The orchestration of cell-cycle reentry and ribosome biogenesis network is critical for cardiac repair.

Rationale: Myocardial infarction (MI) is a severe global clinical condition with widespread prevalence. The adult mammalian heart's limited capacity to generate new cardiomyocytes (CMs) in response to injury remains a primary obstacle in developing effective therapies. Current approaches focus on inducing the proliferation of existing CMs through cell-cycle reentry. However, this method primarily elevates cyclin dependent kinase 6 (CDK6) and DNA content, lacking proper cytokinesis and resulting in the formation of dysfunctional binucleated CMs. Cytokinesis is dependent on ribosome biogenesis (Ribo-bio), a crucial process modulated by nucleolin (Ncl). Our objective was to identify a novel approach that promotes both DNA synthesis and cytokinesis. Methods: Various techniques, including RNA/protein-sequencing analysis, Ribo-Halo, Ribo-disome, flow cytometry, and cardiac-specific tumor-suppressor retinoblastoma-1 (Rb1) knockout mice, were employed to assess the series signaling of proliferation/cell-cycle reentry and Ribo-bio/cytokinesis. Echocardiography, confocal imaging, and histology were utilized to evaluate cardiac function. Results: Analysis revealed significantly elevated levels of Rb1, bur decreased levels of circASXL1 in the hearts of MI mice compared to control mice. Deletion of Rb1 induces solely cell-cycle reentry, while augmenting the Ribo-bio modulator Ncl leads to cytokinesis. Mechanically, bioinformatics and the loss/gain studies uncovered that circASXL1/CDK6/Rb1 regulates cell-cycle reentry. Moreover, Ribo-Halo, Ribo-disome and circRNA pull-down assays demonstrated that circASXL1 promotes cytokinesis through Ncl/Ribo-bio. Importantly, exosomes derived from umbilical cord mesenchymal stem cells (UMSC-Exo) had the ability to enhance cardiac function by facilitating the coordinated signaling of cell-cycle reentry and Ribo-bio/cytokinesis. These effects were attenuated by silencing circASXL1 in UMSC-Exo. Conclusion: The series signaling of circASXL1/CDK6/Rb1/cell-cycle reentry and circASXL1/Ncl/Ribo-bio/cytokinesis plays a crucial role in cardiac repair. UMSC-Exo effectively repairs infarcted myocardium by stimulating CM cell-cycle reentry and cytokinesis in a circASXL1-dependent manner. This study provides innovative therapeutic strategies targeting the circASXL1 signaling network for MI and offering potential avenues for enhanced cardiac repair.

Suppression of circular RNA serum and glucocorticoid-induced kinase 1 elevates antioxidant molecules and angiogenesis in trophoblast cells to attenuate preeclampsia via microRNA-508-3p to target and restrain PUM homolog 1.

AIM: Preeclampsia (PE) is a pregnancy-specific syndrome characterized by hypertension and proteinuria. Recently, multiple circular RNAs (circRNAs) were considered latent clinical diagnostic markers or therapeutic targets. This study was to explore the impact of circRNA serum and glucocorticoid-induced kinase 1 (SGK1) on PE via influencing the microRNA (miR)-508-3p/PUM homolog 1 (PUM1) axis. METHODS: Placental tissues of 34 pregnant women with PE and 34 normal pregnant women were collected to measure circRNA SGK1 (circSGK1), miR-508-3p, and PUM1. Human placental trophoblasts HTR-8/SVneo were transfected with plasmids, thereafter to observe proliferation, migration, invasion, and apoptosis, analyze antioxidant molecules Troxerutin (TXN), Glutamate-cysteine ligase catalytic subunit (GCLC), NAD (P) H-quinone oxidoreductase 1 (NQO1), and determine angiogenesis. After the construction of the PE rat model, antioxidant molecules TXN, GCLC, and NQO1, vascular-associated factor vascular endothelial growth factor A (VEGF-A), and histopathological conditions were tested. Examination of the binding of circSGK1 and miR-508-3p with PUM1 was performed. RESULTS: Our data showed that circSGK1 expression was elevated in the placenta of patients with PE. Silenced circSGK1 or elevated miR-508-3p promoted the growth and antioxidant molecules and angiogenesis in trophoblast cells; CircSGK1 combined with miR-508-3p, and miR-508-3p targeted PUM1. CONCLUSIONS: In summary, suppression of circSGK1 augments antioxidant molecules and angiogenesis in trophoblast cells to attenuate PE via miR-508-3p to target PUM1.

SUMOylation of RNF146 results in Axin degradation and activation of Wnt/ß-catenin signaling to promote the progression of hepatocellular carcinoma.

Aberrant SUMOylation contributes to the progression of hepatocellular carcinoma (HCC), yet the molecular mechanisms have not been well elucidated. RING-type E3 ubiquitin ligase RNF146 is a key regulator of the Wnt/ß-catenin signaling pathway, which is frequently hyperactivated in HCC. Here, it is identified that RNF146 can be modified by SUMO3. By mutating all lysines in RNF146, we found that K19, K61, K174 and K175 are the major sites for SUMOylation. UBC9/PIAS3/MMS21 and SENP1/2/6 mediated the conjugation and deconjugation of SUMO3, respectively. Furthermore, SUMOylation of RNF146 promoted its nuclear localization, while deSUMOylation induced its cytoplasmic localization. Importantly, SUMOylation promotes the association of RNF146 with Axin to accelerate the ubiquitination and degradation of Axin. Intriguingly, only UBC9/PIAS3 and SENP1 can act at K19/K175 in RNF146 and affect its role in regulating the stability of Axin. In addition, inhibiting RNF146 SUMOylation suppressed the progression of HCC both in vitro and in vivo. And, patients with higher expression of RNF146 and UBC9 have the worst prognosis. Taken together, we conclude that RNF146 SUMOylation at K19/K175 promotes its association with Axin and accelerates Axin degradation, thereby enhancing ß-catenin signaling and contributing to cancer progression. Our findings reveal that RNF146 SUMOylation is a potential therapeutic target in HCC.

Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.

Exosomes are well-known key mediators of intercellular communication and contribute to various physiological and pathological processes. Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, transport of MVBs, and MVB fusion with the plasma membrane. Each process is modulated through the competition or coordination of multiple mechanisms, whereby diverse repertoires of molecular cargos are sorted into distinct subpopulations of exosomes, resulting in the high heterogeneity of exosomes. Intriguingly, cancer cells exploit various strategies, such as aberrant gene expression, posttranslational modifications, and altered signaling pathways, to regulate the biogenesis, composition, and eventually functions of exosomes to promote cancer progression. Therefore, exosome biogenesis-targeted therapy is being actively explored. In this review, we systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy.

Influence of Mineral Fertilizer and Manure Application on the Yield and Quality of Maize in Relation to Intercropping in the Southeast Republic of Kazakhstan.

Maize (Zea mays L.) is a valuable forage crop. It is also an essential and promising crop for the Republic of Kazakhstan, cultivated in the southern zone. Some new maize hybrids have been introduced, which have been beneficial for high yields with less fertilizer input. This study aims to introduce the new maize hybrid, Arman 689, for the judicial use of fertilizer and the high yield. This study was carried out in 2015 in the southeast region of Kazakhstan. There are five treatments with various mineral fertilizer and poultry manure doses: 1. control (T0), 2. P60 K100 (T1), 3. N100P60K100 (T2). 4. N100P60K100 + 40 tons of manure/ha (T3), and 5. N100P60K100 + 60 ton of manure/ha (T4). The fertilizers used were ammonium nitrate (N­34.6%), amorphous (N­11.0%, P2O5­46.0%), and potassium chloride KCl (K2O­56%). The results showed that the grain yield ranges from 5.51 t/ha (T0) to 8.49 (T4) t/ha. The protein contents in the maize grain varied from 9%(T0)−11.3%(T4). The grain nitrogen content accounted for 54.2 to 52.0%. The nutrient uptake results by different treatments indicated that nitrogen contributed to 41.5% of the total yield increase. Using manure in combination with mineral fertilizers reduced the payback of the applied resources, as the payback of T2−T4 was 8.8−9.1 kg of grain. With the application of recommended mineral fertilizer (NPK), the protein yield was 0.83 t/ha, 0.33, and 1.22 t/ha higher than T0 and T1 treatments, respectively. There was no significant yield difference under T3 and T4 treatments (p > 0.05). Overall, the treatment, NPK + 40 tons of manure, was proved the ultimate for the Arman hybrid in providing the optimum quantity and quality of maize, as well as reducing the payback cost (8.8−9.1 kg of grain). It is suggested to apply NPK-recommended doses along with manure in maize (Arman hybrid)-based intercropping systems to utilize the resources efficiently.

Graphene Biodevices for Early Disease Diagnosis Based on Biomarker Detection.

The early diagnosis of diseases plays a vital role in healthcare and the extension of human life. Graphene-based biosensors have boosted the early diagnosis of diseases by detecting and monitoring related biomarkers, providing a better understanding of various physiological and pathological processes. They have generated tremendous interest, made significant advances, and offered promising application prospects. In this paper, we discuss the background of graphene and biosensors, including the properties and functionalization of graphene and biosensors. Second, the significant technologies adopted by biosensors are discussed, such as field-effect transistors and electrochemical and optical methods. Subsequently, we highlight biosensors for detecting various biomarkers, including ions, small molecules, macromolecules, viruses, bacteria, and living human cells. Finally, the opportunities and challenges of graphene-based biosensors and related broad research interests are discussed.

7,8-Dihydroxyflavone Enhanced Colonic Cholinergic Contraction and Relieved Loperamide-Induced Constipation in Rats.

BACKGROUND: Whether 7,8-dihydroxyflavone (7,8-DHF), a tyrosine kinase receptor B (TrkB) agonist, modulates colonic smooth muscle motility and/or alleviates constipation has not yet been studied. AIMS: Here, we aimed to determine how 7,8-DHF influences carbachol (CCh)-stimulated contraction of colonic strips and the in vivo effect of 7,8-DHF on constipation. METHODS: Muscle strips were isolated from rat colons for recording contractile tension and performing western blotting. Constipation was induced in rats with loperamide. RESULTS: Although it specifically activated TrkB, 7,8-DHF applied alone neither activated PLCγ1 in the colonic strips nor induced colonic strip contraction. However, 7,8-DHF enhanced CCh-stimulated PLCγ1 activation and strip contraction. The PLCγ1 antagonist U73122 suppressed both CCh-stimulated and 7,8-DHF-enhanced/CCh-stimulated contraction. While clarifying the underlying mechanism, we revealed that 7,8-DHF augmented muscarinic M3 receptor expression in the colonic strips. The M3-selective antagonist tarafenacin specifically inhibited the 7,8-DHF-enhanced/CCh-stimulated contraction of the colonic strips. Since 7,8-DHF increased Akt phosphorylation, and LY294002 (an antagonist of PI3K upstream of Akt) dramatically inhibited both 7,8-DHF-augmented M3 expression and 7,8-DHF-enhanced/CCh-stimulated contractions, we assumed that 7,8-DHF/TrkB/Akt was associated with the modulation of M3 expression in the colonic strips. ANA-12, a specific TrkB antagonist, not only inhibited TrkB activation by 7,8-DHF but also suppressed 7,8-DHF-enhanced cholinergic contraction, 7,8-DHF/CCh-mediated activation of PLCγ1/Akt, and M3 overexpression in colonic strips. In vivo 7,8-DHF, also by promoting intestinal motility and M3 expression, significantly alleviated loperamide-induced functional constipation in rats. CONCLUSIONS: Our results suggest that 7,8-DHF regulates colonic motility possibly via a TrkB/Akt/M3 pathway and may be applicable for alleviating constipation.

Melatonin improves the seed filling rate and endogenous hormonal mechanism in grains of summer maize.

The unpredictable precipitation and water deficit conditions in semiarid regions significantly reduce the yield of summer maize. The exogenous application of plant growth regulators can be used as a strategy to enhance plant stress tolerance and improve the growth and yield of maize under semiarid conditions. Here, we studied the protective role of melatonin application on maize yield using grain filling rate and hormonal crosstalk in maize grains. In the first field experiment, seeds were soaked with melatonin at a concentration of 0 (SM0 ), 25 (SM1 ), 50 (SM2 ), and 75 µM (SM3 ) µM. In contrast, in the second experiment, melatonin was applied on the foliage at the ninth leaf stage at a concentration of 0 (FM0 ), 25 (FM1 ), 50 (FM2 ), and 75 (FM3 ) µM. Our findings showed that melatonin treatments as seed soaking significantly increased single seed weight, seed filling rate in superior, medium and inferior seeds by regulating the hormone levels compared to foliar application. Application of melatonin significantly increased the zeatin+zeatin riboside (Z+ZR), indole-3-acetic acid (IAA), and gibberellic acid (GA) contents. However, it significantly inhibited the contents of abscisic acid (ABA) during the seed filling period. The content of Z+ZR, IAA, and GA was positively correlated with the maximum seed filling rate, seed weight, and mean filling rate in middle, superior and lower seeds, while the ABA was negatively correlated. The ABA content in inferior seeds was positively correlated with the maximum and mean seed filling rate. In semiarid regions, melatonin treatment of SM2 and FM2 significantly increased the dry matter per plant, 100-grain weight, seed filling rate, IAA, Z+ZR, GA contents, ear characteristics, and maize yield.

Hormonal changes with uniconazole trigger canopy apparent photosynthesis and grain filling in wheat crop in a semi-arid climate.

Phytohormones are important for the growth and development of plants. The objective of the experiment was to investigate the effect of foliar application of uniconazole (UCZ) at the four-leaf stage on hormone crosstalk and production of winter wheat. An experiment was carried out during 2015-2016 and 2016-2017 growth season in a semi-arid region, where UCZ at a concentration of 0 (CK, distilled water), 15 (FU15), 30 (FU30), and 45 (FU45) mg L-1 were sprayed on wheat crop at the four-leaf stage at a rate of 138.8 mL m-2. UCZ alters the endogenous hormone contents in flag leaves and in grains. UCZ inhibited gibberellic acid (GA) in flag leaves and in grains where the lower GA with UCZ improved the zeatin + zeatin riboside (Z + ZR) and abscisic acid (ABA) contents. The lower GA and higher Z + ZR and ABA contents with UCZ-treated plants improved the chlorophyll content and canopy apparent photosynthesis (CAP) as well as the grain-filling characteristics. The Z + ZR and ABA in flag leaves were positively correlated with chlorophyll content and CAP value while negatively with GA. Moreover, the Z + ZR and ABA were positively correlated with maximum grain weight, mean grain-filling rate, and maximum grain-filling rate, while negatively with GA level. Treatment FU30 significantly improved the chlorophyll content, CAP value, spike weight, grain-filling characteristics, and hormone contents of Z + ZR and ABA while it decreased the GA level. The hormone crosstalk with UCZ significantly increased the yield of wheat crop, where FU30 treatment performs better.

Nitrogen fertilization affects maize grain yield through regulating nitrogen uptake, radiation and water use efficiency, photosynthesis and root distribution.

High external nitrogen (N) inputs can maximize maize yield but can cause a subsequent reduction in N use efficiency (NUE). Thus, it is necessary to identify the minimum effective N fertilizer input that does not affect maize grain yield (GY) and to investigate the photosynthetic and root system consequences of this optimal dose. We conducted a 4-year field experiment from 2014 to 2017 with four N application rates: 300 (N300), 225 (N225), 150 (N150), and 0 Kg ha-1 (N0) in the Northwest of China. GY was assessed by measuring the photosynthetic capacity and root system (root volume, surface area, length density and distribution). Grain yield decreased by -3%, 7.7%, and 21.9% when the N application rates decreased by 25%, 50%, and 100% from 300 Kg ha-1. We found that yield reduction driven by N reduction was primarily due to decreased radiation use efficiency (RUE) and WUE instead of intercepted photosynthetically active radiation and evapotranspiration. In the N225 treatment, GY, WUE, and RUE were not significantly reduced, or in some cases, were greater than those of the N300 treatment. This pattern was also observed with relevant photosynthetic and root attributes (i.e., high net photosynthetic rate, stomatal conductance, and root weight, as well as deep root distribution). Our results suggest that application of N at 225 Kg ha-1 can increased yield by improving the RUE, WUE, and NUE in semi-arid regions.

Effects of Gibberellin (GA4+7) in Grain Filling, Hormonal Behavior, and Antioxidants in High-Density Maize (Zea mays L.).

Dense plant cultivation is an efficient approach to improve maize production by maximizing the utilization of energy and nutrients. However, dense plant populations may aggravate the abortion rate of young grains, resulting in fewer kernels per ear. The rate and duration of grain-filling play decisive roles in maize grain yield. Therefore, to increase plant density, enhancing the grain-filling rate, extending the growth period of individual maize plants and regulating crop senescence would be the first priority. In this study, we examined the regulatory effects of GA4+7 under two application methods: shanks and silks were moistened by cotton full with GA4+7 solution at concentrations of 0, 10, 60, and 120 mg L-1. The results showed that GA4+7 improved the grain-filling rate by increasing the content of auxin, gibberellin, zeatin, and abscisic acid in grains compared to control plants. In addition, the auxin, gibberellin, and zeatin contents in the grains were positively and significantly correlated with the maximum grain weight and the maximum and mean grain-filling rates. Moreover, GA4+7 increased the activities of superoxide dismutases, catalases, and peroxidases and reduced the malondialdehyde content in leaves compared with untreated plants. At the concentration of 60 mg L-1, GA4+7 showed the greatest effect on shank and silk applications (Sh-60 and Si-60) followed by 10 mg L-1 (Sh-10) for shank treatment and 120 mg L-1 (Si-120) for silk treatment. Our results suggest that a concentration of 60 mg L-1 GA4+7 for shank and silk application may be efficiently used for changing the level of hormones in grains and antioxidant enzymes in ear leaves, which may be useful for enhancing grain-filling rate and delaying leaf senescence, resulting in an increase in maize grain yield.

Angiopoietin-2 induces angiogenesis via exosomes in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a highly vascularized solid tumor. Angiopoietin-2 (ANGPT2) has been described as an attractive target for antiangiogenic therapy. Exosomes are small extracellular vesicles secreted by most cell types and contribute to cell-to-cell communication by delivering functional cargo to recipient cells. The expression of ANGPT2 in tumor-derived exosomes remains unknown. METHODS: We detected the ANGPT2 expression in HCC-derived exosomes by immunoblotting, enzyme-linked immunosorbent assay and immunogold labeling, then observed exosomal ANGPT2 internalization and recycling by confocal laser scanning microscopy, co-immunoprecipitation and immunoblotting. We used two HCC cell lines (Hep3B and MHCC97H) to overexpress ANGPT2 by lentivirus infection or knockdown ANGPT2 by the CRISPR/Cas system, then isolated exosomes to coculture with human umbilical vein endothelial cells (HUVECs) and observed the angiogenesis by Matrigel microtubule formation assay, transwell migration assay, wound healing assay, cell counting kit-8 assay, immunoblotting and in vivo tumorigenesis assay. RESULTS: We found that HCC-derived exosomes carried ANGPT2 and delivered it into HUVECs by exosome endocytosis, this delivery led to a notable increase in angiogenesis by a Tie2-independent pathway. Concomitantly, we observed that HCC cell-secreted exosomal ANGPT2 was recycled by recipient HUVECs and might be reused. In addition, the CRISPR-Cas systems to knock down ANGPT2 significantly inhibited the angiogenesis induced by HCC cell-secreted exosomal ANGPT2, and obviously suppressed the epithelial-mesenchymal transition activation in HCC. CONCLUSIONS: Taken together, these results reveal a novel pathway of tumor angiogenesis induced by HCC cell-secreted exosomal ANGPT2 that is different from the classic ANGPT2/Tie2 pathway. This way may be a potential therapeutic target for antiangiogenic therapy. Video Abstract.

Foliar application of melatonin delay leaf senescence in maize by improving the antioxidant defense system and enhancing photosynthetic capacity under semi-arid regions.

Melatonin is an important plant growth regulator which plays a key role in plant growth and development. The objective of the current research was to evaluate the effect of foliar application of melatonin (MF) on photosynthetic efficiency, antioxidant defense mechanism, and its relation with leaf senescence in maize crop grown in a semi-arid region. A field experiment was conducted during 2017 and 2018 growth season, where melatonin was applied to the foliage at concentrations of 0 (MF0), 25 (MF1), 50 (MF2), and 75 (MF3) µM at the ninth leaf stage. Foliar application of melatonin significantly improved chlorophyll content, net photosynthetic rate, soluble sugar content, and soluble protein content during the process of leaf senescence. The application of melatonin also enhanced antioxidant enzyme activities including superoxide dismutase, catalase, and peroxidase, while reduced malondialdehyde and reactive oxygen species accumulation. Melatonin foliar application also increased total leaf area per plant, grains per ear, thousand grain weight and grain yield of maize crop in a semi-arid region. The application of melatonin significantly improved photosynthetic activity, antioxidant defense mechanism, and yield of maize crop in a semi-arid region, where the most effective treatment was MF2.

Repression of Kisspeptin1 weakens hydrogen peroxide-caused injury in HTR8 cells via adjusting PI3K/AKT/mTOR pathway.

Kisspeptin1 (KISS1) is a tumor metastatic suppressor, and its increased expression is validated in human placenta trophoblast cells. Nonetheless, the actions of KISS1 in hydrogen peroxide (H2 O2 )-impaired human trophoblast HTR8 cells still remain imprecise. This research aims to uncover whether KISS1 can mitigate H2 O2 -triggered cell injury. HTR8 cells were pretreated with 250 µM H2 O2 for 4 hours; the autophagic markers (Beclin-1 and LC3B), cell viability, invasion and apoptosis were appraised. Real-time quantitative polymerase chain reaction and Western blot trials were enforced for the valuation of KISS1 mRNA and protein levels. After si-KISS1 transfection and 3-MA manipulation, the aforesaid biological processes were reassessed for ascertaining the influences of repressed KISS1 in H2 O2 -impaired HTR8 cells. Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was eventually estimated. H2 O2 enhanced Beclin-1 and LC3B expression, restricted cell viability, and invasion, and meanwhile caused apoptosis. The elevation of KISS1 evoked by H2 O2 was observed in HTR8 cells. In addition, silencing KISS1 was distinctly annulled the function of H2 O2 in HTR8 cells. Eventually, we observed that the repression of KISS1 triggered the activation of PI3K/AKT/mTOR in HTR8 cells under H2 O2 management. The diverting research unveiled that KISS1 repression eased H2 O2 -caused HTR8 cells injury via mediating PI3K/AKT/mTOR pathway.

Exogenous melatonin confers drought stress by promoting plant growth, photosynthetic capacity and antioxidant defense system of maize seedlings.

Melatonin is an important biologically active hormone that plays a vital role in plant growth and development. In particular, it has been investigated for its roles in abiotic stress management. The current experiment was carried out to investigate the protective role of melatonin in photosynthetic traits and the antioxidant defense system of maize seedling under drought stress. Maize seedlings were subjected to drought stress (40-45% FC) after two weeks of seedling emergence, followed by a foliar spray (0, 25, 50, 75 and 100 µM) and soil drench of melatonin (0, 25, 50, 75 and 100 µM). Our results indicated that drought stress negatively affected maize seedling and decreased plant growth and development, biomass accumulation, reduced chlorophyll, and carotenoid content, and significantly declined photosynthetic rate and stomatal conductance. On the other hand, reactive oxygen species, soluble protein, and proline content increased under drought stress. However, the application of exogenous melatonin reduced the reactive oxygen species burst and enhanced the photosynthetic activity by protecting from damages through activation of various antioxidant enzymes under drought stress. Foliar application of 100 µM and soil drench of 50 µM melatonin was the most effective treatment concentrations under drought stress. Our current findings hereby confirmed the mitigating potential of melatonin application for drought stress by maintaining plant growth, improving the photosynthetic characteristics and activities of antioxidants enzymes.

Shoot and root traits of summer maize hybrid varieties with higher grain yields and higher nitrogen use efficiency at low nitrogen application rates.

Breeding high-yielding and nitrogen-efficient maize (Zea mays L.) hybrid varieties is a strategy that could simultaneously solve the problems of resource shortages and environmental pollution. We conducted a 2-year field study using four nitrogen application rates (0, 150, 225, and 300 kg N hm-2) and two maize hybrid varieties (ZD958 and QS101) to understand the plant traits related to high grain yields and high nitrogen use efficiency (NUE). We found that ZD958 had a higher grain yield and nitrogen accumulation in the shoots at harvest as well as a higher NUE at lower nitrogen application rates (0 and 150 kg hm-2) than QS101. The grain yields and NUE were almost identical for the two hybrid varieties at nitrogen application rates of 225 and 300 kg N hm-2. Compared with QS101, ZD958 had higher above-ground and below-ground biomass amounts, a deeper root distribution, longer root length, root active absorption area, greater grain filling rate, and higher photosynthetic NUE than QS101 at lower nitrogen application rates. Our results showed that ZD958 can maintain a higher grain yield at lower nitrogen rates in a similar manner to N-efficient maize hybrid varieties. The selection of hybrids such as ZD958 with a deeper root distribution and higher photosynthetic NUE can increase the grain yield and NUE under low nitrogen conditions.

Vps4A mediates the localization and exosome release of ß-catenin to inhibit epithelial-mesenchymal transition in hepatocellular carcinoma.

We previously reported that Vps4A acted as a tumor suppressor by influencing the microRNA profiles of exosomes and their parental cells in hepatocellular carcinoma (HCC). However, the underlying mechanism and if Vps4A contributes to sorting proteins into exosomes are not well known. Here, we performed mass spectrometry analysis of the immunoprecipitated Vps4A complex and confirmed that Vps4A was associated with ß-catenin and CHMP4B. Through this interaction, Vps4A promoted the plasma membrane (PM) localization and exosome release of ß-catenin. Silencing Vps4A or CHMP4B decreased the PM localization and exosome sorting of ß-catenin. Vps4A overexpression decreased ß-catenin signaling pathway and inhibited epithelial-mesenchymal transition (EMT) and motility of HCC cells. And, silencing Vps4A or CHMP4B promoted EMT in HCC. Furthermore, the expression of Vps4A was significantly related to that of several EMT markers in HCC tissues and the level of exosomal ß-catenin in patients with metastatic HCC was significantly lower compared to that of control patients. In conclusion, through the interaction with CHMP4B and ß-catenin, Vps4A regulates the PM localization and exosome sorting of ß-catenin, consequently decreases ß-catenin signaling, and thereby inhibits EMT and metastasis in HCC.

Seed filling in maize and hormones crosstalk regulated by exogenous application of uniconazole in semiarid regions.

In semiarid regions, deficit and unpredictable precipitation results in yield losses. Uniconazole is a plant growth regulator and its application is beneficial in water saving agriculture and improves maize production in semiarid regions. In order to determine the effects of uniconazole application on seed filling and hormonal changes of maize, a field study was conducted in the summer of 2015 and 2016. Seeds were soaked in uniconazole at concentration of 0 (SCK), 25 (S25), 50 (S50), and 75 (S75) mg kg-1, while in the second experiment, uniconazole was applied to the foliage at concentration of 0 (FCK), 25 (F25), 50 (F50), and 75 (F75) mg L-1 at the eight-leaf. Uniconazole application significantly improves the seed filling rates by regulating the endogenous hormones contents. Uniconazole seed soaking treatments improved significantly the seed filling rate of superior, middle, and inferior seeds compared with foliar application treatments. Uniconazole improved significantly the zeatin (Z) + zeatin riboside (ZR) and abscisic acid (ABA) contents while reducing the gibberellic acid (GA) content in the seeds during the process of seed filling. The Z + ZR and ABA contents were significantly positively correlated while the GA content was negatively correlated with maximum seed weight, maximum seed filling rates, and mean seed filling rates. Treatments S25 and F25 significantly improved the above dry matter accumulation plant-1, seed filling rates, ABA, Z + ZR contents, characters of ear, and grain yield while reduced the GA content. It is concluded from our results that the uniconazole application at concentration of 25 mg kg-1 as seed soaking or 25 mg L-1 foliar applied at the eight-leaf stage is beneficial to improve the seed filling rates and grain yield of maize in semiarid regions.

Application of paclobutrazol: a strategy for inducing lodging resistance of wheat through mediation of plant height, stem physical strength, and lignin biosynthesis.

Lodging is a major constraint contributing to poor grain yield and quality of wheat (Triticum aestivum L.) worldwide. The use of plant growth regulators is becoming a foremost agro-chemical approach for minimizing the risk of lodging in cereal crops. The present study was conducted to examine the effects of the paclobutrazol application on culm physical strength, lignin content, and lodging resistance of wheat. Wheat seeds were soaked in paclobutrazol at the concentrations of 0 (CK, as control), 200 (PB1), 300 (PB2), and 400 (PB3) mg L-1. Our results showed that paclobutrazol resulted in a dose-dependent decrease of plant height, internode length, and center of gravity height. Paclobutrazol treatments evidently increased the culm diameter, culm filling degree, and wall thickness of basal internodes, resulting in greater stalk-breaking strength and lodging resistance index (CLRI), where their maximum values were obtained with PB1 treatment. In addition, the activities of lignin-related enzymes were improved by paclobutrazol, particularly at low concentration, which increased the lignin accumulation of the basal internodes of wheat, subsequently improving the capability of stalk lodging resistance. Moreover, the correlation analysis revealed significant correlations between stem diameter, culm filling degree, and lignin with stalk bending strength and CLRI. The paclobutrazol concentration ≥ 300 mg L-1 (PB2 and PB3 treatments) showed inhibitive effects on various culm morphological traits. These results suggest that not only the plant height, but also the lignin contents and physical strength of internodes are closely related with the lodging resistance of wheat, and reduction in plant height along with improved culm morphological characteristics and higher lignin accumulation in basal internodes could effectively relieve the risk of lodging.