Publications by authors named "Yuyan Li"

86 Publications

MiR-18a-5p Promotes Proliferation, Migration, and Invasion of Endometrial Cancer Cells by Targeting THBD.

Crit Rev Eukaryot Gene Expr 2021 ;31(2):63-73

Department of Obstetrics and Gynecology, Dafeng Hospital of Traditional Chinese Medicine, Yancheng, Jiangsu, China.

The purpose of this study was to elucidate the role that the miR-18a-5p/THBD regulatory pathway plays in endometrial cancer (EC), which could provide a theoretical basis for potential therapeutic targets. Differentially expressed genes in EC tissue and normal tissue were determined by bioinformatics analysis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to compare the expression of miR-18a-5p and THBD mRNA in normal human endometrial cells and human EC cells. CCK-8 assay was used to compare the proliferative ability of EC cells in different treatment groups. Transwell assay was used to detect the migratory and invasive abilities of EC cells in different treatment groups. Dual-luciferase assay was used to verify the targeting relationship between miR-18a-5p and THBD. Western blot assay was used to detect THBD protein expression level. qRT-PCR results showed that miR-18a-5p was significantly upregulated in EC cells, and expression of its target gene, THBD, was significantly downregulated. CCK-8 and transwell assays showed that miR-18a-5p could enhance the proliferative, migratory, and invasive abilities of EC cells, whereas THBD could weaken those abilities. Dual-luciferase assay confirmed that miR-18a-5p could negatively regulate THBD expression. In addition, rescue experiments revealed that the oncogenic effect of miR-18a-5p on EC cells was inhibited by THBD overexpression. We conclude that miR-18a-5p could promote the proliferation, migration, and invasion of EC cells by targeting and downregulating THBD expression, and the miR-18a-5p/THBD regulatory pathway might be a therapeutic target. The results of this study may serve as a theoretical basis for related drug development.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2021037776DOI Listing
January 2021

Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma.

Front Cell Dev Biol 2021 8;9:689727. Epub 2021 Jul 8.

State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Immune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. However, the overall response rate to immune checkpoint inhibitor therapy for many cancers is only between 20 and 40%, and even less for colorectal cancer (CRC) patients. Thus, there is an urgent need to develop an efficient immunotherapeutic strategy for CRC. Here, we developed a novel CRC combination therapy consisting of a multiple receptor tyrosine kinase inhibitor (Foretinib) and anti-PD-1 antibody. The combination therapy significantly inhibited tumor growth in mice, led to improved tumor regression without relapse (83% for CT26 tumors and 50% for MC38 tumors) and prolonged overall survival. Mechanistically, Foretinib caused increased levels of PD-L1 via activating the JAK2-STAT1 pathway, which could improve the effectiveness of the immune checkpoint inhibitor. Moreover, the combination therapy remodeled the tumor microenvironment and enhanced anti-tumor immunity by further increasing the infiltration and improving the function of T cells, decreasing the percentage of tumor-associated macrophages (TAMs) and inhibiting their polarization toward the M2 phenotype. Furthermore, the combination therapy inhibited the metastasis of CT26-Luc tumors to the lung in BALB/c mouse by reducing proportions of regulatory T-cells, TAMs and M2 phenotype TAMs in their lungs. This study suggests that a novel combination therapy utilizing both Foretinib and anti-PD-1 antibody could be an effective combination strategy for CRC immunotherapy.
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http://dx.doi.org/10.3389/fcell.2021.689727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298272PMC
July 2021

C3 ester side chain plays a pivotal role in the antitumor activity of Maytansinoids.

Biochem Biophys Res Commun 2021 Aug 15;566:197-203. Epub 2021 Jun 15.

State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, PR China. Electronic address:

Maytansinoids, the chemical derivatives of Maytansine, are commonly used as potent cytotoxic payloads in antibody-drug conjugates (ADC). Structure-activity-relationship studies had identified the C3 ester side chain as a critical element for antitumor activity of maytansinoids. The maytansinoids bearing the methyl group at C3 position with D configuration were about 100 to 400-fold less cytotoxic than their corresponding L-epimers toward various cell lines. The detailed mechanism of how chirality affects the anticancer activity remains elusive. In this study, we determined the high-resolution crystal structure of tubulin in complex with maytansinol, L-DM1-SMe and D-DM1-SMe. And we found the carbonyl oxygen atom of the ester moiety and the tail thiomethyl group at C3 side chain of L-DM1-SMe form strong intramolecular interaction with the hydroxyl at position 9 and the benzene ring, respectively, fixing the bioactive conformation and enhancing the binding affinity. Additionally, ligand-based and structure-based virtually screening methods were used to screen the commercially macrocyclic compounds library, and 15 macrocyclic structures were picketed out as putatively new maytansine-site inhibitors. Our study provides a possible strategy for the rational discovery of next-generation maytansine site inhibitors.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.071DOI Listing
August 2021

The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues.

Biochem Biophys Res Commun 2021 Aug 2;565:29-35. Epub 2021 Jun 2.

State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China; Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. Electronic address:

Microtubule-targeting agents (MTAs) are the most commonly used anti-cancer drugs. At least fourteen microtubule inhibitors and ten antibody drug conjugates (ADCs) linking MTAs are approved by FDA for clinical use in cancer therapy. In current research, we determined the crystal structure of tubulysin analogue TGL in complex with tubulin at a high resolution (2.65 Å). In addition, we summarized all of the previously published high-resolution crystal structures of ligands in the vinca site to provide structural insights for the rational design of the new vinca-site ligands. Moreover, based on the aligned results of the vinca site ligands, we provided three possible routes for designing new tubulysin analogues, namely macrocyclization between the N-14 side chain and the N-9 side chain, the hybird of tubulysin M and phomopsin A, and growing new aryl group at C-21. These designed structures will inspire the development of new MTAs or payloads in cancer therapy.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.086DOI Listing
August 2021

Ultrasensitive Molecular Detection by Imaging of Centimeter-Scale Metasurfaces with a Deterministic Gradient Geometry.

Adv Mater 2021 Jul 4;33(29):e2100270. Epub 2021 Jun 4.

Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China.

Highly sensitive detection of trace amounts of substances is crucial for broad applications in healthcare, environmental monitoring, antiterrorism, etc., where cost effectiveness and portability are often demanded. Here, an ultrasensitive sensor is reported that can detect an angstrom-thick layer of adsorbed molecules through image acquisition and processing. The sensor features a centimeter-scale plasmonic metasurface with spatially varying geometry, where the light scattering is dependent on both the adsorbed substances and spatial locations. When illuminated with narrowband light (such as from a light emitting diode), the intensity pattern recorded on the metasurface changes with the surface-adsorbed molecules, enabling label-free, sensitive, and spectrometer-free molecular detection. The centimeter-scale size of the sensing area interfaces well with consumer-level imaging sensors on mobile devices without the need for microscopic optics and offers a high signal-to-noise ratio by leveraging the multimillion pixels for noise reduction. It is experimentally demonstrated that a single layer of Al O molecules deposited on the sensor, with a thickness of approximately one angstrom, can be detected by analyzing the images taken of the sensing chip. Furthermore, by integrating the sensor into a microfluidic setup, quantitative detection of BSA/anti-BSA immune complex formation events is demonstrated, which agrees well with the Langmuir isotherm model.
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http://dx.doi.org/10.1002/adma.202100270DOI Listing
July 2021

A robust and scalable active-matrix driven digital microfluidic platform based on printed-circuit board technology.

Lab Chip 2021 05;21(10):1886-1896

Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.

Two-dimensional digital microfluidic platforms, on which droplets are actuated by electrowetting on dielectrics, have merits such as dynamic reconfigurability and ease for automation. However, concerns for digital microfluidic platforms based on low-cost printed circuit boards, such as the scalability of the electrode array and the reliability of the device operation, should be addressed before high throughput and fully automatic applications can be realized. In this work we report the progress in addressing those issues by using active-matrix circuitry to automatically drive a large electrode array with enhanced device reliability. We describe the design and the fabrication of a robust and scalable active-matrix driven digital microfluidic platform based on printed-circuit board technology. Reliable actuation of aqueous and organic droplets is achieved using a free-standing double-layer hydrophobic membrane. To demonstrate the versatility of the digital microfluidic platform, a pentapeptide is synthesized on the device within 30 minutes. With these improvements, a fully automatic, scalable, robust, reusable, and low-cost digital microfluidic platform capable of parallel manipulation of a large number of droplets can find numerous applications in chemical engineering, bioengineering and biomedical engineering.
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http://dx.doi.org/10.1039/d1lc00101aDOI Listing
May 2021

The mitochondrial genome of (Diptera: Dolichopodidae).

Mitochondrial DNA B Resour 2021 Apr 15;6(4):1419-1420. Epub 2021 Apr 15.

Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.

The long-legged fly belongs to the subfamily Diaphorinae of Dolichopodidae. The mitogenome of was sequenced, the first representative complete mitogenome from this subfamily. This mitogenome is 15,385 bp in size, includes 13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs. All genes have the same location and coding strand as in other published species of Dolichopodidae. Nucleotide composition is biased toward A and T, which together made up 78.6% of the entire genome. Bayesian inference strongly supported the monophyly of Empidoidea, Empididae and Dolichopodidae, with the phylogenetic relationships within Empidoidea: ((Dolichopodinae + Neurigoninae) + Diaphorinae) + ((Trichopezinae + (Empidinae + Oreogetoninae)) + Ocydromiinae).
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http://dx.doi.org/10.1080/23802359.2021.1911714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057078PMC
April 2021

Correlations of social isolation and anxiety and depression symptoms among patients with breast cancer of Heilongjiang province in China: The mediating role of social support.

Nurs Open 2021 07 3;8(4):1981-1989. Epub 2021 May 3.

Department of Neurosurgery, the Tumor Hospital Affiliated of Harbin Medical University, Harbin, China.

Objectives: To explore the correlations among social isolation and symptoms of anxiety and depression among patients with breast cancer in China and to further verify the mediating role of social support in social isolation and symptoms of depression or anxiety.

Design: A cross-sectional survey.

Settings: The cluster sampling method was conducted for 456 female inpatients diagnosed with breast cancer at the Tumor Hospital Affiliated of Harbin Medical University from April 2019-September 2019.

Methods: Pearson correlation analysis was used for identifying correlations among all the variables. Mediation effect analysis was used to examine the role of social support in social isolation and symptoms of depression or anxiety.

Results: The results showed a prevalence of 73.26% and 70.44% for anxiety and depression symptoms in patients with breast cancer, respectively. Anxiety was significantly negatively correlated with social support (r = -.334, p < .01) and significantly positively correlated with social isolation (r = .369, p < .01). Similarly, depression was significantly negatively correlated with social support (r = -.289, p < .01) and significantly positively correlated with social isolation (r = .466, p < .01). Social support played a mediating role in social isolation and f symptoms of anxiety or depression among these patients.

Conclusions: Social isolation was positively correlated with symptoms of anxiety and depression in patients with breast cancer, respectively. Social support for patients with breast cancer has a mediating effect on the patients' social isolation and symptoms of anxiety and depression. Therefore, the support of family, friends, hospitals, and organizations plays a positive role in reducing social isolation as well as symptoms of depression and anxiety in these patients.
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http://dx.doi.org/10.1002/nop2.876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186692PMC
July 2021

Evaluating the Potential of Using Eggs for Mass-Rearing , a Promising Egg Parasitoid of .

Insects 2021 Apr 26;12(5). Epub 2021 Apr 26.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

Although , a promising parasitoid of , had been successfully reared on the eggs of in some countries, reports from China have argued that it is infeasible. Notably, studies from China have indicated that eggs could be a candidate host. Therefore, to further evaluate the potential of using eggs as hosts, we compared the development and parasitism of on the eggs of and at temperatures between 20-32 °C. Our results showed that developed successfully on both host eggs at all of the tested temperatures, and the developmental duration and thermal requirements at each stage were similar between the two host species. The number of parasitized eggs was greater for than for . . Meanwhile, the emergence rate exceeded 86.6%, and it was significantly higher for than that for . except at 29 °C. This study is the first time estimating the thermal requirements of at each stage. Moreover, we also recorded the morphological characteristics of at each stage. Our results demonstrate that eggs are more suitable than eggs as an alternative host for the mass-rearing of in China. Understanding the thermal requirements and biological parameters contributes greatly to predicting the generation time and providing a reference for the mass-rearing and storage of the parasitoid.
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http://dx.doi.org/10.3390/insects12050384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146682PMC
April 2021

Effects of environmental, social and surgical factors on ovarian reserve: Implications for age-relative female fertility.

Int J Gynaecol Obstet 2021 Sep 11;154(3):451-458. Epub 2021 Feb 11.

Reproductive Medical Center, Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University (Army Medical University, Chongqing, China.

Objective: To investigate new risk factors for female fertility by analyzing the effects of environmental, social, and surgical factors on antral follicle counts (AFC) and anti-Müllerian hormone (AMH) levels.

Methods: A total of 1513 women aged 20-47 years who underwent in vitro fertilization/intracytoplasmic injection treatment in Southwest Hospital from December 2017 to December 2019 were included. Women were assessed for AFC and AMH levels, and completed a questionnaire. Ordinal logistic regression analyses with generalized linear mixed models were used to calculate the adjusted odds ratio (OR) for diminished ovarian reserve.

Results: Adnexal surgery was the only risk factor associated with low AFC in women aged 20-30 years. Younger age at menarche, alcohol drinking, and adnexal surgery are three independent risk factors for AMH decline in women aged 20-30 years. Intense exercise, sleep quality, and adnexal surgery are three independent risk factors for a low AFC in women aged 31-36 years. Alcohol drinking and adnexal surgery are two independent risk factors for AMH decline in women aged 31-36 years.

Conclusion: With age, female fertility becomes sensitive to high-intensity exercise and poor sleep quality. Adnexal surgery and alcohol drinking are two important risk factors for female fertility in women under age 37 years.
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http://dx.doi.org/10.1002/ijgo.13567DOI Listing
September 2021

Dermal toxicity, dermal irritation, and delayed contact sensitization evaluation of oil body linked oleosin-hEGF microgel emulsion transdermal drug delivery for wound healing.

Cutan Ocul Toxicol 2021 Mar 25;40(1):45-53. Epub 2021 Jan 25.

College of Life Science, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun, PR China.

The expression of therapeutic proteins in plant oil body bioreactors has attracted much attention. But its safety is not yet clear. This article determines the risk of safety after using the drug. The oil body-linked oleosin-hEGF microgel emulsion (OBEME) was prepared by mixing the xanthan gum with suitable concentrations in an appropriate proportion. Skin irritation and sensitization reaction were investigated in rats and guinea pigs using OBEME as test article. The OBEME did not produce dermal erythema/eschar or oedema responses. The dermal subacute and subchronic toxicity of OBEME were evaluated in accordance with OECD guidelines. Compared with the control group, the basic physical signs, such as weight, feed, drinking, excretion, and behaviour of experimental animals, were not abnormal. In addition, no abnormality was found in haematological parameters, biochemical indexes, relative organ weight, and histopathological observation of organs, and there was no significant difference compared with normal saline treatment group. Therefore, we conclude that OBEME has no toxic effects and is safe and reliable to be used for topical application.
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http://dx.doi.org/10.1080/15569527.2021.1874008DOI Listing
March 2021

Contraception, unintended pregnancy, and induced abortion within 24 months of delivery in China: a retrospective cohort study.

Contraception 2021 03 27;103(3):144-150. Epub 2020 Dec 27.

NHC Key Lab. of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research), School of Public Health, Fudan University, Shanghai, China.

Objective: To explore the prevalence of contraceptive use, unintended pregnancy, and induced abortions within 24 months postpartum in eastern, central, and western regions of China and in China overall.

Study Design: We conducted a retrospective cohort study and selected women who delivered a live birth between 12 and 24 months before the survey at 60 hospitals in eastern, central, and western regions of China. We used structured questionnaires for data collection and applied life-table analyses to estimate the prevalence of contraception, unintended pregnancy, and abortions. We used clustered log-rank tests to compare trends and rate differences at each time interval between/among regions.

Results: A total of 19,939 postpartum women were contacted, and 18,045 (90.5%) of them agreed to be interviewed. The 6-, 12-, and 24-month rates for modern contraceptive methods were 62.7% (95% confidence interval [CI] 58.9-66.4), 72.4% (95% CI 68.8-75.7), and 73.2% (95% CI 69.6-76.6), respectively. Condoms accounted for 79% of contraceptive initiators. The 6-, 12-, and 24-month rates were 1.4% (95% CI 1.2-1.7), 5.3% (95% CI 4.5--6.1), and 13.1% (95% CI 11.3-14.8) for unintended pregnancy; and 1.1% (95% CI 0.8-1.3), 4.0% (95% CI 3.4-4.6), and 10.4% (95% CI 8.9-11.8) for induced abortion, respectively. By 24 months postpartum, 3-quarters of unintended pregnancies ended in abortion. The 24-month rates of modern contraceptive methods (75.2% vs73.4%, 71.1%), unintended pregnancy (15.3% vs 11.1%, 12.6%), and induced abortion (11.8% vs 9.9%, 9.4%) were higher in the western region relative to the eastern or central regions.

Conclusion: Postpartum contraception use was relatively high in China but dominated by less-effective methods, and these may contribute to higher risks of unintended pregnancy and induced abortion during the postpartum period. Use of long-acting reversible contraceptives and effective and reliable short-acting methods should thus be fostered in postpartum family planning services in China.

Implications: A national postpartum family planning program is needed in China. Service providers should work on counselling postpartum women and their partners with respect to long-acting reversible contraceptive methods, and to effectively and reliably use short-acting methods during the postpartum period.
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http://dx.doi.org/10.1016/j.contraception.2020.12.014DOI Listing
March 2021

The high-resolution X-ray structure of vinca-domain inhibitors of microtubules provides a rational approach for drug design.

FEBS Lett 2021 01 10;595(2):195-205. Epub 2021 Jan 10.

Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Tubulin vinca-domain ligands can inhibit microtubule polymerization, causing cell death in mitosis, and their potential against multiple cancer types has been demonstrated. However, due to drug resistance and toxicities, development of novel vinca-domain ligands is still needed. In this study, we determined the high-resolution crystal structures of vinorelbine, YXD, and Phomopsin A in complex with tubulin at 2.5 Å. Additionally, we recapitulated all previously published high-resolution crystal structures of the vinca binding site to reveal critical residues and the molecular mechanism of vinca-domain ligands interacting with tubulin. Furthermore, we designed putatively novel triazolopyrimidine derivatives by introducing secondary amine groups to establish salt-bridge and H-bond interactions with Asp179 and Asn329 . Our studies provided the structural basis for designing novel tubulin vinca-domain ligands.
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http://dx.doi.org/10.1002/1873-3468.14003DOI Listing
January 2021

Synergetic impacts of precursory climate drivers on interannual-decadal variations in haze pollution in North China: A review.

Sci Total Environ 2021 Feb 19;755(Pt 1):143017. Epub 2020 Oct 19.

Key Laboratory of Meteorological Disaster, Ministry of Education/Joint International Research Laboratory of Climate and Environment Change (ILCEC)/Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters (CIC-FEMD), Nanjing University of Information Science & Technology, Nanjing 210044, China.

North China suffers from severe haze pollution and has received widespread attentions since the winter of 2012. In addition to human activities, climate variability also plays an important role, particularly in the interannual-decadal variations in the number of haze days in North China (HD). Many previous studies separately explored numerous preceding climate drivers, including Arctic sea ice, Eurasia snow and soil moisture, sea surface temperature in Pacific and Atlantic and forcing of Tibetan Plateau, but lacked assessment and analysis of the joint effects. In this study, we reviewed their impacts on HD and associated physical mechanisms. Beyond that, the synergetic effects were newly revealed by the observations and numerical experiments with fixed emissions. The preceding signals explained approximately 66% of the interannual-decadal variations in HD by exciting teleconnection patterns in winter and influencing the local dispersion conditions in North China. Furthermore, some future research directions were identified, such as the subseasonal variations in HD, subseasonal-seasonal prediction of haze by numerical climate models, and changing relationships between HD and climate conditions.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143017DOI Listing
February 2021

DeepLofargram: A deep learning based fluctuating dim frequency line detection and recovery.

J Acoust Soc Am 2020 10;148(4):2182

School of Marine Science and Technology, Northwestern Polytechnical University, Xi'an 710072, China.

This paper investigates the problem of dim frequency line detection and recovery in the so-called lofargram. Theoretically, long enough time integration can always enhance the detection characteristic. But this does not hold for irregularly fluctuating lines. Deep learning has been shown to perform very well for sophisticated visual inference tasks. With the composition of multiple processing layers, very complex high level representations that amplify the important aspects of input while suppressing irrelevant variations can be learned. Hence, DeepLofargram is proposed, composed of a deep convolutional neural network and its visualization counterpart. Plugging into specifically designed multi-task loss, an end-to-end training jointly learns to detect and recover the spatial location of potential lines. Leveraging on this deep architecture, performance limits of low SNR can be achieved as low as -24 dB on average and -26 dB for some. This is far beyond the perception of human vision and significantly improves the state-of-the-art.
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http://dx.doi.org/10.1121/10.0002172DOI Listing
October 2020

Untargeted Metabolomics Reveals the Protective Effect of a Traditional Chinese Herbal Decoction on Cisplatin-Induced Acute Kidney Injury.

Evid Based Complement Alternat Med 2020 10;2020:8524132. Epub 2020 Oct 10.

Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.

Our previous studies have demonstrated that Jian-Pi-Yi-Shen formula (JPYSF), a traditional Chinese herbal decoction, has a renoprotective effect in 5/6 nephrectomy-induced chronic kidney injury. However, the role and potential mechanisms of JPYSF in the treatment of acute kidney injury (AKI) remain unknown. This study was designed to test the beneficial effect of JPYSF in an AKI mouse model and to investigate the underlying mechanism by using metabolomics analysis. The AKI mouse model was induced by a single intraperitoneal injection of cisplatin at a dose of 20 mg/kg. The mice in the treatment group were pretreated orally with JPYSF (18.35 g/kg/d) for 5 days before cisplatin injection. Seventy-two hours after cisplatin injection, serum and kidney samples were collected for biochemical and histological examination. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) was applied to analyze metabolic profiling variations in the kidney. The results showed that pretreatment with JPYSF obviously reduced the levels of serum creatinine and blood urea nitrogen and alleviated renal pathological injury in AKI mice. Orthogonal partial least-squares discriminant analysis (OPLS-DA) score plot revealed a clear separation between the AKI and AKI + JPYSF group. A total of 68 and 87 significantly differentially expressed metabolites were identified in the kidney of AKI mice responding to JPYSF treatment in negative and positive ion mode, respectively. The pivotal pathways affected by JPYSF included vitamin B6 metabolism, alanine, aspartate and glutamate metabolism, lysine biosynthesis, and butanoate metabolism. In conclusion, JPYSF can protect the kidney from cisplatin-induced AKI, which may be associated with regulating renal metabolic disorders.
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http://dx.doi.org/10.1155/2020/8524132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569447PMC
October 2020

[Loss of zona pellucida in oocytes due to compound heterozygous variants of ZP1 gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Jul;37(7):789-791

Reproductive Center of Obstetrics and Gynecology, the First Affiliated Hospital of Army Medical University, Chongqing 400038, China.

Objective: To explore the genetic basis of a patient with primary infertility due to loss of zona pellucida.

Methods: The proband and his parents were subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatics analysis.

Results: The proband was found to harbor compound heterozygous variants of the ZP1 gene in exon 5 c.874C>T(Gln292*) and exon 7 c.1127_1128delCT (p.Ala376GlyTer386), which were respectively inherited from her mother and father.

Conclusion: The compound heterozygous variant of ZP1 gene probably underlie the loss of zona pellucida in oocyte disease in the proband.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.07.021DOI Listing
July 2020

Versatile near-infrared fluorescent probe for in vivo detection of Aβ oligomers.

Bioorg Med Chem 2020 07 12;28(13):115559. Epub 2020 May 12.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21198, China. Electronic address:

Amyloid-β oligomers (AβOs) enrichment in brain is highly related to Alzheimer's pathogenesis, but tracing them in the brain by imaging technique is still a great challenge due to their heterogeneity and metastability. Herein, a new near-infrared (NIR) fluorescent probe, namely, PTO-41, was designed and synthesized to specifically target AβOs. PTO-41 possesses excellent functional properties including optimal fluorescent properties (emission maxima at 680 nm upon interacting with AβOs), high affinity (K = 349 nM), low cell toxicity, desirable lipophilicity (log P = 2.24), and fast wash out from the brain (brain/brain = 5.0). Furthermore, PTO-41 exhibits a high sensitivity toward AβOs in vitro phantom imaging experiments. More importantly, PTO-41 shows great capacity to differentiate between 4-month-old APP/PS1 model mice from age-matched control mice using in vivo imaging. In summary, PTO-41 almost meets all the requirements as a versatile NIR fluorescent probe for the detection of AβOs both in vitro and in vivo.
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http://dx.doi.org/10.1016/j.bmc.2020.115559DOI Listing
July 2020

Combination of astragaloside IV and ACEi ameliorates renal injuries in db/db mice.

Int J Clin Exp Pathol 2020 1;13(5):827-836. Epub 2020 May 1.

Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine Shenzhen, Guangdong, China.

Evidences demonstrated that the effect on anti-proteinuria and renal protection of Chinese herbs combination with ACEi or ARB seemed to be better than ACEi or ARB alone. Astragaloside IV could decrease the urinary albumin excretion rate and could protect against renal injuries linking to its anti-oxidation ability. We aimed to investigate the effect of astragaloside IV combined with ACEi on diabetic nephropathy and to explore whether its underlying mechanism is dependent on anti-oxidation. 8-week-old male experiment mice were randomly assigned to five groups: lean wild type (wt) group, db/db group, db/db + astragaloside IV group, db/db + enalapril group, db/db + combination therapy with astragaloside IV and enalapril group. During the experiment, 24 hours urinary albumin, fasting glucose, body weight, and metabolic parameters were monitored in regular intervals. At the end of the study, tail blood pressure, serum HO, lipid, and liver function were measured and kidney histological injuries were evaluated. Results of the study indicated that combination therapy with astragaloside IV and ACEi further reduced 24 hours urinary albumin excretion rate, blood pressure, and body weight. Combination therapy reduced the foot process width, glomerular base membrane thickness, glomerular tuft cell proliferation, tubular cell atrophy, tubular base membrane thickness, and improved tubular cell proliferation. It modulated the body HO metabolism and up-regulated the expression of the catalase in renal cortex. Astragaloside IV combined with ACEi exerted renal protective effects in db/db mice more significantly than their individual used. The mechanism possibly involved their synergistic effects on anti-oxidation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270657PMC
May 2020

Administration of a mixture of triterpenoids from yeyachun and phenolic acids from danshen ameliorates carbon tetrachloride-induced liver fibrosis in mice by the regulation of intestinal flora.

J Pharmacol Sci 2020 Jul 26;143(3):165-175. Epub 2020 Apr 26.

Pharmacy of College, Hunan University of Chinese Medicine, No. 300 Xueshi Road, Changsha, Hunan, 410208, PR China; Hunan Provincial Engineering Technology Center of Standardization and Function of Chinese Herbal Medicine, No. 300 Xueshi Road, Changsha, Hunan, 410208, PR China. Electronic address:

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.
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http://dx.doi.org/10.1016/j.jphs.2020.04.007DOI Listing
July 2020

Two insulin receptors coordinate oogenesis and oviposition via two pathways in the green lacewing, Chrysopa pallens.

J Insect Physiol 2020 May - Jun;123:104049. Epub 2020 Mar 18.

Key Laboratory for Biology of Plant Diseases and Insect Pests, Ministry of Agriculture, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:

Insulin signalling in insects, as in mammals, regulates various physiological functions, such as reproduction. However, the molecular mechanism by which insulin signals orchestrate ovarian stem cell proliferation, vitellogenesis, and oviposition remains elusive. Here, we investigate the functions of the phosphoinositide 3-kinase (PI3K)-serine/threonine kinase (Akt) pathway, GTPase Ras/mitogen-activated protein kinase (MAPK) pathway, and their downstream messengers in a natural predator, Chrysopa pallens, by the RNAi method. When C. pallens vitellogenin gene 1 (CpVg1) expression was knocked down, the follicle maturation was arrested and total fecundity was reduced. Silencing C. pallens insulin receptor 1 (CpInR1) suppressed Vg transcription and reduced egg mass and hatching rate. Depletion of C. pallens insulin receptor 2 (CpInR2) transcripts lowered Vg transcript level, hampered ovarian development and decreased reproductive output. Knockdown of C. pallens Akt (CpAkt) and C. pallens extracellular-signal-regulated kinase (Cperk) caused phenotypes similar to those caused by knockdown of CpInR2. Disruption of C. pallens transcription factor forkhead box O (CpFoxO) expression caused no significant effects on ovarian development, but sharply impaired total fecundity. Interference with the expression of C. pallens target of rapamycin (CpTor) gene and C. pallens cAMP-response element binding protein (CpCreb) gene led to a down-regulation of Vg transcription, blocking of ovariole growth, and decrease in egg quality. These results suggested the two CpInRs orchestrate oogenesis and oviposition via two signalling pathways to guarantee natural reproduction in the green lacewing, C. pallens.
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http://dx.doi.org/10.1016/j.jinsphys.2020.104049DOI Listing
January 2021

Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis.

BMC Musculoskelet Disord 2020 Feb 14;21(1):99. Epub 2020 Feb 14.

Department of Orthopedics, The Second Affiliated Hospital of Wenzhou Medical University, Yuying Children's Hospital, No.109, Xueyuan West Road, Wenzhou, China.

Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA.

Methods: Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale.

Results: Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores.

Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.
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http://dx.doi.org/10.1186/s12891-020-3120-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023718PMC
February 2020

Theoretical study on the gas-phase reaction mechanism of ammonia with nitrous oxide.

J Mol Model 2020 Feb 4;26(3):48. Epub 2020 Feb 4.

Science and Technology on Aerospace Chemical Power Laboratory, Hubei Institute of Aerospace Chemotechnology, Xiangyang, Hubei, 441003, People's Republic of China.

Applications of nitrous oxide (NO) as an oxidant in green propellants and propulsion systems have attracted a lot of attention. In this study, the reaction pathways for the oxidation of ammonia (NH) with NO were studied using the B3LYP/6-31++G** method of density functional theory (DFT). The results reveal that the reaction between NO and NH proceeds through a chain reaction mechanism. NO reacts with NH to form N and NHO first and then NHO decomposes into NH and O. This process corresponds to the apparent reaction NO+M=N+O+M (M=NH), but the energy barrier of the process (183.49 kJ/mol) is much lower than the direct decomposition reaction of NO=N+O (279.05 kJ/mol). The O radical produced in this process reacts subsequently with NH and NO to produce more radicals such as NH, OH, and NO, which will take part in further reactions like NH+OH=NH+HO and NH+NO=N+HO until the reactants are consumed.
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http://dx.doi.org/10.1007/s00894-020-4291-1DOI Listing
February 2020

Acute myeloid leukemia immune escape by epigenetic CD48 silencing.

Clin Sci (Lond) 2020 Jan;134(2):261-271

Department of Hematology and Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen 518000, China.

Acute myeloid leukemia (AML) is a malignant disorder of hemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions and epigenetic modification. The mechanism of AML immune evasion is not clearly understood. Here we show that CD48 high expression is a favorable prognosis factor that is down-regulated in AML patients, which can help AML evade from NK cell recognition and killing. Furthermore, we demonstrate that CD48 expression is regulated by methylation and that a hypomethylating agent can increase the CD48 expression, which increases the NK cells killing in vitro. Finally, we show that CD48 high expression can reverse the AML immune evasion and activate NK cells function in vivo. The present study suggests that a combination the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.
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http://dx.doi.org/10.1042/CS20191170DOI Listing
January 2020

Highly specific detection of Aβ oligomers in early Alzheimer's disease by a near-infrared fluorescent probe with a "V-shaped" spatial conformation.

Chem Commun (Camb) 2020 Jan 12;56(4):583-586. Epub 2019 Dec 12.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. and Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210098, China.

In this report, we demonstrate a "V-shaped" NIRF probe PTO-29, which can monitor Aβ oligomers with high selectivity. PTO-29 was designed and showed significant response to Aβ oligomers in the fluorescence spectral tests and good properties. In vivo imaging results indicate that 4 month APP/PS1 AD mice have higher signals in the brain than age-matched wild type mice.
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http://dx.doi.org/10.1039/c9cc08894fDOI Listing
January 2020

Correlation between endometrial thickness and perinatal outcome for pregnancies achieved through assisted reproduction technology.

J Perinat Med 2019 Dec;48(1):16-20

Reproductive Medical Center, Department of Obstetrics and Gynecology, Southwest Hospital, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, P.R. China, Tel.: +86-23-13608356955, Fax: +86-23-68754410.

Objective To explore the relationship between endometrial thickness and perinatal outcome in assisted reproductive techniques (ART). Methods A retrospective cohort study was conducted in 1139 infertile women who underwent ART treatment from January 2011 to July 2014. Four groups were divided by endometrial thickness on the human chorionic gonadotropin (HCG) trigger day in fresh embryo transfer cycles or on the progesterone administration day in frozen embryo transfer cycles, as group A (<8 mm), group B (8-10 mm), group C (10-14 mm) and group D (≥14 mm). Two other groups were delineated according to whether uterine lesions were present. The incidence of premature rupture of membranes (PROM), postpartum hemorrhage (PPH) and other common perinatal complications were observed subsequently. Results It was found that the highest incidence of PROM and PPH was in group A (P < 0.05). The incidence of PROM in group B was higher than in groups C and D (P < 0.05). The occurrence of mothers entering the intensive care unit (ICU) was significantly higher in group A than in group B (P < 0.05). However, no significant differences were found in other adverse outcomes. There was no difference in the incidence of adverse perinatal outcome when the endometrial thickness of pre-implantation was not attenuated by uterine lesions. Conclusion The incidence of PROM and PPH increased significantly when the thickness of the endometrium was less than 10 mm before implantation. Correspondingly, the number of mothers treated in the ICU was also higher under these circumstances. To reduce such perinatal placenta-related complications, we should maximize the thickness of the endometrium before transplantation of embryos.
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http://dx.doi.org/10.1515/jpm-2019-0159DOI Listing
December 2019

Bimodal Molecule as NIR-CT Contrast Agent for Hepatoma Specific Imaging.

Anal Chem 2020 01 20;92(1):1138-1146. Epub 2019 Dec 20.

School of Basic Medicine and Clinical Pharmacology , China Pharmaceutical University , Nanjing 211100 , China.

With currently available molecular imaging techniques, hepatocellular carcinoma (HCC), a liver cancer with high mortality rates and poor treatment responses, is mostly diagnosed at its late stage. This is largely due to the lack of highly sensitive contrast agents with high liver specificity. Herein, we report a novel bimodal contrast agent molecule CNCI-1 for the effective detection of HCC at its early stage both in vitro and in vivo. The agent has high liver specificity with effective X-ray computed tomography (CT)/near-infrared (NIR) imaging functions. It has been successfully applied to in vivo NIR imaging with high sensitivity and high selectivity to the HCC region of the HepG2 tumor-xenografted mice model and LM3 orthotopic hepatoma mice model. Moreover, the agent was found to be noninvasive and hepatocarcinoma cells preferential. Furthermore, it also enhanced the tumor imaging by revealing the blood vessels nearby for the CT image acquisition in the VX2 orthotopic hepatoma rabbit model. Our design strategy provides a new avenue to develop the medical relevant bimodal contrast agents for diagnosis of HCC at its early stage.
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http://dx.doi.org/10.1021/acs.analchem.9b04212DOI Listing
January 2020

Development of Near-Infrared Fluorescent Probes for Use in Alzheimer's Disease Diagnosis.

Bioconjug Chem 2020 01 16;31(1):2-15. Epub 2019 Dec 16.

State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing 210009 , China.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder. Currently, there are no available treatments that can effectively stop or reverse the progression of the disease, and existing therapeutics can only alleviate the symptoms. Thus, it remains urgent to develop effective early-stage AD diagnostic methods. In recent years, the search for near-infrared fluorescent (NIRF) probes of AD hallmarks has become a promising research field. In this Review, we will focus on small-molecule NIRF probes used to detect β-amyloid, tau proteins, and reactive oxygen species during the past 4 years. We believe that some new directions we raise herein will benefit the future development of NIRF probes in the field of AD research.
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00695DOI Listing
January 2020

Strategies Targeting Soluble β-Amyloid Oligomers and their Application to Early Diagnosis of Alzheimer's Disease.

Curr Alzheimer Res 2019 ;16(12):1132-1142

Department of Medicinal Chemistry, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 211198, China.

Background: Alzheimer's Disease (AD) is the most common neurodegenerative disorder, and it is still incurable. Early diagnosis and intervention are crucial for delaying the onset and progression of the disease. Mounting evidence indicates that the neurotoxic effects might be attributed to Soluble β-Amyloid Oligomers (SAβO). The SAβO are believed to be neurotoxic peptides more predominant than Aβ plaques in the early stage, and their key role in AD is self-evident. Unfortunately, identification of SAβO proves to be difficult due to their heterogeneous and transient nature. In spite of many obstacles, multiple techniques have recently been developed to target SAβO effectively. This review focuses on the recent progress in the approaches towards SAβO detection in order to shed some light on the future development of SAβO assays.

Methods: Literatures were obtained from the following libraries: Web of Science, PubMed, EPO, SIPO, USPTO. Articles were critically reviewed based on their titles, abstracts, and contents.

Results: A total of 85 papers are referenced in the review. Results are divided into three categories based on the types of detection methods: small molecule fluorescence probes, oligomer-specific antibodies and electrochemical biosensors. Finally, the improvements and challenges of these approaches applied in the early diagnosis of AD were discussed.

Conclusion: This review article covers three kinds of strategies that could be translated into clinic practice and lead to earlier diagnosis and therapeutic interventions of AD.
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http://dx.doi.org/10.2174/1567205016666191031163504DOI Listing
October 2020

Short-term acceptability of the Woman's Condom and influencing factors among internal migrants in China.

BMC Public Health 2019 Oct 29;19(1):1410. Epub 2019 Oct 29.

NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Room 307, 779 old Humin Road, Xuhui District, Shanghai, 200032, People's Republic of China.

Background: The Woman's Condom, a newly designed condom for women, has obtained market approval in China, but it remains relatively unfamiliar to the migrant population. The aim of this study is to evaluate the short-term acceptability of the Woman's Condom and influencing factors among internal migrants.

Methods: A longitudinal study was conducted among 1800 migrants in Beijing, Chongqing, and Shanghai in China between August 2013 and August 2014.Three-level model was implemented with the Statistical Analysis System software (v.9.4 SAS Institute) to analyze within-individual changes, between-individuals effects, and between-group effects.

Results: Three-level model analysis revealed statistically higher short-term acceptability of the Woman's Condom among subjects who lived in Shanghai (β = 6.50, t = 2.76, p < 0.01), unmarried and not in a cohabiting relationship (β = 3.05, t = 2.76, p < 0.01) than those who lived in Beijing, married and in a cohabiting relationship. Female (β = - 1.69, t = - 7.55, p < 0.01) and lower educational attainment (β = - 2.30, t = - 1.94, p = 0.05) were negatively related, while occupations of education, health, and civil staff (β = 1.50, t = 2.92, p < 0.01) were positively related to acceptability. It was predicted that migrants' acceptability of the Woman's Condom would significantly increase over time (β = 1.09, t = 5.54, p < 0.01).

Conclusions: The findings indicate that the Woman's Condom enjoyed relatively high short-term acceptability among migrants in China. In order to popularize the Women's Condoms in migrants, more publicity, consultation and training in open and prosperous areas should be strengthened.
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http://dx.doi.org/10.1186/s12889-019-7625-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819489PMC
October 2019
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