Publications by authors named "Min Long"

114 Publications

Asymmetric Total Synthesis of Taxol.

J Am Chem Soc 2021 Oct 12. Epub 2021 Oct 12.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

Taxol is one of the most famous natural diterpenoids and an important anticancer medicine. Taxol represents a formidable synthetic challenge and has prompted significant interest from the synthetic community. However, in all the previous syntheses of Taxol, there have been no reports of closing the desired eight-membered ring through C1-C2 bond formation. Furthermore, the existence of Taxol-resistant tumors and side effects of Taxol make the development of new approaches to synthesize Taxol and its derivatives highly desirable. Here, we report the asymmetric total synthesis of Taxol using a concise approach through 19 isolated intermediates. The synthetically challenging eight-membered ring was constructed efficiently by a diastereoselective intramolecular SmI-mediated pinacol coupling reaction to form the C1-C2 bond. The unique biomimetic oxygen ene reaction and the newly developed facile tandem C2-benzoate formation and C13 side chain installation improved the efficiency of the synthesis. The mild oxygen ene reaction under light conditions would be an alternative reaction involved in Taxol biosynthesis. This new convergent approach will allow the diverse creation of Taxol derivatives to enable further biological research.
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http://dx.doi.org/10.1021/jacs.1c09637DOI Listing
October 2021

Case Report: A Deletion Variant in the Gene Underlying Woodhouse-Sakati Syndrome in a Chinese Consanguineous Family.

Front Genet 2021 23;12:741323. Epub 2021 Sep 23.

Department of Endocrinology, University-Town Hospital of Chongqing Medical University, Chongqing, China.

Woodhouse-Sakati syndrome (WSS, MIM 241080) is a rare neuroendocrine disease characterized by hair loss, hypogonadism, diabetes, hearing loss, and extrapyramidal syndrome, and is usually caused by mutations in the gene as an inherited disease. plays an important role in mammalian gonadal development and infertility. So far, there have been no WSS reports in China. The patient introduced in this case is from a consanguineous family. The main symptoms of the patient were alopecia and gonadal agenesis. Other symptoms such as hearing loss, intellectual disability, and hyperglycemia were remarkable, and these symptoms are often observed in WSS patients. We found a nonsense mutation in the 11th exon of the gene (Refseq: NM_025000) in the patient and her younger brother, which confirmed the diagnosis of WSS. The genetic results also showed that the mutation was inherited from their healthy first-cousin parents.
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http://dx.doi.org/10.3389/fgene.2021.741323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498701PMC
September 2021

Reductive destruction of multiple nitrated energetics over palladium nanoparticles in the H-based membrane catalyst-film reactor (MCfR).

J Hazard Mater 2021 Aug 31;423(Pt A):127055. Epub 2021 Aug 31.

Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, USA.

Nitrated energetics are widespread contaminants due to their improper disposal from ammunition facilities. Different classes of nitrated energetics commonly co-exist in ammunition wastewater, but co-removal of the classes has hardly been documented. In this study, we evaluated the catalytic destruction of three types of energetics using palladium (Pd) nano-catalysts deposited on H-transfer membranes in membrane catalyst-film reactors (MCfRs). This work documented nitro-reduction of 2,4,6-trinitrotoluene (TNT), as well as, for the first time, denitration of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and pentaerythritol tetranitrate (PETN) over Pd at ambient temperature. The catalyst-specific activity was 20- to 90-fold higher than reported for other catalyst systems. Nitrite (NO) released from RDX and PETN also was catalytically reduced to dinitrogen gas (N). Continuous treatment of a synthetic wastewater containing TNT, RDX, and PETN (5 mg/L each) for more than 20 hydraulic retention times yielded removals higher than 96% for all three energetics. Furthermore, the concentrations of NO and NH were below the detection limit due to subsequent NO reduction with > 99% selectivity to N. Thus, the MCfR provides a promising strategy for sustainable catalytic removal of co-existing energetics in ammunition wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127055DOI Listing
August 2021

Adsorption and Reductive Defluorination of Perfluorooctanoic Acid over Palladium Nanoparticles.

Environ Sci Technol 2021 Sep 9. Epub 2021 Sep 9.

Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, Arizona 85287-5701, United States.

Per- and polyfluoroalkyl substances (PFASs) comprise a group of widespread and recalcitrant contaminants that are attracting increasing concern due to their persistence and adverse health effects. This study evaluated removal of one of the most prevalent PFAS, perfluorooctanoic acid (PFOA), in H-based membrane catalyst-film reactors (H-MCfRs) coated with palladium nanoparticles (PdNPs). Batch tests documented that PdNPs catalyzed hydrodefluorination of PFOA to partially fluorinated and nonfluorinated octanoic acids; the first-order rate constant for PFOA removal was 0.030 h, and a maximum defluorination rate was 16 μM/h in our bench-scale MCfR. Continuous-flow tests achieved stable long-term depletion of PFOA to below the EPA health advisory level (70 ng/L) for up to 70 days without catalyst loss or deactivation. Two distinct mechanisms for Pd-based PFOA removal were identified based on insights from experimental results and density functional theory (DFT) calculations: (1) nonreactive chemisorption of PFOA in a perpendicular orientation on empty metallic surface sites and (2) reactive defluorination promoted by physiosorption of PFOA in a parallel orientation above surface sites populated with activated hydrogen atoms (H). Pd-based catalytic reduction chemistry and continuous-flow treatment may be broadly applicable to the ambient-temperature destruction of other PFAS compounds.
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http://dx.doi.org/10.1021/acs.est.1c03134DOI Listing
September 2021

Pituitary P62 deficiency leads to female infertility by impairing luteinizing hormone production.

Exp Mol Med 2021 Aug 27;53(8):1238-1249. Epub 2021 Aug 27.

Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University, Xinqiao Main Street No. 183, Shapingba, Chongqing, China.

P62 is a protein adaptor for various metabolic processes. Mice that lack p62 develop adult-onset obesity. However, investigations on p62 in reproductive dysfunction are rare. In the present study, we explored the effect of p62 on the reproductive system. P62 deficiency-induced reproductive dysfunction occurred at a young age (8 week old). Young systemic p62 knockout (p62) and pituitary-specific p62 knockout (p62 αGSU) mice both presented a normal metabolic state, whereas they displayed infertility phenotypes (attenuated breeding success rates, impaired folliculogenesis and ovulation, etc.) with decreased luteinizing hormone (LH) expression and production. Consistently, in an infertility model of polycystic ovary syndrome (PCOS), pituitary p62 mRNA was positively correlated with LH levels. Mechanistically, p62 pituitary RNA sequencing showed a significant downregulation of the mitochondrial oxidative phosphorylation (OXPHOS) pathway. In vitro experiments using the pituitary gonadotroph cell line LβT2 and siRNA/shRNA/plasmid confirmed that p62 modulated LH synthesis and secretion via mitochondrial OXPHOS function, especially Ndufa2, a component molecule of mitochondrial complex I, as verified by Seahorse and rescue tests. After screening OXPHOS markers, Ndufa2 was found to positively regulate LH production in LβT2 cells. Furthermore, the gonadotropin-releasing hormone (GnRH)-stimulating test in p62 αGSU mice and LβT2 cells illustrated that p62 is a modulator of the GnRH-LH axis, which is dependent on intracellular calcium and ATP. These findings demonstrated that p62 deficiency in the pituitary impaired LH production via mitochondrial OXPHOS signaling and led to female infertility, thus providing the GnRH-p62-OXPHOS(Ndufa2)-Ca/ATP-LH pathway in gonadotropic cells as a new theoretical basis for investigating female reproductive dysfunction.
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http://dx.doi.org/10.1038/s12276-021-00661-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417229PMC
August 2021

Integrative analysis of lncRNA-miRNA-mRNA-associated competing endogenous RNA regulatory network involved in EV71 infection.

Am J Transl Res 2021 15;13(7):7440-7457. Epub 2021 Jul 15.

Department of Clinical Diagnosis, Tangdu Hospital, Air Force Medical University Xi'an, Shaanxi, China.

The competing endogenous RNA (ceRNA) axis has been shown to play a critical role in the pathogenesis of various viral infections. Generally, the ceRNA network involves long non-coding RNAs (lncRNAs) that act as sponges for miRNA to regulate mRNA expression. However, no information is available regarding the involvement of ceRNA networks in Enterovirus type 71 (EV71) infections. In the present study, data obtained from Gene Expression Omnibus (GEO) database was analyzed using various bioinformatics tools. EV71 infection in rhabdomyosarcoma (RD) cells was associated with differential expression of six lncRNAs, 28 miRNAs, and 349 mRNAs. Gene function enrichment analysis suggested induction of cytoplasmic vesicle process upon EV71 infection. The ceRNA networks were constructed, in which 20 hub genes were predicted by protein-protein interaction. To confirm the MALAT1/miR-194-5p/DUSP1 ceRNA regulatory axis in EV71 infection, real-time quantitative polymerase chain reaction (qRT-PCR) and luciferase reporter assay were performed. The results of the study also revealed the involvement of the MALAT1/miR-194-5p axis in apoptosis induced by EV71 infection, while no association with autophagy was observed. Thus, the present study provided novel insights into the pathogenic mechanism of EV71 infection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340214PMC
July 2021

Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells.

Front Cell Dev Biol 2021 28;9:690536. Epub 2021 May 28.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme catalyzing biosynthesis of guanine nucleotides, aggregates under certain circumstances into a type of non-membranous filamentous macrostructure termed "cytoophidium" or "rod and ring" in several types of cells. However, the biological significance and underlying mechanism of IMPDH assembling into cytoophidium remain elusive. In mouse ovaries, IMPDH is reported to be crucial for the maintenance of oocyte-follicle developmental synchrony by providing GTP substrate for granulosa cell natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system to produce cGMP for sustaining oocyte meiotic arrest. Oocytes and the associated somatic cells in the ovary hence render an exciting model system for exploring the functional significance of formation of IMPDH cytoophidium within the cell. We report here that IMPDH2 cytoophidium forms in the growing oocytes naturally and in the cumulus-enclosed oocytes treated with IMPDH inhibitor mycophenolic acid (MPA). Inhibition of IMPDH activity in oocytes and preimplantation embryos compromises oocyte meiotic and developmental competences and the development of embryos beyond the 4-cell stage, respectively. IMPDH cytoopidium also forms in the granulosa cells of the preovulatory follicles after the surge of luteinizing hormone (LH), which coincides with the resumption of oocyte meiosis and the reduction of IMPDH2 protein expression. In cultured COCs, MPA-treatment causes the simultaneous formation of IMPDH cytoopidium in cumulus cells and the resumption of meiosis in oocytes, which is mediated by the MTOR pathway and is prevented by guanosine supplementation. Therefore, our results indicate that cytoophidia do form in the oocytes and granulosa cells at particular stages of development, which may contribute to the oocyte acquisition of meiotic and developmental competences and the induction of meiosis re-initiation by the LH surge, respectively.
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http://dx.doi.org/10.3389/fcell.2021.690536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194064PMC
May 2021

Antibodies and Vaccines Target RBD of SARS-CoV-2.

Authors:
Long Min Qiu Sun

Front Mol Biosci 2021 22;8:671633. Epub 2021 Apr 22.

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

The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which gives rise to the coronavirus disease 2019 (COVID-19), has caused a serious threat to global public health. On March 11, 2020, the WHO had officially announced COVID-19 as a pandemic. Therefore, it is vital to find effective and safe neutralizing antibodies and vaccines for COVID-19. The critical neutralizing domain (CND) that is contained in the receptor-binding domain (RBD) of the spike protein (S protein) could lead to a highly potent neutralizing antibody response as well as the cross-protection of other strains of SARS. By using RBD as an antigen, many neutralizing antibodies are isolated that are essential to the therapeutics of COVID-19. Furthermore, a subunit vaccine, which is based on the RBD, is expected to be safer than others, thus the RBD in the S protein is a more important target for vaccine development. In this review, we focus on neutralizing antibodies that are targeting RBD as well as the vaccine based on RBD under current development.
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http://dx.doi.org/10.3389/fmolb.2021.671633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100443PMC
April 2021

mGPDH Deficiency leads to melanoma metastasis via induced NRF2.

J Cell Mol Med 2021 06 3;25(11):5305-5315. Epub 2021 May 3.

Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University, Chongqing, China.

Oxidative stress critically influences carcinogenesis and the progression of melanoma, and aggressive malignant melanoma activity is due to its high metastatic ability. Some findings in several cancer cell lines have indicated that mGPDH, a component of the mitochondrial respiratory chain, also modulates oxidative stress. However, the role of mGPDH in melanoma remains elusive. Here, we report that the mGPDH protein level is decreased in human skin melanoma compared to normal skin and decreased in metastatic melanoma compared to primary melanoma. Our in vivo and in vitro experiments indicated that mGPDH depletion accelerated melanoma migration and invasion without affecting proliferation or apoptosis. Mechanistically, we found elevated NRF2 protein levels in human skin melanoma and mGPDH-knockout (ko) metastatic xenografts in the lungs of nude mice. Moreover, in A375 melanoma cells, the loss of mGPDH-induced NRF2 expression but did not affect NRF2 protein degradation. Additionally, melanoma metastasis induced by the loss of mGPDH was rescued by the further down-regulation of NRF2 in vivo and in vitro. Consistently, mGPDH overexpression (oe) depressed NRF2 expression and attenuated the malignant properties of melanoma cells. In conclusion, our findings suggest that mGPDH suppresses melanoma metastasis by inhibiting NRF2 and downstream oxidative signals, highlighting the therapeutic potential of mGPDH for melanoma treatment.
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http://dx.doi.org/10.1111/jcmm.16542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178277PMC
June 2021

H-Based Membrane Catalyst-Film Reactor (H-MCfR) Loaded with Palladium for Removing Oxidized Contaminants in Water.

Environ Sci Technol 2021 05 26;55(10):7082-7093. Epub 2021 Apr 26.

Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, Arizona 85287-5701, United States.

Scalable applications of precious-metal catalysts for water treatment face obstacles in H-transfer efficiency and catalyst stability during continuous operation. Here, we introduce a H-based membrane catalyst-film reactor (H-MCfR), which enables in situ reduction and immobilization of a film of heterogeneous Pd catalysts that are stably anchored on the exterior of a nonporous H-transfer membrane under ambient conditions. In situ immobilization had >95% yield of Pd in controllable forms, from isolated single atoms to moderately agglomerated nanoparticles (averaging 3-4 nm). A series of batch tests documented rapid Pd-catalyzed reduction of a wide spectrum of oxyanions (nonmetal and metal) and organics (e.g., industrial raw materials, solvents, refrigerants, and explosives) at room temperature, owing to accurately controlled H supply on demand. Reduction kinetics and selectivity were readily controlled through the Pd loading on the membranes, H pressure, and pH. A 45-day continuous treatment of trichloroethene (TCE)-contaminated water documented removal fluxes up to 120 mg-TCE/m/d with over 90% selectivity to ethane and minimal (<1.5%) catalyst leaching or deactivation. The results support that the H-MCfR is a potentially sustainable and reliable catalytic platform for reducing oxidized water contaminants: simple synthesis of an active and versatile catalyst that has long-term stability during continuous operation.
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http://dx.doi.org/10.1021/acs.est.1c01189DOI Listing
May 2021

-Chlorophenol (4-CP) Removal by a Palladium-Coated Biofilm: Coupling Catalytic Dechlorination and Microbial Mineralization via Denitrification.

Environ Sci Technol 2021 05 13;55(9):6309-6319. Epub 2021 Apr 13.

Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, Arizona 85287, United States.

Rapid dechlorination and full mineralization of para-chlorophenol (4-CP), a toxic contaminant, are unfulfilled goals in water treatment. Means to achieve both goals stem from the novel concept of coupling catalysis by palladium nanoparticles (PdNPs) with biodegradation in a biofilm. Here, we demonstrate that a synergistic version of the hydrogen (H)-based membrane biofilm reactor (MBfR) enabled simultaneous removals of 4-CP and cocontaminating nitrate. In situ generation of PdNPs within the MBfR biofilm led to rapid 4-CP reductive dechlorination, with >90% selectivity to more bioavailable cyclohexanone. Then, the biofilm mineralized the cyclohexanone by utilizing it as a supplementary electron donor to accelerate nitrate reduction. Long-term operation of the Pd-MBfR enriched the microbial community in cyclohexanone degraders within , , and . In addition, the PdNP played an important role in accelerating nitrite reduction; while NO reduction to NO was entirely accomplished by bacteria, NO reduction to N was catalyzed by PdNPs and bacterial reductases. This study documents a promising option for efficient and complete remediation of halogenated organics and nitrate by the combined action of PdNP and bacterial catalysis.
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http://dx.doi.org/10.1021/acs.est.0c08307DOI Listing
May 2021

Feingold syndrome type 2 in a patient from China.

Am J Med Genet A 2021 07 5;185(7):2262-2266. Epub 2021 Apr 5.

Department of Clinical Laboratory, Shenzhen Nanshan Maternity and Child Healthcare Hospital, Shenzhen, China.

Feingold syndrome type 2 (FGLDS2, MIM614326) is a genetic congenital malformation syndrome, caused by germline heterozygous deletion of MIR17HG on chromosome 13q31, which is extremely rare worldwide. To date, less than 25 patients have been described in the literature. Here, we report on a 3-year-old girl presented with hip dysplasia, polysyndactyly of the left thumb, brachymesophalangy of the fifth digit, microcephaly, intellectual disability, and growth delay. This is likely to be the first case of Feingold syndrome type 2 ever discovered among Chinese population. Through genetic testing and pedigree analysis, she was identified to have a de novo 4.8-Mb microdeletion at chromosome 13q31.3-q32.1, encompassing MIR17HG, GPC5, and GPC6. Additionally, we detected two common compound heterozygous variants (c.919-2A>G and c.147C>G) in SLC26A4 encoding pendrin protein, as well as a novel heterozygous variant c.985_988del in COMP encoding cartilage oligomeric matrix protein. This case report aims to analyze the microdeletion and the three types of variant detected in the patient, and to explore the association between the genotype and phenotype in patients with Feingold syndrome type 2, which may contribute to further understanding and future diagnosis of this disorder.
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http://dx.doi.org/10.1002/ajmg.a.62190DOI Listing
July 2021

Dedicator of Cytokinesis 5 Regulates Keratinocyte Function and Promotes Diabetic Wound Healing.

Diabetes 2021 05 24;70(5):1170-1184. Epub 2021 Feb 24.

Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Department of Endocrinology, Second Affiliated Hospital of Army Medical University, Chongqing, China

Cutaneous wound healing is a fundamental biologic and coordinated process, and failure to maintain this process contributes to the dysfunction of tissue homeostasis, increasing the global burden of diabetic foot ulcerations. However, the factors that mediate this process are not fully understood. Here, we identify the pivotal role of dedicator of cytokinesis 5 (Dock5) in keratinocyte functions contributing to the process of skin wound healing. Specifically, Dock5 is highly upregulated during the proliferative phase of wound repair and is predominantly expressed in epidermal keratinocytes. It regulates keratinocyte adhesion, migration, and proliferation and influences the functions of extracellular matrix (ECM) deposition by facilitating the ubiquitination of transcription factor ZEB1 to activate laminin-332/integrin signaling. Genetic ablation of Dock5 in mice leads to attenuated reepithelialization and granulation tissue formation, and Dock5 overexpression-improved skin repair can be abrogated by LAMA3 knockdown. Importantly, Dock5 expression in the skin edge is reduced in patients and animal models of diabetes, further suggesting a direct correlation between its abundance and healing capability. The rescue of Dock5 expression in diabetic mice causes a significant improvement in reepithelialization, collagen deposition, ECM production, and granulation. Our study provides a potential therapeutic target for wound healing impairment during diabetes.
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http://dx.doi.org/10.2337/db20-1008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173801PMC
May 2021

[Analysis of results of concurrent hearing and deafness genetic screening and follow up of 33 911 newborns].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jan;38(1):32-36

Department of Clinical Laboratory, Shenzhen Nanshan Maternity and Child Health Care Hospital, Shenzhen, Guangdong 518067, China.

Objective: To analyze the results of concurrent hearing and deafness genetic screening and follow up of newborns.

Methods: In total 33 911 babies born to 5 designated hospitals in Nanshan District of Shenzhen city from October 2017 to December 2019 were included. All subjects underwent concurrent hearing and deafness genetic screening covering 21 variants of 4 genes including GJB2, SLC26A4, GJB3 and Mt12SrRNA. For those with positive results, Sanger sequencing was carried out for confirmation.

Results: 93.32% subjects passed the first-round hearing screening, and 87.01% passed the recheck testing. The overall detection rate was 4.18%. The detection rates for GJB2, SLC26A4, GJB3 and Mt12srRNA variants were 1.98%, 1.58%, 0.37% and 0.25%, respectively. 126 and 84 subjects were found with high risk for delayed-onset and drug-induced hearing loss, respectively. In addition, 4 and 5 subjects were found to harbor homozygous/compound heterozygous variants of the GJB2 and SLC26A4 genes, respectively. Concurrent screening showed that subjects (with heterozygous variants) who did not passed the two round hearing test were as follows: GJB2 with 6.75% in the first round and 2.61% in the second round testing, SLC26A4 (3.3%/1.2%), GJB3 (0.72%/0.14%) and 12SrRNA (0.36%/Nil), respectively. Moreover, the No-pass rate in the subjects with homozygous or compound variants in single gene, heterozygous variant in single gene, heterozygous variant in multiple genes, and homozygous variant in GJB3 gene were significantly higher than the subjects with negative results of genetic screening.

Conclusion: Concurrent newborn genetic screening can enhance the effectiveness of hearing screening and enable earlier identification and intervention for children with hearing impairment. Follow-up can improve the diagnostic rate for children who are positive for the concurrent screening. Nevertheless, genetic and hearing screening cannot replace the diagnostic testing. It is necessary to conduct comprehensive analysis for the results of genetic and hearing screening and radiological examinations. Sanger sequencing and next-generation sequencing are critical for ascertain the diagnosis.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200322-00189DOI Listing
January 2021

A high-fat diet: an unexpected role in preventing the metastatic seeding of colorectal cancer.

Signal Transduct Target Ther 2020 11 3;5(1):257. Epub 2020 Nov 3.

State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, 610041, Chengdu, China.

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http://dx.doi.org/10.1038/s41392-020-00386-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609628PMC
November 2020

[Establishment of a vimentin knockout and HIV-1 gp120 transgenic mouse model].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Apr;40(4):519-524

Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.

Objective: To construct a HIV-1 gp120 transgenic mice (gp120 Tg) with vimentin (VIM) gene knockout.

Methods: Female HIV-1 gp120 Tg mice were mated to VIM heterozygote mice (F0). All the offspring mice were derived from these original founders so that both genotypes had the same mixed genetic background. The F1 mice were bred to generate of VIM, VIM, VIM/gp120 Tg and VIM/gp120 Tg mice. PCR was performed for genotyping of the mice, and the expressions of VIM and gp120 in the brain tissues were examined using immunoblotting.

Results: The results of PCR showed the presence of the target bands in VIM, VIM, VIM/gp120 Tg and VIM/gp120 Tg mice. In VIM/gp120 Tg mice, gp120 expression was detected throughout the brain regions while no VIM expression was detected.

Conclusions: We generated gp120 transgenic mouse models with VIM gene knockout, which facilitate the exploration of the role of VIM in gp120-induced neurotoxicity.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.04.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225117PMC
April 2020

Synthetic applications of type II intramolecular cycloadditions.

Chem Soc Rev 2020 Oct 1;49(19):7015-7043. Epub 2020 Sep 1.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.

Type II intramolecular cycloadditions ([4+2], [4+3], [4+4] and [5+2]) have emerged recently as an efficient and powerful strategy for the construction of bridged ring systems. In general, type II cycloadditions provide access to a wide range of bridged bicyclo[m.n.1] ring systems with high regio- and diastereoselectivity in an easy and straightforward manner. In each section of this review, an overview of the corresponding type II cycloadditions is presented, which is followed by highlights of method development and synthetic applications in natural product synthesis. The goal of this review is to provide a survey of recent advances in the field covering literature up to 2020. The review will serve as a useful reference for organic chemists engaged in the total synthesis of natural products containing bridged bicyclo[m.n.1] ring systems and provide strong stimulus for invention and further advances in this exciting research field.
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http://dx.doi.org/10.1039/d0cs00365dDOI Listing
October 2020

Hyperoside Alleviates High Glucose-Induced Proliferation of Mesangial Cells through the Inhibition of the ERK/CREB/miRNA-34a Signaling Pathway.

Int J Endocrinol 2020 21;2020:1361924. Epub 2020 Jul 21.

Center of Medical Experiment Technology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China.

Purpose: Hyperoside, a flavonoid isolated from conventional medicinal herbs, has been demonstrated to exert a significant protective effect in diabetic nephropathy. This study aimed to determine the underlying mechanisms, by which hyperoside inhibits high glucose-(HG-) induced proliferation in mouse renal mesangial cells.

Methods: Mouse glomerular mesangial cells line (SV40-MES13) was used to study the inhibitory effect of hyperoside on cell proliferation induced by 30 mM glucose, which was used to simulate a diabetic condition. Viable cell count was assessed using the Cell Counting Kit-8 and by the 5-ethynyl-20-deoxyuridine incorporation assay. The underlying mechanism involving miRNA-34a was further investigated by quantitative RT-PCR and transfection with miRNA-34a agomir. The phosphorylation levels of extracellular signal-regulated kinases (ERKs) and cAMP-response element-binding protein (CREB) were measured by Western blotting. The binding region and the critical binding sites of CREB in the miRNA-34a promoter were investigated by the chromatin immunoprecipitation assay and luciferase reporter assay, respectively.

Results: We found that hyperoside could significantly decrease HG-induced proliferation of SV40-MES13 cells in a dose-dependent manner, without causing obvious cell death. In addition, hyperoside inhibited the activation of ERK pathway and phosphorylation of its downstream transcriptional factor CREB, as well as the miRNA-34a expression. We further confirmed that CREB-mediated regulation of miRNA-34a is dependent on the direct binding to specific sites in the promoter region of miRNA-34a.

Conclusion: Our cumulative results suggested that hyperoside inhibits the proliferation of SV40-MES13 cells through the suppression of the ERK/CREB/miRNA-34a signaling pathway, which provides new insight to the current investigation on therapeutic strategies for diabetic nephropathy.
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http://dx.doi.org/10.1155/2020/1361924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397715PMC
July 2020

The diagnostic value of the combination of Golgi protein 73, glypican-3 and alpha-fetoprotein in hepatocellular carcinoma: a diagnostic meta-analysis.

Ann Transl Med 2020 Apr;8(8):536

Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

Background: Alpha-fetoprotein (AFP) has been extensively applied in clinical practice to detect and predict postoperative outcomes of patients with hepatocellular carcinoma (HCC). However, due to its low sensitivity and specificity, its efficacy has been questioned. Recently, novel serum biomarkers including Golgi protein 73 (GP73) and glypican-3 (GPC-3) have shown a better discriminatory ability than AFP in detecting early HCC. The results of the combined use of GP73, GPC-3 and AFP in the diagnosis of HCC remain inconclusive. This investigation aimed to evaluate the discriminatory ability of GP73, GPC-3 and AFP to jointly identify HCC using the statistical methods of meta-analysis.

Methods: Comprehensive database searches of, Web of Science, the Cochrane Library, Embase, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure were performed for literature dated up to 1 November, 2019. Studies relating to the diagnostic accuracy of the combination of GP73, GPC-3 and AFP in the identification of HCC were included. A random-effects model was used to pool sensitivity, specificity, the positive and negative likelihood ratios [positive likelihood ratio (PLR) and negative likelihood ratio (NLR), respectively], and the diagnostic odds ratio (DOR). We applied the Fagan nomogram to assess the clinical utility of joint detection. The overall detection accuracy was determined using summary receiver operating characteristic curve (SROC) analysis. Meta-regression analysis of heterogeneity publication bias was analyzed with Stata (version 12.0).

Results: Our meta-analysis focused on 12 studies involving 919 patients with HCC and 1,549 non-HCC patients. Sensitivity, specificity, PLR, NLR and DOR for joint detection, were 0.91 (95% CI: 0.87-0.94), 0.84 (95% CI: 0.77-0.89), 5.83 (95% CI: 4.05-8.40), 0.10 (95% CI: 0.07-0.15), 57.51 (95% CI: 35.92-92.08), respectively, when pooled, and the area under the SROC curve was 0.95.

Conclusions: Current evidence indicates that GP73, GPC-3 and AFP exhibit much better accuracy for the diagnosis of HCC when used in combination rather than alone or in pairs.
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http://dx.doi.org/10.21037/atm.2020.02.89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214882PMC
April 2020

Recent Advances in the Total Synthesis of Natural Products Containing Eight-Membered Carbocycles (2009-2019).

Chem Rev 2020 07 28;120(13):5910-5953. Epub 2020 Apr 28.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.

Natural products containing eight-membered carbocycles constitute a class of structurally intriguing and biologically important molecules such as the famous diterpenes taxol and vinigrol. Such natural products are being increasingly investigated because of their fascinating architectural features and potent medicinal properties. However, synthesis of natural products with cyclooctane moieties has proved to be highly challenging. This review highlights the recently completed total syntheses of natural products with eight-membered carbocycles with a focus on strategic considerations. A collection of 27 representative studies from the literature covering the decade from 2009 to 2019 is described in chronological order with relevant studies grouped together, including syntheses of the same natural product by different research groups using different strategies. Finally, a summary and outlook including a discussion of the major features of each strategy used in the syntheses are presented. This review illustrates the diversity and creativity in the elegant synthetic designs of eight-membered carbocycles. We hope this review will provide timely illumination and beneficial guidance for future synthetic efforts for organic chemists who are interested in this area.
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http://dx.doi.org/10.1021/acs.chemrev.0c00045DOI Listing
July 2020

Adenovirus-mediated anti-AEG-1 ScFv expression driven by stathmin promoter inhibits tumor growth in cervical cancer.

Cancer Cell Int 2020 12;20:79. Epub 2020 Mar 12.

Department of Medical Laboratory, Tangdu Hospital, Airforce Military Medical University, Xinsi Road, Xi'an, 710038 Shaanxi China.

Background: --- is over-expressed in many cancer cells and has multiple key functions in tumor initiation and progression. Currently, targeted-AEG-1 siRNA is one of the most common techniques to down-regulate AEG-1 expression, but the lack of tumor specificity and available delivery system make it difficult to enter clinical trials.

Methods: In this study, we creatively developed an adenovirus-mediated anti-AEG-1 single-chain antibody fragment (ScFv) expression system driven by a tumor specific promoter, and experimented with it in human cervical carcinoma cells to investigate the effect on tumor's proliferation and apoptosis.

Results: The results showed that of HeLa and SiHa cells treated with this recombinant anti-AEG-1 ScFv adenovirus not only inhibited cell growth, but induced apoptosis both in vitro and in vivo. Furthermore, we also observed that the expressions of several apoptosis-related genes like Akt 1 and c-Myc decreased, while NF-κB (p65) and cleaved caspase 3 increased on protein levels in vivo.

Conclusion: We concluded that stathmin promoter-driving anti-AEG-1 ScFv adenoviral system may be a breakthrough for its dual-specificity, and serve as an adjuvant tumor specific therapy method in the treatment for human cervical cancers.
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http://dx.doi.org/10.1186/s12935-020-1159-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068931PMC
March 2020

Total Synthesis of Natural Products with Bridged Bicyclo[m.n.1] Ring Systems via Type II [5 + 2] Cycloaddition.

Acc Chem Res 2020 03 18;53(3):703-718. Epub 2020 Feb 18.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.

Natural products containing bridged ring systems are widely identified and show significant biological activity. The development of efficient synthesis reactions and strategies to construct bridged ring systems is a long-standing but very significant challenge in organic chemistry. In 2014, our group developed a unique type II [5 + 2] cycloaddition reaction that provides a facile and direct methodology for constructing highly functionalized bridged bicyclo[4.3.1], bicyclo[4.4.1], bicyclo[5.4.1], bicyclo[6.4.1], and other bicyclo[m.n.1] systems containing a strained bridgehead double bond. In this Account, we summarize the methodology development and report the results of application of our unique strategy for the total synthesis of several natural products with bridged ring systems (i.e., cyclocitrinol, cerorubenic acid-III, and vinigrol) during the past 5 years in our laboratory. In the first part, we introduce the logic behind the design and discovery of type II [5 + 2] cycloadditions. The substrates can be easily synthesized by a modular approach, followed by base-promoted group elimination under heat to form an oxidopyrylium ylide, which can undergo cycloaddition under relatively mild conditions with a variety of double bonds to generate bridged bicyclo[m.n.1] frameworks in high yield. The diastereocontrol and unique selectivity of this methodology are favorable for further application to the synthesis of complex natural products. In the second part, we highlight our endeavors in the total synthesis of several different types of molecules bearing bridged ring systems using our methodology. The bridged bicyclo[4.4.1] system is the core structure of two different types of natural products, cyclocitrinol and cerorubenic acid-III, that can be efficiently constructed by type II [5 + 2] cycloadditions. The development of suitable strategies and methods for site-selective cleavage of the C-O bond of the oxa-[3.2.1] ring system in the products of type II [5 + 2] cycloadditions is also discussed and highlighted during the syntheses. Moreover, the bridged bicyclo[5.3.1] system is the core structure of vinigrol, which can be constructed through a novel ring contraction sequence of the bicyclo[5.4.1] system formed by a type II [5 + 2] cycloaddition. By combining with a ring contraction cascade, we believe that type II [5 + 2] cycloadditions have the potential to be used as a unified approach to constructing natural products containing bridged bicyclo[m.n.1] frameworks.
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http://dx.doi.org/10.1021/acs.accounts.9b00640DOI Listing
March 2020

Decreased Circulating MANF in Women with PCOS is Elevated by Metformin Therapy and is Inversely Correlated with Insulin Resistance and Hyperandrogenism.

Horm Metab Res 2020 Feb 13;52(2):109-116. Epub 2020 Feb 13.

Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel neurotrophic factor. Although recent studies have suggested that MANF appeared to be associated with insulin resistance, the results have been inconsistent. The aim of our study was to determine the serum MANF levels in women with PCOS and controls, to investigate their relationship to insulin resistance, and to evaluate circulating MANF changes with metformin intervention in PCOS women. We conducted a series of cross-sectional and interventional studies in 90 newly diagnosed patients with PCOS and 60 age- and gender-matched controls. Oral glucose tolerance test and euglycemic-hyperinsulinemic clamps were performed to assess the glucose tolerance and insulin sensitivity. Forty-three women with PCOS were randomly assigned to six months of oral metformin therapy. Serum MANF levels were significantly lower in women with PCOS than in controls. Serum MANF levels were positively correlated with M-value and negatively correlated with body mass index (BMI), body fat percentage (FAT), homeostatic model assessment of insulin resistance (HOMA-IR), and free androgen index (FAI). Multivariate stepwise regression demonstrated that serum MANF levels were independently associated with M-value and FAI. After six months of metformin treatment, there was a significant increase in serum MANF levels in PCOS women. Serum MANF levels are decreased in women with PCOS, and are reversely related to insulin resistance and hyperandrogenism. Metformin treatment elevates serum MANF levels and alleviates insulin resistance and hyperandrogenism in PCOS women.
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http://dx.doi.org/10.1055/a-1082-1080DOI Listing
February 2020

Effect of Oyster Meat Preload on Postmeal Glycemic Control in Healthy Young Adults.

J Am Coll Nutr 2020 08 27;39(6):511-517. Epub 2019 Dec 27.

Central Laboratory, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China.

Evidence suggests that food preload improves postmeal glycemic profiles, but the effects of marine food are poorly understood. Our study aims to verify the regulating effects of premeal oyster meat (OM) on postprandial blood glucose. Edible parts of the flesh of oyster were prepared for a randomized crossover experiment. After overnight fasting, 20 healthy young men consumed 300 mL of preload drinks with 0 g/kg body weight (BW) (control), 0.1 g/kg BW, and 0.2 g/kg BW. Peripheral blood concentrations of glucose and gastrointestinal hormones were measured before preloading at baseline (0 minutes) and at intervals after the preload and after a preset rice meal. The nutrient composition of OM was analyzed. Compared with other doses, 0.2 g/kg BW OM preload induced higher plasma premeal insulin ( < 0.05), C-peptide ( < 0.05), and glucagon-like peptide-1 (GLP-1;  < 0.05) without altering the glucose concentrations during premeal times. By contrast, 0.2 g/kg BW OM induced less secretion of glucose ( < 0.05) and gastric inhibitory peptide (GIP;  < 0.05), but higher secretion of GLP-1 ( < 0.05) than 0.1 g/kg BW of OM after a meal. During the entire experiment (0-170 minutes), OM reduced the blood glucose ( < 0.05) and GIP ( < 0.05), but increased GLP-1 ( < 0.05). OM was rich in protein (78.4%) and low in fat (6%). Glutamic acid, aspartic acids, glycine, and taurine are the amino acids with high content found in OM. OM preload reduces postmeal glycemia in healthy young people with associated changes in gastrointestinal hormone responses. This effect may be attributed to the rich contents of protein and amino acids of OM.
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http://dx.doi.org/10.1080/07315724.2019.1699475DOI Listing
August 2020

Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.

Nat Commun 2019 10 15;10(1):4679. Epub 2019 Oct 15.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.

Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
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http://dx.doi.org/10.1038/s41467-019-12435-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794285PMC
October 2019

Disruptive variants of associate with autism and interfere with neuronal development and synaptic transmission.

Sci Adv 2019 09 25;5(9):eaax2166. Epub 2019 Sep 25.

Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity-related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.
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http://dx.doi.org/10.1126/sciadv.aax2166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760934PMC
September 2019

Asymmetric Total Synthesis of (-)-Vinigrol.

J Am Chem Soc 2019 10 30;141(40):15773-15778. Epub 2019 Sep 30.

Shenzhen Grubbs Institute and Department of Chemistry , Southern University of Science and Technology , Shenzhen 518055 , China.

A new strategy was developed for the asymmetric total synthesis of (-)-vinigrol. The strategy involved a linear sequence of 15 steps from 3-methyl-butanal (14 steps from chloro-dihydrocarvone) and did not need protecting groups. The synthetically challenging 1,5-butanodecahydronaphthalene core was constructed efficiently via a type II intramolecular [5+2] cycloaddition, followed by a unique ring-contraction cascade.
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http://dx.doi.org/10.1021/jacs.9b08983DOI Listing
October 2019

Increased plasma osteopontin levels are associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus.

Cytokine 2020 01 9;125:154837. Epub 2019 Sep 9.

Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) commonly occurs in patients with type 2 diabetes mellitus (T2DM). Osteopontin (OPN) is a multifunctional protein with pleiotropic physiological functions. This study aimed to investigate the interrelation between circulating OPN and NAFLD in T2DM patients. Overall, 249 subjects were classified into 4 groups: 53 patients with NAFLD and T2DM; 57 with newly diagnosed T2DM; 59 with NAFLD; and 80 healthy age- and sex-matched controls. Serum OPN was measured by ELISA. The OPN distribution in the pooled data was divided into quartiles; significant trends across increasing quartiles were estimated by the Cochran-Armitage trend test. Compared with the controls, circulating OPN concentrations were significantly elevated in NAFLD patients and T2DM patients with or without NAFLD. Serum OPN levels were higher in the overweight/obese group than that in the lean group. Circulating OPN levels were positively correlated with CRP, age, BMI, SBP, DBP, HbA1c, UA, TGs, WBCs, neutrophils, FBG, and HOMA-IR and negatively correlated with ADP, albumin and HDL. Age, albumin, HbA1c, HDL and hsCRP were independently related to circulating OPN. The relative risks for NAFLD, T2DM and T2DM with NAFLD increased significantly along with increasing OPN quartiles based on the Cochran-Armitage trend test. OPN is an optimal predictor in the diagnosis of T2DM with NAFLD and T2DM and may contribute to the aggravation of the metabolic state.
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http://dx.doi.org/10.1016/j.cyto.2019.154837DOI Listing
January 2020

Early prediction of preeclampsia and small-for-gestational-age via multi-marker model in Chinese pregnancies: a prospective screening study.

BMC Pregnancy Childbirth 2019 Aug 19;19(1):304. Epub 2019 Aug 19.

Department of Clinical Laboratory, Shenzhen Nanshan Maternity and Child Healthcare Hospital, No.1 Wanxia Road, Nanshan District, Shenzhen, Guangdong, People's Republic of China.

Background: Recent evidence suggests early screening of preeclampsia and small-for-gestational-age (SGA) would benefit pregnancies followed by subsequent prophylactic use of aspirin. Multi-marker models have shown capability of predicting preeclampsia and SGA in first trimester. Yet the clinical feasibility of combined screening model for Chinese pregnancies has not been fully assessed. The aim of this study is to evaluate the applicability of a multi-marker screening model to the prediction of preeclampsia and SGA in first trimester particularly among Chinese population.

Methods: Three thousand two hundred seventy pregnancies meeting the inclusion criteria took first-trimester screening of preeclampsia and SGA. A prior risk based on maternal characteristics was evaluated, and a posterior risk was assessed by combining prior risk with multiple of median (MoM) values of mean arterial pressure (MAP), serum placental growth factor (PLGF) and pregnancy associated plasma protein A (PAPP-A). Both risks were calculated by Preeclampsia PREDICTOR™ software, Perkin Elmer. Screening performance of prior and posterior risks for early and late preeclampsia by using PREDICTOR software was shown by Receiver Operating Characteristics (ROC) curves. The estimation of detection rates and false positive rates of delivery with both preeclampsia and SGA was made.

Results: Eight cases developed early preeclampsia (0.24%) and 35 were diagnosed as late preeclampsia (1.07%). Five with early preeclampsia and ten with late preeclampsia later delivered SGA newborns (0.46%); 84 without preeclampsia gave birth to the SGAs (2.57%). According to ROC curves, posterior risks performed better than prior risks in terms of preeclampsia, especially in early preeclampsia. At 10% false positive rate, detection rates of early and late preeclampsia were 87.50 and 48.57%, detection rates of early and late SGA were 41.67 and 28.00%, respectively. For SGA, detection rates in cases with preeclampsia were much higher than those in absence of it.

Conclusions: This study demonstrates that combined screening model could be useful for predicting early preeclampsia in Chinese pregnancies. Furthermore, the performance of SGA screening by same protocol is strongly associated with preeclampsia.
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http://dx.doi.org/10.1186/s12884-019-2455-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700825PMC
August 2019

Characterization, antioxidant, and anticancer activities of a neutral polysaccharide from Duchesnea indica (Andr.) Focke.

J Food Biochem 2019 07 20;43(7):e12899. Epub 2019 May 20.

Engineering Research Center of Biotechnology for Active Substances, Ministry of Education; Chongqing Key Laboratory of Animal Biology, Chongqing Normal University, Chongqing, China.

A neutral polysaccharide (DIP-1) from Duchesnea indica (Andr.) Focke was obtained by hot water extraction, ethanol precipitation and chromatographic separation (DEAE-52 cellulose anion-exchange column and Sephadex G-100 gel column). The physicochemical properties of DIP-1 were elucidated by gel permeation chromatography, monosaccharide composition, Fourier transform infrared spectrometry, UV-visible spectrophotometry, scanning electron microscope and Congo red test. The results indicated that DIP-1 was consisted of mannose, glucosamine, glucose, galactose and arabinose in a ratio of 1.00:0.42:18.36:14.17:0.81, and its molecular weight was 218.3 kDa. Meanwhile, DIP-1 presented a straight hexahedron structure, but no triple-helical conformation. In antioxidant activity tests, DIP-1 exhibited powerful scavenging activities on hydroxyl, DPPH, ABTS radicals and reducing power in a dose-dependent manner. Especially, DIP-1 demonstrated high inhibitory activities against SKOV-3 and Hep-G2 cells in vitro, with IC values of 1.42 and 1.23 mg/ml, respectively. PRACTICAL APPLICATIONS: D. indica has been used for a long time as a Chinese medicine for therapy of many diseases, including cancer, inflammation, leprosy, fever, bleeding and so on. At present, polysaccharides have attracted comprehensive attention because of a large range of pharmacological and biological properties, including antitumor, antidiabetic, antioxidant and immunomodulatory activity. In the present study, we purified and characterized a neutral polysaccharide from D. indica for the first time. Moreover, the neutral polysaccharide exhibits significant antioxidant and antitumor activities. Therefore, the present study laid a foundation for the high-value application of D. indica polysaccharides in functional food and pharmaceutical industries.
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http://dx.doi.org/10.1111/jfbc.12899DOI Listing
July 2019
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