Publications by authors named "Li Song"

2,235 Publications

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Comprehensive Proteomic Profiling of Aqueous Humor Proteins in Proliferative Diabetic Retinopathy.

Transl Vis Sci Technol 2021 May;10(6)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Purpose: Proliferative diabetic retinopathy (PDR) is a serious ocular disease that can lead to retinal microvascular complications in patients with diabetes mellitus. To date, no studies have explored PDR development by analyzing the aqueous humor (AH). Therefore we carried out tandem mass tag (TMT) proteomic quantification to compare AH protein profiles between PDR and non-PDR subjects.

Methods: We enrolled six PDR and six control (senile cataract) subjects. AH samples were collected during surgery and stored at -80°C. Proteins were extracted, trypsin-digested, and labeled with TMTs for mass spectrometric analysis.

Results: We found 191 proteins to be changed with |log2 (fold change)| ≥1 (P < 0.05 and identification with at least two peptides per protein). Of them, 111 were downregulated, whereas 80 were upregulated in the PDR group. Proteomic bioinformatic analysis indicated that PDR development was related to complement and coagulation cascades, platelet activation, extracellular matrix-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection, PI3K-Akt signaling pathway, cholesterol metabolism, peroxisome proliferator-activated receptor signaling pathways, fat digestion and absorption, and vitamin digestion and absorption pathways.

Conclusions: Comprehensive proteomic profiling of the AH revealed 191 differentially expressed proteins between the two groups. Most of these proteins belong to secretory pathways, and therefore can be used as biomarkers in clinical testing and basic research.

Translational Relevance: Pathway analysis and a review of the literature enabled us to draw a novel biological map that will support further studies on the underlying mechanisms and therapeutic control of PDR development.
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http://dx.doi.org/10.1167/tvst.10.6.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107506PMC
May 2021

Exosomes Promote Pre-Metastatic Niche Formation in Gastric Cancer.

Front Oncol 2021 24;11:652378. Epub 2021 May 24.

Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Gastric cancer has a high rate of metastasis, during which pre-metastatic niches (PMN) provide a supportive environment for the upcoming tumor cells. Exosomes are bilayer vesicles secreted by cells containing biological information that mediates communication between cells. Using exosomes, gastric cancer cells establish PMN remotely in multifarious perspectives, including immunosuppression, stroma remodeling, angiogenesis, mesothelial mesenchymal transformation, and organotropism. In turn, the cell components in PMN secrete exosomes that interact with each other and provide onco-promoting signals. In this review, we highlight the role of exosomes in PMN formation in gastric cancer and discuss their potential values in gastric cancer metastasis diagnosis, prevention, and treatment.
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http://dx.doi.org/10.3389/fonc.2021.652378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180914PMC
May 2021

Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis.

Ther Adv Med Oncol 2021 29;13:17588359211018537. Epub 2021 May 29.

Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, China.

Background: Although immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC), a lack of direct comparisons of various first-line treatments is clouding clinical decision-making. A network meta-analysis was conducted to compare current first-line treatments and identify the optimal regimen for patients with specific characteristics.

Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, Clinical Trials databases were searched from inception to 31 July 2020. Phase II/III randomized controlled trials (RCTs) comparing first-line treatments including chemotherapy, anti-angiogenesis, ICIs, and their combinations for previously untreated stage IIIB/IV or recurrent driver-gene wild-type NSCLC patients were included.

Results: Twenty-six RCTs were identified and included, involving 16,977 patients and a total of 18 regimens. ICI-containing treatments led to significantly prolonged overall survival (OS) compared with ICI-free treatments (0.82, 0.72-0.93). ICI plus chemotherapy had significantly longer progression-free survival (PFS; 0.70, 0.58-0.86) and marginally longer OS (0.90, 0.79-1.05) compared with ICIs alone. Ranking highest in the Bayesian network meta-analysis, pembrolizumab plus chemotherapy, nivolumab plus ipilimumab and chemotherapy, had significantly superior OS than standard chemotherapy with or without bevacizumab treatments. Pembrolizumab-chemotherapy ranked first for OS, 1-year OS rate, and subgroups of non-squamous, PD-L1 ⩾1%, non-smoking, and liver metastasis; while nivolumab-ipilimumab-chemotherapy for squamous, PD-L1 <1%, brain metastasis NSCLC. Furthermore, the ICI-containing bevacizumab-free treatments, such as pembrolizumab plus chemotherapy, nivolumab and ipilimumab with or without chemotherapy, were not significantly different from atezolizumab plus chemotherapy and bevacizumab in OS.

Conclusions: A combination of ICIs with chemotherapy, rather than double ICIs, is the best first-line treatment for advanced wild-type NSCLC, with synergy that leads to better long-term survival. The panoramic view of the relative efficacy of any two regimens with different rankings provides strong evidence for selecting optimal first-line ICIs according to patients' clinical characteristics.
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http://dx.doi.org/10.1177/17588359211018537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165528PMC
May 2021

Repeated 3,3-Dimethyl-1-butanol exposure alters social dominance in adult mice.

Neurosci Lett 2021 Jun 9:136006. Epub 2021 Jun 9.

Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Neurophysiology, Hebei Medicinal University, Shijiazhuang 050017, China; Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medicinal University, Shijiazhuang 050017, China; Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang 050017, China. Electronic address:

The influence of gut microbiota on brain function and brain disorders has been attracted more and more attention. Trimethylamine N-oxide (TMAO), an indirect metabolite of gut microbiota, has been linked to aging, cognitive impairment, and other brain disorders. However, the relationship between TMAO and social behaviors are still poorly understood. Adult male mice were exposed to drinking water containing 3,3- Dimethyl-1-butanol (DMB), an indirect inhibitors of TMAO, for 21 continuous days followed by a series of behavioral tests to detect the effect of DMB exposure on social behaviors, mainly including social dominance test (SDT), bedding preference test (BP), sexual preference test (SP), social interaction test (SI), open field test (OFT), tail suspension test (TST), forced swim test (FST), novelty suppressed feeding test (NSF), and novel object recognition (NOR) task. In the SDT, compared with the control group, the mice treated with DMB (both 0.2% and 1.0%), both high-ranked and low-ranked mice, showed a reduction in the number of victories. There is no statistical difference on sexual preference, anxiety, depression-like behavior phenotype, and memory formation. In conclusion, the present findings provide direct evidence, for the first time, that repeated DMB exposure produces significant effects on social dominance of adult mice, without any effects on sexual preference, anxiety, depression-like behavior phenotype or memory formation, highlighting the regulatory effects of gut-brain interaction on social behaviors.
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http://dx.doi.org/10.1016/j.neulet.2021.136006DOI Listing
June 2021

Cyclic Adenosine Monophosphate-Enhanced Calvarial Regeneration by Bone Marrow-Derived Mesenchymal Stem Cells on a Hydroxyapatite/Gelatin Scaffold.

ACS Omega 2021 Jun 17;6(21):13684-13694. Epub 2021 May 17.

Stomatological Hospital and College, Key Lab. of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, Anhui 230032, China.

Cyclic adenosine monophosphate (cAMP) plays a significant role in inducing new bone formation by mediating various signal pathways. However, cAMP, combined with biomaterials, is rarely investigated to reconstruct calvarial defects. In this study, cAMP was loaded into a hydroxyapatite (HA)/gelatin (Gel) construct and implanted into critical skull defects in rats to evaluate the potential for enhancing skull regeneration. The physiochemical characteristics, the biocompatibility of Gel and HA/Gel scaffolds, and the regenerated bone tissue were assessed. The resulting HA/Gel scaffolds possessed a 3D interconnected porous structure with extensively distributed HA crystals and favorable physiochemical properties. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) within the HA/Gel scaffold showed greater biocompatibility. Compared with the Gel and HA/Gel groups, the cAMP-HA/Gel group revealed the highest bone density, more mature mineralized tissue, and more favorable integration between the new bone and inherent bone as analyzed by cone beam computed tomography and hematoxylin & eosin and Masson staining, respectively. Collectively, our study verified HA/Gel scaffolds as a prospective biomimetic treatment with biocompatibility and the therapeutic potential of cAMP in promoting new bone growth of a skull, which indicates its promise as a growth factor for bone tissue engineering.
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http://dx.doi.org/10.1021/acsomega.1c00881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173563PMC
June 2021

Theoretical investigation of the low lying electronic states of MgGa.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 23;261:119991. Epub 2021 May 23.

School of Physics and Optoelectronic Engineering, Yangtze University, Jingzhou, China. Electronic address:

In this work, we investigate the low-lying electronic states correlated to the first and the second dissociation channels of MgGa molecule, neglecting and including the spin-orbit coupling effect. High-level ab initio calculations have been performed by using the icMRCI + Q method. Potential energy curves, spectroscopic constants, electron configurations and dipole moments are derived and discussed. Molecular structures of several magnesium-group 13 diatomics have been probed and analyzed. Information associated with transition dipole moments, Franck-Condon factors, vibrational branching ratios and radiative lifetimes between the Ω states are also well characterized. It is anticipated this work will provide some inspiration for further studies on MgGa.
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http://dx.doi.org/10.1016/j.saa.2021.119991DOI Listing
May 2021

Substrate Stiffness Regulates Cholesterol Efflux in Smooth Muscle Cells.

Front Cell Dev Biol 2021 18;9:648715. Epub 2021 May 18.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

The infiltration and deposition of cholesterol in the arterial wall play an important role in the initiation and development of atherosclerosis. Smooth muscle cells (SMCs) are the major cell type in the intima. Upon exposure to cholesterol, SMCs may undergo a phenotype switching into foam cells. Meanwhile, the pathological processes of the blood vessel such as cholesterol deposition and calcification induce the changes in the substrate stiffness around SMCs. However, whether substrate stiffness affects the cholesterol accumulation in SMCs and the formation of foam cells is not well-understood. In this study, SMCs were cultured on the substrates with different stiffnesses ranging from 1 to 100 kPa and treated with cholesterol. We found that cholesterol accumulation in SMCs was higher on 1 and 100 kPa substrates than that on intermediate stiffness at 40 kPa; consistently, total cholesterol (TC) content on 1 and 100 kPa substrates was also higher. As a result, the accumulation of cholesterol increased the expression of macrophage marker CD68 and downregulated SMC contractile marker smooth muscle α-actin (ACTA2). Furthermore, the mRNA and protein expression level of cholesterol efflux gene ATP-binding cassette transporter A1 (ABCA1) was much higher on 40 kPa substrate. With the treatment of a liver X receptor (LXR) agonist GW3965, the expression of ABCA1 increased and cholesterol loading decreased, showing an additive effect with substrate stiffness. In contrast, inhibition of LXR decreased ABCA1 gene expression and increased cholesterol accumulation in SMCs. Consistently, when ABCA1 gene was knockdown, the cholesterol accumulation was increased in SMCs on all substrates with different stiffness. These results revealed that substrate stiffness played an important role on SMCs cholesterol accumulation by regulating the ABCA1 expression. Our findings on the effects of substrate stiffness on cholesterol efflux unravel a new mechanism of biophysical regulation of cholesterol metabolism and SMC phenotype, and provide a rational basis for the development of novel therapies.
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http://dx.doi.org/10.3389/fcell.2021.648715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168435PMC
May 2021

Preliminary Study of microRNAs Allele-Specific Targeting in Allergic Rhinitis Patients from Central China.

Comb Chem High Throughput Screen 2021 Jun 3. Epub 2021 Jun 3.

Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, China.

Background: Abnormal expression of miRNA is a common feature in many diseases. Some studies have also emphasized that miRNAs play an important role in asthma and allergic rhinitis (AR). This study attempts to reveal the differences between miRNAs expression and normal nasal mucosa in AR patients by microarray method, so as to further understand the molecular mechanism of AR development.

Method: MiRNA microrrays were used for analyzing six samples of the nasal mucosa of AR and six samples of nonallergic patients. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of some differentially expressed miRNAs was used to confirm the array results. Furthermore, pathway analysis was carried out.

Results: The microarray identified that 64 miRNAs exhibited altered expression in the nasal mucosa of the AR group when compared with the control group. Moreover, the expression levels of ten miRNAs were significantly altered in the AR group. To verify the results of the microarray, three differentially expressed miRNA were determined by RT-PCR, and the results also confirmed these changes. Ten differentially expressed miRNAs were present in the nasal mucosa of AR patients compared with the control group, and three differentially expressed miRNAs, as miR-1244, miR-4651 and miR-7641, were determined by RT-PCR, indicating that they play important roles in the process of AR.

Conclusion: miR-1244, miR-4651 and miR-7641 may play important roles in the process of AR. Sequencing analysis indicated that three kinds of mutations exist in MAPK8 3'UTR, which may play a role in binding with miR-7641, and then influence the AR process. Single miRNA or, more probably, their sets hold the promise for their use as biomarkers of allergic rhinitis. They may also be promising targets in future therapies.
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http://dx.doi.org/10.2174/1386207324666210603112727DOI Listing
June 2021

Hypoxia-induced antizyme inhibitors 2 regulates cisplatin resistance through epithelia-mesenchymal transition pathway in non-small cell lung cancer.

Pulm Pharmacol Ther 2021 May 31;69:102048. Epub 2021 May 31.

Department of Oncology, Fujian Fuzhou Pulmonary Hospital, No. 2 Shangdu Hubian, Cangshan District, Fuzhou, 350000, Fujian, China. Electronic address:

Antizyme inhibitors 2 (AZIN2) was found to be associated with poor prognosis of patients with rectal cancer. However, no studies have reported whether AZIN2 functions in non-small cell lung cancer (NSCLC). This study aimed to investigate the role of AZIN2 in cisplatin (DDP) resistance in NSCLC. We established DDP resistant A549 and H1299 cell lines. The transcriptional and translational expression levels were examined using quantitative real-time polymerase chain reaction and western blot. Cell apoptosis was evaluated by caspase-3 activity and nucleosome ELISA assays. Luciferase reporter assay was employed to evaluate the impact of hypoxia-inducible factor (HIF-1α) on AZIN2 transcription. AZIN2 expression was found to be associated with DDP resistance and poor prognosis in patients with NSCLC. AZIN2 overexpression promoted cell viability, colony formation, and reduced cell apoptosis in H1299 cells and A549 upon DDP treatment. Correspondingly, AZIN2 knockdown significantly inhibited cell viability and colony formation, and increased cell apoptosis upon DDP treatment. Interestingly, AZIN2 expression in NSCLC cells was significantly induced by hypoxia condition. The occupancy of HIF-1α, an important regulator of the hypoxia response, remarkably enriched at the promoter region of AZIN2 under hypoxia condition. In addition, AZIN2 overexpression resulted in epithelial-mesenchymal transition (EMT). The results suggested that hypoxia-induced AZIN2 high expression may contribute to DDP resistance development by promoting the EMT.
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http://dx.doi.org/10.1016/j.pupt.2021.102048DOI Listing
May 2021

CXCL1 Regulated by miR-302e Is Involved in Cell Viability and Motility of Colorectal Cancer Inhibiting JAK-STAT Signaling Pathway.

Front Oncol 2020 17;10:577229. Epub 2021 May 17.

Department of Oncology, The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.

Purpose: This study made a systemic description for the CXCL1-dependent regulatory mechanism in colorectal cancer (CRC).

Methods: Bioinformatics methods were applied to obtain target mRNA CXCL1 and corresponding upstream miRNA. qRT-PCR and Western blot were performed to measure the levels of CXCL1 and miR-302e in CRC tissue and cells. Experiments including CCK-8, wound healing assay, Transwell invasion assay, and flow cytometry were conducted to assess cell biological behaviors. Dual-luciferase reporter assay was carried out for verification of the targeting relationship between CXCL1 and miR-302e. The inhibitor AG490 of JAK-STAT signaling pathway was used to identify the functional mechanism of CXCL1/JAK-STAT underlying progression of CRC, and tumor xenograft experiments were performed for further validation.

Results: CXCL1 was highly expressed in CRC tissue and cells, while miR-302e was poorly expressed. Silencing CXCL1 or overexpressing miR-302e could lead to inhibition of cell proliferation, migration, invasion but promotion of cell apoptosis of CRC. Besides, CXCL1 was identified as a direct target of miR-302e, and CXCL1 could reverse the effect of miR-302e on cell proliferation, migration, invasion, and apoptosis. Furthermore, CXCL1 functioned on CRC cell biological behaviors activation of JAK-STAT signaling pathway.

Conclusion: CXCL1 could be regulated by miR-302e to inactivate JAK-STAT signaling pathway, in turn affecting cell proliferation, migration, invasion, and apoptosis of CRC. Our result provides a potential therapeutic target for CRC treatment.
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http://dx.doi.org/10.3389/fonc.2020.577229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166233PMC
May 2021

Immune-related gene expression signatures in colorectal cancer.

Oncol Lett 2021 Jul 20;22(1):543. Epub 2021 May 20.

R&D Department, Huaxia Bangfu Technology Incorporated, Beijing 100000, P.R. China.

The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (), amyloid β precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with 'adaptive immune responses', 'innate immune responses' and 'cytokine signaling'. The survival analysis found that a high level of expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy.
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http://dx.doi.org/10.3892/ol.2021.12804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157333PMC
July 2021

Advances in aptamer screening and aptasensors' detection of heavy metal ions.

J Nanobiotechnology 2021 Jun 1;19(1):166. Epub 2021 Jun 1.

Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou, 412007, China.

Heavy metal pollution has become more and more serious with industrial development and resource exploitation. Because heavy metal ions are difficult to be biodegraded, they accumulate in the human body and cause serious threat to human health. However, the conventional methods to detect heavy metal ions are more strictly to the requirements by detection equipment, sample pretreatment, experimental environment, etc. Aptasensor has the advantages of strong specificity, high sensitivity and simple preparation to detect small molecules, which provides a new direction platform in the detection of heavy metal ions. This paper reviews the selection of aptamers as target for heavy metal ions since the 21th century and aptasensors application for detection of heavy metal ions that were reported in the past five years. Firstly, the selection methods for aptamers with high specificity and high affinity are introduced. Construction methods and research progress on sensor based aptamers as recognition element are also introduced systematically. Finally, the challenges and future opportunities of aptasensors in detecting heavy metal ions are discussed.
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http://dx.doi.org/10.1186/s12951-021-00914-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171055PMC
June 2021

HCl-Based Hydrothermal Etching Strategy toward Fluoride-Free MXenes.

Adv Mater 2021 May 31:e2101015. Epub 2021 May 31.

National Synchrotron Radiation Laboratory, CAS Center for Excellence in Nanoscience, University of Science and Technology of China, Hefei, Anhui, 230029, P. R. China.

Due to their ultrathin layered structure and rich elemental variety, MXenes are emerging as a promising electrode candidate in energy generation and storage. MXenes are generally synthesized via hazardous fluoride-containing reagents from robust MAX materials, unfortunately resulting in plenty of inert fluoride functional groups on the surface that noticeably decline their performance. Density functional theory calculations are used to show the etching feasibility of hydrochloric acid (HCl) on various MAX phases. Based on this theoretical guidance, fluoride-free Mo C MXenes with high efficiency about 98% are experimentally demonstrated. The Mo C electrodes produced by this process exhibit high electrochemical performance in supercapacitors and sodium-ion batteries owing to the chosen surface functional groups created via the HCl etch process. This strategy enables the development of fluoride-free MXenes and opens a new window to explore their potential in energy-storage applications.
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http://dx.doi.org/10.1002/adma.202101015DOI Listing
May 2021

Upregulation of lnc-ZNF281 Inhibits the Progression of Glioma via the AKT/GSK-3/-Catenin Signaling Pathway.

J Immunol Res 2021 11;2021:5573071. Epub 2021 May 11.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, China.

The purpose of this study is to elucidate the roles and potential underlying mechanisms of long noncoding RNA lnc-ZNF281 in glioma. We performed qRT-PCR to detect the expression levels of lnc-ZNF281 in glioma tissues. The effects of lnc-ZNF281 on the proliferative and migrative abilities of T98G and HS683 glioma cells were examined by cell proliferation assay, colony formation assay, wound-healing assay, and transwell assay. Also, the effects of lnc-ZNF281 on AKT/GSK-3/-catenin pathway were analyzed. The results showed that the expression of lnc-ZNF281 in glioma tissues was decreased compared with normal tissues. lnc-ZNF281 overexpression inhibited the proliferative and migrative abilities of glioma cells, while lnc-ZNF281 knockdown obtained the opposite findings. Besides, overexpression of lnc-ZNF281 in glioma cells inactivated the AKT/GSK-3/-catenin signaling pathway. Furthermore, -catenin activation reversed the suppressive effects of lnc-ZNF281 on glioma cells. Taken together, lnc-ZNF281 inhibits glioma cell proliferation and migration via AKT/GSK-3/-catenin pathway and may serve as a potential target for glioma treatment.
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http://dx.doi.org/10.1155/2021/5573071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131163PMC
May 2021

Reply to the Letter to the Editor.

J Card Surg 2021 May 28. Epub 2021 May 28.

Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

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http://dx.doi.org/10.1111/jocs.15675DOI Listing
May 2021

Phylogenetic and morphological significance of an overlooked flying squirrel (Pteromyini, Rodentia) from the eastern Himalayas with the description of a new genus.

Zool Res 2021 Jul;42(4):389-400

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.

The flying squirrels (Pteromyini, Rodentia) are the most diverse and widely distributed group of gliding mammals. Taxonomic boundaries and relationships within flying squirrels remain an area of active research in mammalogy. The discovery of new specimens of ( ) Thomas, 1921 previously considered a synonym of , in Yunnan Province, China allowed a morphological and genetic reassessment of the status of this taxon. Phylogenetic reconstruction was implemented using sequences of two mitochondrial (12S ribosomal DNA and 16S ribosomal DNA) and one nuclear (interphotoreceptor retinoid-binding protein) gene fragments. Morphological assessments involved examinations of features preserved on skins, skulls, and penises of museum specimens, supplemented with principal component analysis of craniometric data. Together these assessments revealed that this taxon should be recognized not only as a distinct species, and should also be placed within a new genus, described here as .
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.039DOI Listing
July 2021

Effects of dissolved oxygen on the sludge dewaterability and extracellular polymeric substances distribution by bioleaching.

Chemosphere 2021 May 17;281:130906. Epub 2021 May 17.

School of Environment, Henan Normal University, China.

Bioleaching is a biological conditioning technology for sludge, which not only improves sludge dewatering performance but also removes heavy metals from sludge. As the bioleaching process is a comprehensive biological and chemical process, it is necessary to explore the effects of dissolved oxygen (DO) concentrations on bioleaching efficiency. Three bioleaching experiments with different DO concentrations (T1: 0.8-3.1 mg/L, T2: 3.1-5.5 mg/L, T3: 5.5-7.5 mg/L) were conducted for five days. The sludge dewatering efficiency was evaluated using capillary suction time (CST) and specific resistance to filtration (SRF). The relationship between sludge dewaterability and extracellular polymeric substance (EPS) fraction distribution was investigated. In the treatment with the highest DO concentration, the minimum values of SRF and CST were 4.31 × 10 m/kg and 13.5 s, which occurred earlier than the treatment with the lower DO concentrations by approximately 24-48 h. A significant decrease (83.4-93.2%) in tightly bound EPS (TB-EPS) protein (PN) was observed in all treatments, while a positive correlation (r = 0.924, P < 0.01) was observed between SRF and PN content in TB-EPS. A relatively higher abundance of Acidithiobacillus was found with the increase in DO concentration. Additionally, other genera including Metallibacterium, Alicyclobacillus, Acidibacter, Acidocella, and Luteococcus also played important roles in EPS biodegradation. These results revealed that increasing the DO concentration could improve sludge dewatering performance and heavy metal removal by enhancing bioleaching microbial activity, the degradation of PN in TB-EPS, and sludge floc fragmentation, but only if sufficient energy sources were provided.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130906DOI Listing
May 2021

Role of non-coding RNAs in plant immunity.

Plant Commun 2021 May 20;2(3):100180. Epub 2021 Mar 20.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Rice Research Institute, Sichuan Agricultural University at Wenjiang, Chengdu, Sichuan 611130, China.

Crops are exposed to attacks by various pathogens that cause substantial yield losses and severely threaten food security. To cope with pathogenic infection, crops have elaborated strategies to enhance resistance against pathogens. In addition to the role of protein-coding genes as key regulators in plant immunity, accumulating evidence has demonstrated the importance of non-coding RNAs (ncRNAs) in the plant immune response. Here, we summarize the roles and molecular mechanisms of endogenous ncRNAs, especially microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in plant immunity. We discuss the coordination between miRNAs and small interfering RNAs (siRNAs), between lncRNAs and miRNAs or siRNAs, and between circRNAs and miRNAs in the regulation of plant immune responses. We also address the role of cross-kingdom mobile small RNAs in plant-pathogen interactions. These insights improve our understanding of the mechanisms by which ncRNAs regulate plant immunity and can promote the development of better approaches for breeding disease-resistant crops.
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http://dx.doi.org/10.1016/j.xplc.2021.100180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132121PMC
May 2021

Impact of Postprocedural High-Sensitivity C-Reactive Protein on Lipoprotein(a)-Associated Cardiovascular Risk with ST-Segment Elevation Myocardial Infarction With Percutaneous Coronary Intervention.

Am J Cardiol 2021 Jul 15;150:8-14. Epub 2021 May 15.

Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

This study aimed to investigate the impact of high-sensitivity C-reactive protein (hsCRP) on Lipoprotein(a) [Lp(a)] associated cardiovascular risk in patients with ST-segment elevation myocardial infarction (STEMI) underwent percutaneous coronary intervention (PCI). A total of 2318 STEMI-PCI patients were retrospectively recruited, and further stratified based on postprocedural hsCRP levels (≥ 2 vs < 2 mg/L). Major adverse cardiac events (MACE) were defined as all-cause death, myocardial infarction and stroke. During a mean follow-up of 2.5 years, MACE occurred in 159 (6.9%) patients. In the setting of hsCRP ≥ 2mg/L, per unit increase of Lp(a) was associated with a 28% increase of MACE risk (HR: 1.28, 95% CI: 1.09 to 1.49, p = 0.002; p = 0.031 for interaction); increasing tertiles of Lp(a) were significantly related to greater rates of MACE (p = 0.011 for interaction; p = 0.005 for trend across tertiles). Patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.034) when hsCRP ≥ 2mg/L. No similar association between Lp(a) and MACE was noted when hsCRP < 2mg/L. In conclusion, high Lp(a) levels were associated with poor prognosis when hsCRP ≥ 2mg/L, implying systemic inflammation can modulate Lp(a)-associated MACE risk in STEMI-PCI patients. Measurement of Lp(a) in patients with high inflammation risk may identify individuals at high cardiovascular risk.
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http://dx.doi.org/10.1016/j.amjcard.2021.03.038DOI Listing
July 2021

VMAF Oriented Perceptual Coding Based on Piecewise Metric Coupling.

IEEE Trans Image Process 2021 20;30:5109-5121. Epub 2021 May 20.

It has been recognized that videos have to be encoded in a rate-distortion optimized manner for high coding performance. Therefore, operational coding methods have been developed for conventional distortion metrics such as Sum of Squared Error (SSE). Nowadays, with the rapid development of machine learning, the state-of-the-art learning based metric Video Multimethod Assessment Fusion (VMAF) has been proven to outperform conventional ones in terms of the correlation with human perception, and thus deserves integration into the coding framework. However, unlike conventional metrics, VMAF has no specific computational formulas and may be frequently updated by new training data, which invalidates the existing coding methods and makes it highly desired to develop a rate-distortion optimized method for VMAF. Moreover, VMAF is designed to operate at the frame level, which leads to further difficulties in its application to today's block based coding. In this paper, we propose a VMAF oriented perceptual coding method based on piecewise metric coupling. Firstly, we explore the correlation between VMAF and SSE in the neighborhood of a benchmark distortion. Then a rate-distortion optimization model is formulated based on the correlation, and an optimized block based coding method is presented for VMAF. Experimental results show that 3.61% and 2.67% bit saving on average can be achieved for VMAF under the low_delay_p and the random_access_main configurations of HEVC coding respectively.
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http://dx.doi.org/10.1109/TIP.2021.3078622DOI Listing
May 2021

BEZ235 Increases the Sensitivity of Hepatocellular Carcinoma to Sorafenib by Inhibiting PI3K/AKT/mTOR and Inducing Autophagy.

Biomed Res Int 2021 16;2021:5556306. Epub 2021 Apr 16.

Medical School, Anhui University of Science & Technology, Huainan 232001, China.

Acquired resistance of hepatocellular carcinoma (HCC) to sorafenib (SFB) is the main reason for the failure of SFB treatment of the cancer. Abnormal activation of the PI3K/AKT/mTOR pathway is important in the acquired resistance of SFB. Therefore, we investigated whether BEZ235 (BEZ) could reverse acquired sorafenib resistance by targeting the PI3K/mTOR pathway. A sorafenib-resistant HCC cell line Huh7 was established. MTT assay, clone formation assay, flow cytometry, and immunofluorescence were used to analyze the effects of BEZ235 alone or combined with sorafenib on cell proliferation, cell cycle, apoptosis, and autophagy of Huh7 and Huh7 cells. The antitumor effect was evaluated in animal models of Huh7 xenografts . Western blot was used to detect protein levels of the PI3K/AKT/mTOR pathway and related effector molecules. results showed that the Huh7 had a stronger proliferation ability and antiapoptosis effect than did Huh7, and sorafenib had no inhibitory effect on Huh7. SFB + BEZ inhibited the activation of the PI3K/AKT/mTOR pathway caused by sorafenib. Moreover, SFB + BEZ inhibited the proliferation and cloning ability, blocked the cell cycle in the G0/G1 phase, and promoted apoptosis in the two cell lines. The autophagy level in Huh7 cells was higher than in Huh7 cells, and BEZ or SFB + BEZ further promoted autophagy in the two cell lines. , SFB + BEZ inhibited tumor growth by inducing apoptosis and autophagy. We concluded that BEZ235 enhanced the sensitivity of sorafenib through suppressing the PI3K/AKT/mTOR pathway and inducing autophagy. These observations may provide the experimental basis for sorafenib combined with BEZ235 in trial treatment of HCC.
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http://dx.doi.org/10.1155/2021/5556306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079203PMC
April 2021

Roles of Toll-Like Receptor 3 in Human Tumors.

Front Immunol 2021 27;12:667454. Epub 2021 Apr 27.

Department of Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, China.

Toll-like receptor 3 (TLR3) is an important member of the TLR family, which is an important group of pathogen-associated molecular patterns. TLR3 can recognize double-stranded RNA and induce activation of NF-κB and the production of type I interferons. In addition to its immune-associated role, TLR3 has also been detected in some tumors. However TLR3 can play protumor or antitumor roles in different tumors or cell lines. Here, we review the basic signaling associated with TLR3 and the pro- or antitumor roles of TLR3 in different types of tumors and discuss the possible reasons for the opposing roles of TLR3 in tumors.
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http://dx.doi.org/10.3389/fimmu.2021.667454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111175PMC
April 2021

TRUST4: immune repertoire reconstruction from bulk and single-cell RNA-seq data.

Nat Methods 2021 Jun 13;18(6):627-630. Epub 2021 May 13.

Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

We introduce the TRUST4 open-source algorithm for reconstruction of immune receptor repertoires in αβ/γδ T cells and B cells from RNA-sequencing (RNA-seq) data. Compared with competing methods, TRUST4 supports both FASTQ and BAM format and is faster and more sensitive in assembling longer-even full-length-receptor repertoires. TRUST4 can also call repertoire sequences from single-cell RNA-seq (scRNA-seq) data without V(D)J enrichment, and is compatible with both SMART-seq and 5' 10x Genomics platforms.
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http://dx.doi.org/10.1038/s41592-021-01142-2DOI Listing
June 2021

LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway.

Mol Med Rep 2021 Jul 13;24(1). Epub 2021 May 13.

Medical School, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China.

Liver cancer remains one of the leading causes of cancer deaths worldwide. The therapeutic effect of oxaliplatin on liver cancer is often limited by acquired resistance of the cancer cells. Abnormal activation of the PI3K/AKT pathway plays an important role in the acquired resistance of oxaliplatin. The present study investigated the effects of the PI3K inhibitor LY‑294002 and AKT inhibitor MK2206 on the chemosensitivity of oxaliplatin‑resistant liver cancer cells and the molecular mechanism involved. An oxaliplatin‑resistant liver cancer cell line HepG2 was developed. MTT assay, clone formation experiments, flow cytometry and Annexin V‑FITC/PI staining were used to determine the proliferation, cycle and apoptosis of HepG2 cells when oxaliplatin was combined with LY‑294002 or MK2206 treatment. The effects of LY‑294002 and MK‑2206 on the abnormal activation of PI3K/AKT pathway and hypoxia inducible factor (HIF)‑1α protein level in HepG2 cells were detected using western blotting. The results indicated that the PI3K/AKT pathway is stably activated in HepG2 cells. Compared with the AKT inhibitor MK2206, the PI3K inhibitor LY‑294002 more effectively downregulated the phosphorylation levels of p85, p110α, p110β, p110γ and AKT in the PI3K/AKT pathway in HepG2 cells, and more effectively inhibited the proliferation of the cells. LY‑294002 enhanced the chemotherapy sensitivity of HepG2R cells to oxaliplatin by inducing G/G phase arrest and increasing the proportion of apoptotic cells. In addition, LY‑294002 reduced the level of HIF‑1α, which is highly expressed in HepG2 cells. It was concluded that LY‑294002 enhanced the chemosensitivity of liver cancer cells to oxaliplatin by inhibiting the PI3K/AKT signaling pathway, which may be related to the inhibition of HIF‑1α expression. These findings may have clinical significance for the treatment of oxaliplatin‑resistant liver cancer.
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http://dx.doi.org/10.3892/mmr.2021.12147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134878PMC
July 2021

Genome-wide analysis of the soybean root transcriptome reveals the impact of nitrate on alternative splicing.

G3 (Bethesda) 2021 May 10. Epub 2021 May 10.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, Yangzhou University, Yangzhou, Jiangsu 225009, China.

In plants, nitrate acts not only as a signaling molecule that affects plant development but also as a nutrient. The development of plant roots, which directly absorb nutrients, is greatly affected by nitrate supply. Alternative gene splicing plays a crucial role in the plant stress response by increasing transcriptome diversity. The effects of nitrate supply on alternative splicing (AS), however, have not been investigated in soybean roots. We used high-quality high-throughput RNA-sequencing data to investigate genome-wide AS events in soybean roots in response to various levels of nitrate supply. In total, we identified 355 nitrate-responsive AS events between optimal and high nitrate levels (NH), 335 nitrate-responsive AS events between optimal and low nitrate levels (NL), and 588 nitrate-responsive AS events between low and high nitrate levels (NLH). RI and A3SS were the most common AS types; in particular, they accounted for 67% of all AS events under all conditions. This increased complex and diversity of AS events regulation might be associated with the soybean response to nitrate. Functional ontology enrichment analysis suggested that the differentially splicing genes were associated with several pathways, including spliceosome, base excision repair, mRNA surveillance pathway and so on. Finally, we validated several AS events using reverse transcription-polymerase chain reaction to confirm our RNA-seq results. In summary, we characterized the features and patterns of genome-wide AS in the soybean root exposed to different nitrate levels, and our results revealed that AS is an important mechanism of nitrate-response regulation in the soybean root.
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http://dx.doi.org/10.1093/g3journal/jkab162DOI Listing
May 2021

Bioorthogonal catalytic patch.

Nat Nanotechnol 2021 May 10. Epub 2021 May 10.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P. R. China.

Bioorthogonal catalysis mediated by transition metals has inspired a new subfield of artificial chemistry complementary to enzymatic reactions, enabling the selective labelling of biomolecules or in situ synthesis of bioactive agents via non-natural processes. However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. Here, we describe a bioorthogonal catalytic device comprising a microneedle array patch integrated with Pd nanoparticles deposited on TiO nanosheets. This device is robust and removable, and can mediate the local conversion of caged substrates into their active states in high-level living systems. In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug's therapeutic anticancer properties. This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues.
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http://dx.doi.org/10.1038/s41565-021-00910-7DOI Listing
May 2021

Altering Hydrogenation Pathways in Photocatalytic Nitrogen Fixation by Tuning Local Electronic Structure of Oxygen Vacancy with Dopant.

Angew Chem Int Ed Engl 2021 May 7. Epub 2021 May 7.

Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), School of Chemistry and Materials Science, National Synchrotron Radiation Laboratory, and, CAS Center for Excellence in Nanoscience Institution, University of Science and Technology of China, Hefei, Anhui, 230026, China.

To avoid the energy-consuming step of direct N≡N bond cleavage, photocatalytic N fixation undergoing the associative pathways has been developed for mild-condition operation. However, it is a fundamental yet challenging task to gain comprehensive understanding on how the associative pathways (i.e., alternating vs. distal) are influenced and altered by the fine structure of catalysts, which eventually holds the key to significantly promote the practical implementation. Herein, we introduce Fe dopants into TiO nanofibers to stabilize oxygen vacancies and simultaneously tune their local electronic structure. The combination of in situ characterizations with first-principles simulations reveals that the modulation of local electronic structure by Fe dopants turns the hydrogenation of N from associative alternating pathway to associative distal pathway. This work provides fresh hints for rationally controlling the reaction pathways toward efficient photocatalytic nitrogen fixation.
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http://dx.doi.org/10.1002/anie.202104001DOI Listing
May 2021

Prognostic Value of D-dimer in patients with acute coronary syndrome treated by percutaneous coronary intervention: a retrospective cohort study.

Thromb J 2021 May 7;19(1):30. Epub 2021 May 7.

Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.

Background: Associations between D-dimer and outcomes of patients with acute coronary syndromes (ACS) remain controversial. This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI).

Methods: In this observational study, 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The X-tile program was used to determine the optimal D-dimer thresholds for risk stratifications. Cox regression with multiple adjustments was used for outcome analysis. Restricted cubic spline (RCS) analysis was performed to assess the dose-response association between D-dimer and outcomes. The C-index was calculated to evaluate the additional prognostic value of D-dimer when added to clinical risk factors and commonly used clinical risk scores, with internal validations using bootstrapping methods. The primary outcome was all-cause death.

Results: During a median follow-up of 720 days, 225 deaths occurred. Based on the thresholds generated by X-tile, ACS-PCI patients with median (420-1150 ng/mL, hazard ratio [HR]: 1.58, 95 % confidence interval [CI]: 1.14-2.20, P = 0.007) and high (≥ 1150 ng/mL, HR: 1.98, 95 % CI: 1.36-2.89, P < 0.001) levels of D-dimer showed substantially higher risk of death compared to those with low D-dimer (< 420 ng/mL). RCS analysis depicted a constant relation between D-dimer and various outcomes. The addition of D-dimer levels significantly improved risk predictions for all-cause death when combined with the fully adjusted models (C-index: 0.853 vs. 0.845, P = 0.021), the GRACE score (C-index: 0.826 vs. 0.814, P = 0.027), and the TIMI score (C-index: 0.804 vs. 0.776, P < 0.001). The predicted mortality at the median follow-up (two years) was 1.7 %, 5.2 %, and 10.9 % for patients with low, median, and high D-dimer, respectively, which was well matched with the observed mortality (low D-dimer group: 1.2 %, median D-dimer group: 5.2 %, and high D-dimer group: 12.6 %).

Conclusions: For ACS patients treated by PCI, D-dimer level was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and risk scores. Risk stratifications based on D-dimer was plausible to differentiate ACS-PCI patients with higher risk of death.
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http://dx.doi.org/10.1186/s12959-021-00281-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106213PMC
May 2021

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients.

Emerg Microbes Infect 2021 Dec;10(1):1097-1111

Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People's Republic of China.

Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients' antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.
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http://dx.doi.org/10.1080/22221751.2021.1925594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183521PMC
December 2021