Comparative transcriptome analysis and Arabidopsis thaliana overexpression reveal key genes associated with cadmium transport and distribution in root of two Capsicum annuum cultivars.

The molecular mechanisms underlying high and low cadmium (Cd) accumulation in hot pepper cultivars remain unclear. In this study, comparative transcriptome analysis of root between high-Cd (J) and low-Cd (Z) cultivars was conducted under hydroponic cultivation with 0 and 0.4 mg/L Cd, respectively. The results showed that J enhanced the root uptake of Cd by elevating the expression of Nramp5 and counteracting Cd toxicity by increasing the expression of genes, such as NIR1, GLN1, and IAA9. Z reduced Cd accumulation by enhancing the cell wall lignin synthesis genes PAL, COMT, 4CL, LAC, and POD and the Cd transporters ABC, MTP1, and DTX1. Elevated expression of genes related to sulfur metabolism was observed in Z, potentially contributing to its ability to detoxify Cd. To investigate the function of CaCOMT1, an Arabidopsis thaliana overexpression line (OE-CaCOMT1) was constructed. The results revealed that OE-CaCOMT1 drastically increased the lignin content by 38-42% and reduced the translocation of Cd to the aboveground parts by 32%. This study provides comprehensive insights into the mechanisms underlying Cd accumulation in hot pepper cultivars using transcriptome analysis. Moreover, this study elucidates the critical function of CaCOMT1, providing a theoretical foundation for the production of low-Cd vegetables for food safety.

Pan-immune-inflammation and its dynamics: predictors of survival and immune-related adverse events in patients with advanced NSCLC receiving immunotherapy.

OBJECTIVES: Pan-immune-inflammation value (PIV) is defined by the neutrophil, platelet, monocyte, and lymphocyte counts and is associated with immune-checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (aNSCLC). However, PIV is dynamic under therapy and its longitudinal assessment may help predict efficacy. This study investigated the impact of baseline PIV and its dynamics on ICI efficacy and its immune-related adverse events (irAEs). The study additionally attempted to understand the biological significance of PIV. PATIENTS AND METHODS: This retrospective study analyzed the clinical data of 269 consecutive patients with aNSCLC. PIV was calculated at baseline and at weeks 3-4 to determine its association with overall survival (OS), progression-free survival (PFS), and irAEs. RESULTS: Results revealed that low baseline PIV was positively correlated with the incidence of irAEs. Moreover, a low PIV at baseline was significantly associated with a prolonged PFS (median PFS: 10 vs. 7 months, p = 0.0005) and OS (median OS: 29 vs. 21 months, p < 0.0001). When the PIV at baseline and weeks 3-4 was considered together, its low dynamics correlated with a higher incidence of irAEs (p = 0.001), a longer PFS (median PFS, 9 vs. 6 months, p = 0.012), and a longer OS (median OS; 28 vs. 21 months, p = 0.002). CONCLUSION: Thus, PIV at baseline and its dynamics are novel and potent predictors of irAEs, PFS, and OS in patients with aNSCLC receiving immunotherapy. Moreover, the PIV dynamics may be an effective, novel surrogate marker to dynamically observe the efficacy of immunotherapy.

The regulatory role of abscisic acid on cadmium uptake, accumulation and translocation in plants.

To date, Cd contamination of cropland and crops is receiving more and more attention around the world. As a plant hormone, abscisic acid (ABA) plays an important role in Cd stress response, but its effect on plant Cd uptake and translocation varies among plant species. In some species, such as Arabidopsis thaliana, Oryza sativa, Brassica chinensis, Populus euphratica, Lactuca sativa, and Solanum lycopersicum, ABA inhibits Cd uptake and translocation, while in other species, such as Solanum photeinocarpum and Boehmeria nivea, ABA severs the opposite effect. Interestingly, differences in the methods and concentrations of ABA addition also triggered the opposite result of Cd uptake and translocation in Sedum alfredii. The regulatory mechanism of ABA involved in Cd uptake and accumulation in plants is still not well-established. Therefore, we summarized the latest studies on the ABA synthesis pathway and comparatively analyzed the physiological and molecular mechanisms related to ABA uptake, translocation, and detoxification of Cd in plants at different ABA concentrations or among different species. We believe that the control of Cd uptake and accumulation in plant tissues can be achieved by the appropriate ABA application methods and concentrations in plants.

Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant.

As a well-known multimodal-acting antidepressant, vortioxetine is thought to aim at several serotonin (5-HT) receptors and the 5-HT transporter. However, recently more and more proteins besides 5-HT are being reported to participate in the antidepressant mechanism of vortioxetine. As a widely known nuclear hormone receptor, peroxisome proliferator activated receptor α (PPARα) possesses transcriptional activity and is very important in the brain. Several reports have suggested that hippocampal PPARα is implicated in antidepressant responses. Here we speculate that hippocampal PPARα may participate in the antidepressant mechanism of vortioxetine. In this study, chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated gene knockdown methods were used together. It was found that vortioxetine administration significantly reversed the inhibitory actions of both CUMS and CSDS on the hippocampal PPARα expression. Pharmacological blockade of PPARα notably prevented the antidepressant actions of vortioxetine in the CUMS and CSDS models. Moreover, genetic knockdown of PPARα in the hippocampus also significantly blocked the protecting effects of vortioxetine against both CUMS and CSDS. Therefore, the antidepressant effects of vortioxetine in mice require hippocampal PPARα.

The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway.

Depression is a widespread chronic medical illness affecting thoughts, mood, and physical health. However, the limited and delayed therapeutic efficacy of monoaminergic drugs has led to intensive research efforts to develop novel antidepressants. ARN-3236 is the first potent and selective inhibitor of salt-inducible kinase 2 (SIK2). In this study, a multidisciplinary approach was used to explore the antidepressant-like actions of ARN-3236 in mice. Chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, high performance liquid chromatography-tandem mass spectrometry, stereotactic infusion, viral-mediated gene transfer, western blotting, co-immunoprecipitation and immunofluorescence were used together. It was found that ARN-3236 could penetrate the blood-brain barrier. Repeated ARN-3236 administration induced significant antidepressant-like effects in both the CSDS and CUMS models of depression, accompanied with fully preventing the stress-enhanced SIK2 expression and cytoplasmic translocation of cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) in the hippocampus. ARN-3236 treatment also completely reversed the down-regulating effects of CSDS and CUMS on the hippocampal brain-derived neurotrophic factor (BDNF) system and neurogenesis. Moreover, we demonstrated that the hippocampal CRTC1-CREB-BDNF pathway mediated the antidepressant-like efficacy of ARN-3236. Collectively, ARN-3236 possesses strong protecting effects against chronic stress, and could be a novel antidepressant beyond monoaminergic drugs.

Brain imaging findings in dyslexia.

Dyslexia is a brain-based disorder that has been intensively studied in the Western world for more than a century because of its social burden. However, affected individuals in Chinese communities are neither recognized nor formally diagnosed. Previous studies have concentrated on the disadvantages of reading deficits, and few have addressed non-linguistic skills, which are included in the symptoms. In addition, certain dyslexics possess visual spatial talents that have usually been ignored. In this review, we discuss the available information regarding brain imaging studies of dyslexia based on studies in Caucasian subjects. Gray matter deficits have been demonstrated in dyslexics using structural magnetic resonance imaging. Reduced neural activities in the left temporal and left parietal cortices, and diffuse widespread activation patterns in the cerebellum could be detected using functional magnetic resonance imaging. Changes in lactate levels, N-acetylaspartate/choline-containing compounds and N-acetylaspartate/creatine ratios, and phosphomonoester peak area were detected in magnetic resonance spectroscopy studies. Lower fractional anisotropy values in bilateral white matter tracts have been demonstrated by diffusion tensor imaging. Abnormal Broca's area activation was found using positron emission tomography imaging. Increased activities in the right frontal and temporal brain regions were detected using electroencephalography. Reduced hemispheric asymmetry and increased left inferior frontal activation were reported following magnetoencephalography. Although these imaging modalities are not currently diagnostic or prognostic, they are able to provide information on the causes of dyslexia beyond what was previously provided by behavioral or cognition studies.

Thermal and pH stability of betacyanin pigment of Djulis (Chenopodium formosanum) in Taiwan and their relation to antioxidant activity.

The betacyanin pattern of Djulis (Chenopodium fromosanum), a native cereal plant in Taiwan, was reported for the first time. The determination of characteristics of the pigment, including pH and thermal stability and their relation to antioxidant activities, indicated that betacyanin of Djulis exhibited the maximum absorbance at 530 nm and their thermal stability was dependent on the pH. Antioxidant capacities as well as red color of that pigment were significantly positively related with A(530). Therefore, A(530) can be used as a simple index of the antioxidant capacity of that pigment. Four peaks including betanin (47.8%), isobetanin (30.0%) with m/z 551.0, and armaranthin (13.6%), isoamaranthinee (8.6%) with m/z 727.0 were purified from the pigment extract by HPLC and identified through LC/MS. Among them, betanin and isobetanin totally accounted for more than 70% of FRAP reducing power or DPPH scavenging capacity and were a major source of the antioxidant capacities. Our findings of this pigment confirmed that Djulis can be used as a novel source of betanin antioxidants and may provide a basis for its sustainable utilization in the food industry.

Association between MDM2-SNP309 and hepatocellular carcinoma in Taiwanese population.

AIM: To investigate the risk association and compare the onset age of hepatocellular carcinoma (HCC) patients in Taiwan with different genotypes of MDM2-SNP309. METHODS: We analyzed MDM2-SNP309 genotypes from 58 patients with HCC and 138 cancer-free healthy controls consecutively. Genotyping of MDM2-SNP309 was conducted by restriction fragment length polymorphism assay. RESULTS: The proportion of homozygous MDM2-SNP309 genotype (G/G) in cases and cancer-free healthy controls was similar (17.2% vs 16.7%). Multivariate analysis showed that the risk of G/G genotype of MDM2-SNP309 vs wild-type T/T genotype in patients with HCC was not significant (OR = 1.265, 95% CI = 0.074-21.77) after adjustment for sex, hepatitis B or C virus infection, age, and cardiovascular disease/diabetes. Nevertheless, there was a trend that GG genotype of MDM2-SNP309 might increase the risk in HCC patients infected with hepatitis virus (OR = 2.568, 95% CI = 0.054-121.69). Besides, the homozygous MDM2-SNP309 genotype did not exhibit a significantly earlier age of onset for HCC. CONCLUSION: Current data suggest that the association between MDM2-SNP309 GG genotype and HCC is not significant, while the risk may be enhanced in patients infected by hepatitis virus in Taiwan.

Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the single nucleotide polymorphism (SNP309) in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer.

BACKGROUND: It has been suggested that the single nucleotide polymorphism 309 (SNP309, T -> G) in the promoter region of the MDM2 gene is important for tumor development; however, with regards to breast cancer, inconsistent associations have been reported worldwide. It is speculated that these conflicting results may have arisen due to different patient subgroups and ethnicities studied. For the first time, this study explores the effect of the MDM2 SNP309 genotype on Taiwanese breast cancer patients. METHODS: Genomic DNA was obtained from the whole blood of 124 breast cancer patients and 97 cancer-free healthy women living in Taiwan. MDM2 SNP309 genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. The multivariate logistic regression and the Kaplan-Meier method were used for analyzing the risk association and significance of age at diagnosis among different MDM2 SNP309 genotypes, respectively. RESULTS: Compared to the TT genotype, an increased risk association with breast cancer was apparent for the GG genotype (OR = 3.05, 95% CI = 1.04 to 8.95), and for the TG genotype (OR = 2.12, 95% CI = 0.90 to 5.00) after adjusting for age, cardiovascular disease/diabetes, oral contraceptive usage, and body mass index, which exhibits significant difference between cases and controls. Furthermore, the average ages at diagnosis for breast cancer patients were 53.6, 52 and 47 years for those harboring TT, TG and GG genotypes, respectively. A significant difference in median age of onset for breast cancer between GG and TT+TG genotypes was obtained by the log-rank test (p = 0.0067). CONCLUSION: Findings based on the current sample size suggest that the MDM2 SNP309 GG genotype may be associated with both the risk of breast cancer and an earlier age of onset in Taiwanese women.