Publications by authors named "Wenhui Li"

412 Publications

Defining Dravet syndrome: An essential pre-requisite for precision medicine trials.

Epilepsia 2021 Aug 2. Epub 2021 Aug 2.

Department of Medicine, Austin Health, Epilepsy Research Centre, University of Melbourne, Heidelberg, Vic., Australia.

Objective: The classical description of Dravet syndrome, the prototypic developmental and epileptic encephalopathy, is of a normal 6-month-old infant presenting with a prolonged, febrile, hemiclonic seizure and showing developmental slowing after age 1 year. SCN1A pathogenic variants are found in >80% of patients. Many patients have atypical features resulting in diagnostic delay and inappropriate therapy. We aimed to provide an evidence-based definition of SCN1A-Dravet syndrome in readiness for precision medicine trials.

Methods: Epilepsy patients were recruited to the University of Melbourne Epilepsy Genetics Research Program between 1995 and 2020 by neurologists from around the world. Patients with SCN1A pathogenic variants were reviewed and only those with Dravet syndrome were included. Clinical data, including seizure and developmental course, were analyzed in all patients with SCN1A-Dravet syndrome.

Results: Two hundred and five patients were studied at a median age of 8.5 years (range 10 months to 60 years); 25 were deceased. The median seizure-onset age was 5.7 months (range 1.5-20.6 months). Initial seizures were tonic-clonic (52%) and hemiclonic (35%), with only 55% being associated with fever. Only 34% of patients presented with status epilepticus (seizure lasting ≥30 minutes). Median time between first and second seizure was 30 days (range 4 hours to 8 months), and seven patients (5%) had at least 6 months between initial seizures. Median ages at onset of second and third seizure types were 9.1 months (range 3 months-25.4 years) and 15.5 months (range 4 months-8.2 years), respectively. Developmental slowing occurred prior to 12 months in 27%.

Significance: An evidence-based definition of SCN1A-Dravet syndrome is essential for early diagnosis. We refine the spectrum of Dravet syndrome, based on patterns of seizure onset, type, and progression. Understanding of the full spectrum of SCN1A-Dravet syndrome presentation is essential for early diagnosis and optimization of treatment, especially as precision medicine trials become available.
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http://dx.doi.org/10.1111/epi.17015DOI Listing
August 2021

Dynamic functional network connectivity associated with musical emotions evoked by different tempi.

Brain Connect 2021 Jul 26. Epub 2021 Jul 26.

Southwest University, 26463, School of Electronic and Information Engineering, Chongqing, Chongqing, China;

Background:Music tempo has strong clinical maneuverability and positive emotional effect in music therapy, which can directly evoke multiple emotions and dynamic neural changes in the whole-brain. However, the precise relationship between music tempo and its emotional effects remains unclear. The present study aimed to investigate the dynamic functional network connectivity (dFNC) associated with emotions elicited by music at different tempi.

Methods: We obtained emotion ratings of fast- (155-170 bpm), middle- (90 bpm), and slow-tempo (50-60 bpm) piano music from 40 participants both during and after functional magnetic resonance imaging (fMRI). Group independent component analysis (ICA), sliding time window correlations, and k-means clustering were used to assess dFNC of fMRI data. Paired t-tests were conducted to compare the difference of neural networks.

Results: (1) Fast music was associated with higher ratings of emotional valence and arousal, which were accompanied with increasing dFNC between somatomotor (SM) and cingulo-opercular (CO) networks and decreasing dFNC between fronto-parietal and SM networks. (2) Even with stronger activation in auditory (AUD) networks, slow music was associated with weaker emotion than fast music, with decreasing FNC across the brain and the participation of default mode (DM). (3) Middle-tempo music elicited moderate emotional activation with the most stable dFNC in the whole brain.

Conclusion: Faster music increases neural activity in the SM and CO regions, increasing the intensity of the emotional experience. In contrast, slower music was associated with decreasing engagement of AUD and stable engagement of DM, resulting in a weak emotional experience. These findings suggested that the time-varying aspects of functional connectivity can help to uncover the dynamic neural substrates of tempo-evoked emotion while listening to music.
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http://dx.doi.org/10.1089/brain.2021.0069DOI Listing
July 2021

The association between sarcopenia susceptibility and polymorphisms of FTO, ACVR2B, and IRS1 in Tibetans.

Mol Genet Genomic Med 2021 Jul 24:e1747. Epub 2021 Jul 24.

Institute of Biological Anthropology, Jinzhou Medical University, Jinzhou, China.

Background: Hypoxia within the plateau has a negative effect on skeletal muscle and may play a role in the development of sarcopenia in humans. Tibetans having lived in the Qinghai-Tibet Plateau for thousands of years, are a high-risk group for sarcopenia; however, they have a distinctive suite of genetic traits that enable them to tolerate environmental hypoxia and are genetically significantly different from Han Chinese and other lowland populations. Sarcopenia has been consistently found to be associated with single-nucleotide polymorphisms, but few studies have investigated the role of single-nucleotide polymorphisms in a range of muscle phenotypes and sarcopenia in Tibetan peoples.

Methods: Our study aimed to investigate the skeletal muscle mass and fat mass of 160 Tibetans (80 men and 80 women) from Lhasa (altitude of 3600 meters) and analyze the association between the polymorphisms of fat mass and obesity protein (FTO) rs9939609, FTO rs9936385, activin type IIB receptor (ACVR2B) rs2276541, insulin receptor substrate 1 (IRS1) 2943656 and sarcopenia.

Result: FTO rs9939609 and rs9936385 polymorphisms were associated with lower limb skeletal muscle mass and sarcopenia for Tibetan women, and TT homozygotes had a higher risk for sarcopenia. But ACVR2B rs2276541 and IRS1 2943656 polymorphisms were unassociated with sarcopenia in Tibetan.

Conclusion: In Tibetans, FTO rs9939609 and rs9936385 polymorphisms were associated with sarcopenia, and ACVR2B rs2276541 and IRS1 2943656 polymorphisms were unassociated with sarcopenia.
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http://dx.doi.org/10.1002/mgg3.1747DOI Listing
July 2021

Insights into molecular structure, genome evolution and phylogenetic implication through mitochondrial genome sequence of Gleditsia sinensis.

Sci Rep 2021 Jul 21;11(1):14850. Epub 2021 Jul 21.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Gleditsia sinensis is an endemic species widely distributed in China with high economic and medicinal value. To explore the genomic evolution and phylogenetic relationships of G. sinensis, the complete mitochondrial (mt) genome of G. sinensis was sequenced and assembled, which was firstly reported in Gleditsia. The mt genome was circular and 594,121 bp in length, including 37 protein-coding genes (PCGs), 19 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. The overall base composition of the G. sinensis mt genome was 27.4% for A, 27.4% for T, 22.6% for G, 22.7% for C. The comparative analysis of PCGs in Fabaceae species showed that most of the ribosomal protein genes and succinate dehydrogenase genes were lost. In addition, we found that the rps4 gene was only lost in G. sinensis, whereas it was retained in other Fabaceae species. The phylogenetic analysis based on shared PCGs of 24 species (22 Fabaceae and 2 Solanaceae) showed that G. sinensis is evolutionarily closer to Senna species. In general, this research will provide valuable information for the evolution of G. sinensis and provide insight into the phylogenetic relationships within the family Fabaceae.
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http://dx.doi.org/10.1038/s41598-021-93480-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295344PMC
July 2021

Cross-species transmission risk of livestock-associated MRSA: A systematic review and Bayesian meta-analysis of global data.

Prev Vet Med 2021 Jul 9;194:105429. Epub 2021 Jul 9.

Laboratory of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 283 Jianghai Street, Guangzhou, 510310, China. Electronic address:

Although increasing studies have indicated a strong relationship between livestock exposure and methicillin-resistant Staphylococcus aureus (MRSA) carriage in humans, the risk magnitude of cross-species transmission of livestock-associated MRSA (LA-MRSA) is still unclear. This meta-analysis aimed to evaluate the potential effect of livestock exposure on LA-MRSA (including CC398/CC9, scn-negative, and tetracycline-resistant isolates) transmission. The summary estimates were pooled by random-effects models using the DerSimonian & Laird (DL) method and the Bayesian method. Twenty-two studies were included in this meta-analysis. Livestock-exposed people demonstrated a significantly higher rate of livestock-associated S. aureus (LA-SA) carriage than non-exposed people (Bayesian estimates: OR = 5.23 for CC398/CC9; OR = 2.35 for scn-negative isolates; OR = 3.86 for tetracycline-resistant isolates). Similarly, there was a greater positive association between livestock exposure and LA-MRSA carriage in humans ((Bayesian estimates: OR = 7.64 for CC398/CC9; OR = 7.54 for scn-negative isolates; OR = 9.89 for tetracycline-resistant isolates), indicating that livestock exposure increases the risk of LA-MRSA carriage in humans. These findings provide evidence for revealing the high risk of cross-species LA-MRSA transmission by livestock exposure.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105429DOI Listing
July 2021

Universal Strategy for Improving Perovskite Photodiode Performance: Interfacial Built-In Electric Field Manipulated by Unintentional Doping.

Adv Sci (Weinh) 2021 Jul 15:e2101729. Epub 2021 Jul 15.

Guangdong University Key Laboratory for Advanced Quantum Dot Displays, Shenzhen Key Laboratory for Advanced Quantum Dot Displays and Lighting, Department of Electrical & Electronic Engineering, Southern University of Science and Technology, Xueyuan Blvd. 1088, Shenzhen, 518055, P. R. China.

Organic-inorganic halide perovskites have demonstrated significant light detection potential, with a performance comparable to that of commercially available photodetectors. In this study, a general design guideline, which is applicable to both inverted and regular structures, is proposed for high-performance perovskite photodiodes through an interfacial built-in electric field (E) for efficient carrier separation and transport. The interfacial E generated at the interface between the active and charge transport layers far from the incident light is critical for effective charge carrier collection. The interfacial E can be modulated by unintentional doping of the perovskite, whose doping type and density can be easily controlled by the post-annealing time and temperature. Employing the proposed design guideline, the inverted and regular perovskite photodiodes exhibit the external quantum efficiency of 83.51% and 76.5% and responsivities of 0.37 and 0.34 A W , respectively. In the self-powered mode, the dark currents reach 7.95 × 10 and 1.47 × 10 A cm , providing high detectivities of 7.34 × 10 and 4.96 × 10 Jones, for inverted and regular structures, respectively, and a long-term stability of at least 1600 h. This optimization strategy is compatible with existing materials and device structures and hence leads to substantial potential applications in perovskite-based optoelectronic devices.
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http://dx.doi.org/10.1002/advs.202101729DOI Listing
July 2021

Access to highly functionalized imidazolones bearing α-amino acid esters KOH-promoted annulation of amidines, nitrosoarenes and malonic esters.

Org Biomol Chem 2021 Jul;19(29):6473-6477

College of Biomedical Engineering, Taiyuan University of Technology, 79 West Yingze Street, Taiyuan 030024, China.

An efficient approach to obtain highly functionalized imidazolones bearing α-amino acid esters through KOH-mediated one-pot three-component annulation of amidines, nitrosoarenes and malonic esters is reported. This reaction features broad substrate scope, a cheap and readily available promoter, good to high yields for most substrates and mild reaction conditions. The mechanism study shows that the KOH-mediated formation of the imine intermediate via the reaction of nitrosoarenes with malonic esters is a key step.
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http://dx.doi.org/10.1039/d1ob00930cDOI Listing
July 2021

Transcriptionally inactive hepatitis B virus episome DNA preferentially resides in the vicinity of chromosome 19 in 3D host genome upon infection.

Cell Rep 2021 Jun;35(13):109288

National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China. Electronic address:

The hepatitis B virus (HBV) infects 257 million people worldwide. HBV infection requires establishment and persistence of covalently closed circular (ccc) DNA, a viral episome, in nucleus. Here, we study cccDNA spatial localization in the 3D host genome by using chromosome conformation capture-based sequencing analysis and fluorescence in situ hybridization (FISH). We show that transcriptionally inactive cccDNA is not randomly distributed in host nucleus. Rather, it is preferentially accumulated at specialized areas, including regions close to chromosome 19 (chr.19). Activation of the cccDNA is apparently associated with its re-localization, from a pre-established heterochromatin hub formed by 5 regions of chr.19 to transcriptionally active regions formed by chr.19 and nearby chromosomes including chr.16, 17, 20, and 22. This active versus inactive positioning at discrete regions of the host genome is primarily controlled by the viral HBx protein and by host factors including the structural maintenance of chromosomes protein 5/6 (SMC5/6) complex.
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http://dx.doi.org/10.1016/j.celrep.2021.109288DOI Listing
June 2021

A nomogram prediction model for lymph node metastasis in endometrial cancer patients.

BMC Cancer 2021 Jun 29;21(1):748. Epub 2021 Jun 29.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong Province, 250012, P. R. China.

Background: This study aimed to explore the risk factors for lymph node metastasis (LNM) in patients with endometrial cancer (EC) and develop a clinically useful nomogram based on clinicopathological parameters to predict it.

Methods: Clinical information of patients who underwent staging surgery for EC was abstracted from Qilu Hospital of Shandong University from January 1st, 2005 to June 31st, 2019. Parameters including patient-related, tumor-related, and preoperative hematologic examination-related were analyzed by univariate and multivariate logistic regression to determine the correlation with LNM. A nomogram based on the multivariate results was constructed and underwent internal and external validation to predict the probability of LNM.

Results: The overall data from the 1517 patients who met the inclusion criteria were analyzed. 105(6.29%) patients had LNM. According the univariate analysis and multivariate logistic regression analysis, LVSI is the most predictive factor for LNM, patients with positive LVSI had 13.156-fold increased risk for LNM (95%CI:6.834-25.324; P < 0.001). The nomogram was constructed and incorporated valuable parameters including histological type, histological grade, depth of myometrial invasion, LVSI, cervical involvement, parametrial involvement, and HGB levels from training set. The nomogram was cross-validated internally by the 1000 bootstrap sample and showed good discrimination accuracy. The c-index for internal and external validation of the nomogram are 0.916(95%CI:0.849-0.982) and 0.873(95%CI:0.776-0.970), respectively.

Conclusions: We developed and validated a 7-variable nomogram with a high concordance probability to predict the risk of LNM in patients with EC.
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http://dx.doi.org/10.1186/s12885-021-08466-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243766PMC
June 2021

CircRNA_100290 promotes GC cell proliferation and invasion via the miR-29b-3p/ITGA11 axis and is regulated by EIF4A3.

Cancer Cell Int 2021 Jun 28;21(1):324. Epub 2021 Jun 28.

Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning Province, China.

Background: Circular RNAs (circRNAs) have been reported to be important regulators of the development and progression of various carcinomas. However, the role of circRNA_100290 in gastric cancer (GC) is still unclear. This study aimed to investigate the role of circRNA_100290 in GC invasion and metastasis and the possible underlying mechanism.

Methods: The expression of circRNA_100290 in GC cells and tissues was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circRNA_100290 in cell proliferation, migration, and invasion was evaluated in the AGS and HGC-27 cell lines in vitro. Bioinformatics tools, dual-luciferase reporter assays, Western blot assays and qRT-PCR were used to explore the pathways downstream of circRNA_100290. The mechanism underlying the regulation of circRNA_100290 expression was explored using RNA immunoprecipitation, qRT-PCR, and Western blot assays.

Results: The expression of circRNA_100290 was significantly upregulated in GC cells and 102 GC tissues, and high circRNA_100290 expression in GC was closely related to Borrmann's type, lymph node metastasis and tumour-node-metastasis stage. In vitro, knockdown of circRNA_100290 in AGS and HGC-27 cells significantly inhibited cell proliferation, migration, and invasion. Mechanistically, a dual-luciferase reporter assay confirmed the direct interaction between circRNA_100290 and miR-29b-3p, which targets ITGA11, an oncogene that is closely related to epithelial-mesenchymal transition (EMT). In addition, EIF4A3, an RNA-binding protein (RBP), could inhibit the formation of circRNA_100290 by binding to the flanking sites of circRNA_100290. Low EIF4A3 expression in GC was related to a poor prognosis.

Conclusions: Elevated circRNA_100290 expression in GC promotes cell proliferation, invasion and EMT via the miR-29b-3p/ITGA11 axis and might be regulated by EIF4A3. CircRNA_100290 might be a promising biomarker and target for GC therapy.
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http://dx.doi.org/10.1186/s12935-021-01964-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240270PMC
June 2021

Leveraging 16S rRNA Microbiome Sequencing Data to Identify Bacterial Signatures for Irritable Bowel Syndrome.

Front Cell Infect Microbiol 2021 11;11:645951. Epub 2021 Jun 11.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain or discomfort. Previous studies have illustrated that the gut microbiota might play a critical role in IBS, but the conclusions of these studies, based on various methods, were almost impossible to compare, and reproducible microorganism signatures were still in question. To cope with this problem, previously published 16S rRNA gene sequencing data from 439 fecal samples, including 253 IBS samples and 186 control samples, were collected and processed with a uniform bioinformatic pipeline. Although we found no significant differences in community structures between IBS and healthy controls at the amplicon sequence variants (ASV) level, machine learning (ML) approaches enabled us to discriminate IBS from healthy controls at genus level. Linear discriminant analysis effect size (LEfSe) analysis was subsequently used to seek out 97 biomarkers across all studies. Then, we quantified the standardized mean difference (SMDs) for all significant genera identified by LEfSe and ML approaches. Pooled results showed that the SMDs of nine genera had statistical significance, in which the abundance of , and in IBS were higher, while the dominant abundance genera of healthy controls were Ruminococcaceae , , , and . In summary, based on six published studies, this study identified nine new microbiome biomarkers of IBS, which might be a basis for understanding the key gut microbes associated with IBS, and could be used as potential targets for microbiome-based diagnostics and therapeutics.
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http://dx.doi.org/10.3389/fcimb.2021.645951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231010PMC
July 2021

X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3.

PLoS Genet 2021 Jun 23;17(6):e1009608. Epub 2021 Jun 23.

Ministry of Education Key Laboratory of Model Animal for Disease Study, Department of Neurology, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.

The X-linked GRIA3 gene encodes the GLUA3 subunit of AMPA-type glutamate receptors. Pathogenic variants in this gene were previously reported in neurodevelopmental diseases, mostly in male patients but rarely in females. Here we report a de novo pathogenic missense variant in GRIA3 (c.1979G>C; p. R660T) identified in a 1-year-old female patient with severe epilepsy and global developmental delay. When exogenously expressed in human embryonic kidney (HEK) cells, GLUA3_R660T showed slower desensitization and deactivation kinetics compared to wildtype (wt) GLUA3 receptors. Substantial non-desensitized currents were observed with the mutant but not for wt GLUA3 with prolonged exposure to glutamate. When co-expressed with GLUA2, the decay kinetics were similarly slowed in GLUA2/A3_R660T with non-desensitized steady state currents. In cultured cerebellar granule neurons, miniature excitatory postsynaptic currents (mEPSCs) were significantly slower in R660T transfected cells than those expressing wt GLUA3. When overexpressed in hippocampal CA1 neurons by in utero electroporation, the evoked EPSCs and mEPSCs were slower in neurons expressing R660T mutant compared to those expressing wt GLUA3. Therefore our study provides functional evidence that a gain of function (GoF) variant in GRIA3 may cause epileptic encephalopathy and global developmental delay in a female subject by enhancing synaptic transmission.
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http://dx.doi.org/10.1371/journal.pgen.1009608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259962PMC
June 2021

The Application and Development of Deep Learning in Radiotherapy: A Systematic Review.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211016386

Department of Radiation Oncology, 531840The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, Yunnan, China.

With the massive use of computers, the growth and explosion of data has greatly promoted the development of artificial intelligence (AI). The rise of deep learning (DL) algorithms, such as convolutional neural networks (CNN), has provided radiation oncologists with many promising tools that can simplify the complex radiotherapy process in the clinical work of radiation oncology, improve the accuracy and objectivity of diagnosis, and reduce the workload, thus enabling clinicians to spend more time on advanced decision-making tasks. As the development of DL gets closer to clinical practice, radiation oncologists will need to be more familiar with its principles to properly evaluate and use this powerful tool. In this paper, we explain the development and basic concepts of AI and discuss its application in radiation oncology based on different task categories of DL algorithms. This work clarifies the possibility of further development of DL in radiation oncology.
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http://dx.doi.org/10.1177/15330338211016386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216350PMC
June 2021

G9a Regulates Cell Sensitivity to Radiotherapy via Histone H3 Lysine 9 Trimethylation and CCDC8 in Lung Cancer.

Onco Targets Ther 2021 10;14:3721-3728. Epub 2021 Jun 10.

Department of Radiotherapy, Third Affiliated Hospital of Kunming Medical, Yunnan Cancer Hospital, Kunming City, Yunnan Province, People's Republic of China.

Purpose: To investigate the role and underlying mechanism of G9a and CCDC8 in lung cancer radioresistance.

Methods: Western blotting assays were used for G9a, CCDC8, H3K9me3 expression detection. MTT assays and clone formation assays were used for measuring cell proliferation activities. Flow cytometry assays were used for cell apoptosis detection. The enrichment of H3K9me3 in CCDC8 promoter was measured by chromatin immunoprecipitation assay.

Results: G9a and G9a-mediated H3K9me3 are upregulated in radioresistant lung cancer cells (A549/IR cell and XWLC-05/IR cell). Blocking G9a not only promotes radiosensitivity of A549/IR cell and XWLC-05/IR cell but also reduces aggressive behavior of radioresistant A549 cell/IR and XWLC-05/IR cell. In addition, G9a-controlled H3K9me3 is able to binding to the promoter of tumor suppressor gene CCDC8 and suppresses CCDC8 expression. CCDC8 dysregulation is responsible for G9a-mediated radioresistance of A549/IR cell and XWLC-05/IR cell.

Conclusion: G9a and H3K9me3 contribute to the lung cancer radioresistance via modulating CCDC8 expression.
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http://dx.doi.org/10.2147/OTT.S296937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203200PMC
June 2021

Different effects of soybean protein and its derived peptides on the growth and metabolism of subsp. JCM 1190.

Food Funct 2021 Jul;12(13):5731-5744

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, National Soybean Processing Industry Technology Innovation Center, Beijing Technology and Business University, Beijing 100048, China.

Bifidobacterium is a common probiotic that plays a vital role in the intestinal tract. This study aimed to explore the different effects of soybean protein and soybean peptides on the growth and metabolism of Bifidobacterium animalis subsp. animalis JCM 1190. Soybean protein and soybean peptides were digested in vitro, after which different nitrogen source containing media were prepared and used for the monoculture of Bifidobacterium animalis subsp. animalis JCM 1190 and the co-culture of Bifidobacterium animalis subsp. animalis JCM 1190 and Escherichia coli JCM 1649. During the culture process, the viable cell number and lactic acid and acetic acid contents were measured, while non-targeted metabonomics was used to detect the differential metabolites and metabolic pathways. The results showed that soybean protein and soybean peptides promoted the growth and metabolism of Bifidobacterium animalis subsp. animalis JCM 1190, while digested soybean peptides had a better effect. Digested soybean peptides increased the viable cell number and lactic acid and acetic acid contents in the monoculture by regulating glycine, serine, and threonine metabolism, as well as pyruvate metabolism, the TCA cycle, glycolipid metabolism, and other metabolic pathways, balanced the ability of Bifidobacterium animalis subsp. animalis JCM 1190 and Escherichia coli JCM 1649 to utilize nitrogen sources during the early period and enhanced the competitiveness of Bifidobacterium animalis subsp. animalis JCM 1190 during the later period in co-culture.
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http://dx.doi.org/10.1039/d1fo00480hDOI Listing
July 2021

Palmitic acid mediated change of rhizosphere and alleviation of Fusarium wilt disease in watermelon.

Saudi J Biol Sci 2021 Jun 18;28(6):3616-3623. Epub 2021 Mar 18.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northeast Region), Ministry of Agriculture and Rural Development, Northeast Agricultural University, Harbin 150030, China.

Palmitic acid (PA) in root exudates or decaying residues can reduce the incidence of soil-borne diseases and promote the growth of some crop plants. However, the effects of PA on soil-borne pathogens and microbial communities are poorly understood. Here, we investigate the effects of PA on overall watermelon microbial communities and the populations of f.sp (Fon). The effects of PA on the mycelial growth and spore production of Fon were tested , while its effects on Fon, total bacteria and total fungi populations, and microbial communities were evaluated in a pot experiment. The results revealed that all test concentrations of PA inhibited Fon mycelia growth and spore production. The pot experiment showed that 0.5 mM and 1 mM PA reduced Fon but increased total bacteria populations, and 0.5 mM and 1 mM PA 0.5 mM and 1 mM PA promoted the change to a soil type of bacteria soil. Meanwhile, 0.5 mM PA and 1 mM PA altered the community composition of the rhizosphere microorganisms and reduced the relative abundance of two bacterial operational taxonomic units (OTUs) and the two fungal OTUs that were significantly ( < 0.01) related with disease severity and increased that of four bacterial OTUs and the two fungal that were highly significantly ( < 0.01) negatively correlated with the disease severity. These results suggest that application of PA decreased the populations of Fon, changed the rhizosphere microbial composition, reduced the disease severity of Fusarium wilt, and promoted the growth of watermelon.
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http://dx.doi.org/10.1016/j.sjbs.2021.03.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176049PMC
June 2021

LncRNA TUG1/miR-29c-3p/SIRT1 axis regulates endoplasmic reticulum stress-mediated renal epithelial cells injury in diabetic nephropathy model in vitro.

PLoS One 2021 7;16(6):e0252761. Epub 2021 Jun 7.

Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining city, Shandong Province, P.R.China.

Long non-coding RNAs (lncRNAs) are important regulators in diabetic nephropathy. In this study, we investigated the potential role of lncRNA TUG1 in regulating endoplasmic reticulum stress (ERS)-mediated apoptosis in high glucose induced renal tubular epithelial cells. Human renal tubular epithelial cell line HK-2 was challenged with high glucose following transfection with lncRNA TUG1, miR-29c-3p mimics or inhibitor expression plasmid, either alone or in combination, for different experimental purposes. Potential binding effects between TUG1 and miR-29c-3p, as well as between miR-29c-3p and SIRT1 were verified. High glucose induced apoptosis and ERS in HK-2 cells, and significantly decreased TUG1 expression. Overexpressed TUG1 could prevent high glucose-induced apoptosis and alleviated ERS via negatively regulating miR-29c-3p. In contrast, miR-29c-3p increased HK-2 cells apoptosis and ERS upon high glucose-challenge. SIRT1 was a direct target gene of miR-29c-3p in HK-2 cells, which participated in the effects of miR-29c-3p on HK-2 cells. Mechanistically, TUG1 suppressed the expression of miR-29c-3p, thus counteracting its function in downregulating the level of SIRT1. TUG1 regulates miR-29c-3p/SIRT1 and subsequent ERS to relieve high glucose induced renal epithelial cells injury, and suggests a potential role for TUG1 as a promising diagnostic marker of diabetic nephropathy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252761PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183992PMC
June 2021

High-resolution genome-wide association study and genomic prediction for disease resistance and cold tolerance in wheat.

Theor Appl Genet 2021 Jun 1. Epub 2021 Jun 1.

State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, Tai'an 271018, China.

Key Message: High-resolution genome-wide association study (GWAS) facilitated QTL fine mapping and candidate gene identification, and the GWAS based genomic prediction models were highly predictive and valuable in wheat genomic breeding. Wheat is a major staple food crop and provides more than one-fifth of the daily calories and dietary proteins for humans. Genome-wide association study (GWAS) and genomic selection (GS) for wheat stress resistance and tolerance related traits are critical to understanding their genetic architecture for improvement of breeding selection efficiency. However, the insufficient marker density in previous studies limited the utility of GWAS and GS in wheat genomic breeding. Here, we conducted a high-resolution GWAS for wheat leaf rust (LR), yellow rust (YR), powdery mildew (PM), and cold tolerance (CT) by genotyping a panel of 768 wheat cultivars using genotyping-by-sequencing. Among 153 quantitative trait loci (QTLs) identified, 81 QTLs were delimited to ≤ 1.0 Mb intervals with three validated using bi-parental populations. Furthermore, 837 stress resistance-related genes were identified in the QTL regions with 12 showing induced expression by YR and PM pathogens. Genomic prediction using 2608, 4064, 3907, and 2136 pre-selected SNPs based on GWAS and genotypic correlations between the SNPs showed high prediction accuracies of 0.76, 0.73, and 0.78 for resistance to LR, YR, and PM, respectively, and 0.83 for resistance to cold damage. Our study laid a solid foundation for large-scale QTL fine mapping, candidate gene validation and GS in wheat.
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http://dx.doi.org/10.1007/s00122-021-03863-6DOI Listing
June 2021

The Halophyte AP2/ERF Transcription Factor HcTOE3 Positively Regulates Freezing Tolerance in .

Front Plant Sci 2021 13;12:638788. Epub 2021 May 13.

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

The APETALA2 (AP2) and ethylene-responsive element-binding factor (ERF) gene family is one of the largest plant-specific transcription factor gene families, which plays a critical role in plant development and evolution, as well as response to various stresses. () gene is derived from and belongs to the AP2 subfamily with two AP2 DNA-binding domains. Currently, AP2 family mainly plays crucial roles in plant growth and evolution, yet there are few reports about the role of AP2 in abiotic stress tolerance. Here, we report , a new cold-regulated transcription factor gene, which has an important contribution to freezing tolerance. The main results showed that the expression of in the assimilating branches was strongly induced by different abiotic stresses, including high salinity, drought, and extreme temperature (heat, chilling, and freezing), as well as abscisic acid and methyl viologen treatments. Overexpressing gene (OE) induced transgenic plant tolerance to freezing stress. Under freezing treatment, the OE lines showed lower content of malondialdehyde and electrolyte leakage and less accumulation of reactive oxygen species compared with the wild type. However, the survival rates, antioxidant enzyme activities, and contents of osmotic adjustment substance proline were enhanced in transgenic plants. Additionally, the OE lines increased freezing tolerance by up-regulating the transcription level of cold responsive genes (, , , , , and ) and abscisic acid signal transduction pathway genes (, , , and ). Our results suggested that HcTOE3 positively regulated freezing stress and has a great potential as a candidate gene to improve plant freezing tolerance.
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http://dx.doi.org/10.3389/fpls.2021.638788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155596PMC
May 2021

Hyperbaric oxygen therapy for chronic diabetic foot ulcers: An overview of systematic reviews.

Diabetes Res Clin Pract 2021 Jun 17;176:108862. Epub 2021 May 17.

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China. Electronic address:

Objectives: Hyperbaric oxygen therapy in the treatment of diabetic foot ulcer has been widely used in medical practice, but its clinical effect is not clear. The purpose of this overview of systematic reviews is to evaluate the clinical evidence of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers.

Methods: PubMed, Cochrane Library, Web of Knowledge, Embase, MEDLINE, Chinese National Knowledge Infrastructure Database, the Chongqing VIP Database, Chinese Biomedical Database, and Wanfang Database were searched in 1st December 2020. Systematic reviews (SRs) evaluating the effects of Hyperbaric oxygen therapy in people with diabetic foot ulcer were included. Methodological quality of the included SRs was assessed using the AMSTAR-2 tool. The quality of evidence of the primary studies was assessed using GRADE. The integrity of the included SRs was assessed using PRISMA. The bias risk of each SR was assessed using ROBIS evaluation tool.

Results: Eleven SRs/MAs met all inclusion criteria. According to the results of the AMSTAR-2, only 1 included review were rated critically as being of high quality, 6 included review were rated critically as being of medium quality. With PRISMA, the reporting checklist was relatively complete, but some reporting weaknesses remained in the topics of the protocol and registration, search strategy, and additional analyses. Based on the ROBIS tool, only five SRs/MAs had a low risk of bias. With the GRADE system, no high-quality evidence was found, and only 13 outcomes provided moderate-quality evidence.

Conclusions: There is limited clinical evidence to support hyperbaric oxygen therapy in the treatment of diabetic foot ulcers, it is not recommended to routinely apply hyperbaric oxygen therapy to all patients with diabetic foot ulcers, especially those with non-ischemic diabetic foot ulcers. Hyperbaric oxygen therapy has certain potential to promote ulcer healing and reduce amputation rate in patients with ischemic diabetic foot ulcers, but due to the low quality and small quantity of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.
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http://dx.doi.org/10.1016/j.diabres.2021.108862DOI Listing
June 2021

PTTG1 knockdown enhances radiation-induced antitumour immunity in lung adenocarcinoma.

Life Sci 2021 Jul 11;277:119594. Epub 2021 May 11.

Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, PR China. Electronic address:

Aim: Ionizing radiation (IR) can induce local and systemic antitumour immune responses to some degree and augment immunotherapeutic efficacy. IR may also increase residual tumour cell invasion and elicit immunosuppression in the tumour microenvironment (TME). It remains poorly understand, whether IR leads to immune negative response or invasive capacity increases in lung adenocarcinoma (LAC).

Materials And Methods: RNA interference (RNAi) was used to silence pituitary tumour-transforming gene-1 (PTTG1) and SMAD3 expression in LAC cells. A coculture system of tumour cells and PBMCs was constructed. Cells were exposed to different doses (0, 4 and 8 Gy) of X-ray irradiation. Flow cytometric analysis and Transwell assays were applied. An orthotopic Lewis lung cancer (LLC) mouse tumour model was established. Bioluminescence imaging (BLI) was used. LLC tumours were exposed to a single 15 Gy dose of X-ray irradiation.

Key Findings: PTTG1 knockdown reinforced the inhibitory effect of IR on the invasive ability of A549 cells and enhanced the antitumour T cell immunity induced by IR via the transforming growth factor-β1 (TGF-β1)/SMAD3 pathway. Positive antitumour immune response and immunosuppression were simultaneously triggered by a single 15 Gy dose of local tumour irradiation. PTTG1 knockdown weakened invasive capacity and promoted the immune response balance induced by IR to tilt towards active immunity, which contributed to reduce metastasis and prolonged overall survival (OS) in orthotopic LLC tumour-bearing mouse.

Significance: Targeted blockade of PTTG1 and the TGF-β1/SMAD3 pathway may ameliorate the immunosuppressive TME and enhance the systemic antitumour immune response induced by a single high-dose IR treatment.
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http://dx.doi.org/10.1016/j.lfs.2021.119594DOI Listing
July 2021

Efficacy and Safety of Platinum-Based Chemotherapy as First-Line Therapy for Metastatic Triple-Negative Breast Cancer: A Meta-Analysis of Randomized Controlled Trials.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211016369

Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, 531840Tumor Hospital of Yunnan Province, Kunming, Yunnan, China.

Background: Triple-negative breast cancer constitutes approximately 12%-17% of all breast cancer cases, and >33% of patients develop distant metastases. Systemic cytotoxic chemotherapy is the primary treatment for patients with metastatic triple-negative breast cancer; however, the role of first-line platinum-based chemotherapy in these patients remains controversial. This meta-analysis evaluated the efficacy and safety of platinum-based first-line chemotherapy for patients with metastatic triple-negative breast cancer.

Methods: We systematically searched the PubMed, Embase, Cochrane, and Clinical Trials registry databases up to June 1, 2020 to identify randomized controlled trials that investigated platinum-based vs. first-line platinum-free chemotherapy in patients with metastatic triple-negative breast cancer. We used fixed and random effects models to calculate pooled hazard ratios and odds ratios with 95% confidence intervals for progression-free and overall survival, objective response rates, and grade 3 and 4 adverse events.

Results: Four randomized controlled trials ( = 590 patients) were included. Platinum-based chemotherapy significantly increased the objective response rates from 43.1% to 62.7% (odds ratio 2.34, 95% confidence interval 1.66-3.28, < 0.001). Three randomized controlled trials ( = 414 patients) reported survival outcomes. Patients administered platinum-based regimens showed significantly longer progression-free survival (hazard ratio 0.55, 95% confidence interval 0.37-0.82, = 0.004) and a nonsignificant trend toward improved overall survival (hazard ratio 0.76, 95% confidence interval 0.57-1.00, = 0.05). Only 2 studies reported the rates of grade 3 and 4 adverse events; grade 3-4 thrombocytopenia was more commonly associated with platinum-based chemotherapy (odds ratio 7.54, 95% confidence interval 1.37-41.60, = 0.02) and grade 3-4 fatigue with platinum-free chemotherapy (odds ratio 0.23, 95% confidence interval 0.08-0.68, = 0.008).

Conclusions: First-line platinum-based chemotherapy was associated with significantly increased objective response rates, longer progression-free survival, and a nonsignificant trend toward improved overall survival in patients with metastatic triple-negative breast cancer at the high risk of grade 3-4 thrombocytopenia.
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http://dx.doi.org/10.1177/15330338211016369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120541PMC
May 2021

An Engineered Receptor-Binding Domain Improves the Immunogenicity of Multivalent SARS-CoV-2 Vaccines.

mBio 2021 05 11;12(3). Epub 2021 May 11.

Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino-acid fragment of the 1,273-amino-acid S-protein protomer. The RBD is the primary SARS-CoV-2 neutralizing epitope and a critical target of any SARS-CoV-2 vaccine. Here, we show that this RBD conjugated to each of two carrier proteins elicited more potent neutralizing responses in immunized rodents than did a similarly conjugated proline-stabilized S-protein ectodomain. Nonetheless, the native RBD is expressed inefficiently, limiting its usefulness as a vaccine antigen. However, we show that an RBD engineered with four novel glycosylation sites (gRBD) is expressed markedly more efficiently and generates a more potent neutralizing responses as a DNA vaccine antigen than the wild-type RBD or the full-length S protein, especially when fused to multivalent carriers, such as a ferritin 24-mer. Further, gRBD is more immunogenic than the wild-type RBD when administered as a subunit protein vaccine. Our data suggest that multivalent gRBD antigens can reduce costs and doses, and improve the immunogenicity, of all major classes of SARS-CoV-2 vaccines. All available vaccines for coronavirus disease 2019 (COVID-19) express or deliver the full-length SARS-CoV-2 spike (S) protein. We show that this antigen is not optimal, consistent with observations that the vast majority of the neutralizing response to the virus is focused on the S-protein receptor-binding domain (RBD). However, this RBD is not expressed well as an independent domain, especially when expressed as a fusion protein with a multivalent scaffold. We therefore engineered a more highly expressed form of the SARS-CoV-2 RBD by introducing four glycosylation sites into a face of the RBD normally occluded in the full S protein. We show that this engineered protein, gRBD, is more immunogenic than the wild-type RBD or the full-length S protein in both genetic and protein-delivered vaccines.
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http://dx.doi.org/10.1128/mBio.00930-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262850PMC
May 2021

Effects of Physical Stimulation in the Field of Oral Health.

Scanning 2021 7;2021:5517567. Epub 2021 Apr 7.

Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, Shandong 271016, China.

Physical stimulation has been widely used in clinical medicine and healthcare due to its noninvasiveness. The main applications of physical stimulation in the oral cavity include laser, ultrasound, magnetic field, and vibration, which have photothermal, cavitation, magnetocaloric, and mechanical effects, respectively. In addition, the above four stimulations with their unique biological effects, which can play a role at the gene, protein, and cell levels, can provide new methods for the treatment and prevention of common oral diseases. These four physical stimulations have been used as important auxiliary treatment methods in the field of orthodontics, implants, periodontal, dental pulp, maxillofacial surgery, and oral mucosa. This paper systematically describes the application of physical stimulation as a therapeutic method in the field of stomatology to provide guidance for clinicians. In addition, some applications of physical stimulation in specific directions are still at the research stage, and the specific mechanism has not been fully elucidated. To encourage further research on the oral applications of physical stimulation, we elaborate the research results and development history of various physical stimuli in the field of oral health.
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http://dx.doi.org/10.1155/2021/5517567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049832PMC
April 2021

Design of Dimeric Bile Acid Derivatives as Potent and Selective Human NTCP Inhibitors.

J Med Chem 2021 05 27;64(9):5973-6007. Epub 2021 Apr 27.

National Institute of Biological Sciences, Beijing 102206, China.

Dimeric bile acid derivatives (DBADs) were developed and tested for their anti-HBV and anti-HDV activities as sodium taurocholate cotransporting polypeptide (NTCP) inhibitors. DBADs exhibited strong and persistent potency of NTCP inhibition, whereas diverse linkers and constitutions showed distinct inhibition features. Motif aa157-165 on NTCP was shown to be a possible binding site of DBADs; therefore, we determined DBADs' selectivity among NTCPs from different species. A cyclized DBAD scaffold DBA-41 exhibited a high affinity to human NTCP (hNTCP). Intraperitoneal administration of DBA-41 to hNTCP-tg mice induced serum total bile acid elevation. DBA-41 may serve as a biological tool to study NTCP physiological function.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00078DOI Listing
May 2021

Xueshuantong Injection in Treating Deep Venous Thrombosis: A Systematic Review and Trial Sequential Analysis.

Evid Based Complement Alternat Med 2021 7;2021:6622925. Epub 2021 Apr 7.

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Aims: In recent years, the incidence of deep venous thrombosis (DVT) presents an increasing trend year by year. The current evidence regarding the efficacy and safety of Xueshuantong injection for DVT is controversial. This systematic review (SR) aimed to assess the efficacy and safety of Xueshuantong injection in the treatment of DVT systematically and provide an evidence-based reference for clinical treatment.

Methods: Nine electronic databases were used to identify the literature consisting of randomized controlled trials (RCTs) with a date of search of 1 November 2020. Clinical effective rate and incidence rate of adverse events were investigated as primary outcomes. Patency rate of femoral vein, patency rate of popliteal vein, patency rate of posterior tibial vein, circumference difference, activated partial thromboplastin time (APTT), and D-dimer (D-D) were investigated as secondary outcomes. Revman 5.4.1 was used to analyze the results. Analysis of the power of evidence was performed with Trial Sequential Analysis (TSA).

Results: A total of 12 articles including 1018 patients were included. The results of the meta-analysis showed that the clinical effective rate in the experimental group was higher than that in the control group, the incidence rate of adverse events in the experimental group was higher than that in the control group; after the operation, the patency rate of femoral vein, patency rate of popliteal vein, patency rate of posterior tibial vein, circumference difference, APTT, and D-D in the experimental group were significantly improved compared with those in the control group, and the difference between the groups was statistically significant. TSA suggested that the meta-analysis concerning the clinical effectiveness of Xueshuantong injection in the treatment of DVT was of adequate power to reach firm conclusions.

Conclusion: Based on the current analysis, Xueshuantong injection as an add-on treatment provided better treatment effect for DVT with adequate power but this benefit should be considered with caution because of the small number of studies included in the meta-analysis and the high or unclear risk of bias of the included trials, suggesting that further studies are needed.
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http://dx.doi.org/10.1155/2021/6622925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046544PMC
April 2021

Palladium-Catalyzed Decarbonylative Sonogashira Coupling of Terminal Alkynes with Carboxylic Acids.

Org Lett 2021 05 20;23(9):3304-3309. Epub 2021 Apr 20.

Key Laboratory of Ministry of Education for Advanced Materials in Tropical Island Resources, Hainan Provincial Key Lab of Fine Chem, Hainan Provincial Fine Chemical Engineering Research Center, Hainan University, Haikou 570228, China.

A direct decarbonylative Sonogashira coupling of terminal alkynes with carboxylic acids was achieved through palladium catalysis. This reaction did not use overstoichiometric oxidants, thus overcoming the homocoupling issue of terminal alkynes. Under the reaction conditions, a wide range of carboxylic acids including those bioactive ones could couple readily with various terminal alkynes, thus providing a relative general method for preparing internal alkynes.
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http://dx.doi.org/10.1021/acs.orglett.1c00768DOI Listing
May 2021

Recombinant pseudorabies virus with gI/gE deletion generated by overlapping polymerase chain reaction and homologous recombination technology induces protection against the PRV variant PRV-GD2013.

BMC Vet Res 2021 Apr 14;17(1):164. Epub 2021 Apr 14.

College of Veterinary Medicine, South China Agricultural University, 483 Wu Shan Road, Tianhe District, Guangzhou, 510642, Guangdong Province, China.

Background: Since 2011, numerous highly virulent and antigenic variant viral strains have been reported in pigs that were vaccinated against the swine pseudorabies virus. These infections have led to substantial economic losses in the Chinese swine industry.

Results: This study, constructed a novel recombinant vaccine strain with gI/gE deletion (PRV-GD2013-ΔgI/gE) by overlapping PCR and homologous recombination technology. The growth curves and plaque morphology of the recombinant virus were similar to those of the parental strain. However, PRV-GD2013-ΔgI/gE infection was significantly attenuated in mice compared with that of PRV-GD2013. Two-week-old piglets had normal rectal temperatures and displayed no clinical symptoms after being inoculated with 10 TCID PRV-GD2013-ΔgI/gE, indicating that the recombinant virus was avirulent in piglets. Piglets were immunized with different doses of PRV-GD2013-ΔgI/gE, or a single dose of Bartha-K61 or DMEM, and infected with PRV-GD2013 at 14 days post-vaccination. Piglets given high doses of PRV-GD2013-ΔgI/gE showed no obvious clinical symptoms, and their antibody levels were higher than those of other groups, indicating that the piglets were completely protected from PRV-GD2013.

Conclusions: The PRV-GD2013-ΔgI/gE vaccine strain could be effective for immunizing Chinese swine herds against the pseudorabies virus (PRV) strain.
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http://dx.doi.org/10.1186/s12917-021-02861-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048318PMC
April 2021
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