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1.
Int J Mol Sci ; 25(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38928169

ABSTRACT

Plant resistance against biotic stressors is significantly influenced by pathogenesis-related 1 (PR1) proteins. This study examines the systematic identification and characterization of PR1 family genes in sugarcane (Saccharum spontaneum Np-X) and the transcript expression of selected genes in two sugarcane cultivars (ROC22 and Zhongtang3) in response to Ustilago scitaminea pathogen infection. A total of 18 SsnpPR1 genes were identified at the whole-genome level and further categorized into four groups. Notably, tandem and segmental duplication occurrences were detected in one and five SsnpPR1 gene pairs, respectively. The SsnpPR1 genes exhibited diverse physio-chemical attributes and variations in introns/exons and conserved motifs. Notably, four SsnpPR1 (SsnpPR1.02/05/09/19) proteins displayed a strong protein-protein interaction network. The transcript expression of three SsnpPR1 (SsnpPR1.04/06/09) genes was upregulated by 1.2-2.6 folds in the resistant cultivar (Zhongtang3) but downregulated in the susceptible cultivar (ROC22) across different time points as compared to the control in response to pathogen infection. Additionally, SsnpPR1.11 was specifically upregulated by 1.2-3.5 folds at 24-72 h post inoculation (hpi) in ROC22, suggesting that this gene may play an important negative regulatory role in defense responses to pathogen infection. The genetic improvement of sugarcane can be facilitated by our results, which also establish the basis for additional functional characterization of SsnpPR1 genes in response to pathogenic stress.


Subject(s)
Gene Expression Regulation, Plant , Plant Diseases , Plant Proteins , Saccharum , Stress, Physiological , Ustilago , Saccharum/genetics , Saccharum/microbiology , Plant Proteins/genetics , Plant Proteins/metabolism , Ustilago/genetics , Ustilago/pathogenicity , Plant Diseases/microbiology , Plant Diseases/genetics , Stress, Physiological/genetics , Disease Resistance/genetics , Multigene Family , Phylogeny
2.
J Agric Food Chem ; 72(26): 15013-15026, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38907729

ABSTRACT

Soybean ß-conglycinin is a major allergen that adversely affects the nutritional properties of soybean. Soybean deficient in ß-conglycinin is associated with low allergenicity and high nutritional value. Long intergenic noncoding RNAs (lincRNAs) regulate gene expression and are considered important regulators of essential biological processes. Despite increasing knowledge of the functions of lincRNAs, relatively little is known about the effects of lincRNAs on the accumulation of soybean ß-conglycinin. The current study presents the identification of a lincRNA lincCG1 that was mapped to the intergenic noncoding region of the ß-conglycinin α-subunit locus. The full-length lincCG1 sequence was cloned and found to regulate the expression of soybean seed storage protein (SSP) genes via both cis- and trans-acting regulatory mechanisms. Loss-of-function lincCG1 mutations generated using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system led to the deficiency of the allergenic α'-, α-, and ß-subunits of soybean ß-conglycinin as well as higher content of proteins, sulfur-containing amino acids, and free arginine. The dominant null allele LincCG1, and consequently, the ß-conglycinin-deficient phenotype associated with the lincCG1-gene-edited line was stably inherited by the progenies in a Mendelian fashion. The dominant null allele LincCG1 may therefore be exploited for engineering/developing novel hypoallergenic soybean varieties. Furthermore, Cas9-free and ß-conglycinin-deficient homozygous mutant lines were obtained in the T1 generation. This study is the first to employ the CRISPR/Cas9 technology for editing a lincRNA gene associated with the soybean allergenic protein ß-conglycinin. Moreover, this study reveals that lincCG1 plays a crucial role in regulating the expression of the ß-conglycinin subunit gene cluster, besides highlighting the efficiency of employing the CRISPR/Cas9 system for modulating lincRNAs, and thereby regulating soybean seed components.


Subject(s)
Antigens, Plant , CRISPR-Cas Systems , Gene Editing , Globulins , Glycine max , RNA, Long Noncoding , Seed Storage Proteins , Soybean Proteins , Seed Storage Proteins/genetics , Seed Storage Proteins/chemistry , Globulins/genetics , Globulins/metabolism , Globulins/chemistry , Glycine max/genetics , Glycine max/metabolism , Antigens, Plant/genetics , Antigens, Plant/chemistry , Soybean Proteins/genetics , Soybean Proteins/metabolism , Soybean Proteins/chemistry , RNA, Long Noncoding/genetics , Gene Expression Regulation, Plant , Seeds/genetics , Seeds/metabolism , Seeds/chemistry
3.
Plant Sci ; 346: 112147, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38834106

ABSTRACT

The growth and development of soybean plants can be affected by both abiotic and biotic stressors, such as saline-alkali stress and Phytophthora root rot. In this study, we identified a stress-related gene-GmARM-whose promoter contained several hormone-response and stress-regulatory elements, including ABRE, TCA element, STRE, and MBS. qRT-PCR analysis showed that the expression of GmARM was the highest in seeds at 55 days after flowering. Furthermore, this gene was upregulated after exposure to saline-alkali stress and Phytophthora root rot infection at the seedling stage. Thus, we generated GmARM mutants using the CRISPR-Cas9 system to understand the role of this gene in stress response. T3 plants showed significantly improved salt tolerance, alkali resistance, and disease resistance, with a significantly higher survival rate than the wildtype plants. Moreover, mutations in GmARM affected the expression of related stress-resistance genes, indicating that GmARM mutants achieved multiple stress tolerance. Therefore, this study provides a foundation for further exploration of the genes involved in resistance to multiple stresses in soybean that can be used for breeding multiple stress-resistance soybean varieties.

4.
Cell Commun Signal ; 22(1): 292, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802843

ABSTRACT

BACKGROUND: Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. METHODS: A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. RESULTS: Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. CONCLUSIONS: Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.


Subject(s)
Ferroptosis , Hematopoietic Stem Cells , Insulin-Like Growth Factor I , Megakaryocytes , Regeneration , Animals , Hematopoietic Stem Cells/metabolism , Megakaryocytes/metabolism , Megakaryocytes/radiation effects , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/genetics , Ferroptosis/genetics , Mice , Mice, Inbred C57BL , Radiation Injuries/metabolism , Radiation Injuries/pathology , Radiation Injuries/genetics , Signal Transduction/radiation effects
5.
Front Plant Sci ; 15: 1374228, 2024.
Article in English | MEDLINE | ID: mdl-38803599

ABSTRACT

Environmental stresses are the main constraints on agricultural productivity and food security worldwide. This issue is worsened by abrupt and severe changes in global climate. The formation of sugarcane yield and the accumulation of sucrose are significantly influenced by biotic and abiotic stresses. Understanding the biochemical, physiological, and environmental phenomena associated with these stresses is essential to increase crop production. This review explores the effect of environmental factors on sucrose content and sugarcane yield and highlights the negative effects of insufficient water supply, temperature fluctuations, insect pests, and diseases. This article also explains the mechanism of reactive oxygen species (ROS), the role of different metabolites under environmental stresses, and highlights the function of environmental stress-related resistance genes in sugarcane. This review further discusses sugarcane crop improvement approaches, with a focus on endophytic mechanism and consortium endophyte application in sugarcane plants. Endophytes are vital in plant defense; they produce bioactive molecules that act as biocontrol agents to enhance plant immune systems and modify environmental responses through interaction with plants. This review provides an overview of internal mechanisms to enhance sugarcane plant growth and environmental resistance and offers new ideas for improving sugarcane plant fitness and crop productivity.

6.
Crit Rev Biotechnol ; : 1-9, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719539

ABSTRACT

Climate change-related environmental stresses can negatively impact crop productivity and pose a threat to sustainable agriculture. Plants have a remarkable innate ability to detect a broad array of environmental cues, including stresses that trigger stress-induced regulatory networks and signaling pathways. Transcriptional activation of plant pathogenesis related-1 (PR-1) proteins was first identified as an integral component of systemic acquired resistance in response to stress. Consistent with their central role in immune defense, overexpression of PR-1s in diverse plant species is frequently used as a marker for salicylic acid (SA)-mediated defense responses. Recent advances demonstrated how virulence effectors, SA signaling cascades, and epigenetic modifications modulate PR-1 expression in response to environmental stresses. We and others showed that transcriptional regulatory networks involving PR-1s could be used to improve plant resilience to stress. Together, the results of these studies have re-energized the field and provided long-awaited insights into a possible function of PR-1s under extreme environmental stress.

7.
Plants (Basel) ; 13(6)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38592870

ABSTRACT

Sugarcane (Saccharum spp.), a major cash crop that is an important source of sugar and bioethanol, is strongly influenced by the impacts of biotic and abiotic stresses. The intricate polyploid and aneuploid genome of sugarcane has shown various limits for conventional breeding strategies. Nonetheless, biotechnological engineering currently offers the best chance of introducing commercially significant agronomic features. In this study, an efficient Agrobacterium-mediated transformation system that uses the herbicide-resistant CP4-EPSPS gene as a selection marker was developed. Notably, all of the plants that were identified by PCR as transformants showed significant herbicide resistance. Additionally, this transformation protocol also highlighted: (i) the high yield of transgenic lines from calli (each gram of calli generated six transgenic lines); (ii) improved selection; and (iii) a higher transformation efficiency. This protocol provides a reliable tool for a routine procedure for the generation of resilient sugarcane plants.

8.
PLoS One ; 19(4): e0302179, 2024.
Article in English | MEDLINE | ID: mdl-38630728

ABSTRACT

PURPOSE: Acute kidney injury (AKI) is frequent among in-hospital patients with high incidence and mortality. Implementing a series of evidence-based AKI care bundles may improve patient outcomes by reducing changeable standards of care. The aim of this meta-analysis was therefore to appraise the influences of AKI care bundles on patient outcomes. MATERIALS AND METHODS: We explored three international databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) and two Chinese databases (Wanfang Data and China National Knowledge Infrastructure) for studies from databases inception until November 30, 2022, comparing the impact of different AKI care bundles with usual standards of care in patients with or at risk for AKI. The study quality of non-randomized controlled trials and randomized controlled trials was evaluated by the NIH Study Quality Assessment Tool and the Cochrane risk of bias tool. Heterogeneity between studies was appraised by Cochran's Q test and I2 statistics. The possible origins of heterogeneity between studies were assessed adopting Meta-regression and subgroup analyses. Funnel plot asymmetry and Egger regression and Begg correlation tests were performed to discover potential publication bias. Data analysis was completed by software (RevMan 5.3 and Stata 15.0). The primary outcome was short- or long-term mortality. The secondary outcomes involved the incidence and severity of AKI. RESULTS: Sixteen studies containing 25,690 patients and 25,903 AKI episodes were included. In high-risk AKI patients determined by novel biomarkers, electronic alert or risk prediction score, the application of AKI care bundles significantly reduced the AKI incidence (OR, 0.71; 95% CI, 0.53-0.96; p = 0.02; I2 = 84%) and AKI severity (OR, 0.59; 95% CI, 0.39-0.89; p = 0.01; I2 = 65%). No strong evidence is available to prove that care bundles can significantly reduce mortality (OR, 1.16; 95% CI, 0.58-2.30; p = 0.68; I2 = 97%). CONCLUSIONS: The introduction of AKI care bundles in routine clinical practice can effectively improve the outcomes of patients with or at-risk of AKI. However, the accumulated evidence is limited and not strong enough to make definite conclusions.


Subject(s)
Acute Kidney Injury , Patient Care Bundles , Humans , Biomarkers , China
9.
Mol Plant Pathol ; 25(4): e13452, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38619823

ABSTRACT

Phytophthora root and stem rot of soybean (Glycine max), caused by the oomycete Phytophthora sojae, is an extremely destructive disease worldwide. In this study, we identified GmEIL1, which encodes an ethylene-insensitive3 (EIN3) transcription factor. GmEIL1 was significantly induced following P. sojae infection of soybean plants. Compared to wild-type soybean plants, transgenic soybean plants overexpressing GmEIL1 showed enhanced resistance to P. sojae and GmEIL1-silenced RNA-interference lines showed more severe symptoms when infected with P. sojae. We screened for target genes of GmEIL1 and confirmed that GmEIL1 bound directly to the GmERF113 promoter and regulated GmERF113 expression. Moreover, GmEIL1 positively regulated the expression of the pathogenesis-related gene GmPR1. The GmEIL1-regulated defence response to P. sojae involved both ethylene biosynthesis and the ethylene signalling pathway. These findings suggest that the GmEIL1-GmERF113 module plays an important role in P. sojae resistance via the ethylene signalling pathway.


Subject(s)
Fabaceae , Phytophthora , Transcription Factors/genetics , Glycine max/genetics , Ethylenes , Plants, Genetically Modified
10.
Int J Mol Sci ; 25(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38673832

ABSTRACT

Phytophthora root rot is a devastating disease of soybean caused by Phytophthora sojae. However, the resistance mechanism is not yet clear. Our previous studies have shown that GmAP2 enhances sensitivity to P. sojae in soybean, and GmMYB78 is downregulated in the transcriptome analysis of GmAP2-overexpressing transgenic hairy roots. Here, GmMYB78 was significantly induced by P. sojae in susceptible soybean, and the overexpressing of GmMYB78 enhanced sensitivity to the pathogen, while silencing GmMYB78 enhances resistance to P. sojae, indicating that GmMYB78 is a negative regulator of P. sojae. Moreover, the jasmonic acid (JA) content and JA synthesis gene GmAOS1 was highly upregulated in GmMYB78-silencing roots and highly downregulated in overexpressing ones, suggesting that GmMYB78 could respond to P. sojae through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in GmMYB78-overexpressing roots and higher in GmMYB78-silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene GmbZIP25 of GmMYB78. GmbHLH122 was highly induced by P. sojae and could inhibit GmMYB78 expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene GmbZIP25 transcription in susceptible soybean. In conclusion, our data reveal that GmMYB78 triggers soybean sensitivity to P. sojae by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78-GmbZIP25 cascade pathway.


Subject(s)
Cyclopentanes , Disease Resistance , Gene Expression Regulation, Plant , Glycine max , Oxylipins , Phytophthora , Plant Diseases , Plant Proteins , Transcription Factors , Glycine max/genetics , Glycine max/microbiology , Glycine max/parasitology , Glycine max/metabolism , Phytophthora/pathogenicity , Disease Resistance/genetics , Plant Diseases/microbiology , Plant Diseases/parasitology , Plant Diseases/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Cyclopentanes/metabolism , Oxylipins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Plants, Genetically Modified , Plant Roots/microbiology , Plant Roots/genetics , Plant Roots/parasitology , Plant Roots/metabolism
11.
New Phytol ; 242(5): 2093-2114, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38511255

ABSTRACT

Most splicing factors are extensively phosphorylated but their physiological functions in plant salt resistance are still elusive. We found that phosphorylation by SnRK1 kinase is essential for SRRM1L nuclear speckle formation and its splicing factor activity in plant cells. In Arabidopsis, loss-of-function of SRRM1L leads to the occurrence of alternative pre-mRNA splicing events and compromises plant resistance to salt stress. In Arabidopsis srrm1l mutant line, we identified an intron-retention Nuclear factor Y subunit A 10 (NFYA10) mRNA variant by RNA-Seq and found phosphorylation-dependent RNA-binding of SRRM1L is indispensable for its alternative splicing activity. In the wild-type Arabidopsis, salt stress can activate SnRK1 to phosphorylate SRRM1L, triggering enrichment of functional NFYA10.1 variant to enhance plant salt resistance. By contrast, the Arabidopsis srrm1l mutant accumulates nonfunctional NFYA10.3 variant, sensitizing plants to salt stress. In summary, this work deciphered the molecular mechanisms and physiological functions of SnRK1-SRRM1L-NFYA10 module, shedding light on a regulatory pathway to fine-tune plant adaptation to abiotic stress at the post-transcriptional and post-translational levels.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Protein Serine-Threonine Kinases , Salt Tolerance , Alternative Splicing/genetics , Arabidopsis/genetics , Arabidopsis/physiology , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant , Mutation/genetics , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , RNA Splicing/genetics , Salt Stress/genetics , Salt Tolerance/genetics
12.
Front Plant Sci ; 15: 1375934, 2024.
Article in English | MEDLINE | ID: mdl-38525140

ABSTRACT

Sugarcane is the most important sugar and energy crop in the world. During sugarcane breeding, technology is the requirement and methods are the means. As we know, seed is the cornerstone of the development of the sugarcane industry. Over the past century, with the advancement of technology and the expansion of methods, sugarcane breeding has continued to improve, and sugarcane production has realized a leaping growth, providing a large amount of essential sugar and clean energy for the long-term mankind development, especially in the face of the future threats of world population explosion, reduction of available arable land, and various biotic and abiotic stresses. Moreover, due to narrow genetic foundation, serious varietal degradation, lack of breakthrough varieties, as well as long breeding cycle and low probability of gene polymerization, it is particularly important to realize the leapfrog development of sugarcane breeding by seizing the opportunity for the emerging Breeding 4.0, and making full use of modern biotechnology including but not limited to whole genome selection, transgene, gene editing, and synthetic biology, combined with information technology such as remote sensing and deep learning. In view of this, we focus on sugarcane breeding from the perspective of technology and methods, reviewing the main history, pointing out the current status and challenges, and providing a reasonable outlook on the prospects of smart breeding.

13.
Sci Rep ; 14(1): 4209, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378840

ABSTRACT

Deep clustering has been widely applicated in various fields, including natural image and language processing. However, when it is applied to hyperspectral image (HSI) processing, it encounters challenges due to high dimensionality of HSI and complex spatial-spectral characteristics. This study introduces a kind of deep clustering model specifically tailed for HSI analysis. To address the high dimensionality issue, redundant dimension of HSI is firstly eliminated by combining principal component analysis (PCA) with t-distributed stochastic neighbor embedding (t-SNE). The reduced dataset is then input into a three-dimensional attention convolutional autoencoder (3D-ACAE) to extract essential spatial-spectral features. The 3D-ACAE uses spatial-spectral attention mechanism to enhance captured features. Finally, these enhanced features pass through an embedding layer to create a compact data-representation, and the compact data-representation is divided into distinct clusters by clustering layer. Experimental results on three publicly available datasets validate the superiority of the proposed model for HSI analysis.

14.
Mol Neurobiol ; 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38367134

ABSTRACT

Aging and interactions between genetic and environmental factors are believed to be involved the chronic development of Parkinson's disease (PD). Among PD patients, abnormally aggregated α-synuclein is a major component of the Lewy body. Generally, the intranasal route is believed to be a gate way to the brain, and it assists environmental neurotoxins in entering the brain and is related to anosmia during early PD. The current study applies the chronic intranasal application of lipopolysaccharides (LPS) in 4-, 8-, 12- and 16-month-old A53T-α-synuclein (A53T-α-Syn) transgenic C57BL/6 mice at 2-day intervals for a 2-month period, for evaluating the behavioral, pathological, and biochemical changes and microglial activation in these animals. According to our results, after intranasal administration of LPS, A53T-α-Syn mice showed severe progressive anosmia, hypokinesia, selective dopaminergic (DAergic) neuronal losses, decreased striatal dopamine (DA) level, and enhanced α-synuclein accumulation within the substantia nigra (SN) in an age-dependent way. In addition, we found obvious NF-кB activation, Nurr1 inhibition, IL-1ß, and TNF-α generation within the microglia of the SN. Conversely, the wild-type (WT) mice showed mild, whereas A53T-α-Syn mice had moderate PD-like changes among the old mice. This study demonstrated the synergistic effect of intranasal LPS and α-synuclein burden on PD development. Its underlying mechanism may be associated with Nurr1 inhibition within microglia and the amplification of CNS neuroinflammation. The mice with multiple factors, including aging, neuroinflammation, and α-synuclein mutation, have played a significant role in enhancing our understanding of how inflammation and α-synuclein mutation contribute to the neurodegeneration observed in PD.

15.
J Gene Med ; 26(1): e3633, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38017625

ABSTRACT

BACKGROUND: Shikonin, a major component of Lithospermum erythrorhizon, exerts anti-inflammatory and antibacterial effects and expedites wound healing. This study aims to evaluate the anti-inflammatory and antioxidant activities of shikonin in a Sprague-Dawley rat model and cell models using fibroblast and endothelial cells. METHODS: The impact of shikonin on the activity of endothelial cells and fibroblasts was examined by cell counting kit 8 and wound-healing assays. A diabetic rat model was constructed, followed by wound creation for treatment with shikonin. Hematoxylin-eosin staining was used to assess pathological changes, and Masson's trichrome method to detect collagen deposition. Immunohistochemistry using antibodies against proliferating cell nuclear antigen and CD31 was conducted to detect proliferation and vascular density. Enzyme-linked immunosorbent assay and immunohistochemistry were carried out to assess pro-inflammatory and anti-inflammatory factor concentrations. Western blot and immunofluorescence were implemented to analyze oxidative stress-related protein expression. RESULTS: Shikonin induced the activity of both fibroblasts and endothelial cells. Shikonin treatment contributed to facilitated wound healing and higher healing rates in rats. It also resulted in faster lesion debulking in tissues, reduced inflammatory infiltration, increased collagen deposition, and enhanced angiogenesis. Detection of markers at the wounds showed that shikonin accelerated cell proliferation, enhanced tissue remodeling, and inhibited oxidative stress. CONCLUSION: Shikonin stimulates the proliferation and migration of fibroblasts and endothelial cells to promote angiogenesis and tissue remodeling, resulting in faster wound healing.


Subject(s)
Angiogenesis , Endothelial Cells , Naphthoquinones , Rats , Animals , Rats, Sprague-Dawley , Endothelial Cells/metabolism , Wound Healing , Cell Proliferation , Collagen/metabolism , Collagen/pharmacology , Anti-Inflammatory Agents/pharmacology , Fibroblasts , Skin/metabolism
16.
Mil Med Res ; 10(1): 66, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38111039

ABSTRACT

BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.


Subject(s)
Radiation Injuries , Thrombocytopenia , Thrombosis , Humans , Animals , Mice , Megakaryocytes/metabolism , Megakaryocytes/pathology , Thrombocytopenia/etiology , Apoptosis , Nucleotidyltransferases/metabolism , Thrombosis/metabolism
18.
Biomolecules ; 13(10)2023 10 13.
Article in English | MEDLINE | ID: mdl-37892202

ABSTRACT

Sodium bicarbonate stress caused by NaHCO3 is one of the most severe abiotic stresses affecting agricultural production worldwide. However, little attention has been given to the molecular mechanisms underlying plant responses to sodium bicarbonate stress. To understand phosphorylation events in signaling pathways triggered by sodium bicarbonate stress, TMT-labeling-based quantitative phosphoproteomic analyses were performed on soybean leaf and root tissues under 50 mM NaHCO3 treatment. In the present study, a total of 7856 phosphopeptides were identified from cultivated soybeans (Glycine max L. Merr.), representing 3468 phosphoprotein groups, in which 2427 phosphoprotein groups were newly identified. These phosphoprotein groups contained 6326 unique high-probability phosphosites (UHPs), of which 77.2% were newly identified, increasing the current soybean phosphosite database size by 43.4%. Among the phosphopeptides found in this study, we determined 67 phosphopeptides (representing 63 phosphoprotein groups) from leaf tissue and 554 phosphopeptides (representing 487 phosphoprotein groups) from root tissue that showed significant changes in phosphorylation levels under sodium bicarbonate stress (fold change >1.2 or <0.83, respectively; p < 0.05). Localization prediction showed that most phosphoproteins localized in the nucleus for both leaf and root tissues. GO and KEGG enrichment analyses showed quite different enriched functional terms between leaf and root tissues, and more pathways were enriched in the root tissue than in the leaf tissue. Moreover, a total of 53 different protein kinases and 7 protein phosphatases were identified from the differentially expressed phosphoproteins (DEPs). A protein kinase/phosphatase interactor analysis showed that the interacting proteins were mainly involved in/with transporters/membrane trafficking, transcriptional level regulation, protein level regulation, signaling/stress response, and miscellaneous functions. The results presented in this study reveal insights into the function of post-translational modification in plant responses to sodium bicarbonate stress.


Subject(s)
Glycine max , Sodium Bicarbonate , Glycine max/metabolism , Sodium Bicarbonate/pharmacology , Sodium Bicarbonate/metabolism , Plant Proteins/metabolism , Phosphopeptides/chemistry , Phosphopeptides/metabolism , Phosphoproteins/metabolism
19.
Plant Sci ; 337: 111865, 2023 Sep 09.
Article in English | MEDLINE | ID: mdl-37696474

ABSTRACT

Flowering time is an important agronomic character that influences the adaptability and yield of soybean [Glycine max (L.) Merrill]. WRINKLED 1 (WRI1) plays an important regulatory role in plant growth and development. In this study, we found that the expression of GmWIR1a could be induced by long days. Compared with the wild type, transgenic soybean overexpressing GmWRI1a showed earlier flowering and maturity under long days but no significant changes under short days. Overexpression of GmWRI1a led to up-regulated expression of genes involved in the regulation of flowering time. The GmWRI1a protein was able to directly bind to the promoter regions of GmAP1, GmFUL1a, GmFUL2 and up-regulated their expression. GmCOL3 was identified by yeast one-hybrid library screening using the GmWRI1a promoter as bait. GmCOL3 was revealed to be a nucleus-localized protein that represses the transcription of GmWRI1a. Expression of GmCOL3 was induced by short days. Taken together, the results show that overexpression of GmWRI1a promotes flowering under long days by promoting the transcriptional activity of flowering-related genes in soybean, and that GmCOL3 binds to the GmWRI1a promoter and directly down-regulates its transcription. This discovery reveals a new function for GmWRI1a, which regulates flowering and maturity in soybean.

20.
Ren Fail ; 45(2): 2258983, 2023.
Article in English | MEDLINE | ID: mdl-37755332

ABSTRACT

OBJECTIVE: To explore the correlation between neutrophil-to-lymphocyte ratio (NLR) and contrast-induced acute kidney injury (CI-AKI). To develop machine-learning (ML) methods based on NLR and other relevant high-risk factors to establish new and effective predictive models of CI-AKI. Methods: The data of 2230 patients, who underwent elective vascular intervention, coronary angiography and percutaneous coronary intervention were retrospectively collected. The patients were divided into a CI-AKI group and a non-CI-AKI group. Logistic regression was used to analyze the correlation of NLR with CI-AKI and high-risk factors for CI-AKI, and logistic regression (LR), random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and naïve Bayes (NB) models based on NLR and the high-risk factors were established. RESULTS: A high NLR(>2.844) was an independent risk factor for CI-AKI (odds ratio = 2.304, p < 0.001). The area under the ROC curve (AUC) of the NB model was the largest (0.774), indicating that it had the best performance. NLR, serum creatinine concentration, fasting plasma glucose concentration, and use of ß-blocker all accounted for a large proportion of the predictive performance of each model and were the four most important factors affecting the occurrence of CI-AKI. CONCLUSIONS: There was a significant correlation between NLR and CI-AKI The NB model exhibited the best predictive performance out of the five ML models based on NLR exhibited the best predictive performance out of the five ML models.


Subject(s)
Acute Kidney Injury , Neutrophils , Humans , Retrospective Studies , Bayes Theorem , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Lymphocytes , Machine Learning
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