Publications by authors named "Xin Lu"

1,485 Publications

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DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer.

Clin Epigenetics 2021 Oct 13;13(1):190. Epub 2021 Oct 13.

Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No. 128, Shenyang Road, Yangpu District, Shanghai, 200090, China.

High-grade serous ovarian cancer (HGSOC) is the most common type of epigenetically heterogeneous ovarian cancer. Methylation typing has previously been used in many tumour types but not in HGSOC. Methylation typing in HGSOC may promote the development of personalized care. The present study used DNA methylation data from The Cancer Genome Atlas database and identified four unique methylation subtypes of HGSOC. With the poorest prognosis and high frequency of residual tumours, cluster 4 featured hypermethylation of a panel of genes, which indicates that demethylation agents may be tested in this group and that neoadjuvant chemotherapy may be used to reduce the possibility of residual lesions. Cluster 1 and cluster 2 were significantly associated with metastasis genes and metabolic disorders, respectively. Two feature CpG sites, cg24673765 and cg25574024, were obtained through Cox proportional hazards model analysis of the CpG sites. Based on the methylation level of the two CpG sites, the samples were classified into high- and low-risk groups to identify the prognostic information. Similar results were obtained in the validation set. Taken together, these results explain the epigenetic heterogeneity of HGSOC and provide guidance to clinicians for the prognosis of HGSOC based on DNA methylation sites.
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http://dx.doi.org/10.1186/s13148-021-01178-3DOI Listing
October 2021

Quantifying the impacts of human mobility restriction on the spread of coronavirus disease 2019: an empirical analysis from 344 cities of China.

Chin Med J (Engl) 2021 Oct 7;134(20):2438-2446. Epub 2021 Oct 7.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19.

Methods: Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders.

Results: The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities.

Conclusions: Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.
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http://dx.doi.org/10.1097/CM9.0000000000001763DOI Listing
October 2021

Structure and biological activities of glycoproteins and their metabolites in maintaining intestinal health.

Crit Rev Food Sci Nutr 2021 Oct 7:1-16. Epub 2021 Oct 7.

Department of Nursing, Shandong College of Traditional Chinese Medicine, Yantai, PR China.

Glycoproteins formed by covalent links between oligosaccharide and polypeptides are abundant in various food sources. They are less sensitivity to gastrointestinal enzymes, and hence many of them undergo fermentation in the colon by microorganisms. Therefore, the confer various health benefits on the intestinal ecosystem. However, the current understanding of the effect of glycoproteins on intestinal microorganisms and gut health is limited. This is probably due to their heterogeneous structures and complex metabolic programming patterns. The structure and biological activities of glycoproteins and their microbial metabolites were summarized in this review. The metabolic pathways activated by intestinal bacteria were then discussed in relation to their potential benefits on gut health. Food-derived glycoproteins and their metabolites improve gut health by regulating the intestinal bacteria and improving intestinal barrier function, thereby amplifying immune response. The data reviewed here show that food-derived glycoproteins are promising candidates for preventing various gastrointestinal diseases. Further studies should explore the interaction mechanisms between intestinal microorganisms and host metabolites.
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http://dx.doi.org/10.1080/10408398.2021.1987857DOI Listing
October 2021

Novel Stable Isotope-Resolved Metabolomics Method for a Small Number of Cells Using Chip-Based Nanoelectrospray Mass Spectrometry.

Anal Chem 2021 Oct 4;93(41):13765-13773. Epub 2021 Oct 4.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Stable isotope-resolved metabolomics (SIRM) can provide metabolic conversion information of specific targets; it is a powerful tool for cell metabolism studies. The common analytical platform for SIRM is chromatography-mass spectrometry, which requires a large number of cells and is not suitable for precious rare cell analysis. To study a small number of cells, we established a novel SIRM method using chip-based nanoelectrospray mass spectrometry (MS). C-glutamine was taken as an example; the unlabeled and C-labeled cells were cultured and extracted in a 96-well plate and then directly injected into MS and analyzed in full scan mode and parallel reaction monitoring (PRM) mode targeting 44 glutamine-derived metabolites and their isotopologues. To define focused metabolite-related MS2 fragments produced in the PRM, a new strategy was proposed including MS2 exact / matching, MS2 false positive filtering, and MS2 fragment grouping to remove the interfering MS2 ions. In total, 292 and 349 pairs of paired MS2 ions were obtained in positive and negative ionization modes, respectively. By searching spectra databases, 31 targeted metabolites with their isotopologues were identified and their characteristic product ions were confirmed for MS2 quantification. The relative quantification was achieved by MS2 quantification, which showed better sensitivity and accuracy than common MS1-based quantification. Finally, this method was applied to isocitrate dehydrogenase I-mutated glioma cells for revealing the effects of triptolide on glioma cell metabolism using U-C-glutamine as a labeling substrate.
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http://dx.doi.org/10.1021/acs.analchem.1c01507DOI Listing
October 2021

Photocatalytic Decarboxylative [3 + 2] and [4 + 2] Annulation of Enynals and γ,σ-Unsaturated -(Acyloxy)phthalimides by NaI/PPh Catalysis.

Org Lett 2021 Oct 28;23(20):7839-7844. Epub 2021 Sep 28.

Key Laboratory of Jiangxi Province for Persistent Pollutant Control and Resource Recycling, Nanchang Hangkong University, Nanchang 330063, China.

A practical and eco-friendly strategy for the radical-mediated decarboxylative [3 + 2] and [4 + 2] annulation of enynals and γ,σ-unsaturated -(acyloxy)phthalimides through the photoactivation of an electron donor-acceptor (EDA) complex has been developed. A wide range of primary, secondary, and tertiary alkyl -hydroxyphthalimide (NHP) esters can be used as suitable substrates for the synthesis of fused ketones without any transition-metal catalysts or oxidants. This protocol features a broad substrate scope, excellent selectivity, and clean reaction conditions.
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http://dx.doi.org/10.1021/acs.orglett.1c02858DOI Listing
October 2021

GLP-1 and Underlying Beneficial Actions in Alzheimer's Disease, Hypertension, and NASH.

Front Endocrinol (Lausanne) 2021 6;12:721198. Epub 2021 Sep 6.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.
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http://dx.doi.org/10.3389/fendo.2021.721198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450670PMC
September 2021

miR-506 in patients with chronic myeloid leukemia and its effect on apoptosis of K562 cells.

Am J Transl Res 2021 15;13(8):9413-9420. Epub 2021 Aug 15.

Department of Hematology, Xingtai People's Hospital Xingtai 054000, Hebei Province, China.

Objective: To explore the expression of miR-506 in chronic myeloid leukemia (CML) and its influence on the biological function of CML cells.

Methods: Altogether 84 CML patients from February 2012 to September 2014 were obtained as the observation group (OG), and 71 healthy people were taken as the control group (CG). miR-506 was tested using RT-qPCR, and the 5-year survival of patients with high and low expression of miR-506 was compared with the median value of miR-506 as the limit. ROC curve was applied to detect the value of miR-506 in diagnosing CML and predicting the 5-year survival of patients, and K562 cell line was transfected with miR-506 inhibitor and miR-506 mimic for observing its effects on the cell proliferation and apoptosis.

Results: miR-506 in CML patients was evidently lower than that in healthy people, the AUC of diagnosis of miR-506 was 0.883, the total survival of patients with low miR-506 was evidently lower than those with high miR-506, and the AUC of predicted survival of patients was 0.778. The proliferation of cells transfected with miR-506 inhibitor was promoted, the apoptosis and the survival rate reduced.

Conclusion: miR-506 is evidently reduced in CML, and may be applied as a diagnostic and predictive treatment for CML and 5-year related survival; it can also can hinder the viability of K562 cells and promote apoptosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430173PMC
August 2021

miR-497-5p induces apoptosis in K562 cells by downregulating ROCK1.

Am J Transl Res 2021 15;13(8):9278-9284. Epub 2021 Aug 15.

Department of Hematology, Xingtai People's Hospital Xingtai 054000, Hebei Province, China.

Objective: To validate the role of miR-497-5p in apoptosis in K562 cells by targeting Rho-associated kinase isoform 1 (ROCK1).

Methods: From January, 2017 to February, 2019, 57 patients with chronic myeloid leukemia (CML) treated in our hospital were included in patient group, and 50 healthy individuals were recruited as control group. miR-497-5p level in peripheral blood was quantitated using qRT-PCR. After transfecting with miR-497-5p overexpression vector and ROCK1 inhibitor, K562 cells were monitored in terms of proliferation (CCK8 assay), migration and invasion (Transwell), and apoptosis (flow cytometry). Binding loci between miR-497-5p and ROCK1 were predicted, and the targeting relationship was confirmed (dual-luciferase reporter (DLR) assay).

Results: miR-497-5p was poorly expressed in CML ( < 0.05). Forced overexpression of miR-497-5p or inhibition of ROCK1 suppressed malignant processes (proliferation, proliferation, migration and invasion) in K562 cells and induced apoptosis ( < 0.05). DLR assay revealed a decreased luciferase activity after miR-497-5p binding to ROCK1 ( < 0.05).

Conclusion: miR-497-5p induces apoptosis in K562 cells by downregulating ROCK1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430193PMC
August 2021

Universal fluorescence nanoprobes to enhance the sensitivity of immunochromatographic assay for detection of 17β-estradiol in milk.

Food Chem 2021 Sep 1;370:131027. Epub 2021 Sep 1.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, PR China. Electronic address:

The pollution caused by estrogens in the environment and food has received increasing attention. It is still challenging for on-site immunochromatographic assay (ICA) detection of estrogens. The performance of the prepared probes plays a decisive role in the sensitivity and stability of the ICA system. The published probes usually directly couple the detection antibody to the label, ignoring the influence of the label on the activity of the antibody. In this study, 17β-estradiol (E) was used as a model analyte for the ICA system. Two universal probes were constructed based on quantum dot nanobeads (QBs), recombinant protein A (SPA, from Staphylococcus aureus), and rabbit anti-mouse immunoglobulin G antibody (anti-IgG). The probes were prepared by coupling QBs with SPA, releasing anti-E monoclonal antibody (mAb), and maintaining its activity. The prepared universal probes can orient recognize the Fc region of mAb and fully expose its Fab region, improving the detection sensitivity of the ICA system. The free anti-E mAb and the universal probe ([email protected] or [email protected]@anti-IgG) were used as the detection antibodies and signal donors, respectively. The results show that the proposed ICA based on [email protected] and [email protected]@anti-IgG probes could detect E with IC of 8.83 and 0.93 ng/mL, respectively, within 15 min under optimal conditions. The recovery results of ICA based on [email protected] and [email protected]@anti-IgG probes showed good agreement with the findings of the high-performance liquid chromatography (HPLC) analysis for spiked samples. The developed ICA system based on universal probes was superior in terms of sensitivity, rapidity, and applicability, and held great promise for its implementation in detecting environmental and food small-molecule pollutants.
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http://dx.doi.org/10.1016/j.foodchem.2021.131027DOI Listing
September 2021

Investigating the Association between Wake-Up Stroke and Obstructive Sleep Apnea: A Meta-Analysis.

Eur Neurol 2021 Sep 9:1-10. Epub 2021 Sep 9.

Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Background: Management of wake-up stroke (WUS) is always a challenge as no clear time of onset could be ascertained, and how to choose an appropriate therapy remains unclear. Sleep-disordered breathing (SDB) has been regarded as a potential risk factor to WUS, yet no consensus was achieved. Motivated by the need for a deeper understanding of WUS and its association with sleep apnea, meta-analyses summarizing the available evidence of respiratory events and indices were conducted, and sensitivity analysis was also used for heterogeneity.

Methods: Electronic databases were systematically searched, and cross-checking was done for relevant studies. Collected data included demographic characteristics, and sleep apnea parameters were extracted with stroke patients divided into WUS and NWUS groups. Clinical data of stroke patients accompanied with sleep apnea syndrome (OSA, SAS, and severe SAS) were also extracted for meta-analysis.

Results: A total of 13 studies were included in the analysis. The meta-analysis results showed that OSA, SAS, and severe SAS were significantly higher in WUS patients. A significantly higher AHI (WMD 7.74, 95% CI: 1.38-14.11; p = 0.017) and ODI (WMD of 3.85, 95% CI: 0.261-7.438; p = 0.035) than NWUS patients was also observed in the analysis of respiratory indices.

Conclusion: WUS patients have severer SDB problems compared to NWUS patients suggesting that respiratory events during sleep might be underlying the induction of WUS. Besides, the induction of WUS was significantly associated with men rather than women. Therefore, early diagnosis and management of potential WUS patients should benefit from the detection of SDB status and respiratory effects.
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http://dx.doi.org/10.1159/000517916DOI Listing
September 2021

Global gaps in age data based on skeletochronology for amphibians.

Integr Zool 2021 Sep 8. Epub 2021 Sep 8.

Department of Ecology, College of Life Sciences, Wuhan University, Wuhan, China.

Individual age and population age composition are the major concerns of ecologists, evolutionary biologists and conservation biologists. In amphibians, skeletochronology-counting the number of lines of arrested growth deposited in the bone tissue, is the dominant method to determine actual age of an individual. Since 1970s, age data of the ectothermic taxa have been accumulated and increasingly used in comparative studies. Here we make a global assessment for the availability of the data, based on a collection of 369 published papers. For a specific species, more males than females were sampled. Among the extant 8146 amphibian species, only 266 (3.3%) have been skeletochronologically investigated. Of these studied species, 2 (0.9% of 214) belong to caecilians, 56 (7.6% of 740) salamanders and 208 (2.9% of 7192) anurans. A complete paucity of data was seen in 80%, 50%, and 54% of families in the corresponding orders. More temperate species than tropical species were sampled, while the proportion of Palearctic species studied was higher than that in the other 5 biogeographical realms. Species inhabiting semi-aquatic niche were more likely to be studied than fossorial or plant dwellers. Age information of multiple populations (2-48) was available for species with a broad distribution, accounts for 61% of salamander and 43% of anuran species studied. Because these gaps in demographic knowledge can limit our understanding of questions ranging from life history evolution, population dynamics to conservation, we encourage herpetologists to pay more efforts on filling them.
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http://dx.doi.org/10.1111/1749-4877.12584DOI Listing
September 2021

Multiparametric magnetic resonance imaging/magnetic resonance elastography assesses progression and regression of steatosis, inflammation, and fibrosis in alcohol-associated liver disease.

Alcohol Clin Exp Res 2021 Sep 5. Epub 2021 Sep 5.

Radiology, Mayo Clinic, Rochester, Minnesota, USA.

Background: Magnetic resonance imaging (MRI) and MRI-based elastography (MRE) are the most promising noninvasive techniques in assessing liver diseases. The purpose of this study was to evaluate an advanced multiparametric imaging method for staging disease and assessing treatment response in realistic preclinical ALD models.

Methods: We utilized four different preclinical mouse models in our study: Model 1-mice were fed a fast-food diet and fructose water for 48 weeks to induce nonalcoholic fatty liver disease; Model 2-mice were fed chronic-binge ethanol (EtOH) for 10 days or 8 weeks to induce liver steatosis/inflammation. Two groups of mice were treated with interleukin-22 at different time points to induce disease regression; Model 3-mice were administered CCl for 2 to 4 weeks to establish liver fibrosis followed by 2 or 4 weeks of recovery; and Model 4-mice were administered EtOH plus CCl for 12 weeks. Mouse liver imaging biomarkers including proton density fat fraction (PDFF), liver stiffness (LS), loss modulus (LM), and damping ratio (DR) were assessed. Liver and serum samples were obtained for histologic and biochemical analyses. Ordinal logistic regression and generalized linear regression analyses were used to model the severity of steatosis, inflammation, and fibrosis, and to assess the regression of these conditions.

Results: Multiparametric models with combinations of biomarkers (LS, LM, DR, and PDFF) used noninvasively to predict the histologic severity and regression of steatosis, inflammation, and fibrosis were highly accurate (area under the curve > 0.84 for all). A three-parameter model that incorporates LS, DR, and ALT predicted histologic fibrosis progression (r = 0.84, p < 0.0001) and regression (r = 0.79, p < 0.0001) as measured by collagen content in livers.

Conclusion: This preclinical study provides evidence that multiparametric MRI/MRE can be used noninvasively to assess disease severity and monitor treatment response in ALD.
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http://dx.doi.org/10.1111/acer.14699DOI Listing
September 2021

Nontargeted screening method for veterinary drugs and their metabolites based on fragmentation characteristics from ultrahigh-performance liquid chromatography-high-resolution mass spectrometry.

Food Chem 2022 Feb 21;369:130928. Epub 2021 Aug 21.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Nontargeted screening of both veterinary drugs and their metabolites is important for comprehensive safety evaluation of animal-derived foods. In this study, a novel nontargeted screening strategy was developed for veterinary drugs and their metabolites based on fragmentation characteristics from ultrahigh-performance liquid chromatography-high-resolution mass spectrometry. First, an in-house database of mass spectra including 3,710 veterinary drugs and their metabolites was constructed. Second, fragmentation characteristics of parent drugs and their metabolites in mass spectrometry were investigated and summarized. Then, a nontargeted screening procedure was established based on fragmentation characteristics to screen unknown parent drugs and their metabolites. Finally, the strategy was applied to 33 egg samples, and four veterinary drugs and three drug metabolites were determined and identified. These results showed that the developed strategy can realize suspect and nontargeted screening of veterinary drugs and their metabolites, and can also be applied to other animal-derived foods.
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http://dx.doi.org/10.1016/j.foodchem.2021.130928DOI Listing
February 2022

MR Features Based on LI-RADS Ver. 2018 Correlated with Cytokeratin 19 Expression in Combined Hepatocellular Carcinoma-Cholangiocarcinoma.

J Hepatocell Carcinoma 2021 21;8:975-983. Epub 2021 Aug 21.

Shanghai Institute of Medical Imaging, Shanghai, People's Republic of China.

Purpose: To investigate the significance of MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) for identifying the expression of cytokeratin 19 (CK-19) in patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) before surgery.

Patients And Methods: The study enrolled 174 patients pathologically confirmed to have cHCC-CCA according to the 2019 WHO classification. The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the CK-19-positive and CK-19-negative cHCC-CCA groups.

Results: One hundred seventy-four patients (mean age, males vs females: 56.6 ± 10.0 years vs 54.7 ± 14.2 years) were evaluated. The presence of mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement was significantly higher in the CK-19-positive group (all p < 0.05), while nonrim arterial phase hyperenhancement (APHE) was more common in the CK-19-negative group (p = 0.04). The univariate analysis showed that hepatitis B virus infection, CEA > 5 ng/mL, tumor size, nonrim APHE, mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement were significant risk factors for CK-19-positive cHCC-CCA (all p < 0.05). Unfortunately, the multivariate analysis revealed that only corona enhancement (OR = 2.359, p = 0.03) was an independent risk factor associated with CK-19-positive cHCC-CCA.

Conclusion: Corona enhancement is significantly correlated with CK-19 positivity in patients with cHCC-CCA.
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http://dx.doi.org/10.2147/JHC.S325686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387586PMC
August 2021

Social network analysis model for research on organizational structure of the pyramid scheme communication network.

MethodsX 2021 3;8:101259. Epub 2021 Feb 3.

College of Systems Engineering, National University of Defense Technology, Changsha 410072, China.

In this article, we introduce a structural analysis model to analyze the characteristics of the communication network structure of pyramid scheme organizations. This model is a combination of SNA (Social Network Analysis) model, motifs analysis model, and exponential random graph model. It can analyze the network from three aspects: global structure analysis, microstructure analysis, and construction feature analysis. We use this model to analyze the characteristics of multiple aspects of a typical pyramid scheme organization's communication network, and the analysis results effectively expand the understanding of the characteristics of the pyramid scheme organization.•••
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http://dx.doi.org/10.1016/j.mex.2021.101259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374287PMC
February 2021

Comprehensive analysis of coagulation indices for predicting survival in patients with biliary tract cancer.

BMC Cancer 2021 Aug 25;21(1):953. Epub 2021 Aug 25.

Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China.

Background: Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC.

Methods: The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram.

Results: Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging.

Conclusions: The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC.
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http://dx.doi.org/10.1186/s12885-021-08684-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390227PMC
August 2021

Liver stiffness measurement by magnetic resonance elastography is not affected by hepatic steatosis.

Eur Radiol 2021 Aug 25. Epub 2021 Aug 25.

Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Objectives: To evaluate the relationship between biopsy-assessed hepatic steatosis, magnetic resonance imaging (MRI)-assessed proton density fat fraction (PDFF), and magnetic resonance elastography (MRE)-assessed liver stiffness measurement (LSM), in patients with or at risk for nonalcoholic fatty liver disease (NAFLD).

Methods: A retrospective study was performed, encompassing 256 patients who had a liver biopsy and MRI/MRE examination performed within 1 year. Clinical and laboratory data were retrieved from the electronic medical record. Hepatic steatosis and fibrosis were assessed by histopathological grading/staging. First, we analyzed the diagnostic performance of PDFF for distinguishing hepatic steatosis with the receiver operating characteristic analyses. Second, variables influencing LSM were screened with univariant analyses, then identified with multivariable linear regression. Finally, the potential relationship between PDFF and LSM was assessed with linear regression after adjustment for other influencing factors, in patients with diagnosed steatosis (PDFF ≥ 5%).

Results: The diagnostic accuracy of PDFF in distinguishing steatosis grades (S0-3) was above 0.82. No significant difference in LSM was found between patients with S1, S2, and S3 steatosis and between all steatosis grades after patients were grouped according to fibrosis stage. No statistically significant relationship was found between the LSM and PDFF (estimate =  - 0.02, p = 0.065) after adjustment for fibrosis stage and age in patients with diagnosed steatosis (PDFF ≥ 5%).

Conclusions: In patients with NAFLD, the severity of hepatic steatosis has no significant influence on the liver stiffness measurement with magnetic resonance elastography.

Key Points: • The MRI-based proton density fat fraction provides a quantitative assessment of hepatic steatosis with high accuracy. • No significant effect of hepatic steatosis on MRE-based liver stiffness measurement was found in patients with S1, S2, and S3 steatosis and between all steatosis grades after patients were grouped according to fibrosis stage. • After adjusting for fibrosis stage and age, there was no statistically significant relationship between liver stiffness and proton density fat fraction in patients with hepatic steatosis (p = 0.065).
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http://dx.doi.org/10.1007/s00330-021-08225-wDOI Listing
August 2021

Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy.

Hepatobiliary Surg Nutr 2021 Aug;10(4):434-442

Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.

Background: A combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma (HCC) with extrahepatic metastases. Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported.

Methods: Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed.

Results: Nine patients with localized disease who received first-line systemic therapy were enrolled. At baseline, all of them had oligometastatic disease, namely, Barcelona Clinic Liver Cancer stage C (or Chinese Liver Cancer stage IIIB). The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization, and the median time span from systemic therapy to surgery was 3.2 (IQR, 2.8-6.2) months. Three patients achieved a pathological complete response. Six patients underwent laparoscopic surgery, and the other 3 patients underwent open surgery. After a median follow-up of 10.2 (IQR, 8.6-20.0) months, 7 patients survived without disease recurrence, and 2 experienced tumour recurrence. All patients had any-grade AEs, and 55.6% of the patients experienced grade 3 AEs. Fatigue was the most common AE, followed by elevated aminotransferase levels and hypertension.

Conclusions: Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable. This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.
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http://dx.doi.org/10.21037/hbsn-21-188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350994PMC
August 2021

Assessing the stability of one-stage PN/A process through experimental and modelling investigations.

Sci Total Environ 2021 Aug 18;801:149740. Epub 2021 Aug 18.

Advanced Water Management Centre, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address:

The mainstream partial nitritation/anammox (PN/A) process has been intensively studied but its stability remains a key challenge. It is shown here that biofilm thickness can exhibit a critical role in controlling the process stability of mainstream PN/A against dissolved oxygen (DO) variation. In a laboratory moving bed biofilm reactor (MBBR), PN/A performance was initially established in 200 days by controlling a low DO of 0.13 ± 0.07 mg O/L in the bulk liquid, which deteriorated with an increase of DO (0.35 ± 0.13 mg O/L) for over two months, and then rapidly recovered in a month with the initial low DO level re-applied. Biofilm thickness of PN/A carriers was measured during the experiment, which became significantly thinner (367 ± 146 μm) at mainstream conditions. The thin thickness primarily decreased the in-situ consumption rate of nitrite, rather than ammonium, when DO increased from 0.1 to 0.4 mg O/L, due to that the thin thickness can only restrict anammox capacity. These results illustrated the role of biofilm thickness in regulating PN/A performance and microbial activities. Further investigation using an established model revealed the joint contribution of biofilm thickness and DO concentration to PN/A process, while particularly, the biofilm thickness can determine the optimal DO level for maximizing the nitrogen removal efficiency and system robustness against DO variation. These results highlight the need of considering biofilm thickness in PN/A process optimization and stability improvement in low-strength wastewater treatment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149740DOI Listing
August 2021

Systematic evaluation of a series of pectic polysaccharides extracted from apple pomace by regulation of subcritical water conditions.

Food Chem 2022 Jan 11;368:130833. Epub 2021 Aug 11.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

To investigate the influences of different subcritical water conditions on apple pomace pectic polysaccharides (APP) extraction, 20 samples were successfully prepared and systematically analyzed. At low temperature region (100-120 °C), extraction effect was predominant and extracted APP was high molecular weight, esterification degree and galacturonic acid content as well as light color. At middle temperature region (140 °C), the balance of extraction and degradation effects was reached and led to the highest APP yield (14.89%). At high temperature region (160-180 °C), degradation effect was predominant and led to serious degradation of APP and more extraction of co-extracts, which endowed the APP with low viscosity and good antioxidant activities in vitro. Overall, the relationship between different subcritical water conditions and APP properties are preliminarily illuminated, which not only provides a promising way for directed extraction of specific APP, but also promotes the potential application of subcritical water to commercial pectin.
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http://dx.doi.org/10.1016/j.foodchem.2021.130833DOI Listing
January 2022

Pollution characteristics and source analysis of heavy metals in surface sediments of Luoyuan Bay, Fujian.

Environ Res 2021 Aug 19;203:111911. Epub 2021 Aug 19.

Key Laboratory for Humid Subtropical Eco-geographical Processes of the Ministry of Education, Fujian Normal University, Fuzhou, 350007, Fujian, China; School of Geographical Sciences, Fujian Normal University, Fuzhou, 350007, Fujian, China.

The concentrations of eight heavy metals, V, Cr, Co, Ni, Cu, Zn, Cd, and Pb, were analyzed to explore the environmental pollution characteristics, ecological risk levels, and sources of heavy metals in the surface sediments of Luoyuan Bay in Fujian Province. The results indicated that the mean concentrations of V, Cr, Co, Ni, Cu, Zn, Cd, and Pb were 110.44, 97.76, 17.35, 41.99, 36.78, 137.26, 0.09, and 35.81 mg⋅kg, respectively. The mean concentrations of Cr, Cu, and Zn exceeded the first category of the marine sediment quality standards, indicating a moderate regional comprehensive potential ecological hazard level. Due to variable hydrodynamic conditions, high concentrations of heavy metals were observed in the north and low concentrations were observed in the south, with high values generally recorded near steel plants and shipyard docks. Correlation and principal component analyses revealed that the V, Al, Co, Ni, and Pb originated from the weathering and erosion of rocks, and industrial wastewater discharge. Contrastingly, Cu, Zn, Cr, and Cd were mainly associated with the transportation and repair of ships, and marine aquaculture activities.
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http://dx.doi.org/10.1016/j.envres.2021.111911DOI Listing
August 2021

The Prognostic Value of Systemic Inflammation Response Index in Cholangiocarcinoma Patients.

Cancer Manag Res 2021 10;13:6263-6277. Epub 2021 Aug 10.

Department of Liver Surgery, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC) & Chinese Academy of Medical Sciences (CAMS), Beijing, 100730, People's Republic of China.

Purpose: We determined the prognostic value of the systemic inflammation response index (SIRI) in patients with cholangiocarcinoma after surgery and constructed a survival prediction model based on SIRI.

Patients And Methods: We recruited 328 patients with histopathologically confirmed cholangiocarcinoma from 2003 to 2017 and performed Kaplan-Meier survival and Cox analyses to analyze the prognostic value of the SIRI and identify other significant factors. A nomogram involving SIRI and other clinicopathological factors was established based on the training cohort. The concordance index (C-index), decision curve analysis, calibration plots, and Hosmer-Lemeshow test were used to evaluate the clinical utility of the nomogram and to compare it with the traditional TNM staging system. The results were validated using a separate validation cohort.

Results: The patients were randomly divided into the training (n = 232) and validation (n = 96) cohorts. In the training cohort, the independent factors derived from the Cox multivariate analysis were SIRI, platelet-to-lymphocyte ratio, jaundice, γ-glutamyl transpeptidase level, maximal tumor size, N stage, M stage, and radical surgery. Time-dependent receiver operating characteristic (ROC) curves showed higher AUC for SIRI than those for other inflammation-based biomarkers. A nomogram containing all the independent factors showed good discrimination and calibration. The C-index values for overall survival, 0.737 (95% Cl: 0.683-0.791) and 0.738 (95% Cl: 0.679-0.797) in the training and validation cohorts, respectively, were significantly better than those for the TNM staging system [0.576 (95% Cl: 0.515-0.637) and 0.523 (95% Cl: 0.465-0.581), respectively].

Conclusion: SIRI was an independent prognostic factor for cholangiocarcinoma. A prognostic model based on SIRI might help clinicians to stratify patients more precisely and provide individualized treatment.
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http://dx.doi.org/10.2147/CMAR.S317954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364361PMC
August 2021

Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis.

Nat Commun 2021 08 17;12(1):4977. Epub 2021 Aug 17.

Department of Rheumatology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45 hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.
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http://dx.doi.org/10.1038/s41467-021-25246-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371160PMC
August 2021

C12-HSL is an across-boundary signal molecule that could alleviate fungi Galactomyces's filamentation: A new mechanism on activated sludge bulking.

Environ Res 2021 Aug 14;204(Pt A):111823. Epub 2021 Aug 14.

Jilin Engineering Lab for Water Pollution Control and Resources Recovery, Northeast Normal University, Changchun, 130117, China. Electronic address:

Fungal bulking is caused by fungi excessive growth and morphological changes, resulting from the evolution toward fungi dominant activated sludge. Communication across fungi and bacteria boundary that mediated by bacterial signal molecules (SMs) probably is the central induce caused fungal bulking occurrence. In this work, it intended to identify the bacterial SM that affected fungal bulking, and verified its roles in regulate the spore germination and hyphal growth. We found C12-HSL concentration decreased significantly from 12.36 to 3.38 ng/g-VSS (P < 0.05) when fungal sludge bulking happened, and filamentous Galactomyces's relatively abundant was correlatively enriched. To test the effects of this SM, trace commercial C12-HSL was added to pure cultured Galactomyces, in which spore germination rates decreased by 20 % and hyphal extension inhibited by 15 %. Ras1-cAMP-PKA and mitogen-activated protein kinase (MAPK) pathways of Galactomyces were responsible for signal C12-HSL transduction, which inhibited peroxisome biosynthesis, suppressed the biological activity of the actin cytoskeleton, and disrupted intercellular organelle transport. All these results showed C12-HSL was the functional SM that could suppress the development of fungal filamentous. This study provided a new insight into the sludge bulking mechanism from view of cross-kingdom communication.
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http://dx.doi.org/10.1016/j.envres.2021.111823DOI Listing
August 2021

Public Psychosocial and Behavioral Responses in the First Wave of COVID-19 Pandemic: A Large Survey in China.

Front Psychiatry 2021 28;12:676914. Epub 2021 Jul 28.

Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, China.

The COVID-19 has grown into a global pandemic. This study investigated the public psychosocial and behavioral responses through different time periods of the pandemic, and assessed whether these changes are different in age, gender, and region. A three-phase survey was conducted through the DaDui Social Q&A Software for COVID-19. A total of 13,214 effective responses of COVID-19 were collected. Statistical analysis was performed based on their basic information and psychosocial responses. The degree of attention, understanding, and cooperation with preventive and control measures of the disease increased and then decreased. The panic level gradually increased with the epidemic process. The degree of satisfaction with management measures and of confidence in defeating COVID-19 increased throughout the survey. Compared with residents in other areas, respondents from the COVID-19 epicenter (Wuhan) reported a higher degree of self-protection during the outbreak and a significantly lower degree of satisfaction with respect to government prevention and control measures during all phases. Shortages of medical supplies and low testing capacity were reported as the biggest shortcoming in the prevention and control strategies during COVID-19, and an abundance of disorderly and inaccurate information from different sources was the primary cause of panic. Major public health events elicit psychosocial and behavioral changes that reflect the different phases of the biologic curve. Sufficient medical supplies and improved organization and accurate information during epidemics may reduce panic and improve compliance with requested changes in behavior. We need to recognize this natural phenomenon and our public policy preparedness should attempt to move the social/psychological curve to the left in order to minimize and flatten the biologic curve.
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http://dx.doi.org/10.3389/fpsyt.2021.676914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355736PMC
July 2021

Enzymatic Preparation and Structure-activity Relationship of Sesaminol.

J Oleo Sci 2021 Sep 6;70(9):1261-1274. Epub 2021 Aug 6.

Research Centre for Agricultural and Sideline Products Processing, Henan Academy of Agricultural Sciences.

As a valuable natural antioxidant, sesaminol can be used in food and medicine industries, but it is trace in sesame seeds and oil, and it is feasible to prepare sesaminol from sesaminol triglucoside (STG) which is abundant in defatted sesame cake. Therefore, in order to establish an effective enzymatic preparation method and elucidate the antioxidant structure-activity relationship of sesaminol, a suitable glycosidase for preparing sesaminol from STG were screened, enzymatic hydrolysis was optimized by single-factor test and response surface methodology, and finally, the structure-activity relationship of sesaminol was illustrated by comparative molecular field analysis (CoMFA). These results suggested that β-galactosidase was the optimal glycosidase for enzymatic hydrolysis of STG to prepare sesaminol. Under the optimal conditions of a reaction temperature of 50°C, reaction time of 4.0 h, pH of 5.5, substrate concentration of 1.0 mg/mL, and enzyme dosage of 20 mg/mL, the conversion rate of sesaminol was 98.88±0.67%. Sesaminol displayed excellent antioxidant ability in 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC = 0.0011 mg/mL), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonate) (ABTS, IC = 0.0021 mg/mL) radical scavenging activities and Ferric reducing antioxidant power (FRAP, 103.2998 mol/g) compared to other sesaminol derivatives. According to -log (IC of DPPH) and -log (IC of ABTS), CoMFA models were successfully established based on Q >0.5 (Q = 0.558, Q = 0.534). The active site of sesaminol tended to be located on the hydroxyl group of the benzene ring (R position). A positive correlation between the bulky and positively charged groups at the 1H, 3H-furo [3, 4-c] furan group, the small, negatively charged groups at the R position and the antioxidant activity of sesaminol. This study provides an effective method to prepare sesaminol, reveals the structure-activity relationship of sesaminol and provides theoretical basis to design the novel compound.
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http://dx.doi.org/10.5650/jos.ess21112DOI Listing
September 2021

Infection is not rare in patients with idiopathic inflammatory myopathies.

Clin Exp Rheumatol 2021 Jul 21. Epub 2021 Jul 21.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objectives: To assess the prevalence and characteristics of infections in patients with idiopathic inflammatory myopathies (IIM) and analyse risk factors for infection using clinical presentation and biochemical findings of IIM.

Methods: Retrospective review of the medical records of patients with IIM followed up in a single medical centre from January 2008 to January 2018.

Results: Of the 779 patients with IIM, 215 (27.6%) suffered from infections. The prevalence of infection in dermatomyositis (DM) (29.8%) was more than polymyositis (PM) (18.5%). The lung was the most common infection site (66.5%). Multivariate analyses demonstrated that methylprednisolone pulse (MP) (OR=3.22; 95% CI=1.60 - 6.48; p=0.001), age of onset >50 years (OR=1.02; 95% CI=1.00 - 1.03; p=0.011), anti-melanoma differentiation-associated gene 5 (MDA5) antibody (OR=1.93; 95% CI=1.20 - 3.11; p=0.007), lymphocyte count <1200/mm3 (OR=2.85; 95% CI=1.89 - 4.30; p<0.001), and interstitial lung diseases (ILD) (OR=2.03; 95% CI=1.30 - 3.71; p=0.002) are independent risk factors for infection. Survival analysis demonstrated that the three-year survival rate in the infection group was lower than the no-infection group (75.3% vs. 94.7%, p < 0.001).

Conclusions: Among hospitalised individuals with IIM, infection is frequent and the leading cause of mortality. The anti-MDA5 antibody, lymphopenia, ILD, old age, and treatment with MP are contributing factors in the development of infections in patients with IIM.
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July 2021

54 cm Large-Area Flexible Organic Solar Modules with Efficiency Above 13.

Adv Mater 2021 Oct 8;33(39):e2103017. Epub 2021 Aug 8.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.

Development of large-area flexible organic solar cells (OSCs) is highly desirable for their practical applications. However, the efficiency of the large-area flexible OSCs severely lags behind small-area devices. Here, efficient large-area flexible single cells with power conversion efficiency (PCE) of 13.1% and 12.6% for areas of 6 and 10 cm , and flexible modules with a PCE of 13.2% (54 cm ) based on poly(ethylene terephthalate)/Ag grid/silver nanowires (AgNWs):zinc-chelated polyethylenimine (PEI-Zn) composite electrodes are reported. The solution-processed flexible transparent electrode of AgNWs:PEI-Zn shows low surface roughness and good optoelectronic and mechanical properties. PEI-Zn is conductive and optically transparent. It can adhere to and wrap the AgNWs under electrostatic interaction between the negatively charged surface (AgNWs) and positively charged protonated amine groups (in PEI-Zn). It wraps the AgNWs networks and fills the void space to achieve a smooth surface. The flexible electrode is validated in both flexible OSCs and flexible quantum-dots light-emitting diodes (QLEDs). Small-area flexible OSCs show a PCE of 16.1%, and flexible QLEDs show an external quantum efficiency of 13.3%. In the end, a flexible module is demonstrated to charge a mobile phone as a flexible power source (shown in Video S1, Supporting Information).
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http://dx.doi.org/10.1002/adma.202103017DOI Listing
October 2021

An AIE triggered fluorescence probe with three-photon absorption and its biological applications.

Talanta 2021 Nov 26;234:122639. Epub 2021 Jun 26.

Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, 610041, PR China; Department of Chemistry, Key Laboratory of Functional Inorganic Materials Chemistry of Anhui Province, Anhui University, Hefei, 230601, PR China; School of Life Science, Anhui University, Hefei, 230601, PR China. Electronic address:

Three-photon absorption (3 PA) in the near IR region is among the most prominent nonlinear optical (NLO) effects and has attractive applications in chemical/biological sensing and imaging. Yet, rationally constructed molecules with small molecular weight and reasonable 3 PA cross-section has been rarely reported. Herein, we designed a novel three-photon absorption photostable luminogen (namely X1) with enhanced aggregation induced emission (AIE) and the ability to achieve multi-photon imaging with femtosecond laser excitation. X1 was constructed from diaminobenzene and diethylamino salicylaldehyde forming a novel di-Schiff base. It possesses a large conjugated delocalization which exhibits large three-photon absorption (3 PA) cross-section values. We also showed that by using a suitable delivery vector, X1 compound could applied as a live cell imaging probe thus providing a valuable tool to study lipid droplets/lysosome interaction in depth tissues.
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http://dx.doi.org/10.1016/j.talanta.2021.122639DOI Listing
November 2021

Development of a novel analytical method for inflammation and immunity-related metabolites in serum based on liquid chromatography tandem mass spectrometry.

Talanta 2021 Nov 24;234:122631. Epub 2021 Jun 24.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. Electronic address:

Some metabolites have been found to play key roles in inflammation and immunity events that are associated with diseases such as cancer, diabetes and cytokine release syndrome. Characterization upon the inflammation and immunity-related metabolites (IIMs) will be helpful to the assessment of related pathological states. Although these metabolites have been partially reported in previous studies, the methods for specific measurement of them remain lacking. In the present study, a liquid chromatography - mass spectrometry based method was developed for the targeted analyses of 45 IIMs including amino acids, organic acids, phosphatidylcholines (PCs), polyunsaturated fatty acids and hormones selected based on the literature knowledge. Direct extraction with dansyl-chloride in acetonitrile was proved to be the most efficient and time-saving strategy, in which precipitation, extraction and derivatization were integrated. IIMs derivatized for 4 min and quenched for 2 min revealed the most comprehensive abundance. Based on the defined conditions, all the IIMs had a low limit of detection smaller than 1 ng/mL with the linear range greater than three orders of magnitude. The relative standard derivations of intra-day and inter-day precisions were ranged from 2.2% to 13.4% and 1.7% to 19.5%, respectively. The recovery rates and accuracy in low concentration were 98.9% ± 5.6% and 106.7% ± 11.6%, in medium concentration were 97.1% ± 6.8% and 106.9% ± 9.5%, and in high concentration were 98.4% ± 8.9% and 98.1% ± 8.1%, respectively. Matrix effect and stability were ranged from -37.8% to 35.6% and 2.9% to 14.2%, respectively. To show the usefulness of the method, serum IIMs in hepatitis B virus (HBV) infected patients and healthy subjects were determined and compared. Bile acids, lipoxygenase-mediated lipid mediators and non-enzymatic products showed global increases, whereas most of LysoPCs and cyclooxygenase-mediated prostaglandin D2 decreased in HBV serum samples. This study provided a robust approach for the characterization of IIMs.
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http://dx.doi.org/10.1016/j.talanta.2021.122631DOI Listing
November 2021
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