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Lodging reduces maize yield and quality. The improvement in maize lodging resistance has proven to be instrumental in maximizing the yield potential of maize varieties under high-density planting. Tillage practices accommodate larger groups by enhancing soil conditions. This study aimed to elucidate the impact of subsoil tillage in reducing the maize stalk lodging rate. The maize cultivars Xianyu 335 (XY335) and Zhongdan2 (ZD2) were selected for field experiments including two tillage methods, shallow rotary (RT) and subsoil (SS), and two densities, 75,000 plants ha-1 (D1) and 105,000 plants ha-1 (D2), were set up to investigate and analyze the changes of maize lodging rate and the related indexes of lodging resistance under SS and RT conditions. The findings revealed that under high density, as compared to rotary tillage, SS tillage decreased the plant and ear height by 9.01-9.20 cm and 3.50-4.90 cm, respectively. The stalk dry matter accumulation was enhanced by 8.98%-24.98%, while stalk diameter between two and seven internodes increased by 0.47- 4.15 mm. Stalk cellulose increased by 11.83% -12.38%, hemicellulose increased by 6.7%-15.97%, and lignin increased by 9.86%-15.9%. The rind puncture and crushing strength improved by 3.11%-20.06% and 11.90%-27.07%, respectively. The bending strength increased by 6.25%-27.96% and the lodging rate decreased by 1.20%-6.04%. Yield increased by 7.58%-8.17%. At SS tillage when density increased, the index changes in ZD2 were mostly less than those in XY335. The rind penetration strength, bending strength, crushing strength, stalk diameter, and dry matter accumulation all had a negative correlation with the lodging rate. It suggested that SS tillage was beneficial to lodging resistance and, in combination with stalk lodging-resistant varieties, can effectively alleviate the problem of stalk lodging after increased planting density.
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Introduction: To address issues related to shallow soil tillage, low soil nutrient content, and single tillage method in maize production in the Western Inner Mongolia Region, this study implemented various tillage and straw return techniques, including strip cultivation, subsoiling, deep tillage, no-tillage, straw incorporation with strip cultivation, straw incorporation with subsoiling, straw incorporation with deep tillage, and straw incorporation with no tillage, while using conventional shallow spinning by farmers as the control. Methods: We employed Xianyu 696 (XY696) and Ximeng 6 (XM6) as experimental materials to assess maize 100-grains weight, grain filling rate parameters, and grain nutrient quality. This investigation aimed to elucidate how tillage and straw return influence the accumulation of grain material in different maize varieties. Results and discussion: The results indicated that proper implementation of tillage and straw return had a significant impact on the 100-grains weight of both varieties. In comparison to CK (farmer's rotary rotation), the most notable rise in 100-grains weight was observed under the DPR treatment (straw incorporation with deep tillage), with a maximum increase of 4.84% for XY696 and 6.28% for XM6. The proper implementation of tillage and straw return in the field resulted in discernible differences in the stages of improving the grain filling rates of different maize varieties. Specifically, XY696 showed a predominant increase in the filling rate during the early stage (V1), while XM6 exhibited an increase in the filling rates during the middle and late stages (V2 and V3). In comparison to CK, V1 increased by 1.54% to 27.56% in XY696, and V2 and V3 increased by 0.41% to 10.42% in XM6 under various tillage and straw return practices. The proper implementation of tillage and straw return had a significant impact on the nutritional quality of the grains in each variety. In comparison to CK, the DPR treatment resulted in the most pronounced decrease in the soluble sugar content of grains by 25.43% and the greatest increase in the crude fat content of grains by 9.67%. Conclusion: Ultimately, the proper implementation of soil tillage and straw return facilitated an increase in grain crude fat content and significantly boosted grain weight by improving the grouting rate parameters at all stages for various maize varieties. Additionally, the utilization of DPR treatment proved to be more effective. Overall, DPR is the most promising strategy to improve maize yield and the nutritional quality of grain in the long term in the Western Inner Mongolia Region.
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To achieve high maize (Zea mays L.) yields and quality grain, it is necessary to develop stress-resistant cultivars and related cultivation practices, aiming to maximize efficiency. Thus, our objectives were (i) to investigate the impact of tillage practices and maize hybrids (which have improved over time) on yield and its components, and (ii) to characterize the response pattern of maize hybrid grain nutrient quality components to subsoiling. To achieve this, we conducted field trials with five maize hybrids from different eras under two tillage practices: rotary tillage and subsoiling. We compared grain yield, nutritional quality, and other indicators across different tillage conditions from the 1970s to the 2010s. The main results of this study are as follows: under rotary tillage conditions, the 2010s hybrid (DH618) significantly increased yields (9.37-55.89%) compared to hybrids from the 1970s-2000s. After subsoiling, the physiologically mature grains of all hybrids exhibited minimal changes in crude protein and fat content, while there was a significant reduction in the total soluble sugar content of the grains. After subsoiling, there was a substantial 8.14 to 12.79 percent increase in total starch accumulation in the grain for all hybrids during the period of 47-75 days post-anthesis. Furthermore, during the period of 47-75 days after anthesis, the consumption of grain crude protein significantly contributed to the accumulation of total starch in the grains. Ultimately, subsoiling significantly increased the yield of each hybrid and enhanced the total grain starch content at physiological maturity of all hybrids, with the 2010s hybrid (DH618) performing exceptionally well.
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Bone is a major tissue for uranium deposition in human body. Considering mesenchymal stem cells (MSCs) play a vital role in bone formation and injury recovery, studying the mechanism of MSCs responding to uranium poisoning can benefit the understanding of bone damage and repair after uranium exposure. Cellular structural alterations were analyzed via transmission electron microscopy (TEM). Changes in cellular behaviors were assessed through cellular viability, apoptosis, and the production of DNA double-strand breaks (DSBs). In addition, the influence of gap junctional intercellular communication (GJIC) on uranium toxicity was assessed. The disruption of MSCs was elevated with the increase in uranyl nitrate concentration, as shown by TEM micrograph. This was verified by the results of cellular viability and DSB production. Interestingly, the results of apoptosis assay indicated significant apoptosis occurred, which was accompanied with an obvious disruption of cellular membranes. Furthermore, closely contacted cell confluence groups exhibited resistant to uranium poisoning in contrast to sparse growth groups, which can be eliminated with the pretreatment of a GJIC inhibitor in the close connection group. To verify the association between GJIC and cytotoxic effects of uranyl nitrate, GJIC function was evaluated by wound healing and cellular migration. The results showed an inhibition of the healing ratio and migration ability induced by the exposure of uranyl nitrate. The low transfer efficiency of the dye coupling experiment and depressed expression of gap functional protein connexins confirmed the impairment of GJIC function. These results suggest that uranium toxicity is involved with GJIC dysfunction.
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Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.
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Cadmio , Pared Celular , Zinc , Cadmio/toxicidad , Zinc/metabolismo , Zinc/toxicidad , Zinc/farmacología , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/genéticaRESUMEN
Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit a greater array of non-structural proteins compared to low-pathogenic strains, facilitating their ability to induce apoptosis via multiple pathways. Moreover, these viral proteins are adept at dampening host immune responses, thereby bolstering viral replication and persistence. This review delves into the intricate interplay between highly pathogenic coronaviruses and apoptosis, systematically elucidating the molecular mechanisms underpinning apoptosis induction by viral proteins. Furthermore, it explores the potential therapeutic avenues stemming from apoptosis inhibition as antiviral agents and the utilization of apoptosis-inducing viral proteins as therapeutic modalities. These insights not only shed light on viral pathogenesis but also offer novel perspectives for cancer therapy.
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Apoptosis , SARS-CoV-2 , Humanos , SARS-CoV-2/fisiología , Proteínas Virales/metabolismo , Proteínas Virales/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , COVID-19/virologíaRESUMEN
Indocalamus plants are low-growing shrubby bamboos with growth advantages, such as high biomass and strong resistance, and they are rich in germplasm resources in southern China. This study conducted soil lead (Pb) stress experiments on Indocalamus latifolius (Keng) McClure (LA), Indocalamus hunanensis B.M. Yang (HU), Indocalamus chishuiensis Y.L. Yang and Hsueh (CH) and Indocalamus lacunosus Wen (LC). Five Pb treatments (0, 500, 1000, 1500 mg·kg-1 Pb, and 1000 mg·kg-1 Pb + 1000 mg·kg-1 ethylenediamine tetraacetic acid (EDTA)) were established. EDTA was applied to explore the tolerance mechanism of different Indocalamus species after absorbing large amounts of heavy metals. The results were as follows: (1) under Pb treatment, the total relative biomass of LA, HU and LC was <100%, whereas the total relative biomass of CH was >100%; (2) after applying EDTA, the bioconcentration coefficient, translocation factor, and free proline content of the four Indocalamus species increased; and (3) the Pb mobility and distribution rates of the underground parts of the four Indocalamus species were consistently greater than those of the aboveground parts. The Pb mobility and distribution rates in the stems increased after applying EDTA, while those in the leaves decreased, as the plants tended to transfer Pb to their stems, which have lower physiological activity than their leaves.
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A series of K3Nb1-xOF6:xMn4+ fluorescent materials were prepared by the cation exchange method. Phase structure, morphology, emission, excitation spectrum and LED packaging of fluorescent materials were tested. The fluorescent material particles are micron-sized (5 µm-20 µm) and have a micro-rod morphology. It has two absorption bands, with the blue light region (â¼468 nm) being stronger than the ultraviolet region (â¼370 nm). Under the excitation of 468 nm, it shows good narrowband emission in the red light region, mainly with anti-stokes v6 (â¼627 nm), which is caused by the double barrier of the 2Egâ4A2g transition broken by the coupling effect of electron and phonon. The optimum doping concentration was 9.1 %, and as the concentration increased again, the dipole-dipole interaction between Mn4+ resulted in concentration quenching. When the fluorescent material operates at high temperature (150 â), the emission intensity drops to 50.2 % of which at room temperature. At high temperature, the electrons absorb a large amount of heat energy, and the non-radiation transition to 4A2g energy level causes the thermal quenching effect. In addition, the sample also showed good water stability, after 1 h of hydrolysis, the luminescence intensity decreased to 85.6 % of the initial value. The use of LED packaging with fluorescent materials and InGaN-YAG:Ce3+ can effectively reduce the color temperature of LED from 6856 K to 3745 K, and enhance the Color index from 61.5 % to 76.8 %. Which has great potential for development in the fields of plant growth and backlight display technology.
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HIV-1 replication is tightly regulated in host cells, and various restriction factors have important roles in inhibiting viral replication. SAMHD1, a well-known restriction factor, suppresses HIV-1 replication by hydrolyzing intracellular dNTPs, thereby limiting the synthesis of viral cDNA in quiescent cells. In this study, we revealed an additional and distinct mechanism of SAMHD1 inhibition during the postviral cDNA synthesis stage. Using immunoprecipitation and mass spectrometry analysis, we demonstrated the interaction between SAMHD1 and MX2/MxB, an interferon-induced antiviral factor that inhibits HIV-1 cDNA nuclear import. The disruption of endogenous MX2 expression significantly weakened the ability of SAMHD1 to inhibit HIV-1. The crucial region within SAMHD1 that binds to MX2 has been identified. Notably, we found that SAMHD1 can act as a sensor that recognizes and binds to the incoming HIV-1 core, subsequently delivering it to the molecular trap formed by MX2, thereby blocking the nuclear entry of the HIV-1 core structure. SAMHD1 mutants unable to recognize the HIV-1 core showed a substantial decrease in antiviral activity. Certain mutations in HIV-1 capsids confer resistance to MX2 inhibition while maintaining susceptibility to suppression by the SAMHD1-MX2 axis. Overall, our study identifies an intriguing antiviral pattern wherein two distinct restriction factors, SAMHD1 and MX2, collaborate to establish an alternative mechanism deviating from their actions. These findings provide valuable insight into the complex immune defense networks against exogenous viral infections and have implications for the development of targeted anti-HIV therapeutics. IMPORTANCE: In contrast to most restriction factors that directly bind to viral components to exert their antiviral effects, SAMHD1, the only known deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, indirectly inhibits viral replication in quiescent cells by reducing the pool of dNTP substrates available for viral cDNA synthesis. Our study provides a novel perspective on the antiviral functions of SAMHD1. In addition to its role in dNTP hydrolysis, SAMHD1 cooperates with MX2 to inhibit HIV-1 nuclear import. In this process, SAMHD1 acts as a sensor for incoming HIV-1 cores, detecting and binding to them, before subsequently delivering the complex to the molecular trap formed by MX2, thereby immobilizing the virus. This study not only reveals a new antiviral pathway for SAMHD1 but also identifies a unique collaboration and interaction between two distinct restriction factors, establishing a novel line of defense against HIV-1 infection, which challenges the traditional view of restriction factors acting independently. Overall, our findings further indicate the intricate complexity of the host immune defense network and provide potential targets for promoting host antiviral immune defense.
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Infecciones por VIH , VIH-1 , Proteínas de Resistencia a Mixovirus , Proteína 1 que Contiene Dominios SAM y HD , Replicación Viral , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/genética , Humanos , VIH-1/fisiología , VIH-1/genética , Proteínas de Resistencia a Mixovirus/metabolismo , Proteínas de Resistencia a Mixovirus/genética , Infecciones por VIH/virología , Infecciones por VIH/metabolismo , Infecciones por VIH/genética , ADN Viral/metabolismo , ADN Viral/genética , Células HEK293 , Interacciones Huésped-Patógeno , Unión ProteicaRESUMEN
Maize leaf diseases significantly impact yield and quality. However, recognizing these diseases from images taken in natural environments is challenging due to complex backgrounds and high similarity of disease spots between classes.This study proposes a lightweight multi-level attention fusion network (LFMNet) which can identify maize leaf diseases with high similarity in natural environment. The main components of LFMNet are PMFFM and MAttion blocks, with three key improvements relative to existing essential blocks. First, it improves the adaptability to the change of maize leaf disease scale through the dense connection of partial convolution with different expansion rates and reduces the parameters at the same time. The second improvement is that it replaces a adaptable pooling kernel according to the size of the input feature map on the original PPA, and the convolution layer to reshape to enhance the feature extraction of maize leaves under complex background. The third improvement is that it replaces different pooling kernels to obtain features of different scales based on GMDC and generate feature weighting matrix to enhance important regional features. Experimental results show that the accuracy of the LFMNet model on the test dataset reaches 94.12%, which is better than the existing heavyweight networks, such as ResNet50 and Inception v3, and lightweight networks such as DenseNet 121,MobileNet(V3-large) and ShuffleNet V2. The number of parameters is only 0.88m, which is better than the current mainstream lightweight network. It is also effective to identify the disease types with similar disease spots in leaves.
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Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160⯵M) and Zn (800⯵M) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160⯵M + 200⯵M) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160⯵M + 800⯵M) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.
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Género Iris , Metales Pesados , Contaminantes del Suelo , Cadmio/toxicidad , Cadmio/análisis , Zinc/toxicidad , Desarrollo de la Planta , Contaminantes del Suelo/toxicidadRESUMEN
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The dysfunction of zinc homeostasis participates in the early and advancing malignancy of HCC. However, the prognostic ability of zinc homeostasis in HCC has not been clarified yet. Here, we showed a zinc-homeostasis related risk model in HCC. Five signature genes including ADAMTS5, PLOD2, PTDSS2, KLRB1, and UCK2 were screened out via survival analyses and regression algorithms to construct the nomogram with clinical characteristics. Experimental researches indicated that UCK2 participated in the progression of HCC. Patients with higher risk scores always had worse outcomes and were more associated with immune suppression according to the analyses of immune related-pathway activation, cell infiltration, and gene expression. Moreover, these patients were likely to exhibit more sensitivity to sorafenib and other antitumor drugs. This study highlights the significant prognostic role of zinc homeostasis and suggests potential treatment strategies in HCC.
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Aberrant long interspersed element 1 (LINE-1 or L1) activity can cause insertional mutagenesis and chromosomal rearrangements and has been detected in several types of cancers. Here, we show that neddylation, a post-translational modification process, is essential for L1 transposition. The antineoplastic drug MLN4924 is an L1 inhibitor that suppresses NEDD8-activating enzyme activity. Neddylation inhibition by MLN4924 selectively impairs ORF2p-mediated L1 reverse transcription and blocks the generation of L1 cDNA. Consistent with these results, MLN4924 treatment suppresses the retrotransposition activity of the non-autonomous retrotransposons short interspersed nuclear element R/variable number of tandem repeat/Alu and Alu, which rely on the reverse transcription activity of L1 ORF2p. The E2 enzyme UBE2M in the neddylation pathway, rather than UBE2F, is required for L1 ORF2p and retrotransposition. Interference with the functions of certain neddylation-dependent Cullin-really interesting new gene E3 ligases disrupts L1 reverse transcription and transposition activity. Our findings provide insights into the regulation of L1 retrotransposition and the identification of therapeutic targets for L1 dysfunctions.
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Ciclopentanos , Elementos de Nucleótido Esparcido Largo , Pirimidinas , Retroelementos , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Retroelementos/genética , Aberraciones Cromosómicas , Proteínas Cullin/genética , Enzimas Ubiquitina-ConjugadorasRESUMEN
The complexity of the tumor microenvironment (TME) is a crucial factor in lung adenocarcinoma (LUAD) progression. To gain deeper insights into molecular mechanisms of LUAD, we perform an integrative single-cell RNA sequencing (scRNA-seq) data analysis of 377,574 cells from 117 LUAD patient samples. By linking scRNA-seq data with bulk gene expression data, we identify a cluster of prognostic-related UPP1high tumor cells. These cells, primarily situated at the invasive front of tumors, display a stronger association with the immunosuppressive components in the TME. Our cytokine array analysis reveals that the upregulation of UPP1 in tumor cells leads to the increased release of various immunosuppressive cytokines, with TGF-ß1 being particularly prominent. Furthermore, this UPP1 upregulation also elevates the expression of PD-L1 through the PI3K/AKT/mTOR pathway, which contributes to the suppression of CD8 + T cells. Cytometry by time-of-flight (CyTOF) analysis provides additional evidence of the role of UPP1 in shaping the immunosuppressive nature of the TME. Using patient-derived organoids (PDOs), we discover that UPP1high tumors exhibit relatively increased sensitivity to Bosutinib and Dasatinib. Collectively, our study highlights the immunosuppressive role of UPP1 in LUAD, and these findings may provide insights into the molecular features of LUAD and facilitate the development of personalized treatment strategies.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Linfocitos T CD8-positivos , Citocinas , Inmunosupresores , Neoplasias Pulmonares/genética , Fosfatidilinositol 3-Quinasas/genética , Microambiente Tumoral/genéticaRESUMEN
Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.
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Acetatos , Asteraceae , Cadmio , Ciclopentanos , Oxilipinas , Cadmio/metabolismo , Raíces de Plantas/metabolismo , Polisacáridos/metabolismo , Polisacáridos/farmacología , Pectinas/química , Pared Celular/metabolismo , Asteraceae/metabolismoRESUMEN
BACKGROUND: DOCK1 has been reported to be involved in tumor progression and resistance. 1-(2-(30-(trifluoromethyl)-[1,10-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl2(1H)- pyridone (TBOPP) is a selective DOCK1 inhibitor; however, the role and molecular mechanisms of DOCK1 and its inhibition in breast cancer (BC) resistance remain poorly understood. OBJECTIVE: This study aims toinvestigate the underlying mechanisms of DOCK1 in BC resistance. METHODS: DOCK1 or Twist siRNA and Twist plasmid were used to explore the function of DOCK1 in vitro experiments. A mouse xenograft model was used for in vivo experiments. RESULTS: In the present study, we demonstrated that DOCK1 siRNA promoted cisplatin sensitivity in BC cells. Moreover, TBOPP also enhances the therapeutic effect of cisplatin both in vitro and in vivo. Mechanistically, DOCK1 siRNA inhibited EMT. Twist 1 is one of the EMT-inducing transcription factors and is known to induce EMT. To further reveal the effect of DOCK in BC cells, we co-transfected with DOCK1 and Twist1 siRNA to BC cells and found that co-transfection with DOCK1 and Twist siRNA could not further enhance the cisplatin sensitivity of BC cells. Moreover, DOCK1 siRNA failed to reverse the effect of Twist 1 up-regulation. CONCLUSION: Taken together, these results demonstrate that DOCK1 may function as a potential therapeutic target in BC and that combining cisplatin with TBOPP may provide a promising therapeutic strategy for cisplatin-resistant BC patients.
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Stimulatorof interferon genes (STING) is an intracellular sensor of cyclic dinucleotides involved in the innate immune response against pathogen- or self-derived DNA. For years, interferon (IFN) induction of cyclic GMP-AMP synthase (cGAS)-STING has been considered as a canonical pattern defending the host from viral invasion. The mechanism of the cGAS-STING-IFN pathway has been well-illustrated. However, other signalling cascades driven by cGAS-STING have emerged in recent years and some of them have been found to possess antiviral ability independent of IFN. Here, we summarize the current progress on cGAS-STING-mediated nonclassic antiviral activities with an emphasis on the nuclear factor-κB and autophagy pathways, which are the most-studied pathways. In addition, we briefly present the primordial function of the cGAS-STING pathway in primitive species to show the importance of IFN-unrelated antiviral activity from an evolutionary angle. Finally, we discuss open questions that need to be solved for further exploitation of this field.
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Inmunidad Innata , Nucleotidiltransferasas , Humanos , Nucleotidiltransferasas/genética , Transducción de Señal , Interferones , Antivirales/farmacologíaRESUMEN
Pyroptosis, a pro-inflammatory programmed cell death, has been implicated in the pathogenesis of coronavirus disease 2019 and other viral diseases. Gasdermin family proteins (GSDMs), including GSDMD and GSDME, are key regulators of pyroptotic cell death. However, the mechanisms by which virus infection modulates pyroptosis remain unclear. Here, we employed a mCherry-GSDMD fluorescent reporter assay to screen for viral proteins that impede the localization and function of GSDMD in living cells. Our data indicated that the main protease NSP5 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) blocked GSDMD-mediated pyroptosis via cleaving residues Q29 and Q193 of GSDMD. While another SARS-CoV-2 protease, NSP3, cleaved GSDME at residue G370 but activated GSDME-mediated pyroptosis. Interestingly, respiratory enterovirus EV-D68-encoded proteases 3C and 2A also exhibit similar differential regulation on the functions of GSDMs by inactivating GSDMD but initiating GSDME-mediated pyroptosis. EV-D68 infection exerted oncolytic effects on human cancer cells by inducing pyroptotic cell death. Our findings provide insights into how respiratory viruses manipulate host cell pyroptosis and suggest potential targets for antiviral therapy as well as cancer treatment.IMPORTANCEPyroptosis plays a crucial role in the pathogenesis of coronavirus disease 2019, and comprehending its function may facilitate the development of novel therapeutic strategies. This study aims to explore how viral-encoded proteases modulate pyroptosis. We investigated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory enterovirus D68 (EV-D68) proteases on host cell pyroptosis. We found that SARS-CoV-2-encoded proteases NSP5 and NSP3 inactivate gasdermin D (GSDMD) but initiate gasdermin E (GSDME)-mediated pyroptosis, respectively. We also discovered that another respiratory virus EV-D68 encodes two distinct proteases 2A and 3C that selectively trigger GSDME-mediated pyroptosis while suppressing the function of GSDMD. Based on these findings, we further noted that EV-D68 infection triggers pyroptosis and produces oncolytic effects in human carcinoma cells. Our study provides new insights into the molecular mechanisms underlying virus-modulated pyroptosis and identifies potential targets for the development of antiviral and cancer therapeutics.
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Endopeptidasas , Enterovirus Humano D , Interacciones Microbiota-Huesped , Virus Oncolíticos , Piroptosis , SARS-CoV-2 , Humanos , Línea Celular Tumoral , COVID-19/metabolismo , COVID-19/terapia , COVID-19/virología , Endopeptidasas/genética , Endopeptidasas/metabolismo , Enterovirus Humano D/enzimología , Enterovirus Humano D/genética , Infecciones por Enterovirus/metabolismo , Infecciones por Enterovirus/virología , Gasderminas/antagonistas & inhibidores , Gasderminas/genética , Gasderminas/metabolismo , Viroterapia Oncolítica , Virus Oncolíticos/enzimología , Virus Oncolíticos/genética , SARS-CoV-2/enzimología , SARS-CoV-2/genética , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: Drought stress can substantially restrict maize growth and productivity, and global warming and an increasing frequency of extreme weather events are likely to result in more yield losses in the future. Therefore, unraveling the molecular mechanism underlying the response to drought stress is essential for breeding drought-resilient crops. RESULTS: In this study, we subjected the 3-leaf-period plants of two maize inbred lines, a drought-tolerant line (si287) and a drought-sensitive line (X178), to drought stress for seven days while growing in a chamber. Subsequently, we measured physiological traits and analyzed transcriptomic and metabolic profiles of two inbred lines. Our KEGG analysis of genes and metabolites revealed significant differences in pathways related to glycolysis/gluconeogenesis, flavonoid biosynthesis, starch and sucrose metabolism, and biosynthesis of amino acids. Additionally, our joint analysis identified proline, tryptophan and phenylalanine are crucial amino acids for maize response to drought stress. Furthermore, we concentrated on tryptophan (Trp), which was found to enhance tolerance via IAA-ABA signaling, as well as SA and nicotinamide adenine dinucleotide (NAD) consequent reactive oxygen species (ROS) scavenging. We identified three hub genes in tryptophan biosynthesis, indole-3-acetaldehyde oxidase (ZmAO1, 542,228), catalase 1 (ZmCAT1, 542,369), and flavin-containing monooxygenase 6 (ZmYUC6, 103,629,142), High expression of these genes plays a significant role in regulating drought tolerance. Two metabolites related to tryptophan biosynthesis, quinolinic acid, and kynurenine improved maize tolerance to drought stress by scavenging reactive oxygen species. CONCLUSIONS: This study illuminates the mechanisms underlying the response of maize seedlings to drought stress. Especially, it identifies novel candidate genes and metabolites, enriching our understanding of the role of tryptophan in drought stress. The identification of distinct resistance mechanisms in maize inbred lines will facilitate the exploration of maize germplasm and the breeding of drought-resilient hybrids.
Asunto(s)
Plantones , Zea mays , Plantones/genética , Zea mays/genética , Sequías , Triptófano , Especies Reactivas de Oxígeno , Fitomejoramiento , Perfilación de la Expresión Génica , AminoácidosRESUMEN
Objective@#To explore the interaction of multi-target stool DNA (MT-sDNA), intestinal flora and environmental factors in the development of colorectal cancer, so as to provide insights into pathogenesis study of colorectal cancer.@*Methods@#A total of 54 cases of colorectal cancer from the First Affiliated Hospital of Ningbo University were included in the case group and 51 healthy subjects were included in the control group. Demographic information, diet and family history of colorectal cancer were collected by a questionnaire survey. MT-sDNA, intestinal flora, cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and other tumor markers were detected. Interactions of MT-sDNA, intestinal flora and environmental factors with the development of colorectal cancer was analyzed by multifactor dimensionality reduction (MDR), crossover analysis and additive model.@*Results@#The case group included 20 males (37.04%) and 34 females (62.96%), and had a mean age of (64.89±9.72) years. The control group included 24 males (47.06%) and 27 females (52.94%), and had a mean age of (53.94±10.33) years. MDR analysis showed that subjects with both high absolute intestinal flora indexes and positive MT-sDNA had an increased risk of colorectal cancer (OR=3.782, 95%CI: 1.190-5.034). Crossover analysis showed that subjects with positive MT-sDNA and >5 μg/L of CEA had an increased risk of colorectal cancer (OR=2.121, 95%CI: 1.162-4.033). Additive model analysis showed that MT-sDNA had positive additive interaction with CEA (SI=3.687, 95%CI: 1.229-7.238), and MT-sDNA had negative additive interaction with fruit intake (SI=0.145, 95%CI: 0.020-0.753).@*Conclusion@#Positive MT-sDNA can synergistically increase the risk of colorectal cancer with high intestinal flora index and CEA, and fruit intake can reduce the risk of colorectal cancer in MT-sDNA-positive population.