Publications by authors named "Tianzhen Zhang"

144 Publications

Observation of Distinct Spatial Distributions of the Zero and Nonzero Energy Vortex Modes in (Li_{0.84}Fe_{0.16})OHFeSe.

Phys Rev Lett 2021 Mar;126(12):127001

Hefei National Laboratory for Physical Science at Microscale and Department of Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

The energy and spatial distributions of vortex bound state in superconductors carry important information about superconducting pairing and the electronic structure. Although discrete vortex states, and sometimes a zero energy mode, had been observed in several iron-based superconductors, their spatial properties are rarely explored. In this study, we used low-temperature scanning tunneling microscopy to measure the vortex state of (Li,Fe)OHFeSe with high spatial resolution. We found that the nonzero energy states display clear spatial oscillations with a period corresponding to bulk Fermi wavelength; while in contrast, the zero energy mode does not show such oscillation, which suggests its distinct electronic origin. Furthermore, the oscillations of positive and negative energy states near E_{F} are found to be clearly out of phase. Based on a two-band model calculation, we show that our observation is more consistent with an s_{++} wave pairing in the bulk of (Li, Fe)OHFeSe, and superconducting topological states on the surface.
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http://dx.doi.org/10.1103/PhysRevLett.126.127001DOI Listing
March 2021

MicroRNA-146a switches microglial phenotypes to resist the pathological processes and cognitive degradation of Alzheimer's disease.

Theranostics 2021 19;11(9):4103-4121. Epub 2021 Feb 19.

Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and currently has no effective treatment. Mainstream research on the mechanisms and therapeutic targets of AD is focused on the two most important hallmarks, Aβ and Tau, but the results from clinical studies are not encouraging. Abnormal microglial polarization is a clear typical pathological feature in the progression of AD. Microglia can be neuroprotective by degrading and removing Aβ and Tau. However, under AD conditions, microglia transform into a pro-inflammatory phenotype that decreases the phagocytic activity of microglia, damages neurons and promotes the pathology of AD. We previously reported that a miR-146a polymorphism is associated with sporadic AD risk, and the nasal administration of miR-146a mimics reduced cognitive impairment and the main pathological features of AD. However, it is not clear by what mechanism miR-146a resists the pathological process of AD. In this study, we discovered that microglia-specific miR-146a overexpression reduced cognitive deficits in learning and memory, attenuated neuroinflammation, reduced Aβ levels, ameliorated plaque-associated neuritic pathology, and prevented neuronal loss in APP/PS1 transgenic mice. In addition, we found that miR-146a switched the microglial phenotype, reduced pro-inflammatory cytokines and enhanced phagocytic function to protect neurons and . Moreover, transcriptional analysis confirmed that miR-146a opposed the pathological process of AD mainly through neuroinflammation-related pathways. In summary, our results provide sufficient evidence for the mechanism by which miR-146a opposes AD and strengthen the conclusion that miR-146a is a promising target for AD and other microglia-related diseases.
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http://dx.doi.org/10.7150/thno.53418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977456PMC
February 2021

GoNe encoding a class VIIIb AP2/ERF is required for both extrafloral and floral nectary development in Gossypium.

Plant J 2021 May 5;106(4):1116-1127. Epub 2021 Apr 5.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, China.

The floral nectary, first recognized and described by Carl Linnaeus, is a remarkable organ that serves to provide carbohydrate-rich nectar to visiting pollinators in return for gamete transfer between flowers. Therefore, the nectary has indispensable biological significance in plant reproduction and even in evolution. Only two genes, CRC and STY, have been reported to regulate floral nectary development. However, it is still unknown what genes contribute to extrafloral nectary development. Here, we report that a nectary development gene in Gossypium (GoNe), annotated as an APETALA 2/ethylene-responsive factor (AP2/ERF), is responsible for the formation of both floral and extrafloral nectaries. GoNe plants that are silenced via virus-induced gene silencing technology and/or knocked out by Cas9 produce a nectariless phenotype. Point mutation and gene truncation simultaneously in duplicated genes Ne Ne lead to impaired nectary development in tetraploid cotton. There is no difference in the expression of the CRC and STY genes between the nectary TM-1 and the nectariless MD90ne in cotton. Therefore, the GoNe gene responsible for the formation of floral and extrafloral nectaries may be independent of CRC and STY. A complex mechanism might exist that restricts the nectary to a specific position with different genetic factors. Characterization of these target genes regulating nectary production has provided insights into the development, evolution, and function of nectaries and insect-resistant breeding.
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http://dx.doi.org/10.1111/tpj.15223DOI Listing
May 2021

Divergent improvement of two cultivated allotetraploid cotton species.

Plant Biotechnol J 2021 Jan 14. Epub 2021 Jan 14.

Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, Plant Precision Breeding Academy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

Interspecific genomic variation can provide a genetic basis for local adaptation and domestication. A series of studies have presented its role of interspecific haplotypes and introgressions in adaptive traits, but few studies have addressed their role in improving agronomic character. Two allotetraploid Gossypium species, Gossypium barbadense (Gb) and G. hirsutum (Gh) originating from the Americas, are cultivated independently. Here, through sequencing and the comparison of one GWAS panel in 229 Gb accessions and two GWAS panels in 491 Gh accessions, we found that most associated loci or functional haplotypes for agronomic traits were highly divergent, representing the strong divergent improvement between Gb and Gh. Using a comprehensive interspecific haplotype map, we revealed that six interspecific introgressions from Gh to Gb were significantly associated with the phenotypic performance of Gb, which could explain 5%-40% of phenotypic variation in yield and fibre qualities. In addition, three introgressions overlapped with six associated loci in Gb, indicating that these introgression regions were under further selection and stabilized during improvement. A single interspecific introgression often possessed yield-increasing potential but decreased fibre qualities, or the opposite, making it difficult to simultaneously improve yield and fibre qualities. Our study not only has proved the importance of interspecific functional haplotypes or introgressions in the divergent improvement of Gb and Gh, but also supports their potential value in further human-mediated hybridization or precision breeding.
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http://dx.doi.org/10.1111/pbi.13547DOI Listing
January 2021

IL-2 regulates tumor-reactive CD8 T cell exhaustion by activating the aryl hydrocarbon receptor.

Nat Immunol 2021 03 11;22(3):358-369. Epub 2021 Jan 11.

Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.

CD8 T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8 T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8 T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8 T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion.
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http://dx.doi.org/10.1038/s41590-020-00850-9DOI Listing
March 2021

MIXTAs and phytohormones orchestrate cotton fiber development.

Curr Opin Plant Biol 2021 02 6;59:101975. Epub 2020 Dec 6.

Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, College of Agriculture and Biotechnology, Zhejiang University, 310029 Zhejiang, PR China. Electronic address:

Cotton is the largest source of natural fiber for textile industry in the world. Cotton fibers are seed trichomes that make cotton unique among plants. Cotton fibers originate from ovule epidermal cells and serve as an excellent model to study the process of cell differentiation in plants. Characterization of factors contributing to fiber development will help to reveal general mechanisms of cell differentiation in plants. Transcription factors (TFs), especially MYB-MIXTA-like (MML) factors, appear to have evolved unique roles in fiber development. In addition, phytohormones including brassinosteroids, jasmonic acid, GA and auxin also play an important role in regulating fiber development. Here, we summarize the mechanisms of MIXTAs and phytohormones orchestrating cotton fiber development. The progress in understanding molecular basis of fiber development will facilitate future genetic engineering and breeding to improve cotton fiber quality and yield.
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http://dx.doi.org/10.1016/j.pbi.2020.10.007DOI Listing
February 2021

Cell softness regulates tumorigenicity and stemness of cancer cells.

EMBO J 2021 01 4;40(2):e106123. Epub 2020 Dec 4.

Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.

Identifying and sorting highly tumorigenic and metastatic tumor cells from a heterogeneous cell population is a daunting challenge. Here, we show that microfluidic devices can be used to sort marker-based heterogeneous cancer stem cells (CSC) into mechanically stiff and soft subpopulations. The isolated soft tumor cells (< 400 Pa) but not the stiff ones (> 700 Pa) can form a tumor in immunocompetent mice with 100 cells per inoculation. Notably, only the soft, but not the stiff cells, isolated from CD133 , ALDH , or side population CSCs, are able to form a tumor with only 100 cells in NOD-SCID or immunocompetent mice. The Wnt signaling protein BCL9L is upregulated in soft tumor cells and regulates their stemness and tumorigenicity. Clinically, BCL9L expression is correlated with a worse prognosis. Our findings suggest that the intrinsic softness is a unique marker of highly tumorigenic and metastatic tumor cells.
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http://dx.doi.org/10.15252/embj.2020106123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809788PMC
January 2021

Novel Insights Into the Role of N6-Methyladenosine RNA Modification in Bone Pathophysiology.

Stem Cells Dev 2021 Jan 21;30(1):17-28. Epub 2020 Dec 21.

Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China.

Thus far, there are more than known 150 modifications to RNA, in which common internal modifications of mRNA include N6-methyladenosine (m6A), N1-methyladenosine, and 5-methylcytosine. Among them, m6A RNA modification is one of the highest abundance modifications in eukaryotes, regulating mechanisms controlling gene expression at the post-transcription level. As an invertible and dynamic epigenetic marker, m6A base modification influences almost all vital biological processes, cellular components, and molecular functions. Once the m6A modification process is abnormal, a series of diseases-including cancer, neurological diseases, and growth disorders-will be caused. Besides, several base modification activities also have been created by noncoding RNAs (ncRNAs), for instance, microRNAs, and circular RNAs, long ncRNAs, which were dynamically regulated during bone and cartilage pathophysiology processes. Therefore, it has now been clear that dynamic modification on coding RNAs and ncRNAs represents a completely new way to modulate genetic information. In this review, we highlight up-to-date progress and applications of m6A RNA modification in bone and cartilage pathophysiology, and we discuss the pathological roles and underlying molecular mechanism of m6A modifications in osteoarthritis and osteoporosis and osteosarcoma pathogenesis.
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http://dx.doi.org/10.1089/scd.2020.0157DOI Listing
January 2021

Cell Softness Prevents Cytolytic T-cell Killing of Tumor-Repopulating Cells.

Cancer Res 2021 01 9;81(2):476-488. Epub 2020 Nov 9.

Department of Immunology and National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College, Beijing, China.

Biomechanics is a fundamental feature of a cell. However, the manner by which actomysin tension affects tumor immune evasion remains unclear. Here we show that although cytotoxic T lymphocytes (CTL) can effectively destroy stiff differentiated tumor cells, they fail to kill soft tumor-repopulating cells (TRC). TRC softness prevented membrane pore formation caused by CTL-released perforin. Perforin interacting with nonmuscle myosin heavy-chain 9 transmitted forces to less F-actins in soft TRC, thus generating an inadequate contractile force for perforin pore formation. Stiffening TRC allowed perforin the ability to drill through the membrane, leading to CTL-mediated killing of TRC. Importantly, overcoming mechanical softness in human TRC also enhanced TRC cell death caused by human CTL, potentiating a mechanics-based immunotherapeutic strategy. These findings reveal a mechanics-mediated tumor immune evasion, thus potentially providing an alternative approach for tumor immunotherapy. SIGNIFICANCE: Tumor-repopulating cells evade CD8 cytolytic T-cell killing through a mechanical softness mechanism, underlying the impediment of perforin pore formation at the immune synapse site.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2569DOI Listing
January 2021

Role of phasiRNAs from two distinct phasing frames of GhMYB2 loci in cis- gene regulation in the cotton genome.

BMC Plant Biol 2020 May 15;20(1):219. Epub 2020 May 15.

College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China.

Background: Phased small interfering RNA (phasiRNA) is primarily derived from the 22-nt miRNA targeting loci. GhMYB2, a gene with potential roles in cotton fiber cell fate determination, is a target gene of miR828 and miR858 in the generation of phasiRNAs.

Results: In the presented work, through the evaluation of phasing scores and phasiRNA distribution pattern, we found that phasiRNAs from GhMYB2 were derived from the 3' cleavage fragments of 22-nt miR828 and 21-nt miR858 respectively. These two miRNA targeting sites initiated two phasing frames on transcripts of one locus. By means of RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE), we further demonstrated that phasiRNAs derived from the two phasing frames played a role in cis-regulation of GhMYB2. The phasiRNAs derived from GhMYB2 were expressed in the somatic tissues, especially in anther and hypocotyl. We further employed our previous small RNA sequencing data as well as the degradome data of cotton fiber bearing ovules, anthers, hypocotyls and embryogenic calli tissues published in public databases, to validate the expression, phasing pattern and functions of phasiRNAs.

Conclusions: The presenting research provide insights of the molecular mechanism of phasiRNAs in regulation of GhMYB2 loci.
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http://dx.doi.org/10.1186/s12870-020-02430-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227086PMC
May 2020

Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress.

Front Cell Dev Biol 2020 24;8:147. Epub 2020 Mar 24.

Department of Traumatology Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.
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http://dx.doi.org/10.3389/fcell.2020.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105877PMC
March 2020

The transcription factor MML4_D12 regulates fiber development through interplay with the WD40-repeat protein WDR in cotton.

J Exp Bot 2020 06;71(12):3499-3511

National Key Laboratory of Crop Genetics and Germplasm Enhancement, Cotton Research Institute, Nanjing Agricultural University, Nanjing, P. R. China.

In planta, a vital regulatory complex, MYB-basic helix-loop-helix (bHLH)-WD40 (MBW), is involved in trichome development and synthesis of anthocyanin and proanthocyanin in Arabidopsis. Usually, WD40 proteins provide a scaffold for protein-protein interaction between MYB and bHLH proteins. Members of subgroup 9 of the R2R3 MYB transcription factors, which includes MYBMIXTA-Like (MML) genes important for plant cell differentiation, are unable to interact with bHLH. In this study, we report that a cotton (Gossypium hirsutum) seed trichome or lint fiber-related GhMML factor, GhMML4_D12, interacts with a diverged WD40 protein (GhWDR) in a process similar to but different from that of the MBW ternary complex involved in Arabidopsis trichome development. Amino acids 250-267 of GhMML4_D12 and the first and third WD40 repeat domains of GhWDR determine their interaction. GhWDR could rescue Arabidopsis ttg1 to its wild type, confirming its orthologous function in trichome development. Our findings shed more light towards understanding the key role of the MML and WD40 families in plants and in the improvement of cotton fiber production.
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http://dx.doi.org/10.1093/jxb/eraa104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475258PMC
June 2020

Genomic signatures and candidate genes of lint yield and fibre quality improvement in Upland cotton in Xinjiang.

Plant Biotechnol J 2020 Feb 7. Epub 2020 Feb 7.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, China.

Xinjiang has been the largest and highest yield cotton production region not only in China, but also in the world. Improvements in Upland cotton cultivars in Xinjiang have occurred via pedigree selection and/or crossing of elite alleles from the former Soviet Union and other cotton producing regions of China. But it is unclear how genomic constitutions from foundation parents have been selected and inherited. Here, we deep-sequenced seven historic foundation parents, comprising four cultivars introduced from the former Soviet Union (108Ф, C1470, 611Б and KK1543) and three from United States and Africa (DPL15, STV2B and UGDM), and re-sequenced sixty-nine Xinjiang modern cultivars. Phylogenetic analysis of more than 2 million high-quality single nucleotide polymorphisms allowed their classification two groups, suggesting that Xinjiang Upland cotton cultivars were not only spawned from 108Ф, C1470, 611Б and KK1543, but also had a close kinship with DPL15, STV2B and UGDM. Notably, identity-by-descent (IBD) tracking demonstrated that the former Soviet Union cultivars have made a huge contribution to modern cultivar improvement in Xinjiang. A total of 156 selective sweeps were identified. Among them, apoptosis-antagonizing transcription factor gene (GhAATF1) and mitochondrial transcription termination factor family protein gene (GhmTERF1) were highly involved in the determination of lint percentage. Additionally, the auxin response factor gene (GhARF3) located in inherited IBD segments from 108Ф and 611Б was highly correlated with fibre quality. These results provide an insight into the genomics of artificial selection for improving cotton production and facilitate next-generation precision breeding of cotton and other crops.
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http://dx.doi.org/10.1111/pbi.13356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540456PMC
February 2020

Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome.

Sci Immunol 2020 01;5(43)

Department of Immunology and National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College, Beijing 100005, China.

Cytokine release syndrome (CRS) counteracts the effectiveness of chimeric antigen receptor (CAR) T cell therapy in cancer patients, but the mechanism underlying CRS remains unclear. Here, we show that tumor cell pyroptosis triggers CRS during CAR T cell therapy. We find that CAR T cells rapidly activate caspase 3 in target cells through release of granzyme B. The latter cleaves gasdermin E (GSDME), a pore-forming protein highly expressed in B leukemic and other target cells, which results in extensive pyroptosis. Consequently, pyroptosis-released factors activate caspase 1 for GSDMD cleavage in macrophages, which results in the release of cytokines and subsequent CRS. Knocking out GSDME, depleting macrophages, or inhibiting caspase 1 eliminates CRS occurrence in mouse models. In patients, GSDME and lactate dehydrogenase levels are correlated with the severity of CRS. Notably, we find that the quantity of perforin/granzyme B used by CAR T cells rather than existing CD8 T cells is critical for CAR T cells to induce target cell pyroptosis.
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http://dx.doi.org/10.1126/sciimmunol.aax7969DOI Listing
January 2020

Benchmark selectivity -xylene separation by a non-porous molecular solid through liquid or vapor extraction.

Chem Sci 2019 Oct 6;10(38):8850-8854. Epub 2019 Aug 6.

State Key Laboratory of Elemento-Organic Chemistry , College of Chemistry , Nankai University , Tianjin 300071 , China . Email:

Solid-liquid separation of similarly sized organic molecules utilizing sorbents offers the potential for new energy-efficient approaches to a number of important industrial separations such as xylenes (C8) separations. Research on selective C8 sorption has tended to focus upon rigid porous materials such as zeolites and MOFs but has revealed generally weak selectivity that is inconsistent across the range of C8 molecules. Nevertheless, there are a few recent examples of non-porous molecular materials that exhibit relatively high selectivity for -xylene (X) from X/X, approaching that of the current benchmark X sorbent, the zeolite H/ZSM-5. Herein, we report that a L-shaped Ag(i) complex, AgClO (), which crystallizes as a non-porous molecular solid material, offering exceptional performance for X selectivity across the range of C8 isomers with liquid extraction selectivity values of 24.0, 10.4 and 6.2 X, B and X, respectively. The X selectivities over X and B are among the highest yet reported. Moreover, also exhibits strong vapor extraction selectivity and can be regenerated by exposure to vacuum drying.
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http://dx.doi.org/10.1039/c9sc02621eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853085PMC
October 2019

G65V Substitution in Actin Disturbs Polymerization Leading to Inhibited Cell Elongation in Cotton.

Front Plant Sci 2019 15;10:1486. Epub 2019 Nov 15.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Cotton Hybrid R & D Engineering Center (the Ministry of Education), College of Agriculture, Nanjing Agricultural University, Nanjing, China.

The importance of the actin cytoskeleton for proper cell development has been well established in a variety of organisms. Actin protein sequences are highly conserved, and each amino acid residue may be essential for its function. In this study, we report the isolation and characterization of from an upland cotton mutant Ligon lintless-1 (Li), which harbors the G65V substitution in its encoded actin protein. Li mutants exhibit pleiotropic malformed phenotypes, including dwarf plants, distorted organs, and extremely shortened fibers. Cytological analysis showed that the actin cytoskeleton was disorganized and the abundance of F-actin was decreased in the Li cells. Vesicles were aggregated into patches, and excessive cellulose synthase complexes were inserted into the plasma membrane during the secondary cell wall biosynthesis stage, which dramatically affected the morphology of the Li cells. Molecular model prediction suggested that the G65V substitution may affect the three-bodied G-actin interaction during F-actin assembly. Biochemical assays demonstrated that the recombinant GhLi protein disturbs actin dynamics by inhibiting the nucleation and elongation processes. Therefore, our findings demonstrate that the G65V substitution in actin had dominant-negative effects on cell elongation, by disturbing actin polymerization and actin cytoskeleton-based biological processes such as intracellular transportation.
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http://dx.doi.org/10.3389/fpls.2019.01486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873290PMC
November 2019

PAES and PAHs in the surface sediments of the East China Sea: Occurrence, distribution and influence factors.

Sci Total Environ 2020 Feb 5;703:134763. Epub 2019 Nov 5.

Key Laboratory of Marine Ecosystem and Biogeochemistry, State Oceanic Administration & Second Institute of Oceanography, Ministry of Natural Resources, Baochubei Road 36, Hangzhou 310012, PR China.

A total of 29 sediment samples were collected from the East China Sea (ECS), with the Yangtze River estuary and the Zhejiang costal area. These sediment samples were analyzed for 6 phthalate esters (PAEs) and 16 polycyclic aromatic hydrocarbons (PAHs): the ΣPAEs and ΣPAHs concentrations ranged between 1649.5 and 8451.5 ng g (mean = 3446.3 ng g) and 57.5-364.5 ng g (mean = 166.2 ng g), respectively. Overall, the PAEs and PAHs concentrations gradually decreasing in the offshore and southward directions: their compositions and distributions suggest they could have mainly derived from the Yangtze River. In particular, their distribution was influenced by the sources' proximity, hydrodynamics, and sediment geochemistry (i.e., TOC content and grain size). A classical two-end member model was utilized to estimate the fraction of terrestrial organic carbon in the sediments of the ECS. When the sediment was dominated by terrestrial-derived organic matter (OM), the concentrations of PAEs and PAHs were significantly correlated to the TOC content and gran size of the sediments. In contrast, the poor correlation of TOC content and grain size with PAEs in those sediments dominated by marine-derived OM, implied that the distribution of PAEs in the ECS was mainly related to land-based inputs, (especially to that of the Yangtze River). Regardless of the origin of most of the OM contained in the sediments, we observed positive correlations between the TOC content, and grain size of those containing PAHs. These results suggest that the distribution of PAHs in the ECS was not only related to the Yangtze River input, but also to the geochemical characteristics of the sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134763DOI Listing
February 2020

A CC-NBS-LRR gene induces hybrid lethality in cotton.

J Exp Bot 2019 10;70(19):5145-5156

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, China.

Hybrid lethality forms a reproductive barrier that has been found in many eukaryotes. Most cases follow the Bateson-Dobzhansky-Muller genetic incompatibility model and involve two or more loci. In this study, we demonstrate that a coiled-coil nucleotide-binding site leucine-rich repeat (CC-NBS-LRR) gene is the causal gene underlying the Le4 locus for interspecific hybrid lethality between Gossypium barbadense and G. hirsutum (cotton). Silencing this CC-NBS-LRR gene can restore F1 plants from a lethal to a normal phenotype. A total of 11 099 genes were differentially expressed between the leaves of normal and lethal F1 plants, of which genes related to autoimmune responses were highly enriched. Genes related to ATP-binding and ATPase were up-regulated before the lethal syndrome appeared; this may result in the conversion of Le4 into an active state and hence trigger immune signals in the absence of biotic/abiotic stress. We discuss our results in relation to the evolution and domestication of Sea Island cottons and the molecular mechanisms of hybrid lethality associated with autoimmune responses. Our findings provide new insights into reproductive isolation and may benefit cotton breeding.
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http://dx.doi.org/10.1093/jxb/erz312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6793457PMC
October 2019

Overdominance is the major genetic basis of lint yield heterosis in interspecific hybrids between G. hirsutum and G. barbadense.

Heredity (Edinb) 2019 09 22;123(3):384-394. Epub 2019 Mar 22.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Cotton Hybrid R & D Engineering Center (the Ministry of Education), College of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China.

The genetic basis of heterosis has not been resolved for approximately a century, although the role of loci with overdominant (ODO) effects has continued to be discussed by biologists. In the present investigation, a proposed model was studied in Gossypium hirsutum L. introgression lines (ILs) harbouring a segment of G. barbadense. These introgressions were confirmed by a single marker of G. barbadense. These ILs contained 396 quantitative trait loci (QTLs) for 11 yield and non-yield traits that were recorded in the field on homozygous and heterozygous plants for 5 years. After comparing the different types of QTLs between the yield group and the non-yield group, it was found that the yield group had significantly higher ODO QTL ratios. Moreover, 16 ODO QTLs identified for 5 yield-related traits were consistently detected during 5 cotton growing seasons (2010-2011 and 2013-2015): 6 of 7 for boll weight, 3 of 11 for seed-cotton yield per plant, 4 of 17 for boll number, 2 of 13 for lint yield per plant and 1 of 11 for lint percentage. Therefore, we propose that overdominance is the major genetic basis of lint yield heterosis in interspecific hybrids between G. barbadense and G. hirsutum. These findings have important implications in cotton breeding in that the boll weight can be improved by utilizing ODO QTLs via heterosis; thus, the stagnant yield barrier can be smashed to achieve sustainable increases in cotton production. Additionally, this concept can be translated to other field crops for improving their yield potential.
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http://dx.doi.org/10.1038/s41437-019-0211-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781152PMC
September 2019

Gossypium barbadense and Gossypium hirsutum genomes provide insights into the origin and evolution of allotetraploid cotton.

Nat Genet 2019 04 18;51(4):739-748. Epub 2019 Mar 18.

Esquel Group, Wanchai, Hong Kong, China.

Allotetraploid cotton is an economically important natural-fiber-producing crop worldwide. After polyploidization, Gossypium hirsutum L. evolved to produce a higher fiber yield and to better survive harsh environments than Gossypium barbadense, which produces superior-quality fibers. The global genetic and molecular bases for these interspecies divergences were unknown. Here we report high-quality de novo-assembled genomes for these two cultivated allotetraploid species with pronounced improvement in repetitive-DNA-enriched centromeric regions. Whole-genome comparative analyses revealed that species-specific alterations in gene expression, structural variations and expanded gene families were responsible for speciation and the evolutionary history of these species. These findings help to elucidate the evolution of cotton genomes and their domestication history. The information generated not only should enable breeders to improve fiber quality and resilience to ever-changing environmental conditions but also can be translated to other crops for better understanding of their domestication history and use in improvement.
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http://dx.doi.org/10.1038/s41588-019-0371-5DOI Listing
April 2019

Mitochondrial small heat shock protein mediates seed germination via thermal sensing.

Proc Natl Acad Sci U S A 2019 03 14;116(10):4716-4721. Epub 2019 Feb 14.

Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, Zhejiang University, 310029 Zhejiang, China;

Seed germination is an energy demanding process that requires functional mitochondria upon imbibition. However, how mitochondria fine tune seed germination, especially in response to the dynamics of environmental temperature, remains largely unknown at the molecular level. Here, we report a mitochondrial matrix-localized heat shock protein GhHSP24.7, that regulates seed germination in a temperature-dependent manner. Suppression of renders the seed insensitive to temperature changes and delays germination. We show that GhHSP24.7 competes with GhCCMH to bind to the maturation subunit protein GhCcmF to form cytochrome C/C (CytC/C) in the mitochondrial electron transport chain. GhHSP24.7 modulates CytC/C production to induce reactive oxygen species (ROS) generation, which consequently accelerates endosperm rupture and promotes seed germination. Overexpression of 's homologous genes can accelerate seed germination in and tomato, indicating its conserved function across plant species. Therefore, is a critical factor that positively controls seed germination via temperature-dependent ROS generation.
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http://dx.doi.org/10.1073/pnas.1815790116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410843PMC
March 2019

LMI1-like and KNOX1 genes coordinately regulate plant leaf development in dicotyledons.

Plant Mol Biol 2019 Mar 28;99(4-5):449-460. Epub 2019 Jan 28.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China.

Key Message: This report reveals that the LMI1-like and KNOX1 genes coordinately control the leaf development and different combinations of those genes which produce diverse leaf shapes including broad, lobed and compound leaves. Class I KNOTTED1-like homeobox (KNOX1) genes are involved in compound leaf development and are repressed by the ASYMMETRIC LEAVES1 (AS1)-AS2 complex. Cotton plants have a variety of leaf shapes, including broad leaves and lobed leaves. GhOKRA, a LATE MERISTEM IDENTITY 1 (LMI1)-like gene, controls the development of an okra leaf shape. We cloned the corresponding cotton homologs of Arabidopsis thaliana AS1 and AS2 and seven KNOX1 genes. Through virus-induced gene silencing technology, we found that either GhAS1 or GhAS2-silenced cotton plants showed a great change in leaf shape from okra leaves to trifoliolate dissected leaves. In the shoot tips of these plants, the expression of the cotton ortholog of Knotted in A. thaliana 1 (KNAT1), GhKNOTTED1-LIKE2/3/4 (GhKNL2/3/4), was increased. However, GhKNOX1s-silenced plants maintained the wild-type okra leaves. A novel dissected-like leaf in A. thaliana was further generated by crossing plants constitutively expressing GhOKRA with either as1-101 or as2-101 mutant plants. The dissected-like leaves showed two different leaf vein patterns. This report reveals that the LMI1-like and KNOX1 genes coordinately control leaf development, and different combinations of these genes produce diverse leaf shapes including broad leaves, lobed leaves and compound leaves. This is the first report on the artificial generation of compound leaves from simple leaves in cotton.
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http://dx.doi.org/10.1007/s11103-019-00829-7DOI Listing
March 2019

Identifying Functional Genes Influencing Fiber Quality.

Front Plant Sci 2018 9;9:1968. Epub 2019 Jan 9.

Department of Agronomy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

Fiber quality is an important economic index and a major breeding goal in cotton, but direct phenotypic selection is often hindered due to environmental influences and linkage with yield traits. A genome-wide association study (GWAS) is a powerful tool to identify genes associated with phenotypic traits. In this study, we identified fiber quality genes in upland cotton ( L.) using GWAS based on a high-density CottonSNP80K array and multiple environment tests. A total of 30 and 23 significant single nucleotide polymorphisms (SNPs) associated with five fiber quality traits were identified across the 408 cotton accessions in six environments and the best linear unbiased predictions, respectively. Among these SNPs, seven loci were the same, and 128 candidate genes were predicted in a 1-Mb region (±500 kb of the peak SNP). Furthermore, two major genome regions (GR1 and GR2) associated with multiple fiber qualities in multiple environments on chromosomes A07 and A13 were identified, and within them, 22 candidate genes were annotated. Of these, 11 genes were expressed [log(1 + FPKM)>1] in the fiber development stages (5, 10, 20, and 25 dpa) using RNA-Seq. This study provides fundamental insight relevant to identification of genes associated with fiber quality and will accelerate future efforts toward improving fiber quality of upland cotton.
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http://dx.doi.org/10.3389/fpls.2018.01968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334163PMC
January 2019

Spin-Orbit induced phase-shift in BiSe Josephson junctions.

Nat Commun 2019 01 10;10(1):126. Epub 2019 Jan 10.

LPEM, ESPCI Paris, PSL Research University; CNRS; Sorbonne Universités, UPMC University of Paris 6, 10 rue Vauquelin, F-75005, Paris, France.

The transmission of Cooper pairs between two weakly coupled superconductors produces a superfluid current and a phase difference; the celebrated Josephson effect. Because of time-reversal and parity symmetries, there is no Josephson current without a phase difference between two superconductors. Reciprocally, when those two symmetries are broken, an anomalous supercurrent can exist in the absence of phase bias or, equivalently, an anomalous phase shift φ can exist in the absence of a superfluid current. We report on the observation of an anomalous phase shift φ in hybrid Josephson junctions fabricated with the topological insulator BiSe submitted to an in-plane magnetic field. This anomalous phase shift φ is observed directly through measurements of the current-phase relationship in a Josephson interferometer. This result provides a direct measurement of the spin-orbit coupling strength and open new possibilities for phase-controlled Josephson devices made from materials with strong spin-orbit coupling.
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http://dx.doi.org/10.1038/s41467-018-08022-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328588PMC
January 2019

Next-Generation Transgenic Cotton: Pyramiding RNAi with Bt Counters Insect Resistance.

Methods Mol Biol 2019 ;1902:245-256

Agronomy Department, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China.

Transgenic crops expressing Bacillus thuringiensis (Bt) toxins have become a cornerstone in integrated pest management. To counter rapidly increasing pest resistance to transgenic crops producing single Bt toxins, transgenic plant "pyramids" producing two or more Bt toxins targeting the same pest have been widely adopted. However, cross-resistance and antagonism between Bt toxins limit the sustainability of this approach. Here we describe a new type of pyramid combining protection from a Bt toxin and RNA interference (RNAi). We developed and tested transgenic cotton plants producing both Bt toxin Cry1Ac and double-stranded RNA from the global pest Helicoverpa armigera that interferes with its synthesis of juvenile hormone. We discovered that no cross-resistance occurred between these two traits, and they acted independently against a susceptible strain of H. armigera. Computer modeling predicts that if large refuges of non-transgenic host plants are present, pyramided cotton combining Bt and RNAi could delay resistance by 14 to 75 years relative to using Bt cotton alone.
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http://dx.doi.org/10.1007/978-1-4939-8952-2_21DOI Listing
June 2019

Development of Transgenic CryIA(c) + GNA Cotton Plants via Pollen-Tube Pathway Method Confers Resistance to Helicoverpa armigera and Aphis gossypii Glover.

Methods Mol Biol 2019 ;1902:233-244

Agronomy Department, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China.

Elite cotton cultivar Sumian16 was transformed with p7RPSBK-mGNA-NPTII containing Bt (CryIA(c)), Galanthus nivalis agglutinin (GNA) resistance genes, and selectable marker NptII gene via the pollen-tube pathway method, and two fertile transgenic Bt + GNA plants were obtained in the present study. The integration and expression of the Bt and GNA genes were confirmed by molecular biology techniques and insect bioassays. Insect bioassays showed that the transformed plants were highly toxic to bollworm larvae as well as obviously retarding development of aphid populations. PCR analyses and identification of resistance to kanamycin and bollworm showed that the resistance to bollworm for the two transgenic plants was dominantly inherited in a Mendelian manner and the two resistance genes and selectable marker co-segregated from primary transformed parents to the first self-fertilized progeny plants.
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http://dx.doi.org/10.1007/978-1-4939-8952-2_20DOI Listing
June 2019

Inheritance of Transgenes in Transgenic Bt Lines Resistance to Helicoverpa armigera in Upland Cotton.

Methods Mol Biol 2019 ;1902:199-210

Agronomy Department, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China.

Six transgenic Bt cotton cultivars (lines) including GKsu12, GK19, MR1, GK5, 109B, and SGK1 are highly resistant to bollworm from the seedling to boll-setting stages in bioassays with detached cotton leaves, though there are differences in resistant level and Bt toxin content in these transgenic cottons. Genetics analysis reveals that the resistance to Helicoverpa armigera in these six transgenic Bt cotton cultivars (lines) are controlled by one pair of dominant genes. Allelic tests further demonstrate some populations are in Mendel segregation for two nonallelic genes, i.e., the inserted Bt gene in GKsu12 is nonallelic to that of SGK1, GK5, 109B, and GK19, and Bt genes in GK19 and SGK1 are likely inserted in the same or in close proximity (genetically closely linked), while some F produce abnormal segregation patterns, with a segregation of resistance to Helicoverpa armigera which vary between 15:1 and 3:1, though their Bt segregation fit into 15:1 by PCR analysis, suggesting Bt gene silence in these populations. Two genes silence may occur in these populations due to the homologous sequence by crossing since the silenced individuals accounted for 1/16 of the F populations for allelic test. To those silenced populations, one of their parents all showed high resistance to bollworm.
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http://dx.doi.org/10.1007/978-1-4939-8952-2_17DOI Listing
June 2019

Visualization of perforin/gasdermin/complement-formed pores in real cell membranes using atomic force microscopy.

Cell Mol Immunol 2019 06 3;16(6):611-620. Epub 2018 Oct 3.

Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.

Different types of pores ubiquitously form in cell membranes, leading to various types of cell death that profoundly influence the fate of inflammation and the disease status. However, these pores have never truly been visualized to date. Atomic force microscopy (AFM), which is emerging as a powerful tool to analyze the mechanical properties of biomolecules and cells, is actually an excellent imaging platform that allows biological samples to be visualized by probing surface roughness at the level of atomic resolution. Here, membrane pore structures were clearly visualized using AFM. This visualization not only describes the aperture and depth of the pore complexes but also highlights differences among the pores formed by perforin and gasdermins in tumor cell membranes and by complement in immune cell membranes. Additionally, this type of visualization also reveals the dynamic process of pore formation, fusion, and repair.
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http://dx.doi.org/10.1038/s41423-018-0165-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804747PMC
June 2019

Mechanisms by Which Dendritic Cells Present Tumor Microparticle Antigens to CD8 T Cells.

Cancer Immunol Res 2018 09 17;6(9):1057-1068. Epub 2018 Jul 17.

Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Tumor cell-derived microparticles (T-MP) contain tumor antigen profiles as well as innate signals, endowing them with vaccine potential; however, the precise mechanism by which DCs present T-MP antigens to T cells remains unclear. Here, we show that T-MPs activate a lysosomal pathway that is required for DCs presenting tumor antigens of T-MPs. DCs endocytose T-MPs to lysosomes, where T-MPs increase lysosomal pH from 5.0 to a peak of 8.5 via NOX2-catalyzed reactive oxygen species (ROS) production. This increased pH, coupled with T-MP-driven lysosomal centripetal migration, promotes the formation of MHC class I-tumor antigen peptide complexes. Concurrently, endocytosis of T-MPs results in the upregulation of CD80 and CD86. T-MP-increased ROS activate lysosomal Ca channel Mcoln2, leading to Ca release. Released Ca activates transcription factor EB (TFEB), a lysosomal master regulator that directly binds to CD80 and CD86 promoters, promoting gene expression. These findings elucidate a pathway through which DCs efficiently present tumor antigen from T-MPs to CD8 T cells, potentiating T-MPs as a novel tumor cell-free vaccine with clinical applications. .
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http://dx.doi.org/10.1158/2326-6066.CIR-17-0716DOI Listing
September 2018

Circulating Tumor Microparticles Promote Lung Metastasis by Reprogramming Inflammatory and Mechanical Niches via a Macrophage-Dependent Pathway.

Cancer Immunol Res 2018 09 12;6(9):1046-1056. Epub 2018 Jul 12.

Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Despite the frequency of lung metastasis and its associated mortality, the mechanisms behind metastatic tumor cell survival and colonization in the lungs remain elusive. Here, we show that tumor cell-released microparticles (T-MPs) from the primary tumor site play a critical role in the metastatic process. The T-MPs remodeled the lung parenchyma via a macrophage-dependent pathway to create an altered inflammatory and mechanical response to tumor cell invasion. Mechanistically, we show that circulating T-MPs readily enter the lung parenchyma where they are taken up by local macrophages and induce CCL2 production. CCL2 recruits CD11bLy6C inflammatory monocytes to the lungs where they mature into F4/80CD11bLy6C macrophages that not only produce IL6 but also trigger fibrin deposition. IL6 and the deposited fibrin facilitate the survival and growth of tumor-repopulating cells in the lungs by providing chemical and mechanical signals, respectively, thus setting the stage for lung metastasis. These data illustrate that T-MPs reprogram the lung microenvironment promoting metastasis. .
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http://dx.doi.org/10.1158/2326-6066.CIR-17-0574DOI Listing
September 2018