Publications by authors named "Peng Hua"

217 Publications

Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.

Chin Med J (Engl) 2021 Jul 22. Epub 2021 Jul 22.

Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, Guangdong 510440, China Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong 511430, China Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China National Institutes for Food and Drug Control, Beijing 100050, China Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, China Livzon Bio Inc., Zhuhai, Guangdong 519045, China Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China.

Background: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.

Methods: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.

Results: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.

Conclusions: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.

Trial Registration: http://www.chictr.org.cn/index.aspx(No.ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
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http://dx.doi.org/10.1097/CM9.0000000000001702DOI Listing
July 2021

Reactivation of a developmentally silenced embryonic globin gene.

Nat Commun 2021 07 21;12(1):4439. Epub 2021 Jul 21.

MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues.
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http://dx.doi.org/10.1038/s41467-021-24402-3DOI Listing
July 2021

Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2.

Cell Res 2021 Jul 15. Epub 2021 Jul 15.

Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.
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http://dx.doi.org/10.1038/s41422-021-00531-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646PMC
July 2021

Next-generation cytokines for cancer immunotherapy.

Antib Ther 2021 Apr 25;4(2):123-133. Epub 2021 Jun 25.

Key laboratory of Infection and Immunity Institute of Biophysics, Chinese Academy of Sciences, 15 Da Tun Rd, Chaoyang District, Beijing 100101, China.

Most studies focus on the first and second signals of T cell activation. However, the roles of cytokines in immunotherapy are not fully understood, and cytokines have not been widely used in patient care. Clinical application of cytokines is limited due to their short half-life , severe toxicity at therapeutic doses, and overall lack of efficacy. Several modifications have been engineered to extend their half-life and increase tumor targeting, including polyethylene glycol conjugation, fusion to tumor-targeting antibodies, and alteration of cytokine/cell receptor-binding affinity. These modifications demonstrate an improvement in either increased antitumor efficacy or reduced toxicity. However, these cytokine engineering strategies may still be improved further, as each strategy poses advantages and disadvantages in the delicate balance of targeting tumor cells, tumor-infiltrating lymphocytes, and peripheral immune cells. This review focuses on selected cytokines, including interferon-α, interleukin (IL)-2, IL-15, IL-21, and IL-12, in both preclinical studies and clinical applications. We review next-generation designs of these cytokines that improve half-life, tumor targeting, and antitumor efficacy. We also present our perspectives on the development of new strategies to potentiate cytokine-based immunotherapy.
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http://dx.doi.org/10.1093/abt/tbab014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271143PMC
April 2021

An irrigation system for noninvasively estimating intrarenal pressure during flexible ureteroscopy.

Int J Med Robot 2021 Jul 14:e2306. Epub 2021 Jul 14.

Institute of Forming Technology & Equipment, Shanghai Jiao Tong University, Shanghai, China.

Background: High intrarenal pressure (IRP) during flexible ureteroscopy (FURS) may lead to severe complications. Reported methods for measuring IRP are often inconvenient to use, expensive and involve instruments that occupy the narrow ureter.

Methods: We proposed an irrigation system, which can noninvasively estimate IRP based on the principle of fluid mechanics. To determine the feasibility of our system, we conducted irrigation experiments on a kidney phantom and a porcine kidney. The estimated IRPs were compared with the ground truth IRPs.

Results: When no surgical instrument was inserted into the flexible ureteroscope's working channel, our system can estimate IRP with high accuracy. When a surgical instrument was inserted, our system can approximately estimate the level of IRP.

Conclusions: Our proposed irrigation system can noninvasively estimate IRP, presenting a new thought for clinical practice. In future studies, in vivo experiments are needed to further validate and improve the system.
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http://dx.doi.org/10.1002/rcs.2306DOI Listing
July 2021

Taxonomic revision of (Rhamnaceae) from China I: identities of , S. thea var. cordiformis and , with the description of a new species .

PhytoKeys 2021 17;179:13-28. Epub 2021 Jun 17.

CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China Kunming Institute of Botany, Chinese Academy of Sciences Kunming China.

A taxonomic revision of , S. thea var. cordiformis and in China is presented. is revised in terms of morphological characters (habit, branchlet color, phyllotaxis and rachis length), distribution, habitat, and phenology; S. thea var. cordiformis is raised to ; and is excluded from the genus and reduced to the synonym of . Furthermore, a new species, , is erected based on the paratype collections of The new species morphologically differs from in having reddish brown branchlets, opposite or subopposite phyllotaxis, shorter rachises, and flowering in spring or early summer. is factually closest to as they share similar woody-vine habit and larger fruit size, and fruiting in winter, whereas the former can be easily recognized based on its smaller leaf blades, fewer lateral veins, shorter rachises, and ellipsoidal or elliptic-ovoid fruits.
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http://dx.doi.org/10.3897/phytokeys.179.64750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225594PMC
June 2021

GWAS and WGCNA uncover hub genes controlling salt tolerance in maize (Zea mays L.) seedlings.

Theor Appl Genet 2021 Jul 4. Epub 2021 Jul 4.

Key Laboratory of Biology and Genetic Improvement of Maize in Southwest Region, Maize Research Institute, Sichuan Agricultural University, Chengdu, 611130, China.

Keymessage: Two hub genes GRMZM2G075104 and GRMZM2G333183 involved in salt tolerance were identified by GWAS and WGCNA. Furthermore, they were verified to affect salt tolerance by candidate gene association analysis. Salt stress influences maize growth and development. To decode the genetic basis and hub genes controlling salt tolerance is a meaningful exploration for cultivating salt-tolerant maize varieties. Herein, we used an association panel consisting of 305 lines to identify the genetic loci responsible for Na- and K-related traits in maize seedlings. Under the salt stress, seven significant single nucleotide polymorphisms were identified using a genome-wide association study, and 120 genes were obtained by scanning the linkage disequilibrium regions of these loci. According to the transcriptome data of the above 120 genes under salinity treatment, we conducted a weighted gene co-expression network analysis. Combined the gene annotations, two SNaC/SKC (shoot Na content/shoot K content)-associated genes GRMZM2G075104 and GRMZM2G333183 were finally identified as the hub genes involved in salt tolerance. Subsequently, these two genes were verified to affect salt tolerance of maize seedlings by candidate gene association analysis. Haplotypes TTGTCCG-CT and CTT were determined as favorable/salt-tolerance haplotypes for GRMZM2G075104 and GRMZM2G333183, respectively. These findings provide novel insights into genetic architectures underlying maize salt tolerance and contribute to the cultivation of salt-tolerant varieties in maize.
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http://dx.doi.org/10.1007/s00122-021-03897-wDOI Listing
July 2021

Safety and immunogenicity of a recombinant interferon-armed RBD dimer vaccine (V-01) for COVID-19 in healthy adults: A randomised, double-blind, placebo-controlled, phase I trial.

Emerg Microbes Infect 2021 Jul 1:1-48. Epub 2021 Jul 1.

Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, China.

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase Ⅰ clinical trials in humans. A Randomized, double-blind, placebo-controlled phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February, 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive vaccine (10, 25, and 50μg) or placebo (V-01: Placebo=4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed promising safety profile with approximately 25% vaccine related overall adverse events within 30 days and no grade 3 or worse adverse events. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10μg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in phase Ⅱ/Ⅲ clinical trials.
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http://dx.doi.org/10.1080/22221751.2021.1951126DOI Listing
July 2021

Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal-CA1 projection.

BMC Neurosci 2021 Jun 14;22(1):41. Epub 2021 Jun 14.

Department of Neurology, Shanghai Changzheng Hospital, Navy Medical University, Shanghai, 200003, China.

Background: Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer's disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its underlying mechanisms in ameliorating cognitive defects.

Methods: Using behavioral, electrophysiological, optogenetic and morphology approaches to explore how memantine delay the pathogenesis of AD.

Results: Memantine significantly improved the acquisition in Morris water maze (MWM) in APP/PS1 mice without affecting the speed of swimming. Furthermore, memantine enhanced EC to CA1 synaptic neurotransmission and promoted dendritic spine regeneration of EC neurons that projected to CA1.

Conclusions: Our study reveals the underlying mechanism of memantine in the treatment of AD mice.
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http://dx.doi.org/10.1186/s12868-021-00647-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201811PMC
June 2021

Defining genome architecture at base-pair resolution.

Nature 2021 07 9;595(7865):125-129. Epub 2021 Jun 9.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

In higher eukaryotes, many genes are regulated by enhancers that are 10-10 base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7-22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding.
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http://dx.doi.org/10.1038/s41586-021-03639-4DOI Listing
July 2021

miR-24 controls the regenerative competence of hair follicle progenitors by targeting Plk3.

Cell Rep 2021 Jun;35(10):109225

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China; Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address:

Maintaining a suitable level of sensitivity to environmental cues is crucial for proper function of adult stem cells. Here, we explore how the intrinsic sensitivity of skin hair follicle (HF) progenitors to growth stimuli is dynamically regulated. We discover miR-24 is an miRNA whose expression in HF progenitors inversely correlates with their growth potency in vivo. We show that its upregulation in adult skin epithelium leads to blunted responses of HF progenitors to growth cues and retards hair regeneration, while its conditional ablation leads to hyper-sensitized growth responsiveness of HF progenitors and precocious hair regeneration. Mechanistically, we find that miR-24 limits the intrinsic growth competence of HF progenitor by directly targeting Plk3, whose downregulation leads to reduced expression of CCNE1, a key cyclin for cell-cycle entry. These findings reveal an miRNA-mediated dynamic and cell-intrinsic mechanism used by HF progenitors to adapt their regenerative competence for different physiological conditions.
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http://dx.doi.org/10.1016/j.celrep.2021.109225DOI Listing
June 2021

Correlation between ground-glass opacity on pulmonary CT and the levels of inflammatory cytokines in patients with moderate-to-severe COVID-19 pneumonia.

Int J Med Sci 2021 16;18(11):2394-2400. Epub 2021 Apr 16.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, P.R. China.

Comparative analysis of laboratory data in moderate-to-severe COVID-19 patients presenting with or without ground-glass opacities (GGOs). This retrospective study examined 61 patients with moderate-to-severe COVID-19, as defined by the report of the WHO-China Joint Mission on COVID-19. All patients were admitted to the Department of Infectious Diseases, Wuhan Union Hospital from Dec 28, 2019 to Feb 22, 2020 and classified into a GGO group or a non-GGO group based on CT results. The clinical characteristics and laboratory data of the two groups were compared. Data were analyzed using univariate and multivariate analysis, and using receiver operating characteristic (ROC) analysis. Forty-five patients were in the GGO group (73.8%, 21 females, 24 males, mean age 54.8±17.8 years) and 16 were in the non-GGO group (26.2%, 11 females, 5 males, mean age 53±14.9 years). The levels of IL-2, IL-4, and IFN-γ were greater in the GGO group (all P<0.05). ROC analysis indicated that an elevated level of IL-2 was a good predictor of GGO (area under the curve: 0.716, optimal cutoff: 3.205 pg/mL, 53.8% sensitivity, 87.5% specificity, p<0.05). Multivariate analysis showed that IL-2 level was a significant and independent risk factor for lung GGO (OR: 8.167; 95% CI: 1.63, 40.8; P<0.05). There were correlations between GGO in the lungs of patients with moderate-to-severe COVID-19 and the levels of IL-2, IL-4, and INF-γ. IL-2 was a significant and independent risk factor for GGO. These findings provide a basis for studying the mechanism of pulmonary lesions in COVID-19 patients.
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http://dx.doi.org/10.7150/ijms.56683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100652PMC
May 2021

The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation.

Sci Immunol 2021 May;6(59)

Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

The inflammasome promotes inflammation-associated diseases, including cancer, and contributes to the radiation-induced tissue damage. However, the role of inflammasome in radiation-induced antitumor effects is unclear. We observed that tumors transplanted in mice were resistant to radiation treatment compared with tumors in wild-type (WT) mice. To map out which molecule in the inflammasome pathway contributed to this resistant, we investigated the antitumor effect of radiation in several inflammasome-deficient mice. Tumors grown in either or mice remained sensitive to radiation, like WT mice, whereas mice showed radioresistance. Mechanistically, extracellular vesicles (EVs) and EV-free supernatant derived from irradiated tumors activated both Aim2 and Nlrp3 inflammasomes in macrophages, leading to the production of interleukin-1β (IL-1β). IL-1β treatment helped overcome the radioresistance of tumors growing in and mice. IL-1 signaling in dendritic cells (DCs) promoted radiation-induced antitumor immunity by enhancing the cross-priming activity of DCs. Overall, we demonstrated that radiation-induced activation of the AIM2 and NLRP3 inflammasomes coordinate to induce some of the antitumor effects of radiation by triggering IL-1 signaling in DCs, leading to their activation and cross-priming.
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http://dx.doi.org/10.1126/sciimmunol.abc6998DOI Listing
May 2021

Transcriptomic dynamics changes related to anthocyanin accumulation in the fleshy roots of carmine radish ( L.) characterized using RNA-Seq.

PeerJ 2021 7;9:e10978. Epub 2021 Apr 7.

Research Center for Tourism Agriculture Development, Sichuan Tourism College, Chengdu, China.

Carmine radish is famous for containing a natural red pigment (red radish pigment). However, the expression of anthocyanin biosynthesis-related genes during the dynamic development stages of the fleshy roots in carmine radish has not been fully investigated. Here, based on HPLC quantification of anthocyanin levels from our previous study, young fleshy roots of the carmine radish "Hongxin 1" obtained at the dynamic development stages of fleshy roots (seedling stage (SS), initial expansion (IE), full expansion (FE), bolting stage (BS), initial flowering stage (IFS), full bloom stage (FBS) and podding stage (PS)) were used for RNA-Seq. Approximately 126 comodulated DEGs related to anthocyanin biosynthesis (common DEGs in the dynamic growth stages of fleshy roots in carmine radish) were identified, from which most DEGs appeared to be likely to participate in anthocyanin biosynthesis, including two transcription factors, and . In addition, some related proteins, e.g., and , were found as candidate contributors to the regulatory mechanism of anthocyanin synthesis in the fleshy roots of carmine radish. In addition, 11 putative DEGs related to anthocyanin synthesis were evaluated by qRT-PCR via the (2-ΔΔCT) method; the Pearson correlation analysis indicated excellent concordance between the RNA-Seq and qRT-PCR results. Furthermore, GO enrichment analysis showed that "anthocyanin-containing compound biosynthetic process" and "anthocyanin-containing compound metabolic process" were commonly overrepresented in the dynamic growth stages of fleshy roots after the initial expansion stage. Moreover, five significantly enriched pathways were identified among the DEGs in the dynamic growth stages of fleshy roots in carmine radish, namely, flavonoid biosynthesis, flavone and flavonol biosynthesis, diterpenoid biosynthesis, anthocyanin biosynthesis, and benzoxazinoid biosynthesis. In conclusion, these results will expand our understanding of the complex molecular mechanisms of anthocyanin biosynthesis in the fleshy roots of carmine radish and the putative candidate genes involved in this process.
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http://dx.doi.org/10.7717/peerj.10978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035900PMC
April 2021

Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis .

Front Immunol 2021 25;12:642198. Epub 2021 Mar 25.

Transplantation Research and Immunology Group, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.

Humanized immune system (HIS) mouse models are useful tools for the investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. In this study, we address this challenge by using HSPC-NBSGW mice, in which NOD,B6.SCID IL-2r Kit (NBSGW) mice are engrafted with human CD133 hematopoietic stem and progenitor cells (HSPCs) without the need for preconditioning by sublethal irradiation. These HSPCs are enriched in long-term hematopoietic stem cells (LT-HSCs), while NBSGW mice are permissive to human hematopoietic stem cell (HSC) engraftment, thus reducing the cell number required for successful HIS development. B cells reconstitute with the greatest efficiency, including mature B cells capable of class-switching following allogeneic stimulation and, within lymphoid organs and peripheral blood, T cells at a spectrum of stages of maturation. In the thymus, human thymocytes are identified at all major stages of development. Phenotypically distinct subsets of myeloid cells, including dendritic cells and mature monocytes, engraft to a variable degree in the bone marrow and spleen, and circulate in peripheral blood. Finally, we observe human erythrocytes which persist in the periphery at high levels following macrophage clearance. The HSPC-NBSGW model therefore provides a useful platform for the study of human hematological and immunological processes and pathologies.
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http://dx.doi.org/10.3389/fimmu.2021.642198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044770PMC
March 2021

N-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA.

Nat Commun 2021 03 11;12(1):1582. Epub 2021 Mar 11.

Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.

Double-stranded RNA (dsRNA) is a virus-encoded signature capable of triggering intracellular Rig-like receptors (RLR) to activate antiviral signaling, but whether intercellular dsRNA structural reshaping mediated by the N-methyladenosine (mA) modification modulates this process remains largely unknown. Here, we show that, in response to infection by the RNA virus Vesicular Stomatitis Virus (VSV), the mA methyltransferase METTL3 translocates into the cytoplasm to increase mA modification on virus-derived transcripts and decrease viral dsRNA formation, thereby reducing virus-sensing efficacy by RLRs such as RIG-I and MDA5 and dampening antiviral immune signaling. Meanwhile, the genetic ablation of METTL3 in monocyte or hepatocyte causes enhanced type I IFN expression and accelerates VSV clearance. Our findings thus implicate METTL3-mediated mA RNA modification on viral RNAs as a negative regulator for innate sensing pathways of dsRNA, and also hint METTL3 as a potential therapeutic target for the modulation of anti-viral immunity.
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http://dx.doi.org/10.1038/s41467-021-21904-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952553PMC
March 2021

Differences in Immune Responses between Children and Adults with COVID-19.

Curr Med Sci 2021 Feb 13;41(1):58-61. Epub 2021 Feb 13.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Over 85 590 000 individuals have been infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although there have been an increasing number of reports on coronavirus disease 2019 (COVID-19), it is unclear why infected children show milder symptoms than adults. A retrospective case study was performed at two designated hospitals for COVID-19. Patients (56 children and 63 adults) with confirmed SARS-CoV-2 infection and mild pneumonia were randomly enrolled in this study. The median age of the children was 7.0 years, and 51.79% of them were boys. The median age of the adults was 57 years, and 47.62% were men. The most common symptoms were fever, cough, sputum and diarrhoea. There were no significant differences in symptoms between children and adult patients. In terms of immunological indices on admission, adult patients displayed typical leukopenia and markedly higher levels of IL-2, IL-4, and IL-6 than child patients. The elevation of IL-2, IL-4 and IL-6 in adults induced more extensive lung injury. The effective and non-aggressive immune response successfully resisted SARS-CoV-2 invasion and maintained mild symptoms in child patients. The correlation of higher IL-2, IL-4, and IL-6 with the lung injury might be evidence that preventing excessive cytokine production can avoid further lung damage in these patients.
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http://dx.doi.org/10.1007/s11596-021-2318-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881906PMC
February 2021

Nanocomposite NiTi shape memory alloy with high strength and fatigue resistance.

Nat Nanotechnol 2021 04 21;16(4):409-413. Epub 2021 Jan 21.

Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

Many established, but also potential future applications of NiTi-based shape memory alloys (SMA) in biomedical devices and solid-state refrigeration require long fatigue life with 10-10 duty cycles. However, improving the fatigue resistance of NiTi often compromises other mechanical and functional properties. Existing efforts to improve the fatigue resistance of SMA include composition control for coherent phase boundaries and microstructure control such as precipitation and grain-size reduction. Here, we extend the strategy to the nanoscale and improve fatigue resistance of NiTi via a hybrid heterogenous nanostructure. We produced a superelastic NiTi nanocomposite with crystalline and amorphous phases via severe plastic deformation and low-temperature annealing. The as-produced nanocomposite possesses a recoverable strain of 4.3% and a yield strength of 2.3 GPa. In cyclic compression experiments, the nanostructured NiTi micropillars endure over 10 reversible-phase-transition cycles under a stress of 1.8 GPa. We attribute the enhanced properties to the mutual strengthening of nanosized amorphous and crystalline phases where the amorphous phase suppresses dislocation slip in the crystalline phase while the crystalline phase hinders shear band propagation in the amorphous phase. The synergy of the properties of crystalline and amorphous phases at the nanoscale could be an effective method to improve fatigue resistance and strength of SMA.
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http://dx.doi.org/10.1038/s41565-020-00837-5DOI Listing
April 2021

Correction: Yu, D.Q., et al. Microscopic Characteristic and Chemical Composition Analysis of Three Medicinal Plants and Surface Frosts. 2019, , 4548.

Molecules 2021 Jan 13;26(2). Epub 2021 Jan 13.

College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.

The authors would like to correct an error in the title paper [...].
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http://dx.doi.org/10.3390/molecules26020379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828322PMC
January 2021

BET inhibition disrupts transcription but retains enhancer-promoter contact.

Nat Commun 2021 01 11;12(1):223. Epub 2021 Jan 11.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, NIHR Oxford Biomedical Research Centre Haematology Theme, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.

Enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes in higher eukaryotes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. Bromodomain and Extra-Terminal domain (BET) and Mediator proteins have been shown capable of forming phase condensates and are thought to be essential for super-enhancer function. Here, we show that targeting of cells with inhibitors of BET proteins or pharmacological degradation of BET protein Bromodomain-containing protein 4 (BRD4) has a strong impact on transcription but very little impact on enhancer-promoter interactions. Dissolving phase condensates reduces BRD4 and Mediator binding at enhancers and can also strongly affect gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further indicate that enhancer-promoter interactions are not dependent on high levels of BRD4 and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and, at some sites, CTCF and cohesin.
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http://dx.doi.org/10.1038/s41467-020-20400-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801379PMC
January 2021

The complete chloroplast genome sequence of .

Mitochondrial DNA B Resour 2020 Dec 24;5(4):3843-3844. Epub 2020 Dec 24.

School of Ecology and Environmental Sciences and School of Life Sciences, Yunnan University, Kunming, China.

The first complete chloroplast genome (cpDNA) sequence of Brongn. was determined from Illumina HiSeq pair-end sequencing data in this study. The cpDNA is 140,595 bp in length, contains a large single-copy region (LSC) of 82,447 bp, and a small single-copy region (SSC) of 12,626 bp, which were separated by a pair of inverted repeats (IR) regions of 22,761 bp. The genome contains 130 genes, including 83 protein-coding genes, eight ribosomal RNA genes, and 39 transfer RNA genes. The further phylogenomic analysis showed that and clustered in a clade in Poaceae family.
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http://dx.doi.org/10.1080/23802359.2020.1839365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759296PMC
December 2020

An updated tribal classification of Lamiaceae based on plastome phylogenomics.

BMC Biol 2021 01 8;19(1). Epub 2021 Jan 8.

CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.

Background: A robust molecular phylogeny is fundamental for developing a stable classification and providing a solid framework to understand patterns of diversification, historical biogeography, and character evolution. As the sixth largest angiosperm family, Lamiaceae, or the mint family, consitutes a major source of aromatic oil, wood, ornamentals, and culinary and medicinal herbs, making it an exceptionally important group ecologically, ethnobotanically, and floristically. The lack of a reliable phylogenetic framework for this family has thus far hindered broad-scale biogeographic studies and our comprehension of diversification. Although significant progress has been made towards clarifying Lamiaceae relationships during the past three decades, the resolution of a phylogenetic backbone at the tribal level has remained one of the greatest challenges due to limited availability of genetic data.

Results: We performed phylogenetic analyses of Lamiaceae to infer relationships at the tribal level using 79 protein-coding plastid genes from 175 accessions representing 170 taxa, 79 genera, and all 12 subfamilies. Both maximum likelihood and Bayesian analyses yielded a more robust phylogenetic hypothesis relative to previous studies and supported the monophyly of all 12 subfamilies, and a classification for 22 tribes, three of which are newly recognized in this study. As a consequence, we propose an updated phylogenetically informed tribal classification for Lamiaceae that is supplemented with a detailed summary of taxonomic history, generic and species diversity, morphology, synapomorphies, and distribution for each subfamily and tribe.

Conclusions: Increased taxon sampling conjoined with phylogenetic analyses based on plastome sequences has provided robust support at both deep and shallow nodes and offers new insights into the phylogenetic relationships among tribes and subfamilies of Lamiaceae. This robust phylogenetic backbone of Lamiaceae will serve as a framework for future studies on mint classification, biogeography, character evolution, and diversification.
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http://dx.doi.org/10.1186/s12915-020-00931-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796571PMC
January 2021

Genomic atlases of introgression and differentiation reveal breeding footprints in Chinese cultivated rice.

J Genet Genomics 2020 10 25;47(10):637-649. Epub 2020 Nov 25.

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

The long history of cultivation and breeding has left a variety of footprints in the genomes of Asian cultivated rice (Oryza sativa L.). In this study, we focus on two types of genomic footprints, introgression and differentiation, in a population of more than 1200 Chinese rice accessions. We found that a Xian/indica and a temperate Geng/japonica accession respectively contained an average of 19.3-Mb and 6.8-Mb alien introgressed chromosomal segments, of which many contained functional sequence variants, quantitative trait loci, or genes controlling flowering, grain, and resistance traits. Notably, we found most introgressions, including the known heterotic loci Hd3a and TAC1, were distributed differentially between the female and male parents of three-line indica hybrid rice, indicating their potential contribution to heterosis. We also found many differentiated regions between subgroups within a subpopulation contained agronomically important loci, such as DTH7, Hd1 for heading date, and qCT7 for cold tolerance, providing new candidates for studying local adaptation or heterosis. Tracing these footprints allows us to better understand the genetic exchange or differentiation underlying agronomic traits in modern Chinese rice cultivars. These findings also provide potential targets for rice genetic research and breeding.
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http://dx.doi.org/10.1016/j.jgg.2020.10.006DOI Listing
October 2020

The complete chloroplast genome sequence of and its phylogenetic position.

Mitochondrial DNA B Resour 2020 Nov 22;5(3):3807-3809. Epub 2020 Nov 22.

CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, P. R. China.

is a member of the genus , which distributes in Central and South America. Genetic information of would provide guidance for the phylogenetic position of this species. Here, we reported and characterized its complete chloroplast (cp) genome using Illumina pair-end sequencing data. The total chloroplast genome size of this species was 157,211 bp, including inverted repeats (IRs) of 26,103 bp, separated by a large single copy (LSC) and a small single copy (SSC) of 86,749 and 18,256 bp, respectively. A total of 132 genes, including 37 tRNA, 8 rRNA, and 87 protein-coding genes were identified. Phylogenetic analysis showed that formed a monophyletic clade with , and then grouped with . The systematic position of Southeast Asian species needs further studies.
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http://dx.doi.org/10.1080/23802359.2020.1837687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717450PMC
November 2020

The whole genome assembly and evolution analyze of carmine radish () Mitochondrion.

Authors:
Hua Peng Jian Gao

Mitochondrial DNA B Resour 2020 1;5(3):2252-2253. Epub 2020 Jun 1.

Department of Life Sciences and Technology, Yangtze Normal University, Fuling, China.

Carmine radish, which contained a high natural red pigment (red radish pigment), was peculiar produced in Fuling, Chongqing City. Here, the complete nucleotide sequences of the mitochondrial (mt) genome of carmine radish () have been determined with a circular sequence with the lengths of 258,965 bp, comprised of 40 protein-coding genes, 23 tRNA genes, and three ribosomal RNA genes. To demonstrate the evolution of organelles genomes in plants, other plant mitochondrial genomes' evolution were also selected for analyze. The results showed that carmine radish is related to MS_Gensuke and Black radish , as well as related to Brassica nigra and Brassica carinata, comparing with other Brassicaceae species. This study will provide important genetic tools for other Brassicaceae species research and improve yields of economically important plants.
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http://dx.doi.org/10.1080/23802359.2020.1772136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510604PMC
June 2020

PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade.

Nat Commun 2020 09 24;11(1):4835. Epub 2020 Sep 24.

School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China.

Immune checkpoint blockade therapies have shown clinical promise in a variety of cancers, but how tumor-infiltrating T cells are activated remains unclear. In this study, we explore the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. We observe that PD-L1 on DC plays a critical role in limiting T cell responses. Type 1 conventional DCs are essential for PD-L1 blockade and they upregulate PD-L1 upon antigen uptake. Upregulation of PD-L1 on DC is mediated by type II interferon. While DCs are the major antigen presenting cells for cross-presenting tumor antigens to T cells, subsequent PD-L1 upregulation protects them from killing by cytotoxic T lymphocytes, yet dampens the antitumor responses. Blocking PD-L1 in established tumors promotes re-activation of tumor-infiltrating T cells for tumor control. Our study identifies a critical and dynamic role of PD-L1 on DC, which needs to be harnessed for better invigoration of antitumor immune responses.
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http://dx.doi.org/10.1038/s41467-020-18570-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518441PMC
September 2020

Ratiometric fluorescence nanoprobe for monitoring of intracellular temperature and tyrosine based on a dual emissive carbon dots/gold nanohybrid.

Talanta 2020 Nov 14;219:121279. Epub 2020 Jun 14.

Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming,Yunnan Province, 650500,China; Faculty of Land Resource Engineering,Kunming University of Science and Technology,Kunming,Yunnan Province, 650500,China. Electronic address:

A novel dual-emission nitrogen doped carbon dots/gold nanohybrid (NCDs-Au) was designed for specific and sensitive ratiometric detection of intracellular temperature and tyrosine. In this probe, a reductive NCDs was successfully prepared with the use of natural biomass Dendrobium officinale as precursor. The new prepared NCDs acted as both reducers and stabilizers to synthesize a novel NCDs-Au nanohybrid by a facile one-step procedure along with a quantum yield of 14.3%. The prepared nanoprobe showed characteristic fluorescence emissions of NCDs and Au NCs with single-wavelength excitation. Notably, the nanoprobe shows an interesting wavelength-dependent dual response to temperature (448 nm) and tyrosine (660 nm), enabling the two targets to be detected proportionally. As an effective temperature sensor, the nanoprobe exhibited good temperature-dependent fluorescence with a sensational linear response from 5 to 75 °C. In addition, the sensor has a linear response toward tyrosine in the range of 0.5-175 μM with a detection limit of 0.19 μM. Moreover, the fluorescent nanoprobe was successfully applied to ratiometricly monitor the variation of temperature or tyrosine level in cells because of the low cytotoxicity, chemical stability and excellent fluorescence properties. These results suggested that the nanoprobe here has provided the possibility for rapidly biosensing with the acceptable selectivity and sensitivity.
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http://dx.doi.org/10.1016/j.talanta.2020.121279DOI Listing
November 2020

Phyllathin From Phyllanthus Amarus Ameliorates Epileptic Convulsion and Kindling Associated Post-Ictal Depression in Mice via Inhibition of NF-κB/TLR-4 Pathway.

Dose Response 2020 Jul-Sep;18(3):1559325820946914. Epub 2020 Aug 3.

Department of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Background: Epilepsy is a chronic, complex, unprovoked, and recurrent disorder of the nervous system that affected several people worldwide. (PA) has been documented to have neuroprotective potential.

Aim: To evaluate the potential of standardized extract of PA and its possible mechanism of action against the Pentylenetetrazol (PTZ)-induced convulsion and kindling associated post-ictal depression in experimental mice.

Materials And Methods: Phyllathin was isolated from methanolic extract of PA and well-characterized using HPTLC, ESI-MS/MS, and LC/MS. Phyllathin containing a standardized extract of PA (50, 100, and 200 mg/kg) was administered in convulsed and kindled mice, followed by an assessment of various parameters.

Results: The spectral analysis confirmed the molecular formula and weight of phyllanthin as CHO and 418.2342 Da. PA (100 and 200 mg/kg) significantly ameliorated PTZ-induced ( 0.05) duration, onset of tonic-clonic convulsion, and mortality in mice. It also significantly attenuated ( 0.05) PTZ-induced kindling in mice. Alteration in brain GABA, dopamine, and glutamate, NaKATPase, Ca-ATPase activities, and oxido-nitrosative stress in kindled mice was significantly restored ( 0.05) by PA treatment. It also significantly ( 0.05) down-regulated brain mRNA expressions of NF-κB, TNF-α, IL-1β, COX-2, and TLR-4. Histological aberrations induced by PTZ in the brain of a kindled rat was significantly ( 0.05) ameliorated by PA.

Conclusion: Phyllanthin containing a standardized extract of PA exerts its antiepileptic potential via balancing excitatory (glutamate) and inhibitory (GABA) brain monoamines, voltage-gated ion channels (NaK/Ca-ATPase) and inhibition of NF-κB/TLR-4 pathway to ameliorate neuroinflammation (TNF-α, IL-1β, and COX-2) in experimental mice.
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http://dx.doi.org/10.1177/1559325820946914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412921PMC
August 2020

Combined linkage mapping and association analysis reveals genetic control of maize kernel moisture content.

Physiol Plant 2020 Dec 18;170(4):508-518. Epub 2020 Oct 18.

Key Laboratory of Biology and Genetic Improvement of Maize in Southwest Region, Maize Research Institute, Sichuan Agricultural University, Chengdu, 611130, China.

The free moisture in crop kernels after being naturally dried is referred to as kernel moisture content (KMC). Maize KMC reflects grain quality and influences transportation and storage of seeds. We used an IBM Syn10 DH maize population consisting of 249 lines and an association panel comprising 310 maize inbred lines to identify the genetic loci affecting maize KMC in three environments. Using the IBM population detected 13 QTL on seven chromosomes, which were clustered into nine common QTL. Genome-wide association analysis (GWAS) identified 16 significant SNPs across the 3 environments, which were linked to 158 genes across the three environments. Combined QTL mapping and GWAS found two SNPs that were located in two of the mapped QTL, respectively. Twenty-three genes were linked with the loci co-localized in both populations. Of these 181 genes, five have previously been reported to be associated with KMC or to regulate seed development. These associations were verified by candidate gene association analysis. Two superior alleles and one favorable haplotype for Zm00001d007774 and Zm00001d047868 were found to influence KMC. These findings provide insights into molecular mechanisms underlying maize KMC and contribute to the use of marker-assisted selection for breeding low-KMC maize.
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http://dx.doi.org/10.1111/ppl.13180DOI Listing
December 2020
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