Publications by authors named "He Zhang"

1,083 Publications

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STAT3-mediated upregulation of LINC00520 contributed to temozolomide chemoresistance in glioblastoma by interacting with RNA-binding protein LIN28B.

Cancer Cell Int 2022 Aug 9;22(1):248. Epub 2022 Aug 9.

Department of Neurosurgery, Lanzhou University Second Hospital, No. 82, Cuiyingmen, Gansu, 730030, Lanzhou, China.

A considerable number of glioblastoma (GBM) patients developed drug resistance to Temozolomide (TMZ) during chemotherapy, resulting in therapeutic failure and tumor recurrence. However, the exact mechanism of TMZ chemoresistance in GBM is still poorly clarified. As a novel identified lncRNA, LINC00520 was located on chromosome 14 and overexpressed in multiple human cancers. This study was designed and conducted to investigate the role and underlying mechanism of LINC00520 in GBM chemoresistance to TMZ. The qRT-PCR assay demonstrated that LINC00520 was significantly overexpressed in TMZ-sensitive and/or TMZ-resistant GBM cells (P < 0.001). The silencing of LINC00520 markedly reduced the cell viability, suppressed colony formation, induced cell apoptosis and G1/S phase arrest in TMZ-resistant cells (P < 0.001). In contrast, overexpression of LINC00520 conferred TMZ-resistant phenotype of GBM cells in vitro (P < 0.001). The orthotopic xenograft model was established and the results indicated that the volume of tumor xenografts in vivo was markedly inhibited by TMZ treatment after the silencing of LINC00520 (P < 0.001). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay revealed a strong affinity of transcription factor STAT3 to the promoter regions of LINC00520, suggesting that STAT3 mediated the aberrant expression of LINC00520 in GBM. Further experiments demonstrated that LINC00520 could interact with RNA-binding protein LIN28B to inhibit autophagy and reduce DNA damage, thereby contributing to TMZ chemoresistance in GBM. These findings suggested that STAT3/LINC00520/LIN28B axis might be a promising target to improve TMZ chemoresistance of GBM.
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http://dx.doi.org/10.1186/s12935-022-02659-yDOI Listing
August 2022

Serine racemase expression differentiates aging from Alzheimer's brain.

Curr Alzheimer Res 2022 Aug 5. Epub 2022 Aug 5.

Department of Geriatrics, Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock AR, USA; Geriatric Research, Education & Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock AR, USA.

Aging is an inevitable process characterized with progressive loss of physiological integrity and increased susceptibility to cancer, diabetes, cardiovascular, and neurodegenerative diseases; regarding the last, aging is the primary risk factor for Alzheimer's disease (AD), the most common cause of dementia. AD is characterized by brain pathology including extracellular deposition of amyloid aggregation and intracellular accumulation of neurofibrillary tangles composed of hyperphosphorylated tau protein. In addition, losses of synapses and a wide range of neurons are pivotal pathologies in AD brain. Accumulating evidence demonstrates hypoactivation of hippocampal neural networks in the aging brain, whereas AD-related mild cognitive impairment (AD-MCI) is begins with hyperactivation, followed by diminution of hippocampal activity as AD develops. The biphasic trends of the activity of hippocampal neural network are consistent with the alteration of N-methyl-D-aspartate receptor (NMDA-R) activity from aging to prodromal (AD-MCI) to mid-/late stage AD. D-Serine, a product of racemization catalyzed by serine racemase (SR), is an important co-agonist of the NMDA-R which is involved in synaptic events including neurotransmission, synaptogenesis, long-term potentiation (LTP), development, and excitotoxicity. SR and D-serine are decreased in the hippocampus of the aging brain, correlating with impairment of cognitive function. By contrast, SR is increased in AD brain, which is associated with a greater degree of cognitive dysfunction. Emerging studies suggest that D-serine levels in the brain or in cerebral spinal fluid from AD patients are higher than in age-matched controls, but the results are inconsistent. Very recently, serum D-serine levels in AD were reported to correlate with sex and clinical dementia rating (CDR) stage. This review will discuss alterations of NMDA-R and SR in aging and brain, and the mechanisms underlying the differential regulation of SR will be probed. Collectively, we propose that SR may be a molecular switch that distinguishes the effects of aging from those of AD on the brain.
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http://dx.doi.org/10.2174/1567205019666220805105106DOI Listing
August 2022

Three distinct enhancers cooperate for sound receptor hair cell development.

Proc Natl Acad Sci U S A 2022 Aug 4;119(32):e2119850119. Epub 2022 Aug 4.

State Key Laboratory of Neuroscience, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.

Cochlear hair cells (HCs) in the inner ear are responsible for sound detection. For HC fate specification, the master transcription factor Atoh1 is both necessary and sufficient. expression is dynamic and tightly regulated during development, but the -regulatory elements mediating this regulation remain unresolved. Unexpectedly, we found that deleting the only recognized enhancer, defined here as Eh1, failed to impair HC development. By using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), we discovered two additional enhancers: Eh2 and Eh3. Notably, Eh2 deletion was sufficient for impairing HC development, and concurrent deletion of Eh1 and Eh2 or all three enhancers resulted in nearly complete absence of HCs. Lastly, we showed that Atoh1 binds to all three enhancers, consistent with its autoregulatory function. Our findings reveal that the cooperative action of three distinct enhancers underpins effective regulation during HC development, indicating potential therapeutic approaches for HC regeneration.
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http://dx.doi.org/10.1073/pnas.2119850119DOI Listing
August 2022

Maize-peanut rotational strip intercropping improves peanut growth and soil properties by optimizing microbial community diversity.

PeerJ 2022 28;10:e13777. Epub 2022 Jul 28.

College of Agronomy, Shenyang Agricultural University, Shenyang City, Liaoning Province, China.

Rotational strip intercropping (RSI) of cereals and legumes has been developed and widely carried out to alleviate continuous cropping obstacles, to control erosion and to improve field use efficiency. In this study, a four-year fixed-field experiment was carried out in northeast China with three treatments: continuous cropping of maize, continuous cropping of peanuts and rotational strip intercropping of maize and peanut. The results show that crop rotation improved the main-stem height, branch number, lateral branch length, and yield and quality of peanuts; the yield was the highest in 2018, when it was increased by 39.5%. RSI improved the contents of total N, available N, total P, available P, total K and available K; the content of available N was the highest in 2018, with an increase of 70%. Rhizosphere soil urease and catalase activities were significantly increased and were the highest in 2017, reaching 183.13% and 91.21%, respectively. According to a high-throughput sequencing analysis, the rhizosphere soil bacterial richness and specific OTUs decreased in peanut rhizosphere soil, while the fungal increased. There were differences in the bacterial and fungal community structures; specifically, the abundance of Acidobacteria and Planctomycetes increased among bacteria and the abundance of beneficial microorganisms such as Ascomycota increased among fungi. In conclusion, rotational strip intercropping of maize and peanut increased the yield and quality of peanuts and conducive to alleviating the obstacles facing the continuous cropping of peanuts. Among then, soil physicochemical properties, enzyme activity and microbial diversity were significantly affected the yield of peanut.
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http://dx.doi.org/10.7717/peerj.13777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339216PMC
July 2022

Controllable Free Viewpoint Video Reconstruction Based on Neural Radiance Fields and Motion Graphs.

IEEE Trans Vis Comput Graph 2022 Aug 1;PP. Epub 2022 Aug 1.

In this paper, we propose a controllable high-quality free viewpoint video generation method based on the motion graph and neural radiance fields (NeRF). Different from existing pose-driven NeRF or time/structure conditioned NeRF works, we propose to first construct a directed motion graph of the captured sequence. Such a sequence-motion-parameterization strategy not only enables flexible pose control for free viewpoint video rendering but also avoids redundant calculation of similar poses and thus improves the overall reconstruction efficiency. Moreover, to support body shape control without losing the realistic free viewpoint rendering performance, we improve the vanilla NeRF by combining explicit surface deformation and implicit neural scene representations. Specifically, we train a local surface-guided NeRF for each valid frame on the motion graph, and the volumetric rendering was only performed in the local space around the real surface, thus enabling plausible shape control ability. As far as we know, our method is the first method that supports both realistic free viewpoint video reconstruction and motion graph-based user-guided motion traversal. The results and comparisons further demonstrate the effectiveness of the proposed method.
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http://dx.doi.org/10.1109/TVCG.2022.3192713DOI Listing
August 2022

Efficient optical reservoir computing for parallel data processing.

Opt Lett 2022 Aug;47(15):3784-3787

We propose and experimentally demonstrate an optical reservoir computing system in free space, using second-harmonic generation for nonlinear kernel functions and a scattering medium to enhance reservoir nodes interconnection. We test it for one-step and multi-step predication of Mackey-Glass time series with different input-mapping methods on a spatial light modulator. For one-step prediction, we achieve 1.8 × 10 normalized mean squared error (NMSE). For the multi-step prediction, we explore two different mapping methods: linear-combination and concatenation, achieving 16-step prediction with NMSE as low as 3.5 × 10. Robust and superior for multi-step prediction, our approach and design have potential for parallel data processing tasks such as video prediction, speech translation, and so on.
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http://dx.doi.org/10.1364/OL.464288DOI Listing
August 2022

Catalytic degradation of brominated flame retardants in the environment: New techniques and research highlights.

Sci Total Environ 2022 Jul 29;848:157695. Epub 2022 Jul 29.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of the Chinese Academy of Sciences, Beijing 100049, China.

Due to the extensive commercial use of brominated flame retardants (BFRs), human beings are chronically exposed to BFRs, causing great harms to human health, which imposes urgent demands to degrade them in the environment. Among various degradation techniques, catalytic degradation has been proven to be outstanding because of its rapidness and effectiveness. Therefore, much attention has been given to catalytic degradation, especially the extensively studied photocatalytic degradation and nanocatalytic reduction techniques. Recently, some novel advanced catalytic techniques have been developed and show excellent catalytic degradation efficiency for BFRs, including natural substances catalytic degradation, new Fenton catalytic degradation, new chemical reagent catalytic degradation, new material catalytic degradation, electrocatalytic degradation, plasma catalytic degradation, and composite catalytic degradation systems. In addition to the common features of traditional catalytic techniques, these novel techniques possess their own specific advantages in various aspects. Therefore, this review summarized the degradation mechanism of BFRs by the above new catalytic degradation methods under the laboratory conditions, simulated real environment, and real environment conditions, and further evaluated their advantages and disadvantages, aiming to provide some research ideas for the catalytic degradation of BFRs in the environment in the future. We suggested that more attention should focus on features of novel catalytic techniques, including eco-friendliness, cost-effectiveness, and pragmatic usefulness.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157695DOI Listing
July 2022

Surgical Staging of Locally Advanced Cervical Cancer: Current Status and Research Progress.

Front Oncol 2022 6;12:940807. Epub 2022 Jul 6.

Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.

Locally advanced cervical cancer (LACC) has large localized lesions, high recurrence and metastasis rate under standard treatment, and low survival rate. The current guidelines still use concurrent radiotherapy as the gold standard of treatment for locally advanced cervical cancer. Several recent studies have shown that surgical staging has higher accuracy in determining metastasis in the para-aortic lymph nodes, bringing survival benefits to some patients. However, the indications for surgical staging and whether surgical staging can improve prognosis are still controversial. We will review the current status and research progress of surgical staging for locally advanced cervical cancer.
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http://dx.doi.org/10.3389/fonc.2022.940807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296854PMC
July 2022

Phosphorus distribution in the water and sediment of Laizhou Bay and sediment phosphorus release potential.

Sci Total Environ 2022 Jul 20;846:157483. Epub 2022 Jul 20.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875, China.

Phosphorus is an integral component of marine biogeochemistry. This research investigated the environmental behavior of P in Laizhou Bay using high-resolution sampling, P fractionation, and isotherm adsorption. The total dissolved P (TDP) concentration ranged from 8.4 to 61.0 μg/L in the bay water, while total P (TP) concentration ranged from 311.6 to 654.5 mg/kg in the sediment. The TDP concentration in the water was high in the estuarine area of the Yellow River and the southwestern bay under the combined effects of riverine inputs, direct wastewater discharge, and limited water exchange ability. High TP concentrations in the sediment were observed near the mouth of the Yellow River and central bay, mainly due to the movement and settlement of fine suspended particles under the influence of ocean currents. The P in the bay sediment was predominantly in the calcium-bound fraction and was associated with small particles such as silt and clay. The equilibrium P concentration (EPC) ranged from 1.6 to 131.4 μg/L, and P partition coefficient or buffer intensity (K) ranged from 104 L/kg to 880 L/kg. The EPC decreased from the northeastern to southwestern area, while K showed an inverse distribution; therefore, the southwestern bay sediment had high buffer intensity for external P loads. Additionally, ECP increased linearly, and K decreased with exchangeable P (Exc-P) and Fe-bound P (Fe-P) concentrations in the sediment, demonstrating that P sediment-water exchange in LZB was dominated by contributions from Exc-P and Fe-P. These results can aid the understanding of the P sources and geochemistry of coastal ecosystems, particularly sediment P release potential.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157483DOI Listing
July 2022

Stable magnetic CoZn/N-doped polyhedron with self-generating carbon nanotubes for highly efficient removal of bisphenols from complex wastewaters.

J Hazard Mater 2022 Jul 12;439:129584. Epub 2022 Jul 12.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of the Chinese Academy of Sciences, Beijing 100049, China.

Bisphenols have extensively been found in various environmental matrices and caused public concerns due to their endocrine-disrupting potential. Herein, we developed a [email protected] CoZn/nitrogen-doped carbon (CoZn/NC) as a robust adsorbent for bisphenols in wastewaters. The self-generating carbon nanotubes and the open metal sites provided sufficient adsorption sites. The Co component endowed the derivative with strong magnetism facilitating its separation from water. CoZn/NC exhibited exceeding water stability in pH 3 - 12 solution and withstood water up to 15 days. The great applicability of CoZn/NC was validated with 16 real wastewaters from different sources (recoveries exceeding 97.9%). Fast adsorption kinetics were observed with removal efficiencies above 96.5% within 1 min. The adsorption isotherms were well fitted with the Langmuir model, with adsorption capacities of 222, 200, 193, and 321 mg g for bisphenol A, bisphenol F, bisphenol S, and bisphenol AF, respectively. Variations in external conditions, including pH 3 - 9, humic acid (50 mg L), and NaCl (0.1 mol L), had negligible impacts on the adsorption process. The characterizations and density functional theory computation demonstrated that electrostatic, hydrophobic, π - π, and cation- π interactions are the driving forces in this system. The as-prepared CoZn/NC exhibits great promise in real wastewater treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129584DOI Listing
July 2022

Gold nanoparticle-directed autophagy intervention for antitumor immunotherapy inhibiting tumor-associated macrophage M2 polarization.

Acta Pharm Sin B 2022 Jul 16;12(7):3124-3138. Epub 2022 Feb 16.

Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both and models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.
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http://dx.doi.org/10.1016/j.apsb.2022.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293675PMC
July 2022

The global succinylation of SARS-CoV-2-infected host cells reveals drug targets.

Proc Natl Acad Sci U S A 2022 Jul 12;119(30):e2123065119. Epub 2022 Jul 12.

Key Laboratory of Livestock Disease Prevention of Guangdong Province, Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, 510610 Guangzhou, China.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, undergoes continuous evolution, highlighting an urgent need for development of novel antiviral therapies. Here we show a quantitative mass spectrometry-based succinylproteomics analysis of SARS-CoV-2 infection in Caco-2 cells, revealing dramatic reshape of succinylation on host and viral proteins. SARS-CoV-2 infection promotes succinylation of several key enzymes in the TCA, leading to inhibition of cellular metabolic pathways. We demonstrated that host protein succinylation is regulated by viral nonstructural protein (NSP14) through interaction with sirtuin 5 (SIRT5); overexpressed SIRT5 can effectively inhibit virus replication. We found succinylation inhibitors possess significant antiviral effects. We also found that SARS-CoV-2 nucleocapsid and membrane proteins underwent succinylation modification, which was conserved in SARS-CoV-2 and its variants. Collectively, our results uncover a regulatory mechanism of host protein posttranslational modification and cellular pathways mediated by SARS-CoV-2, which may become antiviral drug targets against COVID-19.
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http://dx.doi.org/10.1073/pnas.2123065119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335334PMC
July 2022

Electrochemical Response of Mixed Conducting Perovskite Enables Low-Cost High-Efficiency Hydrogen Sensing.

ACS Appl Mater Interfaces 2022 Jul 18. Epub 2022 Jul 18.

State Key Laboratory of Fire Science, Department of Safety Science and Engineering, University of Science and Technology of China, Hefei 230026, P. R. China.

High-performance noble metal-free gas sensors are crucial for widespread applications in various areas. Non-Nernstian electrochemical sensors have attracted tremendous attention, but are limited by the high cost and low efficiency of Pt electrode. Moreover, responses from different electrodes usually have the same polarity, degrading the sensor performance. Here we report a reverse response on a series of mixed ionic-electronic conductors (MIECs). Exemplary SrFeTiO (SFT50) perovskite shows excellent H sensing properties, including high sensitivity and selectivity, humidity resistance, and long-term stability. Strikingly, the response is positive, as opposed to the usual one. Such an unusual response is ascribed to the change of the surface electrostatic potential due to the gas chemical reaction, which outcompetes traditional mechanisms, thereby reversing the response polarity. A conceptual noble-metal-free sensor with dual oxide electrodes of opposite polarity is designed by substituting SFT50 for the benchmark Pt, achieving a 1.5-2.0× increase in H response, sensitivity, and selectivity and a low limit of detection of 16 ppb. The ideal unity of excellent sensing and unusual polarity for MIECs can be used to optimize the performance of a variety of conventional sensors while reducing the cost. Our findings provide new insights into electrochemical gas sensing and offer a facile approach for developing low-cost high-performance gas sensors.
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http://dx.doi.org/10.1021/acsami.2c09642DOI Listing
July 2022

Metavirome Analysis of Reveals Novel Japanese Encephalitis Virus and Chikungunya Virus.

Front Cell Infect Microbiol 2022 30;12:938576. Epub 2022 Jun 30.

Wenzhou Key Laboratory for Virology and Immunology, Institute of Virology, Wenzhou University, Wenzhou, China.

To explore the specific virome, 6400 C were collected in Honghe autonomous prefecture, China. Abundant virus sequences were obtained from 28 viral families using metavirome sequencing. Herein, several viruses in virome were verified using the PCR technique, which covers Japanese encephalitis virus (JEV), Getah virus, and even Chikungunya virus (CHIKV). Seven JEV gene sequences were amplified successfully, of which JEV-China/CT2016E-1 shared the highest homology with the known JEV sequence isolated in Korea, 1946, with at least 96.1% nucleotide (nt) identity, which belonged to genotype III. Nine CHIKV gene sequences were amplified, which shared the highest with at least 93.0% nt identity with CHIKV from Thailand isolated in 2007, which was assigned to genotype Asian. Remarkably, CHIKV was isolated from in China for the first time. It was initially confirmed that the isolated virus CHIKV-China/CT2016-1 may increase infectivity after passaging in Vero cells from BHK-21 cells. Collectively, our study reveals the diversity, properties, and potential virus susceptibility dynamics of the virome and sheds new perspectives on the viral ecology in other important biological vectors.
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http://dx.doi.org/10.3389/fcimb.2022.938576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280054PMC
July 2022

Multiple Novel Mosquito-Borne Zoonotic Viruses Revealed in Pangolin Virome.

Front Cell Infect Microbiol 2022 29;12:874003. Epub 2022 Jun 29.

Wenzhou Key Laboratory for Virology and Immunology, Institute of Virology, Wenzhou University, Wenzhou, China.

Swab samples were collected from 34 pangolins in Guangxi Province, China. Metavirome sequencing and bioinformatics approaches were undertaken to determine the abundant viral sequences in the viromes. The results showed that the viral sequences belong to 24 virus taxonomic families. To verify the results, PCR combined with phylogenetic analysis was conducted. Some viral sequences including Japanese encephalitis virus (JEV), Getah virus (GETV), and chikungunya virus (CHIKV) were detected. On the basis of the metavirome analysis, seven segments belonging to JEV were further identified through PCR amplification. Sequence comparison showed that, among seven sequences, JEV-China/P2020E-1 displayed the highest nucleotide (80.6%), with the JEV isolated in South Korea, 1988, and all of which belonging to genotype III. Seven CHIKV sequences were detected, with the highest homology (80.6%) to the in Côte d'Ivoire, 1993. Moreover, passage from BHK-21 to Vero cells makes the newly isolated CHIKV-China/P2020-1 more contagious. In addition, the newly verified GETV sequences shared 86.4% identity with the 1955 GETV isolated from Malaysia. Some sudden and recurrent viruses have also been observed from the virome of pangolin in Guangxi Province, China; hence, dissemination tests will be implemented in the future.
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http://dx.doi.org/10.3389/fcimb.2022.874003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277073PMC
June 2022

Artificial Intelligence-Assisted Score Analysis for Predicting the Expression of the Immunotherapy Biomarker PD-L1 in Lung Cancer.

Front Immunol 2022 1;13:893198. Epub 2022 Jul 1.

Department of Pathology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

Programmed cell death ligand 1 (PD-L1) is a critical biomarker for predicting the response to immunotherapy. However, traditional quantitative evaluation of PD-L1 expression using immunohistochemistry staining remains challenging for pathologists. Here we developed a deep learning (DL)-based artificial intelligence (AI) model to automatically analyze the immunohistochemical expression of PD-L1 in lung cancer patients. A total of 1,288 patients with lung cancer were included in the study. The diagnostic ability of three different AI models (M1, M2, and M3) was assessed in both PD-L1 (22C3) and PD-L1 (SP263) assays. M2 and M3 showed improved performance in the evaluation of PD-L1 expression in the PD-L1 (22C3) assay, especially at 1% cutoff. Highly accurate performance in the PD-L1 (SP263) was also achieved, with accuracy and specificity of 96.4 and 96.8% in both M2 and M3, respectively. Moreover, the diagnostic results of these three AI-assisted models were highly consistent with those from the pathologist. Similar performances of M1, M2, and M3 in the 22C3 dataset were also obtained in lung adenocarcinoma and lung squamous cell carcinoma in both sampling methods. In conclusion, these results suggest that AI-assisted diagnostic models in PD-L1 expression are a promising tool for improving the efficiency of clinical pathologists.
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http://dx.doi.org/10.3389/fimmu.2022.893198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286729PMC
July 2022

Deletion of serine racemase reverses neuronal insulin signaling inhibition by amyloid-β oligomers.

J Neurochem 2022 Jul 15. Epub 2022 Jul 15.

School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical University, Wenzhou, China.

Dysregulation of insulin signaling in the Alzheimer's disease (AD) brain has been extensively reported. Serine racemase (SR) modulates insulin secretion in pancreatic islets. This study aimed to examine whether SR regulates insulin synthesis and secretion in neurons, thereby modulating insulin signaling in the AD brain. Srr-knockout (Srr ) mice generated with the CRISPR/Cas9 technique were used. Using immunofluorescence and fluorescence in situ hybridization, levels of insulin protein and insulin(ins2) mRNA were significantly increased in the hippocampal but not in hypothalamic sections of Srr mice compared with WT mice. Real-time quantitative PCR revealed that ins2 mRNA from primary hippocampal neuronal cultures of Srr mice was significantly increased compared with that from cultured neurons of WT mice. Notably, the secretion of proinsulin C-peptide was increased in Srr neurons relative to WT neurons. By examining membrane fractional proteins with immunoblotting, Srr neurons retained ATP-dependent potassium channels on plasmalemma and correspondingly contained higher levels of p-AMPK. After treatment with Aβ42, the phosphorylation levels of insulin receptor substrate at serine 616 636 (p-IRS1 ) were significantly lower, whereas p-AKT and p-AKT were higher in Srr neurons than in WT neurons, respectively. The phosphorylated form of c-Jun N-terminal kinase decreased in the cultured Srr neurons relative to the WT neurons upon Aβ42 treatment. In contrast, phosphorylated protein kinase R remained at the same levels. Further, reactive oxygen species were reduced in cultured Srr neurons under Aβ42 treatment relative to the WT neurons. Collectively, our study indicated that Srr deletion promoted insulin synthesis and secretion of proinsulin C-peptide, thereby reversing insulin resistance by Aβ42. This study suggests that targeting the neuronal SR may be utilized to enhance insulin signaling which is inhibited at the early stage of the AD brain.
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http://dx.doi.org/10.1111/jnc.15664DOI Listing
July 2022

Ultraviolet supercontinuum generation driven by ionic coherence in a strong laser field.

Nat Commun 2022 Jul 14;13(1):4080. Epub 2022 Jul 14.

Department of Physics, National University of Defense Technology, Changsha, China.

Supercontinuum (SC) light sources hold versatile applications in many fields ranging from imaging microscopic structural dynamics to achieving frequency comb metrology. Although such broadband light sources are readily accessible in the visible and near infrared regime, the ultraviolet (UV) extension of SC spectrum is still challenging. Here, we demonstrate that the joint contribution of strong field ionization and quantum resonance leads to the unexpected UV continuum radiation spanning the 100 nm bandwidth in molecular nitrogen ions. Quantum coherences in a bunch of ionic levels are found to be created by dynamic Stark-assisted multiphoton resonances following tunneling ionization. We show that the dynamical evolution of the coherence-enhanced polarization wave gives rise to laser-assisted continuum emission inside the laser field and free-induction decay after the laser field, which jointly contribute to the SC generation together with fifth harmonics. As proof of principle, we also show the application of the SC radiation in the absorption spectroscopy. This work offers an alternative scheme for constructing exotic SC sources, and opens up the territory of ionic quantum optics in the strong-field regime.
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http://dx.doi.org/10.1038/s41467-022-31824-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283425PMC
July 2022

Efficient activation of persulfate by [email protected] in visible-light for tetracycline degradation.

Chemosphere 2022 Jul 7;306:135635. Epub 2022 Jul 7.

School of Environmental and Safety Engineering, Changzhou University, Jiangsu, 213164, China. Electronic address:

A [email protected] material, FeO coated with carbon, was prepared by a simple one-pot hydrothermal method. The [email protected] material was investigated with persulfate (PS) and light to degrade tetracycline (TC) as a function of pH, aeration conditions and quenching. Experimental results suggest that TC was effectively degraded in the [email protected]/PS/Vis system. In addition, due to the availability of different main active species in this catalytic system, TC degradation was possible under both strong acid and strong alkali pH conditions. The presence of dissolved oxygen can also generate oxygen-active species, such as superoxide radicals (O•) and singlet oxygen (O), to decompose TC organic matter in solution. Simply put, [email protected]/PS/Vis catalytic system removed pollutants by the formation of O•, O, hydroxyl radicals (•OH) and sulfate radicals (SO•) species for degrading TC. In addition, the stability of the [email protected] material was found to be outstanding.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135635DOI Listing
July 2022

Recent Progress in Sensing Technology Based on Triboelectric Nanogenerators in Dynamic Behaviors.

Sensors (Basel) 2022 Jun 26;22(13). Epub 2022 Jun 26.

College of Civil Engineering & Architecture, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.

Under the trend of the rapid development of the internet of things (IoT), sensing for dynamic behaviors is widely needed in many fields such as traffic management, industrial production, medical treatment, building health monitoring, etc. Due to the feature of power supply independence and excellent working performance under a low-frequency environment, triboelectric nanogenerators (TENGs) as sensors are attracting more and more attention. In this paper, a comprehensive review focusing on the recent advance of TENGs as sensors for dynamic behaviors is conducted. The structure and material are two major factors affecting the performance of sensors. Different structure designs are proposed to make the sensor suitable for different sensing occasions and improve the working performance of the sensors. As for materials, new materials with stronger abilities to gain or lose electrons are fabricated to obtain higher surface charge density. Improving the surface roughness of material by surface engineering techniques is another strategy to improve the output performance of TENG. Based on the advancement of TENG structures and materials, plenty of applications of TENG-based sensors have been developed such as city traffic management, human-computer interaction, health monitoring of infrastructure, etc. It is believed that TENG-based sensors will be gradually commercialized and become the mainstream sensors for dynamic sensing.
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http://dx.doi.org/10.3390/s22134837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269214PMC
June 2022

New Insights into the Diurnal Rhythmicity of Gut Microbiota and Its Crosstalk with Host Circadian Rhythm.

Animals (Basel) 2022 Jun 29;12(13). Epub 2022 Jun 29.

Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

Unlike the strictly hierarchical organization in the circadian clock system, the gut microbiota rhythmicity has a more complex multilayer network of all taxonomic levels of microbial taxa and their metabolites. However, it is worth noting that the functionality of the gut microbiota rhythmicity is highly dependent on the host circadian clock and host physiological status. Here, we discussed the diurnal rhythmicity of the gut microbiota; its crucial role in host physiology, health, and metabolism; and the crosstalk between the gut microbial rhythmicity and host circadian rhythm. This knowledge lays the foundation for the development of chronotherapies targeting the gut microbiota. However, the formation mechanism, its beneficial effects on the host of gut microbial rhythmicity, and the dynamic microbial-host crosstalk are not yet clear and warrant further research.
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http://dx.doi.org/10.3390/ani12131677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264800PMC
June 2022

FAP α-SMA cancer-associated fibroblast-derived SLPI protein encapsulated in extracellular vesicles promotes ovarian cancer development via activation of PI3K/AKT and downstream signaling pathways.

Mol Carcinog 2022 Jul 8. Epub 2022 Jul 8.

Laboratory of Medical Genetics, School of Medicine, South China University of Technology, Guangzhou, China.

Ovarian cancer is the most lethal gynecological malignancy worldwide with high metastasis and poor prognosis rates. Cancer-associated fibroblasts (CAFs), a heterogeneous population of cells that constitutes a major component of the tumor microenvironment, secrete extracellular vesicles (EVs) loading with proteins, lipids, and RNAs to promote tumorigenesis. However, the specific roles of CAF-derived proteins contained in EVs in ovarian cancer remain poorly understood at present. Using the gene expression microarray analysis, we identified a list of dysregulated genes between the α-SMA CAF and FAP CAF subpopulations, from which secretory leukocyte protease inhibitor (SLPI) was chosen for further validation. Quantitative PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assays were used to assess SLPI expression in ovarian cancer cells, tissues, CAFs, and EVs. Additionally, we evaluated the effects of exogenous SLPI on proliferation, migration, invasion, and adhesion of ovarian cancer cells in vitro. Our results showed SLPI protein was upregulated in CAFs, particularly in the FAP α-SMA CAF subpopulation, and associated with increased tumor grade and decreased overall survival (OS). Importantly, CAF-derived SLPI protein could be encapsulated in EVs for delivery to ovarian cancer cells, thus facilitating cell proliferation, migration, invasion, and adhesion via activating the PI3K/AKT and downstream signaling pathways. Moreover, high plasma expression of SLPI encapsulated in EVs was closely correlated with tumor stage in ovarian cancer patients. Our collective results highlight an oncogenic role of plasma EV-encapsulated SLPI secreted by CAFs in tumor progression for the first time, supporting its potential utility as a prognostic biomarker of ovarian cancer.
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http://dx.doi.org/10.1002/mc.23445DOI Listing
July 2022

LinearAlifold: Linear-Time Consensus Structure Prediction for RNA Alignments.

ArXiv 2022 Jun 29. Epub 2022 Jun 29.

Predicting the consensus structure of a set of aligned RNA homologs is a convenient method to find conserved structures in an RNA genome, which has applications in SARS-CoV-2 diagnostics and therapeutics. However, the state-of-the-art algorithm for this task, RNAalifold, is prohibitively slow for long sequences, due to a cubic scaling with the sequence length, and even slower when analyzing many such sequences, due to a superlinear scaling with the number of homologs, taking 4 days on 200 SARS-CoV variants. We present LinearAlifold, an efficient algorithm for folding aligned RNA homologs that scales linearly with both the sequence length and the number of sequences, based on our recent work LinearFold that folds a single RNA in linear time. Our work is orders of magnitude faster than RNAalifold (e.g., 0.5 hours on the above 200 sequences or 316 times speedup) and achieves comparable accuracies compared to a database of known structures. More interestingly, LinearAlifold's prediction on SARS-CoV-2 correlates well with experimentally determined structures, outperforming RNAalifold. Finally, LinearAlifold supports three modes: minimum free energy (MFE), partition function, and stochastic sampling, each of which takes under an hour for hundreds of SARS-CoV variants, while only the MFE mode of RNAalifold works for them, taking days or weeks.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258297PMC
June 2022

Fatal Gets More Fatal: A COVID-19 Infection With Macrophage Activation Syndrome.

Cureus 2022 Jun 2;14(6):e25591. Epub 2022 Jun 2.

Pulmonary and Critical Care Medicine, Saint Mary's Hospital, Waterbury, USA.

Coronavirus disease 2019 (COVID-19) continues to be fatal despite advances in the understanding of characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), global prevention strategies, new anti-viral treatments, and worldwide vaccination programs. The exact underlying mechanism through which SARS-CoV-2 leads to acute respiratory distress syndrome (ARDS) resulting in intensive care unit admission, mechanical ventilation, and eventually death remains elusive. Cytokine storm is one of the most favorable mechanisms that scientists show remarkable interest to target in randomized clinical trials with promising outcomes. Macrophage activation syndrome (MAS), the most serious form of cytokine storm, requires early recognition and treatment regardless of etiology. Here, we report a 59-year-old gentleman with a COVID-19 infection complicated by MAS. Our aim is to increase awareness of this condition among health care providers as it necessitates prompt diagnosis and treatment due to an extremely poor prognosis.
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http://dx.doi.org/10.7759/cureus.25591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250044PMC
June 2022

Evaluation of the significance of interleukin-6 in the diagnosis of postoperative pneumonia: a prospective study.

BMC Cardiovasc Disord 2022 07 7;22(1):306. Epub 2022 Jul 7.

Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, China.

Background: Postoperative pneumonia (PP) is one of the most common complications after cardiac surgery. This study was designed to access the diagnostic value of interleukin-6 (IL-6) for pneumonia within the first 5 days after cardiac surgery in adults.

Method: This prospective observational study enrolled 694 patients who admitted to our center from 10 October 2020 to 30 June 2021. Blood samples were collected after admission and on five consecutive days after surgery to measure IL-6, procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC) respectively. Combined with clinical data, we assessed the diagnostic performance of different biomarkers using univariate and multifactorial analyses as well as receiver operating characteristic curves (ROC) and the area under the curve (AUC).

Result: Finally, 68 patients were diagnosed with PP (PP Group). In addition, 626 cases were assigned to the control group (Non-PP Group). From postoperative day 1 (POD1) to day 5, IL-6 and PCT levels showed higher diagnostic value (P < 0.001, P < 0.05, respectively); meanwhile, there was no difference in white blood cell counts between the two groups; CRP showed some value from POD2 onwards (P < 0.001). Among these biomarkers, IL-6 on POD1 [AUC: 0.78, 95% confidence interval (CI): 0.71-0.83], IL-6 on POD2 (AUC: 0.77, 95% CI: 0.71-0.82) and CRP levels on POD3 (AUC: 0.77, 95% CI: 0.70-0.84) had the highest diagnostic value. Multivariate analysis found that smoking status [odds ratio(OR): 7.79, 95% CI: 3.05, 19.88, p < 0.001], drinking status (OR: 22.68, 95% CI: 9.29, 55.37, p < 0.001) and hypertension (OR: 2.85, 95% CI: 1.28, 6.35, p = 0.011), IL-6 on POD2 (OR: 1.01, 95% CI: 1.00, 1.01, p = 0.018), mechanical ventilation time (OR: 1.03, 95% CI: 1.00, 1.05, p = 0.040) and intensive care unit stay time (OR: 1.01, 95% CI: 1.00, 1.02, p < 0.001) were independent risk factors for postoperative pneumonia.

Conclusion: Smoking, drinking, hypertension, prolonged duration of mechanical ventilation and intensive care unit stay, and IL-6 on POD2 were independent risk factors for pneumonia after cardiovascular surgery. IL-6 level on POD2 may serve as a promising indicator, better than WBC, PCT and CRP.
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http://dx.doi.org/10.1186/s12872-022-02744-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261039PMC
July 2022

Spatial transcriptome analysis on peanut tissues shed light on cell heterogeneity of the peg.

Plant Biotechnol J 2022 Jul 6. Epub 2022 Jul 6.

Institute of Crop Germplasm Resources, Shandong Academy of Agricultural Sciences, Ji'nan, China.

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http://dx.doi.org/10.1111/pbi.13884DOI Listing
July 2022

Exploring novel systemic therapies for pancreatic cancer: a review of emerging anti-PD-1/PD-L1 combination therapy.

Neoplasma 2022 Jun 30. Epub 2022 Jun 30.

Human Anatomy Laboratory, School of Basic Medicine, Xinxiang Medical University, Henan, China.

Despite attempts to apply single therapy such as surgical treatment, chemotherapy, or radiotherapy, pancreatic cancer (PC) is still one of the most lethal solid tumors. Moreover, immune checkpoint inhibitors against PD-1/PD-L1, which have shown good efficacies against many other solid tumors, have not shown encouraging results in PC treatment. Therefore, some studies are evaluating the efficacies of combination therapies based on anti-PD-1/PD-L1 for PC. In this review, we summarized the emerging anti-PD-1/PD-L1 combination therapies for PC in these years. We realized that anti-PD-1/PD-L1-based combination therapies have the potential to be efficacious in PC treatment, and further relevant studies are needed. Moreover, we elucidated the reasons for the ineffectiveness of anti-PD-1/PD-L1 alone in PC treatment. We concluded that this was mainly because PC has an immunosuppressive tumor microenvironment and develops drug resistance during treatment. Anti-PD-1/PD-L1-based combination therapeutic regimens that alter the immunosuppressive tumor microenvironment and reduce the development of drug resistance in PC are summarized in this review, and we expect that these regimens will achieve good clinical application prospects.
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http://dx.doi.org/10.4149/neo_2022_220306N246DOI Listing
June 2022

Incidence and risk factors of nasogastric feeding intolerance in moderately-severe to severe acute pancreatitis.

BMC Gastroenterol 2022 Jul 2;22(1):327. Epub 2022 Jul 2.

Center of Severe Acute Pancreatitis (CSAP), Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Jiangsu, Nanjing, 210002, People's Republic of China.

Background: The importance of enteral nutrition (EN) in acute pancreatitis (AP) has been emphasised. Nasogastric (NG) feeding has been the preferred route for EN delivery in most AP patients intolerant to oral intake. However, gastric feeding intolerance (GFI) was frequently reported, especially in patients with more severe diseases. This study aimed to investigate the incidence and risk factors for GFI in moderately-severe to severe AP.

Methods: This is a single-centre, retrospective study. All the data were extracted from an electronic database from April 2020 to May 2021. Data were prospectively collected during hospitalisation. Patients diagnosed with moderately-severe to severe AP and admitted within seven days from the onset of abdominal pain were assessed for eligibility. Patients who showed signs of intolerance to gastric feeding and required switching to nasojejunal (NJ) feeding were deemed GFI. Multivariable logistic regression was performed to assess potential risk factors of GFI.

Results: A total of 93 patients were analysed, of whom 24 were deemed GFI (25.8%), and the rest tolerated NG feeding well (n = 69). In patients with GFI, the median time of switching to NJ feeding was five days (interquartile range: 4-7 days) after admission. The multivariable analysis showed that respiratory failure (odds ratio = 3.135, 95% CI: 1.111-8.848, P = 0.031) was an independent risk factor for GFI.The mean daily energy delivery in the following three days after switching to NJ feeding was significantly higher than the first three days after initiation of NG feeding in patients with GFI [920.83 (493.33-1326) vs. 465 (252.25-556.67) kcal, P < 0.001].

Conclusion: GFI is common in moderately-severe to severe AP patients with an incidence of 25.8%, and the presence of respiratory failure may increase the risk of GFI.
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http://dx.doi.org/10.1186/s12876-022-02403-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250174PMC
July 2022

Paraoxonase-1 Facilitates PRRSV Replication by Interacting with Viral Nonstructural Protein-9 and Inhibiting Type I Interferon Pathway.

Viruses 2022 05 31;14(6). Epub 2022 May 31.

State Key Laboratory of Veterinary Biotechnology, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

Paraoxonase-1 (PON1), an esterase with specifically paraoxonase activity, has been proven to be involved in inflammation and infection. Porcine reproductive and respiratory syndrome virus (PRRSV) is still a major concern in pigs and causes severe economic losses to the swine industry worldwide. In this study, the role of PON1 was investigated in porcine alveolar macrophages (PAMs) during PRRSV infection. The results showed that PRRSV replication downregulated PON1, and the knockdown of PON1 significantly decreased PRRSV replication. Similarly, PON1 overexpression could enhance PRRSV replication. Interestingly, we observed that PON1 interacted with PRRSV nonstructural protein 9 (Nsp9), the RNA-dependent RNA polymerase, and the knockdown of PON1 lowered the RNA binding ability of Nsp9, suggesting that PON1 can facilitate Nsp9 function in viral replication. In addition, the knockdown of PON1 expression led to the amplification of type I interferon (IFN) genes and vice versa. In summary, our data demonstrate that PON1 facilitates PRRSV replication by interacting with Nsp9 and inhibiting the type I IFN signaling pathway. Hence, PON1 may be an additional component of the anti-PRRSV defenses.
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http://dx.doi.org/10.3390/v14061203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230610PMC
May 2022
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