Publications by authors named "Huiwen Zhang"

172 Publications

One-step colorimetric detection of Staphylococcus aureus based on target-induced shielding against the peroxidase mimicking activity of aptamer-functionalized gold-coated iron oxide nanocomposites.

Talanta 2021 Sep 1;232:122448. Epub 2021 May 1.

School of Public Health, Jilin University, Changchun, 130021, China. Electronic address:

Staphylococcus aureus (S. aureus) is one of the most threatened food-borne pathogens. Thus, it is necessary to establish fast, portable and reliable tools to realize the identification of S. aureus. Herein, the authors describe an effective colorimetric-based biosensor for the detection of S. aureus in multiple types of samples. Initially, a nanozyme composed of gold and iron oxide nanoparticles was synthesized and further modified with S. aureus-specific aptamer via Au-S bond. By utilizing the intrinsic peroxidase-like activity of the above magnetic conjugates, 3,3',5,5'-tetramethylbenzidine (TMB) can be transferred to oxTMB by oxidation of hydrogen peroxide (HO), resulting in a visible blue color. However, the introduction of S. aureus can turn off the UV-vis absorbance signals of TMB-HO system, due to the identification property of the nanozyme probe. Consequently, the optical density of the mixed solution measured at 652 nm decreased linearly as the concentration of S. aureus increased from 10 to 10 CFU mL, with the visible limit of detection as low as 10 CFU mL. The as-prepared sensor can detect S. aureus in spiked water, milk and urine samples quantitatively during 12 min without any pre-enrichment, separation or washing steps. In our perception, the one-step colorimetric assay show promise in practical on-site detection of S. aureus.
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http://dx.doi.org/10.1016/j.talanta.2021.122448DOI Listing
September 2021

Evaluation of anticancer effects in vitro of new iridium(III) complexes targeting the mitochondria.

J Inorg Biochem 2021 Aug 11;221:111465. Epub 2021 May 11.

School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address:

Iridium(III) complexes have the potential to serve as novel therapeutic drugs for treating tumor. In this work, three new complexes [Ir(ppy)(cdppz)](PF) (1) (ppy = 2-phenylpyridine, cdppz = 11-chlorodipyrido[3,2-a,2',3'-c]phenazine), [Ir(bzq)(cdppz)](PF) (2) (bzq = benzo[h]quinolone) and [Ir(piq)(cdppz)](PF) (3) (piq = 1-phenylisoquinoline) were prepared as well as characterized. MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide) assay revealed that the complex 2 exerted potent cytotoxicity against to various cancer cells lines and particularly for SGC-7901 cells. Meanwhile, the complexes could suppress cell colonies formation and migration ability. Apoptosis assays of AO/EB staining as well as flow cytometry revealed that the synthesized complexes may cause apoptosis of SGC-7901 cells. Moreover, the decline of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS) levels and release of cytochrome c demonstrated the complexes could cause apoptosis mainly through the mitochondrial death pathway and arrest cell at G0/G1 phase. Additionally, the complexes have significant influence on the expression of proteins which is interrelated to cell apoptosis. In summary, our studies provided fundamental information regarding the further study of the possible anticancer mechanisms of iridium (III) complexes.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111465DOI Listing
August 2021

An efficient strategy for cancer therapy using a tumor- and lysosome-targeted organic photothermal agent.

Nanoscale 2021 May;13(19):8790-8794

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Centre of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan, 250014, P. R. China.

A dual-targeted organic photothermal agent for tumor cells and lysosomes was developed. In vitro and in vivo experiments demonstrated that it possessed low cytotoxicity, good biological compatibility, and tumor inhibitory effects.
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http://dx.doi.org/10.1039/d1nr01547hDOI Listing
May 2021

An enzyme nanopocket based on covalent organic frameworks for long-term starvation therapy and enhanced photodynamic therapy of cancer.

Chem Commun (Camb) 2021 Jun;57(44):5402-5405

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

An enzyme nanopocket constructed from a porphyrin-based covalent organic framework (COF) was developed to co-load glucose oxidase (GOx) and catalase (CAT) for long-term starvation therapy and enhanced photodynamic therapy (PDT).
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http://dx.doi.org/10.1039/d0cc07544bDOI Listing
June 2021

Rapid detection of twenty-nine common Chinese glucose-6-phosphate dehydrogenase variants using a matrix-assisted laser desorption/ionization-time of flight mass spectrometry assay on dried blood spots.

Clin Biochem 2021 Apr 18. Epub 2021 Apr 18.

Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address:

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited disease. Current neonatal screening methods for G6PD deficiency primarily rely on the use of biochemical tests. However, only 15%-20% of female carriers were estimated to have been detected using these tests. As a better alternative, DNA-based tests could be used for G6PD deficiency screening. We aimed to develop a matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay for G6PD variant detection.

Methods: A MALDI-TOF MS assay with multiprimer extension (multi-PEX) was developed to rapidly and accurately detect the 29 common G6PD variants in the Chinese population using a dried blood spot as a template. A parallel study screening 571 unrelated neonatal samples using the MALDI-TOF MS and fluorescence quantitative enzymatic assays was performed. All results were confirmed by Sanger sequencing in a blind study.

Results: In 571 unrelated neonatal samples, 34 positive samples, including 26 samples from hemizygous males and eight samples from heterozygous females, were correctly identified, yielding a clinical sensitivity of 100%. The results were validated using Sanger sequencing with 100% concordance. In contrast, the fluorescence quantitative enzymatic assay had a 75% false negative and 88.8% false positive rate for the detection of heterozygous G6PD deficient females.

Conclusions: We established a reliable MALDI-TOF MS assay for G6PD deficiency screening in the Chinese population maximizing the chance of detection of heterozygous G6PD deficient females and reducing the false negative and false positive rates associated with routinely used newborn screening procedures.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.04.012DOI Listing
April 2021

A dual-catalytic nanoreactor for synergistic chemodynamic-starvation therapy toward tumor metastasis suppression.

Biomater Sci 2021 May;9(10):3814-3820

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

Tumor metastasis is extremely deadly for cancer patients and developing effective treatments for deep metastatic tumors remains a major challenge. In this study, we demonstrated a dual-catalytic nanoreactor for tumor metastasis suppression by synergistic Fenton reaction activated chemodynamic therapy (CDT) and glucose oxidase (GOx) initiated starvation therapy. GOx on the surface of hollow mesoporous silica nanoparticles can catalyze the decomposition of intratumoral glucose to generate gluconic acid and H2O2, while Fe3O4 nanoparticles as a Fenton reaction catalyst can in situ catalyze H2O2 to produce highly toxic hydroxyl radicals (˙OH). The oxygen-carrying perfluorohexane (PFC) in the hole of the hollow structures can alleviate the hypoxic environment and promote dual-catalytic reactions. After being disguised by the cancer cell membrane, the delivery efficiency and biological safety of the nanoreactor were effectively improved. The nanoreactor can realize sequential glucose depletion and ˙OH aggregation, which effectively suppress tumor metastasis with negligible side effects.
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http://dx.doi.org/10.1039/d1bm00240fDOI Listing
May 2021

Embedding FeC and FeN on a Nitrogen-Doped Carbon Nanotube as a Catalytic and Anchoring Center for a High-Areal-Capacity Li-S Battery.

ACS Appl Mater Interfaces 2021 May 20;13(17):20153-20161. Epub 2021 Apr 20.

School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, P. R. China.

The biggest obstacles of putting lithium-sulfur batteries into practice are the sluggish redox kinetics of polysulfides and serious "shuttle effect" under high sulfur mass loading and lean-electrolyte conditions. Herein, FeC/[email protected] carbon nanotubes (NCNTs) as multifunctional sulfur hosts are designed to realize high-areal-capacity Li-S batteries. The FeN and FeC particles attached to NCNT can promote the conversion of polysulfides. Besides, NCNT can not only enhance the chemisorption of polysulfides but also increase the special surface area and electrical conductivity by constructing a three-dimensional skeleton network. Integrating the merits of high electrical conductivity, high catalytic activity, and strong chemical binding interaction with lithium polysulfides (LiPSs) to achieve in situ anchoring conversion, the FeC/[email protected] multifunctional hosts realize high sulfur mass loading and accelerate redox kinetics. The novel FeC/[email protected]/S composite cathode exhibits steady cycle ability and a high areal capacity of 9.10 mAh cm with a sulfur loading of 13.12 mg cm at 2.20 mA cm after 50 cycles.
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http://dx.doi.org/10.1021/acsami.1c03358DOI Listing
May 2021

Clinical, Biochemical, and Molecular Analyses of Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients.

Front Genet 2021 23;12:577046. Epub 2021 Mar 23.

Department of Pediatric Endocrinology/Genetics, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare inherited metabolic disorder of fatty acid β-oxidation. The present study aimed to evaluate clinical and biochemical manifestations, and the mutation spectrum of this disorder in a large cohort of Chinese patients.

Methods: A total of 24 patients were enrolled, and blood acylcarnitine and urinary organic acid levels were measured by tandem mass spectrometry and gas chromatography-mass spectrometry (GC-MS), respectively. Mutations in the gene were detected by Sanger or next-generation sequencing. Clinical progression, acylcarnitine spectra, and mutations were analyzed and described in detail.

Results: Among the 24 patients, six cases were diagnosed because of disease onset with symptoms such as vomiting, diarrhea, convulsion, and hypoglycemia; 18 patients without symptoms were diagnosed by newborn screening (NBS). All patients who accepted treatment after diagnosis developed normal intelligence and physique. The concentrations of octanoylcarnitine, the octanoylcarnitine/decanoylcarnitine ratio, and the octanoylcarnitine/acetylcarnitine ratio in the blood and urinary dicarboxylic acid concentrations were consistently elevated. Blood biomarkers failed to decrease after treatment. DNA sequencing revealed seven known and 17 novel mutations in the gene of patients. Mutation p.T150Rfs4 was most frequent, followed by p.R31C, p.F103Y, p.I223T, p.G362E, and c.387+1delG.

Conclusion: Despite biochemical abnormalities, medium-chain acyl-CoA dehydrogenase deficiency showed relatively mild clinical phenotypes with low mortality and optimistic prognoses in China. NBS is crucial for early diagnosis, treatment, and prognosis.
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http://dx.doi.org/10.3389/fgene.2021.577046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025081PMC
March 2021

Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type.

Orphanet J Rare Dis 2021 03 10;16(1):125. Epub 2021 Mar 10.

Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China.

Background: Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center.

Methods: 248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Prenatal data of Hcy levels determined by enzymatic cycling assay, acylcarnitine analysis using liquid chromatography tandem mass spectrometry, organic acid analysis using gas chromatography mass spectrometry, and genetic analysis by direct sequencing of 248 at-risk fetuses were retrospectively reviewed.

Results: For 2.0 and 16.0 μmol/L levels of Hcy AF samples, the relative errors were - 2.5% and 2.8%, respectively. The respective measurement uncertainties were 13.07% and 14.20%. For the 248 at-risk fetuses, 63 fetuses were affected and 185 fetuses were unaffected. Hcy level of 13.20 (6.62-43.30) μmol/L in 63 affected fetuses was significantly higher than that in 185 unaffected fetuses of 2.70 (0.00-5.80) μmol/L, and there was no overlap between the affected and unaffected groups. The diagnostic sensitivity and specificity of Hcy were 100% and 92.05%, respectively. The positive and negative predictive values of the combination of Hcy, propionylcarnitine (C3), ratio of C3 to acetylcarnitine (C2; C3/C2), methylmalonic acid (MMA), and methylcitric acid (MCA) were both 100%. Sixteen fetuses displayed inconclusive genetic results of MMACHC variants, in which seven fetuses were determined to be affected with elevated levels of Hcy, C3, C3/C2 and MMA, and their levels were 18.50 (6.70-43.30) μmol/L, 8.53(5.02-11.91) μmol/L, 0.77 (0.52-0.97), 8.96 (6.55-40.32) mmol/mol Cr, respectively. The remaining nine fetuses were considered unaffected based on a normal amniotic fluid metabolite profile.

Conclusions: Hcy appears to be another characteristic biomarker for the prenatal diagnosis of cblC defect. The combination of Hcy assay with acylcarnitine and organic acid analysis is a fast, sensitive, and reliable prenatal diagnostic biochemical approach. This approach could overcome the challenge of the lack of genetic analysis for families with at-risk cblC defect fetuses.
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http://dx.doi.org/10.1186/s13023-021-01762-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945211PMC
March 2021

Chromosomal microarray analysis in fetuses with high-risk prenatal indications: A retrospective study in China.

Taiwan J Obstet Gynecol 2021 Mar;60(2):299-304

Center for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address:

Objective: The present study aimed to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses with several indications of being at high risk for various conditions.

Materials And Methods: This retrospective analysis included 1256 pregnancies that were prenatally evaluated due to high-risk indications using invasive CMA. The indications for invasive prenatal diagnosis mainly included ultrasound anomalies, high-risk for maternal serum screening (MSS), high-risk for non-invasive prenatal tests (NIPT), family history of genetic disorders or birth defects, and advanced maternal age (AMA). The rate of clinically significant genomic imbalances between the different groups was compared.

Results: The overall prenatal diagnostic yield was 98 (7.8%) of 1256 pregnancies. Clinically significant genomic aberrations were identified in 2 (1.5%) of 132 patients with non-structural ultrasound anomalies, 36 (12.7%) of 283 with structural ultrasound anomalies, 2 (4.5%) of 44 at high-risk for MSS, 38 (26.6%) of 143 at high-risk for NIPT, 11 (3.8%) of 288 with a family history, and 7 (2.1%) of 328 with AMA. Submicroscopic findings were identified in 29 fetuses, 19 of whom showed structural ultrasound anomalies.

Conclusion: The diagnostic yields of CMA for pregnancies with different indications greatly varied. CMA could serve as a first-tier test for structural anomalies, especially multiple anomalies, craniofacial dysplasia, urinary defects, and cardiac dysplasia. Our results have important implications for genetic counseling.
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http://dx.doi.org/10.1016/j.tjog.2021.01.008DOI Listing
March 2021

Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.

Hum Mutat 2021 May 19;42(5):614-625. Epub 2021 Mar 19.

Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Niemann-Pick disease Types A and B (NPA/B) are autosomal recessive disorders caused by variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. This study aimed to describe and characterize a cohort of 118 patients diagnosed with NPA/B based on clinical, biochemical, and molecular findings, and to identify sound correlations between laboratory findings and clinical presentations. Decreased peripheral leukocyte acid sphingomyelinase activity levels and increased plasma 7-ketocholesterol levels were significantly correlated with disease onset and severity of the clinical course. We identified 92 different sequence SMPD1 variants, including 41 novel variants, in 118 NPA/B patients (19 NPA, 24 intermediate type, 75 NPB). The most prevalent mutation was p.Arg602His, which accounted for 9.3% of the alleles. Patients homozygous for p.Arg602His or p.Asn522Ser showed a late-onset form of the NPB phenotype. The homozygous SMPD1 variant p.Tyr500His correlated with the early-onset NPB clinical form. Additionally, homozygous variants p.His284SerfsX18, p.Phe465Ser, and p.Ser486Arg were associated with the neuronopathic NPA clinical form. The homozygous variant p.Arg3AlafsX74 was associated with the intermediate clinical form. Our study contributes to the understanding of the natural history of NPA/B and assists in the development of efficacious treatments for patients afflicted with this devastating lysosomal storage disorder.
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http://dx.doi.org/10.1002/humu.24192DOI Listing
May 2021

Community Composition and Co-Occurrence Patterns of Diazotrophs along a Soil Profile in Paddy Fields of Three Soil Types in China.

Microb Ecol 2021 Mar 3. Epub 2021 Mar 3.

Key Laboratory of Pollution Ecology and Environmental Engineering, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, 110164, China.

Diazotrophs play a key role in biological nitrogen (N) fixation. However, we know little about the distribution of the diazotrophic community along the soil profile in paddy fields. Here, we used Illumina MiSeq sequencing, targeting the nitrogenase reductase (nifH) gene, to investigate changes with depth (0-100 cm) in the diazotrophic community in paddy soils of three regions (Changshu, Hailun, and Yingtan) in China. The results indicated that most diazotrophs belonged to the phylum Proteobacteria, accounting for 78.05% of the total number of sequences. The diazotrophic diversity was generally highest in the 10-20 cm layer, and then significantly decreased with soil depth. Principal coordinate analysis and PERMANOVA indicated that the diazotrophic community structure was significantly affected by region and soil depth. There were obvious differences in the composition of the diazotrophic community between the topsoil (0-40 cm) and the subsoil (40-100 cm). Anaeromyxobacter, Sideroxydans, Methylomonas, Nostoc, Methanocella, and Methanosaeta were enriched in the topsoil, while Geobacter, Azoarcus, Bradyrhizobium, and Dechloromonas were concentrated in the subsoil. Furthermore, co-occurrence network analysis showed that the diazotrophic network in the topsoil was more complex than that in the subsoil. Distance-based redundancy analysis indicated that soil total C and N content and pH were the main factors influencing the vertical variation in the diazotrophic community. These results highlighted that depth has a great impact on the diazotrophic diversity, community composition, and co-occurrence patterns in paddy soil.
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http://dx.doi.org/10.1007/s00248-021-01716-9DOI Listing
March 2021

Numerical simulation of wind field and sand flux in crescentic sand dunes.

Sci Rep 2021 Mar 2;11(1):4973. Epub 2021 Mar 2.

State Key Laboratory Breeding Base of Desertification and Aeolian Sand Disaster Combating, Gansu Desert Control Research Institute, Lanzhou, 730070, China.

Sand flux is the key factor to determine the migration of sand dunes and the erosion to the surrounding environment. There are crescent-shaped sand dunes of various scales in the desert, and there are significant differences in spatial wind field and sand flux among them. However, due to the difficulty of monitoring, it is difficult to continuously observe the spatial wind field and sand flux around the larger crescentic dunes. On the basis of the Reynolds-Average Navier-Stokes (RA-NS) equation and the stress and sand flux model, the distribution of wind field and sand flux of a circular dune with a height of 4.2 m and a length of about 100 m during the four evolutionary periods of the evolution into a crescentic dune was simulated in this study. By comparing with the measured results, we verified that the closer to the leeward side, the more the simulated values of the velocity in wind field and sand flux were in line with the measured results. In order to further analyze the influence of the height of dune and other relevant parameters on sand flux, we simulated the influence on wind field and sand flux by changing the air viscosity and wind velocity of upper boundary. We found that the air viscosity mainly affected the amount of deposited sand on the leeward side of sand dune, while the increase of wind velocity would undoubtedly increase the sand flux of the whole sand dune. In addition, the simulation results also showed that the influence of changes in height of dune on the turbulent intensity of leeward side was very significant, and the turbulent intensity increased with the height of dune. The height changes of tall dunes gradually affected the transport of sand caused by wind flow behind the leeward side because that the rotation of the wind flow would form new vortexes at the large pores behind the leeward side, which would increase the turbulent energy in space and thus would increase the distance of migration of the lifting sand. While the low sand dunes could not form extra small vortexes at the bottom of the leeward side, so the wind velocity was small and the eddy currents behind the leeward side were more stable. The simulation results indicated that wind velocity was not the only reason for increasing the amount of sand flux, and the fluctuation of wind flow caused by turbulence could also stimulate the movement of sand particles on the ground.
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http://dx.doi.org/10.1038/s41598-021-84509-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925693PMC
March 2021

Predominant cellular mitochondrial dysfunction in the TOP3A gene-caused Bloom syndrome-like disorder.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 23;1867(6):166106. Epub 2021 Feb 23.

Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

TOP3A promotes processing of double Holliday junction dissolution and also plays an important role in decatenation and segregation of human mtDNA. Recently, TOP3A mutations have been reported to cause Bloom syndrome-like disorder. However, whether the two function play equal roles in the disease pathogenesis is unclear. We retrospectively studied the disease progression of two siblings with Bloom-like syndrome caused by two novel mutations of TOP3A, p.Q788* and p.D479G. Beside the common clinical manifestations, our patients exhibited liver lipid storage with hepatomegaly. In cellular and molecular biological studies, TOP3A deficiency moderately increased sister chromatid exchanges and decreased cell proliferation compared with BLM or RMI2 deficiency. These changes were rescued by ectopic expression of either of the wildtype TOP3A or TOP3A-D479G. In contrast, reduced mitochondrial ATP generation and oxygen consumption rates observed in TOP3A defective cells were rescued by over-expression of the wildtype TOP3A, but not TOP3A-D479G. Considering the different impact of the TOP3A-D479G mutation on the genome stability and mitochondrial metabolism, we propose that the impaired mitochondrial metabolism plays an important role in the pathogenesis of TOP3A-deficient Bloom-like disease.
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http://dx.doi.org/10.1016/j.bbadis.2021.166106DOI Listing
June 2021

A multicolor sensing system for simultaneous detection of four foodborne pathogenic bacteria based on FeO/MnO nanocomposites and the etching of gold nanorods.

Food Chem Toxicol 2021 Mar 3;149:112035. Epub 2021 Feb 3.

School of Public Health, Jilin University, Changchun, 130021, China. Electronic address:

Food safety problems attributed to foodborne pathogenic bacteria seriously endanger human health and cause substantial economic losses. Novel assays for rapid and sensitive identification of foodborne pathogenic bacteria are highly desired. In this study, a multicolor sensing system has been established for simultaneous determination of four foodborne bacteria by exploiting oxidase mimicking activity of aptamer-functionalized manganese dioxide-coated ferriferrous oxide (apt-FeO/MnO) nanocomposites and oxTMB etching of gold nanorods (AuNRs). Apt-FeO/MnO nanocomposites were used as capture probes to recognize and capture specific bacteria. The captured bacteria blocked the catalytic sites of the magnetic conjugate, which inhibited the catalyzation of oxTMB and further reduced the etching of AuNRs. Consequently, the longitudinal shift of AuNRs decreased linearly with the increase of the concentration of bacteria ranging from 10 to 10 CFU mL. Instrumental detection limits for S. aureus, L. monocytogenes, E. coli O157:H7 and V. parahaemolyticus reached down to 1.3 CFU mL, 1.2 CFU mL, 1.3 CFU mL and 1.4 CFU mL, respectively. And their visual detection limit was as low as 10 CFU mL. The whole detection process only needs 40 min, suggesting that this method is promising in on-site detection of bacteria.
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http://dx.doi.org/10.1016/j.fct.2021.112035DOI Listing
March 2021

Studies of anticancer activity in vivo and in vitro behaviors of liposomes encapsulated iridium(III) complex.

J Biol Inorg Chem 2021 Feb 21;26(1):109-122. Epub 2021 Jan 21.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.

Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq)(DQTT)](PF) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca. Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy.
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http://dx.doi.org/10.1007/s00775-020-01841-9DOI Listing
February 2021

A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients.

Orphanet J Rare Dis 2021 01 7;16(1):22. Epub 2021 Jan 7.

Department of Pediatric Endocrinology/Genetics, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype.

Methods: Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant.

Results: Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients.

Conclusion: Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.
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http://dx.doi.org/10.1186/s13023-020-01632-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792044PMC
January 2021

Clinical and molecular characteristics of 69 Chinese patients with ornithine transcarbamylase deficiency.

Orphanet J Rare Dis 2020 12 3;15(1):340. Epub 2020 Dec 3.

Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: This study aimed to describe the clinical and biochemical features of Chinese patients with ornithine transcarbamylase deficiency (OTCD), and to investigate the mutation spectrum of OTC gene and their potential correlation with phenotype.

Methods: Sixty-nine patients with OTCD were enrolled between 2004 and 2019. Clinical and laboratory data were reviewed retrospectively from medical records.

Results: Fifteen cases (13 males, 2 females) presented with early onset; 53 cases (21 males, 32 females) had late onset, and one female was asymptomatic. The median onset age was 1.5 years (range 1 day-56 years). Urine orotic acid levels were increased in all patients tested, while only 47.6% of patients showed decreased serum levels of citrulline. The peak plasma ammonia levels were higher in early-onset patients than in late-onset patients (P < 0.01). Fifty-four different mutations of OTC gene were identified and 18 of them were novel. R277W (10.6%) was the most common mutation, followed by G195R (4.6%) and A209V (3.0%). By June 2019, 41 patients had survived, 24 were deceased, and 4 were lost to follow-up. Among the survivors, 13 patients had received liver transplantation at a median age of 3 years, with a one-year survival rate of 100%. The mortality of OTCD is extremely high among patients with early onset (80.0% versus 24.5% in patients with late onset).

Conclusions: The evaluation of serum citrulline level is of limited value in diagnosis of OTCD, while urine orotic acid detection and genetic testing are more helpful.
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http://dx.doi.org/10.1186/s13023-020-01606-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712605PMC
December 2020

Flocculation of emulsified oily wastewater by using functional grafting modified chitosan: The effect of cationic and hydrophobic structure.

J Hazard Mater 2021 02 15;403:123690. Epub 2020 Aug 15.

College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.

In this work, modified chitosan flocculants (MCS) was synthesized by using chitosan (CS), acrylamide, cationic monomers and hydrophobic monomers via low-pressure UV-initiated copolymerization. The flocculation performance of MCS was evaluated in emulsified oily wastewater treatment. The effect of cationic and hydrophobic structure on oil removal was studied, and the interactions between these functional groups and the components in oil were also analyzed. Results suggested that MCS flocculants exhibited excellent oil removal efficiency in a wide pH range (2.0‒10). The flocculation efficiency of 91 % was achieved at the dosages of 0.6 mL/L (6 mg/L). During pH of 2.0-10, the optimal cationic and hydrophobic monomer was DMC and VT, respectively. Silane groups were favorable for oil removal than the other hydrophobic structures. The cationic groups expanded the optimal pH range of MCS in flocculation, whereas hydrophobic groups considerably reduced the dosage of MCS. The experimental results showed that alkane, cyclic aromatic hydrocarbon compounds in oil can be easily removed by using MC4, whereas cycloalkanes compounds was effectively removed by MC6 and MC7 because of preferable demulsification capacity, and the hydrophobic interaction, interfacial adsorption and electrostatic attraction played the dominant in flocculation. Thus, the synthesized MCS is favorable for emulsified oily wastewater treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123690DOI Listing
February 2021

Effects of the extract from peanut meal fermented with Bacillus natto and Monascus on lipid metabolism and intestinal barrier function of hyperlipidemic mice.

J Sci Food Agric 2021 Apr 30;101(6):2561-2569. Epub 2020 Oct 30.

Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, China.

Background: Hyperlipidemia is one of the metabolic disorders that poses a great threat to human health. This study is aimed at investigating the potential hypolipidemic properties of extract from peanut meal fermented with Bacillus natto and Monascus in mice fed with a high-fat diet. Herein, 60 male C57BL/6J mice were randomly divided into six groups: four control groups, comprised of a normal group, a model (M) group, a positive control group (atorvastatin 10 mg kg ), and a nonfermented peanut meal extract group (150 mg kg ), and two experimental groups, comprised of a fermented peanut meal extract low-dose group (50 mg kg ) and a fermented peanut meal extract high-dose group (FH, 150 mg kg ).

Results: Body weight (P = 0.001) and levels of serum total cholesterol (P = 0.007), triacylglycerol (P = 0.040), low-density lipoprotein cholesterol (P < 0.001), and leptin (P < 0.001) were remarkably decreased in the FH group, whereas the serum high-density lipoprotein cholesterol levels were increased (P < 0.001) by 78.3% compared with the M group. Ileum tissue stained with hematoxylin and eosin showed that the ileal villus detachments in mice were improved, and the villus height was increased by supplementation with extract from fermented peanut meal. Moreover, the expressions of intestinal ZO-1 (P = 0.003) and occludin (P = 0.013) were elevated in the FH group, compared with the M group.

Conclusion: Extract of peanut meal fermented by B. natto and Monascus can effectively improve hyperlipidemia caused by a high-fat diet in mice, via regulating leptin and blood lipid levels, and protect the intestinal mucosal barrier, which provides evidence for its anti-hyperlipidemia effects and is a research basis for potential industrial development. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10884DOI Listing
April 2021

Diagnostic yield of additional exome sequencing after the detection of long continuous stretches of homozygosity (LCSH) in SNP arrays.

J Hum Genet 2021 Apr 10;66(4):409-417. Epub 2020 Oct 10.

Department of Pediatric Endocrinology and Genetics, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Long continuous stretches of homozygosity (LCSH) are associated with risk of recessive disorders. Though LCSH can be detected by SNP microarrays, additional testing is necessary to clarify the clinical significance. This study is to assess the yield of additional exome sequencing (ES) after LCSH detection and inform the likelihood of eventual diagnosis. In 2226 patients referred to SNP microarrays, 35 patients met the criteria of indicative LCSH. These patients were recruited and went through additional ES. The diagnostic yield was analyzed, and the LCSH pattern was compared between eventually diagnosed cases and those undiagnosed. The results showed additional ES attained a diagnostic yield of 31.4% (11/35), but only one-third of the yield (11.4%, 4/35) was relevant to LCSH. In contrast, two-thirds of the diagnostic variants (20%, 7/35) were de novo or dominantly inherited, irrelevant to the original LCSH finding. No particular LCSH pattern, including the chromosomal coverage or LCSH size, was found to associate with the diagnostic outcome. We concluded that additional ES after LCSH detection could reveal diagnostic variants, but it is strongly recommended to consider all possible inheritance mode, as the diagnostic variants may be irrelevant to the original LCSH finding.
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http://dx.doi.org/10.1038/s10038-020-00854-1DOI Listing
April 2021

Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies.

Orphanet J Rare Dis 2020 10 7;15(1):276. Epub 2020 Oct 7.

Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 KongJiang Road, Shanghai, 200092, China.

Background: Propionic acidemia (PA) is a serious metabolic disorder, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability and validity of a biochemical strategy in the prenatal diagnosis of PA, we conducted a retrospective study of our 11-year experiences at a single center.

Methods: We accumulated data from 78 pregnancies from 58 families referred to our center and provided prenatal diagnosis by directed genetic analysis and/or metabolite measurement using tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GC/MS) of amniotic fluid (AF) samples.

Results: Sixty-five unaffected fetuses (83.33%) and 13 affected fetuses (16.67%) were confirmed in our study. The characteristic metabolites including propionylcarnitine (C3) level, C3/acetylcarnitine (C2) ratio and 2-methylcitric acid (2MCA) level in unaffected and affected groups showed significant differences (P < 0.0001), while the level of 3-hydroxypropionic acid (3HPA) showed no significant difference between the two groups (P > 0.05).Of the 78 pregnancies, 24 fetuses were found to have either one causative pathogenic variant or were without genetic information in the proband. Three of these fetuses had elevated AF levels of C3, C3/C2 ratio, and 2MCA and, thus, were determined to be affected, while the remaining fetuses were determined to be unaffected based on a normal AF metabolite profile. Our genetic and biochemical results were highly consistent with postnatal follow-up results on all unaffected fetuses.

Conclusions: We conclude that a biochemical approach can serve as a fast and convenient prenatal diagnostic method for pregnancies at an increased risk for PA, which could be used in conjunction with genetic testing for precise prenatal diagnosis of this disorder. In our analysis, the characteristic metabolites C3 level, C3/C2 ratio, and 2MCA level in AF supernatant were dependable biochemical markers for diagnosis, of which the C3/C2 ratio appears to be the most reliable biochemical marker for the prenatal diagnosis of PA.
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http://dx.doi.org/10.1186/s13023-020-01539-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539428PMC
October 2020

Staphylococcal Enterotoxin C2 Mutant-Directed Fatty Acid and Mitochondrial Energy Metabolic Programs Regulate CD8 T Cell Activation.

J Immunol 2020 10 16;205(8):2066-2076. Epub 2020 Sep 16.

Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, China; and.

CD8 T cells can switch between fatty acid catabolism and mitochondrial energy metabolism to sustain expansion and their cytotoxic functions. ST-4 is a TCR-enhanced mutant derived from superantigen staphylococcal enterotoxin C2 (SEC2), which can hyperactivate CD4 T cells without MHC class II molecules. However, whether ST-4/SEC2 can enhance metabolic reprogramming in CD8 T cells remains poorly understood. In this study, we found that ST-4, but not SEC2, could induce proliferation of purified CD8 T cell from BALB/c mice in Vβ8.2- and -8.3-specific manners. Results of gas chromatography-mass spectroscopy analysis showed that fatty acid contents in CD8 T cells were increased after ST-4 stimulation. Flow cytometry and Seahorse analyses showed that ST-4 significantly promoted mitochondrial energy metabolism in CD8 T cells. We also observed significantly upregulated levels of gene transcripts for fatty acid uptake and synthesis, and significantly increased protein expression levels of fatty acid and mitochondrial metabolic markers of mTOR/PPARγ/SREBP1 and p38-MAPK signaling pathways in ST-4-activated CD8 T cells. However, blocking mTOR, PPARγ, SREBP1, or p38-MAPK signals with specific inhibitors could significantly relieve the enhanced fatty acid catabolism and mitochondrial capacity induced by ST-4. In addition, blocking these signals inhibited ST-4-stimulated CD8 T cell proliferation and effector functions. Taken together, our findings demonstrate that ST-4 enhanced fatty acid and mitochondria metabolic reprogramming through mTOR/PPARγ/SREBP and p38-MAPK signaling pathways, which may be important regulatory mechanisms of CD8 T cell activation. Understanding the effects of ST-4-induced regulatory metabolic networks on CD8 T cells provide important mechanistic insights to superantigen-based tumor therapy.
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http://dx.doi.org/10.4049/jimmunol.2000538DOI Listing
October 2020

Exploring anticancer efficiency of mitochondria-targeted cyclometalated iridium(III) complexes.

J Inorg Biochem 2020 11 8;212:111215. Epub 2020 Aug 8.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address:

We prepared and characterized new iridium(III) complexes: [Ir(NC)(MPPIP)](PF) (N-C = 2-phenylpyridine 1; benzo[h]quinolone 2; 1-phenylisoquinolone, 3, MPPIP = 2-(4-(4'-methylpiperazin-yl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline). MTT (MTT = 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide) method was used to assay anticancer activities of the complexes 1-3 toward SGC-7901, HeLa, A549, BEL-7402, mouse embryonic fibroblast NIH3T3 cell lines. Complexes 1, 2, 3 are sensitive to A549 cells and display a relatively low IC value of 5.4 ± 0.3, 4.2 ± 0.03 and 3.8 ± 0.2 μM, respectively. The apoptotic efficiency was investigated and the number of apoptotic cells induced by 1, 2 and 3 is 9.92%, 11.30% and 16.00%. The complexes are able to increase intracellular ROS content and lessen the mitochondrial membrane potential. Besides, anti-tumor activity in vivo reveals that complex 3 exhibits moderate effect on inhibiting the tumor growth, and complex 3 has no influence on liver, brain, kidney, lung and heart.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111215DOI Listing
November 2020

Liposome as drug delivery system enhance anticancer activity of iridium (III) complex.

J Liposome Res 2020 Sep 21:1-14. Epub 2020 Sep 21.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, PR China.

Herein an Ir(III) complex [Ir(Hppy)(HMNPIP)](PF) (, Hppy = 2-phenylpyridine, HMNPIP = 2-(1-imidazo[4,5-f][1, 10]phenanthroline-3-yl)-6-methoxy-4-nitrophenol) was prepared and characterized. Due to the low anticancer activity of when administered free drug, we prepared a liposome encapsulated form of to improve the antitumor effect, furthermore, we explored the antitumor mechanism of both forms experiments on HepG2 cells. We investigated the inhibitory efficiency of and on cell viability and proliferation using MTT (MTT = 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide) and colony-forming assay. Intracellular accumulation of reactive oxygen species (ROS) was examined using a fluorescence microscope (High Content Screening System, ImageXpress Micro XLS System, Molecular Devices LLC, Sunnyvale, CA), programmed cell death cells stained with acridine orange/ethidium bromide (AO/EB) using flow cytometry detection and western blot have been performed. An study where HepG2 cells were transplanted into nude nice as xenografts. Tumour volume and body weight were monitored during the 10 days of administration. After encapsulation in liposomes displayed high potency against a variety of tumour cells , especially against HepG2 (IC = 4.6 ± 0.5 μM). Mechanism studies indicated that initiated apoptosis by generating intracellular ROS that regulate lysosomal-mitochondrial dysfunction, followed by microtubule disruption that subsequently leads to a G0/G1 phase of cell cycle arrest. Additionally, significantly curbed tumour growth in nude mice. The tumour inhibitory rate was 51.2% (5.6 mg/kg). Therefore, liposome as a drug delivery system greatly enhances anticancer activity of by a factor of relatively minor side effects.
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http://dx.doi.org/10.1080/08982104.2020.1818779DOI Listing
September 2020

Simultaneous detection of three zoonotic pathogens based on phage display peptide and multicolor quantum dots.

Anal Biochem 2020 11 1;608:113854. Epub 2020 Aug 1.

Department of Hygienic Inspection, School of Public Health, Jilin University, 1163 Xinmin Street, Changchun, 130021, Jilin, China. Electronic address:

With the rapid development of human's exploitation of nature and animal husbandry, zoonoses have become a major public health problem worldwide. It is necessary to establish a rapid, specific and sensitive detection method to screen several zoonotic pathogenic bacteria simultaneously. In this study, phage display technology was used to screen specific peptide of three common zoonotic pathogens, E. coli O157:H7, L. monocytogenes and B. melitensis 16 M. Then, three peptide were obtained, named E2, L4 and B4, which can identify the three pathogens respectively. Three peptide modified with biotin were synthesized and were coupled to streptavidin magnetic beads (MBs) to form peptide-MBs, which enriched the above three pathogens from the samples. Three quantum dot (QD) probes were constructed by coupling three polyclonal antibodies to different fluorescent QD surfaces (QD540, QD580 and QD630). The simultaneous detection method based on peptide-MBs and QDs multicolor fluorescent labeling was established and could detect E. coli O157:H7, L. monocytogenes and B. melitensis 16 M simultaneously. The detection method took about 100 min with the detection limits of 10, 10 and 10 CFU/mL, respectively. The detection method could be also well utilized in real samples.
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http://dx.doi.org/10.1016/j.ab.2020.113854DOI Listing
November 2020

Adsorptive removal of gallic acid from aqueous solution onto magnetic ion exchange resin.

Water Sci Technol 2020 Apr;81(7):1479-1493

School of Civil Engineering and Architecture, Anhui University of Technology, 59 Hudong Road, Maanshan 243002, China E-mail: Engineering Research Center of Biomembrane Water Purification and Utilization Technology, Ministry of Education, Maanshan, Anhui, 243002, China.

Finding an appropriate adsorbent with high adsorption capacity, quick adsorption kinetics and easy regeneration was crucial to the removal of gallic acid (GA) from water and wastewater. Our aims were to investigate whether a magnetic ion exchange (MIEX) resin had the three merits mentioned above, and investigate the feasibility of GA adsorption on MIEX resin, and the adsorption kinetics, equilibrium, thermodynamics, regeneration and mechanism using batch tests. The uptake of GA increased with increasing GA concentration. The GA concentration influenced the time needed to reach equilibrium, but the adsorption could be completed within 120 min. Elevating temperature facilitated the GA removal. The removal percent remained above 95.0% at pH 5.0-11.0. Carbonate and bicarbonate promoted the GA removal; conversely chloride, sulfate and nitrate restrained the GA removal significantly. The adsorption kinetics could be fitted well with the pseudo second-order model, and the film diffusion governed the whole adsorption rate. The equilibrium data followed the Redlich-Peterson isotherm model. The adsorption was a spontaneous, endothermic and entropy driven process. The ion exchange dominated the removal mechanism. The spent MIEX resin was well regenerated by sodium chloride. Therefore, MIEX resin is a potential adsorbent for removing GA quickly and efficiently from water and wastewater.
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http://dx.doi.org/10.2166/wst.2020.236DOI Listing
April 2020

Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches.

Front Genet 2020 20;11:496. Epub 2020 May 20.

Department of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Direct mutation analysis is the major method for glutaric acidemia I (GA-I) prenatal diagnosis, while systemic application of a biochemical strategy is rare. We describe our experiences with metabolite measurement together with mutation analysis in GA-I prenatal diagnosis at a single center over 10 years. The data of genetic analysis and metabolite measurement using gas chromatography/mass spectrometry(GC/MS) and tandem mass spectrometry(MS/MS) in amniotic fluid samples of 44 fetuses from 42 GA-I families referred to our center from 2009 to 2019 were retrospectively analyzed. Among these 44 fetuses, genetic and biochemical results were both available in 39 fetuses. Of these, 6 fetuses were judged as affected and 33 fetuses as unaffected by mutation analysis. The levels of glutarylcarnitine (C5DC), C5DC/octanoylcarnitine (C8), and glutaric acid in the supernatant of amniotic fluid from affected fetuses were significantly higher than those in unaffected fetuses [1.73μmol/L (0.89-4.19) vs. 0.16μmol/L (0.06-0.37), 26.26 (12.4-55.55) vs. 2.23 (1.04-8.44), and 103.94 mmol/mol creatinine (30.37-148.31) vs. 1.01mmol/mol creatinine (0-9.81), respectively; all < 0.0001]. Among all families, two were found to have one causative mutation in the proband, in four pregnancies from these two families, three fetuses were judged as "unaffected" and one was judged as "affected" according to metabolites results. Postnatal follow-up showed a normal phenotype in all unaffected fetuses judged by mutation or metabolite analysis. C5DC, C5DC/C8, and glutaric acid levels in the supernatant of amniotic fluid showed significant differences and no overlap between the affected and unaffected fetuses. Biochemical strategy could be implemented as a quick and convenient method for the prenatal diagnosis of GA-I.
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http://dx.doi.org/10.3389/fgene.2020.00496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251148PMC
May 2020

An iRGD peptide fused superantigen mutant induced tumor-targeting and T lymphocyte infiltrating in cancer immunotherapy.

Int J Pharm 2020 Aug 4;586:119498. Epub 2020 Jun 4.

Institute of Applied Ecology, Chinese Academy of Sciences, 72 WenHua Road, Shenyang 110016, PR China; Key Laboratory of Superantigen Research, Shenyang Bureau of Science and Technology, 72 WenHua Road, Shenyang 110016, PR China.

Solid tumors are intrinsically resistant to immunotherapy because of the major challenges including the immunosuppression and poor penetration of drugs and lymphocytes into solid tumors due to the complicated tumor microenvironment (TME). Our previous study has created a novel superantigen mutant ST-4 to efficiently active the T lymphocytes and alleviate immune suppression. In the present study, to accumulate ST-4 into the TME, we constructed a recombinant protein, ST-4-iRGD, by fusing ST-4 to a tumor-homing peptide, iRGD. We hypothesized that ST-4-iRGD could internalize into the TME through iRGD-mediated tumor targeting and tumor tissue penetrating to activate the regional immunoreaction. The results of in vitro studies showed that ST-4-iRGD achieved improved tumor targeting and cytotoxicity in mouse B16F10 melanoma cells. The iRGD-mediated tumor tissue penetration was further confirmed by imaging and immunofluorescence studies in vivo, wherein higher distribution of ST-4-iRGD was observed in the mouse 4T1 breast tumor model. Moreover, ST-4-iRGD exhibited enhanced anti-solid tumor characteristics and induced improved lymphocyte infiltration in the B16F10 and 4T1 models. In conclusion, using iRGD to facilitate better dissemination of the therapeutic agent ST-4 throughout a solid tumor mass is feasible, and ST-4-iRGD may be a potential candidate for efficient cancer immunotherapy in the future.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119498DOI Listing
August 2020