Publications by authors named "Ye Wu"

545 Publications

Species profiles, in-situ photochemistry and health risk of volatile organic compounds in the gasoline service station in China.

Sci Total Environ 2022 Jun 20:156813. Epub 2022 Jun 20.

School of Environment, State Key Joint Laboratory of Environment Simulation and Pollution Control, Tsinghua University, Beijing 100084, China.

Accompanying with increases in vehicle population and gasoline consumption, gasoline evaporation accounted for an enlarged portion of total volatile organic compound (VOC) emissions in China, raising increasing environmental concerns especially in megacities. In this study, an intensive sampling campaign was performed in a gasoline service station, to reveal emission characteristics, environmental and health impacts of VOCs. It was strikingly found that 24 % of air samples exceeded the national standard of 4 mg/m for non-methane hydrocarbons (NMHCs) on the boundary of the station, with the equipment of Stage I and II controls. VOC groups and species profiles showed that alkanes dominated total VOCs. As typical markers of evaporative loss of gasoline, C4-5 species (i-pentane, n-pentane and n-butane) as well as methyl tert-butyl ether (MTBE) accounted for 49.6 % of VOCs. Species profile and diagnostic ratios indicated the prominent contribution of gasoline evaporative losses from refueling or breathing processes, as well as the interference of vehicle exhaust in the ambient air at the site. Intensive O production was reproduced by the photochemical box model, demonstrating that O formation was co-limited by both VOCs (especially trans-2-butene) and NO. Inhalation health risk assessment proved that exposure to hazardous VOCs caused non-cancer risk (HQ = 3.08) and definitely posed cancer risks at a probability of 1.3 × 10 to workers. Remarkable health risks were mainly imposed by halocarbons, aromatics and alkenes, in which 1,2-dichloropropane caused the highest non-cancer risk (HQ = 1.3) and acted as the primary carcinogen (ICR = 5.1 × 10). This study elucidated the high unqualified rate in gasoline service stations after the implementation of latest standards in China, where new regulations targeted halocarbons and updates in existing vapor recovery systems were suggested for VOC mitigation.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156813DOI Listing
June 2022

Construction and Validation of a UPR-Associated Gene Prognostic Model for Head and Neck Squamous Cell Carcinoma.

Biomed Res Int 2022 6;2022:8677309. Epub 2022 Jun 6.

Fujian Key Laboratory of Oral Diseases and Fujian Provincial Engineering Research Center of Oral Biomaterial and Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, China.

Our study is aimed at constructing and validating a UPR-associated gene signature to predict HNSCC prognosis. We obtained 544 samples of RNA sequencing data and clinical characteristics from TCGA database and randomly grouped the samples into training and testing cohorts (1 : 1 ratio). After identifying 14 UPR-associated genes with LASSO and univariate Cox regression analysis, HNSCC samples were categorized into low-risk (LR) and high-risk (HR) subgroups depending on the risk score. Our analyses indicated that low-risk patients had a much better prognosis in the training and testing cohorts. To predict the HNSCC prognosis with the 14 UPR-associated gene signatures, we incorporated the UPR gene risk score, N stage, M stage, and age into a nomogram model. We further explored the sensitivity to anticancer drugs by using the IC50 analysis in two subgroups from the Cancer Genome Project database. The outcomes showed that the AKT inhibitor III and sorafenib were sensitive anticancer drugs in HR and LR patients, respectively. The immune cell infiltration analysis and GSEA provided strong evidence for elucidating the molecular mechanisms of UPR-associated genes affecting HNSCC. In conclusion, the UPR-associated gene risk score, N stage, M stage, and age can serve as a robust model for predicting prognosis and can improve decision-making at the individual patient level.
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http://dx.doi.org/10.1155/2022/8677309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192238PMC
June 2022

Dynamics of the social construction of knowledge: an empirical study of Zhihu in China.

EPJ Data Sci 2022 4;11(1):35. Epub 2022 Jun 4.

Computational Communication Research Center, Beijing Normal University, Zhuhai, 519087 China.

This study examined how the knowledge market promotes knowledge construction on question-and-answer (Q&A) websites. Data were collected from Zhihu, one of the largest Q&A sites in China. Hierarchical linear modeling was employed to estimate the dynamics of information accumulation, that is, the provision of informative content as factual construction. By employing information accumulation as the objective measure of knowledge construction, we determined that online knowledge construction was facilitated by a competitive marketplace of ideas. In addition, participation, temporal, and discourse features affected the dynamics of information accumulation. In specific, active users contributed significantly less to information accumulation than did ordinary users. Information accumulation shows a naturally decaying process represented as a function of answer order. The time interval between answers at the two preceding time points reduced the informativeness of answers at the subsequent time point. Answers with a higher readability score reduced the informativeness of subsequent answers. The results indicate that knowledge construction on Q&A sites unfolds as a process of mass collaboration among users.

Supplementary Information: The online version contains supplementary material available at 10.1140/epjds/s13688-022-00346-6.
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http://dx.doi.org/10.1140/epjds/s13688-022-00346-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166185PMC
June 2022

Synthesis of Holmium-Oxide Nanoparticles for Near-Infrared Imaging and Dye-Photodegradation.

Molecules 2022 May 30;27(11). Epub 2022 May 30.

Jiangsu Key Laboratory of 3D Printing Equipment and Manufacturing, School of Electrical and Automation Engineering, Nanjing Normal University, Nanjing 210046, China.

The development of multifunctional nanomaterials has received growing research interest, thanks to its ability to combine multiple properties for severing highly demanding purposes. In this work, holmium oxide nanoparticles are synthesized and characterized by various tools including XRD, XPS, and TEM. These nanoparticles are found to emit near-infrared fluorescence (800-1100 nm) under a 785 nm excitation source. Imaging of the animal tissues was demonstrated, and the maximum imaging depth was found to be 2.2 cm. The synthesized nanoparticles also show the capability of facilitating dye (fluorescein sodium salt and rhodamine 6G) degradation under white light irradiation. The synthesized holmium oxide nanoparticles are envisioned to be useful for near-infrared tissue imaging and dye-degradation.
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http://dx.doi.org/10.3390/molecules27113522DOI Listing
May 2022

PTRF/Cavin-1 enhances chemo-resistance and promotes temozolomide efflux through extracellular vesicles in glioblastoma.

Theranostics 2022 16;12(9):4330-4347. Epub 2022 May 16.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

The concentration and duration of intracellular drugs have always been the key factors for determining the efficacy of the treatment. Efflux of chemotherapeutic drugs or anticancer agents is a major reason for multidrug resistance generation in cancer cells. The high expression of polymerase I and transcript release factor (PTRF) is correlated with a worse prognosis in glioma patients. However, the importance of PTRF on temozolomide (TMZ) resistance in glioblastoma (GBM) is poorly understood. TCGA data analysis, CGGA data analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM), clone formation, cell counting kit-8 (cck-8), western blot (WB), immunofluorescence (IF), immunohistochemistry (IHC) and flow cytometry assays were performed to investigate the underlying mechanism and effect of PTRF on TMZ-resistance in a variety of GBM cell lines and GBM patient-derived xenograft (PDX) models. Clone formation, WB, IF, IHC and flow cytometry assays were performed to examine the efficacy of sequential therapy of TMZ followed by CQ in GBM cells and PDX models. The prognosis of GBM patients treated with TMZ was negatively correlated with PTRF expression. Our results reveal that PTRF knockdown significantly decrease proliferation and increase apoptosis in GBM after TMZ treatment. Moreover, PTRF contribute to TMZ-resistance by increasing TMZ efflux through extracellular vesicles (EVs). Furthermore, our results demonstrate that sequential therapy of TMZ followed by CQ significantly promotes the TMZ efficacy against GBM by increasing intracellular TMZ concentration ([TMZ]i). This study highlights that PTRF can act as an independent biomarker to predict the prognosis of GBM patients after TMZ treatment and describes a new mechanism contributing to TMZ-resistance. In addition, this study may provide a novel idea for GBM therapy.
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http://dx.doi.org/10.7150/thno.71763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169358PMC
June 2022

The Clinical Features and Long-Term Follow-Up of Vitamin B6-Responsive Infantile Spasms in a Chinese Cohort.

Front Neurol 2022 12;13:895978. Epub 2022 May 12.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Objective: To analyze the clinical features, treatment, and prognosis of patients with vitamin B6-responsive infantile spasms (IS).

Methods: The clinical features, genetics, and follow-up data of 30 patients were collected and analyzed.

Results: The age of epileptic spasms (ES) onset was from 3 months to 12 months. They all received high doses of vitamin B6 at different times after the onset of ES, ranging from 1 day to 5 months. ES were controlled within 11 days in 93% (28/30) patients, and as late as 1 month and 2 months in the other two patients. In the course of treatment, 28 patients were seizure-free all the time, and seizures of other two patients recurred due to withdrawal of vitamin B6. The available follow-up EEG results of 28 patients were normal in 26 cases, and 81% (21/26) had suppressed epileptic discharges within 6 months. Of the 26 cases with normal follow up EEG, 4 had developmental delay and 22 had normal development. The time for EEG to return to normal in 22 patients with normal development ranged from 14 days to 2 years (mean = 111.5 days; median = 52.5 days). The time for EEG to return to normal in the other 4 patients with development delay ranged from 4 months to 2 years (mean = 375 days; median = 330 days). To the last follow-up, seizures were controlled well in 29 surviving patients, and 21 patients were able to deactivate from all medications without seizures recurrence. Sixteen patients showed varying degrees of developmental delay after onset. After seizure control, the psychomotor development was delayed in 7 patients (one died) until the last follow-up. Genetic analysis did not show any meaningful results.

Conclusion: An observation period of 1-2 weeks is essential to identify patients with vitamin B6-responsive IS. The treatment time could be extended according to the treatment response and EEG changes. It might take a longer time for EEG to return to normal and to stop taking drugs in patients with persistent or unimproved developmental delay. Neurodevelopmental outcomes and prognosis of vitamin B6-responsive IS were relatively favorable.
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http://dx.doi.org/10.3389/fneur.2022.895978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134116PMC
May 2022

Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI.

Neuroimage 2022 Aug 26;257:119327. Epub 2022 May 26.

Vanderbilt Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United States; Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, United States.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.
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http://dx.doi.org/10.1016/j.neuroimage.2022.119327DOI Listing
August 2022

TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling.

Redox Biol 2022 07 18;53:102344. Epub 2022 May 18.

Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Osteosarcoma (OS) is a malignant bone tumor that mainly occurs in adolescents. It is accompanied by a high rate of lung metastasis, and high mortality. Recent studies have suggested the important roles of tripartite motif-containing (TRIM) family proteins in regulating various substrates and signaling pathways in different tumors. However, the detailed functional role of TRIM family proteins in the progression of OS is still unknown and requires further investigations. In this study, we found that tripartite motif-containing 22 (TRIM22) was downregulated in OS tissues and was hence associated with better prognosis. In vitro and in vivo functional analysis demonstrated that TRIM22 inhibits proliferation and metastasis of OS cells. Nuclear factor erythroid 2-related factor 2 (NRF2), a redox regulator, was identified as a novel target for TRIM22. TRIM22 interacts with and accelerates the degradation of NRF2 by inducing its ubiquitination dependent on its E3 ligase activity but independent of Kelch-like ECH-associated protein 1 (KEAP1). Further, a series of gain- and loss-of-function experiments showed that knockdown or overexpression of NRF2 reversed the functions of knockdown or overexpression of TRIM22 in OS. Mechanistically, TRIM22 inhibited OS progression through NRF2-mediated intracellular reactive oxygen species (ROS) imbalance. ROS production was significantly promoted and mitochondrial potential was remarkably inhibited when overexpressing TRIM22, thus activating AMPK/mTOR signaling. Moreover, TRIM22 was also found to inhibit Warburg effect in OS cells. Autophagy activation was found in OS cells which were overexpressed TRIM22, thus leading to autophagic cell death. Treatment with N-Acetylcysteine (NAC), a ROS scavenger or the autophagy inhibitor 3-Methyladenine (3-MA) abolished the decreased malignant phenotypes in TRIM22 overexpressing OS cells. In conclusion, our study indicated that TRIM22 inhibits OS progression by promoting proteasomal degradation of NRF2 independent of KEAP1, thereby activating ROS/AMPK/mTOR/Autophagy signaling that leads to autophagic cell death in OS. Therefore, our findings indicated that targeting TRIM22/NRF2 could be a promising therapeutic target for treating OS.
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http://dx.doi.org/10.1016/j.redox.2022.102344DOI Listing
July 2022

Juvenile Generalized Myasthenia Gravis With AChR and MuSK Antibody Double Positivity: A Case Report With a Review of the Literature.

Front Pediatr 2022 11;10:788353. Epub 2022 May 11.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Myasthenia gravis is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. The presence of both antibodies in the serum of patients with myasthenia gravis has been rarely reported. Case description: A 9-year-old girl was admitted to our hospital with the chief complaints of reduced facial expression for 3 months and unclear speech and choking from drinking water for 2 months. The diagnosis of generalized myasthenia gravis was made based on clinical manifestations, repetitive electrical nerve stimulation, neostigmine tests, specific antibody tests and other auxiliary examinations. We found the rare coexistence of two key antibodies (anti-AChR and anti-MuSK antibodies) in the patient's serum. The patient experienced myasthenic crisis and received respiratory support even though she was taking prednisone therapy. Due to the poor response to treatment with pyridostigmine bromide, glucocorticoids and IVIG, we administered rituximab therapy, and she responded well and achieved clinical remission. This suggests that clinicians should pay more attention to atypical cases and antibody detection. Rituximab should be considered when conventional treatment fails.
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http://dx.doi.org/10.3389/fped.2022.788353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131937PMC
May 2022

[Clinical and cone-beam CT analysis of 368 patients with temporomandibular joint disc perforation in different age groups].

Shanghai Kou Qiang Yi Xue 2022 Feb;31(1):67-70

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Fujian Medical University. Fuzhou 350001, Fujian Province, China. E-mail:

Purpose: The aim of this study was to investigate the clinical characteristics of disc perforation (DP) of temporomandibular joint (TMJ) at different ages. METHODS:Patients with TMJ disc perforation admitted to the Department of Trauma and Temporomandibular Joint Surgery Stomatological Hospital of Wuhan University, from April 2012 to May 2021 were included in this study. They were divided into 6 groups according to different ages. Clinical and CBCT radiographic features were analyzed. Clinical features included maximal interincisal opening, pain, clicking,and occlusal changes. Imaging features included condylar absorption flattening, hyperplasia or osteophyte formation, sclerosis, subchondral cysts, depression defects, and blurred anterior slope. The clinical and imaging characteristics of patients in different age groups were statistically analyzed. SPSS 26.0 software was used for statistical analysis, and Chi-square test was used to compare the distribution of clinical symptoms and imaging features in patients of different ages.

Results: A total of 368 patients were collected, including 24 males, with an average age of 27.63±15.90 years. There were 344 females with an average age of 32.61±15.61 years. The incidence of pain was 21.31%, occlusal change was 50.82%, and condylar absorption flat was 50.82% in the 10-19 age group. The incidence of pain in 20-29 age group was 31.06%, occlusal change was 53.42%, and condylar absorption flattening was 45.34%. In 50-59 age group, the incidence of pain was 83.33%, occlusal changes were 2.38%, and hyperplasia or osteophyte formation was 47.62%. In age group ≥60 years old, the incidence of pain was 82.86%, occlusal changes were 2.86%, and hyperplasia or osteophyte formation was 60%.

Conclusions: In terms of clinical features, patients under 40 years old are more likely to have occlusal changes, while patients over 40 years old are most likely to have joint pain. Radiographically, patients under 40 years old are mainly characterized by bone loss in the condyle, while patients over 40 years old are mainly characterized by condylar hyperplasia.
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February 2022

Associations between IL-23R gene polymorphism (rs10889677 A/C) and ankylosing spondylitis and rheumatoid arthritis susceptibility: A meta-analysis with trial sequential analysis.

Autoimmunity 2022 May 18:1-10. Epub 2022 May 18.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.

Objectives: Autoimmune diseases are a kind of chronic diseases for which the immune system loses tolerance to autoantigens. This meta-analysis' purpose is to determine whether there exists a correlation between IL-23R polymorphism and common autoimmune diseases like ankylosing spondylitis (AS) and rheumatoid arthritis (RA).

Methods: We searched the relevant literatures up to September 2021 and used different effect models for meta-analysis. 95% confidence interval (95% CI) and odds ratio (OR) were used to determine the relationship between rs10889677 (A/C) polymorphism and AS as well as RA. Finally, to promote the reliability of results, the trial sequential analysis (TSA) has also been applied and we searched the data related to autoimmune diseases (AS, RA) on genome-wide association studies (GWAS).

Results: Generally, 31 studies were included. Rs10889677 (A/C) was significantly correlated with the susceptibility to AS and RA among the general individuals ( < .05). Moreover, there existed a relevance between allele A and AS as well as RA in Caucasians ( < .05). AA genotype increased the risk of autoimmune diseases in Mongolians. As a result, the robustness of meta-analysis has further been proved by TSA.

Conclusion: IL-23R (rs10889677 A/C) A allele was a risk gene for AS and RA in the general population, especially in Caucasians. AA genotype increased the risk of AS and RA in Mongolians.
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http://dx.doi.org/10.1080/08916934.2022.2076837DOI Listing
May 2022

Mitigating COVID-19 Transmission in Schools With Digital Contact Tracing.

IEEE Trans Comput Soc Syst 2021 Dec 28;8(6):1302-1310. Epub 2021 Apr 28.

Computational Communication Research CenterBeijing Normal University Zhuhai 519087 China.

Precision mitigation of COVID-19 is in pressing need for postpandemic time with the absence of pharmaceutical interventions. In this study, the effectiveness and cost of digital contact tracing (DCT) technology-based on-campus mitigation strategy are studied through epidemic simulations using high-resolution empirical contact networks of teachers and students. Compared with traditional class, grade, and school closure strategies, the DCT-based strategy offers a practical yet much more efficient way of mitigating COVID-19 spreading in the crowded campus. Specifically, the strategy based on DCT can achieve the same level of disease control as rigid school suspensions but with significantly fewer students quarantined. We further explore the necessary conditions to ensure the effectiveness of DCT-based strategy and auxiliary strategies to enhance mitigation effectiveness and make the following recommendation: social distancing should be implemented along with DCT, the adoption rate of DCT devices should be assured, and swift virus tests should be carried out to discover asymptomatic infections and stop their subsequent transmissions. We also argue that primary schools have higher disease transmission risks than high schools and, thereby, should be alerted when considering reopenings.
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http://dx.doi.org/10.1109/TCSS.2021.3073109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843051PMC
December 2021

The Role of RNA Methyltransferase in Normal and Malignant Hematopoiesis.

Front Oncol 2022 28;12:873903. Epub 2022 Apr 28.

Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.

mA modification is the most common modification in eukaryotes. , as a core methyltransferase of mA modification, plays a vital role in normal and malignant hematopoiesis. Recent studies have shown that is required for normal and symmetric differentiation of hematopoietic stem/progenitor cells (HSPCs). Moreover, strongly impacts the process and development of hematological neoplasms, including the differentiation, apoptosis, proliferation, chemoresistance, and risk of tumors. Novel inhibitors of have been identified and studied in acute myeloid leukemia (AML) cells. STM2457, a selective inhibitor of , has been identified to block proliferation and promote differentiation and apoptosis of AML cells without impacting normal hematopoiesis. Therefore, in our present review, we focus on the structure of , the role of in both normal and malignant hematopoiesis, and the potential of for treating hematological neoplasms.
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http://dx.doi.org/10.3389/fonc.2022.873903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095908PMC
April 2022

Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer.

Theranostics 2022 24;12(7):3456-3473. Epub 2022 Apr 24.

Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Scarce tumor mutation burden and neoantigens create tremendous obstacles for an effective immunotherapy of colorectal cancer (CRC). Oncolytic peptides rise as a promising therapeutic approach that boosts tumor-specific immune responses by inducing antigenic substances. However, the clinical application of oncolytic peptides has been hindered because of structural instability, proteolytic degradation, and undesired toxicity when administered systemically. Based on wasp venom peptide, an optimized stapled oncolytic peptide MP9 was developed with rigid α-helix, protease-resistance, and CRC cell cytotoxicity. By incorporating four functional motifs that include D-peptidomimetic inhibitor of PD-L1, matrix metalloproteinase-2 (MMP-2) cleavable spacer, and MP9 with 4-arm PEG, a novel peptide-polymer conjugate (PEG-MP9-aPDL1) was obtained and identified as the most promising systemic delivery vehicle with PD-L1 targeting specificity and favorable pharmacokinetic properties. We demonstrated that PEG-MP9-aPDL1-driven oncolysis induces a panel of immunogenic cell death (ICD)-relevant damage-associated molecular patterns (DAMPs) both and , which are key elements for immunotherapy with PD-L1 inhibitor. Further, PEG-MP9-aPDL1 exhibited prominent immunotherapeutic efficacy in a CRC mouse model characterized by tumor infiltration of CD8+ T cells and induction of cytotoxic lymphocytes (CTLs) in the spleens. Our findings suggest that PEG-MP9-aPDL1 is an all-in-one platform for oncolytic immunotherapy and immune checkpoint blockade (ICB).
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http://dx.doi.org/10.7150/thno.71129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065177PMC
April 2022

Neuronal STAT3/HIF-1α/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A.

Theranostics 2022 4;12(7):3196-3216. Epub 2022 Apr 4.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Ischemic stroke is an acute and severe neurological disease with high mortality and disability rates worldwide. Polymerase I and transcript release factor (PTRF) plays a pivotal role in regulating cellular senescence, glucose intolerance, lipid metabolism, and mitochondrial bioenergetics, but its mechanism, characteristics, and functions in neuronal cells following the cerebral ischemia-reperfusion (I/R) injury remain to be determined. Transcription factor motif analysis, chromatin immunoprecipitation (ChIP), luciferase and co-Immunoprecipitation (co-IP) assays were performed to investigate the mechanisms of PTRF in neuronal cells after I/R injury. Lentiviral-sgRNA against gene was introduced to HT22 cells, and adeno-associated virus (AAV) encoding a human synapsin (hSyn) promoter-driven construct was transduced a short hairpin RNA (shRNA) against PTRF mRNA in primary neuronal cells and the cortex of the cerebral I/R mice for investigating the role of PTRF in neuronal damage and PLA2G4A change induced by the cerebral I/R injury. Here, we reported that neuronal PTRF was remarkably increased in the cerebral penumbra after I/R injury, and HIF-1α and STAT3 regulated the I/R-dependent expression of PTRF via binding to its promoter in neuronal cells. Moreover, overexpression of neuronal PTRF enhanced the activity and stability of PLA2G4A by decreasing its proteasome-mediated degradation pathway. Subsequently, PTRF promoted reprogramming of lipid metabolism and altered mitochondrial bioenergetics, which could lead to oxidative damage, involving autophagy, lipid peroxidation, and ferroptosis via PLA2G4A in neuronal cells. Furthermore, inhibition of neuronal PTRF/PLA2G4A-axis markedly reduced the neurological deficits, cerebral infarct volumes, and mortality rates in the mice following cerebral I/R injury. Our results thus identify that the STAT3/HIF-1α/PTRF-axis in neurons, aggravating cerebral I/R injury by regulating the activity and stability of PLA2G4A, might be a novel therapeutic target for ischemic stroke.
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http://dx.doi.org/10.7150/thno.71029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065197PMC
April 2022

Two high hierarchical regulators, PuMYB40 and PuWRKY75, control the low phosphorus driven adventitious root formation in Populus ussuriensis.

Plant Biotechnol J 2022 May 5. Epub 2022 May 5.

State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, Harbin, China.

Adventitious rooting is an essential biological process in the vegetative propagation of economically important horticultural and forest tree species. It enables utilization of the elite genotypes in breeding programmes and production. Promotion of adventitious root (AR) formation has been associated with starvation of inorganic phosphate and some factors involved in low phosphorus (LP) signalling. However, the regulatory mechanism underlying LP-mediated AR formation remains largely elusive. We established an efficient experimental system that guaranteed AR formation through short-term LP treatment in Populus ussuriensis. We then generated a time-course RNA-seq data set to recognize key regulatory genes and regulatory cascades positively regulating AR formation through data analysis and gene network construction, which were followed by experimental validation and characterization. We constructed a multilayered hierarchical gene regulatory network, from which PuMYB40, a typical R2R3-type MYB transcription factor (TF), and its interactive partner, PuWRKY75, as well as their direct targets, PuLRP1 and PuERF003, were identified to function upstream of the known adventitious rooting genes. These regulatory genes were functionally characterized and proved their roles in promoting AR formation in P. ussuriensis. In conclusion, our study unveiled a new hierarchical regulatory network that promoted AR formation in P. ussuriensis, which was activated by short-term LP stimulus and primarily governed by PuMYB40 and PuWRKY75.
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http://dx.doi.org/10.1111/pbi.13833DOI Listing
May 2022

Correction to: Rhubarb Alleviates Acute Lung Injury by Modulating Gut Microbiota Dysbiosis in Mice.

Curr Microbiol 2022 Apr 30;79(6):177. Epub 2022 Apr 30.

Department of Respiratory Medicine in Zhejiang Hospital Affiliated to Medical School of Zhejiang University, 1229 Gudun Road, Xihu District, Hangzhou, 310012, Zhejiang, China.

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http://dx.doi.org/10.1007/s00284-022-02885-7DOI Listing
April 2022

Development of a Microenvironment-Responsive Hydrogel Promoting Chronically Infected Diabetic Wound Healing through Sequential Hemostatic, Antibacterial, and Angiogenic Activities.

ACS Appl Mater Interfaces 2022 Apr 25. Epub 2022 Apr 25.

Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Microenvironment-responsive hydrogels present high potential in treating refractory wounds due to their capability of on-demand drug release. In this study, a specially designed hydrogel with smart targeting of refractory wound characteristics was designed to treat chronically infected diabetic wounds. Aminated gelatin reacted with oxidized dextran, forming a hydrogel cross-linked with a dynamic Schiff base, which is sensitive to the low-pH environment in refractory wounds. Nano-ZnO was loaded into the hydrogel for killing microbes. A Paeoniflorin-encapsulated micelle with a ROS-responsive property was fixed to the skeleton of the hydrogel via a Schiff base bond for low-pH- and ROS-stimulated angiogenic activity. The sequential responsiveness of the novel hydrogel enabled smart rescue of the deleterious microenvironment in refractory wounds. This highly biocompatible hydrogel demonstrated antibacterial and angiogenic abilities and significantly promoted healing of chronically infected diabetic wounds via sequential hemostatic, microbe killing, and angiogenic activities. This microenvironment-responsive hydrogel loaded with nZnO and Pf-encapsulated micelles holds great potential as a location-specific dual-response delivery platform for curing refractory, chronically infected diabetic wounds.
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http://dx.doi.org/10.1021/acsami.2c02725DOI Listing
April 2022

Functional Study of Gene Variants Associated with Hypomyelination Leukodystrophy.

Cells 2022 04 9;11(8). Epub 2022 Apr 9.

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227T>G p.(L76R) or c.227T>C p.(L76P) in were identified in two unrelated HLD patients. TMEM163 protein is a zinc efflux transporter localized within the plasma membrane, lysosomes, early endosomes, and other vesicular compartments. It has not been associated with hypomyelination. Functional zinc flux assays in HeLa cells stably-expressing TMEM163 protein variants, L76R and L76P, revealed distinct attenuation or enhancement of zinc efflux, respectively. Experiments using a zebrafish model with knockdown of and (morphants) showed that loss of causes dysplasia of the larvae, locomotor disability and myelin deficit. Expression of human wild type mRNAs in morphants rescues the phenotype, while the L76P and L76R mutants aggravated the condition. Moreover, poor proliferation, elevated apoptosis of oligodendrocytes, and reduced oligodendrocytes and neurons were also observed in zebrafish morphants. Our findings suggest an unappreciated role for TMEM163 protein in myelin development and add to a growing list of genes associated with hypomyelination leukodystrophy.
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http://dx.doi.org/10.3390/cells11081285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031525PMC
April 2022

Comprehensive chemical characterization of gaseous I/SVOC emissions from heavy-duty diesel vehicles using two-dimensional gas chromatography time-of-flight mass spectrometry.

Environ Pollut 2022 Jul 15;305:119284. Epub 2022 Apr 15.

School of Environment, State Key Joint Laboratory of Environment Simulation and Pollution Control, Tsinghua University, Beijing 100084, China; Beijing Laboratory of Environmental Frontiers Technologies, Beijing 100084, China.

Intermediate-volatility and semi-volatile organic compounds (I/SVOCs) are key precursors of secondary organic aerosol (SOA). However, the comprehensive characterization of I/SVOCs has long been an analytical challenge. Here, we develop a novel method of speciating and quantifying I/SVOCs using two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-ToF-MS) by constructing class-screening programs based on their characteristic fragments and mass spectrum patterns. Using this new approach, we then present a comprehensive analysis of gaseous I/SVOC emissions from heavy-duty diesel vehicles (HDDVs). Over three-thousand compounds are identified and classified into twenty-one categories. The dominant compound groups of I/SVCOs emitted by HDDVs are alkanes (including normal and branched alkanes, 37-66%), benzylic alcohols (7-20%), alkenes (3-11%), cycloalkanes (3-9%), and benzylic ketones (1-4%). Oxygenated I/SVOCs (O-I/SVOCs, e.g., benzylic alcohols and ketones) are first quantified and account for >20% of the total I/SVOC mass. Advanced aftertreatment devices largely reduce the total I/SVOC emissions but increase the proportion of O-I/SVOCs. With the speciation data, we successfully map the I/SVOCs into the two-dimensional volatility basis set space, which facilitates a better estimation of SOA. As aging time goes by, approximate 45% difference between the two scenarios after seven-day aging is observed, which confirms the significant impact of speciated I/SVOC emission data on SOA prediction.
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http://dx.doi.org/10.1016/j.envpol.2022.119284DOI Listing
July 2022

[Prospective randomized controlled trial on the effectiveness of low-dose and high-dose intravenous tranexamic acid in reducing perioperative blood loss in single-level minimally invasive transforaminal lumbar interbody fusion].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2022 Apr;36(4):439-445

Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China.

Objective: A prospective randomized controlled trial was conducted to study the effectiveness and safety of intravenous different doses tranexamic acid (TXA) in single-level unilateral minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF).

Methods: The patients treated with single-level unilateral MIS-TLIF between September 2019 and October 2020 were enrolled and randomly classified into low-dose TXA (LD) group (=39), high-dose TXA (HD) group (=39), and placebo-controlled (PC) group (=38). The LD, HD, and PC groups received intravenous TXA 20 mg/kg, TXA 50 mg/kg, the same volume of normal saline at 30 minute before skin incision after general anesthesia, respectively. There was no significant difference on baseline characteristics and preoperative laboratory results among 3 groups (>0.05), including age, gender, body mass index, surgical segments, hematocrit (HCT), hemoglobin (HGB), prothrombin time (PT), international normalized ratio (INR), D-dimer, fibrin degradation products (FDP), activated partial prothromboplastin time (APTT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), urea. The intraoperative blood loss (IBL), postoperative drainage volume, operation time, total blood loss (TBL), hidden blood loss (HBL), blood transfusion, hematological examination indexes on the first day after operation, and the incidence of complications within 1 month were compared among the 3 groups.

Results: There were 3, 2, and 4 patients in the LD, HD, and PC groups who underwent autologous blood transfusion, respectively, and there was no allogeneic blood transfusion patients in the 3 groups. There was no significant difference in IBL, postoperative drainage volume, and operation time between groups (>0.05). The TBL, HBL, and the decreased value of HGB in LD and HD groups were significantly lower than those in PC group (<0.05), and TBL and HBL in HD group were significantly lower than those in LD group (<0.05); the decreased value of HGB between LD group and HD group showed no significant difference (>0.05). On the first day after operation, D-dimer in LD and HD groups were significantly lower than that in PC group (<0.05); there was no significant difference between LD and HD groups (>0.05). There was no significant difference in other hematological indexes between groups (>0.05). All patients were followed up 1 month, and there was no TXA-related complication such as deep venous thrombosis of lower extremity, pulmonary embolism, and epilepsy in the 3 groups.

Conclusion: Intravenous administration of TXA in single-level unilateral MIS-TLIF is effective and safe in reducing postoperative TBL and HBL within 1 day in a dose-dependent manner. Also, TXA can reduce postoperative fibrinolysis markers and do not increase the risk of thrombotic events, including deep venous thrombosis and pulmonary embolism.
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http://dx.doi.org/10.7507/1002-1892.202112015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011080PMC
April 2022

Comprehensive characterization of polycyclic aromatic hydrocarbon emissions from heavy-duty diesel vehicles utilizing GC × GC-ToF-MS.

Sci Total Environ 2022 Aug 11;833:155127. Epub 2022 Apr 11.

School of Environment, State Key Joint Laboratory of Environment Simulation and Pollution Control, Tsinghua University, Beijing 100084, China.

Comprehensive characterization of diesel vehicle emitted polycyclic aromatic hydrocarbon (PAH) emissions is yet to achieve due to the limitation of analytical methods. Therefore, we herein developed a two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-ToF-MS) method and quantified the total PAHs from diesel vehicles based on their characteristic fragments and mass spectral patterns. Overall, the emission factors (EFs) of total PAHs (gas + particle) are observed to range from 4.1 ± 2.5 mg km to 51.4 ± 22.2 mg km under cold-start and hot-start conditions for one China IV and two China VI heavy-duty diesel vehicles (HDDVs), of which the un-speciated PAHs account for more than 97%. Gaseous PAHs (g-PAHs) are dominated by three-ring PAHs, whereas particulate PAHs (p-PAHs) are dominated by two-ring PAHs. The total PAHs partition significantly into the gas phase for whole fleets and cycles, except that five-ring PAHs partition almost completely into the particle phase. The aftertreatment technologies (e.g., diesel particulate filter, DPF) significantly reduce the total PAH emissions by 49.8 ± 33.2%. The minimum toxic equivalency factors (TEFs) are deployed to estimate the toxicity of the total PAHs. Much higher toxicity is obtained than those in previous studies, indicating that the PAH toxicity of diesel vehicle emissions might be largely underestimated.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155127DOI Listing
August 2022

Developing a High-Resolution Emission Inventory of China's Aviation Sector Using Real-World Flight Trajectory Data.

Environ Sci Technol 2022 May 14;56(9):5743-5752. Epub 2022 Apr 14.

School of Environment, State Key Joint Laboratory of Environment Simulation and Pollution Control, Tsinghua University, Beijing 100084, PR China.

Economic growth and globalization have led to a surge in civil aviation transportation demand. Among the major economies in the world, China has experienced a 12-fold increase in terms of total passenger aviation traffic volume since 2000 and is expected to be the largest aviation market soon. To better understand the environmental impacts of China's aviation sector, this study developed a real-world flight trajectory-based emission inventory, which enabled the fine-grained characterization of four-dimensional (time, longitude, latitude, and altitude) emissions of various flight stages. Our results indicated that fuel consumption and CO emissions showed two peaks in altitude distribution: below 1,000 m and between 8,000 and 12,000 m. Various pollutants depicted different vertical distributions; for example, nitrogen oxides (NO) had a higher fraction during the high-altitude cruise stage due to the thermal NO mechanism, while hydrocarbons had a dominant fraction at the low-altitude stages due to the incomplete combustion under low-load conditions. This improved aviation emission inventory approach identified that total emissions of CO and air pollutants from short-distance domestic flights would be significantly underestimated by the conventional great-circle-based approach due to underrepresented calculation parameters (particularly, flight distance, duration, and cruise altitude). Therefore, we suggest that more real-world aviation flight information, especially actual trajectory records, should be utilized to improve assessments of the environmental impacts of aviation.
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http://dx.doi.org/10.1021/acs.est.1c08741DOI Listing
May 2022

Preparation of CSHW with Flue Gas Desulfurization Gypsum.

Materials (Basel) 2022 Apr 6;15(7). Epub 2022 Apr 6.

China MCC5 Group Corp. Ltd., Chengdu 610063, China.

Calcium sulfate hemihydrate whiskers (CSHW), a multi-functional and high value-added building material, were prepared with flue gas desulfurization (FGD) gypsum by hydrothermal method, which could be a reasonable disposal of FGD gypsum. In order to obtain CSHW of a high aspect ratio, a series of manufacturing parameters such as reaction temperature, stirring speed, material-water ratio, and reaction time were investigated. The effect of stabilizing treatment and glycerol concentration on CSHW morphology were also studied by environmental scanning electron microscopy (ESEM) and statistical analysis. The results showed that the optimum preparing conditions of reaction temperature, stirring speed, water-material ratio, and reaction time were 160 °C, 200~300 rpm, 11:1 and 1 h, respectively. Furthermore, stabilizing treatment with octodecyl betaine was necessary for the preparation of CSHW. The final prepared whiskers had smooth surface, uniform morphology, a diameter of 260 nm, and a corresponding aspect ratio of 208.2. Moreover, the addition of glycerol reduced the activity of water, contributing to a lower reaction temperature and much smaller diameter.
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http://dx.doi.org/10.3390/ma15072691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000504PMC
April 2022

Surface-Guided Image Fusion for Preserving Cortical Details in Human Brain Templates.

Med Image Comput Comput Assist Interv 2021 Sep-Oct;12907:390-399. Epub 2021 Sep 21.

Department of Radiology and Biomedical Research Imaging Center (BRIC), The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Human brain templates are a basis for comparison of brain features across individuals. They should ideally capture an atomical details at both coarse and fine scales to facilitate comparison at varying granularity. Brain template construction typically involves spatial normalization and image fusion. While significant efforts have been dedicated to improving brain templates with sophisticated spatial normalization algorithms, image fusion is typically carried out using intensity-based averaging, causing blurring of anatomical structures. Here, we present an image fusion method that exploits cortical surfaces as guidance to help preserve details in brain templates. Our method encodes cortical boundary information given by a cortical surface mesh in a signed distance function (SDF) map. We use the SDF map to help determine localized contributions of the individual images, especially at cortical boundaries, in image fusion. Experimental results demonstrate that our method significantly improves the preservation of fine gyral and sulcal details, resulting in detailed brain templates with good surface-volume agreement.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986340PMC
September 2021

Efficacy of Ketogenic Diet for Infantile Spasms in Chinese Patients With or Without Monogenic Etiology.

Front Pediatr 2022 17;10:842666. Epub 2022 Mar 17.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Objective: The aim of this study was to evaluate the efficacy of the ketogenic diet (KD) for infantile spasms (IS) in patients with and without different causative genetic mutations.

Methods: We retrospectively evaluated the data of 119 infants with IS who underwent whole-exome sequencing (WES) before KD treatment. The KD efficacy was analyzed at the 16th week after initiation. Patients showing ≥ 50% seizure reduction from baseline and/or the disappeared hypsarrhythmia were considered as the responders. Chi-squared tests or two-sided Fisher's exact tests were performed for categorical data and Mann-Whitney -tests for non-parametric and continuous data.

Results: The responder rate to KD in 119 patients was 47.90%. Six different causative monogenic mutations were identified in 32 (26.89%) patients with IS, including ( = 8), ( = 3), ( = 8), ( = 5), ( = 4), and ( = 4). Patients with mutations showed a significantly better response to KD (87.50%) than patients without mutations ( = 0.03). Seven of eight patients with mutations were responders, including five mutations located in functional motifs, and two mutations in the catalytic domain.

Conclusion: KD therapy was effective in infants with IS. Patients with mutations might have a better response to KD treatment.
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http://dx.doi.org/10.3389/fped.2022.842666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8969902PMC
March 2022

Genotype-phenotype correlation and natural history analyses in a Chinese cohort with pelizaeus-merzbacher disease.

Orphanet J Rare Dis 2022 03 28;17(1):137. Epub 2022 Mar 28.

Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.

Background: The natural history and genotype-phenotype correlation of Pelizaeus-Merzbacher disease (PMD) of Chinese patients has been rarely reported.

Method: Patients who met the criteria for PMD were enrolled in our study. Genomic analysis was conducted by multiplex ligation probe amplification (MLPA) and Sanger or whole-exome sequencing (WES). Natural history differences and genotype-phenotype correlations were analyzed.

Result: A total of 111 patients were enrolled in our follow-up study. The median follow-up interval was 53 m (1185). Among PMD patients, developmental delay was the most common sign, and nystagmus and hypotonia were the most common initial symptoms observed. A total of 78.4% of the patients were able to control their head, and 72.1% could speak words. However, few of the patients could stand (9.0%) or walk (4.5%) by themselves. Nystagmus improved in more than half of the patients, and hypotonia sometimes deteriorated to movement disorders. More PLP1 point mutations patients were categorized into severe group, while more patients with PLP1 duplications were categorized into mild group (p < 0.001). Compared to patients in mild groups, those in the severe group had earlier disease onset and had acquired fewer skills at a later age.

Conclusion: PMD patients have early disease onset with nystagmus and hypotonia followed by decreased nystagmus and movement disorders, such as spasticit. Patients with PLP1 duplication were more likely to be categorized into the mild group, whereas patients with point mutations were more likely to be categorized into the severe group.
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http://dx.doi.org/10.1186/s13023-022-02267-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962489PMC
March 2022

Glioma-derived exosomes hijack the blood-brain barrier to facilitate nanocapsule delivery via LCN2.

J Control Release 2022 05 25;345:537-548. Epub 2022 Mar 25.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Department of Neurosurgery, Tianjin Medical University General Hospital and Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China. Electronic address:

Exosomes are small extracellular vehicles which could transport genetic materials and proteins between cells. Although there are reports about exosomes crossing the blood-brain barrier (BBB), the underlying mechanisms still need further study. We found that exosomes from primary brain tumors could upregulate the expression of Lipocalin-2 (LCN2) in bEnd.3 brain microvascular endothelial cells (BMVECs). Furthermore, exosomes increased the membrane fluidity of bEnd.3 cells in an LCN2 dependent manner. Both intraperitoneal injection and caudal vein injection of LCN2 increased the number of nanocapsules crossing the BBB. Evans Blue staining revealed that LCN2 does not interrupt the integrity of the BBB, as observed in the traumatic brain injury model. Tandem mass tags quantitative proteomics and bioinformatics analysis revealed that LCN2 is upregulated by exosomes via the JAK-STAT3 pathway, but not delivered from exosomes. Knocking down LCN2 in bEnd.3 cells significantly abrogated the effect of exosomes on BMVEC membrane fluidity. Previously, we have reported that 2-methacryloyloxyethyl phosphorylcholine (MPC) and a peptide crosslinker could encapsulate mAbs to achieve nanocapsules. The nanocapsules containing choline analogs could effectively penetrate the BBB to deliver therapeutic monoclonal antibodies (tAbs) to the glioma. However, the delivered tAbs could be significantly reduced by blocking the release of exosomes from the gliomas. Application of tAb nanocapsules prior to treatment with MK2206, an AKT pathway inhibitor that has been shown to inhibit the production of exosomes, resulted in a better combination. Insights from this study provide a mechanistic framework with regard to how glioblastomas hijack BMVECs using exosomes. In addition, we provide a strategy for maximizing the effect of the choline-containing nanocapsules and MK2206 combination. These results also demonstrate the therapeutic role of tAbs in glioblastoma and brain tumor metastasis, by shedding new light on strategies that can be used for BBB-penetrating therapies.
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http://dx.doi.org/10.1016/j.jconrel.2022.03.038DOI Listing
May 2022

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study.

Front Pediatr 2022 2;10:846301. Epub 2022 Mar 2.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Vagus nerve stimulation (VNS) is a safe and effective therapy for pediatric patients with drug-resistant epilepsy (DRE). However, in children with DRE, the effects of VNS on autistic behaviors remain controversial. We retrospectively collected data from 10 children with DRE who underwent VNS implantation and regular parameter regulation in three pediatric epilepsy centers, and completed the behavioral assessments, including the autistic behavior checklist and the child behavior checklist, at follow-ups 1 (mean 2.16 years) and 2 (mean 2.98 years). The 10 children maintained stable seizure control between the two follow-ups. Their autistic behaviors, especially in language, social and self-help, were reduced at follow-up 2 compared to follow-up 1 ( = 0.01, = 0.01, respectively). Moreover, these improvements were not associated with their seizure control, whether it was positive or negative. These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger children with DRE comorbidity autism spectrum disorder (ASD).
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http://dx.doi.org/10.3389/fped.2022.846301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924444PMC
March 2022

A Polyphenol-Network-Mediated Coating Modulates Inflammation and Vascular Healing on Vascular Stents.

ACS Nano 2022 Mar 18. Epub 2022 Mar 18.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.

Localized drug delivery from drug-eluting stents (DESs) to target sites provides therapeutic efficacy with minimal systemic toxicity. However, DESs failure may cause thrombosis, delay arterial healing, and impede re-endothelialization. Bivalirudin (BVLD) and nitric oxide (NO) promote arterial healing. Nevertheless, it is difficult to combine hydrophilic signal molecules with hydrophobic antiproliferative drugs while maintaining their bioactivity. Here, we fabricated a micro- to nanoscale network assembly consisting of copper ion and epigallocatechin gallate (EGCG) π-π interactions, metal coordination, and oxidative polymerization. The network incorporated rapamycin and immobilized BVLD by the thiol-ene "click" reaction and provided sustained rapamycin and NO release. Unlike rapamycin-eluting stents, those coated with the EGCG-Cu-rapamycin-BVLD complex favored competitive endothelial cell (EC) growth over that of smooth muscle cells, exhibited long-term antithrombotic efficacy, and attenuated the negative impact of rapamycin on the EC. stent implantation demonstrated that the coating promoted endothelial regeneration and hindered restenosis. Therefore, the polyphenol-network-mediated surface chemistry can be an effective strategy for the engineering of multifunctional surfaces.
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http://dx.doi.org/10.1021/acsnano.2c00642DOI Listing
March 2022
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