Publications by authors named "Yuwen Zhang"

94 Publications

Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats.

Acta Pharm Sin B 2021 Jul 23;11(7):1835-1852. Epub 2021 Jan 23.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.

Rheumatoid arthritis (RA) is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS). The up-regulated cellular membrane expression of G protein coupled receptor kinase 2 (GRK2) of FLS plays a critical role in RA progression, the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor (EP4) signaling and FLS abnormal proliferation. Recently, although our group found that paeoniflorin-6'--benzene sulfonate (CP-25), a novel compound, could reverse FLS dysfunction GRK2, little is known as to how GRK2 translocation activity is suppressed. Our findings revealed that GRK2 expression up-regulated and EP4 expression down-regulated in synovial tissues of RA patients and collagen-induced arthritis (CIA) rats, and prostaglandin E2 (PGE2) level increased in arthritis. CP-25 could down-regulate GRK2 expression, up-regulate EP4 expression, and improve synovitis of CIA rats. CP-25 and GRK2 inhibitors (paroxetine or GSK180736A) inhibited the abnormal proliferation of FLS in RA patients and CIA rats by down-regulating GRK2 translocation to EP4 receptor. The results of microscale thermophoresis (MST), cellular thermal shift assay, and inhibition of kinase activity assay indicated that CP-25 could directly target GRK2, increase the protein stability of GRK2 in cells, and inhibit GRK2 kinase activity. The docking of CP-25 and GRK2 suggested that the kinase domain of GRK2 might be an important active pocket for CP-25. G201, K220, K230, A321, and D335 in kinase domain of GRK2 might form hydrogen bonds with CP-25. Site-directed mutagenesis and co-immunoprecipitation assay further revealed that CP-25 down-regulated the interaction of GRK2 and EP4 controlling the key amino acid residue of Ala321 of GRK2. Our data demonstrate that FLS proliferation is regulated by GRK2 translocation to EP4. Targeted inhibition of GRK2 kinase domain by CP-25 improves FLS function and represents an innovative drug for the treatment of RA by targeting GRK2.
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http://dx.doi.org/10.1016/j.apsb.2021.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343125PMC
July 2021

Integrating basic and applied researches of SARS-CoV-2 into the medical molecular biology teaching.

Biochem Mol Biol Educ 2021 Aug 12. Epub 2021 Aug 12.

The Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.

Molecular biology is an important course for medical postgraduates to understand the practice of modern molecular medicine. At present, molecular biology has been widely used in the prevention, diagnosis, and treatment of clinical medicine. The COVID-19 pandemic forced all universities suspending academic activities and online teaching all over the world, which is a kind of crisis and has become people's memory of the times. The efforts from all sectors of society, include government, research institutions, and enterprises, have gave medical students a profound impact. The integration of memory of the times into molecular biology teaching will enhance students' learning interest and understanding effect.
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http://dx.doi.org/10.1002/bmb.21573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426797PMC
August 2021

Untargeted LC/MS-Based Metabolic Phenotyping of Hypopituitarism in Young Males.

Front Pharmacol 2021 8;12:684869. Epub 2021 Jul 8.

Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Hypopituitarism (Hypo-Pit) is partial or complete insufficiency of anterior pituitary hormones. Besides hormone metabolism, the global metabolomics in Hypo-Pit are largely unknown. We aimed to explore potential biomarkers to aid in diagnosis and personalized treatment. Using both univariate and multivariate statistical methods, we identified 72 differentially abundant features through liquid chromatography coupled to high-resolution mass spectrometry, obtained in 134 males with Hypo-Pit and 90 age matched healthy controls. Hypopituitarism exhibits an increased abundance of metabolites involved in amino acid degradation and glycerophospholipid synthesis, but decreased content of metabolites in steroid hormone synthesis and fatty acid beta-oxidation. Significantly changed metabolites included creatine, creatinine, L-alanine, phosphocholines, androstenedione, hydroprenenolone, and acylcarnitines. In Hypo-Pit patients, the increased ratio of creatine/creatinine suggested reduced creatine uptake and impaired creatine utilization, whereas the decreased level of beta-hydroxybutyrate, acetylcarnitine (C2) and a significantly decreased ratio of decanoylcarnitine (C10) to free carnitine suggested an impaired beta-oxidation. Furthermore, the creatine/creatinine and decanoylcarnitine/carnitine ratio were identified as diagnostic biomarkers for Hypo-Pit with AUCs of 0.976 and 0.988, respectively. Finally, we found that the creatinine and decanoylcarnitine/carnitine ratio could distinguish cases that were sensitive vs. resistant to human chorionic gonadotropin therapy. We provided a global picture of altered metabolic pathways in Hypo-Pit, and the identified biomarkers in creatine metabolism and beta-oxidation might be useful for the preliminary screening and diagnosis of Hypo-Pit.
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http://dx.doi.org/10.3389/fphar.2021.684869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295757PMC
July 2021

Ambient PM-induced brain injury is associated with the activation of PI3K/AKT/FoxO1 pathway.

Environ Sci Pollut Res Int 2021 Jul 15. Epub 2021 Jul 15.

Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Box 249, 130 Dong'an Road, Shanghai, 200032, China.

PM-related neurological and mental diseases, such as cognitive impairment and stroke, tend to cause disability. Six-week-old male C57BL/6 mice were divided into 6 groups and exposed to concentrated PM or filtered air for 2, 4, and 6 months, respectively. The neurobehavioral changes of mice were tested. The weight of the whole brain and olfactory bulbs were recorded at the end of exposure, and the brain structure was observed by hematoxylin and eosin (HE) staining. Serum indicators, mRNA, and protein expressions were detected. The spatial learning memory ability was impaired, and the mice were more anxious after PM exposure. Relative brain weight decreased with age, and PM exposure exceeded the decrease of relative brain weight. Interestingly, superoxide dismutase (SOD) and albumin decreased in the PM-exposed groups although neuronal morphology and other serum indicators did not show significant difference between PM and FA groups. Moreover, PM induced the increase of plasminogen at 2 months but recovered at 4 months and then increased at 6 months again. The results from protein expression and transcriptomic test demonstrated that PI3K/AKT/FoxO1 pathway might be activated after 6-month PM exposure in mice. Indicators albumin, the percentage of albumin over IgG (A/G value), and plasminogen were the main serous changes in mice after early-stage (2 months) and long-term (6 months) PM exposure. In addition, early-stage injury induced by PM might recover at later time point and display significant injury again with the exposure time. PM exposure-induced brain injury might be associated with the activation of PI3K/AKT/FoxO1 pathway.
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http://dx.doi.org/10.1007/s11356-021-15405-0DOI Listing
July 2021

Comprehensive analysis of the prognostic value of the chemokine-like factor-like MARVEL transmembrane domain-containing family in gastric cancer.

J Gastrointest Oncol 2021 Apr;12(2):388-406

Department of Pharmacy, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Background: The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family refers to a family of transcriptional repressor genes. CMTMs are closely associated with the epigenetic regulatory mechanisms and development of multiple malignancies, including gastric cancer. However, their specific biological functions and prognostic values in gastric cancer have yet to be elucidated.

Methods: Tumor sample datasets were retrieved and analyzed using databases including Oncomine, STRING, GEPIA2, cBioportal, and Kaplan-Meier plotter. To investigate the prognostic role of CMTMs in gastric cancer, we applied unsupervised hierarchical clustering analysis of CMTM gene expression patterns.

Results: While the mRNA levels of CMTM1/3/6/7/8 were upregulated in gastric cancer, CMTM2/4/5 showed no statistically significant difference at the mRNA level in patients with gastric cancer. Moreover, the mRNA expressions of different CMTMs exhibited strong correlations with various clinical parameters of patients with gastric cancer, including tumor stage, metastatic lymph node status, status, and tumor grade. Also, the results suggested that elevated levels of CMTM3/5 mRNA had a significant association (P<0.05) with poor overall survival, progression-free survival, and post-progression survival. Conversely, elevated expression of CMTM2/4/6 mRNA had a significant association with better overall survival, progression-free survival, and post-progression survival. Unsupervised hierarchical clustering analysis successfully identified 2 major clusters of patients as follows: signature #1: CMTM4/6/8 and signature #2: CMTM1/2/3/5/7. Signature #2 was closely correlated with poorer overall survival, which indicated that the expression pattern of the CMTM family could be a novel prognostic factor for patients with gastric cancer.

Conclusions: These results suggest that the expression levels of CMTM genes possibly have prognostic value as a biomarker of gastric cancer.
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http://dx.doi.org/10.21037/jgo-21-78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107618PMC
April 2021

miRNA-mRNA Regulatory Network Reveals miRNAs in HCT116 in Response to Folic Acid Deficiency via Regulating Vital Genes of Endoplasmic Reticulum Stress Pathway.

Biomed Res Int 2021 26;2021:6650181. Epub 2021 Apr 26.

School of Life Sciences, Yunnan University, Kunming 650504, China.

Moderate folic acid (FA) intake is an effective strategy that slows colorectal cancer (CRC) progression. However, high consumption of FA may trigger the transition of precancerous tissue towards malignancy. MicroRNAs (miRNAs) are considered to be potential biomarkers of CRC. Thus, identification of miRNAs of dysregulated genes in CRC cells by detailed analysis of mRNA and miRNA expression profile in the context of FA deficiency could substantially increase our understanding of its oncogenesis. mRNA-seq and miRNA-seq analyses were utilized to investigate the expression of miRNAs in FA-deficient CRC cell line-HCT116 through massive parallel sequencing technology. A total of 38 mRNAs and 168 miRNAs were identified to be differentially expressed between CRC groups with or without FA deficiency. We constructed an miRNA-mRNA network for the vital regulatory miRNAs altered in FA-deficient CRC cells. The mRNAs and miRNAs validated by Western blotting and RT-qPCR were consistent with the sequencing results. Results showed that FA deficiency upregulated some miRNAs thereby inhibiting the expression of critical genes in the endoplasmic reticulum (ER) stress pathway. Dysregulated miRNAs in our miRNA-mRNA network could contribute to CRC cell in response to deficient FA. This work reveals novel molecular targets that are likely to provide therapeutic interventions for CRC.
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http://dx.doi.org/10.1155/2021/6650181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096553PMC
May 2021

Visit-to-visit blood pressure variability is associated with arterial stiffness in Chinese adults: A prospective analysis.

J Clin Hypertens (Greenwich) 2021 04 9;23(4):802-812. Epub 2021 Jan 9.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Blood pressure (BP) variability may have its effect on the development of vascular disease. The authors aimed to examine the association between the visit-to-visit variability (VVV) of BP and arterial stiffness in Chinese adults. The authors included 1407 participants from a prospective cohort study of community residents who were ≥40 years, without a history of myocardial infarction or stroke, and with data at the baseline, the second and the third visits in 2008, 2009, and 2013. The VVV of BP was defined as the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV), and the variability independent of the mean (VIM) in BP levels at the 3 visits. Arterial stiffness was measured by brachial-ankle pulse wave velocity (ba-PWV) at the 2nd and the 3rd visits. Levels of ba-PWV change and the occurrence of an elevated ba-PWV increased significantly in the highest tertile of VVV measures of systolic BP (SBP) and pulse pressure (PP) compared with the lowest tertile, respectively. The multivariable regression analysis revealed that VVV measures of SBP and PP were significantly associated with levels of ba-PWV change and the risks of developing an elevated ba-PWV. The odds ratios (ORs) and 95% confidence intervals (CIs) for the risk were 2.12 (1.57-3.12) and 1.92 (1.38-2.68) in participants with the highest versus the lowest tertile of SBP-SD and PP-SD, respectively. No significant association was found for diastolic BP variability measures. The increased long-term variabilities of SBP and PP were associated with an increased risk of arterial stiffness.
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http://dx.doi.org/10.1111/jch.14166DOI Listing
April 2021

[email protected] nanoparticles for MRI-targeted detection in the early lesions of atherosclerosis.

Nanomedicine 2021 04 13;33:102348. Epub 2020 Dec 13.

Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China. Electronic address:

Atherosclerosis can lead to most cardiovascular diseases. Although some biomimetic nanomaterials coated by macrophage membranes have been reported in previous studies of atherosclerosis, to our knowledge, no studies regarding the detection of early lesions of atherosclerosis (foam cells) using such a strategy have yet been reported. In the present study, FeO biomimetic nanoparticles coated with a macrophage membrane ([email protected]) were prepared to investigate the imaging effect on the early lesions of atherosclerosis (foam cells). The results showed that the [email protected] particles are spheres with average diameters of approximately 300 nm. T1 and T2 relaxation values showed that the ratio of r2 to r1 was 26.09. The protein content accounted for approximately 27% of the total weight in [email protected], and [email protected] nanoparticles exhibited high biosafety. Further testing showed that [email protected] effectively targets early atherosclerotic lesions by the specific recognition of integrin α4β1 to VCAM-1. Taken together, [email protected] is a promising contrast agent for the diagnosis of early stage atherosclerosis.
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http://dx.doi.org/10.1016/j.nano.2020.102348DOI Listing
April 2021

G9a/GLP-sensitivity of H3K9me2 Demarcates Two Types of Genomic Compartments.

Genomics Proteomics Bioinformatics 2020 08 5;18(4):359-370. Epub 2020 Dec 5.

MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China. Electronic address:

In the nucleus, chromatin is folded into hierarchical architecture that is tightly linked to various nuclear functions. However, the underlying molecular mechanisms that confer these architectures remain incompletely understood. Here, we investigated the functional roles of H3 lysine 9 dimethylation (H3K9me2), one of the abundant histone modifications, in three-dimensional (3D) genome organization. Unlike in mouse embryonic stem cells, inhibition of methyltransferases G9a and GLP in differentiated cells eliminated H3K9me2 predominantly at A-type (active) genomic compartments, and the level of residual H3K9me2 modifications was strongly associated with B-type (inactive) genomic compartments. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes led to decreased chromatin-nuclear lamina interactions mainly at G9a/GLP-sensitive regions, increased degree of genomic compartmentalization, and up-regulation of hundreds of genes that were associated with alterations of the 3D chromatin. Collectively, our data demonstrated essential roles of H3K9me2 in 3D genome organization.
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http://dx.doi.org/10.1016/j.gpb.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242262PMC
August 2020

Phosphorus fractionation related to environmental risks resulting from intensive vegetable cropping and fertilization in a subtropical region.

Environ Pollut 2021 Jan 20;269:116098. Epub 2020 Nov 20.

College of Resources and Environment, Academy of Agricultural Sciences, Key Laboratory of Efficient Utilization of Soil and Fertilizer Resources, Southwest University, Chongqing, 400716, PR China. Electronic address:

Overuse of phosphorus (P) fertilizer and the resulting soil P accumulation in vegetable production increases the risk of P runoff and leaching. However, P transformations under continuous fertilization and their effects on environmental risk are unclear. The current study examined the effects of long-term P fertilizer application on P fractions in different soil layers, and assessed the correlations between P fractions and environmental risks in intensive vegetable production in a subtropical region. A total of 32 fields were studied, including 8 uncultivated fields and 24 fields continuously used for vegetable production for 1-3, 4-9, or 10-15 years. The results showed that excessive P fertilizer input caused soil P surpluses ranging from 204.6 to 252.4 kg ha yr. Compared to uncultivated fields, vegetable fields contained higher levels of labile P, moderately labile P, sparingly labile P, and non-labile P. The combined percentage of labile P and moderately labile P increased from 55.2% in fields cultivated for 0-3 year to 65.5% in fields cultivated for 10-15 years. The concentrations of soil P fractions were higher at 0-20 cm soil depth than at 20-40 and 40-60 cm soil depth. Soil available P was positively correlated with all soil P fractions except diluted HCl-P or concentrated HCl-P. Long-term vegetable production increased CaCl-P downward movement, which was positively correlated with levels of labile and moderately labile P. The P index indicated a high risk of P losses from the vegetable fields. The P index was on average 3.27-fold higher in the vegetable fields than in uncultivated fields, and was significantly correlated with soil available P and organic and inorganic P fertilizer input. The environmental risk caused by P in vegetable production should be reduced by reducing P fertilizer input so as to maintain soil available P within an optimal range for vegetable production.
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http://dx.doi.org/10.1016/j.envpol.2020.116098DOI Listing
January 2021

Sodium para-aminosalicylic acid inhibits manganese-induced NLRP3 inflammasome-dependent pyroptosis by inhibiting NF-κB pathway activation and oxidative stress.

J Neuroinflammation 2020 Nov 17;17(1):343. Epub 2020 Nov 17.

Department of Toxicology, School of Public Health, Guangxi Medical University, Shuang-yong Road No.22, Nanning, 530021, Guangxi, China.

Background: The activation of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent pyroptosis has been shown to play a vital role in the pathology of manganese (Mn)-induced neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has a positive effect on the treatment of manganism. However, the mechanism is still unclear. We hypothesized that PAS-Na might act through NLRP3.

Methods: The microglial cell line BV2 and male Sprague-Dawley rats were used to investigate the impacts of PAS-Na on Mn-induced NLRP3 inflammasome-dependent pyroptosis. The related protein of the NF-κB pathway and NLRP3-inflammasome-dependent pyroptosis was detected by western blot. The reactive oxygen species and mitochondrial membrane potential were detected by immunofluorescence staining and flow cytometry. The activation of microglia and the gasdermin D (GSDMD) were detected by immunofluorescence staining.

Results: Our results showed that Mn treatment induced oxidative stress and activated the NF-κB pathway by increasing the phosphorylation of p65 and IkB-α in BV2 cells and in the basal ganglia of rats. PAS-Na could alleviate Mn-induced oxidative stress damage by inhibiting ROS generation, increasing mitochondrial membrane potential and ATP levels, thereby reducing the phosphorylation of p65 and IkB-α. Besides, Mn treatment could activate the NLRP3 pathway and promote the secretion of IL-18 and IL-1β, mediating pyroptosis in BV2 cells and in the basal ganglia and hippocampus of rats. But an inhibitor of NF-κb (JSH-23) treatment could significantly reduce LDH release, the expression of NLRP3 and Cleaved CASP1 protein and IL-1β and IL-18 mRNA level in BV2 cells. Interestingly, the effect of PAS-Na treatment in Mn-treated BV2 cells is similar to those of JSH-23. Besides, immunofluorescence results showed that PAS-Na reduced the increase number of activated microglia, which stained positively for GSDMD.

Conclusion: PAS-Na antagonized Mn-induced NLRP3 inflammasome dependent pyroptosis through inhibiting NF-κB pathway activation and oxidative stress.
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http://dx.doi.org/10.1186/s12974-020-02018-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670624PMC
November 2020

R1ρ at high spin-lock frequency could be a complementary imaging biomarker for liver iron overload quantification.

Magn Reson Imaging 2021 01 29;75:141-148. Epub 2020 Oct 29.

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China; Human Phenome Institute, Fudan University, Shanghai, China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China. Electronic address:

Purpose: To compare the correlations among the R1ρ, R2, and R2* relaxation rates with liver iron concentration (LIC) in the assessment of rat liver iron content and explore the application potential of R1ρ in assessing liver iron content.

Methods: Iron dextran (dosage of 0, 25, 50, 100, and 200 mg/kg body weight) was injected into 35 male rats to increase the amount of iron storage in the liver. After one week, all rats were euthanized with isoflurane. A portion of the largest hepatic lobe was extracted to quantify the LIC by inductively coupled plasma, and the remaining liver tissue was stored in 4% buffered paraformaldehyde for 24 h before MRI. Spin-lock preparation with a RARE (rapid acquisition with relaxation enhancement) readout (9 different spin-lock times and 7 different spin-lock frequencies (FSLs)) and multi-echo UTE (ultrashort TE) pulses were developed to quantify R1ρ and R2 * on a Bruker 11.7 T MR system. For comparisons with R1ρ and R2*, R2 was acquired using the CPMG sequence.

Results: Mean R1ρ values displayed dispersion, with decrease in R1ρ at higher FSLs. Spearman's correlation analysis (two-tailed) indicated that the R1ρ values were significantly associated with LIC at FSL = 2000, 2500, and 3000 Hz (r = 0.365 and P = 0.031, r = 0.608 and P < 0.001, and r = 0.764 and P < 0.001, respectively), and were not significantly associated with LIC at FSL = 500, 1000, 1250, and 1500 Hz (all P > 0.05). R2 and R2* showed significant linear correlations with LIC (r = 0.787 and P < 0.001, and r = 0.859 and P < 0.001, respectively). Correlation analysis across R1ρ, R2, and R* also suggested that the correlation strength between R1ρ and R2 and between R1ρ and R* showed an increasing trend with increase in FSL.

Conclusion: In this study, a strong association was observed between R1ρ and LIC at high FSLs further confirming previous findings. The results demonstrated that R1ρ at high FSL might serve as a complementary imaging biomarker for liver iron overload quantification.
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http://dx.doi.org/10.1016/j.mri.2020.10.014DOI Listing
January 2021

The nuclear bodies formed by histone demethylase KDM7A.

Protein Cell 2021 04 16;12(4):297-304. Epub 2020 Sep 16.

MOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Shanghai, 200032, China.

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http://dx.doi.org/10.1007/s13238-020-00783-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019015PMC
April 2021

Molecular regulation of required for maize male fertility and development of a dominant male-sterility system in multiple species.

Proc Natl Acad Sci U S A 2020 09 9;117(38):23499-23509. Epub 2020 Sep 9.

Zhongzhi International Institute of Agricultural Biosciences, Biology and Agriculture Research Center, University of Science and Technology Beijing, 100024 Beijing, China;

Understanding the molecular basis of male sterility and developing practical male-sterility systems are essential for heterosis utilization and commercial hybrid seed production in crops. Here, we report molecular regulation by genic male-sterility gene () and its application for developing a dominant male-sterility system in multiple species. is specifically expressed in maize anthers, encodes a plant homeodomain (PHD) finger protein that functions as a transcriptional activator, and plays a key role in tapetal development and pollen exine formation. ZmMs7 can interact with maize nuclear factor Y (NF-Y) subunits to form ZmMs7-NF-YA6-YB2-YC9/12/15 protein complexes that activate target genes by directly binding to CCAAT box in their promoter regions. Premature expression of in maize by an anther-specific promoter results in dominant and complete male sterility but normal vegetative growth and female fertility. Early expression of downstream genes induced by prematurely expressed ZmMs7 leads to abnormal tapetal development and pollen exine formation in maize lines. The transgenic rice and plants display similar dominant male sterility. Meanwhile, the gene coupled with facilitates the sorting of dominant sterility seeds based on fluorescent selection. In addition, both the recessive male-sterility line and dominant male-sterility line are highly stable under different genetic germplasms and thus applicable for hybrid maize breeding. Together, our work provides insight into the mechanisms of anther and pollen development and a promising technology for hybrid seed production in crops.
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http://dx.doi.org/10.1073/pnas.2010255117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519223PMC
September 2020

Identification of novel candidate pathogenic genes in pituitary stalk interruption syndrome by whole-exome sequencing.

J Cell Mol Med 2020 10 31;24(20):11703-11717. Epub 2020 Aug 31.

Clinical Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pituitary stalk interruption syndrome (PSIS) is a type of congenital malformation of the anterior pituitary, which leads to isolated growth hormone deficiency or multiple hypothalamic-pituitary deficiencies. Many genetic factors have been explored, but they only account for a minority of the genetic aetiology. To identify novel PSIS pathogenic genes, we conducted whole-exome sequencing with 59 sporadic PSIS patients, followed by filtering gene panels involved in pituitary development, holoprosencephaly and midline abnormality. A total of 81 heterozygous variants, distributed among 59 genes, were identified in 50 patients, with 31 patients carrying polygenic variants. Fourteen of the 59 pathogenic genes clustered to the Hedgehog pathway. Of them, PTCH1 and PTCH2, inhibitors of Hedgehog signalling, showed the most frequent heterozygous mutations (22%, seven missense and one frameshift mutations were identified in 13 patients). Moreover, five novel heterozygous null variants in genes including PTCH2 (p.S391fs, combined with p.L104P), Hedgehog acyltransferase (p.R280X, de novo), MAPK3 (p.H50fs), EGR4 (p.G22fs, combined with LHX4 p.S263N) and SPG11 (p.Q1624X), which lead to truncated proteins, were identified. In conclusion, genetic mutations in the Hedgehog signalling pathway might underlie the complex polygenic background of PSIS, and the findings of our study could extend the understanding of PSIS pathogenic genes.
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http://dx.doi.org/10.1111/jcmm.15781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579688PMC
October 2020

Circ_0005075 targeting miR-151a-3p promotes neuropathic pain in CCI rats via inducing NOTCH2 expression.

Gene 2021 Jan 27;767:145079. Epub 2020 Aug 27.

Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, No. 39 Chaoyang Middle Road, Maojian District, Shiyan City 442000, China. Electronic address:

Neuropathic pain is a most challenging diseases worldwide, caused by the injury of nerve system. CircularRNAs (circRNAs) are revealed to be involved in various diseases, includingneuropathic pain. However, the waycircRNAsparticipate in the progress ofneuropathic painstill needs further study. Identifyingthe possible circRNAexpression patterns of neuropathic painis of great significance to understand its underlying mechanism. Previously, circ_0005075 has been regarded as an important oncogene in multiple cancers and it has been characterized as an inflammation‑associated circRNA in various processes. Nevertheless, the functional role of circ_0005075 in neuropathic pain development is still poorly known. In our present study, we observed circ_0005075 was obviously increased in CCI rat models. Knockdown of circ_0005075 repressed thebehaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, loss of circ_0005075 could repress the neuroinflammation via targeting COX-2, IL-6 and TNF-α whereas inducing IL-10 in vivo. Additionally, we predicted miR-151a-3p as the potential target of circ_0005075 using bioinformatics analysis. We displayed that miR-151a-3p was greatly reduced in CCI rats and circ_0005075 reversed the repressive effect of miR-151a-3p on neuropathic pain. For another, NOTCH2 has been shown to induce a variety of intracellular responses correlated withneuropathic pain. Here, we found NOTCH2 expression was strongly induced in CCI rats and miR-151a-3p. In addition, circ_0005075 significantly rescued NOTCH2 expression, which could be repressed by miR-151a-3p. To sum up, we indicated that loss ofcirc_0005075relieved neuropathic pain progression by inducement of miR-151a-3p and inactivation of NOTCH2 signaling.
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http://dx.doi.org/10.1016/j.gene.2020.145079DOI Listing
January 2021

[Effect of pregnant serum folate concentration on newborn's birth weight].

Wei Sheng Yan Jiu 2020 May;49(3):386-396

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To study the effect of pregnant serum folate concentrations on the birth weight.

Methods: This study was a prospective cohort study. Pregnant women aged 18-45 who were examined and delivered in a county in Hebei Province from June 2016 to August 2018 and their newborns were included in the study. A total of 490 women were recruited and collected venous blood before the 20 th week of pregnancy. Basic information of women as well as their use of folic acid supplements was collected at the same time. Newborns' basic information, such as sex and birth weight, had been collected after delivery. The chemiluminescence method was used to determine the serum folate concentrations. Folate concentrations quartile were used as the cut-off point to divide subjects into four groups. The general linear model and multivariate unconditional Logistic regression analysis were used to study the effect of different serum folate concentrations on the infant birthweight.

Results: The age of 490 pregnant women was(27. 9±4. 1) years. The serum folate value P50(P25, P75) was 12. 3(9. 0, 14. 5) ng/mL and its' detection time was(13. 7±2. 6) weeks. 49. 3%(242/490) newborns were male. The average gestational age of the newborns was(39. 1±1. 0) weeks and the average birth weight was(3403±425) g. The birth weight of four groups' newborns were(3408±456) g, (3405±450) g, (3427±418) g and(3374±378) g, respectively. General linear model analysis showed that there was no significant difference in the effect of serum folate levels before the 20 th week of gestation on the birth weight(serum folate concentration<9. 0 ng/mL(β=32. 24, P=0. 55), serum folate concentration 9. 0-12. 2(β=18. 01, P=0. 74), serum folate concentration 12. 3-14. 4(β=42. 27, P=0. 43)]. Multivariate unconditional Logistic regression analysis showed that the group with folate concentration above 14. 5 ng/mL can reduce the risk of small for gestational age(SGA) [(P=0. 02, OR=0. 08(95% CI 0. 01-0. 61)]. Comparing with ghe pregnant women whose serum folate concentration was in 9. 0-12. 4 ng/mL. Hovever, there was no significant difference between the pregnant serum folate levels and large for gestational age(LGA).

Conclusion: There was no significant correlation between serum folate concentrations and the birth weight. But higher folate level may reduce the risk of SGA.
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http://dx.doi.org/10. 19813/j. cnki. weishengyanjiu. 2020. 03. 007DOI Listing
May 2020

Fibronectin-Targeting and Cathepsin B-Activatable Theranostic Nanoprobe for MR/Fluorescence Imaging and Enhanced Photodynamic Therapy for Triple Negative Breast Cancer.

ACS Appl Mater Interfaces 2020 Jul 20;12(30):33564-33574. Epub 2020 Jul 20.

Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

Because of the lack of specific targets, the highly aggressive triple negative breast cancer (TNBC) is unable to benefit from endocrine therapy or conventional targeting therapy. Even worse, current diagnostic and therapeutic approaches have limited value for TNBC. Therefore, developing TNBC-specific theranostic probes for accurate diagnosis and further selective therapy will build a powerful toolbox for TNBC management. In this contribution, we developed a sequential strategy to enhance the specificity of TNBC theranostics. In this theranostic system, a versatile nanoprobe ([email protected]) was integrated legitimately for the fibronectin-targeting MR imaging and CTSB-activatable fluorescence imaging, followed with enhanced photodynamic therapy (PDT) of TNBC. First, the fibronectin overexpressed in the extracellular matrix (ECM) of TNBC was used as a biomarker for targeting theranostics using the Cys-Arg-Glu-Lys-Ala (CREKA) peptide. For another, the fluorescence and PDT capacity of self-developed squaraine photosensitizer (SQ) were prequenched by ultrasmall superparamagnetic iron oxide (USPIO), an MR imaging contrast agent. Once the linker, Gly-Phe-Leu-Gly (GFLG) peptide, was selectively cleaved by TNBC-derived CTSB, the liberated SQ photosensitizer allowed light-up fluorescence imaging and enhanced PDT of TNBC. Remarkably, this research demonstrates that tumor-ECM-targeting and endogenous enzyme-activated nanoprobes open a new avenue for TNBC theranostics.
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http://dx.doi.org/10.1021/acsami.0c10397DOI Listing
July 2020

The Optimized Calculation Method for Insulin Dosage in an Insulin Tolerance Test (ITT): A Randomized Parallel Control Study.

Front Endocrinol (Lausanne) 2020 9;11:202. Epub 2020 Apr 9.

State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To explore the most suitable calculation method for insulin dosage in an insulin tolerance test (ITT) and to evaluate the clinical application value of the optimization coefficient (γ). In this study, 140 adult patients with congenital growth hormone deficiency (GHD) or acquired hypopituitarism were randomized into the following two groups: the conventional group ( = 70) and the optimized group ( = 70). Oral glucose tolerance tests (OGTTs), insulin release tests (IRTs), and ITTs were conducted. For ITTs, insulin doses were the product of body weight (kg) and related coefficient (0.15 IU/kg for the control group and γ IU/kg for the optimized group, respectively). Notably, γ was defined as -0.034 + 0.000176 × AUC + 0.009846 × BMI, which was based on our previous study. In the ITTs, the rate of achieving adequate hypoglycemia with a single insulin dose was significantly higher for the optimized group compared with the conventional group (92.9 vs. 60.0%, < 0.001). The optimized group required higher initial doses of insulin (0.23 IU/kg). Meanwhile, the two groups did not differ significantly in their nadir blood glucose (1.9 vs. 1.9 mmol/L, = 0.828). This study confirmed that the proposed optimized calculation method for insulin dosage in ITTs led to more efficient hypoglycemia achievement, without increasing the incidence of serious adverse events.
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http://dx.doi.org/10.3389/fendo.2020.00202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160329PMC
April 2021

Phylogeny and Functions of LOB Domain Proteins in Plants.

Int J Mol Sci 2020 Mar 26;21(7). Epub 2020 Mar 26.

Zhongzhi International Institute of Agricultural Biosciences, Biology and Agriculture Research Center, University of Science and Technology Beijing, Beijing 100024, China.

Lateral organ boundaries (LOB) domain () genes, a gene family encoding plant-specific transcription factors, play important roles in plant growth and development. At present, though there have been a number of genome-wide analyses on gene families and functional studies on individual LBD proteins, the diverse functions of LBD family members still confuse researchers and an effective strategy is required to summarize their functional diversity. To further integrate and improve our understanding of the phylogenetic classification, functional characteristics and regulatory mechanisms of LBD proteins, we review and discuss the functional characteristics of LBD proteins according to their classifications under a phylogenetic framework. It is proved that this strategy is effective in the anatomy of diverse functions of LBD family members. Additionally, by phylogenetic analysis, one monocot-specific and one eudicot-specific subclade of LBD proteins were found and their biological significance in monocot and eudicot development were also discussed separately. The review will help us better understand the functional diversity of LBD proteins and facilitate further studies on this plant-specific transcription factor family.
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http://dx.doi.org/10.3390/ijms21072278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178066PMC
March 2020

TOPORS, a tumor suppressor protein, contributes to the maintenance of higher-order chromatin architecture.

Biochim Biophys Acta Gene Regul Mech 2020 05 27;1863(5):194518. Epub 2020 Feb 27.

The Fifth People's Hospital of Shanghai, Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China. Electronic address:

In the nucleus, chromosomes are hierarchically folded into active (A) and inactive (B) compartments composed of topologically associating domains (TADs). Genomic regions interact with nuclear lamina, termed lamina-associated domains (LADs). However, the molecular mechanisms underlying these 3D chromatin architectures remain incompletely understood. Here, we investigated the role of a potential tumor suppressor, TOP1 Binding Arginine/Serine Rich Protein (TOPORS), in genome organization. In mouse hepatocytes, chromatin interactions between A and B compartments increase and compartmentalization strength is reduced significantly upon Topors knockdown. Correspondingly, strength of TAD boundaries located at A/B borders is weakened. In the absence of TOPORS, chromatin-lamina interactions decrease and the coverage of LADs reduces from 53.31% to 46.52%. Interestingly, these changes in 3D genome are associated with PML nuclear bodies and PML-associated domains (PADs). Moreover, chromatin accessibility is altered predominantly at intergenic regions upon Topors knockdown, including a subset of enhancers. These alterations of chromatin are concordant with transcriptome changes, which are associated with carcinogenesis. Collectively, our findings demonstrate that TOPORS functions as a regulator in chromatin structure, providing novel insight into the architectural roles of tumor suppressors in higher-order genome organization.
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http://dx.doi.org/10.1016/j.bbagrm.2020.194518DOI Listing
May 2020

The Nuclear Matrix Protein SAFB Cooperates with Major Satellite RNAs to Stabilize Heterochromatin Architecture Partially through Phase Separation.

Mol Cell 2020 01 30;77(2):368-383.e7. Epub 2019 Oct 30.

Key Laboratory of Metabolism and Molecular Medicine of Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; The Fifth People's Hospital of Shanghai and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China. Electronic address:

Interphase chromatin is hierarchically organized into higher-order architectures that are essential for gene functions, yet the biomolecules that regulate these 3D architectures remain poorly understood. Here, we show that scaffold attachment factor B (SAFB), a nuclear matrix (NM)-associated protein with RNA-binding functions, modulates chromatin condensation and stabilizes heterochromatin foci in mouse cells. SAFB interacts via its R/G-rich region with heterochromatin-associated repeat transcripts such as major satellite RNAs, which promote the phase separation driven by SAFB. Depletion of SAFB leads to changes in 3D genome organization, including an increase in interchromosomal interactions adjacent to pericentromeric heterochromatin and a decrease in genomic compartmentalization, which could result from the decondensation of pericentromeric heterochromatin. Collectively, we reveal the integrated roles of NM-associated proteins and repeat RNAs in the 3D organization of heterochromatin, which may shed light on the molecular mechanisms of nuclear architecture organization.
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http://dx.doi.org/10.1016/j.molcel.2019.10.001DOI Listing
January 2020

Activation of Kir2.3 Channels by Tenidap Suppresses Epileptiform Burst Discharges in Cultured Hippocampal Neurons.

CNS Neurol Disord Drug Targets 2019 ;18(8):621-630

Department of Neurology, Huashan Hospital, State Key Laboratory for Medical Neurobiology MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai 200032, China.

Background & Objective: Tenidap, a selective human inwardly rectifying potassium (Kir) 2.3 channel opener, has been reported to have antiepileptic effect in the pilocarpine temporal lobe epilepsy rat model in our previous study. However, the effect of tenidap on neurons and its relationship with the epileptiform bursting charges in neuron is still required to be explored.

Methods: In this study, cyclothiazide (CTZ) induced cultured hippocampal neuron epileptic model was used to study the antiepileptic effect of tenidap and the relationship between Kir2.3 channel and the neuronal epileptiform burst.

Results: Patch clamp recording showed that both acute (2h) and chronic (48h) CTZ pre-treatment all significantly induced robust epileptiform burst activities in cultured hippocampal neurons, and tenidap acutely application inhibited this highly synchronized abnormal activities. The effect of tenidap is likely due to increased activity of Kir2.3 channels, since tenidap significantly enhanced kir current recorded from those neurons. In addition, neurons overexpressing Kir2.3 channels, by transfection with Kir2.3 plasmid, showed a significant large increase of the Kir current, prevented CTZ treatment to induce epileptiform burst discharge.

Conclusion: Our current study demonstrated that over activation of Kir2.3 channel in hippocampal neurons could positively interference with epileptiform burst activities, and tenidap, as a selective Kir2.3 channel opener, could be a potential candidate for seizure therapy.
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http://dx.doi.org/10.2174/1871527318666190807122623DOI Listing
October 2020

Engineering a highly efficient expression system to produce BcaPRO protease in Bacillus subtilis by an optimized promoter and signal peptide.

Int J Biol Macromol 2019 Oct 26;138:903-911. Epub 2019 Jul 26.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, National Engineering Laboratory for Industrial Enzyme, The College of Biotechnology, Tianjin University of Science and Technology, No.29, 13th Avenue, Tianjin Economic and Technological Development Area, Tianjin 300457, PR China. Electronic address:

Bacillus subtilis has been extensively utilized as a host to express heterologous protein used in various industrial processes. Hence, the secretory overproduction of recombinant proteins is highly dependent on the strong promoters and signal peptides with high efficiency in B. subtilis. To enlarge the limited information of signal peptides and promoters suitable for specific proteins expression at a high-level, a series of plasmids carrying various signal peptides and single, dual, or triple promoters were engineered using the coding sequence of reporter protein, alkaline serine protease (BcaPRO) from B. clausii. Finally, the signal peptide DacB was selected from a library composed of 73 Sec-type signal peptides, and the dual promoter P-P demonstrated the best performance. Furthermore, BcaPRO activity was as high as 27,860 U/mL in the supernatant of the recombinant B. subtilis WB600 containing the plasmid with the dual promoter P-P and signal peptide DacB with batch fermentation in a 5-L fermenter after 56 h. It indicated that this new engineered expression system would be potential for high-level BcaPRO expression in B. subtilis.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.07.175DOI Listing
October 2019

The first complete chloroplast genome sequence of and phylogenetic analysis.

Mitochondrial DNA B Resour 2019 Jul 11;4(2):2320-2321. Epub 2019 Jul 11.

College of Horticulture and Landscape, Yunnan Agricultural University, Kunming, China.

is a famous Chinese traditional medicine with long history. In this study, the complete chloroplast (cp) genome of was characterized and assembled using a high-throughput sequencing method. The complete cp genome is 164,008 bp in length, including a large single copy (LSC) region of 89,134 bp and a small single copy (SSC) region of 15,372 bp separated by two inverted repeat (IR) regions of 29,751 bp. A total of 137 genes were identified, including 88 protein-coding genes (PCG), 38 transfer RNA genes, 8 ribosomal RNA genes, and 3 pseudogenes. The phylogenetic analysis revealed that is located in Zingiberaceace, closely related to and with a 100% bootstrap support.
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http://dx.doi.org/10.1080/23802359.2019.1629354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687529PMC
July 2019

High bond difference parameter-induced low thermal transmission in carbon allotropes with sp and sp hybridization.

Phys Chem Chem Phys 2019 Jun 3;21(23):12611-12619. Epub 2019 Jun 3.

The MS2 Discovery Interdisciplinary Research Institute, Wilfrid Laurier University, 75 University Ave. West, Waterloo, Ontario N2L 3C5, Canada.

Carbon allotropes play an important role in the thermal transmission field, while there are huge thermal differences in their thermal conductivities. In this work, thermal transmission in three novel carbon allotropes with sp and sp hybridization has been studied, including T6-carbon, T10 and 3D-C5 by using non-equilibrium molecular dynamic simulations and phonon kinetic theory. Graphene and diamond with standard sp and sp hybridization, respectively, are also examined for comparison. Our results indicate that the thermal conductivities of T6-carbon, T10 and 3D-C5 at room temperature are much lower than those of diamond and graphene. Phonon kinetic theory analysis shows that the lower thermal conductivity of T6-carbon, T10 and 3D-C5 is caused by the combined action of their reduced phonon group velocities and relaxation time. Moreover, the bond difference parameter has been proposed to describe the relationship between bond structures and thermal conductivity in carbon allotropes, which presents a new and convenient method for in-depth understanding the thermal conductivity of carbon allotropes.
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http://dx.doi.org/10.1039/c9cp01029gDOI Listing
June 2019

[Relationship between different feeding methods and growth rate of infants within 6 months in a community in Beijing from 2013 to 2015].

Wei Sheng Yan Jiu 2019 May;48(3):413-417

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To observe the influence of feeding method on early growth rate of infants.

Methods: A retrospective cohort study was conducted with 416 infants born in a community in Beijing from October 2013 to October 2015. Infants fed by breast milk as the sole source of milk food were classed into the breastfeeding group, others were classed into the non-breastfeeding group. The information of physical examination on birth and within 6-month old was collected to analyze the influence of different feeding method on growth rate Z scores of length and body weight within 6-month old infants.

Results: When evaluating the effect of feeding patterns on the growth rate at 1 month, there was no significant difference between the two groups at 0-1 months and 0-3 months old body weight and body length growth rate Z score.When evaluating the effect of feeding patterns on the growth rate at 3 month, the results showed, in the 3-6 months old formula powder feeding group(0.60), the weight growth rate Z score of the infant was higher than that of the predominant breastfeeding group(-0.01).The length-growth rate Z score also showed that the formula powder feeding group(0.40) was higher than the predominant breastfeeding group(-0.03).The weight growth rate Z score of 0-6 months old was higher in the formula powder feeding group(0.90) than in the predominant breastfeeding group(0.60).The body length growth rate Z score was higher in the formula powder feeding group(1.00) than in the predominant breastfeeding group(0.70).

Conclusion: The feeding pattern of infants at 3 months of age will affect their subsequent growth rate. The addition of formula powder may cause the growth rate curve to shift upwards, thereby increasing the risk of overweight and obesity in infants.
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May 2019

Surgical Resection of SCLC: Prognostic Factors and the Tumor Microenvironment.

J Thorac Oncol 2019 05 5;14(5):914-923. Epub 2019 Feb 5.

Georgetown University, Washington DC. Electronic address:

Introduction: Surgery in SCLC is limited to very early stages, but several reports suggest a potential broader role. Little is known of the influence of microenvironment on the biology of SCLC.

Methods: We assessed the clinical prognostic factors in a large series of resected SCLC patients. The prognostic value of programmed cell death ligand 1 (PD-L1) expression in tumor cells and tumor infiltrating lymphocytes (TILs) and the percentage of CD3-, CD20-, CD45- and CD68-positive cells, were also investigated.

Results: Two hundred five SCLC cases were resected between 2005 and 2015 and the median follow-up was 29 months (range: 2 to 135 months). Median survival of all patients was 69 months, and 5-year survival rates were 63.8%, 65.5%, 34.9%, and 0% for pathologic stages I, II, III, and IV, respectively. By multivariate analysis complete resection, cigarette index, lymph node metastatic rate, percentage of CD3-positive cells, PD-L1 expression in tumor cells, and TILs were independent prognostic factors. High PD-L1 expression was present in 3.2% and 33.5% of all tumor samples in tumor cells and TILs, respectively. High PD-L1 expression in tumor cells or TILs correlated with shorter survival, whereas high expression of CD3, CD20, and CD45 correlated with better survival.

Conclusions: Resected stage II SCLC patients have similar survival as stage I, suggesting that surgery could be extended to patients with hilar lymph node involvement. Survival was better in tumors with a higher percentage of T cells and B cells, whereas PD-L1 expression in tumor cells and TILs correlated with worse survival, which suggests a potential role of immunotherapy in resected SCLC.
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http://dx.doi.org/10.1016/j.jtho.2019.01.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510981PMC
May 2019

ZmMs30 Encoding a Novel GDSL Lipase Is Essential for Male Fertility and Valuable for Hybrid Breeding in Maize.

Mol Plant 2019 03 23;12(3):343-359. Epub 2019 Jan 23.

Biology and Agriculture Research Center, University of Science and Technology Beijing, Beijing 100024, China; Beijing Engineering Laboratory of Main Crop Bio-Tech Breeding, Beijing International Science and Technology Cooperation Base of Bio-Tech Breeding, Beijing Solidwill Sci-Tech Co. Ltd., Beijing 100192, China. Electronic address:

Genic male sterility (GMS) is very useful for hybrid vigor utilization and hybrid seed production. Although a large number of GMS genes have been identified in plants, little is known about the roles of GDSL lipase members in anther and pollen development. Here, we report a maize GMS gene, ZmMs30, which encodes a novel type of GDSL lipase with diverged catalytic residues. Enzyme kinetics and activity assays show that ZmMs30 has lipase activity and prefers to substrates with a short carbon chain. ZmMs30 is specifically expressed in maize anthers during stages 7-9. Loss of ZmMs30 function resulted in defective anther cuticle, irregular foot layer of pollen exine, and complete male sterility. Cytological and lipidomics analyses demonstrate that ZmMs30 is crucial for the aliphatic metabolic pathway required for pollen exine formation and anther cuticle development. Furthermore, we found that male sterility caused by loss of ZmMs30 function was stable in various inbred lines with different genetic background, and that it didn't show any negative effect on maize heterosis and production, suggesting that ZmMs30 is valuable for cross-breeding and hybrid seed production. We then developed a new multi-control sterility system using ZmMs30 and its mutant line, and demonstrated it is feasible for generating desirable GMS lines and valuable for hybrid maize seed production. Taken together, our study sheds new light on the mechanisms of anther and pollen development, and provides a valuable male-sterility system for hybrid breeding maize.
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http://dx.doi.org/10.1016/j.molp.2019.01.011DOI Listing
March 2019

Sub-10 nm CuFeS cube for magnetic resonance imaging-guided photothermal therapy of cancer.

Int J Nanomedicine 2018 26;13:7987-7996. Epub 2018 Nov 26.

Department of Orthopedics, The First People's Hospital of Shangqiu, Shangqiu, Henan 476000, China.

Background: Facile synthesis and small size theranostic agents have shown great potential for cancer diagnosis and treatment.

Purpose: A ternary compound (CuFeS), Fe doped copper sulfide, with novel magnetic properties and strong near-infrared absorption was prepared for magnetic resonance imaging (MRI) imaging guided photothermal therapy of cancer.

Patients And Methods: Firstly, the capability of magnetic resonance imaging based on the novel magnetic properties and the photothermal performance due to the strong near-infrared absorption was investigated in vitro. Then, the magnetic resonance imaging guided photothermal therapy for 4T1 tumor-bearing mouse was carried out.

Results: The CuFeS cube with good T-weighted MRI, excellent photothermal performance and low cytotoxicity has been investigated. More importantly, the T-weighted MRI for 4T1 tumor-bearing mouse will get the best contrast effect at tumor site after 8 h of intravenous injection of CuFeS cube. Under the guidance of the T-weighted MRI, the PTT was carried out at 8 h after intravenous injection of CuFeS cube and only the group combined intravenous administration of CuFeS cube and laser irradiation nearly cured the tumor after 14 days.

Conclusion: Our study not only provides a new material for personalized treatment of tumors, but also further promotes potential applications of the cancer theranostic agents.
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http://dx.doi.org/10.2147/IJN.S181056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263250PMC
January 2019
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