CIP1, a CIPK23-interacting transporter, is implicated in Cd tolerance and phytoremediation.

Environmental pollution from cadmium (Cd) presents a serious threat to plant growth and development. Therefore, it's crucial to find out how plants resist this toxic metal to develop strategies for remediating Cd-contaminated soils. In this study, we identified CIP1, a transporter protein, by screening interactors of the protein kinase CIPK23. CIP1 is located in vesicles membranes and can transport Cd2+ when expressed in yeast cells. Cd stress specifically induced the accumulation of CIP1 transcripts and functional proteins, particularly in the epidermal cells of the root tip. CIKP23 could interact directly with the central loop region of CIP1, phosphorylating it, which is essential for the efficient transport of Cd2+. A loss-of-function mutation of CIP1 in wild-type plants led to increased sensitivity to Cd stress. Conversely, tobacco plants overexpressing CIP1 exhibited improved Cd tolerance and increased Cd accumulation capacity. Interestingly, this Cd accumulation was restricted to roots but not shoots, suggesting that manipulating CIP1 does not risk Cd contamination of plants' edible parts. Overall, this study characterizes a novel Cd transporter, CIP1, with potential to enhance plant tolerance to Cd toxicity while effectively eliminating environmental contamination without economic losses.

Dual-stimulus phototherapeutic nanogel for triggering pyroptosis to promote cancer immunotherapy.

Pyroptosis is a highly inflammatory programmed cell death that activates inflammatory response, reverses immunosuppression and promotes systemic immune response for solid tumors treatment. However, the uncontrollable and imprecise process of pyroptosis stimulation leads to a scanty therapeutic effect. Here, we report a GSH/ROS dual response nanogel system (IMs) that can actively target the overexpressed mannose receptor (MR) of cancer cells, serve ultra-stable photothermal capacity of indocyanine green (ICG), induce cell pyroptosis and achieve enhanced tumor immune response. Photo-triggered IMs induce cytoplasmic Ca2+ introgression and activate caspase-3 through photo-activated ICG. The disconnect of SeSe bonds can break the oxidation and reduction balance of tumor cells, causing oxidative stress and synergistically enhancing caspase-3 cleavage, and regulating cell pyroptosis ultimately. Combined with anti-programmed death receptor 1 (anti-PD-1), the nanogel system not only effectivly suppress both primary tumor and distance tumor but also prolong the survival period of mice. This work introduces a strategy to optimize the photothermal performance of ICG and enhances tumor immune response mediated by triggering pyroptosis, which provides an impressive option for immune checkpoint blockade therapy.

Reduction-triggered polycyclodextrin supramolecular nanocage induces immunogenic cell death for improved chemotherapy.

Polycyclodextrin-based supramolecular nanoplatform crosslinked by stimuli-responsive moiety shows great promise in cancer therapy owing to its superior bio-stability and feasible modification of architectures. Here, the endogenous glutathione (GSH)-responsive polycyclodextrin supramolecular nanocages (PDOP NCs) are constructed by covalent crosslinking of multiple ß-cyclodextrin (ß-CD) molecules. The polycyclodextrin provide sites for conjugation of chemotherapeutic doxorubicin (DOX). Meanwhile, the PDOP NCs are stabilized by multiple interactions including host-guest interaction between DOX and ß-CD and hydrogen bonds between ß-CD units. The supramolecular crosslinked structure endowed the nanocage with high stability and drug loading capacity. Tons of GSH-sensitive disulfide linkages in PDOP NCs were broken at tumor cells, promoting tumor-specific DOX release. Besides, the redox equilibrium in tumor microenvironment could be disturbed due to GSH depletion, which further sensitized the DOX effects and alleviated drug resistance, facilitating inducing immunogenic cell death effect for enhanced chemotherapy, thereby achieving efficient tumor suppression and prolonged survival. Thus, the versatile polycyclodextrin-based supramolecular nanocage provides a novel and efficient drug delivery strategy for cancer treatment.

Diselenide-Based Dual-Responsive Prodrug as Pyroptosis Inducer Potentiates Cancer Immunotherapy.

Pyroptosis is demonstrated to trigger antitumor immunity and represents a promising new strategy to potentiate cancer immunotherapy. The number of potent pyroptosis inducers, however, is limited and without tumor-targeting capability, which inevitably causes damage in normal tissues. Herein, a small molecular prodrug of paclitaxel-oxaliplatin is rationally synthesized, which can be covalently self-assembled with diselenide-containing cross-linking (Dse11), producing a diselenide nanoprodrug (DSe@POC) to induce pyroptosis for the first time. The diselenide bonds within DSe@POC can be split by high glutathione in the tumor microenvironment (TME) and reactive oxygen species induced by photodynamic therapy, thus possessing excellent TME on-target effects. Additionally, DSe@POC is able to elicit intense pyroptosis to remodel the immunostimulated TME and trigger a robust immune response. Furthermore, combined αPD-1 therapy effectively inhibits the growth of remote tumors through the abscopal effect, amplifies a long-term immune memory response to reject rechallenged tumors, and prolongs survival. Collectively, DSe@POC, as the first TME dual-responsive diselenide-based pyroptosis inducer, will open up an attractive approach for cancer immunotherapy.

A Dual-Responsive STAT3 Inhibitor Nanoprodrug Combined with Oncolytic Virus Elicits Synergistic Antitumor Immune Responses by Igniting Pyroptosis.

Immune checkpoint blockade (ICB) therapy shows excellent efficacy against malignancies; however, insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (TME) are considered as the two major stumbling blocks to a broad ICB response. Here, a combinational therapeutic strategy is reported, wherein TME-reactive oxygen species/pH dual-responsive signal transducers and activators of transcription 3 inhibitor nanoprodrugs MPNPs are combined with oncolytic herpes simplex virus 1 virotherapy to synergistically ignite pyroptosis for enhancing immunotherapy. MPNPs exhibit a certain level of tumor accumulation, reduce tumor cell stemness, and enhance antitumor immune responses. Furthermore, the simultaneous application of oncolytic viruses (OVs) confers MPNPs with higher tumor penetration capacity and remarkable gasdermin-E-mediated pyroptosis, thereby reshaping the TME and transforming "cold" tumors into "hot" ones. This "fire of immunity" strategy successfully activates robust T-cell-dependent antitumor responses, potentiating ICB effects against local recurrence and pulmonary metastasis in preclinical "cold" murine triple-negative breast cancer and syngeneic oral cancer models. Collectively, this work may pave a new way and offer an unprecedented opportunity for the combination of OVs with nanomedicine for cancer immunotherapy.

Ubiquitin-Specific Protease 2 (OsUBP2) Negatively Regulates Cell Death and Disease Resistance in Rice.

Lesion mimic mutants (LMMs) are great materials for studying programmed cell death and immune mechanisms in plants. Various mechanisms are involved in the phenotypes of different LMMs, but few studies have explored the mechanisms linking deubiquitination and LMMs in rice (Oryza sativa). Here, we identified a rice LMM, rust spots rice (rsr1), resulting from the mutation of a single recessive gene. This LMM has spontaneous reddish-brown spots on its leaves, and displays enhanced resistance to both fungal leaf blast (caused by Magnaporthe oryzae) and bacterial blight (caused by Xanthomonas oryzae pv. oryzae). Map-based cloning showed that the mutated gene in rsr1 encodes a Ubiquitin-Specific Protease 2 (OsUBP2). The mutation of OsUBP2 was shown to result in reactive oxygen species (ROS) accumulation, chloroplast structural defects, and programmed cell death, while the overexpression of OsUBP2 weakened rice resistance to leaf blast. OsUBP2 is therefore a negative regulator of immune processes and ROS production. OsUBP2 has deubiquitinating enzyme activity in vitro, and the enzyme active site includes a cysteine at the 234th residue. The ubiquitinated proteomics data of rsr1 and WT provide some possible target protein candidates for OsUBP2.

Immunomodulatory-Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy.

Cancer immunotherapy is restricted to immune resistance caused by immunosuppressive tumor microenvironment. Pyroptosis involved in antitumor immunotherapy as a new schedule is prospective to reverse immunosuppression. Herein, acidic tumor microenvironment (TME)-evoked MRC nanoparticles (MRC NPs) co-delivering immune agonist RGX-104 and photosensitizer chlorine e6 (Ce6) are reported for pyroptosis-mediated immunotherapy. RGX-104 remodels TME by transcriptional activation of ApoE to regress myeloid-derived suppressor cells' (MDSCs) activity, which neatly creates foreshadowing for intensifying pyroptosis. Considering Ce6-triggered photodynamic therapy (PDT) can strengthen oxidative stress and organelles destruction to increase immunogenicity, immunomodulatory-photodynamic MRC nanodrugs will implement an aforementioned two-pronged strategy to enhance gasdermin E (GSDME)-dependent pyroptosis. RNA-seq analysis of MRC at the cellular level is introduced to first elucidate the intimate relationship between RGX-104 acting on LXR/ApoE axis and pyroptosis, where RGX-104 provides the prerequisite for pyroptosis participating in antitumor therapy. Briefly, MRC with favorable biocompatibility tackles the obstacle of hydrophobic drugs delivery, and becomes a powerful pyroptosis inducer to reinforce immune efficacy. MRC-elicited pyroptosis in combination with anti-PD-1 blockade therapy boosts immune response in solid tumors, successfully arresting invasive metastasis and extending survival based on remarkable antitumor immunity. MRC may initiate a new window for immuno-photo pyroptosis stimulators augmenting pyroptosis-based immunotherapy.

Sustained release of chlorogenic acid-loaded nanomicelles alleviates bone loss in mouse periodontitis.

Periodontitis is a prevalent chronic inflammatory disease that destroys the periodontal supporting tissues, impinges on oral health, and is correlated with an increased risk of systemic disease. Currently, the main drug treatment is antibiotic therapy; however, systemic antibiotic therapy still has various drawbacks such as bacterial resistance, low bioavailability and burst release. It is noteworthy that the local use of non-antibiotic drugs with sustained release characteristics can effectively overcome these problems. It has been documented that chlorogenic acid (CGA) has good anti-inflammatory and antioxidant properties. To achieve the sustained release of CGA, we synthesized CGA-PLGA@PVP nanomicelles by loading CGA onto poly(D,L-lactide-co-glycolide) (PLGA) and modified them with polyvinylpyrrolidone (PVP) for better dispersion. The results demonstrated that CGA-PLGA@PVP nanomicelles could prolong the release time of CGA, and could not only effectively remove reactive oxygen species (ROS) but also downregulate the overexpression of proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW264.7 cells. Moreover, CGA-PLGA@PVP nanomicelles could remain in gingival tissue for more than 24 hours after local injection, inhibit alveolar bone resorption and prevent the progression of periodontitis in a mouse model, showing good biocompatibility. Therefore, CGA-PLGA@PVP nanomicelles have great properties and are expected to be a novel therapeutic strategy for periodontitis.

The miR157-SPL-CNR module acts upstream of bHLH101 to negatively regulate iron deficiency responses in tomato.

Iron (Fe) homeostasis is critical for plant growth, development, and stress responses. Fe levels are tightly controlled by intricate regulatory networks in which transcription factors (TFs) play a central role. A series of basic helix-loop-helix (bHLH) TFs have been shown to contribute to Fe homeostasis, but the regulatory layers beyond bHLH TFs remain largely unclear. Here, we demonstrate that the SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) TF SlSPL-CNR negatively regulates Fe-deficiency responses in tomato (Solanum lycopersicum) roots. Fe deficiency rapidly repressed the expression of SlSPL-CNR, and Fe deficiency responses were intensified in two clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9-generated SlSPL-CNR knock-out lines compared to the wild-type. Comparative transcriptome analysis identified 47 Fe deficiency-responsive genes the expression of which is negatively regulated by SlSPL-CNR, one of which, SlbHLH101, helps regulate Fe uptake genes. SlSPL-CNR localizes the nucleus and interacts with the GTAC and BOX 4 (ATTAAT) motifs in the SlbHLH101 promoter to repress its expression. Inhibition of SlSPL-CNR expression in response to Fe deficiency was well correlated with the expression of the microRNA SlymiR157. SlymiR157-overexpressing tomato lines displayed enhanced Fe deficiency responses, as did SlSPL-CNR loss-of-function mutants. We propose that the SlymiR157-SlSPL-CNR module represents a novel pathway that acts upstream of SlbHLH101 to regulate Fe homeostasis in tomato roots.

Light-responsive hyaluronic acid nanomicelles co-loaded with an IDO inhibitor focus targeted photoimmunotherapy against "immune cold" cancer.

Nanomedicine enabled cancer combination immunotherapy not only sufficiently activates the host immune system, but also reprograms the immunosuppressive microenvironment, representing a new generation approach to treat cancer. Herein, we demonstrated a targeted photo- and immune-active nanoplatform termed NLG919@HA-Ce6 to simultaneously elicit efficient immunogenic cell death (ICD) using the photosensitizer Ce6 and modulate the tryptophan metabolic pathway using an indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919 for the combined photodynamic therapy (PDT) and checkpoint blockade immunotherapy. Against the triple-negative and poorly immunogenic 4T1 breast cancer model, the stable spherical nanomicelle NLG919@HA-Ce6 selectively killed tumour cells via the toxic singlet oxygen upon laser excitation, thus in situ triggering a potent antitumor immune response, as seen via the obvious CRT exposure, ATP release, dendritic cell maturation, etc. Meanwhile, the IDO1-mediated immunosuppression was effectively reprogrammed to an immunostimulatory phenotype, which was accompanied by an enhanced cytotoxic T cell response as well as reduced Treg infiltration in tumour bed. Ultimately, the 4T1 tumour was synergistically suppressed by NLG919@HA-Ce6 due to the outcome of focused PDT, obvious ICD post PDT and IDO1 blockade. This study suggests the promise of NLG919@HA-Ce6 as an alternative simple, stimulative and targeted nanoagent to enable the whole-body photo-immune therapy against "immune cold" cancer.

Acid-Sensitive Supramolecular Nanoassemblies with Multivalent Interaction: Effective Tumor Retention and Deep Intratumor Infiltration.

It remains a conundrum to reconcile the contradiction between effective tumor retention and deep intratumor infiltration for nanotherapeutics due to the sophisticated drug delivery journey. Herein, we reported an acid-sensitive supramolecular nanoassemblies (DCD SNs) based on the multivalent host-gest inclusions of two polymer conjugates for conquering diverse physiological blockages and amplifying therapeutic efficacy. The multiple inclusions of repetitive units on the hydrophilic polymer backbone reinforced the binding affinity and induced robust self-assembly, ameliorating instability of the self-assemblies and facilitating to prolong the drug retention time. By virtue of the acid-sensitive Schiff base linkages, the supramolecular nanoassembly could respond to the unique tumor microenvironment (TME), dissociate, and transform into smaller particles (∼30 nm), thereby efficiently traversing the complicated extracellular matrix and irregular blood vessels to achieve deep intratumor infiltration. The acid-sensitive DCD SNs can absorb a large number of protons in the acidic lysosomal environment, causing the proton sponge effect, which was conducive to their escape from endolysosomes and accelerated lysosomal disruption, so that the active chemotherapeutic doxorubicin (DOX) could enter the nucleus well and exert severe DNA damage to induce apoptosis. This versatile supramolecular nanoplatform is anticipated to be a promising candidate to overcome the limitations of insufficient stability within the circulation and weak intratumor penetration.

Knockdown of CYP24A1 Aggravates 1α,25(OH)2D3-Inhibited Migration and Invasion of Mouse Ovarian Epithelial Cells by Suppressing EMT.

Epithelial-mesenchymal transition (EMT) bestows cancer cells with motile and invasive properties. But for ovarian tissues, EMT plays a physiological role in the postovulatory repair of ovary surface epithelial (OSE) cells. Accumulating data indicated that 1α,25(OH)2D3 decreased both the migration and invasion of various cancer cells by suppressing EMT. However, it remains unclear whether 1α,25(OH)2D3 inhibits the process of EMT during different stages of oncogenic transformation in mouse OSE (MOSE) cells. In present study, a spontaneous malignant transformation model of MOSE cells at three sequential stages (early, intermediate and late) was established in vitro first and then subjected to 1α,25(OH)2D3 treatment to investigate the effect of 1α,25(OH)2D3 on the oncogenic transformation of MOSE cells. We found that 1α,25(OH)2D3 significantly reduced the proliferation and invasion of late malignant transformed MOSE (M-L cells) cells by inhibiting EMT both in vitro and in vivo, but not in intermediate transformed (M-I) cells. Importantly, we found that the levels of CYP24A1 in M-I cells were dramatically higher than that in M-L cells following treatment with 1α,25(OH)2D3. Furthermore, we demonstrated that, in both M-I and M-L cells with CYP24A1 knockdown, 1α,25(OH)2D3 suppressed the proliferation and invasion, and reduced the expression of N-cadherin, Vimentin, ß-catenin and Snail. In addition, knockdown of CYP24A1 suppressed EMT by increasing E-cadherin while decreasing N-cadherin, Vimentin, ß-catenin and Snail. These findings provide support for inhibiting CYP24A1 as a potential approach to activate the vitamin D pathway in the prevention and therapy of ovarian cancer.

Unchanged Pulmonary Function and Increased Prevalence of Subjective Respiratory Symptoms in Non-smoking Workers with Low Cadmium Body Burden.

The study investigated the effects of low cadmium (Cd) burden on the respiratory symptoms and pulmonary function in occupational workers. The study population consisted of 98 nickel-cadmium battery workers. Levels of urine cadmium, urinary creatinine (Cr), and data on the adverse respiratory symptoms and pulmonary function of the participants were measured and collected respectively. The urinary cadmium level in cadmium-exposed workers (n = 53) was within the normal range but greater than 2.4 times than those of the control group (n = 45). Compared with the control group, the cadmium-exposed workers had higher prevalence of all subjective respiratory symptoms studied in the study. The prevalence of cough (30%), phlegm (23%), and upper respiratory tract infection (URTI) (79%) in the exposure group was significantly (P < 0.05) higher than the prevalence of cough (11%), phlegm (7%), and URTI (31%) in the control group respectively. There was no significant difference between the Cd-exposed workers and control group in pulmonary function test. Our findings suggested that adverse subjective respiratory symptoms were increased and pulmonary function were unchanged in low Cd burden workers. Unchanged pulmonary function may be related to age, exposure duration, and distribution of Cd in tissue. These workers need to continue being monitored in longitudinal studies.

Acid-Triggered Charge-Convertible Graphene-Based All-in-One Nanocomplex for Enhanced Genetic Phototherapy of Triple-Negative Breast Cancer.

Highly efficient and stimulus-responsive nanomedicines for cancer treatment are currently receiving tremendous attention. In this study, an acid-triggered charge-reversible graphene-based all-in-one nanocomplex is appropriately designed by surface modification with multilayer polymers and simultaneous co-transportation of photosensitizer indocyanine green (ICG) and oligonucleotide inhibitor of miR-21 (miR-21i) to achieve highly efficient genetic phototherapy in a controlled manner. The nanocomplex (denoted as GPCP/miR-21i/ICG) effectively protects miR-21i from degradation and exhibits excellent photothermal/photochemical reactive oxygen species (ROS) generation as well as fluorescence imaging ability. The cargoes ICG and miR-21i can significantly be released at acidic pH compared with normal physiological medium and escaped from endosomes/lysosomes due to the acid-triggered charge reversal effect. Typically, the released miR-21i downregulate the endogenous miR-21 and result in the upregulation of the target proteins PTEN and Bax, thus increasing the phototherapeutic efficiency of ICG. High in vivo anticancer efficiency against the MDA-MB-231 triple-negative breast cancer (TNBC) model is obtained due to the combination of genetic regulation of miR-21i and the photokilling effect of ICG. This work highlights the great potential of this smart nanocomplex as an attractive modality of gene-photo combined treatment of cancer, especially for intractable TNBC.

Decreased Insulin Secretion but Unchanged Glucose Homeostasis in Cadmium-Exposed Male C57BL/6 Mice.

Cadmium (Cd) is a well-known toxic metal element that is largely distributed in the environment. Cd causes toxicity to most organs. Accumulating evidence suggests that Cd exposure is associated with islet dysfunction and development of diabetes, but the association remains controversial. The aim of this study is to evaluate the possible effects of chronic Cd exposure on glucose metabolism in male C57BL/6 mice. Mice were intraperitoneally injected with CdCl2 solution (1 mg.kg-1) twice a week for 24 weeks. Fasting blood glucose (FBG) levels and body weights were measured weekly. After 24 weeks, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), and fasting serum insulin (FSI) level test were performed. The insulin resistance index (HOMA-IR) and pancreatic ß cell function index (HOMA-ß) were calculated and analyzed. The expression of insulin receptor (IR) in mouse liver was detected by real-time PCR. Pancreatic tissue was collected for histological examination. The results demonstrated that FBG, IPGTT, HOMA-IR, and HOMA-ß were identical between Cd exposure and control mice. In contract, mean fasting serum insulin level, area under the curve (AUC) of IPITT, and IR expression in livers of Cd-exposed mice decreased significantly compared with control mice. Cd administration induced islet atrophy and decreased islet area. The results suggested that Cd exposure decreased insulin secretion and maintained glucose homeostasis in male C57BL/6 mice and that pancreatic functions should be monitored in populations chronically exposed to Cd.

Highly efficient cascading synergy of cancer photo-immunotherapy enabled by engineered graphene quantum dots/photosensitizer/CpG oligonucleotides hybrid nanotheranostics.

Currently, photoimmunotherapy based on a theranostic nanoplatform emerges as a promising modality in advanced cancer therapy. In this study, a new type of versatile nanoassemblies (denoted as PC@GCpD(Gd)) was rationally designed by integrating the polydopamine stabilized graphene quantum dots (GQD)-photosensitizer nanocomposites (denoted as GCpD), immunostimulatory polycationic polymer/CpG oligodeoxynucleotide (CpG ODN) nanoparticles (denoted as PC) and Gd3+/Cy3 imaging probes for dual magnetic resonance/fluorescence imaging-guided photoimmunotherapy. PC@GCpD(Gd) effectively killed the tumor cells through the amplified photothermal and photodynamic effects mediated by GCpD, and contemporaneously delivered CpG ODN to the targeted endosomal Toll-like receptor 9 (TLR9) to continuously stimulate the secretion of proinflammatory cytokines and the maturation of dendritic cells, thereby resulting in the activation and infiltration of T lymphocytes. As a result, PC@GCpD(Gd) achieved robust inhibition efficiency to almost completely suppress the EMT6 murine mammary cancer model under laser irradiation, implying the superior synergy of combined photoimmunotherapy. Moreover, the in vivo delivery and biodistribution of PC@GCpD(Gd) could be tracked using the high-quality bimodal magnetic resonance imaging/fluorescence imaging. This study highlighted the potent prospect of hybrid PC@GCpD(Gd) nanoassemblies for precise cancer photoimmunotherapy with a cascading effect.

AtHB2, a class II HD-ZIP protein, negatively regulates the expression of CsANS, which encodes a key enzyme in Camellia sinensis catechin biosynthesis.

Tea (Camellia sinensis) is an important cash crop that is beneficial to human health because of its remarkable content of catechins. The biosynthesis of catechins follows the flavonoid pathway, which is highly branched. Among the enzymes involved in catechin biosynthesis, ANTHOCYANIDIN SYNTHASE (CsANS) functions at a branch point and play a critical role. Our previous work has showed that the gene encoding CsANS is regulated by light signals; however, the molecular mechanism behind remains unclear. Here, we cloned a full-length CsANS promoter and found that it contained a cis-element recognized by Arabidopsis thaliana HOMEOBOX2 (AtHB2). AtHB2 constitutes one of the class II HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP) proteins, which accumulate in the dark and mediate the shade avoidance response in most angiosperms. To analyze the transcription of CsANS in vivo, ß-glucuronidase and luciferase reporter genes driven by the obtained promoter were introduced into A. thaliana and Nicotiana attenuata, respectively. In both expression systems there were indications that the A. thaliana PRODUCTION OF ANTHOCYANIN PIGMENT1 (AtPAP1), a MYB transcription factor of flavonoid biosynthesis, increased the activity of the CsANS promoter, while AtHB2 could significantly undermine the effect of AtPAP1. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that AtHB2 interacted with the A. thaliana TRANSPARENT TESTA GLABRA 1 (AtTTG1). A yeast three-hybrid assay further suggested that AtHB2 represses the expression of CsANS and regulates its response to light signals through competitive interactions with AtTTG1. These results show that HD-ZIP II proteins participate in light regulation of flavonoid biosynthesis.

[Relationship between Autophagy and Curcumin-induced Anticancer Effect].

Curcumin is a polyphenol extracted from turmeric rhizome and has multiple pharmacological roles. Recently,its anticancer properties have been recognized. Also,curcumin regulates autophagy in tumor cells via signaling pathways including AMP-activated protein kinase,mammalian target of rapamycin,transcription factor EB,Beclin-1,B-cell lymphoma 2,and endoplasmic reticulum stress. Considering the complicated crosstalk between autophagy and apoptosis,in this article we summaize the mechanism of curcumin-induced autophagy and its effect on apoptosis,with an attempt to provide insights on tumor therapy.

Effects of osmotic pressure and pH on citric acid and erythritol production from waste cooking oil by Yarrowia lipolytica.

Erythritol and citric acid could be produced from waste cooking oil (WCO) by Yarrowia lipolytica under different medium conditions, and osmotic pressure together with pH were considered to be the critical factors in this process. High osmotic pressure (2.76 osmol/L) combined with low pH (pH 3.0) promoted the highest yield of erythritol (21.8 g/L) accompanied by low-producing citric acid (2.5 g/L). By contrast, the highest citric acid biosynthesis (12.6 g/L) was detected under a pH of 6.0 and an osmotic pressure of 0.75 osmol/L, when only 4.0 g/L of erythritol was yielded. Moreover, lipase activities in these two media were also detected, and pH 3.0-OP 2.76 was supposed to be more beneficial to lipase activity. Biochemical pathways involved in the biosynthesis of erythritol and citric acid were subsequently investigated, and the products yielded from WCO were assumed to be correlated with the activities of transketolase, erythrose reductase, citrate synthase, and glycerol kinase. However, RT-PCR analysis revealed that mRNA levels of these enzymes did not significantly differ, confirming that metabolic flux regulations of erythritol and citric acid mostly took place at the post-transcriptional level.

OsCLT1, a CRT-like transporter 1, is required for glutathione homeostasis and arsenic tolerance in rice.

Arsenic (As) contamination in a paddy environment can cause phytotoxicity and elevated As accumulation in rice (Oryza sativa). The mechanism of As detoxification in rice is still poorly understood. We isolated an arsenate (As(V))-sensitive mutant of rice. Genomic resequencing and complementation identified OsCLT1, encoding a CRT-like transporter, as the causal gene for the mutant phenotype. OsCLT1 is localized to the envelope membrane of plastids. The glutathione and γ-glutamylcysteine contents in roots of Osclt1 and RNA interference lines were decreased markedly compared with the wild-type (WT). The concentrations of phytochelatin PC2 in Osclt1 roots were only 32% and 12% of that in WT after As(V) and As(III) treatments, respectively. OsCLT1 mutation resulted in lower As accumulation in roots but higher As accumulation in shoots when exposed to As(V). Under As(III) treatment, Osclt1 accumulated a lower As concentration in roots but similar As concentration in shoots to WT. Further analysis showed that the reduction of As(V) to As(III) was decreased in Osclt1. Osclt1 was also hypersensitive to cadmium (Cd). These results indicate that OsCLT1 plays an important role in glutathione homeostasis, probably by mediating the export of γ-glutamylcysteine and glutathione from plastids to the cytoplasm, which in turn affects As and Cd detoxification in rice.