Publications by authors named "Yang Xiang"

1,040 Publications

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miRNA-34b/c regulates mucus secretion in RSV-infected airway epithelial cells by targeting FGFR1.

J Cell Mol Med 2021 Oct 12. Epub 2021 Oct 12.

Department of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, China.

Respiratory syncytial virus (RSV) infection in airway epithelial cells is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV-related LRTI). However, the pathological processes of mucus hypersecretion in RSV-infected airway epithelial cells remains unclear. The current study explores the involvement of miR-34b/miR-34c in mucus hypersecretion in RSV-infected airway epithelial cells by targeting FGFR1. First, miR-34b/miR-34c and FGFR1 mRNA were quantified by qPCR in throat swab samples and cell lines, respectively. Then, the luciferase reporters' assay was designed to verify the direct binding between FGFR1 and miR-34b/miR-34c. Finally, the involvement of AP-1 signalling was assessed by western blot. This study identified that miR-34b/miR-34c was involved in c-Jun-regulated MUC5AC production by targeting FGFR1 in RSV-infected airway epithelial cells. These results provide some useful insights into the molecular mechanisms of mucus hypersecretion which may also bring new potential strategies to improve mucus hypersecretion in RSV disease.
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http://dx.doi.org/10.1111/jcmm.16988DOI Listing
October 2021

Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial.

Lancet Oncol 2021 Oct 5. Epub 2021 Oct 5.

Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Background: Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia.

Methods: This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-care centre in Beijing, China. Women (18-70 years) with high-risk (International Federation of Gynecology and Obstetrics score ≥7) chemorefractory or relapsed gestational trophoblastic neoplasia who had received at least two lines of previously unsuccessful multidrug chemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible for inclusion. Patients received 4-week cycles of intravenous camrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activity and safety were analysed in all patients who received at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT04047017.

Findings: Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18·5 months (IQR 14·6-20·9). The objective response rate was 55% (95% CI 32-77); ten (50%; 95% CI 27-73) patients had complete response. The most common grade 3 treatment-related adverse events were hypertension (five [25%] patients), rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), and aspartate aminotransferase increase (two [10%]). One patient had a treatment-related serious adverse event (aspartate aminotransferase 19-times higher than the upper limit of normal). No grade 4 or 5 treatment-related adverse events were reported.

Interpretation: Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase 2 trials.

Funding: National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals.
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http://dx.doi.org/10.1016/S1470-2045(21)00460-5DOI Listing
October 2021

ZmMPK5 phosphorylates ZmNAC49 to enhance oxidative stress tolerance in maize.

New Phytol 2021 Oct 7. Epub 2021 Oct 7.

College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.

Mitogen-activated protein kinase (MPK) is a critical regulator of the antioxidant defense system in response to various stimuli. However, how MPK directly and exactly regulates antioxidant enzyme activities is still unclear. Here, we demonstrated that a NAC transcription factor ZmNAC49 mediated the regulation of antioxidant enzyme activities by ZmMPK5. ZmNAC49 expression is induced by oxidative stress. ZmNAC49 enhances oxidative stress tolerance in maize, and it also reduces superoxide anion generation and increases superoxide dismutase (SOD) activity. A detailed study showed that ZmMPK5 directly interacts with and phosphorylates ZmNAC49 in vitro and in vivo. ZmMPK5 directly phosphorylates Thr-26 in NAC subdomain A of ZmNAC49. Mutation at Thr-26 of ZmNAC49 does not affect the interaction with ZmMPK5 and its subcellular localization. Further analysis found that ZmNAC49 activates the ZmSOD3 expression by directly binding to its promoter. ZmMPK5-mediated ZmNAC49 phosphorylation improves its ability to bind to the ZmSOD3 promoter. Thr-26 of ZmNAC49 is essential for its transcriptional activity. Besides, ZmSOD3 enhances oxidative stress tolerance in maize. Our results show that phosphorylation of Thr-26 in ZmNAC49 by ZmMPK5 increased its DNA binding activity to the ZmSOD3 promoter, enhanced SOD activity, and thereby improved oxidative stress tolerance in maize.
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http://dx.doi.org/10.1111/nph.17761DOI Listing
October 2021

Construction and Validation of a Platinum Sensitivity Predictive Model With Multiple Genomic Variations for Epithelial Ovarian Cancer.

Front Oncol 2021 16;11:725264. Epub 2021 Sep 16.

Department of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

Platinum-based chemotherapy is still the standard of care after cytoreductive surgery in the first-line treatment for epithelial ovarian cancer. This study aims to integrate novel biomarkers for predicting platinum sensitivity in EOC after initial cytoreductive surgery precisely. To this end, 60 patients were recruited from September 2014 to October 2019. Based on the duration of progress-free survival, 44 and 16 patients were assigned to platinum-sensitive and platinum-resistant group, respectively. Next generation sequencing was performed to dissect the genomic features of ovarian tumors obtained from surgery. Multiple genomic variations were compared between two groups, including single-nucleotide variant, single base or indel signature, loss of heterozygosity (LOH), whole-genome duplication (WGD), and others. The results demonstrated that patients with characteristics including positive SBS10a signature (p < 0.05), or LOH (p < 0.01), or negative WGD (p < 0.01) were significantly enriched in platinum-sensitive group. Consistently, patients with positive SBS10a signature (15.8 10.1 months, p < 0.05), or LOH (16.5 9.2 months, p < 0.05), or negative WGD (16.5 9.1 months, p < 0.05) have significantly longer PFS than those without these genetic features. By integrating these three biomarkers, a lasso regression model was employed to train and test for all patients, with the AUC value 0.864 in platinum sensitivity prediction. Notably, 388 ovarian cancer patients from TCGA dataset were leveraged as independent validation cohort with AUC value 0.808, suggesting the favorable performance and reliability of this model.
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http://dx.doi.org/10.3389/fonc.2021.725264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481766PMC
September 2021

The mutuality of social emotions: How the victim's reactive attitude influences the transgressor's emotional responses.

Neuroimage 2021 Sep 30;244:118631. Epub 2021 Sep 30.

Shanghai Key Laboratory of Mental Health and Psychological Crisis Intervention, School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China; School of Psychological and Cognitive Sciences, Peking University, Beijing 100871, China; School of Business and Management, Shanghai International Studies University, Shanghai 200083, China; Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China. Electronic address:

Would a transgressor be guiltier or less after receiving the victim's forgiving or blaming attitude? Everyday intuitions and empirical evidence are mixed in this regard, leaving how interpersonal attitudes shape the transgressor's reactive social emotions an open question. We combined a social interactive game with multivariate pattern analysis of fMRI data to address this question. Participants played an interactive game in an fMRI scanner where their incorrect responses could cause either high or low pain stimulation to an anonymous co-player. Following incorrect responses, participants were presented with the co-player's (i.e., the victim's) attitude towards the harm (Blame, Forgive, or Neutral). Behaviorally, the victim's attitude and the severity of harm interactively modulated the transgressor's social emotions, with expectation violation serving as a mediator. While unexpected forgiveness following severe harm amplified the participants' guilt, unexpected blame following minor harm reduced the participants' guilt and increased their anger. This role of expectation violation was supported by multivariate pattern analysis of fMRI, revealing a shared neural representation in ventral striatum in the processing of victim's attitude-induced guilt and anger. Moreover, we identified a neural re-appraisal process of guilt in the transgressor, with the involvement of area related to self-conscious processing (i.e., perigenual anterior cingulate cortex) before knowing the victim's attitude transiting to the involvement of other-regarding related area (i.e., temporoparietal junction) after knowing the victim's attitude. These findings uncover the neurocognitive bases underlying the transgressor's social emotional responses, and highlight the importance of the mutuality of social emotions.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118631DOI Listing
September 2021

Editorial: Immunological Mechanisms, Biomarkers and Immunotherapies of Alzheimer's Disease.

Front Aging Neurosci 2021 13;13:733282. Epub 2021 Sep 13.

Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

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http://dx.doi.org/10.3389/fnagi.2021.733282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473822PMC
September 2021

MustSeq, an alternative approach for multiplexible strand-specific 3' end sequencing of mRNA transcriptome confers high efficiency and practicality.

RNA Biol 2021 Sep 29:1-12. Epub 2021 Sep 29.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, Guangdong Province, China.

RNA-seq has been widely used to reveal the molecular mechanism of variants of life process. We have developed an alternative method, MustSeq, which generates multiple second strands along a single 1 strand cDNA by random-priming initiation, immediately after reverse transcription for each RNA extract using sample-barcoded poly-dT primers, then 3' ends-enriching PCR is applied to construct the library. Unlike the conventional RNA seq, MustSeq avoids procedures such as mRNA isolation, fragmentation and RNA 5'-end capture, enables early pooling of multiple samples, and requires only one twentieth of sequencing reads of full-length sequencing. We demonstrate the power and features of MustSeq comparing with TruSeq and NEBNext RNA-seq, two conventional full-length methods and QuantSeq, an industrial 3' end method. In cancer cell lines, the reads distribution of CDS-exon as well as genes, lncRNAs and GO terms detected by MustSeq are closer than QuantSeq to TruSeq. In mouse hepatocarcinoma and healthy livers, MustSeq enriches the same pathways as by NEBNext, and reveals the molecular profile of carcinogenesis. Overall MustSeq is a robust and accurate RNA-seq method allowing efficient library construction, sequencing and analysis, particularly valuable for analysis of differentially expressed genes with a large number of samples. MustSeq will greatly accelerate the application of bulk RNA-seq on different fields, and potentially applicable for single cell RNA-seq.
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http://dx.doi.org/10.1080/15476286.2021.1974208DOI Listing
September 2021

Transcription Factor Phosphorylated by Functioning in ABA-Induced Antioxidant Defense and Enhance Drought Tolerance in Maize.

Biology (Basel) 2021 Sep 10;10(9). Epub 2021 Sep 10.

College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.

Mitogen-activated protein kinase (MAPK) cascades are primary signaling pathways involved in various signaling pathways triggered by abiotic and biotic stresses in plants. The downstream substrate proteins of MAPKs in maize, however, are still limited. Here, we screened a WRKY IIa transcription factor (TF) in maize ( L.), , and found that it is a substrate of . physically interacts with in vitro and in vivo. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis results showed that threonine-59 (Thr-59, T59) was the major phosphorylation site of by . Subcellular localization analysis suggested that acts in the nucleus and that acts in the nucleus and cytoplasmic membrane in the cytosol. Functional analysis revealed that the role of in ABA-induced antioxidant defense depends on . Moreover, overexpression of in maize can enhance drought tolerance and relieve drought-induced oxidative damage in transgenic lines. The above results help define the mechanism of the function of phosphorylated by in ABA-induced antioxidant defense and drought tolerance in maize.
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http://dx.doi.org/10.3390/biology10090893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467104PMC
September 2021

Involvement of epithelia-derived exosomes in chronic respiratory diseases.

Biomed Pharmacother 2021 Nov 21;143:112189. Epub 2021 Sep 21.

Department of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China; Research Center of China-Africa Infectious Diseases, Xiangya School of Medicine Central South University, Changsha, Hunan, China. Electronic address:

Exosomes are tiny membrane lipid bilayer vesicles (φ40-100 nm) formed by the fusion of multivesicular bodies with plasma membrane, which are released extracellular by exocytosis. As natural nanocarriers, exosomes contain a variety of signal substances of the mother cell: nucleic acids, proteins and lipids, etc., which always play a vital role in the transmission of signal molecules between different cells. Epithelial cells are the first-line defense system against various inhaled allergens causing chronic respiratory diseases (CRD), such as asthma and chronic obstructive pulmonary disease (COPD). It's noted that increasing literature shows the exosomes derived from epithelial cells are involved in the pathogenesis of CRD. Moreover, the correlations between exosome cargo and the disease phenotypes show a high potential of using exosomes as biomarkers of CRD. In this review, we mainly focus on the physiological functions of epithelial-derived exosomes and illustrate the involved mechanism of epithelial-derived exosomes in common CRD.
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http://dx.doi.org/10.1016/j.biopha.2021.112189DOI Listing
November 2021

Target-Initiated Great Change in Electrochemical Steric Hindrance for an Assay of Granzyme B Activity.

Anal Chem 2021 10 22;93(39):13382-13388. Epub 2021 Sep 22.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China.

To improve long-term graft patient outcomes and develop more effective antirejection therapies, noninvasive monitoring of acute cellular rejection (ACR) after organ transplantation is urgently needed. As a biomarker of ACR, Granzyme B (GrB) is expected to be applied in the noninvasive monitoring of ACR. Herein, we have developed a method for detecting the GrB activity based on the target-initiated great change in electrochemical steric hindrance by designing a nanoprobe. The nanoprobe is prepared by conjugating a specific peptide, which is responsive to GrB cleavage activity, to gold nanoparticles (AuNPs). Meanwhile, a piece of DNA sequence with G-quadruplex (G4) is attached at the distal end of the peptide. Upon exposure to GrB, the peptide substrate is cleaved to eliminate the steric hindrance between inter-nanoprobes as well as nanoprobe and DNA tetrahedron (TDN), allowing the released DNA strand to hybridize with TDN, giving sensitive signal output. The method can also be used to detect GrB activity in complex biological settings, so it has a great potential for monitoring GrB activity in the blood or urine of graft patients.
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http://dx.doi.org/10.1021/acs.analchem.1c03188DOI Listing
October 2021

Mechanistic study of lncRNA UCA1 promoting growth and cisplatin resistance in lung adenocarcinoma.

Cancer Cell Int 2021 Sep 20;21(1):505. Epub 2021 Sep 20.

Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

Aim: This study aimed to explore the mechanism of LncRNA urothelial carcinoma-associated 1 (UCA1) promoting cisplatin resistance in lung adenocarcinoma (LUAD).

Method: The UCA1 expression level in LUAD cell lines was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We overexpressed UCA1 in A549 cells and downregulated UCA1 in A549/DDP cells by the lentivirus‑mediated technique. Subsequently, in vitro, and in vivo functional experiments were performed to investigate the functional roles of UCA1 in the growth and metastasis of LUAD cell lines. Furthermore, RNA pulldown, mass spectrometry, and RNA immunoprecipitation technique were performed to analyze various downstream target factors regulated by UCA1.

Results: The results revealed a higher UCA1 expression level in A549/DDP cells and LUAD tissues than in A549 cells and adjacent cancer tissues. UCA1 expression was significantly associated with distant metastasis, clinical stage, and survival time of patients with LUAD. UCA1 overexpression significantly increased the proliferation, invasion, clone formation, and cisplatin resistance ability and enhanced the expression levels of proliferating cell nuclear antigen and excision repair cross-complementing gene 1 in A549 cells. However, these trends were mostly reversed after the knockdown of UCA1 in A549/DDP cells. Tumorigenic assays in nude mice showed that UCA1 knockdown significantly inhibited tumor growth and reduced cisplatin resistance. Enolase 1 was the RNA-binding protein (RBP) of UCA1.

Conclusion: Based on the results, we concluded that UCA1 promoted LUAD progression and cisplatin resistance and hence could be a potential diagnostic marker and therapeutic target in patients with LUAD.
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http://dx.doi.org/10.1186/s12935-021-02207-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454127PMC
September 2021

Irradiation Haematopoiesis Recovery Orchestrated by IL-12/IL-12Rβ1/TYK2/STAT3-Initiated Osteogenic Differentiation of Mouse Bone Marrow-Derived Mesenchymal Stem Cells.

Front Cell Dev Biol 2021 3;9:729293. Epub 2021 Sep 3.

Department of Blood Transfusion, The Irradiation Biology Laboratory, The Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.

Purpose: Repairing the irradiation-induced osteogenic differentiation injury of bone marrow mesenchymal stem cells (BM-MSCs) is beneficial to recovering haematopoiesis injury in radiotherapy; however, its mechanism is elusive. Our study aimed to help meet the needs of understanding the effects of radiotherapy on BM-MSC osteogenic potential.

Methods And Materials: Balb/c mice and the BM-MSCs were used to evaluate the irradiation-induced osteogenic differentiation injury . The cellular and molecular characterization were applied to determine the mechanism for recovery of irradiation-derived haematopoiesis injuries.

Results: We report a functional role of IL-12 in acute irradiation hematopoietic injury recovery and intend to dissect the possible mechanisms through BM-MSC, other than the direct effect of IL-12 on hematopoietic stem and progenitor cells (HSPCs). Specifically, we show that early use of IL-12 enhanced the osteogenic differentiation of BM-MSCs through IL-12Rβ1/TYK2/STAT3 signaling; furthermore, IL-12 induced osteogenesis facilitated bone formation and irradiation hematopoiesis recovery when transplanted BM-MSCs in the femur of Balb/c mice. For the mechanism of action, we found that IL-12 receptor beta 1 (IL-12Rβ1) expression of irradiated BM-MSCs was upregulated rapidly, coincidentally consistent with early use of IL-12 induced osteogenic differentiation enhancement. IL-12Rβ1 and tyrosine kinase 2 gene (Tyk2) silencing experiments and phosphotyrosine of signal transducer and activator of transcription 3 (p-STAT3) suppression experiments indicated the IL-12Rβ1/TYK2/STAT3 signaling was essential in IL-12-induced osteogenic differentiation enhancement of BM-MSCs.

Conclusion: These findings suggested that IL-12 may exert BM-MSCs-based hematopoietic recovery by repairing osteogenic differentiation abilities damages through IL-12Rβ1/TYK2/STAT3 signaling pathway post-irradiation.
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http://dx.doi.org/10.3389/fcell.2021.729293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446663PMC
September 2021

Monoamine Oxidases Desensitize Intracellular β1AR Signaling in Heart Failure.

Circ Res 2021 Sep 17. Epub 2021 Sep 17.

Pharmacology, University of California at Davis, UNITED STATES.

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http://dx.doi.org/10.1161/CIRCRESAHA.121.319546DOI Listing
September 2021

Distantly supervised biomedical relation extraction using piecewise attentive convolutional neural network and reinforcement learning.

J Am Med Inform Assoc 2021 Sep 15. Epub 2021 Sep 15.

Department of Knowledge Graph, Baidu International Technology (Shenzhen), Shenzhen, China.

Objective: There have been various methods to deal with the erroneous training data in distantly supervised relation extraction (RE), however, their performance is still far from satisfaction. We aimed to deal with the insufficient modeling problem on instance-label correlations for predicting biomedical relations using deep learning and reinforcement learning.

Materials And Methods: In this study, a new computational model called piecewise attentive convolutional neural network and reinforcement learning (PACNN+RL) was proposed to perform RE on distantly supervised data generated from Unified Medical Language System with MEDLINE abstracts and benchmark datasets. In PACNN+RL, PACNN was introduced to encode semantic information of biomedical text, and the RL method with memory backtracking mechanism was leveraged to alleviate the erroneous data issue. Extensive experiments were conducted on 4 biomedical RE tasks.

Results: The proposed PACNN+RL model achieved competitive performance on 8 biomedical corpora, outperforming most baseline systems. Specifically, PACNN+RL outperformed all baseline methods with the F1-score of 0.5592 on the may-prevent dataset, 0.6666 on the may-treat dataset, and 0.3838 on the DDI corpus, 2011. For the protein-protein interaction RE task, we obtained new state-of-the-art performance on 4 out of 5 benchmark datasets.

Conclusions: The performance on many distantly supervised biomedical RE tasks was substantially improved, primarily owing to the denoising effect of the proposed model. It is anticipated that PACNN+RL will become a useful tool for large-scale RE and other downstream tasks to facilitate biomedical knowledge acquisition. We also made the demonstration program and source code publicly available at http://112.74.48.115:9000/.
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http://dx.doi.org/10.1093/jamia/ocab176DOI Listing
September 2021

Dual aptamer recognition-based G-quadruplex nanowires to selectively analyze cancer-derived exosomes.

Talanta 2021 Dec 29;235:122748. Epub 2021 Jul 29.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, PR China; Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, PR China. Electronic address:

Cancer-derived exosomes have emerged as a valuable biomarker for cancer diagnosis and prognosis. However, the heterogeneity of exosomes often leads to low selectivity based on the single recognition method. Given this, we have developed a dual-aptamer recognition strategy based on G-quadruplex nanowires for selective analysis of exosomes. In this work, target exosomes were first captured by CD63 aptamers modified on magnetic beads (MBs) and then combined with AS1411 aptamer, which shows high binding affinity to nucleolin when forming stable G-quadruplex structure. Then the free myc monomer can spontaneously assemble into higher order G-wire superstructures on the allosteric AS1411, and resulting enhanced fluorescence signal, which can realize sensitive and specific analysis of the target exosomes. This dual-aptamer recognition-based method is simple and universal for different types of exosomes, which is of great significance for clinical cancer diagnosis.
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http://dx.doi.org/10.1016/j.talanta.2021.122748DOI Listing
December 2021

Current Alzheimer disease research highlights: evidence for novel risk factors.

Chin Med J (Engl) 2021 Sep 9;134(18):2150-2159. Epub 2021 Sep 9.

Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.

Abstract: Alzheimer disease (AD) is the most common type of dementia characterized by the progressive cognitive and social decline. Clinical drug targets have heavily focused on the amyloid hypothesis, with amyloid beta (Aβ), and tau proteins as key pathophysiologic markers of AD. However, no effective treatment has been developed so far, which prompts researchers to focus on other aspects of AD beyond Aβ, and tau proteins. Additionally, there is a mounting epidemiologic evidence that various environmental factors influence the development of dementia and that dementia etiology is likely heterogenous. In the past decades, new risk factors or potential etiologies have been widely studied. Here, we review several novel epidemiologic and clinical research developments that focus on sleep, hypoxia, diet, gut microbiota, and hearing impairment and their links to AD published in recent years. At the frontiers of AD research, these findings and updates could be worthy of further attention.
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http://dx.doi.org/10.1097/CM9.0000000000001706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478399PMC
September 2021

Transcatheter closure for postinfarction ventricular septal defect: A meta-analysis of the current evidence.

J Card Surg 2021 Sep 9. Epub 2021 Sep 9.

Department of Cardiovascular Medicine, Sir Run Run Hospital Affiliated Nanjing Medical University, Nanjing, Jiangsu, 211166, China.

Objective: Postinfarction ventricular septal defect (PIVSD) is a severe complication of acute myocardial infarction (AMI). Transcatheter closure (TCC) is an alternative option to surgical repair. This study was undertaken to examine the published literature to provide objective evidence for TCC using a meta-analysis.

Methods: We searched for significant medical and publisher databases. Two reviewers checked the quality of the studies and extracted data. Eligible studies included single-arm studies and comparative studies. Weighted means, pooled event rates, efficacy outcomes and odds ratios (ORs) for immediate shunt reduction (ISR), presence of cardiogenic shock (CS), New York Heart Association (NYHA) class IV, time from AMI to ventricular septal defect (VSD), and time to VSD closure was estimated.

Results: A total of 27 single-arm articles (462 patients) were included. The pooled event rate was 89.7% (95% confidence interval [CI]: 0.772-1.021) for successful device implantation, 80.9% (95% CI: 0.645-0.972) for ISR, 31.5% (95% CI: 0.149-0.482) for 30-day mortality, and 25.3% (95% CI: 0.072-0.434) for 30-day mortality of primary closure at the acute phase. CS (OR = 3.607, 95% CI: 2.301-5.653), NYHA class IV (OR = 6.491, 95% CI: 1.444-29.188) and time to VSD closure were risk predictors for TCC. There was no correlation between defect size (OR = 2.592, 95% CI: 0.380-17.661) and mortality.

Conclusion: TCC should be a relatively safe and minimally invasive method for PIVSD, with an excellent successful device implantation rate and acceptable low 30-day mortality. The procedure appears promising, but its safety and efficacy could only be demonstrated by randomized controlled trials. Therefore, the mortality of data comparing surgery to TCC compels the need for future comparative trials.
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http://dx.doi.org/10.1111/jocs.15989DOI Listing
September 2021

Analysis of the immune checkpoint V-domain Ig-containing suppressor of T-cell activation (VISTA) in endometrial cancer.

Mod Pathol 2021 Sep 7. Epub 2021 Sep 7.

Department of Gynecologic Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

V-domain Ig-containing suppressor of T-cell activation (VISTA) is a novel immune checkpoint protein and a potential immunotherapeutic target. However, its expression in endometrial cancer has not been clearly defined. This study aimed to investigate VISTA expression and determine its associations with clinicopathological features, molecular subtypes, programmed cell death-ligand 1 (PD-L1) expression, CD8+ T-cell count, and survival in a cohort of 839 patients with endometrial cancer. Using direct sequencing of the polymerase epsilon (POLE) exonuclease domain and immunohistochemistry for mismatch repair (MMR) proteins and p53, we stratified endometrial cancers into four molecular subtypes: POLE ultramutated, MMR-deficient, p53-mutant, and nonspecific molecular profile (NSMP). PD-L1, CD8, and VISTA were detected via immunohistochemistry. VISTA was expressed in the immune cells of 76.6% (643/839) of the samples and in the tumor cells of 6.8% (57/839). VISTA positivity in the immune cells was frequent in tumors staged I-III, those with positive PD-L1 or high CD8+ T-cell density, and those representing POLE ultramutated and MMR-deficient subtypes. Furthermore, VISTA positivity in tumor cells was more frequent in clear cell carcinoma samples. VISTA in immune cells was associated with improved survival in the entire cohort as well as in the endometrioid histology, stage I, PD-L1-negative, MMR-deficient, MMR-proficient, and high and low number of CD8+ T-cell-infiltrated tumor subgroups. VISTA in immune cells was a prognostic factor overall, as well as in patients with endometrioid histology, independent of molecular subtype or CD8+ T-cell density. The data produced by this study, which was the largest to focus on VISTA expression in patients with endometrial cancer to date, suggest that VISTA is a predictor of improved survival.
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http://dx.doi.org/10.1038/s41379-021-00901-yDOI Listing
September 2021

Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2.

Signal Transduct Target Ther 2021 09 1;6(1):328. Epub 2021 Sep 1.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.
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http://dx.doi.org/10.1038/s41392-021-00734-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409077PMC
September 2021

Functionalized Tumor-Targeting Nanosheets Exhibiting Fe(II) Overloading and GSH Consumption for Ferroptosis Activation in Liver Tumor.

Small 2021 Oct 27;17(40):e2102046. Epub 2021 Aug 27.

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, P. R. China.

Liver tumor is difficult to cure for its high degree of malignancy and rapid progression characteristics. Ferroptosis as a new model of inducing cell death is expected to break the treatment bottleneck of liver tumors. Here, a strategy to induce ferroptosis in HepG2 cells with acid-degradable tumor targeted nanosheets Cu-Hemin-PEG-Lactose acid (Cu-Hemin-PEG-LA) is proposed. After highly ingested by HepG2 cells, Cu-Hemin-PEG-LA nanosheets are degraded by weak acid and release Cu(II) and hemin, which consuming intracellular glutathione (GSH) content and increasing the expression of heme oxygenase 1 (HMOX1) protein, respectively. Furthermore, the expression of glutathione peroxidase 4 protein (GPX4) is down-regulated by consumption intracellular GSH content via converting GSH into glutathione oxidized (GSSG), which is named the classical mode. The intracellular Fe content is overloaded by the significant up-regulation of HMOX1 expression, which is denoted as nonclassical mode. The synergistic effect of classical and nonclassical mode increased the intracellular lipid reactive oxide species, induced the occurrence of ferroptosis and up-regulated the expression of BH3 interacting domain death agonist (BID), apoptosis-inducing factor (AIF), and endonuclease G proteins (EndoG). The synergistic strategy demonstrate the excellent ferroptosis induction ability and antitumor efficacy in vivo, which provides great potential for the clinical transformation of ferroptosis.
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http://dx.doi.org/10.1002/smll.202102046DOI Listing
October 2021

Nanopore Technology for the Application of Protein Detection.

Nanomaterials (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China.

Protein is an important component of all the cells and tissues of the human body and is the material basis of life. Its content, sequence, and spatial structure have a great impact on proteomics and human biology. It can reflect the important information of normal or pathophysiological processes and promote the development of new diagnoses and treatment methods. However, the current techniques of proteomics for protein analysis are limited by chemical modifications, large sample sizes, or cumbersome operations. Solving this problem requires overcoming huge challenges. Nanopore single molecule detection technology overcomes this shortcoming. As a new sensing technology, it has the advantages of no labeling, high sensitivity, fast detection speed, real-time monitoring, and simple operation. It is widely used in gene sequencing, detection of peptides and proteins, markers and microorganisms, and other biomolecules and metal ions. Therefore, based on the advantages of novel nanopore single-molecule detection technology, its application to protein sequence detection and structure recognition has also been proposed and developed. In this paper, the application of nanopore single-molecule detection technology in protein detection in recent years is reviewed, and its development prospect is investigated.
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http://dx.doi.org/10.3390/nano11081942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400292PMC
July 2021

Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker.

Biomolecules 2021 08 12;11(8). Epub 2021 Aug 12.

Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410013, China.

Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Many recent studies have shown that integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial-mesenchymal transition, and angiogenesis. Therefore, we categorize the research related to integrin β4, starting from its structure and function in tumor tissues, and provide a basic description. Based on its structure and function, we believe that integrin β4 can be used as a tumor marker. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors.
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http://dx.doi.org/10.3390/biom11081197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394641PMC
August 2021

Citrullinated Antigens with Multiple Citrulline Similar Motif in the Diagnosis of Rheumatoid Arthritis: A Preliminary Single-Center Study.

J Immunol Res 2021 10;2021:1891519. Epub 2021 Aug 10.

Leide Biosciences Co., Ltd., Guangzhou, China.

The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946-0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.
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http://dx.doi.org/10.1155/2021/1891519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376434PMC
August 2021

Results with Floxuridine, Actinomycin D, Etoposide, and Vincristine in Gestational Trophoblastic Neoplasias with International Federation of Gynecology and Obstetrics Scores ≥5.

Oncologist 2021 Aug 16. Epub 2021 Aug 16.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Obstetrics and Gynecologic Diseases, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, People's Republic of China.

Background: 5-fluorouracil-based multiagent chemotherapy has been used as the primary treatment for high-risk gestational trophoblastic neoplasia (GTN) in China for a few decades. This study aims to assess the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who had International Federation of Gynecology and Obstetrics (FIGO) scores ≥5.

Materials And Methods: A total of 207 patients with GTN who had FIGO scores ≥5 were treated with FAEV as first-line chemotherapy at Peking Union Medical College Hospital between January 2002 and December 2017. Complete remission (CR), resistance, survival, toxicity, and reproductive outcomes were analyzed.

Results: Of the 207 patients treated with FAEV, 9 (4.3%) required a change of chemotherapy owing to toxicity and 1 (0.5%) died of cerebral hernia 5 weeks after commencing treatment. The remaining 197 patients were assessable to determine the response to FAEV; among them, 168 (85.3%) achieved CR with FAEV and 29 (14.7%) developed resistance to FAEV. The 5-year overall survival rate of the entire cohort was 97.4%. Grade 3-4 neutropenia, thrombocytopenia, and anemia occurred in 28.4%, 6.8%, and 6.2% of cycles, respectively. No acute toxicity-related deaths occurred. Five patients developed acute myeloid leukemia 10-50 months after exposure to chemotherapy; another patient developed duodenal cancer 2 years after completing therapy. Sixty-one patients who preserved fertility wanted to become pregnant; 56 of them conceived.

Conclusion: The FAEV regimen is an effective primary treatment for patients with GTN who have FIGO scores ≥5 and has predictable and manageable toxicity.

Implications For Practice: The most commonly used multiagent chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) is etoposide, methotrexate and actinomycin D/cyclophosphamide and vincristine (EMA/CO) worldwide. However, 5-fluorouracil-based multiagent chemotherapy has been used as a primary treatment for high-risk GTN in China for a few decades. This study evaluated the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who have International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. The study's data demonstrated that FAEV as a primary treatment achieved favorable outcomes for patients with FIGO scores ≥5. Toxicities that result from the FAEV regimen are predictable and manageable. The FAEV regimen may provide another option for the treatment of GTN.
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http://dx.doi.org/10.1002/onco.13943DOI Listing
August 2021

Innate lymphoid cells are double-edged swords under the mucosal barrier.

J Cell Mol Med 2021 Sep 10;25(18):8579-8587. Epub 2021 Aug 10.

Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, China.

As the direct contacting site for pathogens and allergens, the mucosal barrier plays a vital role in the lungs and intestines. Innate lymphoid cells (ILCs) are particularly resident in the mucosal barrier and participate in several pathophysiological processes, such as maintaining or disrupting barrier integrity, preventing various pathogenic invasions. In the pulmonary mucosae, ILCs sometimes aggravate inflammation and mucus hypersecretion but restore airway epithelial integrity and maintain lung tissue homeostasis at other times. In the intestinal mucosae, ILCs can increase epithelial permeability, leading to severe intestinal inflammation on the one hand, and assist mucosal barrier in resisting bacterial invasion on the other hand. In this review, we will illustrate the positive and negative roles of ILCs in mucosal barrier immunity.
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http://dx.doi.org/10.1111/jcmm.16856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435454PMC
September 2021

Structure-function elucidation of a microbial consortium in degrading rice straw and producing acetic and butyric acids via metagenome combining 16S rDNA sequencing.

Bioresour Technol 2021 Nov 3;340:125709. Epub 2021 Aug 3.

College of Engineering and Technology, Southwest University, Chongqing 400715, China.

The characterized microbial consortium can efficiently degrade rice straw to produce acetic and butyric acids in high yields. The rice straw lost 86.9% in weight and degradation rates of hemicellulose, cellulose, and lignin attained were 97.1%, 86.4% and 70.3% within 12 days, respectively. During biodegradation via fermentation of rice straw, average concentrations of acetic and butyric acids reached 1570 mg/L and 1270 mg/L, accounting for 47.2% and 35.4% of the total volatile fatty acids, respectively. The consortium mainly composed of Prevotella, Cellulosilyticum, Pseudomonas, Clostridium and Ruminococcaceae, etc. Metagenomic analyses indicated that glycoside hydrolases (GHs) were the largest enzyme group with a relative abundance of 54.5%. Various lignocellulose degrading enzymes were identified in the top 30 abundant GHs, and were primarily distributed in the dominant genera (Prevotella, Cellulosilyticum and Clostridium). These results provide a new route for the commercial recycling of rice straw to produce organic acids.
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http://dx.doi.org/10.1016/j.biortech.2021.125709DOI Listing
November 2021

[Effects of Mongolian medicine Shaosha-7 on myocardial ischemia/ reperfusion injury of rats].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 Jul;37(4):380-384

MNUMS, International School of Mongolian Medicine, Mongolian National University of Medical Sciences, Ulan Bator 999097-15160, Mongolian.

To investigate the effects of Shaosha-7 in rats with myocardial ischemia-reperfusion injury and its mechanisms. male SD rats were divided into sham operation group (=10), myocardial ischemia-reperfusion injury group (=10), low, medium and high dose of Shaosha-7 groups (=10), and positive drug group (=10). The rats of Shaosha-7 (low, medium and high dose) groups were treated with Shaosha-7 at the doses of 0.4, 0.8 and 1.6 g/kg respectively, once a day for 15 days. The rats of positive drug group were treated with 0.3 g/kg Danshen, once a day for 15 days. The rats of the sham operation group and myocardial ischemia-reperfusion injury were treated with 2 ml/100 g distilled water, once a day for 15 days. After 15 days, the rats of the model group and the treatment group underwent thoracotomy and ligation of coronary artery for 30 minutes, then thoracic cavity was closed after reperfusion. Rats in six groups were executed electrocardiographic examination and their hearts were taken for Hematoxylin-Eosin (HE) staining and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining to observe infarct area and myocardial pathological changes. The contents of cTnI, CK-MB, LDH, MDA, SOD, GSH-Px, TNF-α, IL-18, IL-6 and IL-1 β in serum were detected by ELISA. The expression of NF-кB was detected by immunohistochemistry. Compared with the sham operation group, the infarct size, the levels of cTnI, CK-MB, CK-MB, LDH, MDA, GSH-Px, TNF-α, IL-18, IL-6, IL-1β and NF-кB were increased and the content of SOD were decreased in rats with myocardial ischemia-reperfusion injury. Compared with the rats with myocardial ischemia-reperfusion injury, Shaosha-7 improved the arrhythmia and pathological changes, reduced the infarct area, decreased the contents of cTnI, CK-MB, LDH, MDA, GSH-Px, TNF-α, IL-18, IL-6, IL-1 β, increased the content of SOD, decreased the expression of NF-кB. Mongolian medicine Shaosha-7 can effectively alleviate myocardial ischemia-reperfusion injury in rats. This study provides a theoretical basis for the treatment of myocardial ischemia-reperfusion (I/R) injury with Shaosha-7.
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http://dx.doi.org/10.12047/j.cjap.6114.2021.029DOI Listing
July 2021

Rapid Naked-Eye Tracking of On-Cell Phenotype Based on Dual-Aptamer-Weaved Cascade Assembly of Nanostructures.

Anal Chem 2021 08 4;93(32):11159-11166. Epub 2021 Aug 4.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China.

Phenotypic plasticity is an emerging paradigm for providing biological and clinical insights into cancer initiation, progression, and resistance to therapy. However, it is a great challenge to track phenotypic information on live cells with high levels of sensitivity, specificity, and simplicity, when a specific cancer-cell subset is being targeted. In this work, we have successfully achieved cascade assembly of nanoparticles on the surface of specific cancer cells by designing a dual-aptamer-weaved molecular AND logic system. Taking advantage of spatial addressability, precise controllability, and targeting recognition of the nanostructure assemblies, we can precisely label the target-cell subset in a large population of similar cells and rapidly obtain phenotypic information in response to the surface changes of captured cancer cells. Without sophisticated instruments, we can know the phenotypic information on HepG2 cells in whole blood with a high level of sensitivity and rapid naked-eye tracking of on-cell phenotype changes of HepG2 cells undergoing epithelial-mesenchymal transition.
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http://dx.doi.org/10.1021/acs.analchem.1c01668DOI Listing
August 2021

Effects of hyperbaric oxygen therapy on postoperative recovery after incomplete cervical spinal cord injury.

Spinal Cord 2021 Jul 29. Epub 2021 Jul 29.

People's Liberation Army Hangzhou Sanatorium, Hangzhou, China.

Study Design: A retrospective study of incomplete cervical spinal cord injury (SCI) treated with and without hyperbaric oxygen (HBO) therapy after operation.

Objective: To investigate the effects of hyperbaric oxygen therapy on patients' postoperative recovery after incomplete cervical spinal cord injury.

Setting: Shulan Hangzhou Hospital, Hangzhou, China.

Methods: We analyzed the clinical data of 78 patients admitted in the Orthopedic Department of our hospital from June 2014 to June 2016, due to trauma-induced incomplete cervical spinal cord injury. All study subjects underwent nerve decompression and internal fixation procedures within 2 weeks of injury. The patients were divided into hyperbaric oxygen therapy (HBO) group (n = 40) and non-hyperbaric oxygen therapy (NHBO) group (n = 38) according to the chosen treatment option. The NHBO group only receive the conventional treatment regimen while the HBO group received a combination of conventional treatment and hyperbaric oxygen therapy. The subsequent changes in spinal functions and activities of daily living (ADL) were assessed by The American Spinal Injury Association (ASIA) scale and the Barthel Index at different time points (pretreatment, 1 month and 3 months of treatment, as well as 6 months, 1 year, 2 years, and 3 years after the surgical procedure).

Results: There were no significant differences in age, gender, injury site, and disease condition between patients (p > 0.05). The results showed a significant difference in treatment total effectiveness rate between the HBO and NHBO groups (p < 0.05) (90% and 78.9%, respectively). Analyses of the ASIA scores and Barthel indices between the two groups indicated significant differences at 1 month and 3 months treatment time points, as well as 6 months and 1 year after the initial operation (p < 0.05). It showed that subjects in the HBO group had a better recovery than their NHBO counterparts, with the 1-month treatment time point being the most significant. In addition, the results indicated significant improvements in Barthel Index scores as well as ASIA sensory and motor function scores in both groups after a 1-month treatment, with the HBO group faring significantly better than the NHBO group (p < 0.01).

Conclusions: Our results not only showed that hyperbaric oxygen therapy is safe and effective for the treatment of incomplete cervical spinal cord injury but also indicated that the longer the treatment lasts (therapy initiation within 3 months after the surgical operation), the better the effects. In addition, a correct hyperbaric oxygen therapy leads to a peak in recovery within the first postoperative 3 months and can effectively promote spinal cord functions, reduce the disabilities, and improve patients' quality of life.
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http://dx.doi.org/10.1038/s41393-021-00674-wDOI Listing
July 2021

Foldable Glistening-Free Acrylic Intraocular Lens Biomaterials with Dual-Side Heterogeneous Surface Modification for Postoperative Endophthalmitis and Posterior Capsule Opacification Prophylaxis.

Biomacromolecules 2021 08 21;22(8):3510-3521. Epub 2021 Jul 21.

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

Hydrophobic acrylic intraocular lenses (IOLs) are widely used in cataract treatment for posterior capsule opacification (PCO) prophylaxis. However, undesired glistening and postoperative endophthalmitis are two major potential risks. Hence, a series of poly(2-phenoxyethyl methacrylate--2-phenoxyethyl acrylate--2-ethylhexyl methacrylate) (PPPE) acrylic IOL materials were synthesized for "glistening-free" optimization. The selected PPPE with 2% 2-ethylhexyl methacrylate showed excellent optical, foldable, and thermomechanical properties. The anterior surface of PPPE was coated with polydopamine followed by gentamycin conjugation (PDA/GS). It inhibited bacterial adhesion by 74% and decreased the biofilm thickness by 87%. In inflammatory mimicking conditions, bacterial proliferation was restrained, with acidic-dependent GS release behavior. The surface of PPPE toward the posterior capsule remained hydrophobic. It was conducive to human lens epithelial cell adhesion, collagen IV and fibronectin adsorption, and the following "sealed sandwich structure" formation. In summary, the PPPE with a dual-side heterogeneous surface displayed good application prospects in postoperative endophthalmitis and PCO prevention.
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http://dx.doi.org/10.1021/acs.biomac.1c00582DOI Listing
August 2021
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