpression.
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http://dx.doi.org/10.4155/fmc-2021-0132DOI Listing
July 2021

Prenatal diagnosis of the Dandy-Walker malformation associated with partial trisomy 12p and distal 15q deletion.

J Genet 2021 ;100

Department of Reproductive and Genetics, Hebei General Hospital, Hebei Province, No. 348 West Heping Road, Shijiazhuang 050051, People's Republic of China.

Dandy-Walker malformation (DWM) is characterized by complete or partial agenesis of the cerebellar vermis, cyatic dilatation of the forth ventricle, and enlarged posterior fossa. However, the mechanism is still not completely understood up to now. In this study, we reported a rare case that a foetus with DWM showed partial trisomy 12p and distal 15q deletion. Karyotype analysis and chromosomal microarray analysis (CMA) were not always concordant with each other, and it is suggested that they should be performed for prenatal genetic diagnosis together. DWM is a rare central nervous system malformation, reported in 1/25-30,000 live births, characterized by complete or partial agenesis of the cerebellar vermis, cyatic dilatation of the forth ventricle, and enlarged posterior fossa (Kumar 2001; Klein 2003; Agrawal 2016). The neurological development of children with DWM may range from normal to severely retarded, and cause variable clinical feature. Although several efforts have been made to explore its pathogenesis, however, it is still not completely understood. During the past decade, some genetic loci, microdeletion or duplication have been reported to be associated with DWM, such as 9p trisomy, partial deletions of the long arm of chromosome 13, genes and (von Kaisenberg 2000; McCormack 2003; Grinberg 2004). In the present study, we describe a prenatal diagnosis case that a foetus with DWM on ultrasound scanning accepted genetic testing, and it revealed a microduplication of 12p13.33p11.1 and microdeletion of 15q11.2 in 750K single nucleotide polymorphism (SNP) array, while it showed 46,XX,der(8)(8pter→8q24::12p10→12qter),i(12)(p10) in karyotyping.
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January 2021
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