The osmotic stress-activated receptor-like kinase DPY1 mediates SnRK2 kinase activation and drought tolerance in Setaria.

Plant genomes encode many receptor-like kinases (RLKs) that localize to the cell surface and perceive a wide variety of environmental cues to initiate downstream signaling cascades. Whether these RLKs participate in dehydration stress signaling in plants is largely unknown. DROOPY LEAF1 (DPY1), a leucine-rich repeat (LRR)-RLK, was recently shown to regulate plant architecture by orchestrating early brassinosteroid signaling in foxtail millet (Setaria italica). Here, we show that DPY1 is essential for the acclimation of foxtail millet to drought stress. DPY1 can be phosphorylated and activated in response to osmotic stress and is required for more than half of osmotic stress-induced global phosphorylation events, including the phosphorylation of sucrose nonfermenting kinase 2s (SnRK2s), the central kinases involved in osmotic stress. DPY1 acts upstream of STRESS-ACTIVATED PROTEIN KINASE 6 (SAPK6, a subclass I SnRK2) and is required for full SAPK6 activation, thereby allowing regulation of downstream genes to mount a response against drought stress. These signaling events are largely independent of DPY1-mediated brassinosteroid signaling. The DPY1-SAPK6 module is specific to seed plants and is absent in ancestral nonseed plants. Our findings reveal a dehydration stress-activated RLK that plays an indispensable role in osmotic stress signaling and mediates SnRK2 activation at the cell surface.

Global pattern of organic carbon pools in forest soils.

Understanding the mechanisms of soil organic carbon (SOC) sequestration in forests is vital to ecosystem carbon budgeting and helps gain insight in the functioning and sustainable management of world forests. An explicit knowledge of the mechanisms driving global SOC sequestration in forests is still lacking because of the complex interplays between climate, soil, and forest type in influencing SOC pool size and stability. Based on a synthesis of 1179 observations from 292 studies across global forests, we quantified the relative importance of climate, soil property, and forest type on total SOC content and the specific contents of physical (particulate vs. mineral-associated SOC) and chemical (labile vs. recalcitrant SOC) pools in upper 10 cm mineral soils, as well as SOC stock in the O horizons. The variability in the total SOC content of the mineral soils was better explained by climate (47%-60%) and soil factors (26%-50%) than by NPP (10%-20%). The total SOC content and contents of particulate (POC) and recalcitrant SOC (ROC) of the mineral soils all decreased with increasing mean annual temperature because SOC decomposition overrides the C replenishment under warmer climate. The content of mineral-associated organic carbon (MAOC) was influenced by temperature, which directly affected microbial activity. Additionally, the presence of clay and iron oxides physically protected SOC by forming MAOC. The SOC stock in the O horizons was larger in the temperate zone and Mediterranean regions than in the boreal and sub/tropical zones. Mixed forests had 64% larger SOC pools than either broadleaf or coniferous forests, because of (i) higher productivity and (ii) litter input from different tree species resulting in diversification of molecular composition of SOC and microbial community. While climate, soil, and forest type jointly determine the formation and stability of SOC, climate predominantly controls the global patterns of SOC pools in forest ecosystems.

Microbial Sulfur and Arsenic Oxidation Facilitate the Establishment of Biocrusts during Reclamation of Degraded Mine Tailings.

Degraded tailings generated by the mining of metal ores are major environmental threats to the surrounding ecosystems. Tailing reclamation, however, is often impeded due to adverse environmental conditions, with depleted key nutrients (i.e., nitrogen (N) and phosphorus (P)) and elevated sulfur and metal(loid) concentrations. Formation of biocrusts may significantly accelerate nutrient accumulation and is therefore an essential stage for tailing reclamation. Although suggested to play an important role, the microbial community composition and key metabolisms in biocrusts remain largely unknown and are therefore investigated in the current study. The results suggested that sulfur and arsenic oxidation are potential energy sources utilized by members of predominant biocrust bacterial families, including Beijerinckiaceae, Burkholderiaceae, Hyphomicrobiaceae, and Rhizobiaceae. Accordingly, the S and As oxidation potentials are elevated in biocrusts compared to those in their adjacent tailings. Biocrust growth, as proxied by chlorophyll concentrations, is enhanced in treatments supplemented with S and As. The elevated biocrust growth might benefit from nutrient acquisition services (i.e., nitrogen fixation and phosphorus solubilization) fueled by microbial sulfur and arsenic oxidation. The current study suggests that sulfur- and arsenic-oxidizing microorganisms may play important ecological roles in promoting biocrust formation and facilitating tailing reclamation.

Long term co-application of biochar and fertilizer could increase soybean yield under continuous cropping: insights from photosynthetic physiology.

BACKGROUND: Photosynthesis is the key to crop yield. The effect of biochar on photosynthetic physiology and soybean yield under continuous cropping is unclear. We conducted a long-term field experiment to investigate the effects of co-application of biochar and fertilizer (BCAF) on these parameters. Five treatments were established: F2 (fertilizer), B1F1 (3 t hm-2 biochar plus fertilizer), B1F2 (3 t hm-2 biochar plus reduced fertilizer), B2F1 (6 t hm-2 biochar plus fertilizer), and B2F2 (6 t hm-2 biochar plus reduced fertilizer). RESULTS: BCAF increased chlorophyll and leaf area, enhancing soybean photosynthesis. The net photosynthetic rate (Pn ), transpiration rate (Tr ), stomatal conductance (Gs ), water use efficiency (WUE) and intercellular carbon dioxide (CO2 ) concentration (Ci ) were enhanced by BCAF. In addition, BCAF improved soybean photosystem II (PSII) photosynthetic performance, driving force, potential photochemical efficiency (Fv /F0 ), and quantum yield of electron transfer (φE0 ). Furthermore, BCAF enhanced the accumulation of photosynthetic products, such as soluble proteins, soluble sugars and sucrose content, resulting in higher leaf dry weight. Consequently, BCAF increased the soybean yield, with the highest increase of 41.54% in B2F1. The correlation analysis revealed positive relationships between soybean yield and chlorophyll, leaf area, maximal quantum yield of PSII (Fv /Fm ), electron transport flux per cross-section at t = 0 (ET0 /CS0 ), trapped energy flux per cross-section at t = 0 (TR0 /CS0 ), composite blade driving force (DFTotal ), and leaf dry weight. CONCLUSIONS: We demonstrated that long-term BCAF enhances soybean photosynthesis under continuous planting, reduces fertilizer use and increases yield. This study reveals a novel way and theory to sustainably increase soybean productivity. © 2023 Society of Chemical Industry.

Physiological and transcriptomic analysis of OsLHCB3 knockdown lines in rice.

The photosystem II (PSII) outer antenna LHCB3 protein plays critical roles in distributing the excitation energy and modulating the rate of state transition for photosynthesis. Here, OsLHCB3 knockdown mutants were produced using the RNAi system. Phenotypic analyses showed that OsLHCB3 knockdown led to pale green leaves and lower chlorophyll contents at both tillering and heading stages. In addition, mutant lines exhibited decreased non-photochemical quenching (NPQ) capacity and net photosynthetic rate (Pn) by downregulating the expression of PSII-related genes. Moreover, RNA-seq experiments were performed at both tillering and heading stages. The differentially expressed genes (DEGs) mainly involved in chlorophyll binding response to abscisic acid, photosystem II, response to chitin, and DNA-binding transcription factor. Besides, our transcriptomic and physiological data indicated that OsLHCB3 was essential for binding chlorophyll, but not for the metabolism of chlorophyll in rice. OsLHCB3 RNAi knockdown plants affected the expression of PS II-related genes, but not PS I-related genes. Overall, these results suggest that OsLHCB3 also plays vital roles in regulating photosynthesis and antenna proteins in rice as well as responses to environment stresses. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01387-z.

Association between endometriosis and metabolic syndrome: a cross-sectional study based on the National Health and Nutrition Examination Survey data.

BACKGROUND: Endometriosis has been reported to be associated with metabolism-related diseases, such as hypercholesterolemia and diabetes, while no studies have reported the association between endometriosis and metabolic syndrome. OBJECTIVE: This study aims to explore the association between endometriosis and metabolic syndrome. Also, the association between endometriosis and single metabolic syndrome indicator was explored. METHODS: This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). A total of 2389 participants were finally included for analysis, with 2212 in the non-endometriosis group and 177 in the endometriosis group. Association between endometriosis and metabolic syndrome was explored using multivariate logistic regression analysis, with results shown as odds ratio (OR) with 95% confidence intervals (95%CI). Association between endometriosis and single metabolic syndrome indicator was explored using multivariate liner regression analysis. RESULTS: After adjusting age, race, education level, family poverty to income ratio (PIR), smoking, age at menarche, gravidity, menopause, female hormones use, and dyslipidemia drug use, endometriosis was associated with the higher odds of metabolic syndrome (OR = 1.55, 95%CI: 1.01-2.35). Further adjusting hysterectomy or oophorectomy, we found the similar association despite no statistical significance (OR = 1.47, 95%CI: 0.96-2.25). Moreover, we found endometriosis was associated with the high level of triglyceride (TG) (ß = 0.38, 95%CI: 0.06-0.70). CONCLUSIONS: Our study found the association between endometriosis and metabolic conditions, indicating that metabolic conditions of endometriosis women should be focused, and monitoring the blood lipid levels may be significant in decreasing the risk of metabolic syndrome.

Brassinosteroid homeostasis is critical for the functionality of the Medicago truncatula pulvinus.

Many plant species open their leaves during the daytime and close them at night as if sleeping. This leaf movement is known as nyctinasty, a unique and intriguing phenomenon that been of great interest to scientists for centuries. Nyctinastic leaf movement occurs widely in leguminous plants, and is generated by a specialized motor organ, the pulvinus. Although a key determinant of pulvinus development, PETIOLULE-LIKE PULVINUS (PLP), has been identified, the molecular genetic basis for pulvinus function is largely unknown. Here, through an analysis of knockout mutants in barrelclover (Medicago truncatula), we showed that neither altering brassinosteroid (BR) content nor blocking BR signal perception affected pulvinus determination. However, BR homeostasis did influence nyctinastic leaf movement. BR activity in the pulvinus is regulated by a BR-inactivating gene PHYB ACTIVATION TAGGED SUPPRESSOR1 (BAS1), which is directly activated by PLP. A comparative analysis between M. truncatula and the non-pulvinus forming species Arabidopsis and tomato (Solanum lycopersicum) revealed that PLP may act as a factor that associates with unknown regulators in pulvinus determination in M. truncatula. Apart from exposing the involvement of BR in the functionality of the pulvinus, these results have provided insights into whether gene functions among species are general or specialized.

The Conserved and Specific Roles of the LUX ARRHYTHMO in Circadian Clock and Nodulation.

LUX ARRHYTHMO (LUX) plays a key role in circadian rhythms and flowering. Here, we identified the MtLUX gene which is the putative ortholog of LUX in Medicago truncatula. The roles of MtLUX, in both the nodulation belowground and leaf movement aboveground, were investigated by characterizing a loss-of-function mtlux mutant. MtLUX was required for the control of flowering time under both long-day and short-day conditions. Further investigations showed that the early flowering in the mtlux mutant was correlated with the elevated expression level of the MtFTa1 gene but in a CO-like independent manner. MtLUX played a conserved role in the regulatory interactions with MtLHY, MtTOC1, and MtPRR genes, which is similar to those in other species. Meanwhile, the unexpected functions of MtLUX were revealed in nodule formation and nyctinastic leaf movement, probably through the indirect regulation in MtLHY. Its participation in nodulation is of interest in the context of functional conservation and the neo-functionalization of the products of LUX orthologs.

Three pleiotropic loci associated with bone mineral density and lean body mass.

Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10-8): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10-8, replication p = 1.03 × 10-4), 16q12.2 (rs1421085, discovery p = 2.04 × 10-9, replication p = 6.47 × 10-14) and 18q21.32 (rs11152213, discovery p = 3.47 × 10-8, replication p = 6.69 × 10-6). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.

Rapid and sensitive detection of rotavirus by surface-enhanced Raman scattering immunochromatography.

A surface-enhanced Raman scattering (SERS) immunochromatographic assay (ICA) has been developed for rapid, ultrasensitive, and quantitative detection of rotavirus in feces using double Raman molecule-labeled Au-core Ag-shell nanoparticles. The Raman signals are generated by 5,5'-dithiobis-(2-nitrobenzoic acid) and the intensity of the characteristic peak at 1334-1 cm was detected as the analytical signal. The Raman signals were enhanced by the SERS-enhanced effect of both Au and Ag, the large amount of Raman molecules, and the hot-spot effect in the narrow gap between the Au core and Ag shell. The SERS ICA can quantitatively detect rotavirus in a concentration range of 8- 40,000 pg/mL, with detection limits of 80 pg/mL and 8 pg/mL based on naked eye observation and SERS signal detection, respectively. No cross-reaction was observed from other common pathogens. The standard deviation of the intra- and inter-batch repetitive tests is less than 10%, and the coincidence between SERS ICA and RT-qPCR as well as commercial colloidal gold ICA is 100%. The results indicated that this SERS ICA is able to quantitatively detect rotavirus in feces in 20 min with high sensitivity, selectivity, reproducibility, and accuracy and might be a promising method for the early detection of rotavirus in clinical analysis.

Bisphosphonates and risk of cancers: a systematic review and meta-analysis.

BACKGROUND: It is unclear whether bisphosphonates are associated with risk of cancers. Therefore, this meta-analysis aimed to evaluate the effect of bisphosphonates on overall cancers. METHODS: A search in Pubmed, Embase, Cochrane Library and Web of Science databases was conducted, from the inception date of each resource to September 26, 2019. The summarised effect estimates with 95% CIs were calculated using a random-effect model. Heterogeneity and publication bias were explored. RESULTS: Thirty-four articles were included in this study (4,508,261 participants; 403,196 cases). The results revealed that bisphosphonates significantly decreased the risk of colorectal cancer (RR = 0.89, 95% CI: 0.81-0.98), breast cancer (RR = 0.87, 95% CI: 0.82-0.93) and endometrial cancer (RR = 0.75, 95% CI: 0.61-0.94), but no significant association was observed in all-cause cancer. Furthermore, nitrogen-containing bisphosphonates only had protective effects both on breast cancer (RR = 0.94, 95% CI: 0.90-0.99) and endometrial cancer (RR = 0.70, 95% CI: 0.54-0.92). Non-nitrogen-containing bisphosphonates tended to increase the risk of liver cancer (RR = 2.14, 95% CI: 1.23-3.72) and pancreas cancer (RR = 1.75, 95% CI: 1.32-2.33). CONCLUSION: Bisphosphonates are significantly associated with risk reduction of colorectal, breast and endometrial cancer, especially nitrogen-containing bisphosphonates. It should be noted that non-nitrogen-containing bisphosphonates might increase the risk of liver and pancreas cancer. Large prospective cohort studies are needed to find the causal association between bisphosphonates and risk of cancers.

Four pleiotropic loci associated with fat mass and lean mass.

BACKGROUND: Fat mass and lean mass are two biggest components of body mass. Both fat mass and lean mass are under strong genetic determinants and are correlated. METHODS: We performed a bivariate genome-wide association meta-analysis of (lean adjusted) leg fat mass and (fat adjusted) leg lean mass in 12,517 subjects from 6 samples, and followed by in silico replication in large-scale UK biobank cohort sample (N = 370 097). RESULTS: We identified four loci that were significant at the genome-wide significance (GWS, α = 5.0 × 10-8) level at the discovery meta-analysis, and successfully replicated in the replication sample: 2q36.3 (rs1024137, pdiscovery = 3.32 × 10-8, preplication = 4.07 × 10-13), 5q13.1 (rs4976033, pdiscovery = 1.93 × 10-9, preplication = 6.35 × 10-7), 12q24.31 (rs4765528, pdiscovery = 7.19 × 10-12, preplication = 1.88 × 10-11) and 18q21.32 (rs371326986, pdiscovery = 9.04 × 10-9, preplication = 2.35 × 10-95). The above four pleiotropic loci may play a pleiotropic role for fat mass and lean mass development. CONCLUSIONS: Our findings further enhance the understanding of the genetic association between fat mass and lean mass and provide a new theoretical basis for their understanding.

Nanoenabled Modulation of Acidic Tumor Microenvironment Reverses Anergy of Infiltrating T Cells and Potentiates Anti-PD-1 Therapy.

While tumor-infiltrating cytotoxic T lymphocytes play a critical role in controlling tumor development, they are generally impotent in an acidic tumor microenvironment. Systemic treatment to neutralize tumor acidity thus holds promise for the reversal of the anergic state of T cells and the improvement of T cell-associated immunotherapy. Herein, we report a proof-of-concept of RNAi nanoparticle-mediated therapeutic reversion of tumor acidity to restore the antitumor functions of T cells and potentiate the checkpoint blockade therapy. Our strategy utilized an in vivo optimized vesicular cationic lipid-assisted nanoparticle, as opposed to its micellar counterpart, to mediate systematic knockdown of lactate dehydrogenase A (LDHA) in tumor cells. The treatment resulted in the reprogramming of pyruvate metabolism, a reduction of the production of lactate, and the neutralization of the tumor pH. In immunocompetent syngeneic melanoma and breast tumor models, neutralization of tumor acidity increased infiltration with CD8+ T and NK cells, decreased the number of immunosuppressive T cells, and thus significantly inhibited the growth of tumors. Furthermore, the restoration of tumoral pH potentiated checkpoint inhibition therapy using the antibody of programmed cell death protein 1 (PD-1). However, in immunodeficient B6/ Rag1 -/- and NOG mice, the same treatment failed to control tumor growth, further proving that the attenuation of tumor growth by tumor acidity modulation was attributable to the activation of tumor-infiltrating immune cells.

Role of sucrose in modulating the low-nitrogen-induced accumulation of phenolic compounds in lettuce (Lactuca sativa L.).

BACKGROUND: Phenolic compounds are phytochemicals present in vegetables which contribute to human health. Although nitrogen deficiency and sucrose (Suc) are linked to phenolic production in vegetables, the relationship between them in the regulation of phenolic biosynthesis remains unknown. This study investigated the potential role of Suc in regulating phenolic biosynthesis of lettuce under low-nitrogen (LN) conditions. RESULTS: Our results showed that LN treatment significantly increased Suc content in lettuce by inducing rapid increases in activities of sucrose synthesis-related enzymes. Exogenous Suc further stimulated LN-induced phenolic accumulation in lettuce by upregulating the expression of genes (PAL, CHS, F3H, DFR, F35H and UFGT) involved in phenolic biosynthesis. The opposite effects were true for exogenous 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) application. No changes were observed in chlorophyll content in LN-treated lettuce, in either the presence or absence of Suc application. Notably, exogenous DCMU resulted in decreases of maximum quantum efficiency of photosystem II (PSII) photochemistry, actual efficiency of PSII and electron transport rate in PSII and increase of quantum yield of non-regulated energy dissipation in PSII in lettuce under LN conditions, whereas these effects were reversed on Suc application. Exogenous Suc also increased glutamine synthetase and glutamate synthase activities in LN-treated lettuce. CONCLUSIONS: These results suggest that Suc is involved in LN-induced phenolic production in lettuce by enhancing photosynthetic and nitrogen assimilation efficiency to increase the supply of carbon resources and precursors for phenolic biosynthesis. © 2020 Society of Chemical Industry.

Inhibition of intestinal lipases alleviates the adverse effects caused by high-fat diet in Nile tilapia.

Intestinal lipases are fat-digesting enzymes, which play vital roles in lipid absorption in the intestine. To study the regulation of intestinal lipase activity in systemic lipid metabolism in fish, especially in the metabolic diseases caused by high-fat diet (HFD) feeding, we inhibited intestinal lipases in Nile tilapia to investigate the physiological consequences. In the present study, Nile tilapia were firstly fed with HFD (12% fat) for 6 weeks to establish a fatty fish model. Afterwards, Orlistat as a potent intestinal lipase inhibitor was added into the HFD for the following 5-week feeding trial, with two dietary doses (Orlistat16 group, 16 mg/kg body weight; Orlistat32 group, 32 mg/kg body weight). After the trial, both doses of Orlistat treatment significantly reduced intestinal lipase activity, fat absorption, hepatic lipid accumulation, and gene expression of lipogenesis, whereas increased gene expression of lipid catabolism. Moreover, intestinal lipase inhibition increased immune enzyme activities, antioxidant capacity, and gene expression of anti-inflammatory cytokines, whereas lowered gene expression of pro-inflammatory cytokines. Besides, Orlistat could also improve the structure of the intestine and increase expression of intestinal tight-coupling protein. Taken together, intestinal lipase inhibition alleviated the adverse effects caused by HFD in Nile tilapia. Thus, intestinal lipases played key roles in absorbing dietary lipid and could be a promising target in regulating systemic lipid metabolism in fish.

Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model.

l-Carnitine is essential for mitochondrial ß-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in ß-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal ß-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.

Inhibited autophagy impairs systemic nutrient metabolism in Nile tilapia.

Autophagy is a conserved cellular degradation process through which intracellular components are degraded by the lysosome, but its roles in fish metabolism have not been studied in depth. Therefore, the present study aimed to investigate whether autophagy plays a key role in maintaining metabolic homeostasis in fish. In an 8-week feeding trial, Nile tilapia were fed either a control diet with medium fat and medium carbohydrate (Control), or a control diet supplemented with a classic autophagy inhibitor (chloroquine, CQ). CQ supplementation significantly inhibited autophagy and impaired fish growth and protein synthesis, and the glycolysis was stimulated, accompanied by fat accumulation, high oxidative stress and inflammation. Physiological status and gene expressions suggested that impaired autophagy might be at least one cause of the metabolic diseases which has been commonly seen in aquaculture. These results indicate that inhibition of autophagy could significantly affect the metabolism of lipid, carbohydrate and protein in fish; hence, autophagy could play important roles in maintaining homeostasis of nutrient metabolism in cultured fish.

Alteration of Phenolic Composition in Lettuce (Lactuca sativa L.) by Reducing Nitrogen Supply Enhances its Anti-Proliferative Effects on Colorectal Cancer Cells.

Consumption of vegetables rich in phenolic compounds has become a useful method to reduce the risk of developing several types of cancer. This study investigated the potential relationship between the alteration of phenolic compounds in lettuce induced by reduced nitrogen supply and its anti-proliferative effects on Caco-2 colorectal cancer cells. Our results showed that phenolic extracts from lettuce grown under low nitrogen conditions (LP) exhibited better anti-proliferative effects against Caco-2 cells, in part, by interfering with the cell cycle and inducing apoptosis, compared with those from lettuce supplied with adequate nitrogen. High performance liquid chromatography (HPLC) analysis and correlation analysis indicated that the better anticancer activity of LP may be not only related to the increased phenolic content, but also associated with the increased percentage contribution of quercetin to total phenolics. Taken together, alteration of phenolic composition by reduced nitrogen supply can be an effectively strategy for the development of healthy vegetables as anticancer products.

PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells.

Twist1 is an essential transcription factor required to initiate epithelial-mesenchymal transition (EMT) and promote tumor metastasis. PAQR3 is a newly found tumor suppressor that is frequently downregulated in many types of human cancers. Downregulation of PAQR3 is associated with accelerated metastasis and poor prognosis of the patients with gastric cancers. In this study, we demonstrate that PAQR3 is actively involved in the degradation of Twist1 and whereby regulates EMT and metastasis of gastric cancer cells. PAQR3 overexpression reduces the protein level but not the mRNA level of Twist1. The protein stability and polyubiquitination of Twist1 are altered by PAQR3. PAQR3 forms a complex with Twist1 and BTRC, an E3 ubiquitin ligase. PAQR3 enhances the interaction between Twist1 and BTRC. Twist1 is mobilized from the nucleus to a proteasome-containing structure in the cytoplasm upon overexpression of PAQR3 and BTRC, which is required for PAQR3-induced degradation of Twist1. The Twist1 box domain of the Twist1 protein is required for the interaction of Twist1 with both PAQR3 and BTRC, indispensable for PAQR3-mediated degradation of Twist1. Both BTRC and Twist1 are required for the inhibitory effects of PAQR3 on migration and EMT phenotype of gastric cancers cells. Importantly, Twist1 is indispensable for the inhibitory effect of PAQR3 on metastasis of gastric cancer cells in vivo Collectively, these findings not only pinpoint that Twist1 mediates the modulatory function of PAQR3 on EMT and metastasis but also suggest that targeting Twist1 is a promising strategy to control metastasis of tumors with downregulation of PAQR3.

Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

BACKGROUND: Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. METHODS: A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. RESULTS: The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p < 0.01). In the acute group, the plasma HO-1 levels in the post-treatment group (2.33 ± 2.39) were significantly reduced compared to the pre-treatment group (4.97 ± 3.55) (p < 0.01). On the other hand, the plasma HO-1 levels were higher in the chronic active group (4.43 ± 3.00) than the chronic stable group (2.74 ± 2.23) (p < 0.05). However, the plasma HO-1 levels in the chronic stable group (2.74 ± 2.23) remained higher than the levels in the healthy control group (1.03 ± 0.63) (p < 0.05). The HO-1 levels were positively correlated with the C-reactive protein (CRP) levels in patients with brucellosis (r = 0.707, p < 0.01). CONCLUSIONS: The plasma HO-1 levels can reflect patients' brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.