Cadmium Minimization in Crops: A Trade-Off With Mineral Nutrients in Safe Breeding.

Cadmium (Cd) contamination poses a threat to global crop safety. To address this issue, researchers mainly focused on the Cd, explored mechanism of accumulation to low-Cd breeding technologies and created several low-Cd varieties over the past decades. However, new challenges have emerged, particularly the yield reduction due to disturbances in mineral nutrient balance. The goals of breeding have been transferred from a primary focus on 'low-Cd crops' to 'low-Cd/nutrient-balanced' crops, which means limiting Cd content while maintaining other nutrient elements like iron (Fe), manganese (Mn) and zinc (Zn) at a proper content, thus to meet the future agricultural demands. Here, on a multielement perspective, we reviewed the mechanisms of Cd and mineral nutrient transport system in crops and summarized the research advances in Cd minimization through artificial mutations, natural variations and genetic engineering. Furthermore, the challenge of disruption of mineral nutrients in low-Cd crops was discussed and two potential approaches designing Cd-mineral nutrient-optimized artificial transporters and pyramiding Cd-mineral nutrient-optimized variations were proposed. Aiming at addressing these challenges, these approaches represent promising advancements in the field and offer potential pathways for future research and development in the creation of safe and high-quality crops.

Causal relationship between psoriasis vulgaris and dementia: Insights from Mendelian randomization analysis.

Many clinical studies have demonstrated a correlation between psoriasis vulgaris and dementia, yet this correlation remains controversial. Our study employed the Mendelian randomization (MR) method to investigate the causal relationship between psoriasis vulgaris and dementia. Data were obtained from the summary statistics of the genome-wide association studies from IEU-OpenGWAS project database. In univariate Mendelian randomization (UVMR) analysis, psoriasis vulgaris was used as exposure. Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD) and frontotemporal dementia (FTD) served as the outcomes. In multivariate Mendelian randomization (MVMR) analysis, VaD served as the outcome. The first MVMR analysis used psoriasis vulgaris, mean platelet volume (MPV), platelet distribution width (PDW) and platelet count (PLT) as exposures. The second MVMR analysis used psoriasis vulgaris, vitamin D level and 25 hydroxyvitamin D level as exposures. The main analysis employed the inverse variance weighted method, and the outcomes were evaluated by odds ratio (OR) and 95% confidence interval (95% CI). In UVMR analysis, the results depicted that psoriasis vulgaris was associated with VaD (OR: 0.903, 95% CI: 0.818-0.996, p = 0.041). The results revealed insignificant associations between psoriasis vulgaris and other dementia types. After adjusting the effects of MPV, PDW and PLT in MVMR analysis, the association between psoriasis vulgaris and VaD was no longer significant (p = 0.164). Similarly, after adjusting the effects of vitamin D level and 25 hydroxyvitamin D level in MVMR analysis, the association between psoriasis vulgaris and VaD was also no longer significant (p = 0.533). Our study suggests that psoriasis vulgaris may potentially decrease VaD incidence. However, the causal association between psoriasis vulgaris and VaD may be impeded by platelet-related indices, vitamin D level and 25 hydroxyvitamin D level.

Hypercholesterolemia and the Increased Risk of Vascular Dementia: a Cholesterol Perspective.

PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.

TGF-ß1 and FOXM1 siRNA co-loaded nanoparticles by disulfide crosslinked PEG-PDMAEMA for the treatment of triple-negative breast cancer and its bone metastases in vitro.

INTRODUCTION: Triple-negative breast cancer (TNBC) is characterized by higher malignancy and mortality and is prone to distant metastasis, among which bone is the most common site. It's urgent to explore new strategies for the treatment of TNBC and its bone metastases. METHODS: A tumor environment responsive vector, poly-(dimethylaminoethyl methacrylate)-SS-poly(ethylene glycol)-SS-poly-(dimethylaminoethyl methacrylate) (PDMAEMA-SS-PEG-SS-PDMAEMA), was constructed to co-delivery transforming growth factor-ß1 (TGF-ß1) siRNA and forkhead box M1 (FOXM1) siRNA in MDA-MB-231 cells. The preparation, characterization, in vitro release, stability, and transfection efficiency of nanoparticles were measured. Cell viability, migration, and invasion of MDA-MB-231 cells were determined. Cell chemotactic migration and cell heterogeneity adhesion of MDA-MB-231 cells to the human osteoblast-like cell line MG-63 were determined. RESULTS: PDMAEMA-SS-PEG-SS-PDMAEMA self-assembled with siRNA at N/P of 15:1 into nanoparticles with a particle size of 122 nm. In vitro release exhibited redox and pH sensitivity, and the nanoparticles protected siRNA from degradation by RNase and serum protein, remaining stable at 4 °C with similar transfection efficiency with lipo2000. Nanoparticles co-loaded with TGF-ß1 siRNA and FOXM1 siRNA inhibited the cell viability, migration and invasion of MDA-MB-231 cells, as well as chemotactic migration and heterogeneous adhesion of MDA-MB-231 cells to MG-63 cells, showing a synergetic effect. After gene silencing on TGF-ß1 and FOXM1, the epithelial to mesenchymal transition (EMT) related molecules vimentin mRNA expression decreased while E-cadherin increased. CONCLUSIONS: PDMAEMA-SS-PEG-SS-PDMAEMA was suitable for TGF-ß1 siRNA and FOXM1 siRNA delivery, exhibiting a synergetic inhibition effect on TNBC and its bone metastases, which might be related to its synergetic inhibition on EMT.

Association of sleep characteristics with stroke incidence and all-cause mortality: A cross-sectional study in the United States.

BACKGROUND: Stroke represents a significant health crisis in the United States, claiming approximately 140,000 lives annually and ranking as the fifth leading cause of death. OBJECTIVE: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) for 2005 to 2008, this study examines the correlation between various sleep characteristics and both stroke morbidity and all-cause mortality among U.S. adults. METHODS: We applied logistic regression, Cox regression, and subgroup analyses to a sample of 7,827 adults aged 18 and older from NHANES 2005-2008. The study focused on six sleep characteristics: duration of sleep, sleep onset latency, snoring frequency, number of awakenings, frequency of leg spasms during sleep, and daytime sleepiness, analyzing their impacts on stroke incidence and mortality rates. RESULTS: Participants had an average age of 45.80 ± 0.45 years, with females accounting for 48.13 % of the sample. Analysis revealed significant associations between sleep duration, onset latency, number of awakenings, leg spasms, and daytime sleepiness with stroke incidence. However, these associations weakened with increasing confounders. Additionally, stroke patients showed a higher likelihood of using sleep aids. The influence of sleep disturbances on stroke appeared more pronounced in females and younger demographics. An association was also noted between the number of awakenings, sleep duration, and stroke mortality rates CONCLUSIONS: The study reinforces the critical role of maintaining healthy sleep patterns in preventing strokes and enhancing stroke prognosis, emphasizing specific sleep disturbances as potential risk factors.

Evaluation of Internet-based pharmaceutical care effect on young and middle-aged patients with hypertension by the principal component analysis and the Markov cohort during COVID-19 pandemic.

BACKGROUND: Pharmaceutical care has the potential to improve hypertension control rates in young and middle-aged patients. Due the COVID-19 epidemic, standard intervention methods may not be applicable. We propose establishing an internet-based pharmaceutical care (IPC) route to improve blood pressure control in young and middle-aged patients with hypertension. An evaluation method based on Principal Component Analysis (PCA) and Orthogonal Partial Least-Discriminant Analysis (OPLS-DA) was established to evaluate the effect of the IPC method. METHODS: 1) Internet-based Pharmaceutical care (IPC) was provided by pharmacists mainly using Wechat software for one year after enrollment; 2) PCA and OPLS-DA were applied to analyze questionnaire reliability and data variability; 3) Markov cohort was used to evaluate the IPC effect. RESULTS: Ninety-seven young and middle-aged patients were enrolled. 96 patients received the IPC. 1) The blood pressure control rate increased to 71.88% after IPC in 96 patients. 2) After conducting PCA and OPLS-DA analysis, 10 questions in the questionnaire were significantly improved after the IPC. 3) Markov cohort results showed that patient survival after 28 cycles was 18.62 years and the quality-adjusted life year (QALY) was extended by 5.40 years. The cumulative cost-effectiveness ratio was ¥87.10 per QALY. CONCLUSIONS: The IPC method could significantly improve the blood pressure control rate of patients. The questionnaire analysis method based on PCA and OPLS-DA is an effective method to evaluate the effect of the IPC method. The Markov cohort showed that the IPC had an effect on blood pressure control rate changes. Patients had a strong willingness to pay for IPC.

Characterization of a novel arsenite long-distance transporter from arsenic hyperaccumulator fern Pteris vittata.

Pteris vittata is an arsenic (As) hyperaccumulator that can accumulate several thousand mg As kg-1 DW in aboveground biomass. A key factor for its hyperaccumulation ability is its highly efficient As long-distance translocation system. However, the underlying molecular mechanisms remain unknown. We isolated PvAsE1 through the full-length cDNA over-expression library of P. vittata and characterized it through a yeast system, RNAi gametophytes and sporophytes, subcellular-location and in situ hybridization. Phylogenomic analysis was conducted to estimate the appearance time of PvAsE1. PvAsE1 was a plasma membrane-oriented arsenite (AsIII) effluxer. The silencing of PvAsE1 reduced AsIII long-distance translocation in P. vittata sporophytes. PvAsE1 was structurally similar to solute carrier (SLC)13 proteins. Its transcripts could be observed in parenchyma cells surrounding the xylem of roots. The appearance time was estimated at c. 52.7 Ma. PvAsE1 was a previously uncharacterized SLC13-like AsIII effluxer, which may contribute to AsIII long-distance translocation via xylem loading. PvAsE1 appeared late in fern evolution and might be an adaptive subject to the selection pressure at the Cretaceaou-Paleogene boundary. The identification of PvAsE1 provides clues for revealing the special As hyperaccumulation characteristics of P. vittata.

Exosomal microRNAs shuttling between tumor cells and macrophages: cellular interactions and novel therapeutic strategies.

Extracellular vesicles secreted by tumor microenvironment (TME) cells are vital players in tumor progression through transferring nucleic acids and proteins. Macrophages are the main immune cells in TME and tumor associated macrophages (TAM) express M2 phenotype, which induce tumor proliferation, angiogenesis, invasion, metastasis and immune elimination, resulting in the subsequent evolution of malignancies. There are a high number of studies confirmed that tumor cells and TAM interact with each other through extracellular vesicles in various cancers, like pancreatic ductal adenocarcinoma, gastric cancer, breast cancer, ovarian cancer, colon cancer, glioblastoma, hepatocellular cancer, and lung cancer. Herein, this review summarizes the current knowledge on mechanisms of communications between tumor cells and TAM via extracellular vesicles, mainly about microRNAs, and targeting these events might represent a novel approach in the clinical implications of this knowledge into successful anti-cancer strategies.

Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling.

A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood-brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.

MiR-145 in cancer therapy resistance and sensitivity: A comprehensive review.

MircoRNA (miRNA) are a group of small, non-coding, regulatory RNA with an average length of approximately 22 nucleotides, which mostly modulate gene expression post-transcriptionally through complementary binding to the 3'-untranslated region (3'-UTR) of multiple target genes. Emerging evidence has shown that miRNA are frequently dysregulated in a variety of human malignancies. Among them, microRNA-145 (miR-145) has been increasingly identified as a critical suppressor of carcinogenesis and therapeutic resistance. Resistance to tumor therapy is a challenge in cancer treatment due to the daunting range of resistance mechanisms. We reviewed the status quo of recent advancements in the knowledge of the functional role of miR-145 in therapeutic resistance and the tumor microenvironment. It may serve as an innovative biomarker for therapeutic response and cancer prognosis.