Graphene enhances artemisinin production in the traditional medicinal plant Artemisia annua via dynamic physiological processes and miRNA regulation.

We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%-22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling-related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a âˆ¼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828-AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.

Integrating transcriptome and physiological analyses to elucidate the molecular responses of sorghum to fluxofenim and metolachlor herbicide.

The extensive use of herbicides has raised concerns about crop damage, necessitating the development of effective herbicide safeners. Fluxofenim has emerged as a promising herbicide safener; however, it's underlying mechanism remains unclear. Here, we screened two inbred lines 407B and HYZ to investigate the detoxication of fluxofenim in mitigating metolachlor damage in sorghum. Metolachlor inhibited seedling growth in both 407B and HYZ, while, fluxofenim could significantly restore the growth of 407B, but not effectively complement the growth of HYZ. Fluxofenim significantly increased the activities of glutathione-S-transferase (GST) to decrease metolachlor residue in 407B, but not in HYZ. This implys that fluxofenim may reduce metolachlor toxicity by regulating its metabolism. Furthermore, metolachlor suppressed AUX-related and JA-related genes expression, while up-regulated the expression of SA-related genes. Fluxofenim also restored the expression of AUX-related and JA-related genes inhibited by metolachlor and further increased expression of SA-related genes. Moreover, we noted a significant increase in the content of trans-zeatin O-glucoside (tZOG) and Gibberellin1 (GA1) after the fluxofenim treatment. In conclusion, fluxofenim may reduce the injury of herbicide by affecting herbicide metabolism and regulating hormone signaling pathway.

Genome-Wide Identification and Analysis of the EPF Gene Family in Sorghum bicolor (L.) Moench.

The EPIDERMAL PATTERNING FACTOR (EPF) plays a crucial role in plant response to abiotic stress. While the EPF has been extensively studied in model plants such as Arabidopsis thaliana, there is a lack of research on identifying EPF genes in the whole sorghum genome and its response to drought stress. In this study, we employed bioinformatics tools to identify 12 EPF members in sorghum. Phylogenetic tree analysis revealed that SbEPFs can be categorized into four branches. Further examination of the gene structure and protein conservation motifs of EPF family members demonstrated the high conservation of the SbEPF sequence. The promoter region of SbEPFs was found to encompass cis-elements responsive to stress and plant hormones. Moreover, real-time fluorescence quantitative results indicated that the SbEPFs have a tissue-specific expression. Under drought stress treatment, most SbEPF members were significantly up-regulated, indicating their potential role in drought response. Our research findings establish a foundation for investigating the function of SbEPFs and offer candidate genes for stress-resistant breeding and enhanced production in sorghum.

Study on Modification and Mechanism of Construction Waste to Solidified Silt.

A large amount of silt may be produced in river and lake regulation. It not only occupies land but also pollutes the environment. Therefore, it is urgent to seek effective disposal and utilization methods. Based on the problems of poor stability of stabilized soil and its tendency to soften easily in water, as well as its low strength with low curing agent dosage, this paper proposes a method to improve stabilized soil's solidification effect by adding materials such as cement, lime, fly ash, triethanolamine, sodium hydroxide, sodium silicate, etc., while mixing different grain diameters and quantities of building waste materials and ordinary sand. Using construction waste and ordinary sand as a comparative test, the curing mechanism of construction waste debris on the mechanical properties, permeability, and microstructure of solidified sludge was studied through unconfined compression tests, dry and wet cycle tests, permeability tests, and micro-structure tests such as XRD, MIP, and SEM. The test results show that the strength increases 8.5%~72.1% by adding building waste materials, and it grew with the increase in particle size and amount. It reduced the content of large pore size of solidified sediment and optimized the internal pore structure. At the same time, it formed a new structure filled by rigid skeleton material. Thus, it improved its unit section stress, built up the curing effect and water stability. The findings of this study can be used to modify solidified silt to improve stability and compaction characteristics.

Integration of transcriptome and metabolome analyses reveals sorghum roots responding to cadmium stress through regulation of the flavonoid biosynthesis pathway.

Cadmium (Cd) pollution is a serious threat to plant growth and human health. Although the mechanisms controlling the Cd response have been elucidated in other species, they remain unknown in Sorghum (Sorghum bicolor (L.) Moench), an important C4 cereal crop. Here, one-week-old sorghum seedlings were exposed to different concentrations (0, 10, 20, 50, 100, and 150 µM) of CdCl2 and the effects of these different concentrations on morphological responses were evaluated. Cd stress significantly decreased the activities of the enzymes peroxidase (POD), superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT), and increased malondialdehyde (MDA) levels, leading to inhibition of plant height, decreases in lateral root density and plant biomass production. Based on these results, 10 µM Cd concentration was chosen for further transcription and metabolic analyses. A total of 2683 genes and 160 metabolites were found to have significant differential abundances between the control and Cd-treated groups. Multi-omics integrative analysis revealed that the flavonoid biosynthesis pathway plays a critical role in regulating Cd stress responses in sorghum. These results provide new insights into the mechanism underlying the response of sorghum to Cd.

Advanced nanoparticles that can target therapy and reverse drug resistance may be the dawn of leukemia treatment: A bibliometrics study.

With the development of nanomedicine, more and more nanoparticles are used in the diagnosis and treatment of leukemia. This study aimed to identify author, country, institutional, and journal collaborations and their impacts, assess the knowledge base, identify existing trends, and uncover emerging topics related to leukemia research. 1825 Articles and reviews were obtained from the WoSCC and analyzed by Citespace and Vosviewer. INTERNATIONAL JOURNAL OF NANOMEDICINE is the journal with the highest output. The contribution of FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY is also noteworthy. The three main aspects of research in Nanoparticles-leukemia-related fields included nanoparticles for the diagnosis and treatment of leukemia, related to the type and treatment of leukemia, the specific molecular mechanism, and existing problems of the application of nanoparticles in leukemia. In the future, synthesize nano-drugs that have targeted therapy and chemotherapy resistance according to the mechanism, which may be the dawn of the solution to leukemia. This study offers a comprehensive overview of the Nanoparticles-leukemia-related field using bibliometrics and visual methods for the first time, providing a valuable reference for researchers interested in Nanoparticles-leukemia.

Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets.

Type 1 diabetes (T1D) is an autoimmune disease caused by the immune system attacking and destroying insulin-producing ß cells in the pancreas. Islet transplantation is becoming one of the most promising therapies for T1D patients. However, its clinical use is limited by substantial cell loss after islet infusion, closely related to immune reactions, including instant blood-mediated inflammatory responses, oxidative stress, and direct autoimmune attack. Especially the grafted islets are not only exposed to allogeneic immune rejection after transplantation but are also subjected to an autoimmune process that caused the original disease. Due to the development and convergence of expertise in biomaterials, nanotechnology, and immunology, protective strategies are being investigated to address this issue, including exploring novel immune protective agents, encapsulating islets with biomaterials, and searching for alternative implantation sites, or co-transplantation with functional cells. These methods have significantly increased the survival rate and function of the transplanted islets. However, most studies are still limited to animal experiments and need further studies. In this review, we introduced the immunological challenges for islet graft and summarized the recent developments in immune-protective strategies to improve the outcomes of islet transplantation.

Systematical characterization of GRF gene family in sorghum, and their potential functions in aphid resistance.

Sorghum (Sorghum bicolor) is the fifth important cereal and an industrial energy crop in the world. Growth Regulation Factors (GRFs) play an important role in response to environmental stress, however, the knowledge of GRFs relating to the pest resistance is lacking. Here, we identified 8 GRF genes harboring the typical QLQ (glutamine, leucine, glutamine) and WRC (tryptophan, arginine, cysteine) domains in Sorghum, which could be classified into 4 clades through phylogenetic analysis. The SbGRF genes express in most tissues, while more than half of them express at the highest level in inflorescence. To further investigate their possible role in stress response, we analyzed the transcriptomics data. The results showed that SbGRFs could respond to the abiotic stresses including heat, salt and drought stress. Furthermore, combined the data with qRT-PCR, SbGRF1, 2, 4 and 7 were identified as dominant genes response to the aphid-induced stress. SSR markers close to these genes were also searched. Above all, we summarized the SbGRFs and provided their potential roles in aphid response.

Bioadhesive hydrogel comprising bilirubin/ß-cyclodextrin inclusion complexes promote diabetic wound healing.

CONTEXT: Chronic non-healing diabetic wound therapy is an important clinical challenge. Manipulating the release of bioactive factors from an adhesive hydrogel is an effective approach to repair chronic wounds. As an endogenous antioxidant, bilirubin (BR) has been shown to promote wound healing. Nonetheless, its application is limited by its low water solubility and oxidative degradation. OBJECTIVE: This study developed a bilirubin-based formulation for diabetic wound healing. MATERIALS AND METHODS: Bilirubin was incorporated into ß-CD-based inclusion complex (BR/ß-CD) which was then loaded into a bioadhesive hydrogel matrix (BR/ß-CD/SGP). Scratch wound assays were performed to examine the in vitro pro-healing activity of BR/ß-CD/SGP (25 µg/mL of BR). Wounds of diabetic or non-diabetic rats were covered with BR or BR/ß-CD/SGP hydrogels (1 mg/mL of BR) and changed every day for a period of 7 or 21 days. Histological assays were conducted to evaluate the in vivo effect of BR/ß-CD/SGP. RESULTS: Compared to untreated (18.7%) and BR (55.2%) groups, wound closure was more pronounced (65.0%) in BR/ß-CD/SGP group. In diabetic rats, the wound length in BR/ß-CD/SGP group was smaller throughout the experimental period than untreated groups. Moreover, BR/ß-CD/SGP decreased TNF-α levels to 7.7% on day 3, and elevated collagen deposition and VEGF expression to 11.9- and 8.2-fold on day 14. The therapeutic effects of BR/ß-CD/SGP were much better than those of the BR group. Similar observations were made in the non-diabetic model. DISCUSSION AND CONCLUSION: BR/ß-CD/SGP promotes wound healing and tissue remodelling in both diabetic and non-diabetic rats, indicating an ideal wound-dressing agent.

Disulfiram-loaded copper sulfide nanoparticles for potential anti-glioma therapy.

Disulfiram (DSF) is an effective copper (Cu2+)-dependent antitumor agent. In the present study, we explored use of transferrin (Tf)-modified DSF/copper sulfide (CuS) nanocomplex (Tf-DSF/CuS) for glioma therapy. Tf was used as glioma targeting motifs, DSF as an anticancer agent, and CuS as a source of Cu2+ ions and a photothermal agent. DSF was loaded on CuS by metal-chelation, and released from the nanocomplex under acidic condition. The Tf-DSF/CuS complex exhibited high cytotoxic effect in vitro. Notably, cytotoxic activity was correlated with pH triggered release of Cu2+ which initiated non-toxicity to toxicity switch of DSF. Ultrasound-targeted microbubble destruction (UTMD) technique was used for highly selective accumulation of intravenous injected Tf-DSF/CuS in the glioma orthotopic tumor as compared with the free drugs and non-targeted DSF/CuS groups. Magnetic resonance imaging and pathological examinations showed that Tf-DSF/CuS effectively suppressed tumor growth, with an inhibition ratio of ~85%. Additionally, DSF load did not compromise photothermal conversion ability of CuS nanoparticles. Efficacy of the photothermal ablation therapy of Tf-DSF/CuS was evaluated under 808 nm laser irradiation both in vitro and in vivo. These findings show that copper-sulfide based disulfiram nanoparticles are effective agents for anti-glioma therapy.

A Rapid Pipeline for Pollen- and Anther-Specific Gene Discovery Based on Transcriptome Profiling Analysis of Maize Tissues.

Recently, crop breeders have widely adopted a new biotechnology-based process, termed Seed Production Technology (SPT), to produce hybrid varieties. The SPT does not produce nuclear male-sterile lines, and instead utilizes transgenic SPT maintainer lines to pollinate male-sterile plants for propagation of nuclear-recessive male-sterile lines. A late-stage pollen-specific promoter is an essential component of the pollen-inactivating cassette used by the SPT maintainers. While a number of plant pollen-specific promoters have been reported so far, their usefulness in SPT has remained limited. To increase the repertoire of pollen-specific promoters for the maize community, we conducted a comprehensive comparative analysis of transcriptome profiles of mature pollen and mature anthers against other tissue types. We found that maize pollen has much less expressed genes (>1 FPKM) than other tissue types, but the pollen grain has a large set of distinct genes, called pollen-specific genes, which are exclusively or much higher (100 folds) expressed in pollen than other tissue types. Utilizing transcript abundance and correlation coefficient analysis, 1215 mature pollen-specific (MPS) genes and 1009 mature anther-specific (MAS) genes were identified in B73 transcriptome. These two gene sets had similar GO term and KEGG pathway enrichment patterns, indicating that their members share similar functions in the maize reproductive process. Of the genes, 623 were shared between the two sets, called mature anther- and pollen-specific (MAPS) genes, which represent the late-stage pollen-specific genes of the maize genome. Functional annotation analysis of MAPS showed that 447 MAPS genes (71.7% of MAPS) belonged to genes encoding pollen allergen protein. Their 2-kb promoters were analyzed for cis-element enrichment and six well-known pollen-specific cis-elements (AGAAA, TCCACCA, TGTGGTT, [TA]AAAG, AAATGA, and TTTCT) were found highly enriched in the promoters of MAPS. Interestingly, JA-responsive cis-element GCC box (GCCGCC) and ABA-responsive cis-element-coupling element1 (ABRE-CE1, CCACC) were also found enriched in the MAPS promoters, indicating that JA and ABA signaling likely regulate pollen-specific MAPS expression. This study describes a robust and straightforward pipeline to discover pollen-specific promotes from publicly available data while providing maize breeders and the maize industry a number of late-stage (mature) pollen-specific promoters for use in SPT for hybrid breeding and seed production.

Hyaluronic acid coated bilirubin nanoparticles attenuate ischemia reperfusion-induced acute kidney injury.

Acute kidney injury (AKI) is a common pathological process that is globally associated with a high morbidity and mortality rate. The underlying AKI mechanisms include over-produced reactive oxygen species (ROS), inflammatory cell infiltration, and high levels of inflammatory mediators. Bilirubin is an endogenous compound with antioxidant, anti-inflammatory and anti-apoptotic properties, and could, therefore, be a promising therapeutic candidate. Nanotechnology-mediated therapy has emerged as a novel drug delivery strategy for AKI treatment. In this study, we report a hyaluronic acid (HA) coated ε-polylysine-bilirubin conjugate (PLBR) nanoparticle (nHA/PLBR) that can selectively accumulate in injured kidneys and alleviate the oxidative/inflammatory-induced damage. The in vitro study revealed that nHA/PLBR has good stability, biocompatibility, and exhibited higher antioxidant as well as anti-apoptotic effects when compared to nPLBR or bilirubin. The in vivo study showed that nHA/PLBR could target and accumulate in the injured kidney, effectively relieve oxidative stress and inflammatory reactions, protect the structure and function of the mitochondria, and more importantly, inhibit the apoptosis of tubular cells in an ischemia/reperfusion-induced AKI rat model. Therefore, nHA/PLBR has the capacity to enhance specific biodistribution and delivery efficiency of bilirubin, thereby providing better treatment for AKI in the future.

An updated census of the maize TIFY family.

The TIFY gene family is a plant-specific gene family encoding a group of proteins characterized by its namesake, the conservative TIFY domain and members can be organized into four subfamilies: ZML, TIFY, PPD and JAZ (Jasmonate ZIM-domain protein) by presence of additional conserved domains. The TIFY gene family is intensively explored in several model and agriculturally important crop species and here, yet the composition of the TIFY family of maize has remained unresolved. This study increases the number of maize TIFY family members known by 40%, bringing the total to 47 including 38 JAZ, 5 TIFY, and 4 ZML genes. The majority of the newly identified genes were belonging to the JAZ subfamily, six of which had aberrant TIFY domains, suggesting loss JAZ-JAZ or JAZ-NINJA interactions. Six JAZ genes were found to have truncated Jas domain or an altered degron motif, suggesting resistance to classical JAZ degradation. In addition, seven membranes were found to have an LxLxL-type EAR motif which allows them to recruit TPL/TPP co-repressors directly without association to NINJA. Expression analysis revealed that ZmJAZ14 was specifically expressed in the seeds and ZmJAZ19 and 22 in the anthers, while the majority of other ZmJAZs were generally highly expressed across diverse tissue types. Additionally, ZmJAZ genes were highly responsive to wounding and JA treatment. This study provides a comprehensive update of the maize TIFY/JAZ gene family paving the way for functional, physiological, and ecological analysis.

Polylysine-bilirubin conjugates maintain functional islets and promote M2 macrophage polarization.

Macrophage polarization is one of the main factors contributing to the proinflammatory milieu of transplanted islets. It causes significant islet loss. Bilirubin exhibits protective effects during the islet transplantation process, but the mode of delivering drugs along with the islet graft has not yet been developed. In addition, it remains unclear whether bilirubin or its derivatives can modulate macrophage polarization during islet transplantation. Therefore, this study aimed to develop an ε-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets for protection and to explore its macrophage modulation activities. In in vitro studies, the PLL-BR was shown to tightly adhere to the islet surface. It also exhibited enhanced cytoprotective effects against oxidative and inflammatory conditions by promoting M2-type macrophage polarization. In in vivo studies, the PLL-BR-protected islets successfully prolonged the euglycemia period in diabetic mice and accelerated the blood glucose clearance rate by maintaining the insulin secretion function. Compared to the untreated islets, the PLL-BR-encapsulated islets induced anti-inflammatory responses that were characterized by elevated levels of M2 macrophage markers and local vascularization. In conclusion, PLL-BR can be used as a tool for reprograming macrophage polarization while providing a more efficient immune protection for transplanted islets. STATEMENT OF SIGNIFICANCE: Macrophage polarization is one main factor that caused significant loss of transplanted islets. Bilirubin possesses protective effects toward pancreatic islet, but how to deliver the drug along with the islet graft has not yet been harnessed. More importantly, whether bilirubin or its derivatives could modulate macrophage polarization during the host rejections has also not been answered. In this study, we developed an ε-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets and explore its role in macrophage modulation activities. PLL-BR could attach to the surface of islets and exerted high oxidation resistance and anti-inflammatory effect. For the first time, we demonstrate that bilirubin and its derivatives effectively promoted the M2-type macrophage polarization, and optimize the immune microenvironment for islets survival and function.

Protective Effects of Chitosan-Bilirubin Nanoparticles Against Ethanol-Induced Gastric Ulcers.

PURPOSE: Gastric ulcers (GU) are a disease of the gastrointestinal tract that can be caused by excessive alcohol consumption and heavy use of nonsteroidal anti-inflammatory drugs. GU manifests predominantly as pathological damage, such as extensive inflammatory erosion and superficial bleeding of the gastric mucosa. Oxidative stress damage and the inflammatory response are now considered important predisposing factors for GU, suggesting that antioxidant and anti-inflammatory drugs could be treatments for GU. Nanoparticle drug carriers offer many advantages over conventional drugs, such as improved drug efficiency, increased drug stability, and increased half-life. METHODS: We designed chitosan-bilirubin conjugate (CS-BR) nanoparticles and assessed the anti-inflammatory and antioxidant abilities of CS-BR in gastric epithelial cells. Then, we evaluated the intragastric retention time and the anti-ulcer effects of CS-BR in vivo. RESULTS: The in vitro data showed that CS-BR nanoparticles protect gastric epithelial cells against oxidative/inflammatory injury. The in vivo study demonstrated that CS-BR nanoparticles accumulate permanently in the stomach and exert powerful antioxidant and anti-inflammatory effects against GU. CONCLUSION: This study applied bilirubin to the treatment of GU and confirmed that CS-BR nanoparticles are effective at alleviating acute GU in an experimental model. The findings provide innovative ideas for prophylaxis against or treatment of GU.

Integration of transcriptome and proteome analyses reveal molecular mechanisms for formation of replant disease in Nelumbo nucifera.

The normal growth of Nelumbo nucifera, a widely planted aquatic crop in Asia, was severely ruined by replant disease. The mechanism of replant disease was still unknown in aquatic crops. Complementary transcriptomic and proteomic analyses were performed by comparing seedings of first-year planting (FP) and consecutive planting (CP). 9810 differentially expressed genes (DEGs) were identified between FP and CP. Additionally, 975 differentially expressed proteins (DEPs) were obtained. The correlation of proteome and transcriptome illustrated phenylpropanoid biosynthesis, flavonoid biosynthesis, metabolic pathways, and MAPK signaling pathways were significantly activated. Peroxidase, determined as one of the key proteins in replant disease of N. nucifera, was phylogenetically analyzed. A new depiction of the molecular mechanism causing replant disease in N. nucifera was illustrated. A consecutive monoculture stimulated the generation of reactive oxygen species (ROS) and ethylene, altered the metabolic balance of lignin and flavonoid, and attenuated the activity of antioxidant enzymes through DNA methylation. Therefore, the accumulation of autotoxic allelochemicals and the deficiency of antioxidant enzymes unavoidably suppressed the normal growth and development of replanted N. nucifera.

Decreased miR-144 expression as a non-invasive biomarker for acute myeloid leukemia patients.

MicroRNAs are found to be stable in blood and they demonstrated tissue specific expression patterns. Thus, they may be used as potential non-invasive biomarkers of specific cancers. In the current study, we mainly focused on miR-144, which has never been studied in acute myeloid leukemia (AML). The expression of miR-144 was explored in the bone marrow and peripheral blood of AML patients and healthy control. The correlation between peripheral blood miR-144 level and key clinical parameters, including overall survival and prognostic value, was further explored. We showed that miR-144 was markedly reduced in both the peripheral blood and bone marrow of AML patients compared with healthy controls. Further study revealed that there is a significant correlation between peripheral blood miR-144 level and FAB classification (p=0.0023) and cytogenetics (p=0.001). More importantly, a lower expression of peripheral blood miR-144 level was found to be positively correlated with poorer overall survival rate. In summary, peripheral blood miR-144 may be utilized as a potential novel non-invasive biomarker for AML screening.