Publications by authors named "Yue Huang"

721 Publications

[Tc]Tc-Galacto-RGD integrin αβ-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data.

EJNMMI Res 2021 Jun 13;11(1):59. Epub 2021 Jun 13.

Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [Tc]Tc-Galacto-RGD single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αβ expression, and neovascularization in lung cancer subtypes was also addressed.

Methods: A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prospective study from January 2013 to December 2016. All patients underwent [Tc]Tc-Galacto-RGD imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [Tc]Tc-Galacto-RGD was expressed as the tumour/normal tissue ratio(T/N). The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour specimens were obtained from 66 patients with malignant diseases and 7 with benign disease. Tumour expression levels of αβ, CD31, Ki-67, and CXCR4 were further analysed for the evaluation of biological behaviours.

Results: The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of [Tc]Tc-Galacto-RGD SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αβ expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αβ expression. Integrin αβ expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αβ expression.

Conclusions: [Tc]Tc-Galacto-RGD SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer, integrin expression in the tumour vessel and tumour cell membrane contributes to the tumour uptake.
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http://dx.doi.org/10.1186/s13550-021-00801-xDOI Listing
June 2021

Mosaic de novo gene variant associated with Prader-Willi syndrome.

J Med Genet 2021 Jun 7. Epub 2021 Jun 7.

Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA

Background: Prader-Willi syndrome (PWS) is an imprinting disorder caused by the absence of paternal expressed genes in the Prader-Willi critical region (PWCR) on chromosome 15q11.2-q13. Three molecular mechanisms have been known to cause PWS, including a deletion in the PWCR, uniparental disomy 15 and imprinting defects.

Results: We report the first case of PWS associated with a single-nucleotide variant in a 10-year-old girl presenting with clinical features consistent with PWS, including infantile hypotonia and feeding difficulty, developmental delay with cognitive impairment, excessive eating with central obesity, sleep disturbances, skin picking and related behaviour issues. Whole-exome sequencing revealed a de novo mosaic nonsense variant of the gene (c.73C>T, p.R25X) in 10% of DNA isolated from buccal cells and 19% of DNA from patient-derived lymphoblast cells. DNA methylation study did not detect an abnormal methylation pattern in the locus. Parental origin studies showed a paternal source of an intronic single-nucleotide polymorphism within the locus in proximity to the variant.

Conclusions: This is the first report that provides evidence of a de novo point mutation of paternal origin in as a new disease-causing mechanism for PWS. This finding suggests that gene sequencing should be considered as part of the diagnostic workup in patients with clinical suspicion of PWS.
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http://dx.doi.org/10.1136/jmedgenet-2020-107674DOI Listing
June 2021

Polycentric or monocentric, which kind of spatial structure is better for promoting the green economy? Evidence from Chinese urban agglomerations.

Environ Sci Pollut Res Int 2021 Jun 6. Epub 2021 Jun 6.

Guangxi Institute of Finance and Economics, Guangxi University of Finance and Economics, Nanning, China.

The green economy has gained worldwide attention, especially in the urban agglomerations where population and economic activities are highly concentrated. However, what kind of urban agglomeration spatial structure is more conducive to promoting the green economy? No clear conclusions have been made. To bridge this gap, by employing the data of 16 urban agglomerations in China in 2003-2017 and a comprehensive analytic framework including dynamic panel threshold model, this paper studies the impact of urban agglomeration spatial structure on the green economy and the three subsystems of green economy to shed light on which kind of urban agglomeration spatial structure better drives the green economy. The main findings are shown below: (1) urban agglomeration spatial structural evolution is closely related to green economy, while in the research period, most urban agglomerations are not located in the optimal range of the spatial structure that drives the green economy. (2) Towards polycentric spatial structure is contributive to green economic growth; however, the excessively polycentric could not benefit green economy. (3) The evolution of urban agglomeration spatial structure exerts heterogeneous impacts on the three subsystems when green economy is decomposed into economic subsystem, resources subsystem, and environmental subsystem. Towards polycentric is more conducive to the improvement of economic subsystem and resource subsystem, while the tendency to monocentric drives the environmental subsystem. (4) Lastly, the conclusions enlighten the urban agglomeration development planning and spatial mode for approaching a better performance in green economy.
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http://dx.doi.org/10.1007/s11356-021-14655-2DOI Listing
June 2021

Differences in levels of phosphatidylinositols in healthy and stable Coronary Artery Disease subjects revealed by HILIC-MRM method with SERRF normalization.

PLoS One 2021 4;16(6):e0252426. Epub 2021 Jun 4.

Integrated Bioanalysis, Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, South San Francisco, CA, United States of America.

Quantification of endogenous biomarkers in clinical studies requires careful evaluation of a number of assay performance parameters. Comparisons of absolute values from several clinical studies can enable retrospective analyses further elucidating the biology of a given biomarker across various study populations. We characterized the performance of a highly multiplex bioanalytical method for quantification of phosphatidylinositols (PI). Hydrophilic interaction chromatography (HILIC) and multiple reaction monitoring (MRM) were employed for targeted multiplex quantification. Odd-chain PI species that are not normally present in human plasma were utilized as surrogate analytes (SA) to assess various assay performance parameters and establish a definitive dynamic linear range for PI lipids. To correct for batch effects, Systematic Error Removal using Random Forest (SERRF) normalization algorithm was employed and used to bridge raw values between two clinical studies, enabling quantitative comparison of their absolute values. A high throughput method was developed, qualified, transferred to an automation platform and applied to sample testing in two clinical trials in healthy volunteers (NCT03001297) and stable Coronary Artery Disease (CAD, NCT03351738) subjects. The method demonstrated acceptable precision and accuracy (±30%) over linear range of 1-1000 nM for SA and 8-fold dilutional linearity for endogenous PI. We determined that mean-adjusted average QC performed best for normalization using SERRF. The comparison of two studies revealed that healthy subject levels of PI are consistently higher across PI species compared to CAD subjects identifying a potential lipid biomarker to be explored in future studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252426PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177664PMC
June 2021

Design, Synthesis, and Evaluation of Dihydropyranopyrazole Derivatives as Novel PDE2 Inhibitors for the Treatment of Alzheimer's Disease.

Molecules 2021 May 19;26(10). Epub 2021 May 19.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer's disease (AD). In this study, we obtained ()- as a hit compound with moderate PDE2 inhibitory activity (IC = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Then, we designed and synthesized 28 dihydropyranopyrazole derivatives as PDE2 inhibitors. Among them, compound ()- was the most potent PDE2 inhibitor, with an IC value of 41.5 nM. The molecular docking of PDE2-()- reveals that the 4-(trifluoromethyl)benzyl)oxyl side chain of the compound enters the H-pocket and forms strong hydrophobic interactions with L770/L809/F862, which improves inhibitory activity. The above results may provide insight for further structural optimization of highly potent PDE2 inhibitors and may lay the foundation for their use in the treatment of AD.
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http://dx.doi.org/10.3390/molecules26103034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160813PMC
May 2021

The complex role of PD-L1 in antitumor immunity: a recent update.

Cell Mol Immunol 2021 May 31. Epub 2021 May 31.

Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.1038/s41423-021-00702-yDOI Listing
May 2021

Durable Defect Passivation of the Grain Surface in Perovskite Solar Cells with π-Conjugated Sulfamic Acid Additives.

ACS Appl Mater Interfaces 2021 Jun 28;13(22):26013-26022. Epub 2021 May 28.

State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.

Defect passivation has shown an essential role in improving the efficiency and stability of perovskite solar cells (PSCs). Herein, an efficient and low-cost π-conjugated sulfamic acid additive, 4-aminobenzenesulfonic acid (4-ABSA), is used to realize durable defect passivation of PSCs. The incorporation of 4-ABSA not only constructs a compact and smooth perovskite film but is also capable of passivating both negative- and positive-charged defects derived from under-coordinated lead and halogen ions. Besides, the π-conjugated system in 4-ABSA can induce preferred perovskite crystal orientation and stabilize the coordination effect between 4-ABSA and perovskite grains. As a result, the inverted planar PSC incorporated with 4-ABSA additives demonstrates an improved power conversion efficiency (PCE) from 18.25 to 20.32%. Moreover, this 4-ABSA passivation agent also enhances the stability of devices, which retains 83.5% of its initial efficiency under ambient condition at 60 °C after 27 days. This work provides a π-conjugated sulfamic acid for durable defect passivation of perovskite optoelectronic devices.
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http://dx.doi.org/10.1021/acsami.1c04601DOI Listing
June 2021

Measuring the global, regional, and national burden of multiple myeloma from 1990 to 2019.

BMC Cancer 2021 May 25;21(1):606. Epub 2021 May 25.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, China.

Background: Multiple myeloma (MM) is a major health concern. Understanding the different burden and tendency of MM in different regions is crucial for formulating specific local strategies. Therefore, we evaluated the epidemiologic patterns and explored the risk factors for MM death.

Methods: Data on MM were collected from the 2019 Global Burden of Disease study. We used incidence, mortality, and disability adjusted life-years to estimate the global, regional, and national burden of MM.

Results: In 2019, there were 155,688 (95% UI, 136,585 - 172,577) MM cases worldwide, of which 84,516 (54.3%, 70,924 - 94,910) were of men. The age-standardized incidence rate (ASIR) was 1.72/100,000 persons (95% UI, 1.59-1.93) in 1990 and 1.92/100,000 persons (95% UI, 1.68-2.12) in 2019. The number of MM deaths increased 1.19-fold from 51,862 (95% UI, 47,710-58,979) in 1990 to 113,474 (95% UI, 99,527 - 121,735) in 2019; the age-standardized death rate (ASDR) was 1.42/100,000 persons (95% UI, 1.24-1.52) in 2019. In recent 15 years, ASDR showed a steady tendency for men, and a downward tendency for women. Countries with high social-demographic indexes exhibited a higher ASIR and ASDR. Australasia, North America, and Western Europe had the highest ASIR and ASDR, with 46.3% incident cases and 41.8% death cases. Monaco had the highest ASIR and ASDR, which was almost half as high as the second highest country Barbados. In addition, United Arab Emirates and Qatar had the largest growth multiple in ASIR and ASDR, which was twice the third country Djibouti.

Conclusions: Globally, incident and death MM cases have more than doubled over the past 30 years. The increasing global burden may continue with population aging, whereas mortality may continue to decrease with the progression of medical technology. The global burden pattern of MM was diverse, therefore specific local strategies based on different burden patterns for MM are necessary.
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http://dx.doi.org/10.1186/s12885-021-08280-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152089PMC
May 2021

Exercise Preconditioning Promotes Autophagy to Cooperate for Cardioprotection by Increasing LC3 Lipidation-Associated Proteins.

Front Physiol 2021 5;12:599892. Epub 2021 May 5.

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

The cardioprotection of exercise preconditioning (EP) has been well documented. EP can be divided into two phases that are the induction of exercise preconditioning (IEP) and the protection of exercise preconditioning (PEP). PEP is characterized by biphasic protection, including early exercise preconditioning (EEP) and late exercise preconditioning (LEP). LC3 lipidation-mediated autophagy plays a pivotal role in cardioprotection. This study aimed to investigate the alterations of LC3 lipidation-associated proteins during EP-induced cardioprotection against myocardial injury induced by exhaustive exercise (EE) was used in a rat model of EP. These rats were subjected to an intermittent exercise consisting of four periods, with each period including 10 min of running at 30 m/min and 0% grade (approximately 75% VO) followed by 10 min of intermittent rest. A model of EE-induced myocardial injury was developed by subjecting rats to a consecutive running (30 m/min, 0% grade) till exhaustion. Following EEP, the colocalization of LC3 with Atg7 was significantly increased, and LC3-I, LC3-II, LC3-II/LC3-I, Atg7, Atg4B, and Atg3 levels were significantly increased. Atg7, Atg4B, and Atg3 mRNAs were all significantly upregulated, and LC3 mRNAs tended to be higher. Following LEP, Atg4B, and Atg3 levels were significantly increased. Atg7, Atg4B, and Atg3 mRNAs were all significantly upregulated, and LC3 mRNAs tended to be higher. A group of rats were subjected to EEP followed by EE, and the co-localization of LC3 with Atg7 was significantly increased, while LC3-I, LC3-II, LC3-II/LC3-I, Atg7, Atg4B, and Atg3 levels were also significantly increased. Moreover, there was a significant increase in the co-localization of LC3 with Atg7, LC3-I, LC3-II, Atg7, and Atg4B levels during LEP followed by EE. The formation of autophagosome during LEP followed by EE may have been weaker than that during EEP followed by EE due to the lower lipidation of LC3. EP may promote autophagy to maintain cell homeostasis and survival, which cooperates for cardioprotection of alleviating exhaustive exercise-induced myocardial injury by increasing LC3 lipidation-associated proteins. There is a difference between EEP and LEP in terms of the mechanisms of cardioprotection afforded by these respective conditions. The positive regulation of transcription and translation level of LC3 lipidation-associated proteins may all be involved in the mechanism of EEP and LEP, while compared with LEP, the regulation of translation level of EEP is more positively to promote autophagy.
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http://dx.doi.org/10.3389/fphys.2021.599892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131968PMC
May 2021

A novel visible light-driven TiO photocatalytic reduction for hexavalent chromium wastewater and mechanism.

Water Sci Technol 2021 May;83(9):2135-2145

School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266033, China E-mail:

Titanium dioxide (TiO) photocatalyst was prepared with a sol-gel method and its characterizations were analyzed TiO photocatalytic reduction of Cr was investigated in visible light irradiation and reduction mechanisms were calculated. Prepared TiO is anatase with a bandgap of about 2.95 eV. Experimental results display that almost 100% of Cr is removed by visible light-driven TiO photocatalytic reduction after 120 min when CrO initial concentration is 1.0 mg·L, TiO dosage is 1.0 g·L, and pH value is 3. In acidic aqueous solution, HCrO is the dominant existing form of Cr and is adsorbed by TiO, forming a complex catalyst HCrO/TiO with an increase in wavelength to the visible light zone, demonstrated by UV-Vis diffuse reflection spectroscopy. Based on X-ray photoelectron spectroscopy data, it can be deduced that Cr is adsorbed on the surface of TiO and then reduced to Cr in situ by photoelectrons. Self-assembly of HCrO/TiO complex catalyst and self-reduction of Cr in situ are the key steps to start the visible light-driven TiO photocatalytic reduction. Furthermore, TiO photocatalytic reduction of Cr fits well with pseudo-first-order kinetics and has the potential application to treat chemical industrial wastewater.
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http://dx.doi.org/10.2166/wst.2021.116DOI Listing
May 2021

LBP Protects Hepatocyte Mitochondrial Function via the PPAR-CYP4a2 Signaling Pathway in a Rat Sepsis Model.

Shock 2021 May 13. Epub 2021 May 13.

Department of Pathophysiology, Anhui Medical University, Hefei 230000, China The First Clinical Medical College, Anhui Medical University, Hefei 230000, China Department of Clinical Laboratory, Binhu Hospital, Anhui Medical University, Hefei 230000, China Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Objectives: To explore the role of LBP in metabolism and optimize sepsis treatment.

Design: A sepsis model was established by injecting LPS into LBP-/- rats and WT rats and observing changes in the liver over time (0 h, 1 h, 6 h, and 24 h).

Setting: Detecting liver inflammation and injury. Optimizing the treatment of sepsis.

Subjects: WT rats and LBP-/- rats.

Interventions: We established a sepsis model by injecting LPS intravenously.

Measurements And Main Results: First, we induced sepsis in WT and LBP-/- rats with LPS. The rats were sacrificed, and serum and liver samples were collected at 1 h, 6 h and 24 h after LPS injection. We found that the deletion of LBP reduced LPS-induced liver inflammation and injury at 1 h and 6 h. Ballooning degeneration was clearly present in LBP-/- rat livers at 24 h after LPS injection. We found that mitochondrial damage and ROS levels were higher in LBP-/- rat livers than in WT rat livers at 24 h after LPS injection. According to the transcriptomic results, the PPAR pathway may be the reason for lesions in LBP-/- rats. To further investigate the function of PPARα in sepsis, we inhibited mTOR with rapamycin and examined mitochondrial injury and ROS levels. The levels of mitochondrial damage and ROS were reduced after LBP-/- rats were pretreated with rapamycin in the context of LPS-induced sepsis. Inhibiting CYP4a2, one of the PPARα-target gene products, reduced the level of LPS-induced ROS in LBP-/- rats.

Conclusion: LBP protects hepatic mitochondria against LPS-induced damage via the LBP-PPARα-CYP4a2 signaling pathway.
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http://dx.doi.org/10.1097/SHK.0000000000001808DOI Listing
May 2021

Pathogenic variants in , a chromatin remodeler, cause a range of syndromic neurodevelopmental features.

Sci Adv 2021 May 12;7(20). Epub 2021 May 12.

Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ, USA.

Intellectual disability encompasses a wide spectrum of neurodevelopmental disorders, with many linked genetic loci. However, the underlying molecular mechanism for more than 50% of the patients remains elusive. We describe pathogenic variants in , encoding the ATPase motor of the ISWI chromatin remodeler, as a cause of a previously unidentified neurodevelopmental disorder, identifying 12 individuals with de novo or dominantly segregating rare heterozygous variants. Accompanying phenotypes include mild developmental delay, frequent postnatal short stature and microcephaly, and recurrent dysmorphic features. Loss of function of the SMARCA5 ortholog led to smaller body size, reduced sensory dendrite complexity, and tiling defects in larvae. In adult flies, Iswi neural knockdown caused decreased brain size, aberrant mushroom body morphology, and abnormal locomotor function. loss of function was rescued by wild-type but not mutant SMARCA5. Our results demonstrate that pathogenic variants cause a neurodevelopmental syndrome with mild facial dysmorphia.
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http://dx.doi.org/10.1126/sciadv.abf2066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115915PMC
May 2021

Gradient Porous Structure Templated by Breath Figure Method.

Langmuir 2021 May 5;37(19):6016-6021. Epub 2021 May 5.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. China.

Surfaces with gradient topography are important in various fields but are difficult to fabricate. Herein, we report a facile and robust way to fabricate a surface with gradient topography of porous structure, in one direction, based on the breath figure (BF) method for the first time. The influencing factors including relative humidity (RH), sample immersion time, and solvent composition, affecting the speed, time, and model of the droplet growth, respectively, were investigated to control gradient BF pores with different ranges of pore sizes. Applying appropriate parameters, gradient BF pores with a diameter difference over 400% were prepared on one sample. The mechanism of gradient duration of solvent evaporation at different regions of a sample for fabricating gradient pores was proposed and experimentally verified with recording optical and thermographic changes of the sample in the BF procedure. This new method provides a novel site for gradient topography fabrication.
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http://dx.doi.org/10.1021/acs.langmuir.1c00636DOI Listing
May 2021

Elimination of human cytomegalovirus DNA degradation in urine.

J Med Virol 2021 May 3. Epub 2021 May 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Centers of Biological Products, School of Life Science and School of Public Health, Xiamen University, Xiamen, Fujian, China.

Congenital cytomegalovirus infection (cCMVi) is an important cause of sensorineural hearing loss in newborns. Detection of human cytomegalovirus (HCMV) DNA in urine has been used to screen for cCMVi in newborns. However, the matrix effect of urine on HCMV DNA detection is unclear. To evaluate the matrix effect of urine on HCMV DNA detection and optimize the sample process strategy to eliminate or minimize the impact of urine on HCMV DNA detection, DNA in spiked samples was extracted using different DNA extraction methods, and urine samples that could inhibit HCMV DNA detection were mixed to evaluate the inhibitory substances, inhibitory mechanism, and elimination of the inhibitory effect. The optimal urine sample process strategy was evaluated using 42 adult female urine samples and 42 newborn urine samples spiked with HCMV. Some urine samples were found to inhibit HCMV DNA detection due to DNA degradation. The addition of ≥5 mM EDTA to the urine before extraction eliminated the inhibitory effect of urine and did not affect the detection results of urine exhibiting no inhibition. Of the 42 adult female and 42 newborn urine samples, four and two samples, respectively, could inhibit HCMV DNA detection. However, the inhibitory effects of these six urine samples were eliminated after the addition of EDTA. The collective results indicate that the addition of EDTA can completely eliminate the impact of inhibitors present in urine on HCMV DNA extraction and improve the detection of HCMV in urine.
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http://dx.doi.org/10.1002/jmv.27035DOI Listing
May 2021

Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance.

Cell Metab 2021 Jun 27;33(6):1221-1233.e11. Epub 2021 Apr 27.

Department of Basic Medical Sciences, School of Medicine, Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, THU-PKU Center for Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

The ever-increasing understanding of the complexity of factors and regulatory layers that contribute to immune evasion facilitates the development of immunotherapies. However, the diversity of malignant tumors limits many known mechanisms in specific genetic and epigenetic contexts, manifesting the need to discover general driver genes. Here, we have identified the mA demethylase FTO as an essential epitranscriptomic regulator utilized by tumors to escape immune surveillance through regulation of glycolytic metabolism. We show that FTO-mediated mA demethylation in tumor cells elevates the transcription factors c-Jun, JunB, and C/EBPβ, which allows the rewiring of glycolytic metabolism. Fto knockdown impairs the glycolytic activity of tumor cells, which restores the function of CD8 T cells, thereby inhibiting tumor growth. Furthermore, we developed a small-molecule compound, Dac51, that can inhibit the activity of FTO, block FTO-mediated immune evasion, and synergize with checkpoint blockade for better tumor control, suggesting reprogramming RNA epitranscriptome as a potential strategy for immunotherapy.
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http://dx.doi.org/10.1016/j.cmet.2021.04.001DOI Listing
June 2021

Binaphthyl-prolinol chiral ligands: design and their application in enantioselective arylation of aromatic aldehydes.

Org Biomol Chem 2021 Apr;19(16):3644-3655

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People's Republic of China. and CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, People's Republic of China.

Binaphthyl-prolinol ligands were designed and applied in enantioselective arylation of aromatic aldehydes and sequential arylation-lactonization of methyl 2-formylbenzoate. Under optimized conditions, the reactions provided the desired diarylmethanols and 3-aryl phthalides in up to 96% yields with up to 99% ee and up to 89% yields with up to 99% ee, respectively. In particular, essentially optically pure 3-aryl phthalides (over 99% ee) were obtained in large quantities through recrystallization.
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http://dx.doi.org/10.1039/d1ob00289aDOI Listing
April 2021

A randomized controlled trial of ultrasound-assisted technique versus conventional puncture method for saphenous venous cannulations in children with congenital heart disease.

BMC Anesthesiol 2021 Apr 27;21(1):131. Epub 2021 Apr 27.

Department of Anesthesiology, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Pudong, Shanghai, 200127, China.

Background: The study investigated the success rate of the great saphenous venous catheter placement performed by ultrasound-assisted technique compared with the conventional puncture method in infants and toddlers with congenital heart disease and aimed to assess the efficiency and feasibility of this method within the context of pediatric peripheral venous access.

Methods: We selected infants and toddlers who underwent congenital cardiac surgery in our medical center from June 1, 2020, to September 7, 2020, by convenience sampling. Children were stratified by the presence of the manifesting cardiac types (cyanotic or acyanotic heart disease). They were assigned to the conventional puncture method group or the ultrasound-assisted group through randomly blocked randomization. The primary outcome was the success rate of the first attempt. The second outcomes included the time to cannulation at the first attempt, the redirections of the first attempt, overall puncture time, and overall redirections of efforts. Besides, a binary logistic regression model was implemented to identify the possible variables related to the success rate of the first attempt.

Results: A total of 144 children in our medical center were recruited in the study. The success rate of the first attempt in the ultrasound-assisted group was higher than that of the conventional puncture method group in the stratification of cyanotic children (66.7% vs. 33.3%, P = 0.035). Among children of acyanotic kind, the difference in the success rate of the first attempt between the two groups was not significant (57.6% vs. 42.4%, P = 0.194). Overall puncture time (45.5 s vs. 94 s, P = 0.00) and the time to cannulation at the first attempt (41.0 s vs. 60 s, P = 0.00) in the ultrasound-assisted group was less than the conventional puncture method group. The ultrasound-assisted group also required fewer redirections of the first attempt (three attempts vs. seven attempts, P = 0.002) and fewer total redirections of efforts (two attempts vs. three attempts, P = 0.027) than the conventional puncture method group. The result of binary Logistic regression showed that the success rate of the first attempt was related to age (OR:1.141; 95% CI = 1.010-1.290, P = 0.034), the redirections of the first attempt (OR:0.698; 95% CI = 0.528-0.923, P = 0.012) and the saphenous venous width (OR:1.181; 95% CI = 1.023-1.364, P = 0.023).

Conclusions: The ultrasound-assisted technique improves the saphenous venous cannulation sufficiently in children with difficult peripheral veins. The younger age is associated with a higher likelihood of peripheral venous difficulty. The ultrasound-assisted methods can effectively screen peripheral veins, e.g., selecting thicker diameter peripheral veins, making puncture less uncomfortable, and improving success rates. This method can be used as one of the effective and practical ways of peripheral venipuncture in children, especially in difficult situations. It should be widely applied as one of the alternative ultrasound techniques in the operating room.

Trial Registration: ChiCTR.org.cn ( ChiCTR-2,000,033,368 ). Prospectively registered May 29, 2020.
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http://dx.doi.org/10.1186/s12871-021-01349-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077689PMC
April 2021

Luteolin alleviates polycystic ovary syndrome in rats by resolving insulin resistance and oxidative stress.

Am J Physiol Endocrinol Metab 2021 Jun 26;320(6):E1085-E1092. Epub 2021 Apr 26.

Gynaecology Department Ward 2, Cangzhou Central Hospital, Cangzhou, China.

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by elevated secretion of androgen, commonly associated with insulin resistance (IR), which could exacerbate patient with PCOS. Development of a safe and effective treatment in preventing and treating PCOS will be beneficial to women of reproductive age. Female Sprague-Dawley rats were randomly divided into four groups: sham group treated with vehicle (saline) or luteolin; letrozole and high-fat-diet-induced PCOS group treated with vehicle or luteolin (25, 50, 100 mg/kg ip). Ovary tissue and blood were collected for further analysis. Luteolin normalized estrus cycle and improved ovarian morphology, including reduced polycystic and alleviated the loss of oocytes and corpus luteum in PCOS rats. Serum follicle stimulating hormone and estradiol were reduced, whereas luteinizing hormone and testosterone were elevated in PCOS rats relative to that of sham, which were significantly normalized by luteolin. Notably, luteolin significantly inhibited IR and upregulated protein levels of PI3K p85α and pAKT compared with PCOS rats treated with vehicle. In addition, the activities of antioxidants such as SOD, GPx, CAT, and GSH were reduced in PCOS rats, which were significantly increased by luteolin. Protein and mRNA expressions of Nrf2 and downstream genes such as and were restored by luteolin in PCOS rats. Collectively, this study demonstrated that luteolin inhibited IR by prompting PI3K/AKT signaling pathway and enhanced antioxidative response through the restoration of Nrf2 pathway. Luteolin normalizes the estrus cycle, ovarian morphological changes, improves serum sexual hormone levels, reduces insulin resistance, prompts PI3K/Akt signaling, improves antioxidative response, and upregulates Nrf2 signaling in PCOS rats. Luteolin has a potential to serve as a therapeutic agent in preventing and treating PCOS.
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http://dx.doi.org/10.1152/ajpendo.00034.2021DOI Listing
June 2021

Housing environment and early childhood development in sub-Saharan Africa: A cross-sectional analysis.

PLoS Med 2021 Apr 19;18(4):e1003578. Epub 2021 Apr 19.

Department of Maternal and Child Health, School of Public Health/National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China.

Background: The influence of the safety and security of environments on early childhood development (ECD) has been under-explored. Although housing might be linked to ECD by affecting a child's health and a parent's ability to provide adequate care, only a few studies have examined this factor. We hypothesized that housing environment is associated with ECD in sub-Saharan Africa (SSA).

Methods And Findings: From 92,433 children aged 36 to 59 months who participated in Multiple Indicator Cluster Survey (MICS) in 20 SSA countries, 88,271 were tested for cognitive and social-emotional development using the Early Childhood Development Index (ECDI) questionnaire and were thus included in this cross-sectional analysis. Children's mean age was 47.2 months, and 49.8% were girls. Children were considered developmentally on track in a certain domain if they failed no more than 1 ECDI item in that domain. In each country, we used conditional logistic regression models to estimate the association between improved housing (housing with finished building materials, improved drinking water, improved sanitation facilities, and sufficient living area) and children's cognitive and social-emotional development, accounting for contextual effects and socioeconomic factors. Estimates from each country were pooled using random-effects meta-analyses. Subgroup analyses were conducted by the child's gender, maternal education, and household wealth quintiles. On-track cognitive development was associated with improved housing (odds ratio [OR] = 1.15, 95% CI 1.06 to 1.24, p < 0.001), improved drinking water (OR = 1.07, 95% CI 1.00 to 1.14, p = 0.046), improved sanitation facilities (OR = 1.15, 95% CI 1.03 to 1.28, p = 0.014), and sufficient living area (OR = 1.06, 95% CI 1.01 to 1.10, p = 0.018). On-track social-emotional development was associated with improved housing only in girls (OR = 1.14, 95% CI 1.04 to 1.25, p = 0.006). The main limitations of this study included the cross-sectional nature of the datasets and the use of the ECDI, which lacks sensitivity to measure ECD outcomes.

Conclusions: In this study, we observed that improved housing was associated with on-track cognitive development and with on-track social-emotional development in girls. These findings suggest that housing improvement in SSA may be associated not only with benefits for children's physical health but also with broader aspects of healthy child development.
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http://dx.doi.org/10.1371/journal.pmed.1003578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092764PMC
April 2021

Characterization of Antibody-Drug Conjugate Pharmacokinetics and in Vivo Biotransformation Using Quantitative Intact LC-HRMS and Surrogate Analyte LC-MRM.

Anal Chem 2021 04 9;93(15):6135-6144. Epub 2021 Apr 9.

Integrated Bioanalysis, Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, 121 Oyster Point Boulevard, South San Francisco, California 94080, United States.

Antibody-drug conjugates (ADCs) pose challenges to bioanalysis because of their inherently intricate structures and potential for very complex catabolism. Common bioanalysis strategy is to measure the concentration of ADCs and Total Antibody (Ab) as well as deconjugated warhead in circulation. The ADCs and the Total Ab can be quantified with ligand binding assays (LBA) or with hybrid immunocapture-liquid chromatography coupled with multiple reaction monitoring mass spectrometry (LBA-LC-MRM). With the LBA-LC-MRM approach, a surrogate analyte, often the signature peptide, and released warhead can be used for the quantification of the Total Ab and ADCs, respectively. Recent advances in analytical instrumentation, especially the development of high resolution mass spectrometers (HRMS), have enabled characterization and quantification of intact macromolecules such as ADCs. The LBA-LC-HRMS approach employs immunocapture, followed by chromatographic separation at the macromolecule level and detection of the intact analyte. We developed an intact quantification method with 1-10 μg/mL linear dynamic range using 25 μL of plasma sample volume. This method was qualified for the measurement of naked monoclonal antibody (mAb), a site-specific cysteine-conjugated ADC with drug to antibody ratio ∼2 (DAR2) and a site-nonspecific cysteine-conjugated ADC (DAR8) in rat plasma. Samples from a rat pharmacokinetic (PK) study were analyzed with both methods. For the naked mAb, the results from both assays matched well. For ADCs, new species were observed from the LBA-HRMS method. The results demonstrated that potential biotransformation of the ADC was unveiled using the intact quantification approach while not being observed with traditional LBA-LC-MRM approach. Our work demonstrated an application of novel intact quantification by supporting animal PK studies. Moreover, our results suggest that the intact quantification method can provide novel perspectives on ADC in vivo characterization and quantification, which can benefit future drug candidate optimization as well as the immunogenicity impact evaluation and safety assessment.
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http://dx.doi.org/10.1021/acs.analchem.0c05376DOI Listing
April 2021

Microbiome assembly for sulfonamide subsistence and the transfer of genetic determinants.

ISME J 2021 Apr 5. Epub 2021 Apr 5.

Environmental Microbiome Engineering and Biotechnology Lab, Department of Civil Engineering, The University of Hong Kong, Hong Kong, China.

Antibiotic subsistence in bacteria represents an alternative resistance machinery, while paradoxically, it is also a cure for environmental resistance. Antibiotic-subsisting bacteria can detoxify antibiotic-polluted environments and prevent the development of antibiotic resistance in environments. However, progress toward efficient in situ engineering of antibiotic-subsisting bacteria is hindered by the lack of mechanistic and predictive understanding of the assembly of the functioning microbiome. By top-down manipulation of wastewater microbiomes using sulfadiazine as the single limiting source, we monitored the ecological selection process that forces the wastewater microbiome to perform efficient sulfadiazine subsistence. We found that the community-level assembly selects for the same three families rising to prominence across different initial pools of microbiomes. We further analyzed the assembly patterns using a linear model. Detailed inspections of the sulfonamide metabolic gene clusters in individual genomes of isolates and assembled metagenomes reveal limited transfer potential beyond the boundaries of the Micrococcaceae lineage. Our results open up new possibilities for engineering specialist bacteria for environmental applications.
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http://dx.doi.org/10.1038/s41396-021-00969-zDOI Listing
April 2021

Applications of marine collagens in bone tissue engineering.

Biomed Mater 2021 Apr 1;16(4):042007. Epub 2021 Apr 1.

The Second Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, 510006 Guangzhou, People's Republic of China. East China Institute of Digital Medical Engineering, Shangrao 334000, People's Republic of China.

For decades, collagen has been among the most widely used biomaterials with several biomedical applications. Recently, researchers have shown a keen interest in collagen obtained from marine sources because of its biocompatibility, biodegradability, ease of extractability, safety, low immunogenicity, and low production costs. A wide variety of marine collagen-based scaffolds have been developed for bone tissue engineering, and these scaffolds display excellent biological effects. This review aims to provide an overview of the biological effects of marine collagen in bone engineering, such as promoting osteogenesis and collagen synthesis, inhibiting inflammation, inducing the differentiation of cartilage, and improving bone mineral density. Marine collagen holds great promise as a biomaterial in bone tissue engineering.
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http://dx.doi.org/10.1088/1748-605X/abf0b6DOI Listing
April 2021

Genome of a citrus rootstock and global DNA demethylation caused by heterografting.

Hortic Res 2021 Apr 1;8(1):69. Epub 2021 Apr 1.

Key Laboratory of Horticultural Plant Biology (Ministry of Education), Huazhong Agricultural University, 430070, Wuhan, China.

Grafting is an ancient technique used for plant propagation and improvement in horticultural crops for at least 1,500 years. Citrus plants, with a seed-to-seed cycle of 5-15 years, are among the fruit crops that were probably domesticated by grafting. Poncirus trifoliata, a widely used citrus rootstock, can promote early flowering, strengthen stress tolerance, and improve fruit quality via scion-rootstock interactions. Here, we report its genome assembly using PacBio sequencing. We obtained a final genome of 303 Mb with a contig N50 size of 1.17 Mb and annotated 25,680 protein-coding genes. DNA methylome and transcriptome analyses indicated that the strong adaptability of P. trifoliata is likely attributable to its special epigenetic modification and expression pattern of resistance-related genes. Heterografting by using sweet orange as scion and P. trifoliata as rootstock and autografting using sweet orange as both scion and rootstock were performed to investigate the genetic effects of the rootstock. Single-base methylome analysis indicated that P. trifoliata as a rootstock caused DNA demethylation and a reduction in 24-nt small RNAs (sRNAs) in scions compared to the level observed with autografting, implying the involvement of sRNA-mediated graft-transmissible epigenetic modifications in citrus grafting. Taken together, the assembled genome for the citrus rootstock and the analysis of graft-induced epigenetic modifications provide global insights into the genetic effects of rootstock-scion interactions and grafting biology.
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http://dx.doi.org/10.1038/s41438-021-00505-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012640PMC
April 2021

Preparation and Properties of Benzylsulfonyl-Containing Silicone Copolymers via Ring-opening Copolymerization of Macroheterocyclosiloxane and Cyclosiloxane.

Chemistry 2021 May 30;27(29):7897-7907. Epub 2021 Apr 30.

Key Laboratory of Special Functional Aggregated Materials & Key Laboratory of Colloid and Interface Chemistry (Shandong University), Ministry of Education Department, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250199, P. R. China.

Ring-opening copolymerization (ROCP) of benzylsulfonyl macroheterocyclosiloxane (BSM) and five different cyclosiloxanes was systematically investigated. A general approach for the synthesis of benzylsulfonyl-containing silicone copolymers with various substituents, including methyl, vinyl, ethyl, and phenyl, was developed herein. A series of copolymers with variable incorporation (from 6 % to 82 %) of BSM were obtained by modifying the comonomer feed ratio and using KOH as the catalyst in a mixed solvent of dimethylformamide and toluene. The obtained copolymers exhibited various composition-dependent properties and unique viscoelasticity. Notably, the surface and fluorescent characteristics as well as the glass transition temperatures of the copolymers could be tailored by varying the amount of BSM. Unlike typical sulfone-containing polymers, such as poly(olefin sulfone)s, the prepared copolymers displayed excellent thermal and hydrolytic stability. The universal strategy developed in the present study provides a platform for the design of innovative silicone copolymers with adjustable structures and performance.
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http://dx.doi.org/10.1002/chem.202100309DOI Listing
May 2021

2-(2-Cholesteroxyethoxyl)ethyl 3'-S-glutathionylpropionate and its self-assembled micelles for brain delivery: Design, synthesis and evaluation.

Int J Pharm 2021 May 26;600:120520. Epub 2021 Mar 26.

Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Box 2202C, South Dakota State University, Brookings, SD 57007, United States. Electronic address:

The blood-brain barrier (BBB) is a barrier that prevents almost all large and most small exogenous molecules from reaching the brain. The barrier is the major cause of treatment failure for most brain diseases. Extensive efforts have been made to facilitate drug molecules to cross the BBB. One of the approaches is to employ an endogenous ligand or ligand analogue that can enter the brain through its transporter or receptor at the BBB as a brain-targeting agent. Glutathione (GSH) transporters are richly expressed at the BBB with limited presence in other tissues except kidneys. 2-(2-Cholesteroxyethoxyl)ethyl 3'-S-glutathionylpropionate (COXP), formed by connecting GSH with cholesterol through a linker, was designed as a GSH transporter-mediated brain targeting molecule. The amphiphilic nature of COXP enables the molecule to self-assemble to form micelles with a CMC value of 3.9 μM. By using DiR as a fluorescence tracking agent and the whole-body fluorescence imaging technique, the brain distribution of DiR delivered by COXP micelles in mice was 20 folds higher when compared with free DiR. Interestingly, the brain targeting effect was further enhanced by co-administration of GSH. The low CMC value and effective brain targeting make COXP micelles a promising drug delivery system to the brain.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120520DOI Listing
May 2021

Risk factors for cholesterol polyp formation in the gallbladder are closely related to lipid metabolism.

Lipids Health Dis 2021 Mar 22;20(1):26. Epub 2021 Mar 22.

Department of General Surgery, Xuanwu Hospital, The First Clinical Medical College, Capital Medical University, No.45 Changchun Street, Beijing, China.

Background: The purpose of this study was to assess the risk factors for cholesterol polyp formation in the gallbladder.

Methods: This was a multicenter retrospective study based on pathology. From January 2016 to December 2019, patients who underwent cholecystectomy and non-polyp participants confirmed by continuous ultrasound follow-ups were reviewed. Patients in the cholesterol polyp group were recruited from three high-volume centers with a diagnosis of pathologically confirmed cholesterol polyps larger than 10 mm. Population characteristics and medical data were collected within 24 h of admission before surgery. The non-polyp group included participants from the hospital physical examination center database. They had at least two ultrasound examinations with an interval longer than 180 days. Data from the final follow-up of the non-polyp group were analyzed. The risk factors for cholesterol polyp formation were analyzed by comparing the two groups.

Results: A total of 4714 participants were recruited, including 376 cholesterol polyp patients and 4338 non-polyp participants. In univariate analysis, clinical risk factors for cholesterol polyps were age, male sex, higher body mass index (BMI), higher low-density lipoprotein (LDL), lower high-density lipoprotein (HDL), and higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. In multivariate logistic analysis, independent risk factors were age > 50 years (odds ratio [OR] = 3.02, 95% confidence interval [CI] 2.33-3.91, P < 0.001], LDL > 2.89 mmol/L (OR = 1.38, 95% CI 1.08-1.78, P = 0.011), lower HDL (OR = 1.78 95% CI 1.32-2.44, P < 0.001), AST > 40 IU/L (OR = 3.55, 95% CI 2.07-6.07, P < 0.001), and BMI > 25 kg/m (OR = 1.32, 95% CI 1.01-1.72, P = 0.037).

Conclusions: Age, LDL, HDL, AST, and BMI are strong risk factors for cholesterol polyp formation. Older overweight patients with polyps, accompanied by abnormal lipid levels, are at high risk for cholesterol polyps.
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http://dx.doi.org/10.1186/s12944-021-01452-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983281PMC
March 2021

Applications of marine collagen in bone tissue engineering.

Biomed Mater 2021 Mar 22. Epub 2021 Mar 22.

Orthopedics Department, Guangzhou Hospital of Traditional Chinese Medicine, guangdong university, Guangzhou, 510120, CHINA.

For decades, collagen has been among the most widely used biomaterials with several biomedical applications. Recently, researchers have shown a keen interest in collagen obtained from marine sources because of its biocompatibility, biodegradability, ease of extractability, safety, low immunogenicity, and low production costs. A wide variety of marine collagen-based scaffolds have been developed for bone tissue engineering, and these scaffolds display excellent biological effects. This review aims to provide an overview of the biological effects of marine collagen in bone engineering, such as promoting osteogenesis and collagen synthesis, inhibiting inflammation, inducing the differentiation of cartilage, and improving bone mineral density. Marine collagen holds great promise as a biomaterial in bone tissue engineering.
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http://dx.doi.org/10.1088/1748-605X/abf0b6DOI Listing
March 2021

Altered glycolysis results in drug-resistant in clinical tumor therapy.

Oncol Lett 2021 May 11;21(5):369. Epub 2021 Mar 11.

Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Cancer cells undergo metabolic reprogramming, including increased glucose metabolism, fatty acid synthesis and glutamine metabolic rates. These enhancements to three major metabolic pathways are closely associated with glycolysis, which is considered the central component of cancer cell metabolism. Increasing evidence suggests that dysfunctional glycolysis is commonly associated with drug resistance in cancer treatment, and aberrant glycolysis plays a significant role in drug-resistant cancer cells. Studies on the development of drugs targeting these abnormalities have led to improvements in the efficacy of tumor treatment. The present review discusses the changes in glycolysis targets that cause drug resistance in cancer cells, including hexokinase, pyruvate kinase, pyruvate dehydrogenase complex, glucose transporters, and lactate, as well the underlying molecular mechanisms and corresponding novel therapeutic strategies. In addition, the association between increased oxidative phosphorylation and drug resistance is introduced, which is caused by metabolic plasticity. Given that aberrant glycolysis has been identified as a common metabolic feature of drug-resistant tumor cells, targeting glycolysis may be a novel strategy to develop new drugs to benefit patients with drug-resistance.
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http://dx.doi.org/10.3892/ol.2021.12630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967983PMC
May 2021

A review on the application of spectroscopy to the condiments detection: from safety to authenticity.

Crit Rev Food Sci Nutr 2021 Mar 19:1-16. Epub 2021 Mar 19.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, P. R. China.

Condiments are the magical ingredients that make the food present a richer taste. In recent years, due to the increasing consciousness of food safety and human health, much progress has been made in developing rapid and nondestructive techniques for the evaluation of food condiments safety, authentication, and traceability. The potential of spectroscopy techniques, such as near-infrared (NIR), mid-infrared (MIR), Raman, fluorescence, inductively coupled plasma (ICP), and hyperspectral imaging techniques, has been widely enhanced by numerous applications in this field because of their advantages over other analytical techniques. Following a brief introduction of condiment and safety basics, this review mainly focuses on recent vibrational and atomic spectral applications for condiment nondestructive analysis and evaluation, including (1) chemical hazards detection; (2) microbiological hazards detection; and (3) authenticity concerns. The review shows current spectroscopies to be effective tools that will play indispensable roles for food condiment evaluation. In addition, online/real-time applications of these techniques promise to be a huge growth field in the near future.
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http://dx.doi.org/10.1080/10408398.2021.1901257DOI Listing
March 2021

Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia.

Mol Genet Metab Rep 2021 Jun 3;27:100735. Epub 2021 Mar 3.

Biochemical Genetics, Advanced Diagnostics-Genetics, Genomics and R&D, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, United States of America.

Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for arginase deficiency vary between individual states in the US but often include hyperargininemia and elevated arginine to ornithine (Arg/Orn) ratio. Here, we report 14 arginase deficiency cases, including two patients with positive NBS for hyperargininemia in whom the diagnosis of arginase deficiency was delayed owing to normal or near normal plasma arginine levels on follow-up testing. To improve the detection capability for arginase deficiency, we evaluated plasma Arg/Orn ratio as a secondary diagnostic marker in positive NBS cases for hyperargininemia. We found that plasma Arg/Orn ratio combined with plasma arginine was a better marker than plasma arginine alone to differentiate patients with arginase deficiency from unaffected newborns. In fact, elevated plasma arginine in combination with an Arg/Orn ratio of ≥1.4 identified all 14 arginase deficiency cases. In addition, we examined the impact of age on plasma arginine and ornithine levels. Plasma arginine increased 0.94 μmol/L/day while ornithine was essentially unchanged in the first 31 days of life, which resulted in a similar increasing trend for the Arg/Orn ratio (0.01/day). This study demonstrated that plasma Arg/Orn ratio as a secondary diagnostic marker improved the detection capability for arginase deficiency in newborns with hyperargininemia, which will allow timely detection of arginase deficiency and hence initiation of treatment before developing symptoms.
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http://dx.doi.org/10.1016/j.ymgmr.2021.100735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937551PMC
June 2021