Publications by authors named "Xiao He"

632 Publications

Estimation of Aromatic Secondary Organic Aerosol Using a Molecular Tracer-A Chemical Transport Model Assessment.

Environ Sci Technol 2021 Sep 15. Epub 2021 Sep 15.

Zachry Department of Civil and Environmental Engineering, Texas A&M University, College Station, Texas 77843-3136, United States.

A modified community multiscale air quality model, which can simulate the regional distributions of 2,3-dihydroxy-4-oxopentanoic acid (DHOPA), a marker species for monoaromatic secondary organic aerosol (SOA), was applied to assess the applicability of using the DHOPA to aromatic SOA mass ratio () from smog chamber experiments to estimate aromatic SOA during a three-week wintertime air quality campaign in urban Shanghai. The modeled daily DHOPA concentrations based on the chamber-derived mass yields agree well with the organic marker field measurements ( = 0.79; MFB = 0.152; and MFE = 0.440). Two-thirds of the DHOPA are from the oxidation of ARO1 (lumped less-reactive aromatic species; mostly toluene), with the rest from ARO2 (lumped more-reactive aromatic species; mostly xylenes). Modeled DHOPA is mainly in the particle phase under ambient organic aerosol (OA) loading but could exhibit significant gas-particle partitioning when a higher estimation of the DHOPA vapor pressure is used. The modeled shows a strong dependence on the OA loading when only semivolatile aromatic SOA components are included in the calculations. However, this OA dependence becomes weaker when non-volatile oligomers and dicarbonyl SOA products are considered. A constant value of ∼0.002 is determined when all aromatic SOA components are included, which is a factor of 2 smaller than the commonly applied chamber-based value of 0.004 for toluene. This model-derived value does not show much spatial variation and is not sensitive to alternative estimates of DHOPA vapor pressures and SOA yields, and thus provides an appropriate scaling factor to assess aromatic SOA from DHOPA measurements. This result helps refine the quantification of SOA attributable to monoaromatic hydrocarbons in urban environments and thereby facilitates the evaluation of control measures targeting these specific precursors.
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http://dx.doi.org/10.1021/acs.est.1c03670DOI Listing
September 2021

A fixed multi-site interaction charge model for an accurate prediction of the QM/MM interactions.

Phys Chem Chem Phys 2021 Sep 15. Epub 2021 Sep 15.

Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development, Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

A fixed multi-site interaction charge (FMIC) model was proposed for the accurate prediction of intermolecular electrostatic interactions based on the quantum mechanical linear response of a molecule to an external electric field. In such a model, some additional off-center interaction sites were added for capturing multipole interactions for a given molecule. By multivariate least-square fitting analysis of the calculated QM/MM interactions of a given molecule with the electrostatic environment and the electrostatic potentials of the environment at the pre-defined distributed interaction sites, the FMIC of the molecule was obtained. The model system of CO in myoglobin (Mb) was utilized to demonstrate the derivation of the FMIC. The accuracy of FMIC in predicting the electrostatic interactions between CO and the Mb environment was investigated using 10 000 different Mb-CO configurations generated from the 400 ps QM/MM MD simulation. In comparison to the QM/MM calculations at the B3LYP/aug-cc-pVTZ/ff99SB level, the mean unsigned error (MUE) of the results based on the FMIC model was merely 0.10 kcal mol, and the root mean square error (RMSE) was only 0.13 kcal mol, which are significantly lower than the results predicted by the ESP charge model (MUE = 1.45 kcal mol, and RMSE = 1.7 kcal mol, respectively). The transferability of FMIC was tested by applying the obtained FMIC in the wild type Mb-CO system to the mutants of V68F and H64L Mb-CO systems. The MUEs of the obtained results for 10 000 different configurations are both smaller than 0.2 kcal mol for the V68F and H64L Mb-CO systems in comparison to the B3LYP/aug-cc-pVTZ/ff99SB calculations, and the RMSEs are also lower than 0.2 kcal mol for both mutants. The applications of FMIC were extended to model the electrostatic interactions between a hydrogen fluoride molecule and 492 waters in a truncated octahedron box; our study showed that the FMIC could give satisfactory results with a MUE of 0.12 kcal mol and a RMSE of 0.16 kcal mol in comparison to the B3LYP/aug-cc-pVDZ/TIP3P calculations for 10 000 different configurations generated using the 10 ns classical MD simulation. Therefore, the FMIC method provides an accurate and efficient tool for predicting intermolecular electrostatic interactions, which can be utilized in the future development of molecular force fields.
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http://dx.doi.org/10.1039/d1cp02776jDOI Listing
September 2021

Application of NRS2002 in Preoperative Nutritional Screening for Patients with Liver Cancer.

J Oncol 2021 27;2021:8943353. Epub 2021 Aug 27.

Department of Hepatological Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China.

Objective: To explore the application of NRS2002 in preoperative nutritional screening of patients with liver cancer (LC).

Methods: 60 LC patients treated in the First Affiliated Hospital of Gannan Medical University (January 2018-May 2021) were chosen as the research objects, and split into group J without nutritional risk and group Q with nutritional risk according to the results of NRS2002 to compare the preoperative situation, surgery-related indexes, hematological indexes, postoperative recovery, and incidence of complications between the two groups.

Results: Group J ( = 28) and group Q ( = 32) showed no obvious difference in preoperative situation, and patients' liver function indexes were within the normal range. The duration of surgery in group J was notably shorter compared with group Q ( < 0.05). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), and albumin in group J were notably different from those of group Q ( < 0.001) at 1 day after surgery. ALT and AST in group J were notably different from those of group Q at 3 days after surgery ( < 0.001). No obvious differences were observed in the hematological indexes between the two groups at 5 days after surgery ( > 0.05). The total amount of albumin infusion, postoperative hospitalization time, and hospitalization cost in group J were notably lower compared with group Q ( < 0.001). The incidence of complications in group J was notably lower compared with group Q ( < 0.05).

Conclusion: Postoperative recovery of LC patients is closely related to their preoperative nutritional status, and those with poor nutritional status have a high incidence of postoperative complications and long recovery time. NRS2002 can effectively screen the nutritional status of patients and provide reference for prognosis evaluation.
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http://dx.doi.org/10.1155/2021/8943353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434900PMC
August 2021

The Role of Respiratory Microbiota in Lung Cancer.

Int J Biol Sci 2021 25;17(13):3646-3658. Epub 2021 Aug 25.

Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.

Recently, the impact of microorganisms on tumor growth and metastasis has attracted great attention. The pathogenesis and progression of lung cancer are related to an increase in respiratory bacterial load as well as changes in the bacterial community because the microbiota affects tumors in many ways, including canceration, metastasis, angiogenesis, and treatment. The microbiota may increase tumor susceptibility by altering metabolism and immune responses, promoting inflammation, and increasing toxic effects. The microbiota can regulate tumor metastasis by altering multiple cell signaling pathways and participate in tumor angiogenesis through vascular endothelial growth factors (VEGF), endothelial cells (ECs), inflammatory factors and inflammatory cells. Tumor angiogenesis not only maintains tumor growth at the primary site but also promotes tumor metastasis and invasion. Therefore, angiogenesis is an important mediator of the interaction between microorganisms and tumors. The microbiota also plays a part in antitumor therapy. Alteration of the microbiota caused by antibiotics can regulate tumor growth and metastasis. Moreover, the microbiota also influences the efficacy and toxicity of tumor immunotherapy and chemotherapy. Finally, the effects of air pollution, a risk factor for lung cancer, on microorganisms and the possible role of respiratory microorganisms in the effects of air pollution on lung cancer are discussed.
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http://dx.doi.org/10.7150/ijbs.51376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416743PMC
August 2021

A CTL/M2 macrophage-related four-gene signature predicting metastasis-free survival in triple-negative breast cancer treated with adjuvant radiotherapy.

Breast Cancer Res Treat 2021 Sep 5. Epub 2021 Sep 5.

Department of Cancer Center, Daping Hospital & Army Medical Center of PLA, Third Military Medical University (Army Medical University), No. 10 Changjiang Zhilu, Yuzhong District, Chongqing, 400042, China.

Purpose: This study aimed to develop and validate a prognostic model for metastasis-free survival (MFS) based on genes that may functionally interact with cytotoxic T lymphocytes (CTLs) and M2 macrophages in patients with triple-negative breast cancer (TNBC) who underwent adjuvant radiotherapy.

Methods: The transcriptional and phenotypic profiles of TNBC and other breast cancer subtypes were downloaded from gene expression omnibus (GEO). The abundance of infiltrated immune cells was evaluated through CIBERSORTx or MCP-counter. A weighted linear model, the score for MFS (SMFS), was developed using the least absolute shrinkage and selection operator (LASSO) in GSE58812 and validated in GSE2034 and GSE12276. The biological implication of the SMFS was explored by evaluating its associations with TNBC molecular subtypes and other radiosensitivity- or immune-related signatures.

Results: A model consisting of the PCDH12/ELP3, PCDH12/MSRA, and FAM160B2/MSRA gene expression ratios with non-zero coefficients finally selected by LASSO was developed using GSE58812. In GSE2034 (treatment with adjuvant radiotherapy), the SMFS was significantly associated with MFS in TNBC patients (hazard ratio (HR) = 8.767, 95% confidence interval (CI) 1.856-41.408, P = 0.006) and, to a lesser extent, in non-TNBC patients (HR = 2.888, 95% CI 1.076-7.750, P = 0.035). However, the interaction of subtype (TNBC vs non-TNBC) and the SMFS tended to be significant (P = 0.081). In contrast, the SMFS was not significantly associated with MFS in either TNBC patients (P = 0.499) or non-TNBC patients (P = 0.536) in GSE12276 (treatment without radiotherapy). Among the four TNBC molecular subtypes, the c1 and c4 subtypes exhibited higher CTL infiltration and lower SMFS values than the c2 and c3 subtypes. In addition, the SMFS was positively correlated with the abundance of endothelial cells (r = 0.413, P < 0.001).

Conclusion: The proposed model has the potential to predict MFS in TNBC patients after adjuvant radiotherapy, and the SMFS may represent a measurement of tumor immune suppression.
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http://dx.doi.org/10.1007/s10549-021-06379-1DOI Listing
September 2021

Prevalence of myopia in 3-14-year-old Chinese children: a school-based cross-sectional study in Chengdu.

BMC Ophthalmol 2021 Sep 1;21(1):318. Epub 2021 Sep 1.

Department of Optometry and Vision Science, West China School of Medicine, Sichuan University, 37 Guoxue Xiang, Sichuan Province, Chengdu, China.

Background: The prevalence of myopia among children in Chengdu is unknown. The aim of this study was to determine the prevalence of myopia in 3- to 14-year-old Chinese children in Chengdu.

Methods: This study was a school-based cross-sectional study in children aged 3-14 years. Visual acuity (VA), spherical equivalent error (SER) with noncycloplegic autorefraction, axial length (AL) and corneal radius (CR) were measured.

Results: A total of 19,455 children were recruited for this study. The prevalence of myopia was 38.1 %; the prevalence of low myopia was 26.6 %, that of moderate myopia was 9.8 %, and that of high myopia was 1.7 %. The prevalence of myopia and SER increased with age from 6 years old. The prevalence of myopia was higher, and the SER indicated more severe myopia in the girls than in the boys (40.1 % vs. 36.2 %, χ = 30.67, d = 1, P < 0.001; -0.93 D ± 1.75 D vs. -0.84 D ± 1.74 D, t = 3.613, d=19,453, P < 0.001). The girls had a higher prevalence of myopia and myopic SER than did the boys aged 9 years and older (P < 0.05). Among the myopic children, the rates of uncorrected, undercorrected and fully corrected myopia were 54.8 %, 31.1 and 14.1 %, respectively. AL and AL/CR increased with age from 6 years old, but CR remained stable after 4 years old. The AL was longer, and the CR was flatter in the boys than in the girls aged 3 to 14 years old (P < 0.05).

Conclusions: The prevalence of myopia, AL and AL/CR increased, and the SER became more myopic with age from 6 years old. The girls had a higher prevalence of myopia and myopic SER than did the boys, but the boys had a longer AL, flatter CR and higher AL/CR ratio than did the girls. The rate of uncorrected myopia was very high in the myopic children. More actions need to be taken to decrease the prevalence of myopia, especially uncorrected myopia in children.
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http://dx.doi.org/10.1186/s12886-021-02071-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411514PMC
September 2021

Accurate Prediction of Absorption Spectral Shifts of Proteorhodopsin Using a Fragment-Based Quantum Mechanical Method.

Molecules 2021 Jul 25;26(15). Epub 2021 Jul 25.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Many experiments have been carried out to display different colors of Proteorhodopsin (PR) and its mutants, but the mechanism of color tuning of PR was not fully elucidated. In this study, we applied the Electrostatically Embedded Generalized Molecular Fractionation with Conjugate Caps (EE-GMFCC) method to the prediction of excitation energies of PRs. Excitation energies of 10 variants of Blue Proteorhodopsin (BPR-PR105Q) in residue 105GLN were calculated with the EE-GMFCC method at the TD-B3LYP/6-31G* level. The calculated results show good correlation with the experimental values of absorption wavelengths, although the experimental wavelength range among these systems is less than 50 nm. The ensemble-averaged electric fields along the polyene chain of retinal correlated well with EE-GMFCC calculated excitation energies for these 10 PRs, suggesting that electrostatic interactions from nearby residues are responsible for the color tuning. We also utilized the GMFCC method to decompose the excitation energy contribution per residue surrounding the chromophore. Our results show that residues ASP97 and ASP227 have the largest contribution to the absorption spectral shift of PR among the nearby residues of retinal. This work demonstrates that the EE-GMFCC method can be applied to accurately predict the absorption spectral shifts for biomacromolecules.
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http://dx.doi.org/10.3390/molecules26154486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347797PMC
July 2021

Emerging Threat of Multidrug Resistant Pathogens From Neonatal Sepsis.

Front Cell Infect Microbiol 2021 12;11:694093. Epub 2021 Jul 12.

Department of Laboratory Medicine, Chongqing Health Center for Women and Children, Chongqing, China.

Multidrug-resistant (MDR) pathogens are responsible for a substantial burden of morbidity and mortality from neonatal sepsis; however, data on these sepsis-related pathogens among hospitalized neonates in China are not well characterized. In this study, a total of 240 strains were isolated from four Women and Children's hospitals in Southwest China between 2014 and 2019. Of these included pathogens, 104 (43.33%) were gram-positive bacteria, 129 (53.75%) were gram-negative bacteria, and 7 (2.92%) were fungi. (, 34.01%) and (, 15.35%) were the main pathogen of neonate bacteremia. ST167 were the most prevalent STs in and ST11 in Our study found that (62.71%) was the predominate pathogen of early-onset sepsis, among which 64.86% were MDR. Late-onset sepsis was mainly caused by (28.31%) and (24.78%), with showing that 78.33% of these pathogens were MDR. Notably, the prevalence of EO/LO pathogens were quite different from Indian and south of China. Moreover, we found that (42.06%) was most dominant resistant genes with about a third isolates (31.09%) were positive for . All the carbapenem-resistant were positive for NDM-1. Moreover, late-onset sepsis and antibiotic exposure were significantly associated with MDR infection. Emerging multi-resistant pathogens of sepsis posts a serious threat to neonatal outcomes and emphasizes an urgent need to control their further spread.
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http://dx.doi.org/10.3389/fcimb.2021.694093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312093PMC
August 2021

Discovery of novel pyrazolopyrimidine derivatives as potent mTOR/HDAC bi-functional inhibitors via pharmacophore-merging strategy.

Bioorg Med Chem Lett 2021 Oct 24;49:128286. Epub 2021 Jul 24.

College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.

The mTOR and HDAC dual suppression is meaningful for counteracting drug resistance resulted from kinase mutation and bypass mechanisms. Herein, we communicate our recent discovery of a novel structural series of mTOR/HDAC bi-functional inhibitors featuring the pyrazolopyrimidine core via pharmacophore-merging strategy. More than half of them exerted potent dual-target inhibitory activities. In particular, compound 50 exhibited IC values of 0.49 and 0.91 nM against mTOR and HDAC1, respectively, along with remarkably enhanced anti-proliferative activity (IC = 1.74 μM) against MV4-11 cell line than mTOR inhibitor MLN-0128 (IC = 5.84 μM) and HDAC inhibitor SAHA (IC = 8.44 μM). Its intracellular intervention of both mTOR signaling and HDAC was validated by the Western blot analysis. Moreover, as the first disclosed mTOR/HDAC dual inhibitor with selectivity for some specific HDAC subtypes, it has the potential to alleviate the adverse effects resulted from pan-HDAC inhibition. Attributed to its favorable in vitro performance, compound 50 is valuable for further functional investigation as a polypharmacological anti-cancer agent.
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http://dx.doi.org/10.1016/j.bmcl.2021.128286DOI Listing
October 2021

Clickable amino acid derivative tuned self-assembly of antigen and adjuvant for cancer immunotherapy.

J Control Release 2021 Sep 24;337:306-316. Epub 2021 Jul 24.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China. Electronic address:

Amino acid-tuned self-assembly has become an attractive strategy for constructing various functional materials. Here, a series of dibenzocyclooctyne (DIBO) functionalized amphiphilic amino acid derivatives are designed and screened as building blocks of functional supramolecular self-assembly nanoparticles for cancer immunotherapy. One top-performing supramolecular self-assembly material (named DA6C1) is identified through combinatorial screening, and spherical nanoparticles can be easily prepared by this material tuned multicomponent synergistic self-assembly of ovalbumin (OVA) and CpG oligonucleotide. DA6C1 based nanovaccine can significantly enhance the cellular uptake of OVA and CpG into the same bone marrow derived dendritic cells (BMDCs) and greatly improve the activation of DCs. Moreover, after subcutaneous injection, this nanovaccine flows rapidly to the lymph nodes and elicits strong immune responses to achieve effective prophylactic and therapeutic effect. Therefore, our work highlights the great potential of clickable amino acid derivatives as a convenient and powerful tool to construct nanovaccine for effective immunotherapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.033DOI Listing
September 2021

Paeoniflorin ameliorates oxidase stress in Glutamate-stimulated SY5Y and prenatally stressed female offspring through Nrf2/HO-1 signaling pathway.

J Affect Disord 2021 Nov 17;294:189-199. Epub 2021 Jul 17.

Biomedicine Key Laboratory of Shaanxi Province, school of pharmacy, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, China. Electronic address:

Background: Prenatal stress (PS) can cause brain retardation, reduce the learning and memory ability of the offspring and significantly increase the incidence of depression in offspring. Paeoniflorin (PF), a kind of monoterpenoid glycoside, is one of the main active ingredients of Chinese Medicine Paeonia lactiflora Pall, has anti-inflammation and potential neuroprotective effects. However, few reports have shown that the neuroprotective effects of PF are exerted through ameliorating Glutamate toxicity in vivo and in vitro.

Methods: Here, we used a prenatal restraint stress model and Glu-induced excitotoxic neurotoxicity in SH-SY5Y cells to study the effects of PF.

Results: Our results showed that PF can ameliorate learning and memory impairments and increases the density of hippocampal neurons, typical Golgi-positive pyramidal cells, and neuronal Neurogranin (Ng) expression in PS rat offspring. Furthermore, PF can significantly up-regulate the decrease of Glu-induced SH-SY5Y cell viability. At the same time, PF can significantly reduce apoptosis, ROS, NO levels, and intracellular Ca concentration, and significantly inhibit the increase of mitochondrial membrane potential. Besides, PF significantly increased the expression of Nrf2 and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active-caspase-3, and active-caspase-9.

Conclusions: Our results demonstrate that PF may be an effective treatment in preventing the development of PS-induced learning and memory impairment and have therapeutic potential in Glu-related neurological diseases.
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http://dx.doi.org/10.1016/j.jad.2021.07.054DOI Listing
November 2021

Glucose-Lipopeptide Conjugates Reveal the Role of Glucose Modification Position in Complexation and the Potential of Malignant Melanoma Therapy.

J Med Chem 2021 Aug 20;64(15):11483-11495. Epub 2021 Jul 20.

The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.

Glycosylation and fatty acid modification are promising strategies to improve peptide performance. We previously studied glycosylation and fatty acid modification of the anticancer peptide R-lycosin-I. In this study, we further investigated the co-modification of fatty acids and monosaccharides in R-lycosin-I. A glucose derivative was covalently coupled to the ε-amino group of the Lys residues of the lipopeptide R-C, which was derived from R-lycosin-I modified with dodecanoic acid, and obtained seven glycolipid peptides. They exhibited different cytotoxicity profiles, which may be related to the changes in physicochemical properties and binding ability to glucose transporter 1 (GLUT1). Among them, R-C-4 exhibited the highest cytotoxicity and improved selectivity. A further study demonstrated that R-C-4 showed significant cytotoxicity and antimetastasis activity in murine melanoma cells, melanoma spheroids, and animal models. Our results indicated that the glucose derivative modification position plays important roles in glucose-lipopeptide conjugates, and R-C-4 might be a promising lead for developing anticancer drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00805DOI Listing
August 2021

Spatial and temporal variation of dissolved heavy metals in the Lijiang River, China: implication of rainstorm on drinking water quality.

Environ Sci Pollut Res Int 2021 Jul 17. Epub 2021 Jul 17.

Department of the Earth Sciences, Quaid-I-Azam University Islamabad, Islamabad, 45320, Pakistan.

Lijiang River is an essential drinking water source and natural scenery in the Guilin City. For the first time, implications of rainstorm were taken into consideration by investigating spatial and temporal variation of dissolved heavy metals (HMs) in the Lijiang River water. A total of 68 water samples were collected during low flow (normal) season and high flow (rainstorm) season from 34 sampling sites. Dissolved HMs including Cr, Mn, Co, Cu, Zn, As, Cd, Sb, and Pb were found to meet the respective drinking water standards, while comparatively higher concentration was observed after the rainstorm season, except for Cr. Multivariate statistical analysis showed that Co, Cu, Cr, Zn, Sb, and Pb in normal season were mainly controlled by anthropogenic sources. Furthermore, higher concentrations of Mn, Cu, Cd, Pb, Co, and Zn during the high flow season were attributed to rainstorm. The water quality index (WQI) showed good grades and comparatively lower in rainstorm season. The results of health risk assessment revealed that HMs in Lijiang River posed limited health risk; however, As posed potential health risk specially in rainstorm season. It is suggested to adopt preventive measures for mining activities and industrial waste-water discharge at the river's upstream and downstream.
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http://dx.doi.org/10.1007/s11356-021-15383-3DOI Listing
July 2021

Tissue-specific expression atlas of murine mitochondrial tRNAs.

J Biol Chem 2021 Aug 13;297(2):100960. Epub 2021 Jul 13.

Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China; Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Lab of Genetic and Developmental Disorders, Zhejiang Univrsity, Hangzhou, Zhejiang, China; Key Lab of Reproductive Genetics, Center for Mitochondrial Genetics, Ministry of Education of PRC, Zhejiang University, Hangzhou, Zhejiang, China; Division of Mitochondrial Biomedicine, Zhejiang University-University of Toronto Joint Institute of Genetics and Genome Medicine, Hangzhou, Zhejiang, China. Electronic address:

Mammalian mitochondrial tRNA (mt-tRNA) plays a central role in the synthesis of the 13 subunits of the oxidative phosphorylation complex system (OXPHOS). However, many aspects of the context-dependent expression of mt-tRNAs in mammals remain unknown. To investigate the tissue-specific effects of mt-tRNAs, we performed a comprehensive analysis of mitochondrial tRNA expression across five mice tissues (brain, heart, liver, skeletal muscle, and kidney) using Northern blot analysis. Striking differences in the tissue-specific expression of 22 mt-tRNAs were observed, in some cases differing by as much as tenfold from lowest to highest expression levels among these five tissues. Overall, the heart exhibited the highest levels of mt-tRNAs, while the liver displayed markedly lower levels. Variations in the levels of mt-tRNAs showed significant correlations with total mitochondrial DNA (mtDNA) contents in these tissues. However, there were no significant differences observed in the 2-thiouridylation levels of tRNA, tRNA, and tRNA among these tissues. A wide range of aminoacylation levels for 15 mt-tRNAs occurred among these five tissues, with skeletal muscle and kidneys most notably displaying the highest and lowest tRNA aminoacylation levels, respectively. Among these tissues, there was a negative correlation between variations in mt-tRNA aminoacylation levels and corresponding variations in mitochondrial tRNA synthetases (mt-aaRS) expression levels. Furthermore, the variable levels of OXPHOS subunits, as encoded by mtDNA or nuclear genes, may reflect differences in relative functional emphasis for mitochondria in each tissue. Our findings provide new insight into the mechanism of mt-tRNA tissue-specific effects on oxidative phosphorylation.
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http://dx.doi.org/10.1016/j.jbc.2021.100960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342785PMC
August 2021

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke.

Front Med 2021 Jul 9. Epub 2021 Jul 9.

Department of Nuclear Medicine and Medical PET Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.
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http://dx.doi.org/10.1007/s11684-021-0842-9DOI Listing
July 2021

Clickable amino acid tuned self-assembly of a nucleus-selective multi-component nanoplatform for synergistic cancer therapy.

Chem Sci 2021 May 14;12(24):8394-8400. Epub 2021 May 14.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University Chongqing 401331 China

Nucleus-targeted therapy holds great promise in cancer treatment; however, a lack of effective nucleus-specific delivery significantly limits its application potential. Here, we report a nucleus-targeted synergistic chemo-photodynamic therapy based on the self-assembly of chlorin e6 (Ce6) and doxorubicin (DOX) tuned by clickable dibenzocyclooctyne (DIBO) functionalized lysine () and subsequent reaction with crosslinkers. The assembled nanodrugs with high loading efficiency and long-term stability show enhanced cellular uptake and accumulation in the nucleus, resulting in greatly improved and chemo-photodynamic efficacy. Notably, can promote the rapid self-assembly of Ce6 and DOX in aqueous solution, avoiding the introduction of organic solvents or tedious preparations. In addition, the introduction of the DIBO group can effectively expand the types of self-assembly material and enhance the self-assembly behaviour through a copper-free click reaction. Therefore, we present an effective nucleus-targeted combination drug delivery strategy, which has great potential in the treatment of many diseases.
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http://dx.doi.org/10.1039/d1sc01073eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221198PMC
May 2021

Endoplasmic Reticulum and Its Significance in Periodontal Disease.

Chin J Dent Res 2021 Jun;24(2):79-84

The endoplasmic reticulum has emerged as a modulator that is essential for cellular homeostasis and human health. It is an extensive membranous organelle that acts as a hub for the physiological and pathological processes. In recent years, it has become a topic of interest in studies on the relationship between endoplasmic reticulum homeostasis and system diseases. Periodontal disease is a prevalent chronic disease that affects tooth-supporting tissues, initiated by the interaction between pathogenic bacterial infection and immune defence and resulting in tooth loss. The endoplasmic reticulum participates in the responses to the fluctuating microenvironments in periodontal pathogenesis and regulates periodontal homeostasis. In this review, we present an overview of the significance of endoplasmic reticulum regulation as a multidimensional mediator in periodontal disease and highlight the potential strategies for periodontal regeneration.
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http://dx.doi.org/10.3290/j.cjdr.b1530481DOI Listing
June 2021

Quassinoids from Brucea javanica and attenuates lipopolysaccharide-induced acute lung injury by inhibiting PI3K/Akt/NF-κB pathways.

Fitoterapia 2021 Sep 27;153:104980. Epub 2021 Jun 27.

Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi, PR China. Electronic address:

Four new quassinoids (1-4) and twenty known analogues (5-24) were isolated from the seeds of Brucea javanica. All the compounds belong to tetracyclic quassinoids. The structures of the new compounds were elucidated by comprehensive spectroscopic analysis, including HRESIMS and 1D, 2D NMR. In in vitro bioassays, (5-9, 17-19 and 23) showed inhibitory activities for nitric oxide (NO) release in LPS-activated MH-S macrophages and IC values of 0.11-45.56 μM. Among them, bruceoside B significantly decreased LPS-induced NO, secretion of inflammatory factor cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Western Blot was used to verify the expression of p-IκB-α, IκB-α, p-NF-κB, NF-κB, Bax, Bcl-2, Caspase-3, p-PI3K, PI3K, p-Akt, and Akt proteins in PI3K/Akt/NF-κB signal pathway. Bruceoside B inhibited the activity of Akt and its downstream pathways and reduced the activation of apoptotic. In vivo, it was found that bruceoside B had obvious therapeutic effect on LPS-induced acute lung injury (ALI) in mice, and the effect of tissue section was obvious. The regulatory signal pathway of bruceoside B on inflammation was consistent with the anti-inflammatory pathway in vitro. Therefore, the results implied that bruceoside B has a certain therapeutic effect on inflammation and has a certainly effect on acute lung injury.
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http://dx.doi.org/10.1016/j.fitote.2021.104980DOI Listing
September 2021

Mussel Adhesive Mimetic Silk Sericin Prepared by Enzymatic Oxidation for the Construction of Antibacterial Coatings.

ACS Biomater Sci Eng 2021 07 23;7(7):3379-3388. Epub 2021 Jun 23.

Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, School of Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.

With the rapid development and advancement in orthodontic and orthopedic technologies, the demand for biomedical-grade titanium (Ti) alloys is growing. The Ti-based implants are susceptible to bacterial infections, leading to poor healing and osteointegration, resulting in implant failure or repeated surgical intervention. Silk sericin (SS) is hydrophilic, biocompatible, and biodegradable and could induce a low immunological response . As a result, it would be intriguing to investigate the use of hydrophilic SS in surface modification. In this work, the tyrosine moiety in SS was oxidized by tyrosinase (or polyphenol oxidase) to the 3,4-dihydroxyphenylalanine (DOPA) form, generating the catechol moiety-containing SS (SSC). Inspired by the adhesion of mussel foot proteins, the SSC coatings could be directly deposited onto multiple surfaces in SS and tyrosinase mixed stock solutions to create active surfaces with catechol groups. Further, the SSC-coated Ti surfaces were hybridized with silver nanoparticles (Ag NPs) silver ion (Ag) reduction. The antibacterial properties of the Ag NPs/SS-coated Ti surfaces are demonstrated, and they can prevent bacterial cell adhesion as well as early-stage biofilm formation. In addition, the developed Ag NPs/SSC-coated Ti surfaces exhibited a negligible level of cytotoxicity in L929 mouse fibroblast cells.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00271DOI Listing
July 2021

Investigation on the characteristics and mechanisms of ACE inhibitory peptides by a thorough analysis of all 8000 tripeptides via binding free energy calculation.

Food Sci Nutr 2021 Jun 3;9(6):2943-2953. Epub 2021 May 3.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development School of Chemistry and Molecular Engineering East China Normal University Shanghai China.

Food-derived angiotensin I-converting enzyme (ACE) inhibitory peptides represent a potential source of new antihypertensive. However, their characteristics and binding mechanisms were not well understood. In this study, novel energy calculation and experimentation were combined to elucidate the characteristics and mechanisms of ACE inhibitory tripeptides. ACE inhibitory activity of all 8,000 tripeptides was investigated by in silico experiments. IC values of the five top-rated tripeptides ranged from 5.86 to 21.84 μM. Five hundred top-ranked tripeptides were chosen for detailed structure-activity analysis, and a significant preference for aromatic amino acids at both C- and N-terminus was found. By binding free energy analysis of nine representative tripeptides via MM/GBSA, electrostatic energy was found to be the leading energy that contributed to the binding of ACE with its high affinity tripeptides. Besides, S355, V380, and V518, three residues positioned around the classical binding pockets of ACE, also played a key role in ACE's binding. Therefore, for tripeptides, their binding pockets in ACE were redefined. In conclusion, the characteristics of ACE inhibitory peptides were more deeply illustrated by the thorough analysis of all tripeptides. The energy analysis allows a better understanding of the binding mechanisms of ACE inhibitory peptides, which could be used to redesign the ACE inhibitors for stronger inhibitory activity.
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http://dx.doi.org/10.1002/fsn3.2253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194939PMC
June 2021

Based on Plasma Metabonomics and Network Pharmacology Exploring the Therapeutic Mechanism of on Type 2 Diabetes.

Front Pharmacol 2021 28;12:674379. Epub 2021 May 28.

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, China.

(GP) is a perennial herbal medicine and food homologous plant, which has been reported to have a good hypoglycemic effect. However, its active components and underlying mechanism of action are not clear. Here, we aimed to confirm the effects of GP on type 2 diabetes (T2DM) from several different aspects. We used UPLC/Q-TOF MS to analyze the metabolic patterns, which included blood samples of clinical subjects and / mice to screen for serum metabolic markers and metabolic pathways. We also used network pharmacology to study GP targets in the treatment of T2DM. Data from endogenous metabolites in plasma showed that two common pathways, including glycerol phosphate metabolism and retinol metabolism, were identified in plasma samples of the groups. Finally, Western blot analysis was used to verify the expression of proteins in the PI3K/AKT and AGE-RAGE signaling pathways. The protein expression of AKT, eNOS, iNS, and MAPK was significantly upregulated, and the expression of caspase-8 and caspase-3 was significantly downregulated. Thus, our findings indicated that GP could alleviate insulin resistance by regulating biometabolic markers and key proteins in the PI3K/AKT and AGE-RAGE signaling pathways to treat T2DM.
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http://dx.doi.org/10.3389/fphar.2021.674379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192979PMC
May 2021

Comparative toxicity of rod-shaped nano-CeO2 and nano-CePO4 to lettuce.

Metallomics 2021 07;13(7)

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

The influence of morphology on the biological effects of nanomaterials (NMs) has not been well understood. In the present study, we compared the phytotoxicity of rod-shaped nano-cerium dioxide (R-CeO2) and nano-cerium phosphate (R-CePO4) to lettuce plants. The results showed that R-CeO2 significantly inhibited the root elongation of lettuce, induced oxidative damages, and caused cell death, while R-CePO4 was nontoxic to lettuce. The different distribution and speciation of Ce in plant tissues were determined by transmission electron microscopy (TEM) and X-ray absorption near edge spectroscopy (XANES) combined with linear combination fitting (LCF). The results showed that in the R-CeO2 group, part of Ce was transformed from Ce(IV) to Ce(III), while only Ce(III) was present in the R-CePO4 group. When interacting with plants, R-CeO2 is easier to be dissolved and transformed than R-CePO4, which might be the reason for their different phytotoxicity. Although both are Ce-based NMs and have the same morphology, the toxicity of R-CeO2 seems to come from the released Ce3+ ions rather than its shape. This research emphasizes the importance of chemical composition and reactivity of NMs to their toxicological effects.
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http://dx.doi.org/10.1093/mtomcs/mfab033DOI Listing
July 2021

miR-204-5p inhibits inflammation of synovial fibroblasts in osteoarthritis by suppressing FOXC1.

Authors:
Xiao He Lili Deng

J Orthop Sci 2021 May 24. Epub 2021 May 24.

Pediatric Intensive Care Unit, Chenzhou No. 1 People's Hospital, Chenzhou, Hunan, 423000, PR China.

Background: The paper is aimed at uncovering the mechanism of miR-204-5p in regulating inflammatory responses of human osteoarthritic synovial fibroblasts (SFs).

Methods: IL-1β-induced osteoarthritic SFs were established as an osteoarthritis (OA) cell model. The osteoarthritic SFs were accordingly transfected with mimics-miR-204-5p, inhibitors-miR-204-5 or FOXC1 siRNA. MTT tested the vitality of osteoarthritic SFs by analyzing the cell optical density. The expressions of miR-204-5p, FOXC1, TNF-α, IL-6, PGE2, MMP-1, MMP-13 and COX-2 in osteoarthritic SFs were measured by qRT-PCR, Western blotting and/or ELISA. The binding of miR-204-5p to FOXC1 was verified through luciferase reporter assay. The regulatory effect of miR-204-5p on FOXC1 was also tested in normal SFs.

Results: miR-204-5p was under-expressed and FOXC1 was over-expressed in osteoarthritic SFs. The expressions of FOXC1, TNF-α, IL-6, PGE2, MMP-1, MMP-13 and COX-2 were up-regulated in IL-1β-treated SFs. Up-regulation of miR-204-5p or down-regulation of FOXC1 suppressed the inflammatory responses of osteoarthritic SFs. miR-204-5p negatively regulated FOXC1 by being a sponge in osteoarthritic SFs as well as in normal SFs.

Conclusion: miR-204-5p down-regulates FOXC1 to ameliorate inflammation of SFs in OA.
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http://dx.doi.org/10.1016/j.jos.2021.03.014DOI Listing
May 2021

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10-ERK signaling.

Cell Death Dis 2021 05 25;12(6):537. Epub 2021 May 25.

Department of Laboratory Animal Science, Fudan University, 200032, Shanghai, China.

The chromobox (CBX) proteins mediate epigenetic gene silencing and have been implicated in the cancer development. By analyzing eight CBX family members in TCGA dataset, we found that chromobox 7 (CBX7) was the most strikingly downregulated CBX family member in urinary bladder cancer (UBC), as compared to normal tissues. Though dysregulation of CBX7 has been reported in multiple cancers, its specific role and clinical relevance in UBC remain unclear. Herein, we found that frequent downregulation of CBX7 in UBC specimens, which was due to its promoter hypermethylation, was correlated with poor prognosis. The ectopic expression of CBX7 suppressed UBC cell proliferation, migration, invasion, and cancer stemness, whereas CBX7 depletion promoted cancer cell aggressiveness. Importantly, CBX7 overexpression in UBC cells inhibited tumorigenicity, whereas CBX7 depletion promoted the tumor development, indicating its tumor-suppressive role in UBC. Using RNA-seq and chromosome immunoprecipitation (ChIP) assays, we identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of CBX7, which was negatively modulated by CBX7 in a PRC1-dependent manner and involved in stimulating ERK signaling. Consistently, AKR1B10 overexpression induced cancer cell aggressiveness, whereas suppression of AKR1B10 by siRNA or its small molecular inhibitor, oleanolic acid, reversed the CBX7 deficiency-induced cellular effects. AKR1B10 overexpression was negatively associated with CBX7 downregulation and predicted poor clinical outcomes in UBC patients. Taken together, our results indicate that CBX7 functions as a tumor suppressor to downregulate AKR1B10 and further inactivates ERK signaling. This CBX7/AKR1B10/ERK signaling axis may provide a new therapeutic strategy against UBC.
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http://dx.doi.org/10.1038/s41419-021-03819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149849PMC
May 2021

Atmospheric Kinetics: Bimolecular Reactions of Carbonyl Oxide by a Triple-Level Strategy.

J Am Chem Soc 2021 Jun 24;143(22):8402-8413. Epub 2021 May 24.

Department of Chemistry, Chemical Theory Center, and Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota 55455-0431, United States.

Criegee intermediates in the atmosphere serve as oxidizing agents to initiate aerosol formation, which are particularly important for atmospheric modeling, and understanding their kinetics is one of the current outstanding challenges in climate change modeling. Because experimental kinetics are still limited, we must rely on theory for the complete picture, but obtaining absolute rates from theory is a formidable task. Here, we report the bimolecular reaction kinetics of carbonyl oxide with ammonia, hydrogen sulfide, formaldehyde, and water dimer by designing a triple-level strategy that combines (i) benchmark results close to the complete-basis limit of coupled-cluster theory with the single, double, triple, and quadruple excitations (CCSDTQ/CBS), (ii) a new hybrid meta density functional (M06CR) specifically optimized for reactions of Criegee intermediates, and (iii) variational transition-state theory with both variable rection coordinates and optimized reaction paths, with multidimensional tunneling, and with pressure effects. For (i) we have found that quadruple excitations are required to obtain quantitative reaction barriers, and we designed new composite methods and strategies to reach CCSDTQ/CBS accuracy. The present findings show that (i) the CHOO + HCHO reaction can make an important contribution to the sink of HCHO under wide atmospheric conditions in the gas phase and that (ii) CHOO + (HO) dominates over the CHOO + HO reaction below 10 km.
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http://dx.doi.org/10.1021/jacs.1c02029DOI Listing
June 2021

Neuroprotective effects of aucubin on hydrogen peroxide-induced toxicity in human neuroblastoma SH-SY5Y cells via the Nrf2/HO-1 pathway.

Phytomedicine 2021 Jul 18;87:153577. Epub 2021 Apr 18.

Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xi'an, P.R. China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, P.R. China. Electronic address:

Background: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis.

Purpose: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (HO)-induced injury in SH-SY5Y cells in vitro.

Methods: SH-SY5Y cells were simultaneously treated with AU and HO for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry.

Results: The results showed that AU can significantly increase the HO-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that HO stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In HO-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways.

Conclusion: These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153577DOI Listing
July 2021

Nanoparticles Determination by Laser Ablation Inductively Coupled Plasma Mass Spectrometry.

J Nanosci Nanotechnol 2021 11;21(11):5436-5442

CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, CAS-HKU Joint Laboratory of Metallomics on Health & Environment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

Quantitatively studying the biodistribution and transformation of nanomaterials is of great importance for nanotoxicological evaluation. Recently, laser ablation inductively coupled plasma mass spectrometry has been employed to distinguish nanoparticles (NPs) with their dissolved ions in biological samples. The principle of the proposal is based on a hypothesis that the intact NPs sampled by laser ablation will generate discrete sharp pulses of signals in ICP-MS measurement, being totally different from the continuous, relatively lower signals generated by ions. However, it is still a controversy whether NPs could maintain their intactness during the laser ablation. This work found a way to exactly determine the number of NPs sampled for each LA-ICP-MS measurement. It made possible to reveal the signal profile of a single NP in LA-ICP-MS analysis. The results suggest that AuNR, AgNP and TIO₂ NP were broken into much smaller secondary NPs during the laser ablation, therefore generating continuous signals in the analyzer. There was a certain probability that the fragmentation of large-sized NP or multiple NPs by laser ablation was not sufficient, leaving some NPs unbroken or some secondary NPs with relatively large sizes to generate discrete pulses of signals in the analyzer. When the intactness of NPs during laser ablation cannot be assured, it is impossible to determine the attribution of mass spectrum signals. These findings compromise the reliability of distinguishing NPs from their dissolved ions by LA-ICP-MS.
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http://dx.doi.org/10.1166/jnn.2021.19476DOI Listing
November 2021

DeepBSP-a Machine Learning Method for Accurate Prediction of Protein-Ligand Docking Structures.

J Chem Inf Model 2021 05 12;61(5):2231-2240. Epub 2021 May 12.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

In recent years, machine-learning-based scoring functions have significantly improved the scoring power. However, many of these methods do not perform well in distinguishing the native structure from docked decoy poses due to the lack of decoy structural information in their training data. Here, we developed a machine-learning model, named DeepBSP, that can directly predict the root mean square deviation (rmsd) of a ligand docking pose with reference to its native binding pose. Unlike the binding affinity, the rmsd between the docking poses with reference to their native structures can be straightforwardly determined. By training on a generated data set with 11,925 native complexes and more than 165,000 docked poses, our model shows excellent docking power on our test set and also on the CASF-2016 docking decoy set compared to other major scoring functions. Thus, by combining molecular dockings that generate many poses with the application of DeepBSP, one can more accurately predict the best binding pose that is closest to the native complex structure. This DeepBSP model shall be very useful in picking out poses close to their natives from many poses generated from a dock application.
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http://dx.doi.org/10.1021/acs.jcim.1c00334DOI Listing
May 2021

Nanocellulose-derived carbon/g-CN heterojunction with a hybrid electron transfer pathway for highly photocatalytic hydrogen peroxide production.

J Colloid Interface Sci 2021 Oct 24;599:507-518. Epub 2021 Apr 24.

College of Material Engineering, Fujian Agriculture and Forestry University, Fuzhou 350108, China.

Using oxygen reduction for the photocatalytic production of hydrogen peroxide (HO) has been considered a green and sustainable route. In the present study, to achieve high efficiency, graphitic carbon nitride (g-CN) was obtained using thermal polymerization from a bi-component precursor and was then assembled with cellulose nanofibers. It was found that a small quantity of cellulose nanofibers that generates carbon fibers upon pyrolysis greatly improves the photocatalytic activity compared with that of g-CN alone. The well-defined carbon/g-CN heterojunction-type material exhibits as high as 1.10 mmol Lh of photo-production of HO under visible light, which is 4.2 times higher than that yielded by pristine g-CN from a single precursor. A comprehensive characterization of the photocatalyst enables us to delineate the effect of the carbon nanofiber with respect to porosity, electron-hole separation, band gap regulation, and especially the electron transfer pathway. Our results demonstrate that nanocellulose-derived carbon, when precisely assembled with other functional material such as a photocatalyst, is a promising promoter of their activity.
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http://dx.doi.org/10.1016/j.jcis.2021.04.111DOI Listing
October 2021

Drug-guided screening for pancreatic lipase inhibitors in functional foods.

Food Funct 2021 May 29;12(10):4644-4653. Epub 2021 Apr 29.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Chronic diseases, such as obesity, cause great harm to human health. Conventional drugs have promising therapeutic effects but also cause significant side effects. Functional foods are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, screening for active ingredients in natural foods is difficult. In this study, a novel pancreatic lipase inhibitor screening strategy, guided by the drug molecule orlistat, was combined with experimental verification. Twenty compounds from natural foods were evaluated based on the characteristics of orlistat interaction with pancreatic lipase. The characteristics of 13 molecules were comparable to those of orlistat. The pancreatic lipase inhibition rates of curcumin and sinensetin were 82.42 ± 0.50% and 81.07 ± 2.05%, respectively, and their IC values were 0.971 mM and 0.526 mM, respectively; both the inhibition rates as well as IC values were similar to those of orlistat. Curcumin and sinensetin prevented weight gain in mice by 69.17% and 52.29%, respectively, compared to orlistat. Curcumin and sinensetin did not cause significant organ damage in vivo, but significantly reduced the contents of triglycerides and cholesterol in blood and lipids in the liver, protecting liver function. Furthermore, 57 328 molecules in the Chinese Natural Product Database library were screened, and 20 potentially active molecules, found to be highly efficient in our study, were selected. Thus, we successfully established an efficient and accurate strategy for screening active ingredients in natural foods under the guidance of a drug molecule, providing valuable insights for functional food development.
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http://dx.doi.org/10.1039/d0fo03366aDOI Listing
May 2021
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