Hydrogen peroxide sulfenylates and inhibits the photorespiratory enzyme PGLP1 to modulate plant thermotolerance.

Climate change is resulting in more frequent and rapidly changing temperatures at both extremes that severely affect the growth and production of plants, particularly crops. Oxidative stress caused by high temperatures is one of the most damaging factors for plants. However, the role of hydrogen peroxide (H2O2) in modulating plant thermotolerance is largely unknown, and the regulation of photorespiration essential for C3 species remains to be fully clarified. Here, we report that heat stress promotes H2O2 accumulation in chloroplasts and that H2O2 stimulates sulfenylation of the chloroplast-localized photorespiratory enzyme 2-phosphoglycolate phosphatase 1 (PGLP1) at cysteine 86, inhibiting its activity and promoting the accumulation of the toxic metabolite 2-phosphoglycolate. We also demonstrate that PGLP1 has a positive function in plant thermotolerance, as PGLP1 antisense lines have greater heat sensitivity and PGLP1-overexpressing plants have higher heat-stress tolerance than the wild type. Together, our results demonstrate that heat-induced H2O2 in chloroplasts sulfenylates and inhibits PGLP1 to modulate plant thermotolerance. Furthermore, targeting CATALASE2 to chloroplasts can largely prevent the heat-induced overaccumulation of H2O2 and the sulfenylation of PGLP1, thus conferring thermotolerance without a plant growth penalty. These findings reveal that heat-induced H2O2 in chloroplasts is important for heat-caused plant damage.

Proteome-wide identification of methylglyoxalated proteins in rapeseed (Brassica napus L.).

Methylglyoxal (MG), a highly reactive cellular metabolite, is crucial for plant growth and environmental responses. MG may function by modifying its target proteins, but little is known about MG-modified proteins in plants. Here, MG-modified proteins were pulled down by an antibody against methylglyoxalated proteins and detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. We identified 543 candidate proteins which are involved in multiple enzymatic activities and metabolic processes. A great number of candidate proteins were predicted to localize to cytoplasm, chloroplast, and nucleus, consistent with the known subcellular compartmentalization of MG. By further analyzing the raw LC-MS/MS data, we obtained 42 methylglyoxalated peptides in 35 proteins and identified 10 methylglyoxalated lysine residues in a myrosinase-binding protein (BnaC06G0061400ZS). In addition, we demonstrated that MG modifies the glycolate oxidase and ß-glucosidase to enhance and inhibit the enzymatic activity, respectively. Together, our study contributes to the investigation of the MG-modified proteins and their potential roles in rapeseed.

Pathogen-induced methylglyoxal negatively regulates rice bacterial blight resistance by inhibiting OsCDR1 protease activity.

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight (BB), a globally devastating disease of rice (Oryza sativa) that is responsible for significant crop loss. Sugars and sugar metabolites are important for pathogen infection, providing energy and regulating events associated with defense responses; however, the mechanisms by which they regulate such events in BB are unclear. As an inevitable sugar metabolite, methylglyoxal (MG) is involved in plant growth and responses to various abiotic stresses, but the underlying mechanisms remain enigmatic. Whether and how MG functions in plant biotic stress responses is almost completely unknown. Here, we report that the Xoo strain PXO99 induces OsWRKY62.1 to repress transcription of OsGLY II genes by directly binding to their promoters, resulting in overaccumulation of MG. MG negatively regulates rice resistance against PXO99: osglyII2 mutants with higher MG levels are more susceptible to the pathogen, whereas OsGLYII2-overexpressing plants with lower MG content show greater resistance than the wild type. Overexpression of OsGLYII2 to prevent excessive MG accumulation confers broad-spectrum resistance against the biotrophic bacterial pathogens Xoo and Xanthomonas oryzae pv. oryzicola and the necrotrophic fungal pathogen Rhizoctonia solani, which causes rice sheath blight. Further evidence shows that MG reduces rice resistance against PXO99 through CONSTITUTIVE DISEASE RESISTANCE 1 (OsCDR1). MG modifies the Arg97 residue of OsCDR1 to inhibit its aspartic protease activity, which is essential for OsCDR1-enhanced immunity. Taken together, these findings illustrate how Xoo promotes infection by hijacking a sugar metabolite in the host plant.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion: A case report.

BACKGROUND: Intestinal natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive non-Hodgkin's lymphoma, and its occurrence is closely related to Epstein-Barr virus infection. In addition, the clinical symptoms of NKTCL are not obvious, and the specific pathogenesis is still uncertain. While NKTCL may occur in any segment of the intestinal tract, its distinct location in the periampullary region, which leads clinicians to consider mimics of a pancreatic head mass, should also be addressed. Therefore, there remain huge challenges in the diagnosis and treatment of intestinal NKTCL. CASE SUMMARY: In this case, we introduce a male who presented to the clinic with edema of both lower limbs, accompanied by diarrhea, and abdominal pain. Endoscopic ultrasound (EUS) showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas. Under the guidance of EUS- fine needle biopsy (FNB) with 19 gauge or 22 gauge needles, combined with multicolor flow cytometry immunophenotyping (MFCI) helped us diagnose NKTCL. During treatments, the patient was prescribed the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy regimen. Unfortunately, he died of leukopenia and severe septic shock in a local hospital. CONCLUSION: Clinicians should enhance their understanding of NKTCL. Some key factors, including EUS characteristics, the right choice of FNB needle, and combination with MFCI, are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

Salt stress-induced chloroplastic hydrogen peroxide stimulates pdTPI sulfenylation and methylglyoxal accumulation.

High salinity, an adverse environmental factor affecting about 20% of irrigated arable land worldwide, inhibits plant growth and development by causing oxidative stress, damaging cellular components, and disturbing global metabolism. However, whether and how reactive oxygen species disturb the metabolism of salt-stressed plants remain elusive. Here, we report that salt-induced hydrogen peroxide (H2O2) inhibits the activity of plastid triose phosphate isomerase (pdTPI) to promote methylglyoxal (MG) accumulation and stimulates the sulfenylation of pdTPI at cysteine 74. We also show that MG is a key factor limiting the plant growth, as a decrease in MG levels completely rescued the stunted growth and repressed salt stress tolerance of the pdtpi mutant. Furthermore, targeting CATALASE 2 into chloroplasts to prevent salt-induced overaccumulation of H2O2 conferred salt stress tolerance, revealing a role for chloroplastic H2O2 in salt-caused plant damage. In addition, we demonstrate that the H2O2-mediated accumulation of MG in turn induces H2O2 production, thus forming a regulatory loop that further inhibits the pdTPI activity in salt-stressed plants. Our findings, therefore, illustrate how salt stress induces MG production to inhibit the plant growth.

ELO2 Participates in the Regulation of Osmotic Stress Response by Modulating Nitric Oxide Accumulation in Arabidopsis.

The ELO family is involved in synthesizing very-long-chain fatty acids (VLCFAs) and VLCFAs play a crucial role in plant development, protein transport, and disease resistance, but the physiological function of the plant ELO family is largely unknown. Further, while nitric oxide synthase (NOS)-like activity acts in various plant environmental responses by modulating nitric oxide (NO) accumulation, how the NOS-like activity is regulated in such different stress responses remains misty. Here, we report that the yeast mutant Δelo3 is defective in H2O2-triggered cell apoptosis with decreased NOS-like activity and NO accumulation, while its Arabidopsis homologous gene ELO2 (ELO HOMOLOG 2) could complement such defects in Δelo3. The expression of this gene is enhanced and required in plant osmotic stress response because the T-DNA insertion mutant elo2 is more sensitive to the stress than wild-type plants, and ELO2 expression could rescue the sensitivity phenotype of elo2. In addition, osmotic stress-promoted NOS-like activity and NO accumulation are significantly repressed in elo2, while exogenous application of NO donors can rescue this sensitivity of elo2 in terms of germination rate, fresh weight, chlorophyll content, and ion leakage. Furthermore, stress-responsive gene expression, proline accumulation, and catalase activity are also repressed in elo2 compared with the wild type under osmotic stress. In conclusion, our study identifies ELO2 as a pivotal factor involved in plant osmotic stress response and reveals its role in regulating NOS-like activity and NO accumulation.

The metabolite methylglyoxal-mediated gene expression is associated with histone methylglyoxalation.

Methylglyoxal (MG) is a byproduct of glycolysis that functions in diverse mammalian developmental processes and diseases and in plant responses to various stresses, including salt stress. However, it is unknown whether MG-regulated gene expression is associated with an epigenetic modification. Here we report that MG methylglyoxalates H3 including H3K4 and increases chromatin accessibility, consistent with the result that H3 methylglyoxalation positively correlates with gene expression. Salt stress also increases H3 methylglyoxalation at salt stress responsive genes correlated to their higher expression. Following exposure to salt stress, salt stress responsive genes were expressed at higher levels in the Arabidopsis glyI2 mutant than in wild-type plants, but at lower levels in 35S::GLYI2 35S::GLYII4 plants, consistent with the higher and lower MG accumulation and H3 methylglyoxalation of target genes in glyI2 and 35S::GLYI2 35S::GLYII4, respectively. Further, ABI3 and MYC2, regulators of salt stress responsive genes, affect the distribution of H3 methylglyoxalation at salt stress responsive genes. Thus, MG functions as a histone-modifying group associated with gene expression that links glucose metabolism and epigenetic regulation.

Three-dimensional laparoscopy-assisted bowel resection for cavernous hemangioma of the rectum: Report of two cases.

The safety and feasibility of 3-D laparoscopy-assisted bowel resection were demonstrated in the management of rectal cancer. However, this procedure's role in the management of patients with diffuse cavernous hemangioma of the rectum has not been evaluated. Here, two patients were diagnosed with diffuse cavernous hemangioma of the rectum by colonoscopy and abdominal imaging. One case underwent pull-through transection and coloanal anastomosis in 3-D laparoscopy-assisted surgery. In another patient, 3-D laparoscopy-assisted abdominoperineal resection was performed. The operations were safely performed in both cases. The two patients recovered uneventfully, and satisfactory postoperative outcomes were demonstrated. This report shows that 3-D laparoscopy-assisted bowel resection may be safe and feasible for patients with diffuse cavernous hemangioma of the rectum.

Mesenteric injection of adipose-derived mesenchymal stem cells relieves experimentally-induced colitis in rats by regulating Th17/Treg cell balance.

Efficient delivery routes are critical for the effectiveness of adipose-derived mesenchymal stem cells (ADMSCs) in treating inflammatory bowel disease (IBD). Conventional ADMSC delivery routes include local, intravenous and intraperitoneal injection. Whether mesenteric injection has potential in IBD treatment remains unknown. In the present study, we investigated the therapeutic effects of mesenteric injection of ADMSCs in a trinitrobenzene sulfonic acid-induced rat IBD model and explored whether this treatment affected T helper 17 (Th17)/regulatory T (Treg) cell ratio. The results showed that mesenteric injection of ADMSCs markedly reduced signs of colitis, colon shortening, weight loss and pathological damage. The treatment also decreased serum tumor necrosis factor alpha concentration, increased serum tumor necrosis factor alpha-stimulated gene protein 6 concentration, and augmented repair via proliferation (assessed by evaluating Ki-67 levels) in colonic tissue. Moreover, mesenteric injection of ADMSCs reduced interleukin (IL)-17A and IL-6 mRNA expression, and increased IL-10 and transforming growth factor-beta mRNA expression in colonic tissue. Protein analyses indicated that mesenteric injection of ADMSCs was associated with increased expression of forkhead box P3+ and IL-10 as well as decreased expression of retinoid-related orphan receptor λt and IL-17. Additionally, the treatment inhibited phosphorylation of signal transducer and activator of transcription (STAT) 3 and activated phosphorylation of STAT5. Taken together, these results suggest that mesenteric injection of ADMSCs is a promising approach to treating trinitrobenzene sulfonic acid-induced IBD, and achieves its therapeutic effect by regulating the pro/anti-inflammatory Th17/Treg cell balance.

Nitric oxide is involved in stomatal development by modulating the expression of stomatal regulator genes in Arabidopsis.

As sessile organisms, plants require many flexible strategies to adapt to the environment. Although some environmental signaling pathways regulating stomatal development have been identified, how stomatal regulators are modulated by internal and external signals to determine the final stomatal abundance requires further exploration. In our studies, we found that nitric oxide (NO) promotes stomatal development with increased stomatal index as well as the relative number of meristemoids and guard mother cells [%(M+GMC)] in NO-treated wild-type Arabidopsis plants; this role of NO was further verified in the nox1 mutant, which exhibits higher NO levels, and the noa1 mutant, which exhibits low NO accumulation. To gain insight into the molecular mechanisms underlying the effect of NO, we further assayed the expression of genes involved in stomatal development and found that NO induces the expression of the master regulators SPCH, MUTE and SCRM2 to initiate stomatal development. In addition, MPK6 is also involved in NO-promoted stomatal development, as MPK6 expression was repressed in nox1 and NO-treated plants, and transgenic plants overexpressing MPK6 were less sensitive to SNP treatment in terms of changes in the%(M+GMC). Thus, our study shows that NO promotes the production of stomata by up-regulating the expression of SPCH, MUTE and SCRM2 and down-regulating MPK6 expression.

Overexpression of Rat Neurons Nitric Oxide Synthase in Rice Enhances Drought and Salt Tolerance.

Nitric oxide (NO) has been shown to play an important role in the plant response to biotic and abiotic stresses in Arabidopsis mutants with lower or higher levels of endogenous NO. The exogenous application of NO donors or scavengers has also suggested an important role for NO in plant defense against environmental stress. In this study, rice plants under drought and high salinity conditions showed increased nitric oxide synthase (NOS) activity and NO levels. Overexpression of rat neuronal NO synthase (nNOS) in rice increased both NOS activity and NO accumulation, resulting in improved tolerance of the transgenic plants to both drought and salt stresses. nNOS-overexpressing plants exhibited stronger water-holding capability, higher proline accumulation, less lipid peroxidation and reduced electrolyte leakage under drought and salt conditions than wild rice. Moreover, nNOS-overexpressing plants accumulated less H2O2, due to the observed up-regulation of OsCATA, OsCATB and OsPOX1. In agreement, the activities of CAT and POX were higher in transgenic rice than wild type. Additionally, the expression of six tested stress-responsive genes including OsDREB2A, OsDREB2B, OsSNAC1, OsSNAC2, OsLEA3 and OsRD29A, in nNOS-overexpressing plants was higher than that in the wild type under drought and high salinity conditions. Taken together, our results suggest that nNOS overexpression suppresses the stress-enhanced electrolyte leakage, lipid peroxidation and H2O2 accumulation, and promotes proline accumulation and the expression of stress-responsive genes under stress conditions, thereby promoting increased tolerance to drought and salt stresses.

Salt stress reduces root meristem size by nitric oxide-mediated modulation of auxin accumulation and signaling in Arabidopsis.

The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor N(ω)-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels.

In vivo role of nitric oxide in plant response to abiotic and biotic stress.

Over the past few years, nitric oxide (NO) has emerged as an important regulator in many physiological events, especially in response to abiotic and biotic stress. However, the roles of NO were mostly derived from pharmacological studies or the mutants impaired NO synthesis unspecifically. In our recent study, we highlighted a novel strategy by expressing the rat neuronal NO synthase (nNOS) in Arabidopsis to explore the in vivo role of NO. Our results suggested that plants were able to perform well in the constitutive presence of nNOS, and provided a new class of plant experimental system with specific in vivo NO release. Furthermore, our findings also confirmed that the in vivo NO is essential for most of environmental abiotic stresses and disease resistance against pathogen infection. Proper level of NO may be necessary and beneficial, not only in plant response to the environmental abiotic stress, but also to biotic stress.

[The interactions between the circadian clock and aging].

It is well known that almost all organisms ranging from single cell creatures to human beings exhibit circadian rhythms in physiology and behavior under the control of the internal circadian clock. The internal circadian clock is composed of a master clock which is localized in the suprachiasmatic nucleus and the peripheral clocks located in peripheral tissues such as the liver and heart. Along with aging, the circadian rhythm alters in many aspects, including the amplitude, free-running period and the expression phase. On the other hand, the circadian clock also influences the process of aging. The disorganized circadian rhythm accelerates the aging process. This article briefly reviews the recent progress in the interactions between the circadian clock and aging, and provides evidence to further understand the mechanism of aging and the impact of aging on the organisms.

Low dose streptozotocin (STZ) combined with high energy intake can effectively induce type 2 diabetes through altering the related gene expression.

High energy-intake is a major factor revolved in type 2 diabetes. A number of animal models have been adopted for studying the type 2 diabetes, but they differ greatly from human type 2 diabetes. The objectives of the present study are to set up a suitable animal model, which is similar to the human type 2 diabetes, and then to understand possible molecular mechanisms underlying type 2 diabetes. Twenty five-week-old Wistar male rats were randomized into four groups. One group was fed with basal diet (BD) whereas the others consumed high-energy diet (HD) of 20% sucrose and 10% lard. Four weeks later, BD and one of HD were sampled. Other groups continued to consume HD, but one of them was treated by one injection of streptozotocin (STZ) (30 mg/kg body weight). After another four weeks, all were sacrificed. Changes in body weight were recorded, and levels of glucose, TG, TC, LDL in serum were analyzed by standard methods. Moreover, expressions of genes related to energy metabolism in liver, muscle and fat were measured by real-time RT-PCR. HD had no notable differentiation with BD on bodyweight and serum indices, but it altered gene expressions in a tissue-specific manner. Two receptors of adiponectin, leptin, PPARgamma, UCP2 mRNA levels in fat were up regulated, whereas most of them were down regulated in liver. STZ treatment induced symptoms of diabetes, and the gene expression mentioned above exhibited changes in both tissue- and gene-specific manners. The results suggest that a combination of low dose STZ and high-energy intake can effectively induce type 2 diabetes by altering the related gene expressions in major metabolic tissues.