Publications by authors named "Hailong Liu"

171 Publications

De novo transcriptome assembly and EST-SSR markers development for Zelkova schneideriana Hand.-Mazz. (Ulmaceae).

3 Biotech 2021 Sep 30;11(9):420. Epub 2021 Aug 30.

Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014 China.

Hand.-Mazz. of the Ulmaceae family is a Tertiary relict and economically deciduous tree species endemic to Central and Southern China. In this study, we performed a transcriptome sequencing of using high-throughput sequencing approach to detect polymorphic expressed sequence tag-simple sequence repeats (EST-SSR) markers. A total of 3,235 microsatellite loci were detected from 53,517 unigenes. A set of 30 microsatellite markers were randomly selected to validate in 41 individuals from three populations, of which 10 were polymorphic. The number of alleles per locus ranged from 3 to 11. The observed heterozygosity and expected heterozygosity ranged from 0.366 to 0.829 and 0.439 to 0.848, respectively. These polymorphic SSR primers showed good transferability across different species, and are valuable for future studies on genetic diversity, conservation, phylogeography, and species delimitation in , as well as other species.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02968-5.
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http://dx.doi.org/10.1007/s13205-021-02968-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405759PMC
September 2021

The short-term safety and effectiveness of a new distal perforating stent graft in Type B aortic dissection: a retrospective study.

BMC Cardiovasc Disord 2021 Sep 21;21(1):457. Epub 2021 Sep 21.

Vascular Intervention Department, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China.

Background: Spinal artery ischemia (SCI) events can result from over coverage of the descending thoracic aorta with a coated stent during Thoracic Endovascular Aortic Repair (TEVAR). The aim of this study was to determine whether a new distal perforating stent could reduce the incidence of spinal cord ischemia while remodeling the true lumen.

Methods: TBAD patients treated with Talos stent in the vascular surgery Department of Yan 'an Hospital affiliated to Kunming Medical University between December 2017 and October 2019 were retrospectively analyzed to investigate the short-term safety and effectiveness of Talos stent.

Results: A total of the 20 patients, including 14 males and 6 females, with an average age of 52.65 ± 8.98 years (range 37-68 years), were included in the analysis. Stent-grafts were successfully implanted in all patients under local anesthesia, with a technical success rate of 100%. The average operation time was 50.75 ± 13.01 min. A total of 2 cases (10%) presented chest pain associated with intercostal artery ischemia that was relieved on the 3rd and 5th postoperative day, respectively. Postoperative mean follow-up was 16.15 ± 3.99 months. No paraplegia or other complications occurred. And stenting did not induce new tears. No migration, deformation, or fracture of the stents occurred. There was a significant difference in the remolding of the true lumen preoperatively and at 12 months postoperatively (P < 0.05).

Conclusions: Talos stent has achieved satisfactory clinical treatment results in short term.
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http://dx.doi.org/10.1186/s12872-021-02270-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456669PMC
September 2021

Effects of additive dosage and coagulation bath pH on amphoteric fluorocarbon special surfactant (FS-50) blend PVDF membranes.

Chemosphere 2021 Sep 8;287(Pt 3):132212. Epub 2021 Sep 8.

School of Environmental Science and Resources, Shanxi University, No. 92 Wucheng Road, Taiyuan, 030006, China.

Amphiphilic copolymers containing hydrophilic and hydrophobic blocks represented by surfactants have proven to be more effective for modifying membranes than hydrophilic copolymers. However, studies on the effects of additive and coagulation bath pH on the morphology and properties of surfactant-modified membranes have rarely been reported. Hence, this study aims to investigate the effects of the additive dosage and the coagulation bath pH on the mechanisms of phase inversion and performance improvement of amphoteric fluorocarbon special surfactant (FS-50) blended PVDF membranes. It was observed that the pure water flux increased from 114.68 LMH/bar of the original membrane M0 to 205.02 LMH/bar of the blend membrane M1, and then to 615.88 LMH/bar of the coagulation-bath-regulated membrane MPH9 with a high BSA rejection rate of 90.86%, showing a two-stage jump. The addition of FS-50 promoted the instantaneous phase inversion of the membrane, allowing the blend membrane to exhibit a higher proportion of pore characteristics and stronger permeability. After that, the mechanisms of the membrane phase inversion process affected by the coagulation bath pH were interpreted according to the pH-response characteristics of FS-50 in terms of charge repulsion effect and compressed double-electron layer effect. Furthermore, the cross-sectional morphology and the surface structure of the membrane prepared in acidic and alkaline coagulation baths were significantly affected by the pH of the coagulation bath, exhibiting different features. For one, the porosity of the membranes gradually decreased as the acidity and alkalinity of the coagulation bath increased, and the membrane MPH9 exhibited both maximum surface and overall porosity. For another, the coagulation bath pH did not negatively affect the contact angle, surface roughness and tensile strength of the membranes. Overall, adjusting the dosage of FS-50 and the pH of the coagulation bath is a promising approach to greatly enhance membrane performance.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132212DOI Listing
September 2021

Pro-inflammatory and proliferative microglia drive progression of glioblastoma.

Cell Rep 2021 Sep;36(11):109718

Department of Neurosurgery, The First Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China. Electronic address:

Scant understanding of the glioblastoma microenvironment and molecular bases hampers development of efficient treatment strategies. Analyses of gene signatures of human gliomas demonstrate that the SETD2 mutation is correlated with poor prognosis of IDH1/2 wild-type (IDH-WT) adult glioblastoma patients. To better understand the crosstalk between SETD2 mutant (SETD2-mut) glioblastoma cells and the tumor microenvironment, we leverage single-cell transcriptomics to comprehensively map cellular populations in glioblastoma. In this study, we identify a specific subtype of high-grade glioma-associated microglia (HGG-AM). Further analysis shows that transforming growth factor (TGF)-β1 derived from SETD2-mut/IDH-WT tumor cells activates HGG-AM, exhibiting pro-inflammation and proliferation signatures. Particularly, HGG-AM secretes interleukin (IL)-1β via the apolipoprotein E (ApoE)-mediated NLRP1 inflammasome, thereby promoting tumor progression. HGG-AM present extensive proliferation and infiltration to supplement the activated microglia pool. Notably, TGF-β1/TβRI depletion dramatically reduces HGG-AM density and suppresses tumor growth. Altogether, our studies identify a specific microglia subpopulation and establish the cellular basis of interactions between HGG-AM and glioblastoma cells.
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http://dx.doi.org/10.1016/j.celrep.2021.109718DOI Listing
September 2021

Oxidative stress and EROD activity in Caco-2 cells upon exposure to chlorinated hydrophobic organic compounds from drinking water reservoirs.

Sci Total Environ 2021 Aug 30;804:150015. Epub 2021 Aug 30.

School of Resources and Environment, University of Electronic Science and Technology of China, Chengdu 611731, China.

Our previous studies showed hydrophobic organic compounds (HOCs) in the sediments of drinking water reservoirs caused DNA damage in human cells (Caco-2) after chlorination. However, the main mechanisms remained unclear. This study compared oxidative damage and EROD activity in Caco-2 cells upon exposure to chlorinated HOCs, and the role of antioxidants (catalase, vitamin C and epigallocatechin gallate (EGCG)) in reducing the toxicities was examined. The result showed that chlorinated HOCs induced a 4-fold increase in production of reactive oxygen species (ROS) compared with HOCs. Antioxidants supplement significantly reduced ROS yields and DNA peroxidation. HOCs with relatively higher TEQ were greatly reduced (about 98%) after chlorination, indicating dioxin-like toxicity is not the main factor inducing oxidative damage by chlorinated HOCs. Yet, ROS and the associated oxidative damage seem to be more responsible for causing DNA damage in the cells. Antioxidants including catalase, Vitamin C and EGCG showed protective effect against chlorination.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150015DOI Listing
August 2021

Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide resistance via NF-κB activation.

Cell Death Dis 2021 09 4;12(9):833. Epub 2021 Sep 4.

Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

Caspase-8 is a unique member of caspases with a dual role in cell death and survival. Caspase-8 expression is often lost in some tumors, but increased in others, indicating a potential pro-survival function in cancer. By analyzing transcriptome of enzalutamide-resistant prostate cancer cells, we found that resistance was conferred by a mild caspase-8 upregulation that in turn led to NF-κB activation and the subsequent upregulation of the downstream IL-8. Mechanistically, we found that the pro-survival and enzalutamide-resistance-promoting features of caspase-8 were independent of its proteolytic activity, using a catalytically-inactive caspase-8 mutant. We further demonstrated that caspase-8 pro-apoptotic function was inhibited via cFLIP binding. Moreover, high caspase-8 expression was correlated with a worse prognosis in prostate cancer patients. Collectively, our work demonstrates that enzalutamide-resistance is mediated by caspase-8 upregulation and the consequent increase in NF-κB/IL-8 mediated survival signaling, highlighting caspase-8 and NF-κB as potential therapeutic targets to overcome enzalutamide-resistance in CRPC.
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http://dx.doi.org/10.1038/s41419-021-04126-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418603PMC
September 2021

Plasma fibrinogen, D-dimer, and fibrin degradation product as biomarkers of rheumatoid arthritis.

Sci Rep 2021 Aug 19;11(1):16903. Epub 2021 Aug 19.

Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.

This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), D-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, D-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, D-dimer, and FDP than the controls (P < 0.01). Plasma FIB, D-dimer, and FDP were also increased in active groups of RA patients than those in inactive groups (P < 0.001). ROC curve analyses revealed that the AUC of D-dimer was higher than erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF), and that of FDP was higher than RF in RA patients. In addition, the optimal cut-off value of plasma FIB, D-dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Spearman analysis showed that plasma FIB, D-dimer, and FDP were positively related with DAS28-CRP (P < 0.001) in RA patients. Logistical regression analysis showed that D-dimer (odds ratio 2.862, 95% confidence interval 1.851-5.426, P < 0.001) was an independent variable associated with RA disease activity. FIB, D-dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. D-dimer may act as a novel inflammatory indice for indicating disease activity in RA patients.
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http://dx.doi.org/10.1038/s41598-021-96349-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377052PMC
August 2021

Untargeted and targeted metabolomics profiling reveals the underlying pathogenesis and abnormal arachidonic acid metabolism in laying hens with fatty liver hemorrhagic syndrome.

Poult Sci 2021 Sep 10;100(9):101320. Epub 2021 Jun 10.

College of Veterinary Medicine, Hebei Agricultural University, Baoding 071001, Hebei, China. Electronic address:

As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has become the major factor responsible for the noninfectious cause of mortality in laying hens, which lead to huge economic losses to poultry industry. However, the pathogenesis of FLHS remains unclear. The aim of present study was to identify novel liver metabolites associated with FLHS. Twenty healthy Chinese commercial Jing Fen laying hens aged 90 d were used in present study. After acclimatization for 2 wk, the hens were divided into 2 treatments (n = 10): control group (normal diet) and FLHS group (high-energy low-protein diet). The experiment lasted for 48 d, and the laying hens were killed for blood and liver sampling at the end of the experiment. Blood biochemical indicators and liver pathological changes were examined. Meanwhile, the changes in liver metabolic profile were investigated with the application of metabolomics approach. Significant increased levels of alanine aminotransferase, aspartate aminotransferase, low density lipoprotein, total cholesterol and triglycerides, decreased high density lipoprotein (P < 0.01), and hepatic steatosis were observed in hens of FLHS group, which suggested FLHS was successfully established in this study. Distinct changes in metabolite patterns in liver between control and FLHS group were observed by partial least-squares discriminant analysis. In total, 42 liver metabolites including tyrosine, glutathione, carnitine, linoleic acid, uric acid, arachidonic acid (ARA), lactate and lysophosphatidylcholine (14: 0) were identified and considered to be related with pathogenesis of FLHS. Pathway analysis revealed that these metabolites were mainly involved in amino acid metabolism, fatty acid metabolism, ARA metabolism, glucose metabolism and glycerophospholipid metabolism. Furthermore, targeted metabolomics found that ARA metabolites such as prostaglandins and hydroxyeicosatetraenoic acids were significantly increased in FLHS group (P < 0.05). In conclusion, our data showed that liver metabolites and ARA metabolism were linked to the pathophysiology of FLHS, which provided a basis for understanding the pathogenesis of FLHS in laying hens.
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http://dx.doi.org/10.1016/j.psj.2021.101320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319003PMC
September 2021

A novel 4-gene signature model simultaneously predicting malignant risk of oral potentially malignant disorders and oral squamous cell carcinoma prognosis.

Arch Oral Biol 2021 Sep 30;129:105203. Epub 2021 Jun 30.

State Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Objective: Oral squamous cell carcinoma (OSCC) is often diagnosed at late stage with a poor prognosis. The study hereunder aimed to construct a multi-gene model to simultaneously promote early diagnosis of OSCC by evaluating malignant risk of oral potentially malignant disorders (OPMDs) and predict prognosis.

Materials And Methods: 3 GEO datasets including OPMDs and OSCC samples were obtained for overlapping differentially expressed genes (DEGs) being screened. The predictive model was built with optimal DEGs by SVM algorithm, estimated by receiver operator characteristic curves and validated for double prediction via oral cancer-free survival (for malignant risk of OPMDs) and overall survival time (for OSCC) analysis respectively compared to other models. The protein expression of biomarkers in the model was validated in human samples by immunohistochemistry.

Results: A novel predictive model of 4-gene signature was built based on 12 common DEGs revealed from 3 GEO datasets. It could well distinguish OSCC from OPMDs and normal tissues. Both oral cancer-free survival and overall survival time analysis were significantly poorer in high-risk patients than in low-risk ones in Kaplan Meier survival curve respectively. The protein expression of biomarkers in OSCC was with significant difference compared to normal and OPMDs.

Conclusions: The novel 4-gene signature model presents strong ability in simultaneous prediction of the malignant risk of OPMDs and OSCC progression, potentially benefiting both the early diagnosis and therapeutic outcomes of OSCC.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105203DOI Listing
September 2021

A new Ti-based IMAC nanohybrid with high hydrophilicity and enhanced absorption capacity for the selective enrichment of phosphopeptides.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Aug 29;1179:122851. Epub 2021 Jun 29.

College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. Electronic address:

Ti-based immobilized metal affinity chromatography (IMAC) nanomaterial has shown high potential in phosphoproteome mass-spectrometric (MS) analysis. However, the limited surface area and poor solubility will greatly restrict its use in phosphoproteome research. To overcome these two key drawbacks, a novel Ti-based IMAC nanomaterial was prepared by Ti-bonded β-cyclodextrin (β-CD) anchored on the surface of carbon nanotubes (CNTs) (denoted as COOH-CNTs-CD-Ti) and successfully applied as a biofunctional adsorbent for selectively enriching trace phosphopeptides. In the selective enrichment process, CNTs provided greater surface area for the absorption of phosphopeptides, while β-CD also offered a greater opportunity for the interaction between phosphopeptides and Ti. COOH-CNTs-CD-Ti with the aforementioned properities exhibited higher selectivity for phosphopeptides from the standard protein digests, the tryptic digests of nonfat milk and human serum, showing a great selective enrichment capability towards complex biological samples.
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http://dx.doi.org/10.1016/j.jchromb.2021.122851DOI Listing
August 2021

Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data.

Clin Cancer Res 2021 Aug 10;27(16):4634-4641. Epub 2021 Jun 10.

Department of Oncology, Central Hospital of Shaoyang, Shaoyang, China.

Purpose: Patients with HER2-positive (HER2) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce.

Experimental Design: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2 MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR), and overall response rate (ORR) were analyzed.

Results: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS ( = 0.0072) and PFS ( = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months = 0.19; OS: 20.67 vs. 12.43 months = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR).

Conclusions: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0474DOI Listing
August 2021

Reusable membrane with multifunctional skin layer for effective removal of insoluble emulsified oils and soluble dyes.

J Hazard Mater 2021 08 17;415:125677. Epub 2021 Mar 17.

State Key Laboratory of Heavy Oil Processing, School of Materials Science and Engineering, China University of Petroleum, Qingdao 266580, Shandong, PR China. Electronic address:

The organic pollutants, typical of emulsified oils and soluble organic dyes, is commonly found in wastewater, however simultaneous removal of them remains challenging because of their difference in surface charge, molecule size, and solubility in water. Inspired by the water purification of the earth's multilayer strata, a fibrous membrane with multifunctional skin is fabricated by coupling sub-micrometer pores layer of polyaniline (PANI) and nano molecular brush of polyacrylic acid (PAA)/polyethyleneimine (PEI) on polyacrylonitrile membrane, for cross-scale organic pollution/water separation. This ultrathin skin of PANI/PAA/PEI is endowed with sub-micrometer pores and strong hydration, which can effectively prevent tiny oil droplets from entering or adhering the membrane pores. Furthermore, this skin with double electric layer can selectively adsorb and even filtrate anionic/cationic dyes by protonation and deprotonation effect in different pH solutions. The synergy of these features enables this membrane with ultra-high water flux (>3000 L m h bar), oil rejection rates (>99.6%), and anionic/cationic dyes adsorbability (>49.1 mg/g). Besides, the membrane also exhibits desirable reusability, excellent mechanical durability and outstanding acid/alkali resistance, promising for removal of insoluble emulsified oils and soluble organic dyes in wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125677DOI Listing
August 2021

Full Color and Grayscale Painting with 3D Printed Low-Index Nanopillars.

Nano Lett 2021 Jun 21;21(11):4721-4729. Epub 2021 May 21.

Engineering Product Development Pillar, Singapore University of Technology and Design, 8 Somapah Road, Singapore 487372, Singapore.

Sculpting nanostructures into different geometries in either one or two dimensions produces a wide range of colorful elements in microscopic prints. However, achieving different shades of gray and control of color saturation remain challenging. Here, we report a complete approach to color and grayscale generation based on the tuning of a single nanostructure geometry. Through two-photon polymerization lithography, we systematically investigated color generation from the basic single nanopillar geometry in low-refractive-index ( < 1.6) material. Grayscale and full color palettes were achieved that allow decomposition onto hue, saturation, and brightness values. This approach enabled the "painting" of arbitrary colorful and grayscale images by mapping desired prints to precisely controllable parameters during 3D printing. We further extend our understanding of the scattering properties of the low-refractive-index nanopillar to demonstrate grayscale inversion and color desaturation and steganography at the level of single nanopillars.
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http://dx.doi.org/10.1021/acs.nanolett.1c00979DOI Listing
June 2021

Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.

Bioorg Med Chem 2021 06 1;40:116182. Epub 2021 May 1.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

The ubiquitin proteasome pathway (UPP) plays a critical role in the maintenance of cell homeostasis and the development of diseases, such as cancer and neurodegenerative disease. A series of novel tripeptide propylene oxide compounds as proteasome inhibitors were designed, synthesized and biologically investigated in this manuscript. The enzymatic activities of final compounds against 20S human proteasome were investigated and structure-activity relationship (SAR) was summarized. Some potent compounds were further evaluated to inhibit the proliferation of multiple myeloma (MM) cancer cell lines RPMI8226 and U266B. The results showed that some compounds were active against MM cancer cell lines with IC values of less than 50 nM. The microsomal metabolic stabilities in human, rat and mice species were carried out and the results showed that compounds 30 and 31 were stable enough to be in vivo investigated. The in vivo pharmacokinetic results showed that compounds 30 and 31 had acceptable biological parameters for both ig and iv administrations. In vivo antitumor activities of compounds 30 and 31 with the doses of 100 mg/kg and 50 mg/kg BIW were performed by using RPMI8226 xenograft nude mouse model. Toxicities of compounds 30 and 31 were not observed during the experiment and dose dependent effect was obvious and the tumor volume was greatly inhibited.
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http://dx.doi.org/10.1016/j.bmc.2021.116182DOI Listing
June 2021

Discovery of novel pyrimidine molecules containing boronic acid as VCP/p97 Inhibitors.

Bioorg Med Chem 2021 05 23;38:116114. Epub 2021 Mar 23.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China. Electronic address:

Valine-containing protein (VCP) is a member of the adenosine triphosphate family involved in a variety of cellular activities. VCP/p97 is capable of maintaining protein homeostasis and mediating the degradation of misfolded polypeptides by the ubiquitin-proteasome system (UPS). In this manuscript, a series of novel p97 inhibitors with pyrimidine as core structure were designed, synthesized and biologically evaluated. Based on the enzymatic results, a detailed structure-activity relationship discussion of the synthesized compounds was carried out. Furthermore, cellular activities of the compounds with enzymatic potency of less than 200 nM were investigated by using A549 and RPMI8226 cell lines. Among the screened inhibitors, compound 17 (IC, 54.7 nM) showed good enzymatic activity. Investigation of cellular activities with non-small cell lung cancer A549 and multiple myeloma (MM) RPMI8226 further confirmed the potency of 17 with the IC values of 2.80 μM and 0.86 μM, respectively. Compound 17 is now being developed as a candidate. Finally, docking studies were carried out to explore the possible binding mode between the active inhibitor 17 and p97.
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http://dx.doi.org/10.1016/j.bmc.2021.116114DOI Listing
May 2021

Spectrum of Chest CT Findings in a Familial Cluster of COVID-19 Infection.

Radiol Cardiothorac Imaging 2020 Feb 13;2(1):e200025. Epub 2020 Feb 13.

Department of Radiology, Guangdong Hospital of Traditional Chinese Medicine, Zhuhai, 519000, China (T.L., P.H., H.L., L.H., M.L., W.X., X.H., J.C.) and Department of Radiology, Guangdong Hospital of Traditional Chinese Medicine, No. 111 Dade Road, Guangzhou, 510000, China (B.L.).

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http://dx.doi.org/10.1148/ryct.2020200025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233390PMC
February 2020

[Bushentongluo recipe (BSTL) attenuates bone destruction by inhibiting NF-κB/RANK/RANKL pathway in collagen-induced arthritis (CIA) rats].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Mar;37(3):205-211

Department of Rheumatology and Bone Disease, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China.

Objective To investigate the therapeutic effect of Bushentongluo recipe (BSTL) on bone destruction and its inhibiting effect on NF-κB/RANK/RANKL pathway in collagen-induced arthritis (CIA) rats. Methods SD rats were randomly divided into blank control group, CIA model group, methotrexate (MTX, 1 mg/kg) group, BSTL 0.5 g/kg and 2 g/kg groups, with 10 rats in each. Except the control group, the other rats were injected subcutaneously with type 2 collagen(Col2) at the base of the tail to establish CIA models. After exposure to MTX or BSTL recipe for consecutive 28 days, the pathological change of joint tissues was examined by HE staining. Immunohistochemistry was used to detect NF-κB p65 expression in synovial tissues. The cytokines and anti-Col2 levels were analyzed by ELISA. Western blotting was used to detect the expression of RANKL, RANK and osteoprotegerin (OPG) proteins. Results Compared with the CIA model group, the rats treated with 2 g/kg BSTL for 28 days had lower paw volume, arthritis index (AI), serum levels of IL-1β, IL-18, TNF-α, anti-Col2-IgG, anti-Col2-IgG2a, RANK and RANKL, and higher level of serum OPG. Besides, Western blotting showed that the expression of NF-κB p65, RANK and RANKL proteins decreased, but the expression of OPG protein increased in BSTL 2 g/kg group. Conclusion BSTL can alleviate the rheumatoid arthritis by down-regulating the expression of NF-κB p65, RANKL, RANK proteins, up-regulating OPG protein, and inhibiting systemic inflammation.
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March 2021

Genome-wide identification of microRNAs involved in the somatic embryogenesis of Eucalyptus.

G3 (Bethesda) 2021 04;11(4)

Guangxi Key Laboratory of Superior Timber Trees Resource Cultivation, Guangxi Forestry Research Institute, Nanning 530002, China.

MicroRNAs (miRNAs) are small noncoding RNAs (18-24 nt) and function in many biological processes in plants. Although Eucalyptus trees are widely planted across the world, our understanding of the miRNA regulation in the somatic embryogenesis (SE) of Eucalyptus is still poor. Here we reported, for the first time, the miRNA profiles of differentiated and dedifferentiated tissues of two Eucalyptus species and identified miRNAs involved in SE of Eucalyptus. Stem and tissue culture-induced callus were obtained from the subculture seedlings of E. camaldulensis and E. grandis x urophylla and were used as differentiated and dedifferentiated samples, respectively. Small RNA sequencing generated 304.2 million clean reads for the Eucalyptus samples (n = 3) and identified 888 miRNA precursors (197 known and 691 novel) for Eucalyptus. These miRNAs were mainly distributed in chromosomes Chr03, Chr05, and Chr08 and can produce 46 miRNA clusters. Then, we identified 327 and 343 differentially expressed miRNAs (DEmiRs) in the dedifferentiation process of E. camaldulensis and E. grandis x urophylla, respectively. DEmiRs shared by the two Eucalyptus species might be involved in the development of embryonic callus, such as MIR156, MIR159, MIR160, MIR164, MIR166, MIR169, MIR171, MIR399, and MIR482. Notably, we identified 81 upregulated and 67 downregulated miRNAs specific to E. camaldulensis, which might be associated with the high embryogenic potential. Target prediction and functional analysis showed that they might be involved in longevity regulating and plant hormone signal transduction pathways. Further, using the gene expression profiles, we observed the negative regulation of miRNA-target pairs, such as MIR160~ARF18, MIR396~GRF6, MIR166~ATHB15/HD-ZIP, and MIR156/MIR157~SPL1. Interestingly, transcription factors such as WRKY, MYB, GAMYB, TCP4, and PIL1 were found to be regulated by the DEmiRs. The genes encoding PIL1 and RPS21C, regulated by upregulated miRNAs (e.g., egd-N-miR63-5p, egd-N-miR63-5p, and MIR169,) were downregulated exclusively in the dedifferentiation of E. camaldulensis. This is the first time to study the miRNA regulation in the dedifferentiation process of Eucalyptus and it will provide a valuable resource for future studies. More importantly, it will improve our understanding of miRNA regulation during the somatic embryogenesis of Eucalyptus and benefit the Eucalyptus breeding program.
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http://dx.doi.org/10.1093/g3journal/jkab070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049409PMC
April 2021

Multiphoton Upconversion Enhanced by Deep Subwavelength Near-Field Confinement.

Nano Lett 2021 Apr 9;21(7):3044-3051. Epub 2021 Mar 9.

Department of Chemistry and The N.1 Institute for Health, National University of Singapore, Singapore 117543, Singapore.

Efficient generation of anti-Stokes emission within nanometric volumes enables the design of ultracompact, miniaturized photonic devices for a host of applications. Many subwavelength crystals, such as metal nanoparticles and two-dimensional layered semiconductors, have been coupled with plasmonic nanostructures for augmented anti-Stokes luminescence through multiple-harmonic generation. However, their upconversion process remains inefficient due to their intrinsic low absorption coefficients. Here, we demonstrate on-chip, site-specific integration of lanthanide-activated nanocrystals within gold nanotrenches of sub-25 nm gaps via bottom-up self-assembly. Coupling of upconversion nanoparticles to subwavelength gap-plasmon modes boosts 3.7-fold spontaneous emission rates and enhances upconversion by a factor of 100 000. Numerical investigations reveal that the gap-mode nanocavity confines incident excitation radiation into nanometric photonic hotspots with extremely high field intensity, accelerating multiphoton upconversion processes. The ability to design lateral gap-plasmon modes for enhanced frequency conversion may hold the potential to develop on-chip, background-free molecular sensors and low-threshold upconversion lasers.
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http://dx.doi.org/10.1021/acs.nanolett.1c00232DOI Listing
April 2021

The action difference of metabolic regulators on carbon conversion during different agricultural organic wastes composting.

Bioresour Technol 2021 Jun 25;329:124902. Epub 2021 Feb 25.

Heilongjiang Province Environmental Science Research Institute, Harbin 150056, China.

The purpose of this study is to explore the action characteristics of metabolic regulators like adenosine tri-phosphate (ATP) and malonic acid (MA) during rice straw (RS) and fruit and vegetable waste (FVW) composting. Results showed that due to the easy degradation difference, ATP and MA reduced CO emission in RS and FVW, respectively. Moreover, adding ATP and MA increased humic acids (HA) content in FVW more significantly (p < 0.05), especially for ATP. However, adding MA accelerated organic matter degradation during RS composting, which was basically consistent with CO emission, but it was not effective in promoting HA formation. Furthermore, the microbial community was reshaped by adding ATP and MA. Eventually, structural equation model further confirmed that adding metabolic regulators enhanced the biotic and abiotic pathways of HA formation, and the promotion effect of adding ATP was more obvious. The study has great practical significance for the dispose of agricultural waste.
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http://dx.doi.org/10.1016/j.biortech.2021.124902DOI Listing
June 2021

Eco-friendly flame retardant and dripping-resistant of polyester/cotton blend fabrics through layer-by-layer assembly fully bio-based chitosan/phytic acid coating.

Int J Biol Macromol 2021 Apr 5;175:140-146. Epub 2021 Feb 5.

School of Textile and Garment, Anhui Polytechnic University, Wuhu 241000, China; Technology Public Service Platform for Textile Industry of Anhui Province, Wuhu 241000, China.

Polyester/cotton blend fabrics are widely used in clothing and household textiles which combine the comfort of cotton and excellent mechanical strength of polyester. However, their high flammability due to the special "wick effect" resulting from the different thermal decomposition process of cotton and polyester causes greatly potential fire hazards. In this study, fully bio-based intumescent flame retardant (IFR) coating of chitosan/phytic acid (CS/PA) was layer-by-layer (LBL) assembly constructed on polyester/cotton blend fabrics. The LOI value of polyester/cotton blend fabric which was LBL assembly coated by 20 bilayers CS/PA reached 29.2%. And the dripping of coated fabric was eliminated. The results of cone calorimetry test confirmed CS/PA coating greatly improved the flame retardancy of polyester/cotton blend fabrics. Thermogravimetric analysis (TGA) results showed CS/PA coating changed the thermal decomposition process to promote the char formation of polyester/cotton blend fabrics. CS/PA coating on fabric could form the IFR system which acts through both condensed phase action by the catalysis dehydration reaction to forming stable char and gas phase action by the blowing effect. This research provides a new strategy to eco-friendly flame retardant and dripping-resistant for polyester/cotton blend fabrics by bio-based IFR system through facile LBL assembly method.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.023DOI Listing
April 2021

Potential use of molecular and structural characterization of the gut bacterial community for postmortem interval estimation in Sprague Dawley rats.

Sci Rep 2021 01 8;11(1):225. Epub 2021 Jan 8.

Department of Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.

Once the body dies, the indigenous microbes of the host begin to break down the body from the inside and play a key role thereafter. This study aimed to investigate the probable shift in the composition of the rectal microbiota at different time intervals up to 15 days after death and to explore bacterial taxa important for estimating the time since death. At the phylum level, Proteobacteria and Firmicutes showed major shifts when checked at 11 different intervals and emerged at most of the postmortem intervals. At the species level, Enterococcus faecalis and Proteus mirabilis showed a downward and upward trend, respectively, after day 5 postmortem. The phylum-, family-, genus-, and species-taxon richness decreased initially and then increased considerably. The turning point occurred on day 9, when the genus, rather than the phylum, family, or species, provided the most information for estimating the time since death. We constructed a prediction model using genus-level data from high-throughput sequencing, and seven bacterial taxa, namely, Enterococcus, Proteus, Lactobacillus, unidentified Clostridiales, Vagococcus, unidentified Corynebacteriaceae, and unidentified Enterobacteriaceae, were included in this model. The abovementioned bacteria showed potential for estimating the shortest time since death.
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http://dx.doi.org/10.1038/s41598-020-80633-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794466PMC
January 2021

Structural multi-colour invisible inks with submicron 4D printing of shape memory polymers.

Nat Commun 2021 Jan 4;12(1):112. Epub 2021 Jan 4.

Engineering Product Development, Singapore University of Technology and Design, Singapore, 487372, Singapore.

Four-dimensional (4D) printing of shape memory polymer (SMP) imparts time responsive properties to 3D structures. Here, we explore 4D printing of a SMP in the submicron length scale, extending its applications to nanophononics. We report a new SMP photoresist based on Vero Clear achieving print features at a resolution of ~300 nm half pitch using two-photon polymerization lithography (TPL). Prints consisting of grids with size-tunable multi-colours enabled the study of shape memory effects to achieve large visual shifts through nanoscale structure deformation. As the nanostructures are flattened, the colours and printed information become invisible. Remarkably, the shape memory effect recovers the original surface morphology of the nanostructures along with its structural colour within seconds of heating above its glass transition temperature. The high-resolution printing and excellent reversibility in both microtopography and optical properties promises a platform for temperature-sensitive labels, information hiding for anti-counterfeiting, and tunable photonic devices.
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http://dx.doi.org/10.1038/s41467-020-20300-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782480PMC
January 2021

The complete chloroplast genome of and its phylogenetic position within Ulmaceae.

Mitochondrial DNA B Resour 2020 28;5(3):2182-2183. Epub 2020 May 28.

Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China.

The complete chloroplast genome sequence of the Tertiary relict tree was reported in this study. The chloroplast genome is 158,875 bp in length with a typical angiosperm quantitative structure consisting of a large single copy (87,412 bp) and a small single copy (18,683 bp) separated by a pair of inverted repeat (26,390 bp). Genome annotation revealed a total of 129 genes comprising 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenomic analysis based on the whole plastomes indicated that and formed a well-supported monophyletic clade sister to genus in Ulmaceae.
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http://dx.doi.org/10.1080/23802359.2020.1768947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510571PMC
May 2020

Rewritable color nanoprints in antimony trisulfide films.

Sci Adv 2020 Dec 16;6(51). Epub 2020 Dec 16.

Singapore University of Technology and Design, 8 Somapah Road, Singapore 487372, Singapore.

Materials that exhibit large and rapid switching of their optical properties in the visible spectrum hold the key to color-changing devices. Antimony trisulfide (SbS) is a chalcogenide material that exhibits large refractive index changes of ~1 between crystalline and amorphous states. However, little is known about its ability to endure multiple switching cycles, its capacity for recording high-resolution patterns, nor the optical properties of the crystallized state. Unexpectedly, we show that crystalline SbS films that are just 20 nm thick can produce substantial birefringent phase retardation. We also report a high-speed rewritable patterning approach at subdiffraction resolutions (>40,000 dpi) using 780-nm femtosecond laser pulses. Partial reamorphization is demonstrated and then used to write and erase multiple microscale color images with a wide range of colors over a ~120-nm band in the visible spectrum. These solid-state, rapid-switching, and ultrahigh-resolution color-changing devices could find applications in nonvolatile ultrathin displays.
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http://dx.doi.org/10.1126/sciadv.abb7171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744068PMC
December 2020

Transcriptome analysis identifies genes involved in the somatic embryogenesis of Eucalyptus.

BMC Genomics 2020 Nov 18;21(1):803. Epub 2020 Nov 18.

Guangxi Key Laboratory of Superior Timber Trees Resource Cultivation, Guangxi Forestry Research Institute, 23 Yongwu Road, Nanning, 530002, Guangxi, China.

Background: Eucalyptus, a highly diverse genus of the Myrtaceae family, is the most widely planted hardwood in the world due to its increasing importance for fiber and energy. Somatic embryogenesis (SE) is one large-scale method to provide commercial use of the vegetative propagation of Eucalyptus and dedifferentiation is a key step for plant cells to become meristematic. However, little is known about the molecular changes during the Eucalyptus SE.

Results: We compared the transcriptome profiles of the differentiated and dedifferentiated tissues of two Eucalyptus species - E. camaldulensis (high embryogenetic potential) and E. grandis x urophylla (low embryogenetic potential). Initially, we identified 18,777 to 20,240 genes in all samples. Compared to the differentiated tissues, we identified 9229 and 8989 differentially expressed genes (DEGs) in the dedifferentiated tissues of E. camaldulensis and E. grandis x urophylla, respectively, and 2687 up-regulated and 2581 down-regulated genes shared. Next, we identified 2003 up-regulated and 1958 down-regulated genes only in E. camaldulensis, including 6 somatic embryogenesis receptor kinase, 17 ethylene, 12 auxin, 83 ribosomal protein, 28 zinc finger protein, 10 heat shock protein, 9 histone, 122 cell wall related and 98 transcription factor genes. Genes from other families like ABA, arabinogalactan protein and late embryogenesis abundant protein were also found to be specifically dysregulated in the dedifferentiation process of E. camaldulensis. Further, we identified 48,447 variants (SNPs and small indels) specific to E. camaldulensis, including 13,434 exonic variants from 4723 genes (e.g., annexin, GN, ARF and AP2-like ethylene-responsive transcription factor). qRT-PCR was used to confirm the gene expression patterns in both E. camaldulensis and E. grandis x urophylla.

Conclusions: This is the first time to study the somatic embryogenesis of Eucalyptus using transcriptome sequencing. It will improve our understanding of the molecular mechanisms of somatic embryogenesis and dedifferentiation in Eucalyptus. Our results provide a valuable resource for future studies in the field of Eucalyptus and will benefit the Eucalyptus breeding program.
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http://dx.doi.org/10.1186/s12864-020-07214-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672952PMC
November 2020

The chronic effect of cortisol on orchestrating cerebral blood flow and brain functional connectivity: evidence from Cushing's disease.

Metabolism 2021 02 14;115:154432. Epub 2020 Nov 14.

Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, PR China. Electronic address:

Background: Cortisol has long been considered to play a crucial role in the pathogenesis of stress-related disorders. Cushing's disease (CD) provides an excellent "hyperexpression model" to investigate the chronic effects of cortisol on brain physiology and cognition. Previous studies have shown that cortisol is associated with neurophysiological alterations in animal models, which has also been examined by neural activity and cerebral blood flow (CBF) in human studies. However, the manner in which cortisol affects the coupling between brain activity and metabolic demand remains largely unknown.

Methods: Here we used functional magnetic resonance imaging and arterial-spin-labeling imaging to investigate neurophysiological coupling by examining the ratio of CBF and functional connectivity strength (FCS) in 100 participants (47 CD patients and 53 healthy controls).

Results: The results showed that CD was associated with lower CBF-FCS coupling predominantly in regions involving cognitive processing, such as the left dorsolateral prefrontal cortex and precuneus, as well as greater CBF-FCS coupling in subcortical structures, including the bilateral thalamus, right putamen, and hippocampus (P < 0.05, false discovery rate corrected). Moreover, regions with disrupted CBF-FCS coupling were associated with cortisol dosage and cognitive decline in CD patients.

Conclusions: Together, these findings elucidate the effect of cortisol excess on cerebral microenvironment regulation and associated cognitive disturbances in the human brain.
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http://dx.doi.org/10.1016/j.metabol.2020.154432DOI Listing
February 2021

PRKCA D463H Mutation in Chordoid Glioma of the Third Ventricle: A Cohort of 16 Cases, Including Two Cases Harboring BRAFV600E Mutation.

J Neuropathol Exp Neurol 2020 11;79(11):1183-1192

Departments of Pathology and Neurosurgery, San Bo Brain Hospital, Capital Medical University, Haidian District, Beijing, China.

Chordoid gliomas (CG) of the third ventricle are characterized by chordoid and glial features, but the extent of histological variations across CG is not fully understood. Herein, we report 16 consecutive cases of CG. All 16 patients had histories of headache and vision loss; their median age was 41.7 years at the surgery. Histological examination revealed typical features of CG, including cords of epithelioid cells within the mucinous stroma and lymphoplasmacytic infiltration. Two cases exhibited atypical histological features including histiocyte-like cells. PRKCA mutation was found in 14 cases, including the 2 with histiocytic features. BRAFV600E mutation was found only in the 2 cases with histiocytic features. The patients underwent gross total tumor resection without radiotherapy or chemotherapy. Three patients died between 1 and 4 months postsurgery. Only one had a recurrence. Eleven were alive at the most recent follow-up (range: 2-58 months). These data indicate that PRKCA mutation was a good diagnostic marker for CG and additionally suggest that histiocyte-like features can be present in CG in association with BRAF mutations.
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http://dx.doi.org/10.1093/jnen/nlaa107DOI Listing
November 2020

CRISPR screening of porcine sgRNA library identifies host factors associated with Japanese encephalitis virus replication.

Nat Commun 2020 10 14;11(1):5178. Epub 2020 Oct 14.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, 430070, Wuhan, P. R. China.

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, the host factors critical for its entry, replication, and assembly are poorly understood. Here, we design a porcine genome-scale CRISPR/Cas9 knockout (PigGeCKO) library containing 85,674 single guide RNAs targeting 17,743 protein-coding genes, 11,053 long ncRNAs, and 551 microRNAs. Subsequently, we use the PigGeCKO library to identify key host factors facilitating JEV infection in porcine cells. Several previously unreported genes required for JEV infection are highly enriched post-JEV selection. We conduct follow-up studies to verify the dependency of JEV on these genes, and identify functional contributions for six of the many candidate JEV-related host genes, including EMC3 and CALR. Additionally, we identify that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPGs sulfurylation, facilitate JEV entry into porcine cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this study identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to treat and prevent diseases caused by JEV.
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http://dx.doi.org/10.1038/s41467-020-18936-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560704PMC
October 2020
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