Publications by authors named "Zhiyong Liu"

566 Publications

Antibiotic Combined with Epitope-Specific Monoclonal Antibody Cocktail Protects Mice Against Bacteremia and Acute Pneumonia from Methicillin-Resistant Infection.

J Inflamm Res 2021 30;14:4267-4282. Epub 2021 Aug 30.

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, 400038, People's Republic of China.

Purpose: We previously reported that monoclonal antibody (mAb) cocktail improves survival in infection. In this study, we used acute pneumonia model and lethal sepsis model to investigate the efficacy of antibiotic combined with epitope-specific mAb cocktail in treating MRSA252 infection.

Methods: MRSA252 was challenged by tail vein injection or tracheal intubation to establish sepsis model or pneumonia model. One hour after infection, the mice received a single intravenous injection of normal saline, vancomycin, and vancomycin combined monoclonal antibody, linezolid alone or linezolid combined monoclonal antibody. Daily record survival rate (total 7 days), bacterial load, histology, cytokine analysis of serum and alveolar lavage fluid, and in vitro determination of the neutralizing ability of antibodies to SEB toxin and Hla toxin explained the mechanism of antibody action.

Results: The mAb cocktail combined with low doses of vancomycin or linezolid improved survival rates in acute pneumonia model (70%, 80%) and lethal sepsis model (80%, 80%). Epitope-specific monoclonal antibodies reduced bacterial colonization in the kidneys and lungs of mice and inhibited the biological functions of the toxins Hla and SEB in vitro. Compared to the antibiotic alone or PBS groups, the combination group had higher levels of IL-1α, IL-1β and IFN-γ and lower levels of IL-6, IL-10, TNF-α. Further, the combination of antibiotic and mAb cocktail improved infection survival against the clinical MRSA isolates in a lethal sepsis model.

Conclusion: This study demonstrates a novel method to treat people with low immunity against drug-resistant infections.
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http://dx.doi.org/10.2147/JIR.S325286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415768PMC
August 2021

Broadening the Spectral Response of Perovskite Photodetector to the Solar-Blind Ultraviolet Region through Phosphor Encapsulation.

ACS Appl Mater Interfaces 2021 Sep 8. Epub 2021 Sep 8.

State Key Laboratory of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Hybrid perovskite photodetectors generally exhibit brilliant performance for photodetecting in the visible spectrum but poor detectability in the solar-blind ultraviolet (UV) region. To break through the bottleneck, we demonstrate a novel strategy to broaden the spectral response of perovskite photodetectors to the solar-blind UV region through phosphor encapsulation. The high photoluminescence quantum yield trichromatic phosphor capping layer achieves an extended spectral response to the solar-blind UV region through effectively down-converting the incident UV light into visible light. In addition, an external quantum efficiency of up to 12.13%@265 nm is achieved without bias voltage, while the initial value is near zero. The corresponding spectral responsivity and detectivity are 0.0269 A/W and 7.52 × 10 Jones, respectively. Thus, the photodetectors show a high photocurrent and on/off ratio, increasing by roughly 2 orders of magnitude. Moreover, the photodetectors exhibit a large linear dynamic range of 105 dB, fast response times of 50.16/51.99 μs, and excellent stability. The practical applications for flame detection and UV-based communication are further explored. This work provides a new way to achieve UV light detection based on perovskite photodetectors. Perhaps, it may also be a promising alternative for wide-band gap semiconductors to realize the urgent pursuit of UV detection.
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http://dx.doi.org/10.1021/acsami.1c09719DOI Listing
September 2021

Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells.

Elife 2021 09 3;10. Epub 2021 Sep 3.

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

Mammalian cochlear outer hair cells (OHCs) are essential for hearing. Severe hearing impairment follows OHC degeneration. Previous attempts at regenerating new OHCs from cochlear supporting cells (SCs) have been unsuccessful, notably lacking expression of the key OHC motor protein, Prestin. Thus, regeneration of Prestin+ OHCs represents a barrier to restore auditory function in vivo. Here, we reported the successful in vivo conversion of adult mouse cochlear SCs into Prestin+ OHC-like cells through the concurrent induction of two key transcriptional factors known to be necessary for OHC development: and . Single-cell RNA sequencing revealed the upregulation of 729 OHC genes and downregulation of 331 SC genes in OHC-like cells. The resulting differentiation status of these OHC-like cells was much more advanced than previously achieved. This study thus established an efficient approach to induce the regeneration of Prestin+ OHCs, paving the way for in vivo cochlear repair via SC transdifferentiation.
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http://dx.doi.org/10.7554/eLife.66547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439656PMC
September 2021

Neuroprotective effects of metformin on cerebral ischemia-reperfusion injury by regulating PI3K/Akt pathway.

Brain Behav 2021 Sep 2. Epub 2021 Sep 2.

Department ofMedicine, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, shannxi 710061, P. R. China.

Metformin (Met) is a commonly used drug in the treatment of type 2 diabetes. Currently, it has been found that Met can effectively reduce the incidence of stroke and exert anti-inflammatory effects. However, its role in ischemia-reperfusion (I/R)-induced nerve injury remains unclear. This study aims to investigate the neuroprotective effects of Met in I/R-induced neuron injury as well as the underlying mechanism. A middle cerebral artery occlusion (MCAO) model was established in Sprague Dawley (SD) rats, which were then treated with different doses of Met. Neurological deficits of rats were measured at different times post-surgery. TTC staining was done to observe the volume of cerebral infarction. HE staining was performed to observe pathological changes of brain tissues. Immunohistochemistry was performed to observe the expression of inflammatory factors in the cerebral tissues. qRT-PCR method was used to detect the relative expression of PI3K, Akt mRNA in cells after 24 h of drug action. Western blot method was used to detect the expression of PI3K, p-PI3K, Akt, and p-Akt in hippocampus. What is more, in vitro experiments were performed on BV2 microglia to verify the role of Met against oxygen-glucose deprivation (OGD). As a result, Met dose-dependently attenuated neurological deficits and neuronal apoptosis. Besides, Met administration also significantly reduced BV2 cells apoptosis and inflammatory response. Mechanistically, Met inactivated PI3K/Akt pathway induced by I/R and OGD, while it upregulated PI3K. In conclusion, Met protected rats from cerebral I/R injury via reducing neuronal apoptosis and microglial inflammation through PI3K/Akt pathway.
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http://dx.doi.org/10.1002/brb3.2335DOI Listing
September 2021

Weakly Aligned Feature Fusion for Multimodal Object Detection.

IEEE Trans Neural Netw Learn Syst 2021 Aug 26;PP. Epub 2021 Aug 26.

To achieve accurate and robust object detection in the real-world scenario, various forms of images are incorporated, such as color, thermal, and depth. However, multimodal data often suffer from the position shift problem, i.e., the image pair is not strictly aligned, making one object has different positions in different modalities. For the deep learning method, this problem makes it difficult to fuse multimodal features and puzzles the convolutional neural network (CNN) training. In this article, we propose a general multimodal detector named aligned region CNN (AR-CNN) to tackle the position shift problem. First, a region feature (RF) alignment module with adjacent similarity constraint is designed to consistently predict the position shift between two modalities and adaptively align the cross-modal RFs. Second, we propose a novel region of interest (RoI) jitter strategy to improve the robustness to unexpected shift patterns. Third, we present a new multimodal feature fusion method that selects the more reliable feature and suppresses the less useful one via feature reweighting. In addition, by locating bounding boxes in both modalities and building their relationships, we provide novel multimodal labeling named KAIST-Paired. Extensive experiments on 2-D and 3-D object detection, RGB-T, and RGB-D datasets demonstrate the effectiveness and robustness of our method.
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http://dx.doi.org/10.1109/TNNLS.2021.3105143DOI Listing
August 2021

A recombinant selective drug-resistant M. bovis BCG enhances the bactericidal activity of a second-line anti-tuberculosis regimen.

Biomed Pharmacother 2021 Aug 21;142:112047. Epub 2021 Aug 21.

State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Diseases, Guangzhou 510530, China; Guangzhou National Laboratory, Guangzhou 510320, China. Electronic address:

Drug-resistant tuberculosis (DR-TB) poses a new threat to global health; to improve the treatment outcome, therapeutic vaccines are considered the best chemotherapy adjuvants. Unfortunately, there is no therapeutic vaccine approved against DR-TB. Our study assessed the therapeutic efficacy of a recombinant drug-resistant BCG (RdrBCG) vaccine in DR-TB. We constructed the RdrBCG overexpressing Ag85B and Rv2628 by selecting drug-resistant BCG strains and transformed them with plasmid pEBCG or pIBCG to create RdrBCG-E and RdrBCG-I respectively. Following successful stability testing, we tested the vaccine's safety in severe combined immune deficient (SCID) mice that lack both T and B lymphocytes plus immunoglobulins. Finally, we evaluated the RdrBCG's therapeutic efficacy in BALB/c mice infected with rifampin-resistant M. tuberculosis and treated with a second-line anti-TB regimen. We obtained M. bovis strains which were resistant to several second-line drugs and M. tuberculosis resistant to rifampin. Notably, the exogenously inserted genes were lost in RdrBCG-E but remained stable in the RdrBCG-I both in vitro and in vivo. When administered adjunct to a second-line anti-TB regimen in a murine model of DR-TB, the RdrBCG-I lowered lung M. tuberculosis burden by 1 log. Furthermore, vaccination with RdrBCG-I adjunct to chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG-I showed almost the same virulence as its parent BCG Tice strain in SCID mice. Our findings suggested that the RdrBCG-I was stable, safe and effective as a therapeutic vaccine. Hence, the "recombinant" plus "drug-resistant" BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.
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http://dx.doi.org/10.1016/j.biopha.2021.112047DOI Listing
August 2021

Aminoesterenamide Achieved by Three-Component Reaction Heading toward Tailoring Covalent Adaptable Network with Great Freedom.

Macromol Rapid Commun 2021 Aug 21:e2100394. Epub 2021 Aug 21.

School of Chemistry and Chemical Engineering, State Key Laboratory for Metal Matrix Composite Materials, Shanghai Key Lab of Electrical Insulation & Thermal Ageing, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.

Covalent adaptable networks (CANs) have recently received extensive interests due to their reprocessability and repairability. Rethinking the libraries of the published CANs, most of them are fabricated by one/two-component reactions and few cases utilize multi-component reactions to construct CANs while multi-component reactions are conductive to tailoring the properties of polymers due to their structural designability and flexible choice of raw materials. A novel kind of dynamic covalent bond named aminoesterenamide is presented through three-component reaction between acetoacetyl, amine and isocyanate. Aminoesterenamide exhibits thermal reversibility through dissociating into vinylogous urethane and isocyanate. When it is used to prepare CANs, the synthesized polymer networks can be reprocessed many times via the exchange reaction between aminoesterenamides. Moreover, the forming of aminoesterenamide involving three starting components imparts CANs with great freedom to tailor their properties. Therefore, the authors believe this method that utilizes three-component reaction to fabricate CANs would bring new stories and perspectives to the exploration of new types of CANs.
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http://dx.doi.org/10.1002/marc.202100394DOI Listing
August 2021

A single amino acid residue substitution in BraA04g017190.3C, a histone methyltransferase, results in premature bolting in Chinese cabbage (Brassica rapa L. ssp. Pekinensis).

BMC Plant Biol 2021 Aug 13;21(1):373. Epub 2021 Aug 13.

Liaoning Key Laboratory of Genetics and Breeding for Cruciferous Vegetable Crops, Department of Horticulture, Shenyang Agricultural University, 110866, Shenyang, People's Republic of China.

Background: Flowering is an important inflection point in the transformation from vegetative to reproductive growth, and premature bolting severely decreases crop yield and quality.

Results: In this study, a stable early-bolting mutant, ebm3, was identified in an ethyl methanesulfonate (EMS)-mutagenized population of a Chinese cabbage doubled haploid (DH) line 'FT'. Compared with 'FT', ebm3 showed early bolting under natural cultivation in autumn, and curled leaves. Genetic analysis showed that the early-bolting phenotype was controlled by a single recessive nuclear gene. Modified MutMap sequencing, genotyping analyses and allelism test provide strong evidence that BrEBM3 (BraA04g017190.3 C), encoding the histone methyltransferase CURLY LEAF (CLF), was the strongly candidate gene of the emb3. A C to T base substitution in the 14th exon of BrEBM3 resulted in an amino acid change (S to F) and the early-bolting phenotype of emb3. The mutation occurred in the SET domain (Suppressor of protein-effect variegation 3-9, Enhancer-of-zeste, Trithorax), which catalyzes site- and state-specific lysine methylation in histones. Tissue-specific expression analysis showed that BrEBM3 was highly expressed in the flower and bud. Promoter activity assay confirmed that BrEBM3 promoter was active in inflorescences. Subcellular localization analysis revealed that BrEBM3 localized in the nucleus. Transcriptomic studies supported that BrEBM3 mutation might repress H3K27me3 deposition and activate expression of the AGAMOUS (AG) and AGAMOUS-like (AGL) loci, resulting in early flowering.

Conclusions: Our study revealed that an EMS-induced early-bolting mutant ebm3 in Chinese cabbage was caused by a nonsynonymous mutation in BraA04g017190.3 C, encoding the histone methyltransferase CLF. These results improve our knowledge of the genetic and genomic resources of bolting and flowering, and may be beneficial to the genetic improvement of Chinese cabbage.
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http://dx.doi.org/10.1186/s12870-021-03153-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361648PMC
August 2021

Lateral Ventricular Meningiomas: Clinical Features, Radiological Findings and Long-Term Outcomes.

Cancer Manag Res 2021 4;13:6089-6099. Epub 2021 Aug 4.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Purpose: Lateral ventricle meningioma (LVM) is a rare type of intracranial meningioma, which has been rarely studied. It has different clinical features, imaging features, and long-term results from other locations. This study investigated the epidemiology, clinical characteristics and prognosis of LVM and comprehensively describes its characteristics.

Methods: This article analyzes the LVMs that were diagnosed pathologically in West China hospital between January 1, 2009 and July 1 2020. Demographic information, imaging characteristics and prognostic factors are discussed. Data analysis was performed using SPSS 23.0 and R version 3.5.3.

Results: We collected 7202 meningiomas and 195 LVMs (136 females; median age, 46 years; range, 5-81 years) were included in this study. Gross total resection was completed in 189 patients. The OS rate was 93.8%, and the recurrence rate was 5.2%. Multivariate regression analysis showed that sex (P = 0.01) and tumor size (P = 0.018) were related to WHO grade. Postoperative KPS (P = 0.003) was associated with OS. WHO grade (P = 0.025), extent of tumor resection (P < 0.001), and hospital day (P=0.028) were associated with recurrence.

Conclusion: LVMs require long-term follow-up, individualized treatment, and follow-up strategies to be formulated according to the relevant risk factors.
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http://dx.doi.org/10.2147/CMAR.S320651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349535PMC
August 2021

RNA-sequencing profiling analysis of pericyte-derived extracellular vesicle-mimetic nanovesicles-regulated genes in primary cultured fibroblasts from normal and Peyronie's disease penile tunica albuginea.

BMC Urol 2021 Aug 6;21(1):103. Epub 2021 Aug 6.

Department of Urology and National Research Center for Sexual Medicine, Inha University School of Medicine, 7-206, 3rd St, Shinheung-Dong, Jung-Gu, Incheon, 22332, Republic of Korea.

Background: Peyronie's disease (PD) is a severe fibrotic disease of the tunica albuginea that causes penis curvature and leads to penile pain, deformity, and erectile dysfunction. The role of pericytes in the pathogenesis of fibrosis has recently been determined. Extracellular vesicle (EV)-mimetic nanovesicles (NVs) have attracted attention regarding intercellular communication between cells in the field of fibrosis. However, the global gene expression of pericyte-derived EV-mimetic NVs (PC-NVs) in regulating fibrosis remains unknown. Here, we used RNA-sequencing technology to investigate the potential target genes regulated by PC-NVs in primary fibroblasts derived from human PD plaque.

Methods: Human primary fibroblasts derived from normal and PD patients was cultured and treated with cavernosum pericytes isolated extracellular vesicle (EV)-mimetic nanovesicles (NVs). A global gene expression RNA-sequencing assay was performed on normal fibroblasts, PD fibroblasts, and PD fibroblasts treated with PC-NVs. Reverse transcription polymerase chain reaction (RT-PCR) was used for sequencing data validation.

Results: A total of 4135 genes showed significantly differential expression in the normal fibroblasts, PD fibroblasts, and PD fibroblasts treated with PC-NVs. However, only 91 contra-regulated genes were detected among the three libraries. Furthermore, 20 contra-regulated genes were selected and 11 showed consistent changes in the RNA-sequencing assay, which were validated by RT-PCR.

Conclusion: The gene expression profiling results suggested that these validated genes may be good targets for understanding potential mechanisms and conducting molecular studies into PD.
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http://dx.doi.org/10.1186/s12894-021-00872-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344132PMC
August 2021

Mapping Genome-wide Binding Sites of Prox1 in Mouse Cochlea Using the CUT&RUN Approach.

Neurosci Bull 2021 Aug 5. Epub 2021 Aug 5.

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

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http://dx.doi.org/10.1007/s12264-021-00757-xDOI Listing
August 2021

Boosting cancer therapy efficiency photoinduced radical production.

Chem Sci 2021 Jul 15;12(27):9500-9505. Epub 2021 Jun 15.

Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology 130 Meilong Road Shanghai 200237 China

Current cancer therapy has been restricted by the hypoxic microenvironment of tumors, especially for strongly oxygen-dependent photodynamic therapy. To defeat tumor hypoxia, an oxygen-irrelevant radical nanogenerator, , is developed by the co-assembly of iodized polymer and NIR photosensitizer , and further evaluated as a remote controllable free radical generation platform for enhancing antitumor efficiency. The radical nanogenerator can be excited by NIR light to produce ROS through transfer of energy to oxygen and induce the formation of toxic iodine radicals electron transfer to . Notably, unlike conventional tumor treatments, such a radical nanogenerator is controllable and insusceptible to oxygen concentration. Moreover, benefiting from the strong NIR emission of , the distribution of the radical nanogenerator can be monitored without incorporating other imaging agents. This radical nanogenerator treatment will no doubt broaden the family of antitumor strategies by using non-oxygen radicals, which is significant for reference in the development of promising anticancer agents.
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http://dx.doi.org/10.1039/d1sc01220gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278883PMC
July 2021

A hybrid erbium(III)-bacteriochlorin near-infrared probe for multiplexed biomedical imaging.

Nat Mater 2021 Jul 29. Epub 2021 Jul 29.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and iChem, Fudan University, Shanghai, People's Republic of China.

Spectrally distinct fluorophores are desired for multiplexed bioimaging. In particular, monitoring biological processes in living mammals needs fluorophores that operate in the 'tissue-transparent' near-infrared (NIR) window, that is, between 700 and 1,700 nm. Here we report a fluorophore system based on molecular erbium(III)-bacteriochlorin complexes with large Stokes shift (>750 nm) and narrowband NIR-to-NIR downconversion spectra (full-width at half-maximum ≤ 32 nm). We have found that the fast (2 × 10 s¹) and near-unity energy transfer from bacteriochlorin triplets to the erbium(III) I level overcomes the notorious vibrational overtones quenching, resulting in bright and long-lived (1.73 μs) 1,530 nm luminescence in water. We demonstrate the excitation/emission-multiplexed capability of the complexes in the visualization of dynamic circulatory and metabolic processes in living mice, and through skull tracking of cancer cell metastases in mouse brain. This hybrid probe system facilitates robust multiplexed NIR imaging with high contrast and spatial resolution for applications ranging from fluorescence-guided surgery, diagnostics and intravital microscopy.
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http://dx.doi.org/10.1038/s41563-021-01063-7DOI Listing
July 2021

Deep Penetration of Nanolevel Drugs and Micrometer-Level T Cells Promoted by Nanomotors for Cancer Immunochemotherapy.

J Am Chem Soc 2021 Aug 28;143(31):12025-12037. Epub 2021 Jul 28.

The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing University, Nanjing 210008, China.

The ability of nanomotors to promote the deep penetration of themselves and the loaded drugs in diseased tissues has been proposed and confirmed. However, whether such motion behavior of the nanomotors can also promote deep penetration of micrometer-sized immune cells in the diseased microenvironment, which is important for the immunotherapy of some diseases, has not been mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that can move in the tumor microenvironment, focusing on its motion behavior and the role of NO, the beneficial product released during movement from this kind of nanomotor, in regulating the infiltration behavior and activity of immune cells. It can be found that the drug-loaded nanomotors with both NO-releasing ability and motility can promote the normalization of the tumor vasculature system and the degradation of the intrinsic extracellular matrix (ECM), which can significantly improve the tumor infiltration ability of T cells in vivo. The efficiency of T-cell infiltration in tumor tissue in vivo increased from 2.1 to 28.2%. Both subcutaneous and intraperitoneal implantation tumor models can validate the excellent antitumor effect of drug-loaded NO-driven nanomotors. This combination of motility of the power source from nanomotors and their physiological function offers a design idea for therapeutic agents for the future immunotherapy of many diseases.
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http://dx.doi.org/10.1021/jacs.1c03071DOI Listing
August 2021

Plutonium isotopes and radionuclides in corals around Weizhou land in Beibu Gulf, China.

Appl Radiat Isot 2021 Oct 22;176:109873. Epub 2021 Jul 22.

Guangxi Key Laboratory for Relativistic Astrophysics, School of Physical Science and Technology, Guangxi University, Nanning, 530004, China.

Plutonium isotopes in the coral were determined with chemical separation method using AG 1-X8 and AG-MP-1M anion exchange resins and sector field inductively coupled plasma mass spectrometry (SF-ICP-MS) in order to elucidate the activity concentration and source of Pu around Weizhou land in Beibu Gulf, China. Furthermore, the activity concentrations of other radionuclides (U, Ra, Th, Cs, K and Pb) were measured by a HPGe spectrometer. The activity concentration of Pu in the coral is determined to be in the range of 8.95-27.84 mBq/kg. The Pu/Pu atom ratios in the samples range from 0.173 to 0.225, indicating that the main source of plutonium in this area is global fallout while the contribution of PPG is about 30%. Further, the activity concentrations of U, Th, K and Ra are determined to be in the range of 18.72-64.63, 1.37-20.8, 29.78-72.52 and 3.48-61.97 Bq/kg, respectively.
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http://dx.doi.org/10.1016/j.apradiso.2021.109873DOI Listing
October 2021

Nomograms for Predicting Overall Survival Among Patients with Craniopharyngiomas at Initial Diagnosis: A SEER Population-Based Analysis.

Int J Gen Med 2021 15;14:3517-3527. Epub 2021 Jul 15.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: Craniopharyngiomas (CPs) are relatively rare benign tumor located in the central nervous system (CNS). This study investigates the related risk factors of survival of craniopharyngiomas and develops a simple but detailed method predicting prognosis based on the Surveillance, Epidemiology, and End Results (SEER) database in order to improve the clinic management of CPs.

Methods: Between 2004 and 2017, 1213 patients diagnosed with craniopharyngiomas registered at the program and were included in the SEER-21 registry database. Overall survival (OS) curves were plotted with the Kaplan-Meier method and significance was determined by Log rank test. Single- and multiple-factor regression analyses were made using Cox proportional hazards model to identify independent predictors related to OS. Subsequently, we developed a nomogram with those factors to predict 3-, 5- and 10-year OS of craniopharyngiomas patients.

Results: We identified 1213 patients with craniopharyngioma. The OS rates at 3, 5, and 10 years after diagnosis were 89.1%, 86.2%, and 83%. Age, ethnicity, tumor size and radiation therapy were confirmed to be predictors correlating with OS at initial diagnosis. In multivariate analysis, we found that younger age (P<0.001), smaller tumor size (P<0.001), white ethnicity (P<0.001) and radiation therapy (P=0.004) were the factors that remained significantly associated with better survival. A nomogram was successfully constructed and validated by ROC, calibration plots and C-index of 0.773 (95% CI, 0.708-0.838).

Conclusion: The well-calibrated nomogram is the first clinical prediction model for predicting the prognosis for patients with craniopharyngiomas at initial diagnosis. Our study indicates that the surgical effect is not clear. Younger white patients with radiotherapy have a better prognosis, and the gross total resection (GTR) was not effective in prolonging the OS of a patient compared to no surgery and subtotal resection (STR).
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http://dx.doi.org/10.2147/IJGM.S320643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290489PMC
July 2021

Correction to: A somatic mutation in PIK3CD unravels a novel candidate gene for lymphatic malformation.

Orphanet J Rare Dis 2021 Jul 19;16(1):321. Epub 2021 Jul 19.

Department of Otolaryngology-Head and Neck Surgery, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.

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http://dx.doi.org/10.1186/s13023-021-01946-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290575PMC
July 2021

Correction to: Aldose reductase deficiency inhibits LPS-induced M1 response in macrophages by activating autophagy.

Cell Biosci 2021 Jul 18;11(1):135. Epub 2021 Jul 18.

Institute of Neurosciences, Fourth Military Medical University, Xi'an, 710032, China.

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http://dx.doi.org/10.1186/s13578-021-00652-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287750PMC
July 2021

Ultrafast, Self-Powered, and Charge-Transport-Layer-Free Ultraviolet Photodetectors Based on Sequentially Vacuum-Evaporated Lead-Free CsAgBiBr Thin Films.

ACS Appl Mater Interfaces 2021 Aug 15;13(30):35949-35960. Epub 2021 Jul 15.

State Key Laboratory of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Researchers have focused on perovskite-based ultraviolet photodetectors due to their significance in fundamental scientific and practical applications. However, toxicity and instability hold back their mass production and commercialization. The lead-free CsAgBiBr double perovskite, promised to be an alternative, is fabricated mostly by spin coating, which restricts the practical application in high-resolution image sensors. Herein, we demonstrate a sequential vacuum evaporation method for the fabrication of the CsAgBiBr film. A self-powered ultraviolet photodetector based on the evaporated CsAgBiBr thin film is further constructed without any carrier-transport layers, for the first time. The best-performing device has a high on/off ratio of 6.6 × 10, and its response time is fast, less than 6.13 μs. Moreover, the as-prepared devices exhibit salient stability under harsh operational conditions (continuous illumination, high temperature, and humidity). In addition, the pixelated image sensor containing a 25 × 25 CsAgBiBr photodetector array achieves a proof-of-concept special pattern recognition. Our work paves the way for new-generation ultraviolet image sensors composed of environmentally friendly and high-performance perovskite photodetector arrays.
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http://dx.doi.org/10.1021/acsami.1c08613DOI Listing
August 2021

Integrated mRNA-seq and miRNA-seq analysis of goat fibroblasts response to strain M5-90.

PeerJ 2021 29;9:e11679. Epub 2021 Jun 29.

Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, Animal Genetic Engineering Key Lab of Haikou, College of Animal Science and Technology, Hainan University, Hainan Key Lab of Tropical Animal Reproduction, Haikou, Hainan, China.

Brucellosis is a globally zoonotic bacterial disease of humans and various animals including goats, sheep, and cattle. M5-90, a live attenuated vaccine strain, has been widely used to prevent brucellosis in goats and sheep. However, the molecular mechanisms governing protective immunity response in non-professional phagocytes infected with M5-90 have not been fully investigated, especially in goats. In our research, goat fibroblasts were used as in vitro models to determine these mechanisms by transcriptome analysis. After incubating with M5-90 3 h, the infected goat fibroblasts were collected at 0 h, 4 h, 24 h, 48 h and 72 h for RNA-seq. The results indicated that there were totally 11,819 differentially expressed genes (DEGs) and 777 differentially expressed (DE) miRNAs found in experiment groups compared with the control groups (|log2(Foldchange)|≥1, FDR<0.05). GO and KEGG enrichment analyses revealed that down-regulated genes were involved in the riboflavin metabolism and positive regulation of IL-8 secretion pathway. The up-regulated genes were mainly involved in adaptive immunity, including TNF signaling pathway, MAPK signaling pathway and JAK/STAT pathway. Additionally, cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity and toll-like receptor signaling pathway, which associated with innate immunity pathways, were also induced. Based on the Pearson correlation coefficients and prediction results of TargetScan and miRanda, the miRNA-mRNA networks of , and were constructed and verified in goat fibroblasts by qPCR, which demonstrated that goat fibroblasts displayed immunomodulatory properties. Our findings provide a deeper insight into the host miRNA-driven defense mechanism and reveal the transcriptome changes involved in the innate and adaptive immune response of the goats to infection.
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http://dx.doi.org/10.7717/peerj.11679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253117PMC
June 2021

PIEZO2 mediates ultrasonic hearing via cochlear outer hair cells in mice.

Proc Natl Acad Sci U S A 2021 Jul;118(28)

School of Life Sciences, Tsinghua University, Beijing, China 100084;

Ultrasonic hearing and vocalization are the physiological mechanisms controlling echolocation used in hunting and navigation by microbats and bottleneck dolphins and for social communication by mice and rats. The molecular and cellular basis for ultrasonic hearing is as yet unknown. Here, we show that knockout of the mechanosensitive ion channel PIEZO2 in cochlea disrupts ultrasonic- but not low-frequency hearing in mice, as shown by audiometry and acoustically associative freezing behavior. Deletion of in outer hair cells (OHCs) specifically abolishes associative learning in mice during hearing exposure at ultrasonic frequencies. Ex vivo cochlear Ca imaging has revealed that ultrasonic transduction requires both PIEZO2 and the hair-cell mechanotransduction channel. The present study demonstrates that OHCs serve as effector cells, combining with PIEZO2 as an essential molecule for ultrasonic hearing in mice.
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http://dx.doi.org/10.1073/pnas.2101207118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285978PMC
July 2021

Sjögren's Syndrome and Viral Infections.

Rheumatol Ther 2021 Sep 5;8(3):1051-1059. Epub 2021 Jul 5.

Department of Rheumatism Immunity, Wuhan University, Renmin Hospital, 238 Jiefang Road, Wuchang, Wuhan, 430060, China.

Sjögren's syndrome (SS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This leads to dryness of the main mucosal surfaces such as the mouth, eyes, nose, larynx, pharynx, and vagina. Although there is little morbidity data at the initial diagnosis, SS may be a serious disease, with extra mortality caused by hematological cancer. The cause of SS is unknown, but factors postulated to play a role include genetic and environmental factors, hormonal abnormality, and viral infection. Under the influence of these factors, the immune system becomes abnormal and the tissue is damaged. In this study, we summarize recent developments in our understanding of the relationship between SS and viral infections, including Epstein-Barr virus (EBV), hepatitis C virus (HCV), human T cell lymphotropic virus type 1 (HTLV-1), cytomegalovirus (CMV), and human immunodeficiency virus (HIV).
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http://dx.doi.org/10.1007/s40744-021-00334-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380615PMC
September 2021

Structures and absolute configurations of phomalones from the coral-associated fungus Parengyodontium album sp. SCSIO 40430.

Org Biomol Chem 2021 Jul 29;19(27):6030-6037. Epub 2021 Jun 29.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. and University of Chinese Academy of Sciences, Beijing 100049, China and Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China and Sanya Institute of Oceanology, SCSIO, Yazhou Scientific Bay, Sanya 572000, China.

Coral-associated microorganisms are likely to play an important role in host defense by the production of antimicrobials. Six new chromanones, namely, phomalichenones H-M (5, 6, and 8-11), and ten known analogues (1-4, 7, and 12-16) were isolated from the coral-associated fungus Parengyodontium album sp. SCSIO 40430. Their structures were elucidated by comprehensive spectroscopic analyses. In addition, the structure of 8 was confirmed by X-ray crystallographic analysis. Resolution using a chiral column showed that each of the compounds 1-8 was an enantiomeric mixture with variable enantiomeric excess (ee) values. Their absolute configurations were determined by a comparison of the experimental and calculated ECD data and by a modified Mosher's method. A plausible biosynthetic scheme was proposed for the production of 1-16. Compounds 2, 3, 13, and 14 were found to be active against Mycobacterium tuberculosis H37Ra with MIC values of 16-64 μg mL.
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http://dx.doi.org/10.1039/d1ob00869bDOI Listing
July 2021

Evaluation of a Cryptococcal Antigen Lateral Flow Assay and Cryptococcal Antigen Positivity at a Large Public Hospital in Atlanta, Georgia.

Open Forum Infect Dis 2021 Jun 12;8(6):ofab123. Epub 2021 Mar 12.

Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, Georgia, USA.

Background: is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected persons worldwide, and there are scarce recent data on cryptococcal antigen (CrAg) positivity in the United States We sought to determine the frequency of cryptococcal disease and compare the performance of a CrAg lateral flow assay (LFA) versus latex agglutination (LA) test.

Methods: All patients from Grady Health System in Atlanta who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg testing as part of clinical care from November 2017 to July 2018 were included. Percentage positivity and test agreement were calculated.

Results: Among 467 patients, 557 diagnostic tests were performed; 413 on serum and 144 on CSF. The mean age was 44 years, and most were male (69%) and had HIV (79%). Twenty-four (6.4%, 95% confidence interval [CI] = 4.1-9.4) patients were serum CrAg positive, and 8 (5.8%, 95% CI = 2.6-11.2) individuals tested positive for CSF CrAg. Although overall agreement between the LA and LFA was substantial to high for CSF (κ = 0.71, 95% CI = 0.51-0.91) and serum (κ = 0.93, 95% CI = 0.86-1.00), respectively, there were important discrepancies. Five patients had false-positive CSF LA tests that affected clinical care, and 4 patients had discordant serum tests.

Conclusions: We found a moderately high proportion of cryptococcal disease and important discrepancies between the LA test and LFA. Clinical implications of these findings include accurate detection of serum CrAg and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events.
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http://dx.doi.org/10.1093/ofid/ofab123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233569PMC
June 2021

and are candidate genes for differential diagnosis between pre-chemotherapy embryonic and alveolar rhabdomyosarcoma in pediatric patients.

Pediatr Investig 2021 Jun 18;5(2):106-111. Epub 2021 Jun 18.

Department of Otolaryngology, Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. More than 90% of cases are classified as embryonic RMS (ERMS) or alveolar RMS (ARMS). ERMS has a worse prognosis than ARMS. Early differential diagnosis is of paramount importance for optimization of treatment.

Objective: To identify genes that are differentially expressed between ARMS and ERMS, which can be used for accurate rhabdomyosarcoma classification.

Methods: Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes (DEGs) were identified. Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined. The expression of these seven candidate genes was validated by immunohistochemical analysis of pre-chemotherapy ARMS and ERMS specimens.

Results: The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin-embedded ARMS and ERMS tissues, while EGFR abundance was only marginally different between these two RMS subtypes.

Interpretation: DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre-chemotherapy pediatric patients.
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http://dx.doi.org/10.1002/ped4.12278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212716PMC
June 2021

An ultra-stable bio-inspired bacteriochlorin analogue for hypoxia-tolerant photodynamic therapy.

Chem Sci 2020 Nov 26;12(4):1295-1301. Epub 2020 Nov 26.

Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology 130 Meilong Road Shanghai 200237 China.

Photodynamic therapy (PDT) greatly suffers from the weak NIR-absorption, oxygen dependence and poor stability of photosensitizers (PSs). Herein, inspired by natural bacteriochlorin, we develop a bacteriochlorin analogue, tetrafluorophenyl bacteriochlorin (), by one-step reduction of tetrafluorophenyl porphyrin (). can realize deep tissue penetration, benefitting from the strong NIR absorption. The reactive oxygen species (ROS) generation capacity of can retain around 60% with a 1.0 cm-thick pork skin as the barrier. Besides, could not only produce oxygen-dependent O, but also generate less oxygen-dependent O ˙ and ˙OH to achieve excellent PDT even in hypoxic tumors. Moreover, exhibits an ultra-high stability and it is almost unchanged even under visible light at room temperature for 15 months. Interestingly, the high reactivity of the fluorophenyl group makes it easy for to produce derivatives. A biocompatible nanogel could be directly formed by blending with SH-PEG-SH. The nanogel displays excellent photodynamic efficacy and . Thus, would be a promising PS for the clinical PDT of deep tumors.
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http://dx.doi.org/10.1039/d0sc05525eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179026PMC
November 2020

Multi-labelled proteins recognition for high-throughput microscopy images using deep convolutional neural networks.

BMC Bioinformatics 2021 Jun 15;22(Suppl 3):327. Epub 2021 Jun 15.

High Performance Computer Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China.

Background: Proteins are of extremely vital importance in the human body, and no movement or activity can be performed without proteins. Currently, microscopy imaging technologies developed rapidly are employed to observe proteins in various cells and tissues. In addition, due to the complex and crowded cellular environments as well as various types and sizes of proteins, a considerable number of protein images are generated every day and cannot be classified manually. Therefore, an automatic and accurate method should be designed to properly solve and analyse protein images with mixed patterns.

Results: In this paper, we first propose a novel customized architecture with adaptive concatenate pooling and "buffering" layers in the classifier part, which could make the networks more adaptive to training and testing datasets, and develop a novel hard sampler at the end of our network to effectively mine the samples from small classes. Furthermore, a new loss is presented to handle the label imbalance based on the effectiveness of samples. In addition, in our method, several novel and effective optimization strategies are adopted to solve the difficult training-time optimization problem and further increase the accuracy by post-processing.

Conclusion: Our methods outperformed the SOTA method of multi-labelled protein classification on the HPA dataset, GapNet-PL, by above 2% in the F1 score. Therefore, experimental results based on the test set split from the Human Protein Atlas dataset show that our methods have good performance in automatically classifying multi-class and multi-labelled high-throughput microscopy protein images.
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http://dx.doi.org/10.1186/s12859-021-04196-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207617PMC
June 2021

Construction and Identification of New Molecular Markers of Triple-Negative Breast Cancer Stem Cells.

Front Oncol 2021 28;11:647291. Epub 2021 May 28.

Department of Breast Surgery, Breast Cancer Center, Tai'an Central Hospital, Tai'an, China.

We screened the TNBC stem cells using phage display (PD) and acquired the specific binding clones; and then the positive phage DNAs were amplified and extracted, synthesized with specific polypeptides, and labeled with fluorescein isothiocyanate (FITC). Finally, we identified the specificity of the polypeptides and . Human breast cancer cell line MDA-MB-231 and human mammary gland cell line hs578bst were chosen in our study, and MDA-MB-231 breast cancer stem cells (BCSCs) were cultured and identified by flow cytometry. The phage peptide library was screened using MDA-MB-231 BCSCs, the positive phage clones were identified by ELISA, and the DNA of the positive phages was extracted and sent to a biotechnology company for sequencing. According to the sequencing results, a specific polypeptide was synthesized and labeled with FITC. In the end, the specificity of a polypeptide to BCSCs was identified and . The MDA-MB-231 BCSCs were cultured and enriched with the "serum and serum-free alternate" method. The BCSCs were found to have characteristics of CD44/CD24 epithelial surface antigen (ESA) and ALDH with flow cytometry. The phage was enriched to 200-fold after three rounds of screening for MDA-MB-231 BCSCs. The positive phages were sequenced; then a polypeptide named M58 was synthesized according to sequencing results. Polypeptide M58 has a specific affinity to MDA-MB-231 BCSCs and . Specific polypeptides binding to MDA-MB-231 BCSCs were screened out by PD screening method, which laid a theoretical foundation for the targeted therapy and further research of BCSCs.
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http://dx.doi.org/10.3389/fonc.2021.647291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193032PMC
May 2021

TdPm60 identified in wild emmer wheat is an ortholog of Pm60 and constitutes a strong candidate for PmG16 powdery mildew resistance.

Theor Appl Genet 2021 Sep 8;134(9):2777-2793. Epub 2021 Jun 8.

Institute of Evolution, University of Haifa, Mt. Carmel, 3498838, Haifa, Israel.

Key Message: We identified TdPm60 alleles from wild emmer wheat (WEW), an ortholog of Pm60 from T. urartu, which constitutes a strong candidate for PmG16 mildew resistance. Deployment of PmG16 in Israeli modern bread wheat cultivar Ruta improved the resistance to several local Bgt isolates. Wild emmer wheat (WEW), the tetraploid progenitor of durum and bread wheat, is a valuable genetic resource for resistance to powdery mildew fungal disease caused by Blumeria graminis f. sp. tritici (Bgt). PmG16 gene, derived from WEW, confers high resistance to most tested Bgt isolates. We mapped PmG16 to a 1.4-cM interval between the flanking markers uhw386 and uhw390 on Chromosome 7AL. Based on gene annotation of WEW reference genome Zavitan_V1, 34 predicted genes were identified within the ~ 3.48-Mb target region. Six genes were annotated as associated with disease resistance, of which TRIDC7AG077150.1 was found to be highly similar to Pm60, previously cloned from Triticum urartu, and resides in the same syntenic region. The functional molecular marker (FMM) for Pm60 (M-Pm60-S1) co-segregated with PmG16, suggesting the Pm60 ortholog from WEW (designated here as TdPm60) as a strong candidate for PmG16. Sequence alignment identified only eight SNPs that differentiate between TdPm60 and TuPm60. Furthermore, TdPm60 was found to be present also in the WEW donor lines of the powdery mildew resistance genes MlIW172 and MlIW72, mapped to the same region of Chromosome 7AL as PmG16, suggesting that TdPm60 constitutes a candidate also for these genes. Furthermore, screening of additional 230 WEW accessions with Pm60 specific markers revealed 58 resistant accessions from the Southern Levant that harbored TdPm60, while none of the susceptible accessions showed the presence of this gene. Deployment of PmG16 in Israeli modern bread wheat cultivar Ruta conferred resistance against several local Bgt isolates.
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http://dx.doi.org/10.1007/s00122-021-03858-3DOI Listing
September 2021
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