The phosphatidylethanolamine-binding proteins OsMFT1 and OsMFT2 regulate seed dormancy in rice.

Seed dormancy is crucial for optimal plant life-cycle timing. However, domestication has largely diminished seed dormancy in modern cereal cultivars, leading to challenges such as pre-harvest sprouting (PHS) and subsequent declines in yield and quality. Therefore, it is imperative to unravel the molecular mechanisms governing seed dormancy for the development of PHS-resistant varieties. In this study, we screened a mutant of BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR4 (OsbHLH004) with decreased seed dormancy and revealed that OsbHLH004 directly regulates the expression of 9-CIS-EPOXYCAROTENOID DIOXYGENASE3 (OsNCED3) and GIBBERELLIN 2-OXIDASE6 (OsGA2ox6) in rice (Oryza sativa). Additionally, we determined that two phosphatidylethanolamine-binding proteins, MOTHER OF FT AND TFL1 and 2 (OsMFT1 and OsMFT2; hereafter OsMFT1/2) interact with OsbHLH004 and Ideal Plant Architecture 1 (IPA1) to regulate their binding capacities on OsNCED3 and OsGA2ox6, thereby promoting seed dormancy. Intriguingly, FT-INTERACTING PROTEIN1 (OsFTIP1) interacts with OsMFT1/2 and affects their nucleocytoplasmic translocation into the nucleus, where OsMFT1/2-OsbHLH004 and OsMFT1/2-IPA1 antagonistically modulate the expression of OsNCED3 and OsGA2ox6. Our findings reveal that OsFTIP1-mediated inhibition of nuclear translocation of OsMFT1/2 and the dynamic transcriptional modulation of OsNCED3 and OsGA2ox6 by OsMFT1/2-OsbHLH004 and OsMFT1/2-IPA1 complexes in seed dormancy in rice.

The tetratricopeptide repeat protein OsTPR075 promotes heading by regulating florigen transport in rice.

Rice (Oryza sativa) is one of the most important crops worldwide. Heading date is a vital agronomic trait that influences rice yield and adaption to local conditions. Hd3a, a proposed florigen that primarily functions under short-day (SD) conditions, is a mobile flowering signal that promotes the floral transition in rice. Nonetheless, how Hd3a is transported from leaves to the shoot apical meristem (SAM) under SDs remains elusive. Here, we report that FT-INTERACTING PROTEIN9 (OsFTIP9) specifically regulates rice flowering time under SDs by facilitating Hd3a transport from companion cells (CCs) to sieve elements (SEs). Furthermore, we show that the tetratricopeptide repeat (TPR) protein OsTPR075 interacts with both OsFTIP9 and OsFTIP1 and strengthens their respective interactions with Hd3a and the florigen RICE FLOWERING LOCUS T1 (RFT1). This in turn affects the trafficking of Hd3a and RFT1 to the SAM, thus regulating flowering time under SDs and long-day conditions, respectively. Our findings suggest that florigen transport in rice is mediated by different OsFTIPs under different photoperiods and those interactions between OsTPR075 and OsFTIPs are essential for mediating florigen movement from leaves to the SAM.

Unprecedented Organogermanium Functionalized GeIV-SbIII-Templating Polyoxotungstate Nanocluster for Photothermal-Chemodynamic Cancer Therapy.

The function-oriented synthesis of polyoxometalate (POM) nanoclusters has become an increasingly important area of research. Herein, the well-known broad-spectrum anticancer drug Ge-132 which contains GeIV as potential heteroatoms and carboxyl coordination sites, is introduced to the POM system, leading to the first organogermanium functionalized GeIV-SbIII-templating POM nanocluster Na4[H2N(CH3)2]16 H18[Sm4(H2O)12W4O14Ge(CH2CH2COOH)]2[SbW9O33]4[Ge(CH2CH2COOH) SbW15O54]2·62H2O (1). An unprecedented organogermanium templating Dawson-like [Ge(CH2CH2COOH)SbW15O54]12- building block is discovered. To take advantage of the potential pharmaceutical activity of such an organogermanium-functionalized POM cluster, 1 is further composited with gold nanoparticles (NPs) to prepare 1-Au NPs, which doubles the blood circulation time of 1-based nanodrug. Efficient separation of photogenerated charges in 1-Au NPs largely boosts the photothermal conversion efficiency (PCE = 55.0%), which is nearly 2.1 times that of either single 1 (PCE = 26.7%) or Au NPs (PCE = 26.2%), and simultaneously facilitate the generation of toxic activate reactive oxygen species in tumor microenvironment. Based on these findings, it is demonstrated that 1-Au NPs are a multifunctional and renal clearable nanomedicine with great potential in photoacoustic imaging guiding photothermal-chemodynamic therapy for breast cancer.

SNAC1-OsERF103-OsSDG705 module mediates drought response in rice.

Drought stress profoundly hampers both plant growth and crop yield. To combat this, plants have evolved intricate transcriptional regulation mechanisms as a pivotal strategy. Through a genetic screening with rice genome-scale mutagenesis pool under drought stress, we identified an APETALA2/Ethylene Responsive Factor, namely OsERF103, positively responds to drought tolerance in rice. Combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we pinpointed c. 1000 genes directly influenced by OsERF103. Further results revealed that OsERF103 interacts with Stress-responsive NAC1 (SNAC1), a positive regulator of drought tolerance in rice, to synergistically regulate the expression of key drought-related genes, such as OsbZIP23. Moreover, we found that OsERF103 recruits a Su(var)3-9,enhancer of zeste and trithorax-domain group protein 705, which encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase to specifically affect the deposition of H3K4me3 at loci like OsbZIP23 and other genes linked to dehydration responses. Additionally, the natural alleles of OsERF103 are selected during the domestication of both indica and japonica rice varieties and exhibit significant geographic distribution. Collectively, our findings have unfurled a comprehensive mechanistic framework underlying the OsERF103-mediated cascade regulation of drought response. This discovery not only enhances our understanding of drought signaling but also presents a promising avenue for the genetic improvement of drought-tolerant rice cultivars.

Injectable Hydrogels of Amphiphilic Vitamin E Derivatives for Locoregional Chemotherapy.

Vitamin E derivatives are particularly effective in chemotherapy drug development because they are nontoxic, biocompatible, and selective. Among them, α-tocopheryl succinate (α-TOS) can act synergistically with some chemotherapeutic agents. However, its hydrophobicity limits its systemic administration, and localized formulations are not available. Herein, we developed an injectable hydrogel based on self-assembled micelles of a triblock amphiphilic derivative of α-TOS (PEG-2VES), in which doxorubicin (DOX) was encapsulated in the core of the micelles for combined chemotherapy. A molecule of α-TOS was grafted onto each end of poly(ethylene glycols) (PEGs) of different lengths. Hydrogels were prepared by dissolving the polymers or the DOX-loaded micelles in water at room temperature. The subcutaneously injected hydrogels kept their shape and sustainably released the payloads over 7 days without any noticeable inflammatory response. In vitro and in vivo results confirmed the synergistic antitumor effects of the hydrogel and loaded drug. Furthermore, DOX-loaded hydrogels showed greater therapeutic efficiency and fewer toxic side effects than DOX alone. Overall, this hydrogel acts as a multifunctional system that can deliver drug, improve the therapeutic effect, and minimize drug toxicity.

An alanine to valine mutation of glutamyl-tRNA reductase enhances 5-aminolevulinic acid synthesis in rice.

KEY MESSAGE: An alanine to valine mutation of glutamyl-tRNA reductase's 510th amino acid improves 5-aminolevulinic acid synthesis in rice. 5-aminolevulinic acid (ALA) is the common precursor of all tetrapyrroles and plays an important role in plant growth regulation. ALA is synthesized from glutamate, catalyzed by glutamyl-tRNA synthetase (GluRS), glutamyl-tRNA reductase (GluTR), and glutamate-1-semialdehyde aminotransferase (GSAT). In Arabidopsis, ALA synthesis is the rate-limiting step in tetrapyrrole production via GluTR post-translational regulations. In rice, mutations of GluTR and GSAT homologs are known to confer chlorophyll deficiency phenotypes; however, the enzymatic activity of rice GluRS, GluTR, and GSAT and the post-translational regulation of rice GluTR have not been investigated experimentally. We have demonstrated that a suppressor mutation in rice partially reverts the xantha trait. In the present study, we first determine that the suppressor mutation results from a G → A nucleotide substitution of OsGluTR (and an A → V change of its 510th amino acid). Protein homology modeling and molecular docking show that the OsGluTRA510V mutation increases its substrate binding. We then demonstrate that the OsGluTRA510V mutation increases ALA synthesis in Escherichia coli without affecting its interaction with OsFLU. We further explore homologous genes encoding GluTR across 193 plant species and find that the amino acid (A) is 100% conserved at the position, suggesting its critical role in GluTR. Thus, we demonstrate that the gain-of-function OsGluTRA510V mutation underlies suppression of the xantha trait, experimentally proves the enzymatic activity of rice GluRS, GluTR, and GSAT in ALA synthesis, and uncovers conservation of the alanine corresponding to the 510th amino acid of OsGluTR across plant species.

A meta-analysis of combined generic-covered stent-graft with or without bare-metal stent for refractory variceal bleeding.

Objectives: The meta-analysis was conducted to systematically assess the efficacy and safety of generic stent-graft/bare-stent combination compared with Fluency stent alone in transjugular intrahepatic portosystemic shunt procedure for refractory variceal bleeding. Methods: PubMed, EMBASE, Scopus, Web of Science and the Cochrane Database were searched for relevant studies from January 1990 to September 2020; outcome measures studied were primary patency, hepatic encephalopathy, survival, re-bleeding and portal venous pressure. Results: Four studies (1 randomised controlled trial and 3 retrospective studies) with 449 subjects (157 patients in the combined stent group and 292 patients in the covered stent group) were included. No significant difference was observed in the incidence of mortality (hazard ratio [HR] = 1.069, 95% confidence interval [CI] [0.524, 2.178]), hepatic encephalopathy (odds ratio [OR] = 0.860, 95% CI [0.341, 2.169], P = 0.750) and re-bleeding (OR = 1.049, 95% CI [0.226, 4.881], P = 0.951). Compared with Fluency stent alone, combination therapy was associated with moderate decrease in outcomes on the post-operative portal venous pressure (standard mean difference [SMD] -0.210, 95% CI [-0.418, -0.001], P = 0.049) and was not associated with significant decrease in outcomes on the pre-operative portal venous pressure (SMD - 0.129, 95% CI [-0.336, 0.078], P = 0.223). The primary patency was significantly lower in the Fluency/bare-stent combination group (HR = 0.473, 95% CI [0.288, 0.776]). Conclusions: Generic stent-graft/bare-stent combination therapy was associated with significantly lower primary patency compared to Fluency stent alone.

OsFTIP1-Mediated Regulation of Florigen Transport in Rice Is Negatively Regulated by the Ubiquitin-Like Domain Kinase OsUbDKγ4.

Flowering time is a critical agronomic trait that determines successful seed production and adaptation of crop plants. Photoperiodic control of this process in flowering plants is mediated by the long-distance mobile signal called florigen partly encoded by FLOWERING LOCUS T (FT) in Arabidopsis thaliana and its orthologs in other plant species. Despite the progress in understanding FT transport in the dicot model Arabidopsis, the mechanisms of florigen transport in monocots, which provide most of the biomass in agriculture, are unknown. Here, we show that rice FT-INTERACTING PROTEIN1 (OsFTIP1), a member of the family of multiple C2 domain and transmembrane region proteins (MCTPs) and the closest ortholog of Arabidopsis FTIP1, is required for export of RICE FLOWERING LOCUS T 1 (RFT1) from companion cells to sieve elements. This affects RFT1 movement to the shoot apical meristem and its regulation of rice flowering time under long days. We further reveal that a ubiquitin-like domain kinase γ4, OsUbDKγ4, interacts with OsFTIP1 and modulates its degradation in leaves through the 26S proteasome, which in turn affects RFT1 transport to the shoot apical meristem. Thus, dynamic modulation of OsFTIP1 abundance in leaves by a negative regulator OsUbDKγ4 is integral to the role of OsFTIP1 in mediating RFT1 transport in rice and provides key evidence for a conserved role of FTIP1-like MCTPs in mediating florigen transport in flowering plants.

DOFT and DOFTIP1 affect reproductive development in the orchid Dendrobium Chao Praya Smile.

FLOWERING LOCUS T (FT) in Arabidopsis encodes the florigen that moves from leaves to the shoot apical meristem to induce flowering, and this is partly mediated by FT-INTERACTING PROTEIN 1 (FTIP1). Although FT orthologs have been identified in some flowering plants, their endogenous roles in Orchidaceae, which is one of the largest families of flowering plants, are still largely unknown. In this study, we show that DOFT and DOFTIP1, the orchid orthologs of FT and FTIP1, respectively, play important roles in promoting flowering in the orchid Dendrobium Chao Praya Smile. Expression of DOFT and DOFTIP1 increases in whole plantlets during the transition from vegetative to reproductive development. Both transcripts are present in significant levels in reproductive organs, including inflorescence apices, stems, floral buds, and open flowers. Through successful generation of transgenic orchids, we have revealed that overexpression or down-regulation of DOFT accelerates or delays flowering, respectively, while alteration of DOFT expression also greatly affects pseudobulb formation and flower development. In common with their counterparts in Arabidopsis and rice, DOFTIP1 interacts with DOFT and affects flowering time in orchids. Our results suggest that while DOFT and DOFTIP1 play evolutionarily conserved roles in promoting flowering, DOFT may have evolved with hitherto unknown functions pertaining to the regulation of storage organs and flower development in the Orchidaceae family.

A Triterpene-Based bioactive drug delivery system for combined chemotherapy of liver cancer.

Carrier materials always account for the majority particularly in nanosized formulations, which are administrated along with the active ingredient part might result in metabolism related toxicity. The usage of bioactive excipients could not only reduce the sided effect but also provide additional therapeutic effects. In the present study, a triterpene based micellar drug delivery system was developed using a bioactive solanesol derivative. Solanesylamine was prepared firstly followed by conjugating with poly (ethylene glycol) using maleic acid amide linkage. The amphiphilic drug carrier PEGylated (2-propyl-3-methylmaleic acid)-block-solanesol amine (mPEG-CDM-NH-SOL) could be formed into micelles and loaded with doxorubicin (DOX) inside. The micelles were about 112 nm in size and the drug loading content was about 5.97 wt%. An acid triggered drug release behavior was obviously observed for the DOX loaded pH-sensitive micelle mPEG-CDM-NH-SOL-DOX. While not for DOX-loaded micelles without pH-sensitivity (mPEG-NHS-NH-SOL). CCK8 assay showed that the micelles of PEGylated solanesylamines exhibited certain inhibitory effect on tumor cells at high concentration and the pH sensitive ones seemed more toxic. In vivo studies showed that the pH sensitive mPEG-CDM-NH-SOL-DOX had a superior anti-tumor effect, indicating its great potential in cancer treatment.

Mitigating growth-stress tradeoffs via elevated TOR signaling in rice.

Rice production accounts for approximately half of the freshwater resources utilized in agriculture, resulting in greenhouse gas emissions such as methane (CH4) from flooded paddy fields. To address this challenge, environmentally friendly and cost-effective water-saving techniques have become widely adopted in rice cultivation. However, the implementation of water-saving treatments (WSTs) in paddy-field rice has been associated with a substantial yield loss of up to 50% as well as a reduction in nitrogen use efficiency (NUE). In this study, we discovered that the target of rapamycin (TOR) signaling pathway is compromised in rice under WST. Polysome profiling-coupled transcriptome sequencing (polysome-seq) analysis unveiled a substantial reduction in global translation in response to WST associated with the downregulation of TOR activity. Molecular, biochemical, and genetic analyses revealed new insights into the impact of the positive TOR-S6K-RPS6 and negative TOR-MAF1 modules on translation repression under WST. Intriguingly, ammonium exhibited a greater ability to alleviate growth constraints under WST by enhancing TOR signaling, which simultaneously promoted uptake and utilization of ammonium and nitrogen allocation. We further demonstrated that TOR modulates the ammonium transporter AMT1;1 as well as the amino acid permease APP1 and dipeptide transporter NPF7.3 at the translational level through the 5' untranslated region. Collectively, these findings reveal that enhancing TOR signaling could mitigate rice yield penalty due to WST by regulating the processes involved in protein synthesis and NUE. Our study will contribute to the breeding of new rice varieties with increased water and fertilizer utilization efficiency.

Nanosized Assemblies from Amphiphilic Solanesol Derivatives for Anticancer Drug Delivery.

Unexpected functionalities of pharmaceutical excipients have been found in some cases. Preplanned introduction of excipients with therapeutic effects might not only reduce the risks of metabolism-related toxicity but also provide synergistic therapeutic effects. Herein, natural original solanesol (SOL), one of the isoprene compounds with some pharmacological activities, was selected to prepare a series of amphiphilic derivatives by chemical modification, and drug delivery systems for oncotherapy were established. Three derivatives, including solanesyl bromide (SOL-Br), monosolanesolsolanesyl succinate (MSS), and solanesylthiosalicylate (STS), were synthesized and formulated into nanosized self-assemblies for doxorubicin (DOX) encapsulation. Meanwhile, polyethylene glycol (PEG) derivatives were synthesized as the stabilizer of solanesol-based self-assemblies, among which hydrazine-poly(ethylene glycol)-hydrazine (PEG6000-DiHZ) was found to be more reliable. The optimized molar ratio between PEG6000-DiHZ and solanesol derivatives was found to be 2:1, considering the drug-loading capacity of self-assemblies. Consistent release profiles were found for the DOX-loaded self-assemblies, in which about 75-80% DOX was cumulatively released within 60 h at pH 5.0. The three DOX-loaded self-assemblies were found to be homogeneous spheres with average particle sizes in the range of 100-200 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Blank self-assemblies were found to have an inhibiting ability toward MCF-7 and HepG-2 cancer cells, which might originate from the inherent nature of solanesol derivatives. In vivo pharmacodynamic experiments demonstrated that blank self-assemblies had certain inhibitory effect on tumor growth compared with the controls. Further enhanced effects were also found for the drug-loaded self-assemblies due to the synergistic anti-tumor effect existing between the drug and the carriers. This work has presented a simple and effective strategy to prepare a therapeutic carrier by direct assembling of the therapeutic compound without PEGylation steps, by which the therapeutic carrier materials could take their effect directly and synergistically along with the loaded drugs.

Quercetin inclusion complex gels ameliorate radiation-induced brain injury by regulating gut microbiota.

Radiation-induced brain injury (RIBI) is a serious adverse effect of radiotherapy. RIBI has garnered considerable clinical attention owing to its powerful effects on brain function and cognition; however, no effective treatment is available. The microbiota-gut-brain axis theory is a novel concept of treating RIBI by regulating gut microbiota. Quercetin, a particularly common flavonoid compound, has a wide range of biological activities and can regulate gut microbiota; however, it has poor solubility and dispersibility. In the present study, oral gels of inclusion complex comprising quercetin and HP-ß-CD were prepared, which increased quercetin dispersion and extended its release time in the intestinal tract. First, the relative abundance and diversity of gut microbiota in RIBI mice changed after oral administration of quercetin inclusion complex gels (QICG). Second, the spontaneous activity behavior and short-term memory ability as well as anxiety level were improved. Third, changes in physical symptoms were observed, including a decrease in TNF-α and IL-6 levels. H&E staining revealed that gut epithelial injury and intestinal inflammation as well as hippocampal inflammation were ameliorated. Antibiotics treatment (Abx) mice were developed to disrupt the mice's original gut microbiota composition. No significant improvement was observed in behavior or histopathology after oral administration of QICG in Abx mice of RIBI, indicating that the effect of QICG on improving RIBI was regulated by intestinal microbiota. Finally, the QICG preparation is efficient, exerting a protective effect on RIBI by regulating gut microbiota via the microbiota-gut-brain axis, which provides a novel idea for RIBI treatment.

The OsbHLH002/OsICE1-OSH1 module orchestrates secondary cell wall formation in rice.

Transcriptional regulation of secondary cell wall (SCW) formation is strictly controlled by a complex network of transcription factors in vascular plants and has been shown to be mediated by a group of NAC master switches. In this study, we show that in a bHLH transcription factor, OsbHLH002/OsICE1, its loss-of-function mutant displays a lodging phenotype. Further results show that OsbHLH002 and Oryza sativa homeobox1 (OSH1) interact and share a set of common targets. In addition, the DELLA protein SLENDER RICE1, rice ortholog of KNOTTED ARABIDOPSIS THALIANA7, and OsNAC31 interact with OsbHLH002 and OSH1 and regulate their binding capacity on OsMYB61, a key regulatory factor in SCW development. Collectively, our results indicate OsbHLH002 and OSH1 as key regulators in SCW formation and shed light on molecular mechanisms of how active and repressive factors precisely orchestrate SCW synthesis in rice, which may provide a strategy for manipulating plant biomass production.

A rice F-box gene, OsFbx352, is involved in glucose-delayed seed germination in rice.

F-box proteins play diverse roles in regulating numerous physiological processes in plants. This study isolated a gene (OsFbx352) from rice encoding an F-box domain protein and characterized its role in seed germination. Expression of OsFbx352 was upregulated by abscisic acid (ABA). The transcripts of OsFbx352 were increased upon imbibition of rice seeds and the increase was markedly suppressed by glucose. Germination of seeds with overexpression of OsFbx352 was less suppressed by glucose than that of wild-type seeds, while glucose had greater inhibition for germination of seeds with knockdown of OsFbx352 by RNA interference (RNAi) than that of wild-type seeds. The differential response of germination of the transgenic and wild-type seeds to glucose may be accounted for by differences in ABA content among overexpressing, RNAi, and wild-type seeds such that overexpression of OsFbx352 and knockdown of OsFbx352 led to lower and higher ABA contents, respectively, than that of wild-type seeds in the presence of glucose. Overexpression of OsFbx352 led to a reduction in expression of genes responsible for ABA synthesis (OsNced2, OsNced3) and an increase in expression of genes encoding ABA catabolism (OsAba-ox2, OsAba-ox3) in the presence of glucose. These findings indicate that OsFbx352 plays a regulatory role in the regulation of glucose-induced suppression of seed germination by targeting ABA metabolism.

Rapid and Low-Cost Detection of Millet Quality by Miniature Near-Infrared Spectroscopy and Iteratively Retaining Informative Variables.

Traditional chemical methods for testing the fat content of millet, a widely consumed grain, are time-consuming and costly. In this study, we developed a low-cost and rapid method for fat detection and quantification in millet. A miniature NIR spectrometer connected to a smartphone was used to collect spectral data from millet samples of different origins. The standard normal variate (SNV) and first derivative (1D) methods were used to preprocess spectral signals. Variable selection methods, including bootstrapping soft shrinkage (BOSS), the variable iterative space shrinkage approach (VISSA), iteratively retaining informative variables (IRIV), iteratively variable subset optimization (IVSO), and competitive adaptive reweighted sampling (CARS), were used to select characteristic wavelengths. The partial least squares regression (PLSR) algorithm was employed to develop the regression models aimed at predicting the fat content in millet. The results showed that the proposed 1D-IRIV-PLSR model achieved optimal accuracy for fat detection, with a correlation coefficient for prediction (Rp) of 0.953, a root mean square error for prediction (RMSEP) of 0.301 g/100 g, and a residual predictive deviation (RPD) of 3.225, by using only 18 characteristic wavelengths. This result highlights the feasibility of using this low-cost and high-portability assessment tool for millet quality testing, which provides an optional solution for in situ inspection of millet quality in different scenarios, such as production lines or sales stores.

Nanoparticle-Containing Hyaluronate Solution for Improved Lubrication of Orthopedic Ceramics.

Premature failure caused by inadequate lubrication of an artificial joint is a major problem. Inspired by engine lubrication, in which various additives are used to enforce the oil lubricant, here, a bench test of a biomimetic lubricating fluid containing different substances was carried out. Bovine serum albumin (BSA), in the form of both molecules and nanoparticles, was used as a functional additive. Compared with BSA molecules, BSA nanoparticles dispersed in HA solution served as more effective additives in the biomimetic lubrication fluid to minimize the friction and wear of ceramic orthopedic materials made of zirconium dioxide (ZrO2). Meanwhile, a tribo-acoustic study indicated that the "squeaking" problem associated with ZrO2 could be suppressed by the biomimetic fluid. Together with a cytotoxicity assessment, the BSA nanoparticle-incorporated biomimetic fluid was confirmed as a potential reagent for use in the clinic to maintain an even longer service life of artificial joints.

Therapeutic carrier based on solanesol and hyaluronate for synergistic tumor treatment.

The administration of nanodrugs can lead to metabolism related systemic toxicity due to the use of inert carriers in large quantities. Carrier materials that offer therapeutic effects are therefore a promising means of addressing this limitation. Herein, a hyaluronate-based nanocarrier was prepared from hyaluronic acid (HA) and solanesol. Solanesyl thiosalicylate (STS) derived from solanesol has certain antitumor effects and was used to modify HA. The conjugate (HA-STS) self-assembled into nanoparticles acting as a drug carrier. The synthesis of the conjugates was confirmed by 1H NMR spectroscopy. Doxorubicin (DOX) was loaded into the HA-STS nanoparticles with a relatively high content of 6.0%. pH-sensitive drug release behavior was achieved by introducing a hydroazone bond between STS and HA. A cytotoxicity assay indicated that the blank nanoparticles had an antitumor effect, which was enhanced by loading with an additional drug. Moreover, in vivo antitumor experiments indicated that the HA-STS-DOX showed superior tumor inhibition compared with free DOX, as well as lower cardiotoxicity and hepatotoxicity, demonstrating the advantages of the bioactive drug vehicles in cancer therapy.

The OsFTIP6-OsHB22-OsMYBR57 module regulates drought response in rice.

Plants have evolved a sophisticated set of mechanisms to adapt to drought stress. Transcription factors play crucial roles in plant responses to various environmental stimuli by modulating the expression of numerous stress-responsive genes. However, how the crosstalk between different transcription factor families orchestrates initiation of the key transcriptional network and the role of posttranscriptional modification of transcription factors, especially in cellular localization/trafficking in response to stress in rice, remain still largely unknown. In this study, we isolated an Osmybr57 mutant that displays a drought-sensitive phenotype through a genetic screen for drought stress sensitivity. We found that OsMYBR57, an MYB-related protein, directly regulates the expression of several key drought-related OsbZIPs in response to drought treatment. Further studies revealed that OsMYBR57 interacts with a homeodomain transcription factor, OsHB22, which also plays a positive role in drought signaling. We further demonstrate that OsFTIP6 interacts with OsHB22 and promotes the nucleocytoplasmic translocation of OsHB22 into the nucleus, where OsHB22 cooperates with OsMYBR57 to regulate the expression of drought-responsive genes. Our findings have revealed a mechanistic framework underlying the OsFTIP6-OsHB22-OsMYBR57 module-mediated regulation of drought response in rice. The OsFTIP6-mediated OsHB22 nucleocytoplasmic shuttling and OsMYBR57-OsHB22 regulation of OsbZIP transcription ensure precise control of expression of OsLEA3 and Rab21, and thereby regulate the response to water deficiency in rice.

Physiological mechanisms underlying OsNAC5-dependent tolerance of rice plants to abiotic stress.

To understand the functions of transcription factor OsNAC5 in response to abiotic stress, we generated transgenic rice plants with knockdown OsNAC5 by RNA-interfered (RNAi) and overexpressing OsNAC5, and investigated the effects of cold, drought and salt stress on wild-type (WT), RNAi and overexpression rice lines. Our results demonstrated that RNAi lines became less tolerant to these stresses than WT plants, while overexpression of OsNAC5 in Arabidopsis and rice enhanced tolerance to these stresses. The mechanisms underlying the changes in tolerance of the transgenic rice plants to abiotic stresses were explored by measuring free proline (Pro) and soluble sugar contents in WT and transgenic plants. Accumulation of Pro and soluble sugars was positively correlated with OsNAC5 expression levels. The less accumulation of Pro in RNAi lines may be accounted for by inhibition of Pro synthesis and transport at transcriptional levels. In addition, knockdown and overexpression of OsNAC5 enhanced and reduced accumulation of malondialdehyde and H(2)O(2), suggesting that knockdown of OsNAC5 renders RNAi plants more susceptible to oxidative damage. The RNAi lines displayed higher Na(+)/K(+) ratio due to greater accumulation of Na(+) ions than WT under salt stress conditions, and expression of genes encoding tonoplast Na(+)/H(+) antiporter was lower in RNAi lines than in WT under both control and salt-stressed conditions. Seed germination of RNAi and overexpression plants was more and less inhibited by salt and mannitol than that of WT, respectively. Seed germination of overexpression and RNAi plants was more and less sensitive than that of WT to ABA. These findings highlight the important role of OsNAC5 played in the tolerance of rice plants to abiotic stress by regulating downstream targets associated with accumulation of compatible solutes, Na(+) ions, H(2)O(2) and malondialdehyde.