Publications by authors named "Mengna Zhang"

50 Publications

Source apportionment of potentially toxic elements in soils of the Yellow River Delta Nature Reserve, China: The application of three receptor models and geostatistical independent simulation.

Environ Pollut 2021 Jul 22;289:117834. Epub 2021 Jul 22.

College of Geography and Environment, Shandong Normal University, Ji'nan, 250014, China. Electronic address:

The Yellow River Delta (YRD) wetland, the most important estuary wetland in eastern China, has an important ecosystem service function. Rapid and intensive development has inevitably led to the accumulation of potentially toxic elements (PTEs) in soils. Therefore, identifying quantitative sources and spatial distributions of PTEs is essential for soil environmental protection in the YRD. A total of 240 topsoil samples (0-20 cm) were collected in the Yellow River Delta Nature Reserve (YRDNR) and analyzed the PTE contents. To avoid the biases of the single receptor model, positive matrix factorization, factor analysis with nonnegative constraints, and maximum likelihood principal component analysis-multivariate curve resolution-alternating least squares were used for source apportionment of soil PTEs. To promote the efficiency of multivariate geostatistical simulation, a minimum/maximum autocorrelation factor-sequential Gaussian simulation was built to map the spatial patterns of PTEs. Three factors were derived by the three receptor models, and their contributions to the source explanation were similar. As, Cr, Cu, Mn, Ni, and Zn originated from natural sources, with contributions of 85.6%-96.4 %. A total of 61.5 % of Hg was associated with atmospheric deposition of coal combustion and wastewater from upstream. Agricultural activities and oil exploitation contributed 33.5 % and 15.9 % of the Cd and Pb concentrations. Spatial distributions of soil PTEs were controlled by sedimentary grain size. A total of 47.2 % of the total study area was identified as hazardous area for Cd, 10.3 % for As, and 5.4 % for Hg. This work is expected to provide references for soil pollution assessment and management of YRDNR.
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http://dx.doi.org/10.1016/j.envpol.2021.117834DOI Listing
July 2021

Immune-related genes and correlate with tumor sites and predict poor survival in pancreatic adenocarcinoma.

Future Oncol 2021 Aug 22;17(23):3061-3076. Epub 2021 Jun 22.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

The aim of this study was to identify the immune- and locus-associated genes in pancreatic ductal adenocarcinoma and evaluate their value in prognosis. The pancreatic ductal adenocarcinoma stromal and immune scores were calculated with the estimation of stromal and immune cells in malignant tumor tissues using expression data algorithm. The authors screened the differentially expressed genes to generate immune- and stromal-related differentially expressed genes. Next, the authors conducted weighted correlation network analysis to find the gene sets related to tumor sites. and were identified as the site- and immune-related genes in pancreatic ductal adenocarcinoma, and their high expression in pancreatic head cancer exhibited high immune scores and predicted unfavorable prognosis. The authors identified and as immune- and locus-associated genes, and their high expression predicted a poor prognosis.
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http://dx.doi.org/10.2217/fon-2020-1012DOI Listing
August 2021

Aqueous Self-Assembly of Block Copolymers to Form Manganese Oxide-Based Polymeric Vesicles for Tumor Microenvironment-Activated Drug Delivery.

Nanomicro Lett 2020 Jun 11;12(1):124. Epub 2020 Jun 11.

Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-020-00447-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770723PMC
June 2020

Brain injury in preterm infants with surgical necrotizing enterocolitis: clinical and bowel pathological correlates.

Pediatr Res 2021 Jun 8. Epub 2021 Jun 8.

Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.

Background: The objective of this study was to determine the risk factors and outcomes of white matter brain injury (WMBI) on magnetic resonance imaging (MRI) at term-equivalent age in infants with surgical necrotizing enterocolitis (NEC).

Methods: This retrospective study compared clinical/pathological information between infants with and those without WMBI.

Results: Out of 69 infants with surgical NEC, 17 (24.6%) had mild WMBI, 13 (18.8%) had moderate WMBI, and six (8.7%) had severe WMBI on the brain MRI. Several clinical factors (gestational age, more red blood cell (RBC) transfusions before NEC onset, pneumoperitoneum, earlier NEC onset age, postoperative ileus, acute kidney injury (AKI) by serum creatinine, postnatal steroids, hospital stay) and histopathological findings (necrosis, hemorrhage) had univariate associations with WMBI. Associations with RBC transfusion (odds ratio (OR) 23.6 [95% confidence interval (CI): 4.73-117.97]; p = 0.0001), age at NEC onset (OR 0.30 [95%CI: 0.11-0.84]; p = 0.021), necrosis (OR 0.10 [95%CI: 0.01-0.90]; p = 0.040), and bowel hemorrhage (OR 7.79 [95%CI: 2.19-27.72]; p = 0.002) persisted in multivariable association with grade 3-4 WMBI. The infants with WMBI had lower mean motor, cognitive, language scores, and higher ophthalmic morbidity at 2 years of age.

Conclusions: The WMBI was most likely associated with earlier NEC onset, higher RBC transfusions, and less necrosis and greater hemorrhage lesions on intestinal pathology in preterm infants with surgical NEC.

Impact: In preterm infants with surgical NEC, brain MRI showed injury in the white matter in 52%, gray matter in 10%, and cerebellar region in 30%. Preterm infants with severe WMBI (grade 3-4) had less necrosis and greater hemorrhagic lesions on histopathology of the bowel. Preterm infants with WMBI were more likely to have a more severe postoperative course, AKI, and longer length of hospitalization. Neuroprotective strategies to prevent brain injury in preterm infants with surgical NEC are needed with the goal of improving the neurodevelopmental outcomes.
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http://dx.doi.org/10.1038/s41390-021-01614-3DOI Listing
June 2021

CDK inhibitors in cancer therapy, an overview of recent development.

Am J Cancer Res 2021 15;11(5):1913-1935. Epub 2021 May 15.

Department of Orthopaedics, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University Wuhan 430071, China.

Dysregulated cell division, which leads to aberrant cell proliferation, is one of the key hallmarks of cancer. Therefore, therapeutic targets that block cell division would be effective for cancer treatment. Cell division is mainly controlled by a complex composed of cyclin and cyclin dependent kinases (CDKs). To date, the CDK inhibitors (CDKIs), specifically the ones that block the enzyme activity of CDK4 and CDK6 (CDK4/6), have been approved by FDA for the treatment of metastatic hormone receptor positive breast cancer. However, due to the non-selectivity and significant toxicity, most of the first generation CDK inhibitors (so called pan-CDK inhibitors that target several CDKs), have not been approved for clinical application. Despite this, great efforts and progress have been made to enable pan-CDK inhibitors application in the clinical setting. Notably, the development of combination therapy strategies in recent years has made it possible to reduce the toxicity and side effects of pan-CDK inhibitors. Thus, as a combination therapy approach, pan-CDK inhibitors regain great potential in clinical application. In this review, we introduced the CDK family members and discussed their major functions in cell cycle controlling. Then, we summarized the research progress regarding CDK inhibitors, especially those other than CDK4/6 inhibitors. We reviewed first-generation pan-CDKIs Flavopiridol and Roscovitine, and second-generation CDKIs Dinaciclib, P276-00, AT7519, TG02, Roniciclib, RGB-286638 by focusing on their developing stages, clinical trials and targeting cancers. The specific CDKIs, which targets to increase specificity and decrease the side effects, were also discussed. These CDKIs include CDK4/6, CDK7, CDK9, and CDK12/13 inhibitors. Finally, the efficacy and discrepancy of combination therapy with CDK inhibitors and PD1/PDL1 antibodies were analyzed, which might give insights into the development of promising strategy for cancer treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167670PMC
May 2021

Research on carbon emission efficiency in the Chinese construction industry based on a three-stage DEA-Tobit model.

Environ Sci Pollut Res Int 2021 May 11. Epub 2021 May 11.

China Institute of Manufacturing Development, Nanjing University of Information Science &Technology, Nanjing, 210044, China.

The traditional data envelopment analysis (DEA) model usually ignores the influence of external environmental factors and random interference. This can easily lead to deviations in efficiency estimates. In order to solve this problem, a three-stage DEA model was used to better reflect the carbon emission efficiency of Chinese construction industry (CEECI) (2006-2017) from the perspective of non-management factors. The internal influencing factors of CEECI are analyzed by the Tobit model, which provides a more accurate basis for formulating policies. It is found that the CEECI is significantly affected by the GDP, the level of industrialization, the degree of opening-up, technological innovation, and energy structure. After excluding environmental factors and random interference, the average CEECI increased by 16%. The resulting calculations are noteworthy in three aspects. First, there are significant regional differences in the CEECI. Both the multi-polarization phenomenon of CEECI and regional differences also reduced gradually over time. Second, the CEECI can be decomposed into pure carbon emission efficiency (PCEE) and scale efficiency (SE), which is mainly caused by SE. Excluding external environmental factors and random interference will have a specific impact on the CEECI. All the 30 provinces are divided into four categories to analyze the reasons and solutions of the differences in the CEECI in provinces. Third, many factors had inhibitory effects on the CEECI, PCEE, and SE; these included energy structure optimization, labor force number, total power of construct ion equipment, and construction intensity in the construction industry. Nevertheless, the development level of the construction industry did have a significant positive effect.
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http://dx.doi.org/10.1007/s11356-021-14298-3DOI Listing
May 2021

Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort.

Mol Genet Genomic Med 2021 Jun 5;9(6):e1689. Epub 2021 May 5.

Department of Medical Genetics, Capital Institute of Pediatrics, Beijing, China.

Objective: We determined the yield, genetic spectrum, and actual origin of de novo mutations (DNMs) for infantile spasms (ISs) in a Chinese cohort. The efficacy of levetiracetam (LEV) for STXBP1-related ISs was explored also.

Methods: Targeted sequencing of 153 epilepsy-related candidate genes was applied to 289 Chinese patients with undiagnosed ISs. Trio-based amplicon deep sequencing was used for all DNMs to distinguish somatic/mosaic mutations from germline ones.

Results: Total of 26 DNMs were identified from 289 recruited Chinese patients with undiagnosed ISs. Among them, 24 DNMs were interpreted as pathogenic mutations based on American College of Medical Genetics and Genomics guidelines, contributing to 8.3% (24/289) of diagnosis yield in the Chinese IS cohort. CDKL5 and STXBP1 are the top genes with recurrent DNMs, accounting for 3.1% (9/289) of yield. Further deep resequencing for the trio members showed that 22.7% (5/22) of DNMs are actually somatic in the proband or a parent. These somatic carriers presented milder seizure attacks than those with true germline DNMs. After treatment with LEV for half a year, three patients with DNM in STXBP1 showed improved clinical symptoms, including seizure-free and normal electroencephalogram, except for a patient with a second DNM in DIAPH3.

Significance: Our study confirmed the contribution and genetic spectrum of DNMs in Chinese IS patients. Somatic mutation account for a quarter of DNMs in IS cases. Treatment with LEV improved the prognosis of STXBP1-related ISs.
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http://dx.doi.org/10.1002/mgg3.1689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222834PMC
June 2021

Spinal endomorphins attenuate burn-injury pain in male mice by inhibiting p38 MAPK signaling pathway through the mu-opioid receptor.

Eur J Pharmacol 2021 Jul 30;903:174139. Epub 2021 Apr 30.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, And Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, Gansu, 730000, China. Electronic address:

Burn injury is one of the main causes of mortality worldwide and frequently associated with severe and long-lasting pain that compromises the quality of patient life. Several studies have shown that the mu-opioid system plays an important role in burn pain relief. In this study, we investigated the spinal antinociception induced by the endogenous mu-opioid receptor (MOR) agonists endomorphins and explored their mechanisms of actions in burn injury-induced pain model. Our results showed that intrathecal injection of endomorphin-1 and -2 dose-dependently attenuated mechanical allodynia and thermal hyperalgesia via the mu-opioid receptor in mice on day 3 after burn injury, which was consistent with the data obtained from the mu-opioid receptor knockout mice. Western blot showed that the phosphorylation levels of extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) in ipsilateral spinal cord tissues were significantly up-regulated after burn injury. Intrathecal injection of endomorphins selectively inhibited the activation of p38 MAPK on day 3 after burn injury via the mu-opioid receptor. Further studies found that repeated application of the specific p38 MAPK inhibitor SB203580 dose-dependently inhibited burn-injury pain, as well as the activation of spinal p38 MAPK. Taken together, our present study demonstrates that intrathecal injection of endomorphins attenuates burn-injury pain in male mice by affecting the spinal activation of p38 MAPK via the mu-opioid receptor.
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http://dx.doi.org/10.1016/j.ejphar.2021.174139DOI Listing
July 2021

Identification of a prognostic and therapeutic immune signature associated with hepatocellular carcinoma.

Cancer Cell Int 2021 Feb 10;21(1):98. Epub 2021 Feb 10.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent and inflammation-associated cancers. The tumor microenvironment (TME) plays an essential role in HCC development and metastasis, leading to poor prognosis. The overall TME immune cells infiltration characterizations mediated by immune-related genes (IRGs) remain unclear. In this study, we aimed to investigate whether immune-related genes could be indicators for the prognosis of HCC patients and TME cell infiltration characterization as well as responses to immunotherapy.

Methods: We obtained differentially expressed immune-related genes (DE IRGs) between normal liver tissues and liver cancer tissues from The Cancer Genome Atlas (TCGA) database. To identify the prognostic genes and establish an immune risk signature, we performed univariable Cox regression survival analysis and the Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the DE IRGs by robust rank aggregation method. Cox regression analysis was used to identify independent prognostic factors in HCC. We estimated the immune cell infiltration in TME via CIBERSORT and immunotherapy response through TIDE algorithm.

Results: We constructed an immune signature and validated its predictive capability. The immune signature included 7 differentially expressed IRGs: BIRC5, CACYBP, NR0B1, RAET1E, S100A8, SPINK5, and SPP1. The univariate and multivariate cox analysis showed that the 7-IRGs signature was a robust independent prognostic factor in the overall survival of HCC patients. The 7-IRG signature was associated with some clinical features, including gender, vascular invasion, histological grade, clinical stage, T stage. We also found that the 7-IRG signature could reflect the infiltration characterization of different immunocytes in the tumor microenvironment (TME) and had a good correlation with immune checkpoint molecules, revealing that the poor prognosis might be partly due to immunosuppressive TME. The Tumour Immune Dysfunction and Exclusion (TIDE) analysis data showed that the 7-IRG signature had great potential for indicating the immunotherapy response in HCC patients. The mutation analysis demonstrated a significant difference in the tumor mutation burden (TMB) between the high- and low-risk groups, partially explaining this signature's predictive value.

Conclusion: In a word, we constructed and validated a novel, immune-related prognostic signature for HCC patients. This signature could effectively indicate HCC patients' survival and immunotherapy response. And it might act as potential immunotherapeutic targets for HCC patients.
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http://dx.doi.org/10.1186/s12935-021-01792-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877064PMC
February 2021

Real-Time Screening of Omega-7 Phospholipids in Marine Biological Resources Using an iKnife-Rapid-Evaporative-Ionization-Mass-Spectrometry-Based Lipidomics Phenotype.

J Agric Food Chem 2021 Jan 12. Epub 2021 Jan 12.

Collaborative Innovation Center of Seafood Deep Processing, Zhejiang Province Joint Key Laboratory of Aquatic Products Processing, Institute of Seafood, Zhejiang Gongshang University, Hangzhou, Zhejiang 310012, People's Republic of China.

Omega-7 (n-7) phospholipids were bioactive substances in marine animals. In this study, a fast lipidomics phenotyping approach for real-time screening of n-7 phospholipids in five kinds of economic seafood, salmon, prawn, bluefin tuna, hairtail, and butterfish, was established using iKnife rapid evaporative ionization mass spectrometry (REIMS). The n-7 phospholipids were structurally characterized and quantitatively analyzed, and the profiles were statistically analyzed by multivariate recognition analysis. It indicated that the difference of n-7 phospholipids in seafood samples was significant ( < 0.05), with (cum) and (cum) values of >0.9. The proportion of n-7 phospholipids in salmon was the highest (20.43%), followed by bluefin tuna, prawn, hairtail, and butterfish. The ions of / 742.54 (PC 16:1-18:1), 768.55 (PC 16:1-20:2), 697.48 (PE 16:1-18:1), and 699.48 (PE 16:1-18:0) were the main n-7 phospholipids. The effectiveness of iKnife REIMS was further verified by hydrophilic interaction chromatography mass spectrometry and gas chromatography. The results demonstrated that proposed iKnife REIMS was an excellent technique for front-line screening of n-7 phospholipids in a large variety of marine biological resources.
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http://dx.doi.org/10.1021/acs.jafc.0c05442DOI Listing
January 2021

Synthesis and Biological Characterization of Cyclic Disulfide-Containing Peptide Analogs of the Multifunctional Opioid/Neuropeptide FF Receptor Agonists That Produce Long-Lasting and Nontolerant Antinociception.

J Med Chem 2020 12 3;63(24):15709-15725. Epub 2020 Dec 3.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.

In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized. The cyclized analogs and their linear counterparts behaved as multifunctional agonists at both opioid and NPFF receptors and produced potent analgesia without tolerance development. In comparison to , cyclized peptide exhibited sevenfold more potent μ-opioid receptor agonistic activity . Interestingly, the cyclized analog possessed an improved stability in the brain and an increased blood-brain barrier permeability compared to the parent peptide and produced more potent analgesia after supraspinal or subcutaneous administration with improved duration of action of 4 h. In addition, antinociceptive tolerance of analog was greatly reduced after subcutaneous injection compared to fentanyl, as was the rewarding effect, withdrawal reaction, and gastrointestinal inhibition.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01367DOI Listing
December 2020

Titania-coated fibrous silica (TiO/KCC-1) core-shell microspheres based solid-phase extraction in clam (Corbicula fluminea) using hydrophilic interaction liquid chromatography and mass spectrometry.

Food Res Int 2020 11 8;137:109408. Epub 2020 Jun 8.

Collaborative Innovation Center of Seafood Deep Processing, Zhejiang Province Joint Key Laboratory of Aquatic Products Processing, Institute of Seafood, Zhejiang Gongshang University, Hangzhou, China. Electronic address:

Clam (Corbicula fluminea) contains significant amount of phospholipids, and the profile of phospholipids could be used as an index for nutrition evaluation. In this study, a titania-coated fibrous silica (TiO/KCC-1) core-shell microsphere based solid-phase extraction (SPE) and hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) method was developed to study the phospholipids in clam. The structure and morphology of TiO/KCC-1 were characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD), and ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS). The analytical results indicated that the phospholipid molecular species (PMS) could be extracted in a cleaner manner after TiO/KCC-1 SPE, benefiting from the enhanced signals and decreased MS noise of phospholipids. Based on the principal component analysis (PCA) and partial least squares regression discriminant analysis (PLS-DA) models, the PMS with the most obvious beneficiaries of TiO/KCC-1 SPE were identified, e.g. PC 16:0/20:5 (m/z 824.6), PC 16:0/22:6 (m/z 850.6), PE 18:1/18:2 (m/z 740.4), and PE 18:0/22:6 (m/z 790.5). Finally, the proposed method was validated to be sensitive and precise. This study provides an efficient tool to analyze the phospholipids in clam and the prospect to use this method for future applications in various samples.
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http://dx.doi.org/10.1016/j.foodres.2020.109408DOI Listing
November 2020

COVID-19: gastrointestinal symptoms from the view of gut-lung axis.

Eur J Gastroenterol Hepatol 2021 05;33(5):610-612

Department of Gastroenterology, Zhongnan Hospital of Wuhan University.

The main symptoms of coronavirus disease 2019 (COVID-19) are respiratory manifestations, while some confirmed patients developed gastrointestinal symptoms or even initially presented digestive symptoms. The link between pneumonia and gastrointestinal symptoms caused by severe acute respiratory symptoms coronavirus 2 focused our attention on the concept of 'gut-lung axis'. In this review, we discuss the inevitability and possible mechanisms of the occurrence of intestinal symptoms or intestinal dysfunction in COVID-19 from the perspective of the gut-lung axis, as well as the influence of the imbalance of intestinal homeostasis on the respiratory symptoms of COVID-19. The interaction between lung and intestine might lead to a vicious cycle of pulmonary and intestinal inflammation which may be a potential factor leading to the death of patients with COVID-19.
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http://dx.doi.org/10.1097/MEG.0000000000001984DOI Listing
May 2021

Risk factors and characteristics associated with nonalcoholic fatty liver disease in patients with ischemic colitis.

Eur J Gastroenterol Hepatol 2020 Oct 29. Epub 2020 Oct 29.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University.

Background: Ischemic colitis (IC) was investigated to be associated with dyslipidemia and subcutaneous adipose tissue. Nonalcoholic fatty liver disease (NAFLD) is associated with ischemic diseases such as coronary heart disease, ischemic stroke. But there is a paucity of data regarding the association between NAFLD and IC. NAFLD may be associated with the treatment and prognosis of IC. We investigated risk factors and characteristics associated with NAFLD in patients with IC.

Methods: Patients with IC (NAFLD: 34 and controls: 81) from Zhongnan Hospital were investigated retrospectively from January 2012 to December 2018. Clinical data were compared by chi-square tests or independent samples T-tests. Binary logistic regressions and Kaplan-Meier analysis were performed to evaluate risk factors and prognosis, respectively.

Results: NAFLD was diagnosed in 28.19% patients with IC. In the logistic regression analysis, hypertension [odds ratio (OR) 3.523; P = 0.019], elevated alanine aminotransferase (ALT) (OR 6.278; P = 0.048), elevated triglyceride (OR 4.667; P = 0.003) and increased weight (OR 1.055; P = 0.039) were risk factors of NAFLD in patients with IC. Patients with NAFLD were more likely to require the vasodilators (P = 0.011) and get a relapse of IC (P = 0.011).

Conclusion: NAFLD was found in 28.19% of patients with IC. Hypertension, increased weight, elevated ALT and triglyceride are independent predictors of NAFLD in patients with IC. NAFLD in patients with IC is associated with a greater probability of requiring for the vasodilators. NAFLD in IC and period of bowel rest are risk factors for the recurrence of IC.
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http://dx.doi.org/10.1097/MEG.0000000000001986DOI Listing
October 2020

FATP2-targeted therapies - A role beyond fatty liver disease.

Pharmacol Res 2020 11 4;161:105228. Epub 2020 Oct 4.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan 430071, China. Electronic address:

Fatty acid transport protein 2 (FATP2) is a multifunctional protein whose specific function is determined by the type of located cell, its intracellular location, or organelle-specific interactions. In the different diseases setting, a newfound appreciation for the biological function of FATP2 has come into view. Two main functions of FATP2 are to activate long-chain fatty acids (LCFAs) as a very long-chain acyl-coenzyme A (CoA) synthetase (ACSVL) and to transport LCFAs as a fatty acid transporter. FATP2 is not only involved in the occurrence of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), but also plays an important role in lithogenic diet-induced cholelithiasis, the formation of cancer tumor immunity, the progression of chronic kidney disease (CKD), and the regulation of zoledronate-induced nephrotoxicity. Herein, we review the updated information on the role of FATP2 in related diseases. In particular, we discuss the new functions of FATP2 and propose that FATP2 is a potential clinical biomarker and therapeutic target. In conclusion, regulatory strategies for FATP2 may bring new treatment options for cancer and lipid metabolism-related disorders.
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http://dx.doi.org/10.1016/j.phrs.2020.105228DOI Listing
November 2020

Current state and future of co-inhibitory immune checkpoints for the treatment of glioblastoma.

Cancer Biol Med 2020 08;17(3):555-568

Key Laboratory of Cancer Center, Chinese PLA General Hospital, Beijing 100853, China.

In the interaction between a tumor and the immune system, immune checkpoints play an important role, and in tumor immune escape, co-inhibitory immune checkpoints are important. Immune checkpoint inhibitors (ICIs) can enhance the immune system's killing effect on tumors. To date, impressive progress has been made in a variety of tumor treatments; PD1/PDL1 and CTLA4 inhibitors have been approved for clinical use in some tumors. However, glioblastoma (GBM) still lacks an effective treatment. Recently, a phase III clinical trial using nivolumab to treat recurrent GBM showed no significant improvement in overall survival compared to bevacizumab. Therefore, the use of immune checkpoints in the treatment of GBM still faces many challenges. First, to clarify the mechanism of action, how different immune checkpoints play roles in tumor escape needs to be determined; which biomarkers predict a benefit from ICIs treatment and the therapeutic implications for GBM based on experiences in other tumors also need to be determined. Second, to optimize combination therapies, how different types of immune checkpoints are selected for combined application and whether combinations with targeted agents or other immunotherapies exhibit increased efficacy need to be addressed. All of these concerns require extensive basic research and clinical trials. In this study, we reviewed existing knowledge with respect to the issues mentioned above and the progress made in treatments, summarized the state of ICIs in preclinical studies and clinical trials involving GBM, and speculated on the therapeutic prospects of ICIs in the treatment of GBM.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476097PMC
August 2020

Crosstalk Between Liver Macrophages and Surrounding Cells in Nonalcoholic Steatohepatitis.

Front Immunol 2020 24;11:1169. Epub 2020 Jun 24.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Nonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease (NAFLD), is emerging as a leading cause of progressive liver fibrosis and end-stage liver disease. Liver macrophages, mainly composed of Kupffer cells (KCs) and monocyte-derived macrophages (MoMFs), play a vital role in NASH progression and regression. Recent advances suggest that cell-cell communication is a fundamental feature of hepatic microenvironment. The reprogramming of cell-cell signaling between macrophages and surrounding cells contributes to the pathogenesis of NASH. In this review, we summarize the current knowledge of NASH regarding the composition of liver macrophages and their communication with surrounding cells, which are composed of hepatocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs) and other immune cells. We also discuss the potential therapeutic strategies based on the level of macrophages.
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http://dx.doi.org/10.3389/fimmu.2020.01169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326822PMC
April 2021

The prognostic and clinicopathological value of tumor-associated macrophages in patients with colorectal cancer: a systematic review and meta-analysis.

Int J Colorectal Dis 2020 Sep 14;35(9):1651-1661. Epub 2020 Jul 14.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Purpose: There is a growing literature on the significance of tumor-associated macrophages (TAMs) in colorectal cancer (CRC). However, the role of TAMs in predicting the prognosis of CRC remains controversial. The current study aims to determine the prognostic and clinicopathological value of different types and distribution of TAMs in CRC.

Methods: A comprehensive literature search of PubMed, Embase, and Cochrane Library databases was conducted from the inception to 1 September 2019. The correlations of TAMs with overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and clinicopathological characteristics were analyzed.

Results: A total of 5,575 patients from 29 studies were included in this meta-analysis. The pooled hazard ratios (HRs) indicated that high density of pan-macrophages in tumor invasive margin (IM) was associated with better OS (HR = 0.57, 95%CI = 0.38-0.85), DFS (HR = 0.32, 95%CI = 0.19-0.52), and CSS (HR = 0.56, 95%CI = 0.41-0.77). Moreover, the high density of pan-macrophages in tumor center (TC) was correlated with better DFS (HR = 0.66, 95%CI = 0.45-0.96). However, high expression of M2 macrophages in TC was associated with poor DFS (HR = 2.42, 95%CI = 1.45-4.07) and CSS (HR = 1.74, 95%CI = 1.24-2.44). High M2 macrophages density in IM was also associated with short DFS (HR = 2.81, 95%CI = 1.65-4.77). In addition, the results showed that high density of pan-macrophages in IM was associated with no tumor metastasis, while high M2 macrophages density in TC was correlated with poor tumor differentiation.

Conclusion: High Pan-TAMs density in IM has a positive effect on the prognosis of CRC patients, while high density M2 macrophage infiltration in TC is a strong indicator of poor prognosis.
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http://dx.doi.org/10.1007/s00384-020-03686-9DOI Listing
September 2020

Carboxypeptidase A6 was identified and validated as a novel potential biomarker for predicting the occurrence of active ulcerative colitis.

J Cell Mol Med 2020 08 22;24(15):8803-8813. Epub 2020 Jun 22.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Ulcerative colitis (UC) is a chronic, highly heterogeneous intestinal inflammation with changes in epithelial function and tissue damage. However, the pathogenesis is still unclear between active UC and inactive UC. Herein, weighted gene co-expression network analysis was applied to explore the gene modules related to active UC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to further investigate the underlying mechanism of selected genes. We found that in the blue module (r = -.72), carboxypeptidase A6 (CPA6) was chosen to validate because of its high intra-modular connectivity and module membership. In the test sets, the expression level of CPA6 was down-regulated in active UC compared with inactive UC and normal colon. Furthermore, CPA6 expression was decreased primarily in the descending colon and only in mucosa affected by active UC. The receiver operating characteristic curve indicated that CPA6 expression had a performed well in diagnosing active UC from inactive UC (area under the curve = 0.99). Importantly, anti-tumour necrosis factor (TNF) treatment (infliximab and golimumab) significantly increased the CPA6 expression. Finally, GSEA and GSVA found that extracellular matrix receptor, inflammatory response and epithelial-mesenchymal transition were highly enriched in active UC with low CPA6 expression. In conclusion, CPA6 was identified and validated as a novel potential biomarker for predicting the occurrence of active UC, probably through regulating extracellular matrix or immune response.
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http://dx.doi.org/10.1111/jcmm.15517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412415PMC
August 2020

VF-13, a chimeric peptide of VD-hemopressin(α) and neuropeptide VF, produces potent antinociception with reduced cannabinoid-related side effects.

Neuropharmacology 2020 09 13;175:108178. Epub 2020 Jun 13.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, And Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address:

Pharmacological evidence indicated a functional interaction between neuropeptide FF (NPFF) and cannabinoid systems, and the cannabinoids combined with the NPFF receptor agonist neuropeptide VF (NPVF) produced antinociception without tolerance. In the present study, VF-13, a chimeric peptide containing the pharmacophores of the endogenous cannabinoid peptide VD-hemopressin(α) (VD-Hpα) and NPVF, was synthesized and pharmacologically evaluated. In vitro, VF-13 significantly upregulated the phosphorylated level of extracellular signal-regulated kinase 1/2 (ERK1/2) in CHO cells stably expressing CB1 receptors and inhibited forskolin-induced cAMP accumulation in HEK293 cells stably expressing NPFF or NPFF receptors. Moreover, VF-13 induced neurite outgrowth in Neuro 2A cells via CB1 and NPFF receptors. These results suggest that VF-13 exhibits multifunctional agonism at CB1, NPFF and NPFF receptors in vitro. Interestingly, intracerebroventricular VF-13 produced dose-dependent antinociception in mouse models of tail-flick and carrageenan-induced inflammatory pain via the TRPV1 receptor. In contrast, the reference compound (m)VD-Hpα-NH induced CB1 receptor-mediated supraspinal antinociception. Additionally, subcutaneous injection of (m)VD-Hpα-NH and VF-13 produced significant antinociception in carrageenan-induced inflammatory pain model. In the tetrad assay, our data demonstrated that VF-13 elicited hypothermia, but not catalepsy and hypoactivity after intracerebroventricular injection. Notably, VF-13 produced non-tolerance forming antinociception over 6 days treatment in both acute and inflammatory pain models. Furthermore, VF-13 had no apparent effects on gastrointestinal transit, pentobarbitone-induced sedation, food intake, and motor coordination at the supraspinal level. In summary, VF-13, a novel chimeric peptide of VD-Hpα and NPVF, produced non-tolerance forming antinociception in preclinical pain models with reduced cannabinoid-related side effects.
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http://dx.doi.org/10.1016/j.neuropharm.2020.108178DOI Listing
September 2020

Spinal administration of the multi-functional opioid/neuropeptide FF agonist BN-9 produced potent antinociception without development of tolerance and opioid-induced hyperalgesia.

Eur J Pharmacol 2020 Aug 13;880:173169. Epub 2020 May 13.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address:

Chronic opioids treatment is impeded by the development of analgesic tolerance and opioid-induced hyperalgesia. Recent studies have shown that multi-functional opioid compounds produce analgesic activities with limited side effects. We developed a novel multi-functional peptide targeting opioid and neuropeptide FF receptors named BN-9, which produced potent and non-tolerance forming antinociceptive effect after supraspinal and systemic administrations. In the present study, the analgesic properties and potential side effects of intrathecal BN-9 were investigated in a range of preclinical rodent models. In complete Freund's adjuvant-induced inflammatory pain model, intrathecal BN-9 dose-dependently produced analgesic effect via opioid receptors, and the spinal antinociceptive effect was augmented by the neuropeptide FF receptor antagonist RF9. In contrast, in plantar incision-induced postoperative pain model, BN-9 exhibited potent anti-allodynic effect via opioid receptors and, at least partially, neuropeptide FF receptors. In mouse models of acetic acid-induced visceral pain and formalin pain, BN-9-induced spinal antinociception was mainly mediated by opioid receptors, independent of neuropeptide FF receptors. Furthermore, at the spinal level, chronic treatments with BN-9 did not lead to analgesic tolerance and cross-tolerance to morphine. Moreover, opioid-induced hyperalgesia was observed after repeated administration of morphine, but not BN-9. Taken together, our present study suggests that intrathecal BN-9 produces potent and non-tolerance forming antinociception, and does not cause opioid-induced hyperalgesia. Thus, BN-9 might serve as a promising lead compound in the development of multi-functional opioid analgesics with minimized side effects.
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http://dx.doi.org/10.1016/j.ejphar.2020.173169DOI Listing
August 2020

Central and peripheral modulation of gastrointestinal transit in mice by DN-9, a multifunctional opioid/NPFF receptor agonist.

Neurogastroenterol Motil 2020 08 12;32(8):e13848. Epub 2020 Apr 12.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Background: The nonapeptide DN-9 functions as a multifunctional agonist to opioid and neuropeptide FF (NPFF) receptors and exhibits antinociceptive effects at the central and peripheral levels.

Methods: The effects of DN-9 on small and colonic intestinal transit were evaluated using the upper gastrointestinal (GI) transit test and colonic bead expulsion assay, respectively. Opioid and NPFF receptor antagonists were used to investigate the mechanisms of DN-9-induced GI inhibition. Furthermore, the agonism of the DN-9 analog [Phg ]-DN-9 to opioid and NPFF receptors was tested by the cAMP assay.

Key Results: Intracerebroventricular administration of DN-9 dose-dependently slowed upper GI transit and colonic expulsion via mu- and kappa-opioid receptors in the brain, independent of the delta-opioid receptor. Similarly, intraperitoneal injection of DN-9 dose-dependently inhibited GI propulsion via the peripheral opioid receptors. DN-9-induced GI transit inhibitions were significantly aggravated by the NPFF receptor antagonist RF9. Moreover, the DN-9 analog [Phg ]-DN-9, an agonist at mu-, delta-, and kappa-opioid receptors but not NPFF receptors, inhibited GI more potently than DN-9. In addition, intracerebroventricular NPFF significantly attenuated the central inhibitory effects induced by [Phg ]-DN-9 and morphine. However, central and peripheral injections of NPFF or RF9 almost had no significant effects on GI transit by itself.

Conclusion And Inferences: Intracerebroventricular and intraperitoneal administrations of DN-9 inhibit GI transit via opioid receptors in mice by central and peripheral mechanisms, respectively. In addition, the NPFF agonism of DN-9 possesses antiopioid effects on GI transit, which might explain the reduced constipation at the antinociceptive doses.
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http://dx.doi.org/10.1111/nmo.13848DOI Listing
August 2020

Revision of the Oriental Chaetocnema species (Coleoptera, Chrysomelidae, Galerucinae, Alticini).

Zootaxa 2019 Nov 15;4699(1):zootaxa.4699.1.1. Epub 2019 Nov 15.

School of Applied Chemistry and Biological Technology, Shenzhen Polytechnic, Shenzhen, Guangdong 518055, China. Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

The Oriental species of Chaetocnema Stephens, 1831 are revised. There are 85 valid species, including 19 new species: C. angustifrons sp. nov.; C. appendiculata sp. nov.; C. baoshanica sp. nov.; C. dapitanica sp. nov.; C. glabra sp. nov.; C. greenica sp. nov.; C. jinxiuensis sp. nov.; C. hongkongensis sp. nov.; C. latapronota sp. nov.; C. midimpunctata sp. nov.; C. nigrilata sp. nov.; C. parafusiformis sp. nov.; C. paragreenica sp. nov.; C. paraumesaoi sp. nov.; C. purerulea sp. nov.; C. reteimpunctata sp. nov.; C. sabahensis sp. nov.; C. subbasalis sp. nov.; C. trapezoida sp. nov.                Fifteen new synonyms are proposed: C. assamensis Scherer, 1969 (syn. nov.) = C. hainanensis Chen, 1932; C. birmanica Jacoby, 1892 (syn. nov.) = C. malayana Baly, 1877; C. ebenina Warchalowski, 1973 (syn. nov.) = C. yiei Kimoto, 1970; C. flavipennis Medvedev, 1996 (syn. nov.) = C. granulicollis Jacoby, 1896; C. harita Maulik, 1926 (syn. nov.) = C. westwoodi Baly, 1877; C. himalayana Medvedev, 1993 (syn. nov.) = C. melonae Chen, 1934; C. kwangsiensis Chen, 1939 (syn. nov.) = C. hainanensis Chen, 1932; C. loriae Jacoby, 1905 (syn. nov.) = C. nigrica Motschulsky, 1858; C. nepalensis Scherer, 1969 (syn. nov.) = C. bella Baly, 1877; C. nitens Baly, 1877 (syn. nov.) = C. nigrica Motschulsky, 1858; C. placida Jacoby, 1896 (syn. nov.) = C. bella Baly 1877; C. shanensis Bryant, 1939 (syn. nov.) = C. bella Baly 1877; C. subcostata Jacoby, 1889 (syn. nov.) = C. wallacei Baly, 1877; C. vietnamica Chen Wang, 1980 (syn. nov.) = C. modigliani Jacoby, 1896; C. vietnamica Medvedev, 2009 (syn. nov.) = C. wallacei Baly, 1877.                C. vietnamica Medvedev, 2001 is a new junior homonym of C. vietnamica Chen Wang, 1980.                C. melonae Chen, 1934 status restored and resurrected from synonymy with C. duvivieri Jacoby, 1892 in Medvedev, 2001: 613. Two subspecies are raised to species level: C. taiwanensis Chûjô, 1965 new status for C. tonkinensis taiwanensis Chûjô, 1965 and C. yunnanica Heikertinger, 1951 new status for C. discreta yunnanica Heikertinger, 1951.                Lectotypes are designated for 25 species: C. minuta Jacoby, 1896; C. granulicollis Jacoby, 1896; C. kwangsiensis Chen, 1939; C. longipunctata Maulik, 1926; C. montivaga Maulik, 1926; C. basalis Baly, 1877; C. parvula Baly, 1877; C. nitens Baly, 1877; C. geniculata Jacoby, 1896; C. simplicifrons (Baly, 1876); C. sticta Maulik, 1926; C. sumatrana Jacoby, 1896; C. wallacei Baly, 1877; C. alticola Maulik, 1926; C. belli Jacoby 1904; C. cognata Baly, 1877; C. squarrosa Baly, 1877; C. concinnipennis Baly, 1877; C. malayana Baly, 1877; C. birmanica Jacoby, 1892; C. merguiensis Bryant, 1941; C. pusaensis Maulik, 1926; C. singala Maulik, 1926; C. westwoodi Baly, 1877; C. harita Maulik, 1926.
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http://dx.doi.org/10.11646/zootaxa.4699.1.1DOI Listing
November 2019

The jumping mechanism of flea beetles (Coleoptera, Chrysomelidae, Alticini), its application to bionics and preliminary design for a robotic jumping leg.

Zookeys 2020 24;915:87-105. Epub 2020 Feb 24.

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Flea beetles (Coleoptera, Chrysomelidae, Galerucinae, Alticini) are a hyperdiverse group of organisms with approximately 9900 species worldwide. In addition to walking as most insects do, nearly all the species of flea beetles have an ability to jump and this ability is commonly understood as one of the key adaptations responsible for its diversity. Our investigation of flea beetle jumping is based on high-speed filming, micro-CT scans and 3D reconstructions, and provides a mechanical description of the jump. We reveal that the flea beetle jumping mechanism is a catapult in nature and is enabled by a small structure in the hind femur called an 'elastic plate' which powers the explosive jump and protects other structures from potential injury. The explosive catapult jump of flea beetles involves a unique 'high-efficiency mechanism' and 'positive feedback mechanism'. As this catapult mechanism could inspire the design of bionic jumping limbs, we provide a preliminary design for a robotic jumping leg, which could be a resource for the bionics industry.
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http://dx.doi.org/10.3897/zookeys.915.38348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052025PMC
February 2020

In situ and real-time authentication of Thunnus species by iKnife rapid evaporative ionization mass spectrometry based lipidomics without sample pretreatment.

Food Chem 2020 Jul 27;318:126504. Epub 2020 Feb 27.

Zhejiang Province Joint Key Laboratory of Aquatic Products Processing, Institute of Seafood, Zhejiang Gongshang University, Hangzhou, China. Electronic address:

Tuna adulteration and mislabeling are serious problem worldwide and have caused economic loss and consumer rights violation. In this study, an electrometric knife (iKnife) coupling rapid evaporative ionization mass spectrometry (REIMS) and a multivariate recognition model were developed and employed for in situ and real-time authentication of four tuna species without sample preparation. The results showed that the lipidomic profiles were successfully acquired and the differences in fatty acids and phospholipids were statistically analyzed to be significant (p < 0.05). The model displayed the superb classification accuracy (>93%) and validation (R(Y) = 0.992, Q = 0.986), and the main contributors of m/z 817.64, m/z 809.68, etc. were screened out to be used as potential biomarkers. Based on this technique, the identity of blind tuna samples could be unambiguously authenticated with the results displayed on a monitor screen directly. This study provided a front-line rapid detection method to prove the authenticity of tuna species.
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http://dx.doi.org/10.1016/j.foodchem.2020.126504DOI Listing
July 2020

Magnetic supramolecular polymer: Ultrahigh and highly selective Pb(II) capture from aqueous solution and battery wastewater.

Chemosphere 2020 Jun 27;248:126042. Epub 2020 Jan 27.

MOE Key Laboratory of Yellow River and Huai River Water Environmental and Pollution Control, Henan Key Laboratory for Environmental Pollution Control, School of Environment, Henan Normal University, Xinxiang, Henan, 453007, PR China. Electronic address:

For the practical capture of heavy metal ions from wastewater, fabricating environmental friendly adsorbents with high stability and super adsorption capacity are pursuing issue. In this work, we develop magnetic supramolecular polymer composites (M-SMP) by using a simple two-step hydrothermal method. Systematical characterizations of morphological, chemical and magnetic properties were conducted to confirm the formation of M-SMP composites. The resulting M-SMP composites were applied to remove Pb(II) from aqueous solution and from real battery wastewater, and easy separation was achieved using a permanent magnet. By investigating the effects of various parameters, we optimized their operating condition for Pb(II) adsorption by the M-SMP. The uptake of Pb(II) onto M-SMP fitted well the pseudo-second-order and Langmuir isotherm models, and favourable thermodynamics showed a spontaneous endothermic process. The SMP endowed M-SMP with ultrahigh adsorption capacity for Pb(II) (946.9 mg g at pH = 4.0, T = 298 K), remarkable selectivity, satisfactory stability and desirable recyclability. In Pb-contaminated lead-acid battery industrial wastewater, the concentration of Pb(II) declined from 18.070 mg L to 0.091 mg L, which meets the current emission standard for the battery industry. These merits, combined with simple synthesis and convenient separation, make M-SMP an outstanding scavenger for the elimination of industrial Pb(II) wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126042DOI Listing
June 2020

Electric Soldering Iron Ionization Mass Spectrometry Based Lipidomics for in Situ Monitoring Fish Oil Oxidation Characteristics during Storage.

J Agric Food Chem 2020 Feb 6;68(7):2240-2248. Epub 2020 Feb 6.

Collaborative Innovation Center of Seafood Deep Processing, Zhejiang Province Joint Key Laboratory of Aquatic Products Processing, Institute of Seafood , Zhejiang Gongshang University , Hangzhou , 310018 China.

An electric soldering iron ion source (ESII) coupling with rapid evaporative ionization mass spectrometry (REIMS) was developed and used for in situ monitoring the dynamic variation trend in oxidation characteristics of fish oil during storage. The lipidomics profiles of fish oil stored at various days were acquired by ESII-REIMS. The fatty acid and triacylglycerol species were structurally identified, and their abundances were analyzed according to multivariate statistical models mainly including principle component analysis as well as orthogonal partial least-squares analysis. On the shared and unique structure plot, the ions of / 255.23, 281.24, 877.72, and 901.72 displayed the most significant variation among the oxidized fish oil samples. Based on receiver operating characteristic curve analysis with an optimal Youden index of 0.91, these markers were further verified. The variation of viscosity and volatiles were also evaluated to further verify the oxidation characteristics of fish oil. The study demonstrated that ESII-REIMS technology used as an advanced detection method could ensure fish oil quality during storage.
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http://dx.doi.org/10.1021/acs.jafc.9b06406DOI Listing
February 2020

Real-Time Monitoring of the Oxidation Characteristics of Antarctic Krill Oil () during Storage by Electric Soldering Iron Ionization Mass Spectrometry-Based Lipidomics.

J Agric Food Chem 2020 Feb 27;68(5):1457-1467. Epub 2020 Jan 27.

Collaborative Innovation Center of Seafood Deep Processing, Zhejiang Province Joint Key Laboratory of Aquatic Products Processing, Institute of Seafood , Zhejiang Gongshang University , Hangzhou 310018 , China.

Antarctic krill oil (AKO) is susceptible to oxidation due to the high unsaturation degree of bioactive substances. Herein, a lipidomics method for in situ monitoring of the dynamic oxidation characteristics in AKO was explored based on electric soldering iron ion source (ESII) coupling with rapid evaporative ionization mass spectrometry (REIMS). The lipidomics profiles of AKO at different storage periods were successfully acquired. On the basis of principal component analysis and orthogonal partial least-squares analysis, the obtained REIMS data were employed to build a multivariate recognition model. The ions of 707.50, 721.50, 833.49, and 837.54 contributed the most significant effect on the multivariate data model for the authentication of different AKO samples. Besides, the variation of viscosity, astaxanthin, and volatile compounds were also evaluated to corroborate the oxidation characteristics. The results indicated that the ESII-REIMS technology could be applied as an advanced rapid detection method to secure oil and fat quality during storage.
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http://dx.doi.org/10.1021/acs.jafc.9b07370DOI Listing
February 2020

Physical information of 2705 PCR-based molecular markers and the evaluation of their potential use in wheat.

J Genet 2019 Sep;98

College of Agriculture, Ludong University, Yantai 264025, Shandong, People's Republic of China.

Genetic information of polymerase chain reaction (PCR)-based markers, one of the main tools of genetics and genomics research in wheat, have been well documented in wheat. However, the physical position in relation to these markers has not yet been systematically characterized. Aim of this study was to characterize the physical information of thousands of widely used molecular markers.We first assigned 2705 molecular markers to wheat physical map, of which 86.1% and 84.7% were the best hits to chromosome survey sequencing (CSS) project (CSS-contigs) and International Wheat Genome Sequencing Consortium Reference Sequence v1.0 (IWGSC RefSeq v1.0), respectively. Physical position of 96.2% markers were predicated based on BLAST analysis, were in accordance with that of the previous nullisomic/aneuploidy/linkage analysis. A suggestive high-density physical map with 4643 loci was constructed, spanning 14.01 Gb (82.4%) of the wheat genome, with 3.02 Mb between adjacent markers. Both forward and reverse primer sequences of 1166 markers had consistent best hits to IWGSC RefSeq v1.0 based on BLAST analysis, and the corresponding allele sizes were characterized. A detailed physical map with 1532 loci was released, spanning 13.93 Gb (81.9%) of the wheat genome, with 9.09 Mb between adjacent markers. Characteristic of recombination rates in different chromosomal regions was discussed. In addition, markers with multiple sites were aligned to homoeologous sites with a consistent order, confirming that a collinearity existed among A, B and D subgenomes. This study facilitates the integration of physical and genetical information of molecular markers, which could be of value for use in genetics and genomics research such as gene/QTL map-based cloning and marker-assisted selection.
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September 2019

Spinal DN-9, a Peptidic Multifunctional Opioid/Neuropeptide FF Agonist Produced Potent Nontolerance Forming Analgesia With Limited Side Effects.

J Pain 2020 Mar - Apr;21(3-4):477-493. Epub 2019 Sep 12.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China. Electronic address:

The development of multitarget opioid drugs has emerged as an attractive therapeutic strategy to eliminate opioid-related side effects. Our previous study developed a series of opioid and neuropeptide FF pharmacophore-containing chimeric peptides, including DN-9 (Tyr-D.Ala-Gly-NMe.Phe-Gly-Pro-Gln-Arg-Phe-NH), which produced potent nontolerance forming analgesia at the supraspinal level. In the present study, the antinociceptive effects of DN-9 in a series of preclinical pain models and the potential side-effects were investigated at the spinal level in mice. In the tail-flick test, intrathecal injection of DN-9 produced potent analgesia with an ED value at 1.33 pmol, and the spinal antinociception of DN-9 was mainly mediated by μ- and κ-opioid receptors. In addition, DN-9-induced spinal antinociception was augmented by the neuropeptide FF receptors antagonist. Furthermore, DN-9 could decrease both the frequency and amplitude of sEPSCs in lamina IIo neurons of the spinal cord, which were mediated by opioid receptors. In contrast to morphine, chronic intrathecal treatments with DN-9 did not induce analgesic tolerance, c-Fos expression or microglial activation. Intrathecal injection of DN-9 showed potent analgesia with antinociceptive ED values between .66 and 55.04 pmol in different pain models, including the formalin test, acetic acid-induced writhing test, carrageenan-induced inflammatory pain and neuropathic pain. Moreover, DN-9 did not show side effects in locomotor function and coordination, gastrointestinal transit inhibition, the cardiovascular system, and body temperature regulation at antinociceptive doses. Taken together, the present study showed DN-9 produced effective, nontolerance forming analgesia with reduced side effects at the spinal level. DN-9 might be a promising compound for developing multifunctional opioid analgesics with limited adverse effects. PERSPECTIVE: This article presents the potent and nontolerance forming analgesia effects of DN-9 in a series of preclinical pain models with less opioid related adverse effects at the spinal level in mice. This study also demonstrates that DN-9 has translational potential into an intrathecal analgesic.
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http://dx.doi.org/10.1016/j.jpain.2019.08.016DOI Listing
September 2019
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