Publications by authors named "Yue Wang"

3,702 Publications

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Ferroptosis-Strengthened Metabolic and Inflammatory Regulation of Tumor-Associated Macrophages Provokes Potent Tumoricidal Activities.

Nano Lett 2021 Jul 22. Epub 2021 Jul 22.

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, People's Republic of China.

Modulation of tumor-associated macrophages (TAMs) holds promise for cancer treatment, mainly relying on M1 signaling activation and pro-inflammatory promotion. Nevertheless, the antitumor activity is often limited by the anti-inflammatory factors in the tumor microenvironment. Moreover, the metabolic function of TAMs is also critical to tumor progression. However, there are a few strategies that can simultaneously regulate both inflammatory and metabolic functions to achieve safe and potent antitumor activation of TAMs. Herein, we demonstrate that an iron-based metal organic framework nanoparticle and a ferroptosis-inducing agent synergistically induce mitochondrial alternation in TAMs, resulting in a radical metabolic switch from mitochondrial oxidative phosphorylation to glycolysis, which is resistant to anti-inflammatory stimuli challenge. The ferroptosis stress strengthened by the nanoformulation also drives multiple pro-inflammatory signaling pathways, enabling macrophage activation with potent tumoricidal activities. The ferroptosis-strengthened macrophage regulation strategy present in this study paves the way for TAM-centered antitumoral treatment to overcome the limitations of conventional methods.
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http://dx.doi.org/10.1021/acs.nanolett.1c01401DOI Listing
July 2021

Expert consensus on the application of the magnetic anchoring and traction technique in thoracoscopic and laparoscopic surgery.

Hepatobiliary Pancreat Dis Int 2021 Jul 7. Epub 2021 Jul 7.

Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address:

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http://dx.doi.org/10.1016/j.hbpd.2021.06.007DOI Listing
July 2021

Prediction of premyopia and myopia in Chinese preschool children: a longitudinal cohort.

BMC Ophthalmol 2021 Jul 21;21(1):283. Epub 2021 Jul 21.

Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

Backgrounds: Myopia has become a global public health problem. Children with early onset of myopia are at particular risk of complications associated with myopia. Younger children and children with greater initial myopic refractive errors are at a greater risk of myopia progression. Therefore, it is essential to identify subjects at high risk of developing myopia to facilitate myopia prevention in the early stage, especially during the preschool period. The purpose of this study was to determine whether premyopia and myopia in preschool children can be predicted by easily obtainable parameters.

Methods: Data was collected in a population-based cohort. Comprehensive examinations included height, weight, refraction, axial length (AL), and corneal radius of curvature (CR), with a follow-up of 2 years. Parental myopia history was obtained from a questionnaire. Myopia was defined as spherical equivalent (SE) ≤ - 0.50 D. Premyopia was defined as - 0.50 D < SE ≤ + 0.75 D. Multivariate linear regression models were fitted to determine the associations between these parameters at baseline and future SE. To predict premyopia and myopia, Cox proportional hazard regression analysis coupled with a nomogram was used.

Results: A total of 830 children (433 boys and 397 girls) were included (40.83 ± 3.43 months old at baseline). A significantly negative relationship was observed in the multivariate analysis between baseline AL, AL/CR, two myopic parents, and the future SE after adjusting for age and gender (coefficient = - 0.291, coefficient = - 5.791, coefficient = - 0.273, respectively, both p <  0.001). Higher baseline AL, AL/CR (hazard ratio (HR) = 4.916, HR = 2.979, respectively, comparing the top quartile with the bottom quartile, both p <  0.001) and two myopic parents (HR = 1.756, compared to no myopic parents, p = 0.001) were associated with a higher risk of future onset of premyopia. From the nomogram, AL/CR was found to have the most enormous effect on survival. Different baseline AL and AL/CR values (both Log Rank p <  0.001) had different survival curves.

Conclusions: AL and AL/CR could be used as obtainable indicators for identifying subjects at high risk of developing premyopia and myopia in young preschool children.
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http://dx.doi.org/10.1186/s12886-021-02045-8DOI Listing
July 2021

The role of long noncoding RNA THAP9-AS1 in the osteogenic differentiation of dental pulp stem cells via the miR-652-3p/VEGFA axis.

Eur J Oral Sci 2021 Jul 19:e12790. Epub 2021 Jul 19.

Department of Prosthodontics, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, Shandong, China.

Dental pulp stem cells (DPSCs) are multipotent and may play crucial roles in dentin-pulp regeneration. Recent studies have revealed that long noncoding RNAs (lncRNAs) are implicated in the osteogenic differentiation of DPSCs. However, the specific role and potential mechanisms of the lncRNA trihydroxyacetophenone domain containing nine antisense RNA 1 (THAP9-AS1) during osteogenic differentiation of DPSCs remain unknown. In the present study, we determined that THAP9-AS1 expression was upregulated during osteogenic differentiation of DPSCs. Moreover, we investigated the biological functions of THAP9-AS1 during osteogenic differentiation of DPSCs by loss-of-function assays. THAP9-AS1 knockdown inhibited osteogenic differentiation of DPSCs by decreasing alkaline phosphatase activity, alkaline phosphatase-positive cell ratio, mineralizing matrix and mRNA, and protein levels of early osteogenic-markers. We also found that THAP9-AS1 interacted with miR-652-3p, whose downstream gene target is vascular endothelial growth factor A (VEGFA). In addition, rescue assays indicated that VEGFA rescued the effects of THAP9-AS1 knockdown during osteogenic differentiation of DPSCs. In summary, we verified that knockdown of THAP9-AS1 inhibits osteogenic differentiation of DPSCs via the miR-652-3p/VEGFA axis. Our findings may be helpful to extend research on the mechanisms underlying osteogenic differentiation of DPSCs.
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http://dx.doi.org/10.1111/eos.12790DOI Listing
July 2021

Remarkable Improvement of Thermoelectric Performance in Ga and Te Cointroduced CuSnS.

Inorg Chem 2021 Jul 21. Epub 2021 Jul 21.

School of Materials and Chemical Engineering, Ningbo University of Technology, Ningbo 315016, China.

Ternary sulfide CuSnS (CTS) receives growing interest in photocatalytic and gas sensing applications; however, limited attention has been paid to the application in thermoelectrics in virtue of its intrinsic high carrier concentration. In this work, a high figure of merit of Ga (ZT) and Te cointroduced CTS with the composition of (CuSnS)(GaTe) ( = 0.105) has been realized via synergistic optimization of the electronic and thermal transport properties. The incorporation of Ga into CTS results in a downshift of both the conduction and valence bands, which effectively promotes the active hybridization of Sn 5s and S 3p orbitals near the Fermi level () and optimizes the carrier concentration. In the meantime, the lattice thermal conductivity (κ) generally decreases on account of the local internal distortion induced by Ga(Te) substitution at the Cu(S) site. Moreover, the phonon transport is greatly suppressed above ∼725 K attributed to the melting of the second-phase Te on the grain boundaries. Consequently, the highest ZT value of ∼0.96 is obtained at 798 K. This value is ∼3.6 times that of the pristine CTS and ranks the highest in the CTS system to date.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01028DOI Listing
July 2021

Comparative Study of the Genetic Diversity, Antimicrobial Resistance, and Pathogenicity of Isolates from Clinical Patients and Healthy Individuals.

Biomed Environ Sci 2021 Jun;34(6):454-464

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Objective: This study was performed to compare the genetic diversity, virulence, and antimicrobial resistance of strains isolated from patients and healthy individuals.

Methods: A total of 38 clinical strains and 19 strains from healthy individuals were isolated from the samples collected in Ma'anshan City, Anhui Province. Their taxonomy was investigated using concatenated - sequences, and their resistance to 12 antibiotics was evaluated. The pathogenicity of these strains was examined through beta-hemolysis, protease activity, and virulence gene assays.

Results: The 57 strains were divided into 55 sequence types. Of these types, 21 were novel, suggesting that their genetic diversity was high. These isolates could be divided into 7 species, and the positive rates of beta-hemolysis and protease activity were 49.1% and 73.7%, respectively. The detection rate of clinical patients in terms of beta-hemolysis and protease activity was higher than that of healthy individuals. Among the four most common strains, had the highest detection rate of virulence genes. The multidrug resistance rate of the clinical isolates was much higher than that of the strains isolated from healthy individuals.

Conclusions: The taxonomy, virulence properties, and antibiotic resistance of isolates from patients differ from those of the isolates from healthy individuals.
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http://dx.doi.org/10.3967/bes2021.062DOI Listing
June 2021

Globalization and environment: Effects of international trade on emission intensity reduction of pollutants causing global and local concerns.

Authors:
Ting Ma Yue Wang

J Environ Manage 2021 Jul 17;297:113249. Epub 2021 Jul 17.

School of Public Policy and Management, Tsinghua University, Beijing, China. Electronic address:

International trade's impact on the pollution reduction, especially varied reduction effects dealing with global or local pollutants has not been thoroughly researched empirically. We explored effects of international trade participation on both the carbon dioxide emission intensity and sulfur dioxide emission intensity with a panel data of 179 major countries during 20 years when globalization thrived. Carbon dioxide causing climate change is a global concern. While sulfur dioxide is one major air pollutant causing local health problems. Empirically, international trade participation mainly reduces carbon dioxide emission intensity but not sulfur dioxide emission intensity. Also, trade in goods form is more effective than in service form. However, international trade participation does little to improving a country's overall technology level, implying that regulation enhancement under international norm is the main mechanism. Compared with developed countries, developing countries can reduce both kinds of pollutant emission intensities more effectively by participating into international trade. A case study of China's entering into World Trade Organization (WTO)'s impact on pollutant reduction can provide more evidence. Also, developing countries with higher industrialization level experiences a bigger improvement in cleaner production. And developing countries with higher democratization level pay more attention to reduce local environmental concerns.
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http://dx.doi.org/10.1016/j.jenvman.2021.113249DOI Listing
July 2021

STAU2 binds a Complex RNA Cargo that changes temporally with production of diverse intermediate progenitor cells during mouse corticogenesis.

Development 2021 Jul 16. Epub 2021 Jul 16.

Neural Stem Cell Institute, Regenerative Research Foundation, Rensselaer, NY 12144, USA.

STAU2 is a double-stranded RNA-binding protein enriched in the nervous system. During asymmetric divisions in the developing mouse cortex, STAU2 preferentially distributes into the intermediate progenitor cell (IPC), delivering RNA molecules that can impact IPC behavior. Corticogenesis occurs on a precise time-schedule, raising the hypothesis that the cargo STAU2 delivers into IPCs changes over time. To test this, we combine RNA-immunoprecipitation with sequencing (RIP-seq) over four stages of mouse cortical development, generating a comprehensive cargo profile for STAU2. A subset of the cargo was 'stable', present at all stages, and involved in chromosome organization, macromolecule localization, translation, and DNA repair. Another subset was 'dynamic', changing with cortical stage, and involved in neurogenesis, cell projection organization, neurite outgrowth, and included cortical layer markers. Notably, the dynamic STAU2 cargo included determinants of IPC versus neuronal fates and genes contributing to abnormal corticogenesis. Knockdown of one STAU2 target, Taf13, previously linked to microcephaly and impaired myelination, reduced oligodendrogenesis in vitro. We conclude that STAU2 contributes to the timing of corticogenesis by binding and delivering complex and temporally-regulated RNA cargo into IPCs.
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http://dx.doi.org/10.1242/dev.199376DOI Listing
July 2021

99mTc-Pyrophosphate Retention in Atelectatic Pulmonary Tissues of a Patient With Transthyretin Cardiac Amyloidosis.

Clin Nucl Med 2021 Jul 14. Epub 2021 Jul 14.

From the Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract: A 61-year-old man was hospitalized for suspected cardiac amyloidosis. 99mTc-Pyrophosphate scintigraphy showed intense radiotracer uptake in the heart compared with the ribs, suggestive of transthyretin cardiac amyloidosis. Subsequent genetic test showed missense mutations in the transthyretin gene, which confirmed the diagnosis. Incidentally, a regional radiotracer uptake was seen in the bilateral lungs, respectively, corresponding to areas of atelectasis on the localizing CT of the SPECT/CT. Attention should be paid to radiotracer retention in lung atelectasis as it influences the H/CL (heart-to-contralateral lung) ratio calculation and may hinder the diagnosis of cardiac amyloidosis based on the quantitative H/CL ratio.
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http://dx.doi.org/10.1097/RLU.0000000000003816DOI Listing
July 2021

Monitoring Antihypertensive Medication Adherence by LC-MS/MS: Method Establishment and Clinical Application.

J Cardiovasc Pharmacol 2021 Jul 9. Epub 2021 Jul 9.

Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China, 210029 Fu Foundation School of Engineering and Applied Science, Columbia University, NY, USA, 10027 Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, China, 030009 Department of Cardiology, East Hospital Affiliated Tongji University, Shanghai, China, 200120 Frontage Labs, Shanghai, 201203 Hangzhou Calibra Diagnostic Ltd., Hangzhou, China, 310030 Division of Cardiology, Department of Medicine, College of Physicians & Surgeons, Columbia University, NY, USA, 10032.

Abstract: Proper medication compliance is critical for the integrity of clinical practice, directly related to the success of clinical trials to evaluate both pharmacological and device-based therapies. Here, we established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to accurately detect 55 chemical entities in human urine sample, which accounting for the most commonly used 172 antihypertensive drugs in China. The established method had good accuracy, intra-day and inter-day precision for all analyses in both bench tests and validated in 21 hospitalized patients. We utilized this method to monitor and ensure drug compliance, and exclude the inferring impacts of medication compliance as a key confounder for our pivotal trial of a catheter-based, renal mapping and selective renal denervation to treat hypertension. It is found that in the urine samples from 92 consecutive subjects, 85 subjects (92.4%) were consistent with their prescriptions after 28 days run-in periods, 90 (97.8%) and 85 (95.5%) patients completely complied with their medications during the 3-month and 6-month follow-up period, respectively. Thus, using LC-MS/MS method with specificity, accuracy and precision, we ensured drug compliance of patients, excluded the key confounder of drug interferences and ensured the quality of our device-based clinical trial for treatment of hypertension.
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http://dx.doi.org/10.1097/FJC.0000000000001105DOI Listing
July 2021

Low serum IgG4 level: a potential diagnostic biomarker for IgA nephropathy.

Ann Transl Med 2021 May;9(9):781

Department of Nephrology, Peking University Third Hospital, Beijing, China.

Background: In contrast to intense investigations of galactose-deficient immunoglobulin A (IgA)1 specific immunoglobulin G (IgG), little is known about the IgG subclasses in IgA nephropathy (IgAN). Low IgG4 levels in IgAN were noticed in our preliminary experiment. We aimed to verify the low IgG4 levels and investigate the related immune mechanism in IgAN.

Methods: A total of 112 healthy controls (HC) and 112 newly diagnosed IgAN patients were enrolled in this study. Patients with idiopathic membranous nephropathy (IMN), minimal change disease (MCD), or lupus nephritis (LN) were selected as disease controls (DC) (n=122). Serum IgG4 and IgG levels were detected by enzyme-linked immunosorbent assay (ELISA). The IgG4 B, T helper 1 (Th1), and Th2 cells were measured by flow cytometry. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic value of IgG4.

Results: Both IgG4 levels and IgG4/IgG in IgAN were lower than HC and DC (all P<0.001). Severe IgAN displayed lower IgG4 levels than mild IgAN (P=0.039). Patients with higher risk of renal progression (>50%) demonstrated lower IgG4 levels than lower-risk (≤15%) patients (P=0.019). The cutoff value of IgG4 in differentiating IgAN from HC and DC was 0.26 mg/mL [sensitivity 98.2%, specificity 82.4%, area under the curve (AUC): 0.941, P<0.0001] and 0.17 mg/mL (sensitivity 90.2%, specificity 85.2%, AUC: 0.937, P<0.0001), respectively. IgG4/IgG displayed similar diagnostic and differential ability. The IgG4 B/B cells (P<0.0001) and Th2/Th (P=0.042) of IgAN were lower than HC.

Conclusions: Serum IgG4 levels were low in IgAN. Lower IgG4 levels indicated more severe disease conditions and higher risk of renal progression. Low serum IgG4 seemed to be a potential diagnostic biomarker for IgAN. Decreased IgG4 B cells and Th2 cells may contribute to the low IgG4 levels in IgAN.
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http://dx.doi.org/10.21037/atm-20-7007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246212PMC
May 2021

The genomic characteristics of different progression patterns in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Ann Transl Med 2021 May;9(9):779

Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Fast progression (FP), hyperprogressive disease (HPD), and early death (ED) are the newly reported cancer progression patterns in response to immune checkpoint inhibitor (ICI) treatment. This study aimed to investigate the clinical and genomic characteristics of FP, HPD, and ED following the ICI treatment of advanced non-small cell lung cancer (NSCLC).

Methods: We retrospectively reviewed 117 patients with advanced NSCLC who were treated with ICIs from March 2017 to October 2019. FP was defined as (I) time to treatment failure (TTF) <1.5 months; and (II) ≥50% increase in the sum of the longest diameter (SLD) of target lesions. HPD was defined as (I) TTF <2 months; and (II) ≥50% change in tumor growth rate compared with before ICI initiation. ED was defined as overall survival (OS) <3 months. Tissue samples from 18 FP/HPD/ED patients and 5 partial response (PR) patients were subjected to genomic profiling. Genomic data from 693 tumor mutational burden- and histology-matched lung cancer samples were retrieved from an internal database as a control.

Results: FP, HPD, and ED occurred in 7.21%, 9.38%, and 11.97% patients, respectively. The progression-free survival was comparable among the 3 groups. The median overall survival for FP, HPD, and ED were 3.19, 11.2, and 1.84 months, respectively. The genomic landscape revealed 1 amplification, 1 fusion, 6 mutations, 1 amplification, 1 amplification, and 1 fusion among the 18 patients with FP/HPD/ED. Compared with the Control group, ED patients showed higher mutation frequencies for (P<0.01), (P<0.01), and (P=0.04). Mutations in (P=0.018) and (P=0.04) were more common in FP patients; HPD patients showed more frequent mutations (P<0.001).

Conclusions: We demonstrated different genomic characteristics across different progression patterns following ICI treatment, which might assist clinicians in the prediction of a patient's response, identifying candidates for more effective ICI therapy.
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http://dx.doi.org/10.21037/atm-20-6910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246171PMC
May 2021

Compression-coding-based surface measurement using a digital micromirror device and heterodyne interferometry of an optical frequency comb.

Opt Express 2021 Jul;29(14):22240-22251

We propose a compression-coding-based surface measurement method that combines single-pixel imaging and heterodyne interference using an optical frequency comb. The real and imaginary parts of the heterodyne interference signals are used to obtain the depth information rapidly. By optimizing the ordering of the Hadamard measurement basis, we reconstruct a three-step sample with heights of approximately 10, 20, and 30 µm without an iterative operation in 6 ms, with a precision of 5 nm. Compared with the uncompressed measurement, the sampling times reduced to 20%, and the measurement time reduced by five times without measurement accuracy loss. The proposed method is effective for rapid measurements, particularly for objects with a simple surface topography.
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http://dx.doi.org/10.1364/OE.432112DOI Listing
July 2021

Inactivating the mannose-ethanolamine phosphotransferase Gpi7 confers caspofungin resistance in the human fungal pathogen .

Cell Surf 2021 Dec 23;7:100057. Epub 2021 Jun 23.

Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.

Understanding the molecular mechanisms governing antifungal resistance is crucial for identifying new cellular targets for developing new antifungal therapeutics. In this study, we performed a transposon-mediated genome-wide genetic screen in haploid to identify mutants resistant to caspofungin, the first member of the echinocandin class of antifungal drugs. A mutant exhibiting the highest resistance possessed a transposon insertion that inactivates a gene encoding the mannose-ethanolamine phosphotransferase. Deleting in diploid caused similar caspofungin resistance. 7Δ/Δ cells showed significantly elevated cell wall chitin content and enhanced phosphorylation of Mkc1, a core component of the PKC-MAPK cell-wall integrity pathway. Deleting suppressed the chitin elevation and caspofungin resistance of 7Δ/Δ cells, but overexpressing the dominant inactive form of , an upstream activator of PKC-MAPK signaling, did not. Transcriptome analysis uncovered 406 differentially expressed genes in 7Δ/Δ cells, many related to cell wall construction. Our results suggest that deletion impairs cell wall integrity, which triggers the cell-wall salvage mechanism via the PKC-MAPK pathway independently of Rho1, resulting in the compensatory chitin synthesis to confer caspofungin resistance.
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http://dx.doi.org/10.1016/j.tcsw.2021.100057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254124PMC
December 2021

Epigenetic Control of circHNRNPH1 in Postischemic Myocardial Fibrosis through Targeting of TGF-β Receptor Type I.

Mol Ther Nucleic Acids 2021 Sep 19;25:93-104. Epub 2020 Aug 19.

Department of Cardiology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Hongkou District, Shanghai, China.

Postischemic myocardial fibrosis is a factor for the development of cardiac dysfunction and malignant cardiac arrhythmias, and no effective therapy is currently available. Circular RNAs are emerging as important epigenetic players in various biological functions; however, their roles in cardiac fibrosis are unknown. With the use of a rat model of postischemic myocardial fibrosis, we identified an increase in circHNRNPH1 in the ischemic myocardium after myocardial infarction, particularly in cardiac fibroblasts. In cardiac fibroblasts, circHNRNPH1 was responsive to transforming growth factor β1 (TGF-β1), the principal profibrotic factor. The downregulation of circHNRNPH1, in contrast to its overexpression, promoted myofibroblast migration and α-smooth muscle actin and collagen I expression and inhibited myofibroblast apoptosis. The recombinant adeno-associated virus 9 (rAAV9)-mediated, cardiac-specific knockdown of circHNNRPH1 accordingly facilitated cardiac fibrosis and aggravated cardiac dysfunction. Mechanistically, circHNRNPH1 colocalized with and sponged microRNA (miR)-216-5p in the cytoplasm of cardiac fibroblasts to induce SMAD7 (protein family of signal transduction component of the canonical transforming growth factor-β signaling pathway) expression, accelerating the degradation of TGF-β receptor I. Thus, our results indicated that circHNRNPH1 negatively regulates the fibrogenesis of cardiac fibroblasts and may provide a new therapeutic strategy for postischemic myocardial fibrosis.
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http://dx.doi.org/10.1016/j.omtn.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250456PMC
September 2021

Rice Root Hair Phenotypes Imaged by Cryo-SEM.

Bio Protoc 2021 Jun 5;11(11):e4037. Epub 2021 Jun 5.

Research Centre for Plant RNA Signaling, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.

Cryo-scanning electron microscopy (cryo-SEM) was first introduced for scientific use in the 1980s. Since then, cryo-SEM has become a routine technique for studying the surfaces and internal structures of biological samples with a high water content. In contrast to traditional SEM, cryo-SEM requires no sample pretreatment processes; thus, we can obtain the most authentic images of the sample shape and structure. Cryo-SEM has two main steps: cryoprocessing of samples and scanning electron microscopy (SEM) observation. The cryoprocessing step includes preparation of the cooled slushing station, cooling of the preparation chamber, sample preparation, and sputtering. The sample is then transferred to an SEM cold stage for observation. We used cryo-SEM to study rice root hair tissues, but the methods and protocols can be applied to other root systems. This protocol optimizes the two key operation steps of reducing the humidity in the growth chamber and previewing the samples before sputtering and can more quickly obtain high-quality images.
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http://dx.doi.org/10.21769/BioProtoc.4037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249913PMC
June 2021

Power of Hypoperfusion in Predicting Recurrent Transient Ischemic Attacks: Protocol of a Prospective Cohort Study.

Front Hum Neurosci 2021 24;15:654383. Epub 2021 Jun 24.

Department of Neurology, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

Transient ischemic attack (TIA) has a high incidence of recurrent vascular events. Hypoperfusion is one of the factors that are closely correlated with 7-day recurrence of TIA. This study aimed to evaluate the power of hypoperfusion shown on magnetic resonance (MR) perfusion imaging in predicting the incidence of 7-day recurrence of ischemic events after TIA. REATTACK is a prospective multi-centered cohort study on the correlation between MR perfusion and TIA recurrence. Ninety patients aged ≥18 years with recent (<7 days after onset) clinical TIA will be continuously included. All the patients will undergo diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) assessments within 24 h after the onset of TIA. The subjects will then be divided into a PWI positive group and a PWI negative group according to the time-to-maximum of the residue function ( ). PWI will be repeated after 7 days and in 3 months. The primary clinical outcome will be the recurrence of TIA within 7 days after the onset of TIA. Secondary outcomes will be the recurrence of TIA in 3 months and modified Rankin scale (mRS) score. A chi-square test will be performed to compare the difference in the incidence of recurrent TIA between the two groups, and rank sum test in the mRS score. Multivariate logistic regression will be simultaneously performed to analyze the risk factors for the recurrence of TIA. The results of this study will confirm whether abnormal helps to identify the patients with TIA who have high risks of recurrent ischemic events. This would largely improve the prognosis of patients with TIA. www.chictr.org.cn, registration number: ChiCTR2000031863, registered on 12 April 2020.
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http://dx.doi.org/10.3389/fnhum.2021.654383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264133PMC
June 2021

Hypoxia associated lncRNA HYPAL promotes proliferation of gastric cancer as ceRNA by sponging miR-431-5p to upregulate CDK14.

Gastric Cancer 2021 Jul 11. Epub 2021 Jul 11.

Gastric Cancer Department, Liaoning Province Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang City, 110042, Liaoning Province, China.

Gastric cancer (GC) is a common malignant solid tumor that is characterized by high hypoxia. The transcription of genes associated with hypoxia affects tumor occurrence and development. Long non-coding RNAs (lncRNAs) have been reported to play important roles in cancer development. In this study, we screened for differentially expressed ncRNAs (non-coding RNA) and mRNAs between hypoxia-inducible factor-1 (HIF-1α) knockdown GC cells and scrambled GC cells. Microarray data revealed that HIF-1α regulated the expression of LINC01355 (Hypoxia Yield Proliferation Associated LncRNA, HYPAL). HYPAL was found to be significantly upregulated in GC cells and tissues and was correlated with poor GC prognosis. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that HIF-1α promoted HYPAL expression by binding the promoter region. A regulatory network for the competing endogenous RNA (ceRNA) was constructed using bioinformatics tools. Mechanistic studies revealed that HYPAL acted as a ceRNA of miR-431-5p to regulate CDK14 expression. Carcinogenic effects of HYPAL were evaluated in vitro and in vivo. The HIF-1α/HYPAL/miR-431-5p/CDK14 (Cyclin-dependent kinase 14) axis activated the Wnt/β-catenin signaling pathway and induced GC cell proliferation while inhibiting apoptosis. In conclusion, HYPAL is a potential molecular target for GC therapy.
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http://dx.doi.org/10.1007/s10120-021-01213-5DOI Listing
July 2021

Dihydrotanshinone I inhibits aortic valve interstitial cell calcification via the SMAD1/5/8/NF-κB/ERK pathway.

Biomed Pharmacother 2021 Jul 10;139:111674. Epub 2021 May 10.

Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China. Electronic address:

Objectives: In calcific aortic valve disease (CAVD), the valve interstitial cells (VIC) osteogenic phenotype changes can lead to thickening and calcification of the valve leaflets,eventually lead to restricted valve movement and life-threatening. This study aims to investigate the effect and mechanism of dihydrotanshinone I (DHI) on osteogenic medium (OM) induced osteogenic phenotypic transition of porcine valve interstitial cells (PVICs), which can provide theoretical and scientific basis for clinical intervention in CAVD.

Methods And Results: Immunohistochemical methods were used to detect the expression of osteogenic indicators Runx2, OPN and inflammation indicators IL-1β and p-NF-κB in valve specimens of CAVD patients(N = 3) and normal controls(N = 1). PVICs stimulated by osteoblastic medium (OM) were treated with or without DHI. CCK8, ALP and Alizarin Red S staining were used to detect cell growth and calcification, respectively. The results showed that under the treated with DHI, compared with OM, the formation of calcium nodules was reduced, and the expression of calcification-related markers Runx2 and OPN were down-regulated, which quantified by qRT-PCR and western blot. In addition, on the basis of OM induction, DHI also inhibited the phosphorylation of the NF-κB/ERK1/2 and SMAD1/5/8 signaling pathway.

Conclusion: DHI (10 μM) treatment can reverse the osteogenic phenotypic transition of PVICs induced by osteogenic medium, and the mechanism may be related to NF-κB、ERK 1/2 and Smad1/5/8 pathways.
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http://dx.doi.org/10.1016/j.biopha.2021.111674DOI Listing
July 2021

Prognostic Nomograms Based on Three Lymph Node Classification Systems for Resected Gastric Adenocarcinoma: A Large Population-Based Cohort Study and External Validation.

Ann Surg Oncol 2021 Jul 9. Epub 2021 Jul 9.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, China.

Backgrounds: The optimal lymph node classification system for prognostic assessment in gastric adenocarcinoma (GAC) patients who undergo lymph node dissection remains unclear. Therefore, this study aimed to compare prognostic nomograms based on AJCC N stage, lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS) to evaluate the prognosis and differentiate risk subgroups of patients with resected GAC.

Patients And Methods: We collected 4633 patients with resected stage I-III GAC receiving chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Independent prognostic factors were selected by Cox regression analyses, based on which nomograms were constructed. External validation was performed in 228 cases from Nanjing Drum Tower Hospital. Kaplan-Meier survival analysis was used to evaluate the effect of postoperative radiotherapy (PORT) for different lymph node classifications.

Results: Multivariate analysis indicated that age, grade, primary site, T stage, N stage, LNR, LODDS, and radiotherapy were independent predictors. Good discrimination power and high consistency of calibration plots were obtained from the LODDS system nomogram. The LODDS classification could more precisely differentiate risk subgroups and improve the discrimination of the resected GAC prognosis. A user-friendly webserver of LODDS system was built based on the nomogram for convenient clinical application.

Conclusions: The LODDS seems to be the most reliable lymph node classification in predicting the prognosis of patients with resected GAC and should be recommended in clinical prognostic assessment. Incorporating LODDS into the staging system will enable clinicians to more accurately predict prognosis and guide radiotherapy regimen decisions.
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http://dx.doi.org/10.1245/s10434-021-10299-1DOI Listing
July 2021

Mutations of predict response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

J Clin Transl Res 2021 Jun 5;7(3):386-413. Epub 2021 Jun 5.

Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

Background And Aim: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the current gold standard treatment for muscle-invasive urothelial bladder cancer (MIBC). Nonetheless, some MIBC patients showed limited pathological response after NAC. Herein, we used whole-exome sequencing (WES) to identify genetic mutations in MIBC that can predict NAC response.

Methods: Forty MIBC patients were enrolled in this study, in which 33 were successfully examined by WES and Sanger sequencing in the discovery cohort (=13) and the validation cohort (=20), respectively. ANNOVAR software was used to identify the potential mutations based on the data of WES. In addition, tumor-specific somatic mutations including single nucleotide variants and indels were called with the muTECT and Strelka software. The mutational analysis of specific genes was carried out based on the data from cBioPortal for Cancer Genomics.

Results: In the discovery cohort, the mutation frequencies of , , , , , , and were significantly higher in 13 MIBC patients. Specifically, the presence of somatic mutations of , , , , , , , , and in NAC responder signifies that these mutations were potential predictors of pathological response to NAC. Furthermore, somatic mutations of , , , , , , and were exclusively identified in NAC nonresponders, suggesting that these mutations may participate in the process of NAC resistance. In the validation cohort, the somatic mutations of , , and were significantly enriched in NAC responders while the somatic mutation of was significantly enriched in NAC nonresponders. Furthermore, survival analysis revealed that the patients expressing mutated have a longer overall survival and disease- or progression-free survival than the patients acquiring wild-type .

Conclusion: The somatic mutation of can be a potential predictive biomarker of NAC response in MIBC patients.

Relevance For Patients: MIBC patients bearing mutated display a pathological response to NAC and have a significantly longer overall survival or disease/progression-free survival as compared to the patients bearing wild-type . Thus, the somatic mutation of is a potential biomarker for predicting response to NAC in MIBC patients, assisting doctors in making the clinical decision.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259609PMC
June 2021

Tangeretin maintains antioxidant activity by reducing CUL3 mediated NRF2 ubiquitination.

Food Chem 2021 Jun 27;365:130470. Epub 2021 Jun 27.

Laboratory of Fruit Quality Biology/The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Fruit Science Institute, Zhejiang University, Zijingang Campus, Hangzhou 310058, China. Electronic address:

To explore the antioxidant capacity of citrus flavonoids under different evaluation systems, chemical and biological methods were engaged to determine the antioxidant abilities of flavanones and polymethoxyflavones. Results showed that flavanones exhibited good antioxidant activity, while polymethoxyflavones had a weak ability to scavenge free radicals. Both flavanones and polymethoxyflavones exerted the ability to inhibit HO-induced oxidative stress, but the effective concentration of polymethoxyflavones was lower. Further exploration showed that neohesperidin and tangeretin selectively regulated antioxidant enzyme activity, both in vitro and in vivo. Tangeretin also maintained the expression of antioxidant enzymes in L02 cells and in ICR mice liver. The mechanism exploration showed that both neohesperidin and tangeretin promoted the expression of NRF2 and inhibit the expression of KEAP1, but tangeretin could inhibit the ubiquitination of NRF2 by inhibiting CUL3. The mechanism was verified by CUL3 gene silencing. This study demonstrates a novel antioxidant mechanism of natural products.
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http://dx.doi.org/10.1016/j.foodchem.2021.130470DOI Listing
June 2021

ASO Visual Abstract: Prognostic Nomograms Based on Three-Lymph-Node Classification Systems for Resected Gastric Adenocarcinoma: A Large Population-Based Cohort Study and External Validation.

Ann Surg Oncol 2021 Jul 8. Epub 2021 Jul 8.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.

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http://dx.doi.org/10.1245/s10434-021-10348-9DOI Listing
July 2021

Emerging Diagnostic Potential of Tumor-derived Exosomes.

J Cancer 2021 16;12(16):5035-5045. Epub 2021 Jun 16.

College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.

Exosomes carry genetic information originating from their parental cells, raising their possibility as novel noninvasive biomarkers for cancer. Tumor-derived exosomes (TEXs) have a variety of endogenous cargos that reflect the pathophysiology status and information of tumor cells. TEXs are increasingly being recognized as potential biomarkers for cancer diagnosis prognosis, and monitoring. It is important to develop a variety of sensitive methods, including probes and biomaterials to isolate exosomes. A variety of approaches for detecting exosomes have been established. By combining exosome DNA and RNA sequencing tools, exosome proteomics analysis and immunoassay technology, it is expected that exosomes will gain widespread use in the diagnosis and treatment of cancer.
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http://dx.doi.org/10.7150/jca.59391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247367PMC
June 2021

Temporal rank of clinical characteristics and prognosis of anti-N-methyl-d-aspartate receptor encephalitis.

Brain Behav 2021 Jul 7. Epub 2021 Jul 7.

Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Objectives: Early recognition and intervention of patients with the anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis are important to achieve a better prognosis. The study aims to summarize the real-world perspectives of anti-NMDAR encephalitis patients in China via electronic medical records (EMRs).

Methods: Using EMRs of patients from 2013 to 2019 from West China Hospital in China, a retrospective research was conducted to demonstrate the temporary rank of clinical characteristics and disease prognosis of anti-NMDAR encephalitis. The modified Rankin Scale (mRS) scores were used to divide the anti-NMDAR-encephalitis into two groups (poor prognosis vs. good prognosis). Chi-square test and logistic regression were used to analyze factors associated with prognosis.

Results: Here, 78 patients were included. The most common clinical characteristics are cognitive dysfunction (86.0%) and thought disorder (86.0%). Cognitive dysfunction, thought disorder, and seizures tended to appear soon after prodrome symptoms. Logistics analysis results showed that cognitive dysfunction (OR = 4.48, 95% CI = 1.09-18.47), the score of (GCS ≤ 8) (OR = 4.52, 95% CI = 1.18-17.32), positive antibodies in serum (OR = 4.89, 95% CI = 1.19-20.13) and delay immunotherapy (OR = 4.76, 95% CI = 1.79-12.60) were risk factors of poor clinical outcomes.

Conclusions: There are two peaks in the development of autoimmune encephalitis (AE). The first peak is cognitive dysfunction, and the second peak is autonomic dysfunction. Cognitive dysfunction and GCS score ≤8 at admission, antibodies positive in serum, and delay immunotherapy were risk factors for a poor prognosis at discharge.
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http://dx.doi.org/10.1002/brb3.2277DOI Listing
July 2021

Nonsurgical Treatment for Congenital Auricular Deformities: A Systematic Review and Meta-analysis.

Aesthetic Plast Surg 2021 Jul 6. Epub 2021 Jul 6.

Department of Plastic and Reconstructive Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.

Background: The effectiveness and safety of non-surgical correction for congenital auricular deformities (CADs) remain unclear owing to a lack of high-level evidence. This systematic review and meta-analysis aimed to estimate the overall success and complication rates of the non-surgical correction for CAD.

Methods: We searched PubMed, Medline, and Cochrane Library for eligible studies. The pooled success and complication rates of non-surgical correction were estimated using a random effects model. Subgroup analyses were performed to compare the success rates between patients treated with splints and molding systems, between those younger and older than 6-weeks, and among those with different types of CADs.

Results: The review yielded 14 studies. The pooled success rate of non-surgical treatment was 93% (95% CI: 88%-97%). The success rates with splints and commercialized molding systems were 94% and 92%, respectively. The success rate was higher if non-surgical correction was initiated before age 6 weeks (96% vs. 82%). Prominent ears showed a lower success rate (85%) than other types of CADs (all > 90%). The pooled complication rate was 18% (95% CI: 10%-29%). Complications, including skin wound, irritation, and rash, were mild and easily treatable.

Conclusion: The non-surgical correction of CADs is highly effective and safe. Splints and molding systems offer similar effectiveness. Non-surgical correction is more beneficial if applied within 6 weeks of birth. Prominent ears have a lower, but still acceptable, success rate compared to other types of CAD. We recommend the early use of non-surgical correction to achieve favorable outcomes.

Level Of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-021-02427-9DOI Listing
July 2021

Keystone taxa-mediated bacteriome response shapes the resilience of the paddy ecosystem to fungicide triadimefon contamination.

J Hazard Mater 2021 Sep 9;417:126061. Epub 2021 May 9.

Institute of Pesticide and Environmental Toxicology, College of Agriculture & Biotechnology, Zhejiang University, Hangzhou 310058, China; Global Education Program for AgriScience Frontiers, Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan. Electronic address:

The increasing input of fungicides has emerged as a global concern for agroecosystem stability and sustainability. Agroecosystem resilience has been linked to microbiome response, however, is not well understood. Focusing on a widespread triazole-class fungicide triadimefon in the paddy ecosystem, we characterized that the soils and sediments were dominant triadimefon reservoirs with the peak level at 195 μg kg and 31.3 μg kg, respectively, but essential for the resilience of paddy ecosystem to triadimefon. In paddy simulation models, the half-life of triadimefon in soil-sediment was 8.4-28.9 days, while it was prolonged to 86.6-115.5 days after elimination of resident microbial community. Phospholipid fatty acid profiling and high-throughput sequencing showed that the distinctive bacterial community responses contributed to variable degradation of triadimefon in paddy soils and sediments. Sphingomonas and Xanthomonas were identified as positive responders of the keystone taxa in the responsive bacteriome, whereas Enterobacter were negative responders that declined over time. Synthetic assemblages combined with quantitative polymerase chain reaction further validated that Sphingomonas and Xanthomonas were involved in sustaining soil-sediment resilience to triadimefon contamination. Collectively, our results revealed that the shaping of soil and sediment bacteriomes was responsible for the resilience of the paddy agroecosystem to fungicide contamination.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126061DOI Listing
September 2021

Genome-wide analysis of genomic imprinting in the endosperm and allelic variation in flax.

Plant J 2021 Jul 6. Epub 2021 Jul 6.

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China.

Genomic imprinting is an epigenetic phenomenon that causes biased expression of maternally and paternally inherited alleles. In flowering plants, genomic imprinting predominantly occurs in the triploid endosperm and plays a vital role in seed development. In this study, we identified 248 candidate imprinted genes including 114 maternally expressed imprinted genes (MEGs) and 134 paternally expressed imprinted genes (PEGs) in flax (Linum usitatissimum L.) endosperm using deep RNA sequencing. These imprinted genes were neither clustered in specific chromosomal regions nor well conserved among flax and other plant species. MEGs tended to be expressed specifically in the endosperm, whereas the expression of PEGs was not tissue-specific. Imprinted single nucleotide polymorphisms differentiated 200 flax cultivars into the oil flax, oil-fiber dual purpose flax and fiber flax subgroups, suggesting that genomic imprinting contributed to intraspecific variation in flax. The nucleotide diversity of imprinted genes in the oil flax subgroup was significantly higher than that in the fiber flax subgroup, indicating that some imprinted genes underwent positive selection during flax domestication from oil flax to fiber flax. Moreover, imprinted genes that underwent positive selection were related to flax functions. Thirteen imprinted genes related to flax seed size and weight were identified using a candidate gene-based association study. Therefore, our study provides information for further exploration of the function and genomic variation of imprinted genes in the flax population.
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http://dx.doi.org/10.1111/tpj.15411DOI Listing
July 2021

Review of 602 Microtia Reconstructions: Revisions and Specific Recommendations for Each Subtype.

Plast Reconstr Surg 2021 Jul 2. Epub 2021 Jul 2.

Department of Ear Reconstruction Plastic Surgery Hospital Chinese Academy of Medical Sciences Beijing, People's Republic of China.

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http://dx.doi.org/10.1097/PRS.0000000000008399DOI Listing
July 2021

NIR-Activated Multimodal Photothermal/Chemodynamic/Magnetic Resonance Imaging Nanoplatform for Anticancer Therapy by Fe(II) Ions Doped MXenes (Fe-Ti C ).

Small 2021 Jul 5:e2101705. Epub 2021 Jul 5.

Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructures and School of Physics, Nanjing University, Nanjing, 210093, China.

2D MXene, Ti C (TC), has displayed enormous potential in applications in photothermal therapy (PTT), attributing to its biocompatibility and outstanding photothermal conversion capability. However, some tumor ablations are difficult to be realized completely by monotherapy due to the essential defects of monotherapy and intricate tumor microenvironment (TME). In this work, the appropriate doped Fe ions are anchored into the layers of 2D ultrathin TC nanosheets (TC NSs) to synthesize a novel multifunctional nanoshell of Fe(II)-Ti C (FTC) through interlayer electrostatic adsorption. FTC possesses superior photothermal conversion efficiency (PTCE) than TC NSs, attributing to the enhanced conductivity promoted by interlaminar ferrous ion-channels. Moreover, Fenton reaction based on ferrous ions endows FTC the abilities of reactive oxide species (ROS) releasing and glutathione (GSH) suppression triggered by near-infrared (NIR) laser, featuring splendid biocompatibility and curative effect in hypoxic TME. Meanwhile, magnetic resonance imaging (MRI) responding in FTC reveals the potential as an integrated diagnosis and treatment nanoplatform. FTC could provide new insights into the development of multimoded synergistic nanoplatform for biological applications, especially breaking the shackles of MXenes merely used as a photo-thermal agent (PTA), adopting it to bioimaging sensor and drug loading.
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http://dx.doi.org/10.1002/smll.202101705DOI Listing
July 2021