Publications by authors named "Fenfen Wang"

67 Publications

Genetic diversity, forensic characteristics and phylogenetic analysis of the Qiongzhong aborigines residing in the tropical rainforests of Hainan Island via 19 autosomal STRs.

Ann Hum Biol 2021 Jul 21:1-8. Epub 2021 Jul 21.

First Clinical Medical College, Hainan Medical University, Haikou, China.

Background: The genetic landscape of the Qiongzhong aborigines, who reside in "the Heart of Hainan," is still unclear. The Goldeneye™ DNA ID System 20 A is available for forensic and population genetics applications.

Aim: To obtain genetic polymorphisms of 19 autosomal STR loci in the Qiongzhong aborigines, and to explore the genetic relationships with a total of 69,132 people from forty-five populations.

Subjects And Methods: Genotype data on 19 autosomal STRs were collected from 724 Qiongzhong aborigines and phylogenetic relationships were conducted by multidimensional scaling analysis (MDS), principal component analysis (PCA) and neighbor-joining (N-J) phylogenetic tree construction.

Results: No evidence of deviation from Hardy-Weinberg equilibrium was identified. A total of 233 distinct alleles were observed with allele frequencies ranging from 0.0007 to 0.5375. The combined power of discrimination (CPD) and combined power of exclusion (CPE) for the 19 autosomal STR loci were 1-8.28 × 10 and 0.999999987, respectively.

Conclusion: Our phylogenetic results demonstrated that (a) the populations of Southeast Asian countries have thorough integrations with southern China in terms of ethnicity and genetics due to long-term cultural and trade exchanges, and (b) based on genetic and linguistic analysis, the Qiongzhong aborigines have a close relationship with Fujian Han Chinese.HighlightsThe STR landscape of Qiongzhong aborigines inhabited in Hainan tropical rainforests was depicted by 19 autosomal STRs.A total of 69,132 people from forty-five populations were selected for a more extensive examination of genetic similarities and differences by multivariate statistical methods (MDS, PCA and N-J tree construction).The genetic analyses indicated that the populations of Southeast Asian countries are very genetically close to southern Chinese populations.From the genetic and linguistic perspective, the Qiongzhong aborigines have a close relationship with Han Chinese from Fujian Province.
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http://dx.doi.org/10.1080/03014460.2021.1951352DOI Listing
July 2021

Genome-Wide Analysis of the Gene Family and Identification of Flavonoids in .

Molecules 2021 Jun 6;26(11). Epub 2021 Jun 6.

Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing 100093, China.

is a multifunctional deciduous tree that is both a food and a source of traditional Chinese medicine for both humans and animals. Further analysis of the UGT gene family is of great significance to the utilization of . The substrates of plant genes include highly diverse and complex chemicals, such as flavonoids and terpenes. In order to deepen our understanding of this family, a comprehensive analysis was performed. Phylogenetic analysis showed that 155 were divided into 15 subgroups. A conserved motif analysis showed that proteins in the same subgroups possessed similar motif structures. Tandem duplication was the primary driving force for the expansion of the gene family. The global promoter analysis indicated that they were associated with complex hormone regulatory networks and the stress response, as well as the synthesis of secondary metabolites. The expression pattern analysis showed that the expression level of in leaves and roots was higher than that in fruits and stems. Next, we determined the composition and content of flavonoids, the main products of the reaction. A total of 19 compounds were isolated and analyzed by UPLC-ESI-MS/MS in 3 species of including , , and , and the number of compounds was different in these 3 species. The total flavonoid content and antioxidant capacities of the three species were analyzed respectively. All assays exhibited the same trend: the hybrid paper mulberry showed a higher total flavonoid content, a higher total phenol content and higher antioxidant activity than the other two species. Overall, our study provides valuable information for understanding the function of in the biosynthesis of flavonoids.
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http://dx.doi.org/10.3390/molecules26113449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200958PMC
June 2021

Insights From Y-STRs: Forensic Characteristics, Genetic Affinities, and Linguistic Classifications of Guangdong Hakka and She Groups.

Front Genet 2021 24;12:676917. Epub 2021 May 24.

School of Forensic Medicine, Southern Medical University, Guangzhou, China.

Guangdong province is situated in the south of China with a population size of 113.46 million. Hakka is officially recognized as a branch of Han Chinese, and She is the official minority group in mainland China. There are approximately 25 million Hakka people who mainly live in the East and North regions of China, while there are only 0.7 million She people. The genetic characterization and forensic parameters of these two groups are poorly defined (She) or still need to be explored (Hakka). In this study, we have genotyped 475 unrelated Guangdong males (260 Hakka and 215 She) with Promega PowerPlex Y23 System. A total of 176 and 155 different alleles were observed across all 23 Y-STRs for Guangdong Hakka (with a range of allele frequencies from 0.0038 to 0.7423) and Guangdong She (0.0047-0.8605), respectively. The gene diversity ranged from 0.4877 to 0.9671 (Guangdong Hakka) and 0.3277-0.9526 (Guangdong She), while the haplotype diversities were 0.9994 and 0.9939 for Guangdong Hakka and Guangdong She, with discrimination capacity values of 0.8885 and 0.5674, respectively. With reference to geographical and linguistic scales, the phylogenetic analyses showed us that Guangdong Hakka has a close relationship with Southern Han, and the genetic pool of Guangdong Hakka was influenced by surrounding Han populations. The predominant haplogroups of the Guangdong She group were O2-M122 and O2a2a1a2-M7, while Guangdong She clustered with other Tibeto-Burman language-speaking populations (Guizhou Tujia and Hunan Tujia), which shows us that the Guangdong She group is one of the branches of Tibeto-Burman populations and the Huonie dialect of She languages may be a branch of Tibeto-Burman language families.
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http://dx.doi.org/10.3389/fgene.2021.676917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181459PMC
May 2021

Activation of GCN2 in macrophages promotes white adipose tissue browning and lipolysis under leucine deprivation.

FASEB J 2021 06;35(6):e21652

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

We have previously shown that leucine deprivation stimulates browning and lipolysis in white adipose tissue (WAT), which helps to treat obesity. Adipose tissue macrophages (ATMs) significantly influence WAT browning and lipolysis. However, it is unclear whether ATMs are involved in leucine deprivation-induced browning and lipolysis in WAT; the associated signals remain to be elucidated. Here, we investigated the role of ATMs and the possible mechanisms involved in WAT browning and lipolysis under leucine-deprivation conditions. In this study, macrophages were depleted in mice by injecting clodronate-liposomes (CLOD) into subcutaneous white adipose tissues. Then, mice lacking general control nonderepressible 2 kinase (GCN2), which is a sensor of amino acid starvation, specifically in Lyz2-expressing cells, were generated to investigate the changes in leucine deprivation-induced WAT browning and lipolysis. We found leucine deprivation decreased the accumulation and changed the polarization of ATMs. Ablation of macrophages by CLOD impaired WAT browning and lipolysis under leucine-deprivation conditions. Mechanistically, leucine deprivation activated GCN2 signals in macrophages. Myeloid-specific abrogation of GCN2 in mice blocked leucine deprivation-induced browning and lipolysis in WAT. Further analyses revealed that GCN2 activation in macrophages reduced the expression of monoamine oxidase A (MAOA), resulting in increased norepinephrine (NE) secretion from macrophages to adipocytes, and this resulted in enhanced WAT browning and lipolysis. Moreover, the injection of CL316,243, a β3-adrenergic receptor agonist, and inhibition of MAOA effectively increased the level of NE, leading to the enhancement of browning and lipolysis of WAT in myeloid GCN2 knockout mice under leucine deprivation. Collectively, our results demonstrate a novel function of GCN2 signals in macrophages, that is, regulating WAT browning and lipolysis under leucine deprivation. Our study provides important hints for possible treatment for obesity.
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http://dx.doi.org/10.1096/fj.202100061RRDOI Listing
June 2021

The forensic landscape and the population genetic analyses of Hainan Li based on massively parallel sequencing DNA profiling.

Int J Legal Med 2021 Jul 13;135(4):1295-1317. Epub 2021 Apr 13.

School of Forensic Medicine, Southern Medical University, Guangzhou, 510515, China.

Due to the formation of the Qiongzhou Strait by climate change and marine transition, Hainan island was isolated from the mainland southern China during the Last Glacial Maximum. Hainan island, located at the southernmost part of China and separated from the Leizhou Peninsula by the Qiongzhou Strait, laid on one of the modern human northward migration routes from Southeast Asia to East Asia. The Hlai language-speaking Li minority, the second largest population after Han Chinese in Hainan island, is the direct descendants of the initial migrants in Hainan island and has unique ethnic properties and derived characteristics; however, the forensic-associated studies on Hainan Li population are still insufficient. Hence, 136 Hainan Li individuals were genotyped in this study using the MPS-based ForenSeq™ DNA Signature Prep Kit (DNA Primer Set A, DPMA) to characterize the forensic genetic polymorphism landscape, and DNA profiles were obtained from 152 different molecular genetic markers (27 autosomal STRs, 24 Y-STRs, 7 X-STRs, and 94 iiSNPs). A total of 419 distinct length variants and 586 repeat sequence sub-variants, with 31 novel alleles (at 17 loci), were identified across the 58 STR loci from the DNA profiles of Hainan Li population. We evaluated the forensic characteristics and efficiencies of DPMA, demonstrating that the STRs and iiSNPs in DPMA were highly polymorphic in Hainan Li population and could be employed in forensic applications. In addition, we set up three datasets, which included the genetic data of (i) iiSNPs (27 populations, 2640 individuals), (ii) Y-STRs (42 populations, 8281 individuals), and (iii) Y haplogroups (123 populations, 4837 individuals) along with the population ancestries and language families, to perform population genetic analyses separately from different perspectives. In conclusion, the phylogenetic analyses indicated that Hainan Li, with a southern East Asia origin and Tai-Kadai language-speaking language, is an isolated population relatively. But the genetic pool of Hainan Li influenced by the limited gene flows from other Tai-Kadai populations and Hainan populations. Furthermore, the establishment of isolated population models will be beneficial to clarify the exquisite population structures and develop specific genetic markers for subpopulations in forensic genetic fields.
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http://dx.doi.org/10.1007/s00414-021-02590-3DOI Listing
July 2021

Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma.

Mol Cancer 2021 03 29;20(1):57. Epub 2021 Mar 29.

Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.

Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.
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http://dx.doi.org/10.1186/s12943-021-01352-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006369PMC
March 2021

Natural population re-sequencing detects the genetic basis of local adaptation to low temperature in a woody plant.

Plant Mol Biol 2021 Apr 2;105(6):585-599. Epub 2021 Mar 2.

Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing, 100093, China.

Key Message: Total of 14 SNPs associated with overwintering-related traits and 75 selective regions were detected. Important candidate genes were identified and a possible network of cold-stress responses in woody plants was proposed. Local adaptation to low temperature is essential for woody plants to against changeable climate and safely survive the winter. To uncover the specific molecular mechanism of low temperature adaptation in woody plants, we sequenced 134 core individuals selected from 494 paper mulberry (Broussonetia papyrifera), which naturally distributed in different climate zones and latitudes. The population structure analysis, PCA analysis and neighbor-joining tree analysis indicated that the individuals were classified into three clusters, which showed forceful geographic distribution patterns because of the adaptation to local climate. Using two overwintering phenotypic data collected at high latitudes of 40°N and one bioclimatic variable, genome-phenotype and genome-environment associations, and genome-wide scans were performed. We detected 75 selective regions which possibly undergone temperature selection and identified 14 trait-associated SNPs that corresponded to 16 candidate genes (including LRR-RLK, PP2A, BCS1, etc.). Meanwhile, low temperature adaptation was also supported by other three trait-associated SNPs which exhibiting significant differences in overwintering traits between alleles within three geographic groups. To sum up, a possible network of cold signal perception and responses in woody plants were proposed, including important genes that have been confirmed in previous studies while others could be key potential candidates of woody plants. Overall, our results highlighted the specific and complex molecular mechanism of low temperature adaptation and overwintering of woody plants.
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http://dx.doi.org/10.1007/s11103-020-01111-xDOI Listing
April 2021

TWIST1 expression and clinical significance in type I endometrial cancer and premalignant lesions: A retrospective clinical study.

Medicine (Baltimore) 2020 Nov;99(48):e23397

Department of Gynecologic Oncology.

The aim of this study was to assess the correlation of TWIST1 expression with clinical parameters and the prognosis of type I endometrial cancer (EC).This retrospective study enrolled 345 patients. Immunohistochemical staining was performed on 55 normal endometrium (NE) samples, 27 atypical hyperplasia (AH) samples, and 263 type I EC samples. The association between TWIST1 staining and clinical characteristics and survival was evaluated by univariate and multivariate analyses.We found significantly higher TWIST1 expression in patients with AHs and type I ECs than NEs, but there was no significant difference between TWIST1 expression in AHs and type I ECs. Aberrant TWIST1 expression was significantly associated with clinical parameters, indicating poor prognosis and shorter patient survival. Pearsons Chi-Squared test showed that high TWIST1 expression was significantly associated with a shorter disease-free survival and overall survival. More importantly, multivariate analysis showed that high TWIST1 expression, in addition to myometrial invasion, lymph vascular space invasion, and lymph node metastasis, was an independent predictor of worse DFS in patients with type I ECs.Our findings suggest that TWIST1 might be useful in diagnosing ECs and predicting prognosis in patients with AHs and type I ECs.
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http://dx.doi.org/10.1097/MD.0000000000023397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710231PMC
November 2020

Highly Bidirectional Bendable Actuator Engineered by LCST-UCST Bilayer Hydrogel with Enhanced Interface.

ACS Appl Mater Interfaces 2020 Dec 24;12(49):55290-55298. Epub 2020 Nov 24.

Key Laboratory of Functional Polymer Materials of the Ministry of Education and College of Chemistry, Nankai University, Tianjin 300071, P. R. China.

Thermoresponsive hydrogel-based actuators are highly important for fundamental research and industrial applications, while the preparation of temperature-driven bilayer hydrogel actuators with rapid response to bend and recover properties remains a challenge. To date, most temperature-driven bilayer hydrogel actuators are based on polymers only with a lower critical solution temperature (LCST) or with an upper critical solution temperature (UCST), which need more time to bend and recover just in a small range of bending angle. Herein, we propose a new strategy to design and synthesize a fully temperature-driven bilayer hydrogel actuator, which consists of a poly(-acryloyl glycinamide) (NAGA) layer with a UCST-type volume phase change and a poly(-isopropyl acrylamide) (NIPAM)-Laponite nanocomposite layer with an LCST-type volume phase change. Due to the complementary UCST and LCST behavior of the two selected polymers, both layers have opposite thermoresponsive swelling and shrinkage properties at low and high temperatures; this imbues the hydrogel actuator with rapid thermoresponsive bending and recovery ability, as well as a large bending angle. In addition, the incorporation of Laponite nanosheets in PNIPAM layer not only improves the mechanical property of actuators but also provides the excellent bonding ability of the two-layer interface, which prevents delamination caused by excessive local stress on the interface during the bending process. Thanks to high-performance behavior, the actuator can act as an effective and sensitive actuator, such as a gripper to capture, transport, and release an object, or as an electrical circuit switch to turn on and off a light-emitting diode (LED). Overall, such hydrogel actuator may provide new insights for the design and fabrication of artificial intelligence materials.
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http://dx.doi.org/10.1021/acsami.0c17085DOI Listing
December 2020

Effect of settling time on the adsorption of Cs onto AMP in the AMP-coprecipitation method.

Mar Pollut Bull 2020 Dec 3;161(Pt B):111713. Epub 2020 Oct 3.

Laboratory of Marine Isotopic Technology and Environmental Risk Assessment, Third Institute of Oceanography, Ministry of Natural Resource, 184 Daxue Road, Xiamen 361005, China.

Ten sets of experiments with different settling times were conducted to investigate the effect of settling time on the adsorption of Cs in seawater onto ammonium phosphomolybdate (AMP). The weight yields of AMP and Cs yields in all groups were generally higher than 90%. The average weight yields of AMP in each group varied from 91.8 ± 0.5 to 95.9 ± 0.6% (1 SD), and the average Cs yields in each group varied from 88.3 ± 3.0 to 97.8 ± 3.7% (1 SD). The results showed that equilibrium between Cs and AMP is established immediately after the addition of stable Cs carrier and AMP, implying that the solution could be filtered immediately after the coprecipitation forms. IAEA seawater proficiency test exercises also confirmed that the AMP precipitate does not need to be treated statically in the case of 2 g AMP and 3.7 mg Cs carrier in a seawater sample solution. The modified AMP preconcentration method simultaneously meets the requirements of routine and nuclear emergency monitoring of Cs in seawater.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111713DOI Listing
December 2020

Forensic characteristics and phylogenetic analyses of one branch of Tai-Kadai language-speaking Hainan Hlai (Ha Hlai) via 23 autosomal STRs included in the Huaxia Platinum System.

Mol Genet Genomic Med 2020 10 30;8(10):e1462. Epub 2020 Aug 30.

School of Basic Medicine and Life Science, Hainan Medical University, Haikou, China.

Background: Hainan Island, located in the South China Sea and separated from the Leizhou Peninsula by Qiongzhou Strait, is the second largest island after Taiwan in China. With the expansion of Han Chinese and the gradual formation of "South Hlai and North Han", nowadays, Hainan Hlai is the second largest population after Han Chinese in Hainan Island. Ha Hlai, distributed in southwest and southern Hainan Island, is the dominant branch of Hlai and speaks Ha localism.

Methods: We utilized the Huaxia Platinum PCR Amplification System (including 23 autosomal STRs and 2 sex-linked markers) to obtain the first STR profiling batch of 657 Ha Hlai individuals (497 males and 160 females). In order to explore the genetic relationships between the studied Ha Hlai and other reference populations with different language families, population genetic analyses, including PCA, MDS, STRUCTURE, and phylogenetic analysis, were conducted based upon the raw data and allelic frequencies of the polymorphic autosomal STR markers.

Results: In total, 271 distinct alleles were observed at the 23 STR loci. The number of diverse alleles ranged from 7 at TPOX locus to 23 at FGA locus, and the allelic frequencies varied from 0.0008 to 0.5533. In addition, the CPE and CPD were 1-7.39 × 10 and 1-3.13 × 10 , respectively. The phylogenetic analyses indicated that Ha Hlai is a Tai-Kadai language-speaking and relatively isolated population which has a close genetic and geographical relationship with Hainan Hlai, and M95 is the dominant haplogroup in Ha Hlai (56.18%).

Conclusion: The 23 autosomal STR genetic markers were highly polymorphic as well as potentially useful for forensic applications in Hainan Ha Hlai population. The phylogenetic analyses demonstrated that small geographic scale gene flows could not be ignored and the shaping of the unique gene pool for each population was the combination effects of geographic, language, and cultural isolations.
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http://dx.doi.org/10.1002/mgg3.1462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549582PMC
October 2020

Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia: a literature review of pharmaceutical and clinical aspects.

Eur J Hosp Pharm 2020 Jun 26. Epub 2020 Jun 26.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Objectives: The rate of dermal toxicity has been shown to increase in patients receiving pegylated liposomal doxorubicin (PLD), particularly palmar-plantar erythrodysesthesia (PPE). However, it is difficult to diagnose and treat PLD-related PPE due to its delayed dermal performance, unclear pathogenetic mechanism, and the lack of specific preventive measures. The aim of this study was to provide potential management strategies for PPE associated with PLD.

Methods: The current article reviews the available data regarding the pharmacological and clinical aspects of PLD, including the formulation and pharmacokinetics of PLD, dose and schedule contribution to PPE, concomitant drugs affecting skin toxicity of PLD, the pathogenesis of PPE, and preventive measures and treatment of PLD-related PPE.

Results: The long circulation structure of polyethylene glycol liposomes may be one of the reasons for PPE. PLD has radically different pharmacokinetic characteristics, including prolonged blood circulation time, decreased body distribution volume, and slow clearance. Altering the schedules and doses of PLD or combining it with platinum compounds can optimise clinical efficacy and minimise the occurrence of PPE. Doses of 150-200 mg of pyridoxine daily have been widely used for the prevention and treatment of PPE. Regional cooling and plasma filtration have been used for PPE prophylaxis.

Conclusions: To date, the mechanism of PPE induced by PLD remains unclear, and no complete preventive medication has been established. Further research and prospective randomised studies are needed to understand the management options in PLD-related PPE.
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http://dx.doi.org/10.1136/ejhpharm-2020-002311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077615PMC
June 2020

Impact of the Fukushima Dai-ichi Nuclear Power Plant Accident on dolphin fishes in the Northwest Pacific.

Chemosphere 2020 Oct 4;257:127267. Epub 2020 Jun 4.

Key Laboratory of Particle and Radiation Imaging (Ministry of Education) and Department of Engineering Physics, Tsinghua University, Beijing, 100084, China. Electronic address:

More than 9 years since the Fukushima Dai-ichi Nuclear Power Plant Accident (FDNPPA), the impact of FDNPPA on marine biota is being revealed. In this work, the evolution of FDNPPA derived Cs, Cs and Ag in dolphin fishes (Coryphaena hippurus) in the Northwest Pacific from Dec. 2011 to Sept. 2018 were studied. Bioconcentration factors (BCF) of radiocesium (29-69 with the average of 48) in dolphin fishes were calculated. The background level of Cs in dolphin fishes (<0.14 Bq/kg) before FDNPPA was estimated. The radioactive levels of these three radionuclides in dolphin fishes decreased with time. Among them, Cs and Ag decreased at the half-lives of 158 days and 54 days at the population level, respectively. After May 2014, Cs and Ag cannot be detected and the activity of Cs returned to the background level before FDNPPA. Radiation dose assessment demonstrated that it was far from causing radiation harm to dolphin fishes in the open ocean of Northwest Pacific and humans who ingested them.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127267DOI Listing
October 2020

Impact of the Fukushima Dai-ichi Nuclear Power Plant Accident on the neon flying squids in the Northwest Pacific from 2011 to 2018.

Environ Pollut 2020 Sep 28;264:114647. Epub 2020 Apr 28.

Laboratory of Marine Isotopic Technology and Environmental Risk Assessment, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, 361005, China.

Following nine years since the Fukushima Dai-ichi Nuclear Power Plant Acciden (FDNPPA), it might be the time to draw a much clearer conclusion for the impact of FDNPPA on marine biota. In this work, the evolution of the FDNPPA derived Cs, Cs and Ag in the neon flying squids in the Northwest Pacific from 2011 to 2018 were studied. The background level of Cs in neon flying squids (<0.10 Bq/kg with the average of 0.017 Bq/kg) before FDNPPA were estimated. The radioactive levels of Cs, Cs and Ag in neon flying squids decreased with time. Cs and Ag decreased at the half-lives of 7.6 months and 5.7 months at the population level, respectively. After May 2014, Cs and Ag cannot be detected and Cs activities returned to the background level before FDNPPA. BCFs of cesium isotopes (3.7-17.7 with the average of 10.8) and Ag (∼7 × 10) for neon flying squids were estimated. The amount of Ag released into the Northwest Pacific (∼20-∼26 TBq) were firstly calculated using a Cs/Ag method. Radiation dose assessment demonstrated that it was far from causing radiation harm to neon flying squids in the open ocean of Northwest Pacific and humans who ingested these neon flying squids.
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http://dx.doi.org/10.1016/j.envpol.2020.114647DOI Listing
September 2020

WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/β-catenin pathway.

Cell Oncol (Dordr) 2020 Jun 16;43(3):489-503. Epub 2020 Apr 16.

Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.

Purpose: Persistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion.

Methods: WNT1 and miR-34a expression levels were assessed in primary cervical lesions using immunohistochemistry and qRT-PCR, respectively. The cellular effects and the expression of its associated genes were examined in cervical SCC-derived Siha and Caski cells after siRNA-WNT1 (downregulation) or miR-34a mimic (upregulation) treatment. A cervical SCC xenograft mouse model was used to investigate the in vivo effects of miR-34a overexpression. HPV-16 E6/E7 expression was inhibited by gene promoter siRNA targeting, after which the levels of miR-34a and WNT1 were examined.

Results: WNT1 protein upregulation was found to be associated with a poor prognosis in cervical SCC patients. In vitro assays in Siha and Caski cells revealed that WNT1 downregulation decreased cell proliferation and invasion, inhibited WNT/β-catenin activation and affected the expression of E-cadherin and P-cadherin. MiR-34a upregulation resulted in decreased WNT1 expression. An inverse correlation between miR-34a and WNT1 expression was also observed in primary cervical SCC tissues. In addition, we found that MiR-34a could regulate an E-cadherin to P-cadherin switch (E-P cadherin switch) to inhibit cell proliferation and tumorigenesis in vitro and in vivo via inactivation of the WNT1/β-catenin pathway. Finally, we found that decreased HPV-16 E6/E7 expression resulted in miR-34a upregulation and WNT1 downregulation in Siha and Caski cells.

Conclusions: From our results we conclude that WNT1, as a target of miR-34a, can promote cervical SCC cell proliferation and invasion by induction of an E-P cadherin switch via the WNT1/β-catenin pathway. Our results may provide new options for the treatment of patients with cervical SCC.
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http://dx.doi.org/10.1007/s13402-020-00506-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214512PMC
June 2020

Interplay of Lewis and Brønsted Acid Sites in Zr-Based Metal-Organic Frameworks for Efficient Esterification of Biomass-Derived Levulinic Acid.

ACS Appl Mater Interfaces 2019 Sep 23;11(35):32090-32096. Epub 2019 Aug 23.

School of Chemical Engineering and Light Industry , Guangdong University of Technology , Guangzhou Higher Education Mega Center , Guangzhou 510006 , China.

We report the performance of UiO-66 and its Brønsted acid functionalized derivative, UiO-66-(COOH), as heterogeneous catalysts for levulinic acid esterification with ethanol. Importantly, compared with UiO-66, UiO-66-(COOH) displayed superior catalytic performance (up to 97.0 ± 1.1% yield of ethyl levulinate) attributed to the synergistic effect between Lewis acidic Zr clusters and Brønsted acidic -COOH groups. Furthermore, UiO-66-(COOH) was stable and reusable without an appreciable loss in catalytic activity for at least five consecutive cycles. This study demonstrates that the interplay of Brønsted and Lewis acid sites in zirconium metal-organic frameworks leads to more efficient catalytic conversion of a biomass feedstock to biofuel, and with further hypothesis driven research, additional materials that show promise as candidates for catalytic conversion of biomass feedstocks to biofuels and valuable chemicals can be developed.
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http://dx.doi.org/10.1021/acsami.9b07769DOI Listing
September 2019

Dual Cross-linked Vinyl Vitrimer with Efficient Self-Catalysis Achieving Triple-Shape-Memory Properties.

Macromol Rapid Commun 2019 Oct 8;40(19):e1900313. Epub 2019 Aug 8.

Department of Physics and Astronomy, McMaster University, Hamilton, Ontario, L8S 4M1, Canada.

As an emerging class of dynamic cross-linked network, vitrimers have attracted much attention due to the combination of mechanical advantages of thermosets and recyclability of thermoplastics at an elevated temperature. In particular, most vitrimers with multi-shape memory properties usually involve more than one thermal transition or molecular switch, which might pose a challenge for facile sample fabrication and potentially limits their applications. In pursuit of a more universal and simple route, utilizing commercially available and inexpensive reagents to prepare shape-memory vitrimers with dual cross-linked network from vinyl monomer-derived prepolymers is reported here. Copolymerization of desired vinyl monomers gives prepolymers containing carboxyl and zinc carboxylate groups, which are later converted into vitrimers in a single step by post-curing with diglycidylether of bisphenol A. The Zn ions can not only act as physical crosslinking points through ionic coordination interactions, thus providing the triple-shape-memory properties, but also play the role of catalyst to activate transesterification in the dynamic covalent network. This new self-catalyzed vitrimer has excellent transesterification efficiency, triple-shape-memory properties, and can be sufficiently healed and reprocessed at an elevated temperature. The proposed molecular design of self-catalyzed materials opens a new avenue toward commercially relevant fabrication of high-performance vitrimers with multiple shape-memory properties.
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http://dx.doi.org/10.1002/marc.201900313DOI Listing
October 2019

Autophagy inhibition prevents glucocorticoid-increased adiposity via suppressing BAT whitening.

Autophagy 2020 03 18;16(3):451-465. Epub 2019 Jun 18.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

The mechanisms underlying glucocorticoid (GC)-increased adiposity are poorly understood. Brown adipose tissue (BAT) acquires white adipose tissue (WAT) cell features defined as BAT whitening under certain circumstances. The aim of our current study was to investigate the possibility and mechanisms of GC-induced BAT whitening. Here, we showed that one-week dexamethasone (Dex) treatment induced BAT whitening, characterized by lipid droplet accumulation, in vitro and in vivo. Furthermore, autophagy and ATG7 (autophagy related 7) expression was induced in BAT by Dex, and treatment with the autophagy inhibitor chloroquine or adenovirus-mediated ATG7 knockdown prevented Dex-induced BAT whitening and fat mass gain. Moreover, Dex-increased ATG7 expression and autophagy was mediated by enhanced expression of BTG1 (B cell translocation gene 1, anti-proliferative) that stimulated activity of CREB1 (cAMP response element binding protein 1). The importance of BTG1 in this regulation was further demonstrated by the observed BAT whitening in adipocyte-specific BTG1-overexpressing mice and the attenuated Dex-induced BAT whitening and fat mass gain in mice with BTG1 knockdown in BAT. Taken together, we showed that Dex induces a significant whitening of BAT via BTG1- and ATG7-dependent autophagy, which might contribute to Dex-increased adiposity. These results provide new insights into the mechanisms underlying GC-increased adiposity and possible strategy for preventing GC-induced side effects via the combined use of an autophagy inhibitor. ACADL: acyl-Coenzyme A dehydrogenase, long-chain; ACADM: acyl-Coenzyme A dehydrogenase, medium-chain; ACADS: acyl-Coenzyme A dehydrogenase, short-chain; ADIPOQ: adiponectin; AGT: angiotensinogen; Atg: autophagy-related; BAT: brown adipose tissue; BTG1: B cell translocation gene 1, anti-proliferative; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; CIDEA: cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; CPT1B: carnitine palmitoyltransferase 1b, muscle; CPT2: carnitine palmitoyltransferase 2; CQ: chloroquine; Dex: dexamethasone; eWAT: epididymal white adipose tissue; FABP4: fatty acid binding protein 4, adipocyte; FFAs: free fatty acids; GCs: glucocorticoids; NRIP1: nuclear receptor interacting protein 1; OCR: oxygen consumption rate; PBS: phosphate-buffered saline; PPARA: peroxisome proliferator activated receptor alpha; PPARG: peroxisome proliferator activated receptor gamma; PPARGC1A: peroxisome proliferator activated receptor, gamma, coactivator 1 alpha; PRDM16: PR domain containing 16; PSAT1: phosphoserine aminotransferase 1; RB1: RB transcriptional corepressor 1; RBL1/p107: RB transcriptional corepressor like 1; SQSTM1: sequestosome 1; sWAT: subcutaneous white adipose tissue; TG: triglycerides; UCP1: uncoupling protein 1 (mitochondrial, proton carrier); WT: wild-type.
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http://dx.doi.org/10.1080/15548627.2019.1628537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999619PMC
March 2020

High-performance polyurethane nanocomposites based on UPy-modified cellulose nanocrystals.

Carbohydr Polym 2019 Sep 9;219:191-200. Epub 2019 May 9.

Key Laboratory of Functional Polymer Materials of the Ministry of Education and College of Chemistry, Nankai University, Tianjin 300071, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China. Electronic address:

Densely H-bonding assemblies are the key strategy found by nature to enhance the rupture strength of natural polymers without sacrificing their toughness, such as spider silk, while it still remains a great challenge using such intriguing strategy to prepare high-performance synthesized polymer or biopolymer enhanced polymer nanocomposites. To address this challenge, we report here a bio-inspired strategy using densely H-bonding assembly for facile fabrication of high performance polyurethane (PU) nanocomposites reinforced by hydroxyl-rich cellulose nanocrystals (CNCs) functionalized with 2-ureido-4-[1 H]-pyrimidinone motifs (CNC-UPy) containing self-complementary hydrogen bonds. These PU/CNC-UPy nanocomposites showed remarkably improved mechanical strength without sacrificing the elongation at break and toughness compared to pure PU matrix. Differential scanning calorimetry(DSC) results indicated that CNC-UPy could induce the formation of long range ordering of hard segment domains, due to the strong hydrogen bonding interactions between UPy motifs attached on CNC-UPy and PU matrix. Furthermore, wide angle X-ray diffraction (WAXD) measurements demonstrated that the strain-induced crystallization (SIC) was enhanced significantly by introducing CNC-UPy into PU, leading to a large stress at break. The enhanced interfacial H-bonding interactions between CNC and PU though UPy anchoring could overcome the inherent trade-off between the stiffness and toughness of polymer composites. The proposed bio-inspired strategy using densely H-bonding assembly will be with more extensive application prospects.
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http://dx.doi.org/10.1016/j.carbpol.2019.05.029DOI Listing
September 2019

Exosomal let-7d-3p and miR-30d-5p as diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors.

Mol Cancer 2019 04 2;18(1):76. Epub 2019 Apr 2.

Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Cervical cancer screening through detection and treatment of high-grade cervical intraepithelial neoplasia (CIN) is most successful in cancer prevention. However, the accuracy of the current cervical cancer screening tests is still low. The aim of this study was to develop a more accurate method based on circulating exosomal miRNAs. The miRNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 121 plasma samples from healthy volunteers, cervical carcinoma patients, and CIN patients. A panel with eight differentially expressed exosomal miRNAs was identified to distinguish patients in the CIN II+ group (including advanced CIN II patients) from those in the CIN I- group (including CIN I patients and healthy volunteers). Let-7d-3p and miR-30d-5p showed significant difference between cervical tumors and adjacent normal tissues (P < 0.005), exhibited a consistent trend in plasma samples, and were further validated in 203 independent plasma samples. Integrating these two miRNAs yielded an AUC value of 0.828 to distinguish patients in CIN II+ group from those in CIN I- group. Further integrating them into a cytological test-based model resulted in a higher AUC of 0.887, while the AUC value based on the cytological test alone was 0.766. In summary, plasma exosomal miR-30d-5p and let-7d-3p are valuable diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors. Further validation using large sample sizes is required for clinical diagnosis.
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http://dx.doi.org/10.1186/s12943-019-0999-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446401PMC
April 2019

A Chromosome-Scale Genome Assembly of Paper Mulberry (Broussonetia papyrifera) Provides New Insights into Its Forage and Papermaking Usage.

Mol Plant 2019 05 26;12(5):661-677. Epub 2019 Feb 26.

Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing 100093, China; ChuangGou Science & Technology Co. Ltd., Beijing 100049, China. Electronic address:

Paper mulberry (Broussonetia papyrifera) is a well-known woody tree historically used for Cai Lun papermaking, one of the four great inventions of ancient China. More recently, Paper mulberry has also been used as forage to address the shortage of feedstuff because of its digestible crude fiber and high protein contents. In this study, we obtained a chromosome-scale genome assembly for Paper mulberry using integrated approaches, including Illumina and PacBio sequencing platform as well as Hi-C, optical, and genetic maps. The assembled Paper mulberry genome consists of 386.83 Mb, which is close to the estimated size, and 99.25% (383.93 Mb) of the assembly was assigned to 13 pseudochromosomes. Comparative genomic analysis revealed the expansion and contraction in the flavonoid and lignin biosynthetic gene families, respectively, accounting for the enhanced flavonoid and decreased lignin biosynthesis in Paper mulberry. Moreover, the increased ratio of syringyl-lignin to guaiacyl-lignin in Paper mulberry underscores its suitability for use in medicine, forage, papermaking, and barkcloth making. We also identified the root-associated microbiota of Paper mulberry and found that Pseudomonas and Rhizobia were enriched in its roots and may provide the source of nitrogen for its stems and leaves via symbiotic nitrogen fixation. Collectively, these results suggest that Paper mulberry might have undergone adaptive evolution and recruited nitrogen-fixing microbes to promote growth by enhancing flavonoid production and altering lignin monomer composition. Our study provides significant insights into genetic basis of the usefulness of Paper mulberry in papermaking and barkcloth making, and as forage. These insights will facilitate further domestication and selection as well as industrial utilization of Paper mulberry worldwide.
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http://dx.doi.org/10.1016/j.molp.2019.01.021DOI Listing
May 2019

Highly efficient photothermal nanoagent achieved by harvesting energy via excited-state intramolecular motion within nanoparticles.

Nat Commun 2019 02 15;10(1):768. Epub 2019 Feb 15.

Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Institute of Molecular Functional Materials, Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China.

The exciting applications of molecular motion are still limited and are in urgent pursuit, although some fascinating concepts such as molecular motors and molecular machines have been proposed for years. Utilizing molecular motion in a nanoplatform for practical application has been scarcely explored due to some unconquered challenges such as how to achieve effective molecular motion in the aggregate state within nanoparticles. Here, we introduce a class of near infrared-absorbing organic molecules with intramolecular motion-induced photothermy inside nanoparticles, which enables most absorbed light energy to dissipate as heat. Such a property makes the nanoparticles a superior photoacoustic imaging agent compared to widely used methylene blue and semiconducting polymer nanoparticles and allow them for high-contrast photoacoustic imaging of tumours in live mice. This study not only provides a strategy for developing advanced photothermal/photoacoustic imaging nanoagents, but also enables molecular motion in a nanoplatform to find a way for practical application.
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http://dx.doi.org/10.1038/s41467-019-08722-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377612PMC
February 2019

BKCa participates in E2 inducing endometrial adenocarcinoma by activating MEK/ERK pathway.

BMC Cancer 2018 Nov 16;18(1):1128. Epub 2018 Nov 16.

Department of Gynecologic Oncology, Women's Hospital, Zhejiang University, School of Medicine, Xueshi Road 1, Hangzhou, Zhejiang, 310006, People's Republic of China.

Background: The large-conductance, voltage-gated, calcium (Ca (2+))-activated potassium channel (BKCa) plays an important role in regulating Ca (2+) signaling and cell physiological function, and is aberrantly expressed in some types of cancers. The present study focuses on identifying the oncogenic potential and clinical significance of BKCa in endometrial adenocarcinoma, as well as exploring the mechanistic relevance by 17β -estradiol (E2) inducing aberrant activation of MEK1/2 and ERK1/2 via BKCa.

Methods: The expression of BKCa, ERK1/2 and p-ERK1/2 were examined by immunohistochemical staining in 263 cases, including 185 primary types I endometrial cancer tissues, 38 atypical endometrial hyperplasia tissues and 40 normal endometrium tissues. Cell growth, cycle, apoptosis rate, migration and invasion was separately tested in Ishikawa cells using siRNA-BKCa and/or E2 treatment, as well as the expression of these interested proteins by western blot analysis.

Results: We showed that expression of BKCa is significantly elevated in 185 types I endometrial adenocarcinoma tissues compared to those of the normal endometrium and atypical endometrial hyperplasia tissues. Furthermore, in vitro observations revealed that down-regulation of BKCa expression inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, suppressed cell migration and invasion in Ishakiwa cells, and decreased the expression of p-MEK1/2 and p-ERK1/2. Additionally, RNAi-mediated knockdown of BKCa attenuated the increased cellular growth and invasion, as well as the elevated expression of p-MEK1/2 and p-ERK1/2 proteins, induced by E2 stimulation. More importantly, the aberrant expression of BKCa and p-ERK1/2 were closely related with poor prognostic factors in type I endometrial cancer, and up-regulated expression of p-ERK1/2 was significantly associated with shorter disease-free survival (DFS) and overall survival (OS) and was an independent prognostic factor in type I endometrial cancer patients.

Conclusion: Our results demonstrated that BKCa and the key downstream effectors p-ERK1/2 could be involved in important signaling pathways in initiation and development of endometrial adenocarcinoma and may provide a new therapeutic approach for women with endometrial cancer.
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http://dx.doi.org/10.1186/s12885-018-5027-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240221PMC
November 2018

Manganese in blood cells as an exposure biomarker in manganese-exposed workers healthy cohort.

J Trace Elem Med Biol 2018 Jan 19;45:41-47. Epub 2017 Sep 19.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China. Electronic address:

Elevated exposure to manganese (Mn) has long been a public health concern. However, there is currently no consensus on the best exposure biomarker. Here we aimed to investigate the exposomic characteristics of plasma metals among Mn-exposed workers and explore the potential biomarkers of Mn exposure in the blood pool. First, total sixteen plasma metals (Calcium, Magnesium, Iron, Zinc, Copper, Selenium, Lead, Chromium, Arsenic, Manganese, Nickel, Molybdenum, Cadmium, Mercury, Thallium, and Cobalt) were determined among 40 occupationally Mn-exposed subjects. Second, Mn levels in both plasma and blood cells were detected among 234 workers from the manganese-exposed workers healthy cohort (MEWHC), respectively. Analysis of plasma metal exposome showed that the plasma Mn concentrations were positively correlated to plasma Fe (r=0.361), Ni (r=0.363), Cr (r=0.486), and Hg (r=0.313) (all p<0.05). Mn concentrations in plasma were not significantly correlated to external exposure levels (p=0.200), and it was further confirmed among the 234 subjects (p=0.452). However, Mn concentrations in blood cells progressively increased as the external exposure dose increased (low-exposure group vs high-exposure group, median 11.53μg/L vs 20.41μg/L, p=0.001). Our results suggest that Mn in blood cells, but not plasma, could serve as a potential internal exposure biomarker. Larger validation studies are needed to establish the utility of this biomarker.
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http://dx.doi.org/10.1016/j.jtemb.2017.09.016DOI Listing
January 2018

The relationship between PTSD, depression and negative life events: Ya'an earthquake three years later.

Psychiatry Res 2018 01 12;259:358-363. Epub 2017 Sep 12.

Institute of Emergency Management and Reconstruction in Post-disaster, Sichuan University, Chengdu 610065, China. Electronic address:

PTSD (Posttraumatic Stress Disorder) is a common post-disaster psychological condition which research has shown to have comorbidity with depression. To explore the relationship between PTSD and depression further, a cross-sectional study design was adopted. Three years after the Ya'an earthquake, 4137 adolescents (mean age 15.12) who had personally experienced the earthquake were assessed. The study results showed that PTSD significantly predicted future depression, with the effect being partially mediated by the negative life events after the earthquake. Gender was not found to be a significant moderator between PTSD and depression.
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http://dx.doi.org/10.1016/j.psychres.2017.09.017DOI Listing
January 2018

A retrospective analysis on 1901 women with high grade cervical intraepithelial neoplasia by colposcopic biopsy.

Eur J Obstet Gynecol Reprod Biol 2017 Oct 5;217:53-58. Epub 2017 Jul 5.

Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd#2, Hangzhou, Zhejiang 310006, China; Key Laboratory of Women's Reproductive Health of Zhejiang Province, Xueshi Rd#2, Hangzhou, Zhejiang 310006, China. Electronic address:

Objective: Clinically, an unbefitting management for high grade squamous intraepithelial lesion (HSIL) may result from an inaccurate diagnosis by colposcopy bioposy.The study aimed to assess the diagnostic accuracy by colposcopic biopsy and evaluate the associated factors in diagnosing HSIL.

Study Design: Clinical data of 1901 women who were primarily diagnosed as HSIL by colposcopic biopsy and then underwent definitive surgery within six-month interval in Women's Hospital, School of Medicine, Zhejiang University during 2009-2015, were retrospectively collected. The diagnostic accuracy of HSIL by colposcopic biopsy was assessed and the correlations between diagnostic accuracy and clinic-pathological variables were calculated by univariate and multivariate analysis using the pathological diagnosis by definitive surgery as a reference standard.

Results: The accordance rate of HSIL diagnosis between colposcopic biopsy and definitive surgery was 80.6%, with an under-diagnosis rate of 5.8% and an over-diagnosis rate of 13.6%. Cytology≤low grade squamous intraepithelial lesion(LSIL) (OR:1.599;95%CI:1.185-2.160), colposcopy≤LSIL (OR:2.083;95%CI:1.537-2.824), endocervical curettage (ECC)≤LSIL(OR:2.813;95%CI:2.051-3.857), and lesion without gland involved (OR:1.751;95%CI:1.299-2.361) were independent risk factors for over-diagnosis of HSIL. Women with≥3 risk factors had a 5.078-flod higher risk for over-diagnosis of HSIL compared to those with≤1 risk factor. Irregular vaginal bleeding (OR:2.570,95%CI:1.668-3.960), colposcopy=HSIL (OR:1.699,95%CI:1.022-2.824), ECC=HSIL (OR:2.666, 95%CI:1.728-4.113), and multiple biopsies (OR:1.818, 95%CI:1.153-2.868) were independent risk factors for under-diagnosis of HSIL. Women with ≥3 risk factors had a 5.710-flod higher risk for under-diagnosis of HSIL compared to those with ≤1 risk factor.

Conclusions: The diagnostic accuracy of HSIL by colposcopic biopsy is about 80% and associated with some factors including symptom, cytology result, colposcopy diagnosis, and biopsy number. These variables may be predictors for over-diagnosis or under-diagnosis of HSIL by colposcopic biopsy.
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http://dx.doi.org/10.1016/j.ejogrb.2017.07.005DOI Listing
October 2017

Radioactive impacts on nekton species in the Northwest Pacific and humans more than one year after the Fukushima nuclear accident.

Ecotoxicol Environ Saf 2017 Oct 8;144:601-610. Epub 2017 Jul 8.

Laboratory of Marine Isotopic Technology and Environmental Risk Assessment, Third Institute of Oceanography, State Oceanic Administration, 184 Daxue Road, Xiamen 361005, China.

This study investigated the radioactive impacts on 10 nekton species in the Northwest Pacific more than one year after the Fukushima Nuclear Accident (FNA) from the two perspectives of contamination and harm. Squids were especially used for the spatial and temporal comparisons to demonstrate the impacts from the FNA. The radiation doses to nekton species and humans were assessed to link this radioactivity contamination to possible harm. The total dose rates to nektons were lower than the ERICA ecosystem screening benchmark of 10μGy/h. Further dose-contribution analysis showed that the internal doses from the naturally occurring nuclide Po were the main dose contributor. The dose rates from Cs, Cs, Sr and Ag were approximately three or four orders of magnitude lower than those from naturally occurring radionuclides. The Po-derived dose was also the main contributor of the total human dose from immersion in the seawater and the ingestion of nekton species. The human doses from anthropogenic radionuclides were ~ 100 to ~ 10,000 times lower than the doses from naturally occurring radionuclides. A morbidity assessment was performed based on the Linear No Threshold assumptions of exposure and showed 7 additional cancer cases per 100,000,000 similarly exposed people. Taken together, there is no need for concern regarding the radioactive harm in the open ocean area of the Northwest Pacific.
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http://dx.doi.org/10.1016/j.ecoenv.2017.06.042DOI Listing
October 2017

Triage for management of cervical high-grade squamous intraepithelial lesion patients with positive margin by conization: a retrospective analysis.

Front Med 2017 Jun 10;11(2):223-228. Epub 2017 May 10.

Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.

The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion (HSIL) patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 (47.06%) patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma (3 stage IA1 and 1 stage IA2 patients). Univariate analysis showed that patient age > 35 years (P = 0.005), menopausal period > 5 years (P = 0.0035), and multiple-quadrant involvement (P = 0.001) were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement (P = 0.001; OR, 3.701; 95%CI, 1.496-9.154) was an independent risk factor for residual disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider reconization or re-assessment.
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http://dx.doi.org/10.1007/s11684-017-0517-8DOI Listing
June 2017

Hepatitis C Virus Nonstructural 5A Protein (HCV-NS5A) Inhibits Hepatocyte Apoptosis through the NF-κb/miR-503/bcl-2 Pathway.

Mol Cells 2017 Mar 27;40(3):202-210. Epub 2017 Mar 27.

Department of Gastroenterology, The Second Affiliated Hospital, Nanchang University, Nanchang 330006, China.

The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor (TNF)-α. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship. Chromatin immunoprecipitation was used to identify the combination of NF-κB and miR-503. We found that overexpression of NS5A inhibited TNF-αinduced hepatocellular apoptosis via regulating miR-503 expression. The cell viability of the TNF-α induced Hep-mock cells was significantly less than the viability of the TNF-α induced Hep-NS5A cells, which demonstrates that NS5A inhibited TNF-α-induced HepG2 cell apoptosis. Under TNF-α treatment, miR-503 expression was decreased and cell viability and B-cell lymphoma 2 (bcl-2) expression were increased in the Hep-NS5A cells. Moreover, the luciferase reporter gene experiment verified that bcl-2 was a direct target of miR-503, NS5A inhibited TNF-α-induced NF-κB activation and NF-κB regulated miR-503 transcription by combining with the miR-503 promoter. After the Hep-NS5A cells were transfected with miR-503 mimics, the data indicated that the mimics could reverse TNF-α-induced cell apoptosis and blc-2 expression. Collectively, our findings suggest a possible molecular mechanism that may contribute to HCV treatment in which NS5A inhibits NF-κB activation to decrease miR-503 expression and increase bcl-2 expression, which leads to a decrease in hepatocellular apoptosis.
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http://dx.doi.org/10.14348/molcells.2017.2299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386958PMC
March 2017

Identification of genes and signaling pathways associated with diabetic neuropathy using a weighted correlation network analysis: A consort study.

Medicine (Baltimore) 2016 Nov;95(47):e5443

Department of Endocrinology, The First Hospital Affiliated to Xi'an Jiaotong University Department of Endocrinology, The First Affiliated Hospital of Xi'an Medical University, Xi'an Department of Endocrinology, Yan'an University Affiliated Hospital, Yan'an, China.

Background: The molecular mechanisms behind diabetic neuropathy remains to be investigated.

Methods: This is a secondary study on microarray dataset (GSE24290) downloaded from Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI), which included 18 nerve tissue samples of progressing diabetic neuropathy (fibers loss ≥500 fibers/mm) and 17 nerve tissue samples of nonprogressing diabetic neuropathy (fibers loss ≤100 fibers/mm). Differentially expressed genes (DEGs) were screened between progressing and nonprogressing diabetic neuropathy. With the DEGs obtained, a weighted gene coexpression network analysis was conducted to identify gene clusters associated with diabetic neuropathy. Diabetes-related microRNAs (miRNAs) and their target genes were predicted and mapped to the genes in the gene clusters identified. Consequently, a miRNA-gene network was constructed, for which gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Potential drugs for treatment of diabetic neuropathy were also predicted.

Results: Total 370 upregulated and 379 downregulated DEGs were screened between nonprogressing and progressing diabetic neuropathy. Has-miR-377, has-miR-216a, and has-miR-217 were associated with diabetes. Inflammation was the most significant GO term. The peroxisome proliferator-activated receptor (PPAR) pathway and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway were significantly KEGG pathways significantly enriched with PPAR gamma (PPARG), stearoyl-CoA desaturase (SCD), cluster of differentiation 36 (CD36), and phosphoenolpyruvate carboxykinase 1 (PCK1).

Conclusion: The study suggests that PPARG, SCD, CD36, PCK1, AMPK pathway, and PPAR pathway may be involved in progression of diabetic neuropathy.
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http://dx.doi.org/10.1097/MD.0000000000005443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134881PMC
November 2016
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