Publications by authors named "Lei Fang"

738 Publications

Global disease burden of stroke attributable to high fasting plasma glucose in 204 countries and territories from 1990 to 2019: An analysis of the Global Burden of Disease Study.

J Diabetes 2022 Aug 4. Epub 2022 Aug 4.

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

Background: High fasting plasma glucose (HFPG) is the leading risk factor contributing to the increase of stroke burden in the past three decades. However, the global distribution of stroke burden specifically attributable to HFPG was not studied in depth. Therefore, we analyzed the HFPG-attributable burden in stroke and its subtypes in 204 countries and territories from 1990 to 2019.

Methods: Detailed data on stroke burden attributable to HFPG were obtained from the Global Burden of Disease Study 2019. The numbers and age-standardized rates of stroke disability-adjusted life years (DALYs), deaths, years lived with disability, and years of life lost between 1990 and 2019 were estimated by age, sex, and region.

Results: In 2019, the age-standardized rate of DALYs (ASDR) of HFPG-attributable stroke was 354.95 per 100 000 population, among which 49.0% was from ischemic stroke, 44.3% from intracerebral hemorrhage, and 6.6% from subarachnoid hemorrhage. The ASDRs of HFPG-attributable stroke in lower sociodemographic index (SDI) regions surpassed those in higher SDI regions in the past three decades. Generally, the population aged over 50 years old accounted for 92% of stroke DALYs attributable to HFPG, and males are more susceptible to HFPG-attributable stroke than females across their lifetime.

Conclusions: Successful key population initiatives targeting HFPG may mitigate the stroke disease burden. Given the soaring population-attributable fractions of HFPG for stroke burden worldwide, each country should assess its disease burden and determine targeted prevention and control strategies.
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http://dx.doi.org/10.1111/1753-0407.13299DOI Listing
August 2022

Age-Related Differences of Cortical Topology Across the Adult Lifespan: Evidence From a Multisite MRI Study With 1427 Individuals.

J Magn Reson Imaging 2022 Aug 3. Epub 2022 Aug 3.

Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China.

Background: Healthy aging is usually accompanied by alterations in brain network architecture, influencing information processing and cognitive performance. However, age-associated coordination patterns of morphological networks and cognitive variation are not well understood.

Purpose: To investigate the age-related differences of cortical topology in morphological brain networks from multiple perspectives.

Study Type: Prospective, observational multisite study.

Population: A total of 1427 healthy participants (59.1% female, 51.75 ± 19.82 years old) from public datasets.

Field Strength/sequence: 1.5 T/3 T, T1-weighted magnetization prepared rapid gradient echo (MP-RAGE) sequence.

Assessment: The multimodal parcellation atlas was used to define regions of interest (ROIs). The Jensen-Shannon divergence-based individual morphological networks were constructed by estimating the interregional similarity of cortical thickness distribution. Graph-theory based global network properties were then calculated, followed by ROI analysis (including global/nodal topological analysis and hub analysis) with statistical tests.

Statistical Tests: Chi-square test, Jensen-Shannon divergence-based similarity measurement, general linear model with false discovery rate correction. Significance was set at P < 0.05.

Results: The clustering coefficient (q = 0.016), global efficiency (q = 0.007), and small-worldness (q = 0.006) were significantly negatively quadratic correlated with age. The group-level hubs of seven age groups were found mainly distributed in default mode network, visual network, salient network, and somatosensory motor network (the sum of these hubs' distribution in each group exceeds 55%). Further ROI-wise analysis showed significant nodal trajectories of intramodular connectivities.

Data Conclusion: These results demonstrated the age-associated reconfiguration of morphological networks. Specifically, network segregation/integration had an inverted U-shaped relationship with age, which indicated age-related differences in transmission efficiency.

Evidence Level: 2 TECHNICAL EFFICACY: Stage 1.
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http://dx.doi.org/10.1002/jmri.28318DOI Listing
August 2022

iTRAQ-based quantitative proteomic analysis of the liver regeneration termination phase after partial hepatectomy in mice.

J Proteomics 2022 Jul 29:104688. Epub 2022 Jul 29.

Core Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Liver regeneration (LR) is an important biological process after liver injury. As the "brake" in the process of LR, the termination phase of LR not only suppresses the continuous increase in liver volume but also effectively promotes the recovery of liver function. However, the mechanisms underlying the termination phase of LR are still not clear. In our study, we used isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis to determine the protein expression profiles of livers in the termination phase of mouse LR after partial hepatectomy (PH). We found that the expression of 197 proteins increased gradually during LR; in addition, 187 proteins were upregulated and 264 proteins were downregulated specifically in the termination phase of LR. The GO analysis of the proteins revealed the upregulation of "cell-cell adhesion" and "translation" and the downregulation of the "oxidation-reduction process". The KEGG pathway analysis showed that "biosynthesis of antibiotics" and "ribosomes" were significantly upregulated, while "metabolic pathways" were significantly downregulated. These analyses indicated that the termination phase of LR mainly focuses on restoring cellular structure and function. Differentially expressed proteins such as SNX5 were also screened out from biological processes. SIGNIFICANCE: The key regulatory factors in the termination phase of LR were studied by iTRAQ-based proteomics to lay a foundation for further study of the molecular mechanism and biomarkers of the termination phase of LR. This study will guide the clinical perioperative management of patients after hepatectomy.
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http://dx.doi.org/10.1016/j.jprot.2022.104688DOI Listing
July 2022

Regulating the spin state of single-atom doped covalent triazine frameworks for efficient nitrogen fixation.

J Colloid Interface Sci 2022 Jul 19;627:931-941. Epub 2022 Jul 19.

Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, China. Electronic address:

Covalent triazine frameworks (CTFs), served as a versatile platform, can form expedient metal-N single-atom coordination sites as promising catalytic centers. To seek out excellent candidate catalysts of M/CTFs (M = Transition metal) for nitrogen reduction reaction (NRR), a "five-step" strategy involving spin states has been established for hierarchical high-throughput screening and reveals strong coordination ability of the CTFs, outstanding conductivity of the M/CTFs, effective adsorption and activation of N* attributed to the electron transfer and orbital hybridization between the M/CTFs and N*. Among the potential candidates, the Cr/CTF is screened out to be an excellent one for nitrogen fixation, which can not only inhibit hydrogen evolution reaction (HER) greatly but also has good thermodynamic stability (E =  -4.40 eV), narrow band gap (E = 0.03 eV), moderate adsorption energy (E =  -0.84 eV), large activation energy (ΔG* = -0.71 eV) and a theoretical Faradaic efficiency of 100%. The spin state has been confirmed to be an important descriptor of catalytic activity and the two-state reactivity (TSR) is validated to exist in the NRR. Reaction mechanism with different spin states of Cr/CTF has been demonstrated to give a great impact on the nitrogen fixation, providing solid theoretical support for the design of more efficient NRR catalysts.
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http://dx.doi.org/10.1016/j.jcis.2022.07.090DOI Listing
July 2022

Health beliefs toward lung cancer screening among Chinese American high-risk smokers: Interviews based on Health Belief Model.

Int J Nurs Sci 2022 Jul 23;9(3):378-388. Epub 2022 Jun 23.

School of Nursing, University of California at Los Angeles, Los Angeles, CA, United States.

Objective: This study aims to explore health beliefs toward lung cancer screening with low dose computed tomography among Chinese American high-risk smokers.

Methods: Guided by the Health Belief Model, semi-structured individual interviews were conducted with Chinese American high-risk smokers via phone. Additional questionnaires on demographic information, history of smoking and lung cancer screening were collected via email or phone before the interview, depending on participants' preference. Content analysis was used to extract meaningful and significant themes in the dataset. Constant comparison analysis and process coding were used to categorize and code data.

Results: Data saturation was reached after interviewing 12 participants. Chinese American high-risk smokers perceived a low susceptibility to lung cancer, since they believed various protective factors of lung cancer (e.g., doing exercise, healthy diet, etc.) reduced their risk of getting lung cancer. All the participants perceived a high severity of lung cancer. They acknowledged lung cancer would have a huge impact on their life. Perceived benefits of lung cancer screening were accurate in most aspects although minor confusions were still noticed among this population. Perceived barriers varied on participants', physicians', and institutional levels. High-risk Chinese American smokers had little confidence to screening for lung cancer. Cues to action for them to screening for lung cancer included recommendations from health care providers, support from family members and friends, and information shared on Chinese-based social media.

Conclusions: Misconceptions and barriers to screening for lung cancer existed widely among Chinese American high-risk smokers. Intervention programs and targeted health education should be implemented to promote lung cancer screening among this population.
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http://dx.doi.org/10.1016/j.ijnss.2022.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305017PMC
July 2022

The RalGAPα1-RalA signal module protects cardiac function through regulating calcium homeostasis.

Nat Commun 2022 Jul 25;13(1):4278. Epub 2022 Jul 25.

State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.

Sarcoplasmic/endoplasmic reticulum calcium ATPase SERCA2 mediates calcium re-uptake from the cytosol into sarcoplasmic reticulum, and its dysfunction is a hallmark of heart failure. Multiple factors have been identified to modulate SERCA2 activity, however, its regulation is still not fully understood. Here we identify a Ral-GTPase activating protein RalGAPα1 as a critical regulator of SERCA2 in cardiomyocytes through its downstream target RalA. RalGAPα1 is induced by pressure overload, and its deficiency causes cardiac dysfunction and exacerbates pressure overload-induced heart failure. Mechanistically, RalGAPα1 regulates SERCA2 through direct interaction and its target RalA. Deletion of RalGAPα1 decreases SERCA2 activity and prolongs calcium re-uptake into sarcoplasmic reticulum. GDP-bound RalA, but not GTP-bound RalA, binds to SERCA2 and activates the pump for sarcoplasmic reticulum calcium re-uptake. Overexpression of a GDP-bound RalA mutant in the heart preserves cardiac function in a mouse model of heart failure. Our findings have therapeutic implications for treatment of heart failure.
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http://dx.doi.org/10.1038/s41467-022-31992-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314365PMC
July 2022

A Machine Learning Model Based on Genetic and Traditional Cardiovascular Risk Factors to Predict Premature Coronary Artery Disease.

Front Biosci (Landmark Ed) 2022 Jul;27(7):211

Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, 510260 Guangzhou, Guangdong, China.

Background: Premature coronary artery disease (PCAD) has a poor prognosis and a high mortality and disability rate. Accurate prediction of the risk of PCAD is very important for the prevention and early diagnosis of this disease. Machine learning (ML) has been proven a reliable method used for disease diagnosis and for building risk prediction models based on complex factors. The aim of the present study was to develop an accurate prediction model of PCAD risk that allows early intervention.

Methods: We performed retrospective analysis of single nucleotide polymorphisms (SNPs) and traditional cardiovascular risk factors (TCRFs) for 131 PCAD patients and 187 controls. The data was used to construct classifiers for the prediction of PCAD risk with the machine learning (ML) algorithms LogisticRegression (LRC), RandomForestClassifier (RFC) and GradientBoostingClassifier (GBC) in scikit-learn. Three quarters of the participants were randomly grouped into a training dataset and the rest into a test dataset. The performance of classifiers was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity and concordance index. R packages were used to construct nomograms.

Results: Three optimized feature combinations (FCs) were identified: RS-DT-FC1 (rs2259816, rs1378577, rs10757274, rs4961, smoking, hyperlipidemia, glucose, triglycerides), RS-DT-FC2 (rs1378577, rs10757274, smoking, diabetes, hyperlipidemia, glucose, triglycerides) and RS-DT-FC3 (rs1169313, rs5082, rs9340799, rs10757274, rs1152002, smoking, hyperlipidemia, high-density lipoprotein cholesterol). These were able to build the classifiers with an AUC >0.90 and sensitivity >0.90. The nomograms built with RS-DT-FC1, RS-DT-FC2 and RS-DT-FC3 had a concordance index of 0.94, 0.94 and 0.90, respectively, when validated with the test dataset, and 0.79, 0.82 and 0.79 when validated with the training dataset. Manual prediction of the test data with the three nomograms resulted in an AUC of 0.89, 0.92 and 0.83, respectively, and a sensitivity of 0.92, 0.96 and 0.86, respectively.

Conclusions: The selection of suitable features determines the performance of ML models. RS-DT-FC2 may be a suitable FC for building a high-performance prediction model of PCAD with good sensitivity and accuracy. The nomograms allow practical scoring and interpretation of each predictor and may be useful for clinicians in determining the risk of PCAD.
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http://dx.doi.org/10.31083/j.fbl2707211DOI Listing
July 2022

Association Between Gene Polymorphism and Cervical Cancer in the Northeast Chinese Han Population.

Front Genet 2022 27;13:860727. Epub 2022 Jun 27.

Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.

The purpose of this study was to investigate the relationship between gene polymorphism and genetic susceptibility to cervical cancer in the Han population in Northeast China. In this case-control study, the genotypes and alleles of rs8067378 in the gene were analyzed by multiplex polymerase chain reaction (PCR) and next-generation sequencing methods in 482 cervical cancer (CC) patients, 775 cervical squamous intraepithelial lesion (SIL) patients, and 495 healthy women. The potential relationships between the SNP of the gene with SIL and CC were analyzed by multivariate logistic regression analysis combined with 10,000 permutation tests. In the comparison between the SIL group and the control group, the genotype and allele distribution frequencies of rs8067378 SNP of the gene were statistically significant ( = 0.0493 and = 0.0202, respectively). The allele distribution frequencies of rs8067378 were also statistically significant in the comparison between high-grade cervical squamous intraepithelial lesion (HSIL) and low-grade cervical squamous intraepithelial lesion (LSIL) groups with control group ( = 0.0483 and = 0.0330, respectively). Logistic regression analysis showed that after adjusting for age, the rs8067378 SNP of the gene was significantly associated with the reduced risk of SIL under the dominant model ( = 0.0213, OR = 0.764, CI = 0.607-0.961) and the additive model ( = 0.0199, OR = 0.814, and CI = 0.684-0.968), and its mutant gene G may play a role in the progression of healthy people to LSIL and even HSIL as a protective factor. However, there was no significant association between cervical cancer and its subtypes with the control group ( > 0.05). After 10,000 permutations, there was still no correlation that has provided evidence for the accuracy of our study. The results of this study showed that rs8067378 single nucleotide polymorphism of the gene may reduce the risk of SIL and protect the susceptibility to cervical precancerous lesions in the Northeast Chinese Han population, but it has no significant correlation with the progression of cervical cancer.
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http://dx.doi.org/10.3389/fgene.2022.860727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271821PMC
June 2022

Novel anilinopyrimidine derivatives as potential EGFR Inhibitors: Design, Synthesis, biological activity study.

Bioorg Med Chem 2022 Jul 5;70:116907. Epub 2022 Jul 5.

Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China. Electronic address:

EGFR is an important target for the development of new generation of EGFR kinase inhibitors without drug resistance. In this work, a series of anilinopyrimidine derivatives that targeting EGFR were designed, synthesized, and evaluated in vitro for the inhibitory effect on triple mutations kinases and cell lines. Based on the pharmacology data, the anilinopyrimidine derivatives showed high inhibitory activity on triple mutations kinases (EGFR and EGFR) as well as the cell line Ba/F3 with highly expression of EGFR. In addition, the anilinopyrimidine derivatives had a more than 50-fold selectivity towards EGFR as compared with EGFR. In vivo antitumor activity test also indicated that 8j had good pharmacokinetic parameters, low toxicity and better inhibitory activity. Overall, the anilinopyrimidine derivatives could be regarded as promising candidates for the further development of novel EGFR inhibitors for clinical application.
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http://dx.doi.org/10.1016/j.bmc.2022.116907DOI Listing
July 2022

TRIM24 is an insulin-responsive regulator of P-bodies.

Nat Commun 2022 Jul 8;13(1):3972. Epub 2022 Jul 8.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, 210061, China.

Insulin is a potent inducer of mRNA transcription and translation, contributing to metabolic regulation. Insulin has also been suggested to regulate mRNA stability through the processing body (P-body) molecular machinery. However, whether and how insulin regulates mRNA stability via P-bodies is not clear. Here we show that the E3-ligase TRIM24 is a critical factor linking insulin signalling to P-bodies. Upon insulin stimulation, protein kinase B (PKB, also known as Akt) phosphorylates TRIM24 and stimulates its shuttling from the nucleus into the cytoplasm. TRIM24 interacts with several critical components of P-bodies in the cytoplasm, promoting their polyubiquitylation, which consequently stabilises Pparγ mRNA. Inactivation of TRIM24 E3-ligase activity or prevention of its phosphorylation via knockin mutations in mice promotes hepatic Pparγ degradation via P-bodies. Consequently, both knockin mutations alleviate hepatosteatosis in mice fed on a high-fat diet. Our results demonstrate the critical role of TRIM24 in linking insulin signalling to P-bodies and have therapeutic implications for the treatment of hepatosteatosis.
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http://dx.doi.org/10.1038/s41467-022-31735-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270398PMC
July 2022

Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer.

Adv Mater 2022 Jun 27:e2205462. Epub 2022 Jun 27.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Lung metastasis is challenging in patients with triple-negative breast cancer (TNBC). Surgery is always not available due to the dissemination of metastatic foci and most drugs are powerless because of poor retention at metastatic sites. TNBC cells generate an inflamed microenvironment and overexpress adhesive molecules to promote invasion and colonization. Herein, "walking dead" TNBC cells are developed through conjugating anti-PD-1 (programmed death protein 1 inhibitor) and doxorubicin (DOX)-loaded liposomes onto cell corpses for temporal chemo-immunotherapy against lung metastasis. The walking dead TNBC cells maintain plenary tumor antigens to conduct vaccination effects. Anti-PD-1 antibodies are conjugated to cell corpses via reduction-activated linker, and DOX-loaded liposomes are attached by maleimide-thiol coupling. This anchor strategy enables rapid release of anti-PD-1 upon reduction conditions while long-lasting release of DOX at inflamed metastatic sites. The walking dead TNBC cells improve pulmonary accumulation and local retention of drugs, reprogram the lung microenvironment through damage-associated molecular patterns (DAMPs) and PD-1 blockade, and prolong overall survival of lung metastatic 4T1 and EMT6-bearing mice. Taking advantage of the walking dead TNBC cells for pulmonary preferred delivery of chemotherapeutics and checkpoint inhibitors, this study suggests an alternative treatment option of chemo-immunotherapy to augment the efficacy against lung metastasis.
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http://dx.doi.org/10.1002/adma.202205462DOI Listing
June 2022

Role of hepatic lipid species in the progression of nonalcoholic fatty liver disease.

Am J Physiol Cell Physiol 2022 Aug 27;323(2):C630-C639. Epub 2022 Jun 27.

Huanggang Institute of Translation Medicine, Huanggang, China.

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease due to the global pandemic of metabolic diseases. Dysregulation of hepatic lipid metabolism plays a central role in the initiation and progression of NAFLD. With the advancement of lipidomics, an increasing number of lipid species and underlying mechanisms associating hepatic lipid components have been revealed. Therefore, the focus of this review is to highlight the links between hepatic lipid species and their mechanisms mediating the pathogenesis of NAFLD. We first summarized the interplay between NAFLD and hepatic lipid disturbances. Next, we focused on reviewing the role of saturated fatty acids, cholesterol, oxidized phospholipids, and their respective intermediates in the pathogenesis of NAFLD. The mechanisms by which monounsaturated fatty acids and other pro-resolving mediators exert protective effects are also addressed. Finally, we further discussed the implication of different analysis approaches in lipidomics. Evolving insights into the pathophysiology of NAFLD will provide the opportunity for drug development.
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http://dx.doi.org/10.1152/ajpcell.00123.2022DOI Listing
August 2022

Nuclear receptor estrogen-related receptor gamma suppresses colorectal cancer aggressiveness by regulating Wnt/β-catenin signalling.

Carcinogenesis 2022 Jun 21. Epub 2022 Jun 21.

Department of Pathology, The First Affiliated Hospital, Shandong First Medical University& Shandong Qianfoshan Hospital, Jinan, Shandong, China.

Colorectal cancer is the predominant cause of cancer-related death worldwide, because of lack of effective therapeutic targets. Estrogen-related receptor gamma (ESRRG), which belongs to the family of nuclear receptors, functions as an important element regulating gene transcription. In our report, we identified ESRRG as a potential tumor suppressor. The decreased level of ESRRG was initially observed in CRC and was highly associated with poor prognosis. ESRRG overexpression abrogated cell growth and metastasis in vitro and in vivo. Mechanistically, ESRRG repressed the epithelial-to-mesenchymal transition (EMT) process and antagonized Wnt signaling by regulating β-catenin degradation. In addition, significant ESRRG hypermethylation was found in CRC and inversely correlated with its expression. Consistently, the expression of ESRRG was induced after treatment with DNA demethylating agent 5-AZA. Taken together, these findings define a tumor-suppressive role of ESRRG in CRC, providing a potential novel therapeutic approach for this cancer.
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http://dx.doi.org/10.1093/carcin/bgac054DOI Listing
June 2022

Design, synthesis and bioactivity evaluation of favorable evodiamine derivative scaffold for developing cancer therapy.

Eur J Med Chem 2022 Sep 15;239:114530. Epub 2022 Jun 15.

School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address:

Natural product evodiamine is one of the most privileged scaffolds in drug discovery and is suitable for derivatization, which can be conducted quickly for structure optimization and structure-activity relationship research. In this work, a comprehensive SAR study on evodiamine scaffold with N14-3'-fluorophenyl substituted was completed, and compounds with high anti-tumor activity and good inhibitory effect on Top1 and Top2 were screened out. Tested evodiamine derivatives exhibited excellent broad-spectrum anti-tumor activity. Among them, compound 8b revealed 55.15% and 55.50% inhibition for Top1 and Top2 at 25 μM, as well as 0.16 and 0.13 μM IC value for MGC-803 and SGC-7901 cells, respectively; compound 9a revealed 70.50% and 71.81% inhibition for Top1 and Top2 at 25 μM, as well as 0.22 and 0.27 μM IC value for MGC-803 and SGC-7901 cells, respectively. The further biological evaluation showed that they could functionally induce apoptosis, significantly arrest the cell cycle at the G2/M phase, and markedly inhibit cell proliferation, migration and invasion. In addition, compound 9a performed a tumor inhibitory rate of 36.35% and showed no apparent toxicity in vivo. Overall, these optimized protocols will advance the progression of cancer chemotherapy and can be used to expand the options for screening therapeutic cancer drugs.
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http://dx.doi.org/10.1016/j.ejmech.2022.114530DOI Listing
September 2022

Thoracoscopic approach to the resection of idiopathic azygos vein aneurysm: a case report.

J Cardiothorac Surg 2022 Jun 20;17(1):163. Epub 2022 Jun 20.

Jiujiang Clinical Precision Medicine Research Center, Jiujiang, 332000, Jiangxi, China.

Background: Azygos vein aneurysm (AVA) is a rare thoracic pathological entity that mimics a posterior mediastinal mass. However, the pathogenesis of primary azygos vein aneurysms is not clear and its pathology is still being discussed. Some of the AVA are asymptomatic and usually discovered accidentally by routine physical examination.

Case Presentation: We report the case of a 37-year-old woman who had an azygos vein arch aneurysm with no obvious clinical symptoms. With the analysis of clinical features of the case and AVA morphological characteristics, the AVA was found by a chest computed tomography. Then, enhanced chest computed tomography showed a soft-tissue mass (4.9 × 3.7 × 3.2 cm) in the right posterior mediastinum, which was connected to the superior vena cava and significantly enhanced with contrast agent stratification. The density of the tumor in the delayed stage was the same as that in the azygos vein. The patient underwent video-assisted thoracoscopic surgery. Histopathological evaluation of the surgical biopsy specimen proved to be a completely thrombosed aneurism of the azygos vein arch.

Conclusions: AVA is a rare pathology that must be taken into consideration during the differential diagnosis of right posterior mediastinal masses. Thoracoscopic surgery is one of the most preferred treatment options for azygos vein aneurysm.
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http://dx.doi.org/10.1186/s13019-022-01908-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210694PMC
June 2022

Deletion of the cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis.

Ann Transl Med 2022 May;10(10):538

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.

Background: Sepsis is associated with a high mortality rate. A major cause of death in sepsis patients is respiratory failure, which is characterized by oxidative injury, epithelial apoptosis, and increased lung permeability. MicroRNAs (miRs) are important regulators of sepsis progression.

Methods: This study aimed to explore the role of in sepsis in mice. Experimental sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP).

Results: CLP significantly induced systemic inflammation, lung permeability, and lung epithelial apoptosis with downregulated messenger RNA (mRNA) levels of antioxidant enzymes. The knockout mice had a lower 48-hour survival rate, higher plasma tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels, and greater pulmonary permeability compared with wild-type mice after CLP. CLP also markedly increased interstitial hemorrhage, collapsed more alveolar sacs, and increased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive and Bcl-2-associated X (Bax)-positive cells in knockout lung tissues, with elevated mRNA levels of and reduced activities of catalase (Cat), glutathione peroxidase 1(Gpx1). negatively regulated 14-3-3ζ expression evidenced in knockout lungs and the A549 cell line. In lipopolysaccharide (LPS)-induced A549 cells, overexpression remarkably suppressed the production of reactive oxygen species, inhibited cell apoptosis, and enhanced levels of protein and related enzymes.

Conclusions: Deletion of the cluster aggravated sepsis-induced oxidative injury of lung epithelial cells.
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http://dx.doi.org/10.21037/atm-22-1024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201188PMC
May 2022

Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

Acta Pharmacol Sin 2022 Jun 15. Epub 2022 Jun 15.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.
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http://dx.doi.org/10.1038/s41401-022-00930-6DOI Listing
June 2022

Scanning Imaging Study of Patients with Parkinson's Disease Lower Urinary Tract Dysfunction Based on Linear Equation.

Scanning 2022 27;2022:9506328. Epub 2022 May 27.

Urinary Surgery, The 80th Group Army Hospital of the People's Liberation Army, Weifang, Shandong 261021, China.

A predictive method based on a linear equation was proposed to study the factors influencing lower urinary tract dysfunction in Parkinson's disease. A 10-month follow-up of 200 selected Parkinson's patients from January to December 2020 used a linear regression equation to analyze whether depletion function was associated with a specific nonmotor function loss, and a linear regression equation was used for analysis. A loss of emptiness function was used to determine whether there are complications associated with lower motor function and cognitive function. The experimental results showed that dysuria in Parkinson's disease was related to the following nonmotility disorders: gastrointestinal dysfunction (OR 2.52, 95% CI 1.57-3.92, < 0.001), cardiovascular dysfunction (OR 2.31, 95% CI 1.23~4.11, = 0.014), respiratory dysfunction (OR 1.72, 95% CI 1.32~3.24, = 0.029), cutaneous autonomic dysfunction (OR 1.91, 95% CI 1.15~3.08, = 0.023), and sleep disorders (OR 2.01, 95% CI 1.32~3.14, = 0.001). In addition, dysuria was associated with higher UPDRS-III (regression coefficient 1.74, 95% CI 0.56-2.67, = 0.001). Thus, nonmotor disorders have been shown to be associated with early impairment.
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http://dx.doi.org/10.1155/2022/9506328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166962PMC
June 2022

Neural stemness unifies cell tumorigenicity and pluripotent differentiation potential.

J Biol Chem 2022 07 4;298(7):102106. Epub 2022 Jun 4.

Shenzhen Research Institute of Nanjing University, Shenzhen, China; MOE Key Laboratory of Model Animals for Disease Study and State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China. Electronic address:

Neural stemness is suggested to be the ground state of tumorigenicity and pluripotent differentiation potential. However, the relationship between these cell properties is unclear. Here, by disrupting the neural regulatory network in neural stem and cancer cells and by serial transplantation of cancer cells, we show that tumorigenicity and pluripotent differentiation potential are coupled cell properties unified by neural stemness. We show that loss of neural stemness via inhibition of SETDB1, an oncoprotein with enriched expression in embryonic neural cells during vertebrate embryogenesis, led to neuronal differentiation with reduced tumorigenicity and pluripotent differentiation potential in neural stem and cancer cells, whereas enhancement of neural stemness by SETDB1 overexpression caused the opposite effects. SETDB1 maintains a regulatory network comprising proteins involved in developmental programs and basic cellular functional machineries, including epigenetic modifications (EZH2), ribosome biogenesis (RPS3), translation initiation (EIF4G), and spliceosome assembly (SF3B1); all of these proteins are enriched in embryonic neural cells and play active roles in cancers. In addition, SETDB1 represses the transcription of genes promoting differentiation and cell cycle and growth arrest. Serial transplantation of cancer cells showed that neural stemness, tumorigenicity, and pluripotent differentiation potential were simultaneously enhanced; these effects were accompanied by increased expression of proteins involved in developmental programs and basic machineries, including SETDB1 and the abovementioned proteins, as well as by increased alternative splicing events. These results indicate that basic machineries work together to define a highly proliferative state with pluripotent differentiation potential and also suggest that neural stemness unifies tumorigenicity and differentiation potential.
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http://dx.doi.org/10.1016/j.jbc.2022.102106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254501PMC
July 2022

Construction of Physical Education Quality Evaluation Index and Analysis with Wearable Device.

Authors:
Lei Fang

Comput Intell Neurosci 2022 26;2022:1190394. Epub 2022 May 26.

Jilin Agricultural Science and Technology University, Jilin 132101, China.

As an important part of the education system, college physical education directly affects the comprehensive development of college students' physical and mental quality. It is necessary to build a scientific and efficient evaluation index of college physical education teaching quality. Physical fitness monitoring is an important indicator for the quality evaluation of physical education. However, how to achieve lightweight, portable, and high-accuracy quantitative physical fitness monitoring is currently a major challenge. In order to solve the above challenges, this paper proposes a method of constructing a physical education quality evaluation index based on wearable devices. The wearable device collects human ECG signals, calculates the exercise intensity of participating students, and realizes quantitative evaluation of the quality of physical education teaching. Aiming at the problems of complex equipment and low accuracy of the existing exercise intensity detection methods, this paper proposes an ECG signal wave group detection algorithm based on a one-dimensional convolutional neural network (1D-CNN) to obtain the heart rate variability signal more accurately. After obtaining the ECG feature vector, the SVM classifier is used to predict the exercise intensity. In order to verify the effectiveness of the method in this paper, the real data collected from students of one university and a public available dataset are selected for experiments. The experimental results show that the method proposed in this paper achieves a good performance.
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http://dx.doi.org/10.1155/2022/1190394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162814PMC
June 2022

Traditional Chinese Medicine and Sarcopenia: A Systematic Review.

Front Aging Neurosci 2022 13;14:872233. Epub 2022 May 13.

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Sarcopenia has become a key challenge for healthy aging in older adults. However, it remains unclear whether traditional Chinese medicine can effectively treat sarcopenia. This systematic review analyzes the current evidence for the effect of traditional Chinese medicine (TCM) on sarcopenia. We searched for articles regarding sarcopenia treated by TCM in Cochrane library, PubMed, SinoMed, Web of Science, Embase, and the China National Knowledge Infrastructure (from inception until 10 December 2021). Two researchers independently screened the literature in accordance with the inclusion and exclusion criteria designed by PICOS principles. The risk of bias was assessed by the Cochrane Risk of Bias (ROB) tool. The quality of evidence was assessed by the grading of recommendations, assessment, development, and evaluation (GRADE). Participants' characteristics, interventions, and the relevant results of the included studies were extracted and synthesized in a narrative way. The total number of participants in the 21 included studies was 1,330. Most of the studies evaluated physical function ( = 20) and muscle strength ( = 18), and a small number of studies ( = 6) assessed muscle mass. Overall, it was found that TCM had a positive impact on muscle strength (grip strength, chair stand test) and physical function (6-m walking speed, timed up and go test, sit and reach) in patients with sarcopenia, inconsistent evidence of effects on muscle mass. However, the small sample size of the included studies led to imprecision in the results, and the presence of blinding of the studies, allocation concealment, and unreasonable problems with the control group design made the results low grade. Among these results, the quality of evidence for grip strength ( = 10) was of medium grade, and the quality of evidence related to the remaining indicators was of low grade. This systematic review showed that traditional Chinese Qigong exercises and Chinese herbal medicine have a positive and important effect on physical performance and muscle strength in older adults with sarcopenia. Future high-quality multicenter randomized controlled trials (RCTs) with large samples are needed to determinate whether acupuncture and other therapies are effective in treating sarcopenia.
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http://dx.doi.org/10.3389/fnagi.2022.872233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136040PMC
May 2022

The promotive effect of grafts with the double-stranded peroneus longus tendon and with the four-stranded hamstring tendon on reconstruction of the posterior cruciate ligament injury.

Orthop Traumatol Surg Res 2022 May 25:103336. Epub 2022 May 25.

Department of Orthopaedics, Affiliated Hospital of Nantong University, No.20 Xisi Road, Nantong, Jiangsu 226001, China. Electronic address:

Introduction: Posterior cruciate ligament (PCL) injury hampers the rotational stability and stability front to back of the knee joint, seriously affecting the quality of life of patients. Some studies have reported that the peroneus longus tendon (PLT) has sufficient length and strength.

Hypothesis: We hypothesized that the PLT can be used as a novel appropriate material for PCL reconstruction therapy.

Materials And Methods: Herein, we systematically analysed the clinical effect of the double-stranded PLT and the four-stranded hamstring tendon in the reconstruction of the PCL and compared the effectiveness and safety of these two surgical approaches in the reconstruction of PCL injury. A total of 48 patients with complete rupture of the PCL were divided into Group A (reconstructed with the double-stranded PLT, 25 cases) and Group B (reconstructed with the four-stranded hamstring tendon, 23 cases).

Results: The patients were followed up for more than 1 year. The intraoperative time for tendon extraction was significantly shorter in Group A than Group B. Twenty-four months after operation, patients in the two groups showed the alleviated tibial posterior displacement and the increased IKDC score, Lysholm score and Tegner score. Nevertheless, these scores showed no significant differences between the two groups. Additionally, compared with the therapy using the four-stranded hamstring tendon, therapy using the double-stranded PLT is simpler and safer.

Discussion: Both surgical methods are effective in the treatment of PCL injury. The PLT could be a good choice for PCL injury reconstruction material, especially when the four-stranded hamstring tendon is accidentally damaged or ineffective. Our study may provide guidance for the clinical treatment of PCL injury.

Level Of Evidence: III, retrospective study.
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http://dx.doi.org/10.1016/j.otsr.2022.103336DOI Listing
May 2022

PFKP alleviates glucose starvation-induced metabolic stress in lung cancer cells via AMPK-ACC2 dependent fatty acid oxidation.

Cell Discov 2022 May 31;8(1):52. Epub 2022 May 31.

NUS Graduate School Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore, Singapore.

Cancer cells adopt metabolic reprogramming to promote cell survival under metabolic stress. A key regulator of cell metabolism is AMP-activated protein kinase (AMPK) which promotes catabolism while suppresses anabolism. However, the underlying mechanism of AMPK in handling metabolic stress in cancer remains to be fully understood. In this study, by performing a proteomics screening of AMPK-interacting proteins in non-small-cell lung cancer (NSCLC) cells, we discovered the platelet isoform of phosphofructokinase 1 (PFKP), a rate-limiting enzyme in glycolysis. Moreover, PFKP was found to be highly expressed in NSCLC patients associated with poor survival. We demonstrated that the interaction of PFKP and AMPK was greatly enhanced upon glucose starvation, a process regulated by PFKP-associated metabolites. Notably, the PFKP-AMPK interaction promoted mitochondrial recruitment of AMPK which subsequently phosphorylated acetyl-CoA carboxylase 2 (ACC2) to enhance long-chain fatty acid oxidation, a process helping maintenance of the energy and redox homeostasis and eventually promoting cancer cell survival under glucose starvation. Collectively, we revealed a critical non-glycolysis-related function of PFKP in regulating long-chain fatty acid oxidation via AMPK to alleviate glucose starvation-induced metabolic stress in NSCLC cells.
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http://dx.doi.org/10.1038/s41421-022-00406-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156709PMC
May 2022

Design, Synthesis, and Biological Evaluation of Novel Evodiamine Derivatives as Potential Antihepatocellular Carcinoma Agents.

J Med Chem 2022 06 31;65(11):7975-7992. Epub 2022 May 31.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China.

Evodiamine has many biological activities. Herein, we synthesize 23 disubstituted derivatives of N14-phenyl or the E-ring of evodiamine and conduct systematic structure-activity relationship studies. antiproliferative activity indicated that compounds and dramatically inhibited the proliferation of Huh7 (IC = 0.05 or 0.04 μM, respectively) and SK-Hep-1 (IC = 0.07 or 0.06 μM, respectively) cells. Furthermore, compounds and could double inhibit topoisomerases I and II, inhibit invasion and migration, block the cell cycle to the G2/M stage, and induce apoptosis as well. Additionally, compounds and could also inhibit the activation of HSC-T6 and reduce the secretion of collagen type I to slow down the progression of liver fibrosis. Most importantly, compound (TGI = 60.36%) inhibited tumor growth more significantly than the positive drug sorafenib. To sum up, compound has excellent potential as a strong candidate for the therapy of hepatocellular carcinoma.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00520DOI Listing
June 2022

Retrieving a disrupted gene encoding phospholipase A for fibre enhancement in allotetraploid cultivated cotton.

Plant Biotechnol J 2022 May 28. Epub 2022 May 28.

Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, Plant Precision Breeding Academy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

After polyploidization originated from one interspecific hybridization event in Gossypium, Gossypium barbadense evolved to produce extra-long staple fibres than Gossypium hirsutum (Upland cotton), which produces a higher fibre yield. The genomic diversity between G. barbadense and G. hirsutum thus provides a genetic basis for fibre trait variation. Recently, rapid accumulation of gene disruption or deleterious mutation was reported in allotetraploid cotton genomes, with unknown impacts on fibre traits. Here, we identified gene disruptions in allotetraploid G. hirsutum (18.14%) and G. barbadense (17.38%) through comparison with their presumed diploid progenitors. Relative to conserved genes, these disrupted genes exhibited faster evolution rate, lower expression level and altered gene co-expression networks. Within a module regulating fibre elongation, a hub gene experienced gene disruption in G. hirsutum after polyploidization, with a 2-bp deletion in the coding region of GhNPLA1D introducing early termination of translation. This deletion was observed in all of the 34 G. hirsutum landraces and 36 G. hirsutum cultivars, but not in 96% of 57 G. barbadense accessions. Retrieving the disrupted gene GhNPLA1D using its homoeolog GhNPLA1A achieved longer fibre length in G. hirsutum. Further enzyme activity and lipids analysis confirmed that GhNPLA1A encodes a typical phospholipase A and promotes cotton fibre elongation via elevating intracellular levels of linolenic acid and 34:3 phosphatidylinositol. Our work opens a strategy for identifying disrupted genes and retrieving their functions in ways that can provide valuable resources for accelerating fibre trait enhancement in cotton breeding.
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http://dx.doi.org/10.1111/pbi.13862DOI Listing
May 2022

Population-Scale Polymorphic Short Tandem Repeat Provides an Alternative Strategy for Allele Mining in Cotton.

Front Plant Sci 2022 6;13:916830. Epub 2022 May 6.

Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, Plant Precision Breeding Academy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

Short tandem repeats (STRs), which vary in size due to featuring variable numbers of repeat units, are present throughout most eukaryotic genomes. To date, few population-scale studies identifying STRs have been reported for crops. Here, we constructed a high-density polymorphic STR map by investigating polymorphic STRs from 911 accessions. In total, we identified 556,426 polymorphic STRs with an average length of 21.1 bp, of which 69.08% were biallelic. Moreover, 7,718 (1.39%) were identified in the exons of 6,021 genes, which were significantly enriched in transcription, ribosome biogenesis, and signal transduction. Only 5.88% of those exonic STRs altered open reading frames, of which 97.16% were trinucleotide. An alternative strategy STR-GWAS analysis revealed that 824 STRs were significantly associated with agronomic traits, including 491 novel alleles that undetectable by previous SNP-GWAS methods. For instance, a novel polymorphic STR consisting of GAACCA repeats was identified in , with its (GAACCA) allele increasing fiber length by 1.96-4.83% relative to the (GAACCA) allele. The database CottonSTRDB was further developed to facilitate use of STR datasets in breeding programs. Our study provides functional roles for STRs in influencing complex traits, an alternative strategy STR-GWAS for allele mining, and a database serving the cotton community as a valuable resource.
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http://dx.doi.org/10.3389/fpls.2022.916830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120961PMC
May 2022

Huangkui Capsule Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Macrophage Activation by Suppressing Inflammation and Oxidative Stress in Mice.

Evid Based Complement Alternat Med 2021 22;2021:6626483. Epub 2021 Sep 22.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225009, China.

Background: Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells.

Methods: Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance.

Results: LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24 h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF and IL-6 in RAW 264.7 cells.

Conclusions: These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.
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http://dx.doi.org/10.1155/2021/6626483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068299PMC
September 2021

Investigation of anti-aging of SBS modified bitumen containing surface organic layered double hydroxide.

RSC Adv 2021 Jun 23;11(36):22131-22139. Epub 2021 Jun 23.

College of Civil Engineering, Fuzhou University Fuzhou 350108 P. R. China

To improve the anti-aging ability of SBS modified bitumen (SMB), layered double hydroxide (LDH) organically modified by hexadecyltrimethoxysilane was prepared and utilized for the modification of SMB. According to X-ray photoelectron spectroscopy, hexadecyltrimethoxysilane has been grafted into LDH through chemical bonding. Compared with LDH, the hydrophilicity of organic LDH (OLDH) was obviously reduced, and OLDH possessed better dispersibility and stability in SMB, because of the decrease of hydroxyl and the introduced organo-functional groups on the surface of LDH. The addition of OLDH and LDH can ameliorate the high temperature behavior of SMB, especially OLDH. After aging, bitumen was oxidized and SBS was degraded, which resulted in the physical and rheological property deterioration of SMB. LDH can alleviate the destruction of aging on the performance and chemical structure of SMB. Furthermore, the improvement of LDH on the anti-aging ability of SMB has been further enhanced after hexadecyltrimethoxysilane organic modification.
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http://dx.doi.org/10.1039/d1ra04042aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034233PMC
June 2021

Topological Design of Highly Anisotropic Aligned Hole Transporting Molecular Bottlebrushes for Solution-Processed OLEDs.

J Am Chem Soc 2022 May 26;144(18):8084-8095. Epub 2022 Apr 26.

DuPont, Electronics and Imaging Division, Marlborough, Massachusetts 01752, United States.

Polyvinyl polymers bearing pendant hole transport functionalities have been extensively explored for solution-processed hole transport layer (HTL) technologies, yet there are only rare examples of high anisotropic packing of the HT moieties of these polymers into substrate-parallel orientations within HTL films. For small molecules, substrate-parallel alignment of HT moieties is a well-established approach to improve overall device performance. To address the longstanding challenge of extension from vapor-deposited small molecules to solution-processable polymer systems, a fundamental chemistry tactic is reported here, involving the positioning of HT side chains within macromolecular frameworks by the construction of HT polymers having bottlebrush topologies. Applying state-of-the-art polymer synthetic techniques, various functional subunits, including triphenylamine (TPA) for hole transport and adhesion to the substrate, and perfluoro alkyl-substituted benzyloxy styrene for migration to the air interface, were organized with exquisite control over the composition and placement throughout the bottlebrush topology. Upon assembling the HT bottlebrush (HTB) polymers into monolayered HTL films on various substrates through spin-casting and thermal annealing, the backbones of HTBs were vertically aligned while the grafts with pendant TPAs were extended parallel to the substrate. The overall design realized high TPA π-stacking along the out-of-plane direction of the substrate in the HTLs, which doubled the efficiency of organic light-emitting diodes compared with linear poly(vinyl triphenylamine)s.
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http://dx.doi.org/10.1021/jacs.2c00420DOI Listing
May 2022

Acute Silica Exposure Triggers Pulmonary Inflammation Through Macrophage Pyroptosis: An Experimental Simulation.

Front Immunol 2022 7;13:874459. Epub 2022 Apr 7.

Clinical Medical Research Center for Women and Children Diseases, Maternal and Child Health Care Hospital of Shandong Province, Shandong University, Jinan, China.

Silica is an essential substrate of various materials, and inhaling silica induces pulmonary diseases potentially associated with macrophage pyroptosis. Utilizing silica of micro- and nano- sizes, we explored the role of macrophage pyroptosis in silica-induced pulmonary inflammation. Under the transmission electron microscopy, we found that the internalization of silica nanoparticle induced membrane rupture and increased the number of intracellular vacuoles, and both sizes of silica could suppress cell viability and proliferation. Also, silica-exposed macrophages generated higher levels of ROS, together with the upregulated expression of NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-6. However, the expression of these proteins was suppressed after removing ROS or NLRP3. In addition, we found increased expression of TLR4 and NF-κB responsible for silica recognition and pyroptosis priming after silica exposure. For studies, we established animal model by intratracheally instilling 5 mg of silica into mice with/without NLRP3 inhibition. Four weeks later, we found diffused infiltration of inflammatory cells and enhanced collagen hyperplasia partially reversed by additional treatment with MCC950, so as the expression of pyroptotic molecules and proinflammatory cytokines. In particular, the dual immunofluorescent staining showed co-expression of macrophage-specific biomarker F4/80 and NLRP3 within the cells, and silica of nano-size showed more potent toxicity and pathogenicity than that of the micro-sized particles both and . To sum up, macrophage pyroptosis is an upstream event of silica-induced pulmonary inflammation promoted by ROS through the TLR4/NLRP3/NF-κB signaling axis.
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http://dx.doi.org/10.3389/fimmu.2022.874459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021383PMC
April 2022
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