Publications by authors named "Na Gao"

354 Publications

The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants.

Mar Drugs 2021 Aug 27;19(9). Epub 2021 Aug 27.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.

Fucosylated glycosaminoglycan (FG) from sea cucumber is a potent anticoagulant by inhibiting intrinsic coagulation tenase (iXase). However, high-molecular-weight FGs can activate platelets and plasma contact system, and induce hypotension in rats, which limits its application. Herein, we found that FG from (TaFG) and FG from (HfFG) at 4.0 mg/kg (i.v.) could cause significant cardiovascular and respiratory dysfunction in rats, even lethality, while their depolymerized products had no obvious side effects. After injection, native FG increased rat plasma kallikrein activity and levels of the vasoactive peptide bradykinin (BK), consistent with their contact activation activity, which was assumed to be the cause of hypotension in rats. However, the hemodynamic effects of native FG cannot be prevented by the BK receptor antagonist. Further study showed that native FG induced in vivo procoagulation, thrombocytopenia, and pulmonary embolism. Additionally, its lethal effect could be prevented by anticoagulant combined with antiplatelet drugs. In summary, the acute toxicity of native FG is mainly ascribed to pulmonary microvessel embolism due to platelet aggregation and contact activation-mediated coagulation, while depolymerized FG is a safe anticoagulant candidate by selectively targeting iXase.
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http://dx.doi.org/10.3390/md19090487DOI Listing
August 2021

A radical-mediated multicomponent cascade reaction for the synthesis of azide-biindole derivatives.

Chem Commun (Camb) 2021 Sep 23;57(76):9696-9699. Epub 2021 Sep 23.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P. R. China.

A radical-mediated, one-pot, multicomponent cascade reaction was developed for the synthesis of azide-biindole derivatives. Mechanistic studies demonstrated that the nitrogen-centred free radical was formed by the reaction of heterocyclic N-H with Cu and PIFA and initiated the cascade reaction with indole to obtain the biindole intermediate. The biindole intermediate then reacted with sodium azide in the presence of Cu catalyst and PIFA to form the final products. This methodology may be useful for constructing other azido heterocycles.
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http://dx.doi.org/10.1039/d1cc03853bDOI Listing
September 2021

The role of CD8 Granzyme B T cells in the pathogenesis of Takayasu's arteritis.

Clin Rheumatol 2021 Sep 7. Epub 2021 Sep 7.

Department of Rheumatology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China.

Objective: T cell-mediated immune response plays a key role in Takayasu arteritis (TAK). Although previous studies have showed the roles of CD4T cell and its subsets in TAK, the change of CD8 T cell subsets remains unclear. This study investigated the role of CD8 T cell subsets in TAK.

Methods: The study consisted of 56 TA patients and 51 healthy controls. The percentages of CD8T cells, CD8GranzymeB T cells, CD8Perforin T cells, and CD8IFN-γ T cells in blood samples were analyzed by flow cytometry.

Results: We found that the percentages of CD8GranzymeB T cells (P = 0.030), CD8Perforin T cells (P = 0.000), and CD8IFN-γ T cells (P = 0.002) in CD8T cells were higher in TAK patients compared to control group. After 6 months of treatment, the proportion of CD8T cells in lymphocytes were significantly lower in TAK patients than the baseline assessment (P = 0.033). A lower ratio of CD8GranzymeB T cells/CD8 T cells were showed in TAK patents after treatment compared with TAK patients before treatments (P = 0.011). The change of CD8GranzymeB T cells/CD8 T cells ratio was positively correlated with the change of ITAS (r = 0.721, P = 0.002) and ITAS-A (r = 0.637, P = 0.008). Finally, the immunofluorescence staining showed the infiltration of CD8 Granzyme B cells in the aortic tissue of TAK patients.

Conclusion: Our results disclose that the CD8 T lymphocytes may play a role in TAK pathogenesis. Targeting CD8GranzymeB T lymphocytes or Granzyme B inhibitors could be a potential therapeutic approach for the treatment of TAK. Key Points • Our study investigated role the of CD8 T cell subsets in TAK. • We found the percentages of CD8GranzymeB T cells, CD8Perforin T cells, and CD8IFN-γ T cells in CD3CD8T cells were higher in TAK patients. • The proportion of CD8T cells in lymphocytes and the ratio of CD8GranzymeB T cells/CD8 T cells were significantly lower in TAK patients after treatment.
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http://dx.doi.org/10.1007/s10067-021-05903-4DOI Listing
September 2021

Lycopene Aggravates Acute Gastric Injury Induced by Ethanol.

Front Nutr 2021 17;8:697879. Epub 2021 Aug 17.

Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, China.

Lycopene is an important natural red pigment with strong singlet oxygen and peroxide free radical quenching ability. Ethanol directly destroys the epithelial cells of gastric mucosa, causing oxidative damage and inflammation. To evaluate the effect of lycopene on the ethanol induced gastric injury, 112 adult male Kunming mice were randomly divided into normal control, lycopene control, gastric injury control, omeprazole (20 mg/kg) positive control, and lycopene experimental groups (at doses of 10, 50, 100, and 150 mg/kg body weight) in this study. The general and pathological evaluation, gastric secretion, as well as the levels of antioxidant and inflammatory factors were detected. In lycopene experimental groups, the amount of gastric juice were lower than that in the gastric injury control group; the levels of T-SOD, and the levels of MDA and inflammatory factors (MMP-9 and MCP-1) decreased. However, general and pathological evaluation of gastric tissues revealed that lycopene (especially at high doses) could aggravate acute gastric mucosal injury induced by ethanol. Therefore, lycopene (especially at high doses) aggravates acute gastric mucosal injury caused by ethanol, but this was not due to oxidative stress or inflammatory factors. In lycopene control group, the levels of MTL, T-SOD, and NO increased, but the levels of ALT and AST decreased, indicating that lycopene has a protective effect on the stomach and liver when ethanol wasn't taken. It reminds us that, when alcohol is consumed in large quantities, consumption of lycopene products should be carefully considered.
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http://dx.doi.org/10.3389/fnut.2021.697879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415829PMC
August 2021

Epidemiological and clinical characteristics of the chikungunya outbreak in Ruili City, Yunnan Province, China.

J Med Virol 2021 Aug 28. Epub 2021 Aug 28.

Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.
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http://dx.doi.org/10.1002/jmv.27302DOI Listing
August 2021

Differential effects of viral nucleic acid sensor signaling pathways on testicular Sertoli and Leydig cells.

Endocrinology 2021 Aug 28. Epub 2021 Aug 28.

School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.

The human testis can be infected by a large number of RNA and DNA viruses. While various RNA virus infections may induce orchitis and impair testicular functions, DNA virus infection rarely affects the testis. Mechanisms underlying the differential effects of RNA and DNA viral infections on the testis remain unclear. In the current study, we therefore examined the effects of viral RNA and DNA sensor signaling pathways on mouse Sertoli cells (SC) and Leydig cells (LC). The local injection of viral RNA analogue polyinosinic-polycytidylic acid (poly(I:C)) into the testis markedly disrupted spermatogenesis, whereas the injection of the herpes simplex virus (HSV) DNA analogue HSV60 did not affect spermatogenesis. Poly(I:C) dramatically induced the expression of the pro-inflammatory cytokines TNF-α and IL-6 in SC and LC through Toll-like receptor 3 and IFN-β promoter stimulator 1 signaling pathways, impairing the integrity of the blood-testis barrier and testosterone synthesis. Poly(I:C)-induced TNF-α production thus plays a critical role in the impairment of cell functions. In contrast, HSV60 predominantly induced the expression of type 1 interferons and antiviral proteins via the DNA sensor signaling pathway, which did not affect testicular cell functions. Accordingly, the Zika virus induced high levels of TNF-α in SC and LC and impaired their respective cellular functions, whereas HSV-2 principally induced antiviral responses and did not impair such functions. These results provide insights into the mechanisms by which RNA viral infections impair testicular functions.
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http://dx.doi.org/10.1210/endocr/bqab180DOI Listing
August 2021

CD8 T lymphocyte is a main source of interferon-gamma production in Takayasu's arteritis.

Sci Rep 2021 Aug 24;11(1):17111. Epub 2021 Aug 24.

Department of Rheumatology, Capital Medical University Affiliated Anzhen Hospital, 2 Anzhen Road, Chaoyang District, Beijing, China.

Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu's arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3IFN-γ cells in peripheral blood CD3 cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3CD8IFN-γ cells/CD3IFN-γ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3CD4IFN-γ/ CD3CD8IFN-γ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3CD8IFN-γ/CD3IFN-γ ratio was positively correlated with CD3IFN-γcells/ CD3cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3CD4IFN-γ/CD3IFN-γ ratio (r = - 0.845, P < 0.001). IFN-γ secreted by CD3CD8 T cells is an important source of serum IFN-γ in TAK patients.
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http://dx.doi.org/10.1038/s41598-021-96632-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384861PMC
August 2021

Use of proteomics to identify mechanisms of hepatocellular carcinoma with the CYP2D6*10 polymorphism and identification of ANGPTL6 as a new diagnostic and prognostic biomarker.

J Transl Med 2021 08 19;19(1):359. Epub 2021 Aug 19.

Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, 450052, Henan, China.

Background: Although an association between the cytochrome P4502D6 (CYP2D6) *10 (100C>T) polymorphism and hepatocellular carcinoma (HCC) is known, the mechanism remains unclear. Here we aimed to explore mechanisms of CYP2D6*10 (100C>T) polymorphism conferring to HCC, and screen markers for HCC.

Methods: Label-free global proteome profiling with 34 normal livers and peritumor tissue from 61 HCC patients was performed, and angiopoietin-like protein-6 (ANGPTL6) was evaluated in 2 liver samples validation cohorts and 2 blood specimens validation cohorts.

Results: We found a significantly decreased frequency of TT in HCC patients which reduced HCC susceptibility by 69.2% and was accompanied by lowered enzymatic activity for CYP2D6. Proteomic analysis revealed 1342 differentially expressed proteins (DEPs) that were associated with HCC and 88 DEPs were identified as 100 TT-related proteins, likely underlying the susceptibility to HCC. Twenty-two upregulated DEPs and 66 downregulated DEPs were mainly related to lipid metabolism and the extracellular matrix, respectively. High ANGPTL6 was associated with a higher risk to HCC and worse prognosis. ANGPTL6 was both an independent risk factor and an independent prognostic factor for HCC and exhibited strong potential for predicting HCC occurrence, with comparable AUC values and higher sensitivity compared with alpha-fetoprotein.

Conclusions: The TT genotype-associated decreased risk of HCC appears to be related to lowered CYP2D6 activity and altered protein expression in the tumor microenvironment, and ANGPTL6 is a promising new diagnostic and prognostic biomarker for HCC. Our findings reveal new mechanistic insights for polymorphisms related to HCC risk and provide avenues for screening for HCC.
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http://dx.doi.org/10.1186/s12967-021-03038-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375140PMC
August 2021

Structural characterization of oligosaccharides from free radical depolymerized fucosylated glycosaminoglycan and suggested mechanism of depolymerization.

Carbohydr Polym 2021 Oct 24;270:118368. Epub 2021 Jun 24.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China. Electronic address:

Free radical depolymerization is a common method in structural analysis of polysaccharides, the major challenge is the analysis of the cleavage site and characterization of newly formed ends in this reaction. Here, a fucosylated glycosaminoglycan from H. fuscopunctata (HfFG) was depolymerized by HO and a series of oligosaccharides were purified and their structures were elucidated. For non-reducing ends of the trisaccharides were intact GalNAc, the cleavage site should mainly be the β(1,3) linkages between GlcA and GalNAc in the backbone of FG. Meanwhile, the reducing ends of the disaccharides and trisaccharides were almost dicarboxylic acid derivatives of GlcA, possibly arising from oxidative breaking of the CC bond of GlcA at the reducing ends. In addition, glycosidic linkages in D-GalNAc-β(1,4)-D-GlcA and L-FucS-α(1,3)-D-GlcA located at the reducing end could be cleaved, and the released GalNAc were oxidized to N-acetylgalactosaminic acid.
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http://dx.doi.org/10.1016/j.carbpol.2021.118368DOI Listing
October 2021

A novel p-dimethylaminophenylether-based fluorescent probe for the detection of native ONOO in cells and zebrafish.

Analyst 2021 Sep 2;146(17):5264-5270. Epub 2021 Aug 2.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

Peroxynitrite (ONOO) is a highly reactive substance, and plays an essential part in maintaining cellular homeostasis. It is crucial to monitor the ONOO level in cells in normal and abnormal states. We introduced a p-dimethylaminophenylether-based fluorescent probe PDPE-PN, which could be synthesized readily. The new probe had prominent sensitivity and specificity, and a fast response towards ONOO. The spectral performance of probe PDPE-PN was outstanding and the limit of detection was 69 nM. Probe PDPE-PN with low toxicity was applied to detect endogenous/exogenous ONOO in RAW 264.7 macrophages and zebrafish. Importantly, successful application of the new receptor opens up new ideas for the design of ONOO probes.
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http://dx.doi.org/10.1039/d1an00608hDOI Listing
September 2021

Different Effects of Total Bilirubin on 90-Day Mortality in Hospitalized Patients With Cirrhosis and Advanced Fibrosis: A Quantitative Analysis.

Front Med (Lausanne) 2021 23;8:704452. Epub 2021 Jun 23.

Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China.

Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the "TB-mortality correlation curves." The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.
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http://dx.doi.org/10.3389/fmed.2021.704452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260970PMC
June 2021

Five distinct fucan sulfates from sea cucumber Pattalus mollis: Purification, structural characterization and anticoagulant activities.

Int J Biol Macromol 2021 Sep 9;186:535-543. Epub 2021 Jul 9.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

Fucan sulfates from echinoderm possess characteristic structures and various biological activities. Herein, comprehensive methods including enzymolysis, ion-exchange chromatography and size exclusion chromatography lead to the purification of five fucan sulfates (FSI, FSII, FSIII, FSIV, FSV) from the sea cucumber Pattalus mollis. Chemical composition analysis showed that they were all composed of l-fucose. Their sulfate content was determined by a conductimetric method. The molecular weight (Mw) of FSI, FSII, FSIII, FSIV and FSV were measured as 238.3 kDa, 81.0 kDa, 82.0 kDa, 23.2 kDa and 6.12 kDa, respectively. Detailed NMR spectroscopic analysis revealed that the structural sequence of FSI and FSII was →3)-l-Fuc-α(1→, where Fuc were Fuc (10%), Fuc (44%), Fuc (10%), Fuc (36%), that of FSIII was →4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1→, where Fuc and Fuc were in equal molar, and that FSIV was →4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1→4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → 4)-l-Fuc-(α1 → . This is the first report that such a diversity of fucan sulfates were obtained from the same sea cucumber species. Biological activity showed that FSI, FSII, FSIII and FSIV exhibited potent anticoagulant by prolonging the APTT. Among them, FSII, FSIII and FSIV showed the similar potency, while FSI owned the strongest. Structure-activity relationships analysis showed that molecular weight and sulfation degree should be the crucial factors for the activity.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.049DOI Listing
September 2021

Enzyme-triggered DNA nanomimosa: A ratiometric nanoprobe for RNase H activity sensing in living cells.

Talanta 2021 Oct 24;233:122547. Epub 2021 May 24.

Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, PR China. Electronic address:

Since ribonuclease H (RNase H) exhibits its importance in a variety of cellular processes. It is necessary to establish strategy for RNase H detection. In this work, we are enlightened by mimosa, a natural plant which can fold in response to stimuli, to construct a DNA tetrahedron-based nanoprobe, termed DNA nanomimosa, to sensing RNase H activity based on fluorescent resonance energy transfer (FRET). The DNA nanomimosa was self-assembled from four DNA chains and one RNA chain. One of the four DNA chains contains a FRET-paired fluorophores-labeled hairpin DNA structures which is unfolded by the RNA chain through hybridization. Without RNase H, the RNA chain separate the two FRET-paired fluorophores in hairpin DNA structure, giving a feeble FRET signal. However, the presence of RNase H can selectively digest the RNA strand in RNA/unfolded-hairpin DNA section, resulting in the hairpin DNA configuration changed from "unfolded" state to "folded" state and further turn on the FRET signal. The DNA nanomimosa can be applied to achieve the determination of RNase H activity by recording the emission intensity of donor and acceptor fluorophores. This strategy shows a low detection limit by 0.017 U/mL, good specificity, and distinct advantages like the self-delivery ability, good biocompatibility, and the capacity to minimize the effects of fluctuations. This design provides a potential application in ribonuclease research and could be expanded for other biomedical research and clinical diagnostics.
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http://dx.doi.org/10.1016/j.talanta.2021.122547DOI Listing
October 2021

Polydopamine nanodots-based cost-effective nanoprobe for glucose detection and intracellular imaging.

Anal Bioanal Chem 2021 Aug 25;413(19):4865-4872. Epub 2021 Jun 25.

Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, People's Republic of China.

The cellular glucose detection remains a vital topic, which could provide some essential information about the glucose-based pathological and physiological processes. In this study, a smart polydopamine nanodots-based cost-effective fluorescence turn-on nanoprobe (denoted as PDA-Ag-GOx) for intracellular glucose detection is established. Silver nanoparticles (AgNPs) are directly formed in one step by the reduction of fluorescent polydopamine nanodots (PDADs) which have much phenolic hydroxyls on the surface. The fluorescence of PDADs could be quenched by AgNPs through surface plasmon-enhanced energy transfer (SPEET) from donor PDADs to acceptor AgNPs. Glucose oxidase (GOx) is modified on the PDA-Ag NPs by covalent bond. In the presence of glucose, GOx could catalyze glucose to produce HO and gluconic acid. The generated acid and HO would degrade AgNPs into Ag, the PDADs release and restore its fluorescence. The proposed nanoprobe has some advantages, such as cost-effective, easy preparation, and excellent selectivity toward glucose, which could be successfully utilized to intracellular glucose imaging.
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http://dx.doi.org/10.1007/s00216-021-03447-9DOI Listing
August 2021

Multiple fields manipulation on nitride material structures in ultraviolet light-emitting diodes.

Light Sci Appl 2021 16;10:129. Epub 2021 Jun 16.

Engineering Research Center of Micro-nano Optoelectronic Materials and Devices, Ministry of Education, Fujian Key Laboratory of Semiconductor Materials and Applications, CI center for OSED, College of Physical Science and Technology, Xiamen University, 361005 Xiamen, China.

As demonstrated during the COVID-19 pandemic, advanced deep ultraviolet (DUV) light sources (200-280 nm), such as AlGaN-based light-emitting diodes (LEDs) show excellence in preventing virus transmission, which further reveals their wide applications from biological, environmental, industrial to medical. However, the relatively low external quantum efficiencies (mostly lower than 10%) strongly restrict their wider or even potential applications, which have been known related to the intrinsic properties of high Al-content AlGaN semiconductor materials and especially their quantum structures. Here, we review recent progress in the development of novel concepts and techniques in AlGaN-based LEDs and summarize the multiple physical fields as a toolkit for effectively controlling and tailoring the crucial properties of nitride quantum structures. In addition, we describe the key challenges for further increasing the efficiency of DUV LEDs and provide an outlook for future developments.
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http://dx.doi.org/10.1038/s41377-021-00563-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206881PMC
June 2021

Multiple fields manipulation on nitride material structures in ultraviolet light-emitting diodes.

Light Sci Appl 2021 Jun 16;10(1):129. Epub 2021 Jun 16.

Engineering Research Center of Micro-nano Optoelectronic Materials and Devices, Ministry of Education, Fujian Key Laboratory of Semiconductor Materials and Applications, CI center for OSED, College of Physical Science and Technology, Xiamen University, 361005, Xiamen, China.

As demonstrated during the COVID-19 pandemic, advanced deep ultraviolet (DUV) light sources (200-280 nm), such as AlGaN-based light-emitting diodes (LEDs) show excellence in preventing virus transmission, which further reveals their wide applications from biological, environmental, industrial to medical. However, the relatively low external quantum efficiencies (mostly lower than 10%) strongly restrict their wider or even potential applications, which have been known related to the intrinsic properties of high Al-content AlGaN semiconductor materials and especially their quantum structures. Here, we review recent progress in the development of novel concepts and techniques in AlGaN-based LEDs and summarize the multiple physical fields as a toolkit for effectively controlling and tailoring the crucial properties of nitride quantum structures. In addition, we describe the key challenges for further increasing the efficiency of DUV LEDs and provide an outlook for future developments.
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http://dx.doi.org/10.1038/s41377-021-00563-0DOI Listing
June 2021

Consistent Alterations of Human Fecal Microbes after Transplantation into Germ-free Mice.

Genomics Proteomics Bioinformatics 2021 Jun 9. Epub 2021 Jun 9.

MOE Key Laboratory of Molecular Biophysics, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; College of Life Science, Henan Normal University, Xinxiang 453007, China. Electronic address:

Fecal microbiota transplantation (FMT) of human fecal samples into germ-free (GF) mice is useful for establishing causal relationships between the gut microbiota and human phenotypes. However, due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms, it may not be possible to replicate human phenotypes in mice through FMT; similarly, treatments that are effective in mouse models may not be effective in humans. In this study, we aimed to identify human gut microbes that undergo significant and consistent changes (i.e., in relative abundances) after transplantation into GF mice in multiple experimental settings. We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human-mouse pairs. Strikingly, on average, we found that only 47% of the human gut microbes could be re-established in mice at the species level, among which more than 1/3 underwent significant changes (referred to as "variable taxa"). Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimental settings. Consequently, about 1/3 of human samples changed their enterotypes, i.e., significant changes in their leading species after FMT. Mice fed with a controlled diet showed a lower enterotype change rate (23.5%) than those fed with a noncontrolled diet (49.0%), suggesting a possible solution for rescue. Most of the variable taxa have been reported to be implicated in human diseases, with some recognized as the causative species. Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes, provide useful information for researchers using mice in gut microbiota studies, and call for additional validations after FMT. An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.
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http://dx.doi.org/10.1016/j.gpb.2020.06.024DOI Listing
June 2021

Angiotensin II induces cognitive decline and anxiety-like behavior via disturbing pattern of theta-gamma oscillations.

Brain Res Bull 2021 Sep 6;174:84-91. Epub 2021 Jun 6.

College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, 300071, Tianjin, PR China. Electronic address:

Hypertension is the most common chronic disease accompanied by cognitive decline and anxiety-like behavior. Angiotensin II (Ang II) induces hypertension by activating angiotensin II receptor subtype 1 (AT1R). The purpose of the study was to examine the potential underlying mechanism of alterations in cognition and anxiety-like behavior induced by Ang II. Adult C57 mice were intraperitoneal injected with either 1 mg/kg/d Ang II or saline individually for 14 consecutive days. Ang II resulted in cognitive decline and anxious like behavior in C57 mice. Moreover, Ang II disturbed bidirectional synaptic plasticity and neural oscillation coupling between high theta and gamma on PP (perforant pathway)-DG (dentate gyrus) pathway. In addition, Ang II decreased the expression of N-methyl-d-aspartate receptor (NR) 2A and NR 2B and increased the expression of GABAR α1. The data suggest that Ang II disturb neural oscillations via altering excitatory and inhibitory (E/I) balance and eventually damage cognition and anxiety-like behavior in mice.
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http://dx.doi.org/10.1016/j.brainresbull.2021.06.002DOI Listing
September 2021

Continuous flooding stimulates root iron plaque formation and reduces chromium accumulation in rice (Oryza sativa L.).

Sci Total Environ 2021 Sep 17;788:147786. Epub 2021 May 17.

Key Laboratory of Information Traceability for Agricultural Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.

Chromium (Cr) contamination in rice poses a serious threat to human health. Therefore, we conducted pot experiments to investigate the influence of water management regimes on the formation of iron plaque on rice roots, and its effect on the accumulation and translocation of Cr in rice grown on contaminated soil. The results showed that water management regimes, including continuous and intermittent flooding, exerted notable effects on soil solution concentrations of Cr(VI) and Cr(III) through changes in redox potential, pH, and dissolved Fe(II) concentrations. In particular, 69.2%-71.8% of Cr(VI) was reduced to Cr(III) under continuous flooding, whereas only 33.3%-38.6% was reduced under intermittent flooding conditions. Additionally, continuous flooding created a rhizosphere environment favorable to the formation of iron plaque. The amount of iron plaque formed increased by 28.2%-47.2% under continuous flooding conditions as compared with that under intermittent flooding conditions. Moreover, compared with intermittent flooding, under continuous flooding, more Cr (18.0%-23.9%) was adsorbed in the iron plaque, thereby sequestering Cr and reducing its mobility. The Cr concentrations in rice root, straw, husk, and grain under continuous flooding conditions were, respectively, 32.0%-36.5%, 32.7%-36.3%, 34.2%-46.9%, and 25.4%-37.7% lower than those under intermittent flooding conditions. Therefore, continuous flooding caused a substantial decrease in the Cr concentrations in rice tissues, as well as an increased distribution of Cr in the iron plaque that acted as a barrier to reduce Cr transfer to the rice roots. These results indicate that continuous flooding irrigation was effective in minimizing the accumulation of Cr in rice plants, as it not only enhanced Cr(VI) reduction in the soil but also improved the blocking capacity of the iron plaque.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147786DOI Listing
September 2021

Emerging Role of Exosomes in Liquid Biopsy for Monitoring Prostate Cancer Invasion and Metastasis.

Front Cell Dev Biol 2021 4;9:679527. Epub 2021 May 4.

Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China.

Prostate cancer (PCa) is the most common solid tumor in men. While patients with local PCa have better prognostic survival, patients with metastatic PCa have relatively high mortality rates. Existing diagnostic methods for PCa rely on tissue biopsy and blood prostate-specific antigen (PSA) detection; however, the PSA test does not detect aggressive PCa. Liquid biopsy is a promising technique to overcome tumor heterogeneity in diagnosis, provide more comprehensive information, and track tumor progression over time, allowing for the development of treatment options at all stages of PCa. Exosomes containing proteins and nucleic acids are potential sources of tumor biomarkers. Accumulating evidence indicates that exosomes play important roles in cell communication and tumor progression and are suitable for monitoring PCa progression and metastasis. In this review, we summarize recent advances in the use of exosomal proteins and miRNAs as biomarkers for monitoring PCa invasion and metastasis and discuss their feasibility in clinical diagnosis.
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http://dx.doi.org/10.3389/fcell.2021.679527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129505PMC
May 2021

Infant rhesus macaques as a non-human primate model of Bordetella pertussis infection.

BMC Infect Dis 2021 May 3;21(1):407. Epub 2021 May 3.

Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, 650118, Yunnan, China.

Background: The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s-1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved.

Methods: In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis.

Results: Upon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p.

Conclusion: These results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.
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http://dx.doi.org/10.1186/s12879-021-06090-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091708PMC
May 2021

A dual-functional biomimetic-mineralized nanoplatform for glucose detection and therapy with cancer cells .

J Mater Chem B 2021 05;9(18):3885-3891

Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering. Beijing Institute of Technology, Beijing, 100081, P. R. China.

Glucose detection is a crucial topic in the diagnosis of numerous diseases, such as hypoglycemia or diabetes mellitus. Research indicates that people with diabetes mellitus are at a higher risk of developing various types of cancer. A nanoplatform that combines both diabetes diagnosis and cancer therapy might be regarded as a more effective way to solve the above-mentioned problem. However, none of the known sensors has a smart strategy that can work as a fluorescent glucose sensor and a cancer therapeutic platform simultaneously. Here, we developed a pH responsive biomimetic-mineralized nanoplatform (denoted as [email protected]) for glucose detection in serum samples and applied it to treat the tumor cells combined chemotherapy with the starvation therapy in vitro. Doxorubicin (DOX) and glucose oxidase (GOx) were loaded through the mesoporous CaCO3-PDA nanoparticles (m-CaCO3-PDA NPs). The fluorescence of DOX is quenched as a result of fluorescence resonance energy transfer (FRET) caused by the broad absorption of m-CaCO3-PDA NPs. The nanoplatform would recover fluorescence under lower pH values due to the catalytic reaction of GOx with glucose or tumor microenvironment (TME), which leads to the elimination of FRET. Its application as a glucose sensor is indicated with a linear relationship in the range of 0.01-1.0 mM of glucose and limit of detection is calculated by 6 μM. This nanoplatform also has a TME-responsive antitumor effect and fluorescence imaging functionality, which provide a new idea for cancer therapy together with glucose monitoring in diabetes.
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http://dx.doi.org/10.1039/d1tb00324kDOI Listing
May 2021

Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from , a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods.

Mar Drugs 2021 Apr 11;19(4). Epub 2021 Apr 11.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber . As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration () was at about 1 h, and the peak concentration () was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life() was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.
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http://dx.doi.org/10.3390/md19040212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069088PMC
April 2021

Clinical features and prognostic factors of pediatric idiopathic sudden hearing loss from moderate to profound degree.

Am J Otolaryngol 2021 Sep-Oct;42(5):103027. Epub 2021 Apr 16.

ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200031, China. Electronic address:

Background: The pediatric idiopathic sudden sensorineural hearing loss (PISSNHL) is not rare in the clinics, however, the prognostic factors of PISSNHL are still unclear.

Objectives: To investigate the clinical and audiologic characteristics associated with prognosis in PISSNHL.

Material And Methods: Clinical and audiological characteristics and possible prognostic factors were retrospectively evaluated in 76 PISSNHL patients aged less than 19 years.

Results: Hearing loss was moderate in nine patients, severe in 21 patients, profound in 46 patients. Among five types of audiogram, 3.9% were classified as ascending, 11.8% as descending, 25.0% as flat, 55.3% as profound, and 3.9% as concave. The recovery rate according to Siegel's criteria was 55.3%. There was no significant difference between the recovery group and the poor recovery group in terms of age, sex, laterality of hearing loss, the onset of treatment, and accompanying symptoms (p > 0.05). The initial hearing levels and the audiogram type were significantly different in the two groups (p < 0.001) according to univariate analysis, while only the initial hearing level was significantly different (p = 0.046) according to multivariate analysis.

Conclusions And Significance: Prognosis of PISSNHL was mainly related to initial hearing at onset. An initial hearing level greater than 80 dB was a poor prognostic factor.
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http://dx.doi.org/10.1016/j.amjoto.2021.103027DOI Listing
April 2021

Structural Characterization and Heparanase Inhibitory Activity of Fucosylated Glycosaminoglycan from .

Mar Drugs 2021 Mar 18;19(3). Epub 2021 Mar 18.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.

Unique fucosylated glycosaminoglycans (FG) have attracted increasing attention for various bioactivities. However, the precise structures of FGs usually vary in a species-specific manner. In this study, HfFG was isolated from and purified by anion exchange chromatography with the yield of ~0.9%. HfFG was composed of GlcA, GalNAc and Fuc, its molecular weight was 47.3 kDa, and the -OSO/-COO molar ratio was 3.756. HfFG was depolymerized by a partial deacetylation-deaminative cleavage method to obtain the low-molecular-weight HfFG (dHfFG). Three oligosaccharide fragments (Fr-1, Fr-2, Fr-3) with different molecular weights were isolated from the dHfFG, and their structures were revealed by 1D and 2D NMR spectroscopy. HfFG should be composed of repeating trisaccharide units -{(L-FucS-α1,3-)d-GlcA-β1,3-d-GalNAc-β1,4-}-, in which sulfated fucose (FucS) includes Fuc, Fuc and Fuc residues linked to O-3 of GlcA in a ratio of 45:35:20. Furthermore, the heparanase inhibitory activities of native HfFG and oligosaccharide fragments (Fr-1, Fr-2, Fr-3) were evaluated. The native HfFG and its oligosaccharides exhibited heparanase inhibitory activities, and the activities increased with the increase of molecular weight. Additionally, structural characteristics such as sulfation patterns, the terminal structure of oligosaccharides and the presence of fucosyl branches may be important factors affecting heparanase inhibiting activity.
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http://dx.doi.org/10.3390/md19030162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003118PMC
March 2021

Selection for Cheaper Amino Acids Drives Nucleotide Usage at the Start of Translation in Eukaryotic Genes.

Genomics Proteomics Bioinformatics 2021 Mar 16. Epub 2021 Mar 16.

Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address:

Coding regions have complex interaction among multiple selective forces, which are manifested as biases in nucleotide composition. Previous studies have revealed a decreasing GC gradient from the 5'- to 3'- ends of coding regions in various organisms. We confirmed that this gradient is universal in eukaryotic genes but the decrease only starts from the ∼25 codon. This trend is mostly found in nonsynonymous (ns) sites at which the GC gradient is universal across the eukaryotic genome. Increased GC contents at ns sites result in cheaper amino acids, indicating universal selection for energy efficiency toward the N-terminus of encoded proteins. Within a genome, the decreasing GC gradient intensifies from lowly- to highly-expressed genes (more and more protein products), further supporting this hypothesis. This reveals a conserved selective constraint for cheaper amino acids at the translation start that drives the increased GC contents at ns sites. Elevated GC contents can facilitate transcription but result in a more stable local secondary structure around the start codon and subsequently impede translation initiation. Conversely, the GC gradient at fourfold- and twofold- synonymous sites varied across species. They could decrease or increase, suggesting different constraints acting at the GC contents of different codon sites in different species. This study reveals that the overall GC contents at the translation start are consequences of complex interactions among several major biological processes that shaped the nucleotide sequences, especially efficient energy usage.
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http://dx.doi.org/10.1016/j.gpb.2021.03.002DOI Listing
March 2021

Development and validation of nomograms for predicting blood loss in placenta previa with placenta increta or percreta.

Ann Transl Med 2021 Feb;9(4):287

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.

Background: To develop the risk prediction model of intraoperative massive blood loss in placenta previa with placenta increta or percreta.

Methods: This study included 260 patients, of whom 179 were allocated to the development group and 81 to the validation group. Univariate and multivariate logistic regression analyses were used to identify characteristics that were associated with massive blood loss (≥2,500 mL) during cesarean section. A nomogram was constructed based on regression coefficients. Receiver-operating characteristic curve, calibration curve, and decision curve analyses were applied to assess the discrimination, calibration, and performance of the model.

Results: Two models were constructed. The preoperative feature model (model A) consisted of vascular lacunae within the placenta and hypervascularity of the uterine-placental margin, uterine serosa-bladder wall interface, and cervix. The preoperative and surgical feature model (model B) consisted of an emergency cesarean section, no preoperative balloon placement of the abdominal aorta, and the previously mentioned four ultrasound signs. Model B had better discrimination than model A (area under the curve: development group: 0.839 0.732; validation group: 0.829 0.736). Model B showed a higher area under the decision curve than model A in both the training and validation groups.

Conclusions: The preoperative and surgical feature model for placenta previa with placenta increta or percreta can improve the early identification and management of patients who are at high risk of intraoperative massive blood loss.
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http://dx.doi.org/10.21037/atm-20-5160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944278PMC
February 2021

Oligosaccharides from fucosylated glycosaminoglycan prevent breast cancer metastasis in mice by inhibiting heparanase activity and angiogenesis.

Pharmacol Res 2021 04 2;166:105527. Epub 2021 Mar 2.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

The invasion and metastasis of tumor cells are the hallmarks of malignant diseases and the greatest obstacle to overcome. Heparanase-mediated degradation of heparan sulfate (HS) is the critical process for tumor angiogenesis and metastasis, therefore, heparanase become an attractive target for cancer research. Herein, we reported a native fucosylated glycosaminoglycan (nHG) extracted from sea cucumber Holothuria fuscopunctata and a depolymerized nHG (dHG) and its contained oligosaccharides (hs17, hs14, hs11, hs8 and hs5), acting as heparanase inhibitors. nHG and its derivatives have the ability to bind with heparanase directly, leading to significant inhibition of heparanase activity. Moreover, their apparent binding affinity to heparanase was comparable to their inhibitory effect, which was elevated along with the increase of chain length, similar to the effect of heparins. In addition, oligosaccharides inhibited the migration and invasion of 4T1 mammary carcinoma cells and human umbilical vein endothelial cells (HUVECs) and also suppressed tube formation in Matrigel matrix and angiogenesis in the chick chorioallantoic membrane (CAM) assay. In the metastatic mouse model, oligosaccharides exhibited practical antimetastatic effects on 4T1 mammary carcinoma cells. According to the reported anticoagulant activity and the low bleeding tendency of dHG and its oligosaccharides, the use of the oligosaccharides may lead to better effects on tumor patients with thrombosis tendency.
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http://dx.doi.org/10.1016/j.phrs.2021.105527DOI Listing
April 2021

Zika virus disrupts the barrier structure and Absorption/Secretion functions of the epididymis in mice.

PLoS Negl Trop Dis 2021 03 5;15(3):e0009211. Epub 2021 Mar 5.

Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Several studies have demonstrated that Zika virus (ZIKV) damages testis and leads to infertility in mice; however, the infection in the epididymis, another important organ of male reproductive health, has gained less attention. Previously, we detected lesions in the epididymis in interferon type I and II receptor knockout male mice during ZIKV infection. Herein, the pathogenesis of ZIKV in the epididymis was further assessed in the infected mice after footpad inoculation. ZIKV efficiently replicated in the epididymis, and principal cells were susceptible to ZIKV. ZIKV infection disrupted the histomorphology of the epididymis, and the effects were characterized by a decrease in the thickness of the epithelial layer and an increase in the luminal diameter, especially at the proximal end. Significant inflammatory cell infiltration was observed in the epididymis accompanied by an increase in the levels of interleukin (IL)-6 and IL-28. The expression of tight junction proteins was downregulated and associated with disordered arrangement of the junctions. Importantly, the expression levels of aquaporin 1 and lipocalin 8, indicators of the absorption and secretion functions of the epididymis, were markedly reduced, and the proteins were redistributed. These events synergistically altered the microenvironment for sperm maturation, disturbed sperm transport downstream, and may impact male reproductive health. Overall, these results provide new insights into the pathogenesis of the male reproductive damage caused by ZIKV infection and the possible contribution of epididymal injury into this process. Therefore, male fertility of the population in areas of ZIKV epidemic requires additional attention.
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http://dx.doi.org/10.1371/journal.pntd.0009211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968736PMC
March 2021

Protoplast fusion between Blakeslea trispora 14,271 (+) and 14,272 (-) enhanced the yield of lycopene and β-carotene.

World J Microbiol Biotechnol 2021 Mar 2;37(4):58. Epub 2021 Mar 2.

Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, 272067, China.

Blakeslea trispora, a heterothallic Zygomycota with two mating types (termed "plus" and "minus"), is an ideal source of lycopene and β-carotene. The lycopene and β-carotene yields when the two type strains are used for fermentation separately are lower than those when they are joint together. To enhance the yield of lycopene and β-carotene in B. trispora, protoplast fusion technology was carried out between ATCC 14,271 (+) and ATCC 14,272 (-). After protoplast preparation, protoplast fusion, fusion sorting, fusion regeneration, and high-throughput screening, two fusions (Fu-1and Fu-2) with high lycopene and β-carotene yields were obtained. The lycopene yields of Fu-1 and Fu-2 were increased to 0.60 mg/gDW and 0.90 mg/gDW, which were respectively 3.62- and 5.44-fold those of 14,271 and 1.76- and 2.64-fold those of 14,272. The β-carotene yields of Fu-1 and Fu-2 were increased to 22.07 mg/gDW and 36.93 mg/gDW, which were respectively 1.72- and 2.89-fold those of 14,271 and 1.23- and 2.06-fold those of 14,272. In this study, the protoplast fusion technique was successfully used in Blakeslea trispora, providing new ideas for improving lycopene and β-carotene production.
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http://dx.doi.org/10.1007/s11274-021-03023-4DOI Listing
March 2021
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