Integrated physiological, transcriptomic and metabolomic analyses provide insights into phosphorus-mediated cadmium detoxification in Salix caprea roots.

Phosphorus (P) plays a crucial role in facilitating plant adaptation to cadmium (Cd) stress. However, the molecular mechanisms underlying P-mediated responses to Cd stress in roots remain elusive. This study investigates the effects of P on the growth, physiology, transcriptome, and metabolome of Salix caprea under Cd stress. The results indicate that Cd significantly inhibits plant growth, while sufficient P alleviates this inhibition. Under Cd exposure, P sufficiency resulted in increased Cd accumulation in roots, along with reduced oxidative stress levels (superoxide anion and hydrogen peroxide contents were reduced by 16.8% and 30.1%, respectively). This phenomenon can be attributed to the enhanced activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), as well as increased levels of antioxidants including ascorbic acid (AsA) and flavonoids under sufficient P conditions. A total of 4208 differentially expressed genes (DEGs) and 552 differentially accumulated metabolites (DAMs) were identified in the transcriptomic and metabolomic analyses, with 2596 DEGs and 113 DAMs identified among treatments with different P levels under Cd stress, respectively. Further combined analyses reveal the potential roles of several pathways in P-mediated Cd detoxification, including flavonoid biosynthesis, ascorbate biosynthesis, and plant hormone signal transduction pathways. Notably, sufficient P upregulates the expression of genes including HMA, ZIP, NRAMP and CAX, all predicted to localize to the cell membrane. This may elucidate the heightened Cd accumulation under sufficient P conditions. These findings provide insights into the roles of P in enhancing plant resistance to Cd stress and improving of phytoremediation.

Phosphorus deficiency-induced cell wall pectin demethylesterification enhances cadmium accumulation in roots of Salix caprea.

Regions affected by heavy metal contamination frequently encounter phosphorus (P) deficiency. Numerous studies highlight crucial role of P in facilitating cadmium (Cd) accumulation in woody plants. However, the regulatory mechanism by which P affects Cd accumulation in roots remains ambiguous. This study aims to investigate the effects of phosphorus (P) deficiency on Cd accumulation, Cd subcellular distribution, and cell wall components in the roots of Salix caprea under Cd stress. The results revealed that under P deficiency conditions, there was a 35.4% elevation in Cd content in roots, coupled with a 60.1% reduction in Cd content in shoots, compared to the P sufficiency conditions. Under deficient P conditions, the predominant response of roots to Cd exposure was the increased sequestration of Cd in root cell walls. The sequestration of Cd in root cell walls increased from 37.1% under sufficient P conditions to 66.7% under P deficiency, with pectin identified as the primary Cd binding site under both P conditions. Among cell wall components, P deficiency led to a significant 31.7% increase in Cd content within pectin compared to P sufficiency conditions, but did not change the pectin content. Notably, P deficiency significantly increased pectin methylesterase (PME) activity by regulating the expression of PME and PMEI genes, leading to a 10.4% reduction in the degree of pectin methylesterification. This may elucidate the absence of significant changes in pectin content under P deficiency conditions and the concurrent increase in Cd accumulation in pectin. Fourier transform infrared spectroscopy (FTIR) results indicated an increase in carboxyl groups in the root cell walls under P deficiency compared to sufficient P treatment. The results provide deep insights into the mechanisms of higher Cd accumulation in root mediated by P deficiency.

Exosomal circRNA HIPK3 knockdown inhibited cell proliferation and metastasis in prostate cancer by regulating miR-212/BMI-1 pathway.

Prostate cancer (PCa) is the second frequent malignancy among men in the world. Exosomal circular RNAs (circRNAs) have been reported to function in PCa progression. The current study aimed to investigate the role of exosomal circRNA homeodomain-interacting protein kinase 3 (circHIPK3) in PCa development. Exosomes were extracted from serum and cells utilizing commercial kit, and identified by transmission electron microscopy (TEM), Western blot assay and nanoparticle tracking analyzer. Relative expression of circHIPK3, microRNA (miR)-212 and B-cell specific MMLV insertion site-1 (BMI-1) was examined by quantitative realtime PCR or Western blot assay. Receiver Operating Characteristic (ROC) analysis was conducted to assess the diagnostic potential of exosomal miR-212. Cell viability, and metastasis including migration and invasion, were detected by Methyl thiazolyl tetrazolium (MTT) assay and Transwell assay, respectively. Cell apoptosis was monitored using flow cytometry. The interaction between miR-212 and circHIPK3 or BMI-1 was validated by dual-luciferase reporter assay. Xenograft tumor assay was employed to explore the role of exosomal circHIPK3 in vivo. Exosomal circHIPK3 was increased in serum of PCa patients, and could discriminate PCa patients from normal volunteers. Depletion of exosomal circHIPK3 or overexpression of exosomal miR-212 reduced viability, migration and invasion, but promoted cell apoptosis in PCa cells, which was attenuated by miR-212 inhibition or BMI-1, respectively. MiR-212 targeted BMI-1, and downregulated BMI-1 expression. Exosomal circHIPK3 knockdown also suppressed tumor growth in vivo. Exosomal circHIPK3 knockdown inhibited PCa progression by regulating miR-212/BMI-1 axis, at least in part, offering a new insight into the molecular mechanism of PCa.

Sexual differences in root growth and antioxidant characteristics in Salix viminalis exposed to cadmium stress.

NOVELTY STATEMENT: Salix viminalis, a dioecious shrub willow, has been widely used in phytoremediation, yet sexually differences in tolerance to cadmium of which remained unclear. This study focused on different responses to cadmium stress between roots of male and female S. viminalis. Results show that male plants of S. viminalis have stronger cadmium tolerance than female plants, which indicates male S. viminalis should be more considered to be applied for phytoremediation and ecological restoration of cadmium-accumulated soil considering cadmium tolerance characteristics. The findings can provide valuable evidence and insights for researches focused on phytoremediation with dioecious woody plants and sexual dimorphism under abiotic stress.

Conceptual Barriers to Palliative Care and Enlightenment From Chuang-tze's Thoughts.

This paper claims that palliative care (PC) is a suitable approach for offering comprehensive support to patients with life-threatening illness and unavoidable asthenia, to enhance their quality of life in aging and chronic illness. There are however some conceptual barriers to accessing that care on the Chinese Mainland: (1) Death-denying culture and society; (2) Misguidance and malpractice derived from the biomedical model; (3) Prejudice against PC and certain deviant understandings of filial piety culture. To counter these obstacles, the study introduces the philosophy of Chinese Taoist Chuang-tze to enlighten the public from ignorance and remove some illusions about death and dying; inspire people to face and accept illness and death calmly, and keep harmony and inner peace of mind to alleviate suffering, with the aim of providing wisdom and a shift of attitude toward life and death. Chuang-tze's thoughts are consistent with the provision of palliative care, and to a certain degree, can promote its acceptability and delivery, and the conception of good death in practice.

The Dynamics of Circulating Monocyte Subsets and Intra-Plaque Proliferating Macrophages during the Development of Atherosclerosis in ApoE-/- Mice.

To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE-/- mice, we randomly assigned 84 ApoE-/- mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE-/- mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

Discordance Between VASP Phosphorylation and Platelet Aggregation in Defining High On-Clopidogrel Platelet Reactivity After ST-Segment Elevation Myocardial Infarction.

To investigate potential clinical characteristics associated with discordance between platelet vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry (FCM) assay and light transmission aggregometry (LTA) in defining high on-clopidogrel platelet reactivity (HPR) after ST-segment elevation myocardial infarction (STEMI). In this study, platelet responsiveness was measured by the above 2 methods simultaneously on day 1 and on day 6 of STEMI onset in 90 consecutive patients who underwent primary percutaneous coronary intervention. The FCM-derived platelet reactivity index and LTA-derived platelet aggregation rate were both significantly reduced after dual antiplatelet therapy on day 6. Multiple variable-adjusted logistic regression analysis revealed that smoking (odds ratio [OR]: 4.507, 95% confidence interval [CI]: 1.123-18.09, P = .034) and onset-to-admission time (per 1 hour increase, OR: 1.196, 95% CI: 1.023-1.398, P = .025) both were independent predictors for the discordance between the 2 methods. Additionally, improved correlation and concordance was observed in nonsmokers compared with smokers. Our data show that smoking and prolonged onset-to-admission time are associated with discordance between platelet VASP-P and LTA in defining HPR after STEMI, which should be considered when planning personalized antiplatelet therapy.

The Kinetics of Circulating Monocyte Subsets and Monocyte-Platelet Aggregates in the Acute Phase of ST-Elevation Myocardial Infarction: Associations with 2-Year Cardiovascular Events.

In experimental myocardial infarction (MI), a rise in cell counts of circulating monocyte subsets contributes to impaired myocardial healing and to atherosclerotic plaque destabilization. In humans, the prognostic role of monocyte subsets in patients suffering ST-elevation MI (STEMI) is still unclear. In the present study, we aimed to determine the kinetics of the 3 monocyte subsets (classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes), as well as the subset-specific monocyte-platelet aggregates (MPA), in acute STEMI followed by primary percutaneous coronary intervention (PCI), and their relationships with cardiovascular outcomes during a 2-year follow-up.Monocyte subsets and MPA were measured in 100 STEMI patients receiving primary PCI on days 1, 2, 3, 5, and 7 of symptom onset, which were compared with 60 stable coronary heart disease patients and 35 healthy volunteers. From day 1 to day 7, significant increases in the counts of CD14++CD16+ monocytes and CD14++CD16+ MPA were observed, with peak levels on day 2. During a median follow-up of 2.0 years, 28 first cardiovascular events (defined as cardiovascular death, nonfatal ischemic stroke, recurrent MI, need for emergency or repeat revascularization, and rehospitalization for heart failure) were recorded. After adjustment for confounders, CD14++CD16+ monocytosis (day 1 [HR: 3.428; 95% CI: 1.597-7.358; P = 0.002], day 2 [HR: 4.835; 95% CI: 1.106-21.13; P = 0.04], day 3 [HR: 2.734; 95% CI: 1.138-6.564; P = 0.02], and day 7 [HR: 2.647; 95% CI: 1.196-5.861; P = 0.02]), as well as increased levels of CD14++CD16+ MPA measured on all time points (days 1, 2, 3, 5, and 7), had predictive values for adverse cardiovascular events.In conclusion, our data show the expansion of the CD14++CD16+ monocyte subset during acute phase of STEMI has predictive values for 2-year adverse cardiovascular outcomes in patients treated with primary PCI. Future studies will be warranted to elucidate whether CD14++CD16+ monocytes may become a target cell population for new therapeutic strategies after STEMI.

Effect of periodontitis on erectile function and its possible mechanism.

INTRODUCTION: Periodontitis is one of the important risk factors resulting in cardiovascular diseases. Erectile dysfunction (ED) is strongly correlated with cardiovascular diseases. The expression of endothelial nitric oxide synthase (eNOS) in penile tissue has an important role in the mechanism of erection. AIM: To investigate the effect of periodontitis on erectile function and the possible mechanism. METHODS: After induction of periodontitis in rat, the ratio of maximum intracavernosal pressure/mean arterial pressure (ICPmax /MAP)×100, the expression of eNOS in penile tissue, the level of serum C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α), and the ultrastructural changes of the cavernous tissue were examined and compared between periodontitis rats (group A) and control rats (group B). MAIN OUTCOME MEASURE: Periodontitis significantly decrease not only the ICPmax/MAP×100 and the expression of eNOS but also the activity of NOS and the level of cyclic guanosine monophosphate (cGMP) in cavernous tissue of rat. RESULTS: After electrostimulation by 3 and 5 voltage, the ratio of ICPmax /MAP×100 in group A was significantly less than that in group B (19.54±6.16 vs. 30.45±3.12; 30.91±5.61 vs. 50.52±9.52, respectively; P<0.05).The level of serum CRP and TNF-α in group A is significantly higher in group B (P<0.05).The quantitative real-time reverse transcription polymerase chain reaction study demonstrated no statistically significant difference in the expression of mRNA of eNOS in cavernous tissue between the two groups (P>0.05). But there was significant decrease in eNOS protein of the cavernous tissue in group A than in group B (P<0.05). Total NOS activity and cGMP level in cavernosal tissue were significantly lower in group A than in group B (P<0.05). There was no significant alternation occurred in the ultrastructures of penile cavernous tissue. CONCLUSIONS: The function of penile erection is impaired by periodontitis. The decreased in the expression of eNOS and NOS activity in penile cavernous tissue caused by mild systemic inflammatory status in periodontitis may be one of the important risk factors of ED.

[Effects of Ginsenoside RB1 on neural cell apoptosis and expressions of Bcl-2 and Bax in rats following subjected to cerebral ischemia-reperfusion].

OBJECTIVE: To observe the effects of Ginsenoside Rb1 (GRb1) on neuronal cell apoptosis and the expressions of Bcl-2 and Bax in rats after cerebral ischemia-reperfusion so as to investigate the neuroprotective mechanism of GRb1. METHDOS: The model of cerebral ischemia-reperfusion was established by occluding rat middle cerebral artery for 2 h. The rats were randomly divided into two groups: ischemia-reperfusion group (I/R group) and GRb1 treat group (GRb1 group). GRb1 (40 mg/kg, i.p.) was administered immediately to rats after the onset of reperfusion. Two groups were further subdivided 7 subgroups according to various reperfusion time (3 h, 12 h, 1 d, 2 d, 3 d, 5 d and 10 d, n=4 per time point). HE staining was used to observe histological features. TUNEL and immunohistochemical method were used to analyze the cell apoptosis and expressions of Bcl-2 and Bax, respectively. RESULTS: Compared with I/R group, GRb1 reduced pathological changes, and decreased the number of apoptotic neural cells (P<0.05 on 12 h, 1 d, 2 d and 3 d) and up-regulated the number of Bcl-2 positive cells (P<0.05 on 12 h, 1 d, 3 d, 5 d and 10 d), and meanwhile down-regulated the number of Bax positive cells (P<0.05 on 3 h, 12 h, 1 d, 2 d, 3 d, 5 d and 10 d) in the ipsilateral hemisphere. CONCLUSION: The neuroprotective effect of GRb1 on cerebral ischemia-reperfusion injury is related to inhibit neuronal apoptosis and to up-regulate the expression of Bcl-2 with down-regulating the expression of Bax.