Ampholytic ion-exchange magnetic beads: a promising tool for selecting short fragments in circulating cell-free DNA analysis.

Objective: For liquid biopsy of cancer, the extraction of circulating cell-free DNA (cfDNA) from plasma is required. We evaluated the efficacy of use of magnetic submicron particles coated with abundant small zwitterions (MSP-ZEWBs) for extracting short fragments of cfDNA. Methods: We developed and optimized an MSP-ZEWB-based cfDNA extraction method using ampholytic ion-exchange materials and compared its results with those using a control kit. We measured the cfDNA concentration by quantitative polymerase-chain-reaction and using the Qubit method and analyzed cfDNA fragmentation patterns using a bioanalyzer. Results: The fragment size of cfDNA isolated from glycine hydrochloric acid at a pH of 2.2 exhibited a better alignment with the DNA marker. The highest DNA intensity was observed at the final concentration of 0.8% polyethylene glycol 8000. The intensity of cfDNA decreased significantly when isolated from plasma with DNA marker using MSP-ZEWBs with an adsorption buffer containing guanidine hydrochloride or isothiocyanoguanidine. All fragments were successfully extracted using MSP-ZEWBs from both plasma and phosphate-buffered saline. Notably, the intensity of short cfDNA fragments isolated using MSP-ZEWBs remained consistent for recovery of long DNA fragments. indicating a potential selective of small fragments. Conclusion: The extraction of plasma cfDNA with MSP-ZEWBs requires no protein denaturation, shows resistance to cells remaining in plasma, and demonstrates higher overall efficiency and better reproducibility than other extraction methods. Use of MSP-ZEWBs may greatly enhance liquid biopsy of cancers through the analysis of plasma cfDNA in clinical practice.

Exploring the Relationship of Leisure Travel with Loneliness, Depression, and Cognitive Function in Older Adults.

Loneliness, depression, and cognitive decline are pressing concerns among older adults. This study examines the association between leisure travel participation and these health outcomes in older adults, aiming to provide further evidence of the benefits of leisure travel. Using nationally representative historical data from the 2006 household survey of the Health and Retirement Study, this study conducted a series of regression analyses to investigate the relationship between traveling and the three health outcomes, adjusting for age, sex, race, marital status, education, total wealth, annual income, and difficulty with daily activities. The results reveal that travel patterns in terms of distance are significantly associated with loneliness, depression, and cognitive function. Long-distance travel is positively related to higher cognitive function and a reduction in depressive symptoms, along with lower levels of loneliness, reinforcing the notion that leisure travel can potentially act as a catalyst for improved cognitive and mental health by offering opportunities for enhancing social connections and forming new relationships. The findings on the relationships between participation in leisure travel and mental and cognitive health contribute to the body of evidence supporting the therapeutic value of leisure travel in promoting healthy aging and enhancing the overall well-being in older adults.

NAD Pathways in Diabetic Coronary Heart Disease: Unveiling the Key Players.

Diabetic coronary heart disease is a global medical problem that poses a serious threat to human health, and its pathogenesis is complex and interconnected. Nicotinamide adenine dinucleotide (NAD) is an important small molecule used in the body that serves as a coenzyme in redox reactions and as a substrate for non-redox processes. NAD levels are highly controlled by various pathways, and increasing evidence has shown that NAD pathways, including NAD precursors and key enzymes involved in NAD synthesis and catabolism, exert both positive and negative effects on the pathogenesis of diabetic coronary heart disease. Thus, the mechanisms by which the NAD pathway acts in diabetic coronary heart disease require further investigation. This review first briefly introduces the current understanding of the intertwined pathological mechanisms of diabetic coronary heart disease, including insulin resistance, dyslipidemia, oxidative stress, chronic inflammation, and intestinal flora dysbiosis. Then, we mainly review the relationships between NAD pathways, such as nicotinic acid, tryptophan, the kynurenine pathway, nicotinamide phosphoribosyltransferase, and sirtuins, and the pathogenic mechanisms of diabetic coronary heart disease. Moreover, we discuss the potential of targeting NAD pathways in the prevention and treatment of diabetic coronary heart disease, which may provide important strategies to modulate its progression.

Responses of lettuce (Lactuca sativa L.) growth and soil properties to conventional non-biodegradable and new biodegradable microplastics.

Residual plastic films in soils are posing a potential threat to agricultural ecosystem. However, little is known about the impacts of microplastics (MPs) derived from biodegradable and non-biodegradable plastic films on plant-soil systems. Here, we carried out a pot experiment using soil-cultivated lettuce treated by two types of MPs, degradable poly(butylene adipate-co-terephthalate) (PBAT-MPs) and non-biodegradable polyethylene (PE-MPs). MPs resulted in different degrees of reduction in shoot biomass, chlorophyll content, photosynthetic parameters, and leaf contents of nitrogen (N), phosphorus (P), and potassium (K), accelerated accumulation of hydrogen peroxide and superoxide, and increased malondialdehyde content in lettuce leaves. Moreover, MPs obviously decreased contents of total N, nitrate, ammonium, and available K in soils, and increased available P, thus altering soil nutrient availability. MPs also significantly decreased proportions of macroaggregates, and decreased soil electrical conductivity and microbial activity. PBAT-MPs had significantly greater impacts on oxidative damage, photosynthetic rate, soil aggregation, microbial activity, and soil ammonium than those of PE-MPs. Our results suggested that MPs caused oxidative damages, nutrient uptake inhibition, soil properties alteration, ultimately leading to growth reduction, and PBAT-MPs exhibited stronger impacts. Therefore, it is urgent to further study the ecological effects of MPs, especially biodegradable MPs, on soil-plant systems.

Detection of ustilaginoidins in rice samples by immunoassay based on monoclonal antibodies prepared from hemiustilaginoidin-derived haptens.

Ustilaginoidins are a class of bis-naphtho-γ-pyrone mycotoxins to threaten humans, animals and environment. Ustilaginoidins are produced by Villosiclava virens, the rice false smut pathogen. To prepare antibodies for quantitatively analyzing ustilaginoidins in rice samples, hemiustilaginoidins D and F from the laccase gene deficiency mutant of V. virens respectively reacted with diazonium 4-aminobenzoic acid to obtain haptens with a carboxyl group, which further reacted with bovine serum albumin or ovalbumin to get their complete antigens. Two monoclonal antibodies (mAbs) designated as 4A12C6 and 5F4F6 were developed by immunization. The relationships between mAb sensitivity and 20 ustilaginoidins were described. 4A12C6 was chosen for further analysis as it could recognize main ustilaginoidins and was more sensitive than 5F4F6. The achieved indirect competitive enzyme-linked immunosorbent assay (icELISA) based on 4A12C6 had a half maximal inhibitory concentration (IC50) of 0.76 ng/mL and working range of 0.2-2.8 ng/mL to ustilaginoidin A. The results of ustilaginoidins-contaminated rice samples by icELISA detection were consistent with those determined by HPLC‒DAD detection. Therefore, we developed a new strategy to get haptens from the biosynthetic precursors with half structures of ustilaginoidins. The achieved icELISA was demonstrated as a convenient method to monitor ustilaginoidin content in rice samples, and showed that the contents of total ustilaginoidins from the rice cultivars with low resistance to rice false smut were more than those of high resistance cultivars.

Travel and Social Isolation of People With Spinal Cord Injury.

Background: People with spinal cord injury (SCI) are at high risk for social isolation because they face barriers to social participation owing to limitations in physical functioning, secondary health conditions, and environmental barriers. Research has shown that social isolation, an objective lack of contact with others, can lead to loneliness, mental health issues, and low life satisfaction. Leisure travel, which involves interactions with others, may have the potential to reduce social isolation. Objectives: To explore the association of travel participation with social isolation among people with SCI. Methods: A total of 11,091 cases from 2016-2021 in the SCI Model Systems database were included in the study. Participants were categorized into low and high social isolation groups. A hierarchical logistic regression was performed with social isolation as the dependent variable and travel groups as the independent variable, while controlling for age, family income, and health conditions. Results: Travel participation is negatively associated with social isolation. People with SCI who traveled for one to two nights (odd ratio [OR] 0.52, 95% CI 0.40-0.67), three to four nights (OR 0.56, 95% CI 0.43-0.72), or more than five nights (OR 0.41, 95% CI 0.35-0.49) in the past 12 months are less likely to be socially isolated compared to those who have not traveled in the past 12 months. Conclusion: Travel participation may help reduce the social isolation of individuals with SCI. Therapists and rehabilitation professionals should design effective travel training programs that encourage patients with SCI to travel more often.

[Neurobehavioral damage and Th17 cell infiltration in mice exposed to nano carbon black].

OBJECTIVE: The effects of nano-carbon black on neural behavior and Th17 cell infiltration in mice were investigated by establishing a mice model of subacute dynamic inhalation of carbon black aerosol. METHODS: 36 SPF grade male C57BL/6 mice were randomly divided into a control group(clean air), a low carbon black group(15 mg/m~3), and a high carbon black group(30 mg/m~3). Nano-carbon black particles were blown into the dynamic exposure cabinet by aerosol generator for 28 days. Morris water maze test and open field test were used to detect the neural behavior of mice. The pathological changes of prefrontal cortex in mice were observed by HE staining. The proportion of Th17/CD4~+ cells in peripheral blood and brain tissue of mice was detected by flow cytometry. Western blotting was used to detect the protein expression of interleukin(IL)-17 and IL-23 in the prefrontal cortex of mice. RESULTS: The result of open field test showed that compared with the control group, the central area residence time and standing times of mice in the low and high carbon black groups decreased significantly(P<0.05), and the defecation times of mice in the high carbon black group increased significantly(P<0.05). The central area residence time of mice in the high carbon black group was significantly lower than that in the low carbon black group(P<0.05). The Morris water maze result showed that the escape latency of the high carbon black group mice on the 3rd day was significantly higher than that of the control group(P<0.05). Meanwhile, the escape latency of the carbon black group mice on the 4th day was significantly higher than that of the control group(P<0.05). The positioning navigation test showed that the number of mice crossing the platform in the high carbon black group was significantly higher than that in the control group(P<0.05). The HE staining result showed that the neural cells in the prefrontal cortex of the control group mice were round, the cytoplasm was plump and evenly distributed, and the nucleus was clearly visible in an oval shape. The low carbon black group showed that the neural cells were deep staining of nerve cells, blurred structure, and nuclear pyknosis. The high carbon black group further intensified. The flow cytometry result showed that compared with the control group, the percentage of Th17/CD4~+T cells in the peripheral blood of the carbon black group mice was significantly increased, and the high carbon black group mice were significantly higher than the low carbon black group(P<0.05). Meanwhile, the percentage of Th17/CD4~+T cells in the brain tissue of carbon black treated mice significantly increased(P<0.05). The high carbon black group was significantly higher than the low carbon black group(P<0.05). Western blotting result showed that compared with the control group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the carbon black group mice brain tissue was significantly increased(P<0.05). Compared with the low carbon black group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the high carbon black group mice brain tissue was significantly increased(P<0.05). The difference was statistically significant. CONCLUSION: Nano-carbon black exposure can lead to an increase in Th17 cells in peripheral blood and brain tissue of mice, which in turn promotes damage to the prefrontal cortex of mice, and ultimately causes neurobehavioral changes in mice.

Elicitation with hydrogen peroxide promotes growth, phenolic-enrichment, antioxidant activity and nutritional values of two hydroponic lettuce genotypes.

Dietary vegetables rich in bioactive compounds are major responsible for promoting human health. Herein, the effect of hydrogen peroxide (H2O2), an important signaling compound, on growth and quality of two hydroponic lettuce genotypes was investigated. The maximum enhancement of growth traits was shown in lettuce elicited with 10 mmol/L H2O2, while 40 mmol/L H2O2 significantly reduced above growth traits. H2O2 elicitation increased pigment contents and photosynthetic process, which consequently caused enhancements of phenolic compounds, ascorbic acid, glutathione, carotenoids, soluble sugars, free amino acids, soluble protein, minerals, and antioxidant capacity, while above alterations appeared in a genotype-dependent manner. The phenolic accumulation was correlated with improved activity of phenylalanine ammonia lyase (PAL) and expression levels of genes related to phenolic biosynthesis, including PAL, chalcone synthase, flavanone 3-hydroxylase, dihydroflavonol-4 reductase, and UDP-glucose: flavonoid 3-O-glucosyltransferase. Therefore, elicitation with H2O2 is a promising strategy to develop lettuce with high bioactive compounds and biomass.

Ginsenoside Rb1 Promotes Hepatic Glycogen Synthesis to Ameliorate T2DM Through 15-PGDH/PGE2/EP4 Signaling Pathway.

Purpose: Ginsenoside Rb1 (Rb1), one of the crucial bioactive constituents in Panax ginseng C. A. Mey., possesses anti-type 2 diabetes mellitus (T2DM) property. Nevertheless, the precise mechanism, particularly the impact of Rb1 on hepatic glycogen production, a crucial process in the advancement of T2DM, remains poorly understood. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is responsible for prostaglandin E2 (PGE2) inactivation. A recent study has reported that inhibition of 15-PGDH promoted hepatic glycogen synthesis and improved T2DM. Therefore, herein, we aimed to investigate whether Rb1 ameliorated T2DM through 15-PGDH/PGE2-regulated hepatic glycogen synthesis. Methods: By combining streptozotocin with a high-fat diet, we successfully established a mouse model for T2DM. Afterward, these mice were administered Rb1 or metformin for 8 weeks. An insulin-resistant cell model was established by incubating LO2 cells with palmitic acid. Liver glycogen and PGE2 levels, the expression levels of 15-PGDH, serine/threonine kinase AKT (AKT), and glycogen synthase kinase 3 beta (GSK3ß) were measured. Molecular docking was used to predict the binding affinity between 15-PGDH and Rb1. Results: Rb1 administration increased the phosphorylation levels of AKT and GSK3ß to enhance glycogen synthesis in the liver of T2DM mice. Molecular docking indicated that Rb1 had a high affinity for 15-PGDH. Moreover, Rb1 treatment resulted in the suppression of elevated 15-PGDH levels and the elevation of decreased PGE2 levels in the liver of T2DM mice. Furthermore, in vitro experiments showed that Rb1 administration might enhance glycogen production by modulating the 15-PGDH/PGE2/PGE2 receptor EP4 pathway. Conclusion: Our findings indicate that Rb1 may enhance liver glycogen production through a 15-PGDH-dependent pathway to ameliorate T2DM, thereby offering a new explanation for the positive impact of Rb1 on T2DM and supporting its potential as an effective therapeutic approach for T2DM.

A Novel and Efficient Phthalate Hydrolase from Acinetobacter sp. LUNF3: Molecular Cloning, Characterization and Catalytic Mechanism.

Phthalic acid esters (PAEs), which are widespread environmental contaminants, can be efficiently biodegraded, mediated by enzymes such as hydrolases. Despite great advances in the characterization of PAE hydrolases, which are the most important enzymes in the process of PAE degradation, their molecular catalytic mechanism has rarely been systematically investigated. Acinetobacter sp. LUNF3, which was isolated from contaminated soil in this study, demonstrated excellent PAE degradation at 30 °C and pH 5.0-11.0. After sequencing and annotating the complete genome, the gene dphAN1, encoding a novel putative PAE hydrolase, was identified with the conserved motifs catalytic triad (Ser201-Asp295-His325) and oxyanion hole (H127GGG130). DphAN1 can hydrolyze DEP (diethyl phthalate), DBP (dibutyl phthalate) and BBP (benzyl butyl phthalate). The high activity of DphAN1 was observed under a wide range of temperature (10-40 °C) and pH (6.0-9.0). Moreover, the metal ions (Fe2+, Mn2+, Cr2+ and Fe3+) and surfactant TritonX-100 significantly activated DphAN1, indicating a high adaptability and tolerance of DphAN1 to these chemicals. Molecular docking revealed the catalytic triad, oxyanion hole and other residues involved in binding DBP. The mutation of these residues reduced the activity of DphAN1, confirming their interaction with DBP. These results shed light on the catalytic mechanism of DphAN1 and may contribute to protein structural modification to improve catalytic efficiency in environment remediation.

[Latest Findings in Key Research Areas of Precision Nursing for Chronic Diseases in Older Adults].

The advent of the era of biomedical big data has helped promote the development of precision nursing. Precision nursing for chronic diseases in older adults is an interdisciplinary research field in which accurate individualized data are utilized to carry out early screening and health management of older adult populations at high risk for chronic diseases and early intervention of diseases, which plays an important role in improving the prognosis of diseases and the health level of the older adult population. Herein, we introduced the concept of precision nursing, and discussed the latest research findings in the key areas of precision nursing for chronic diseases in older adults, including precision symptom management in cancer patients and precision nursing in older patients with multimorbidity. At present, research concerning precise symptom management of cancer patients is mainly focused on prediction modelling for risks of symptoms, longitudinal change trajectories, core symptom identification, etc. Investigations in the precise nursing of cancer patients are conducted in the following areas, risk prediction, the timing of interventions, and intervention targets. Research on precision nursing for multimorbidity is mainly focused on assessment of chronic disease multimorbidity, multimorbidity pattern recognition, and health management of multimorbidity. We also discussed potential opportunities and challenges of precision nursing in the future, in order to provide a scientific basis for the improving the practice and theories of precision nursing. In the future, precision nursing will play an ever more important role in uncovering pathogenic information, the diagnosis and treatment of diseases, the health of the research population, and the promotion of medical research.

15-Hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates hepatic abnormal lipid metabolism, ER stress, and inflammation through PGE2/EP4 in T2DM mice.

Type 2 diabetes mellitus (T2DM) is a rapidly growing epidemic that results in increased morbidity, mortality, and soaring medical costs. Prostaglandin E2 (PGE2), a vital lipid mediator, has been reported to protect against hepatic steatosis, inflammation, endoplasmic reticulum (ER) stress, and insulin resistance, indicating its potential therapeutic role in T2DM. PGE2 can be degraded by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). SW033291, an inhibitor of 15-PGDH, has been reported to increase PGE2 levels, however, the effect of SW033291 in T2DM remains to be explored. This study aims to evaluate whether SW033291 protects against T2DM and explore its potential mechanisms. A T2DM mouse model was established through high-fat diet/streptozotocin injection, while palmitic acid-treated mouse primary hepatocytes were used as insulin-resistant cell models. SW033291 treatment reduced body weight, fat weight, fasting blood glucose, and improved impaired glucose tolerance and insulin resistance in T2DM mice. More importantly, SW033291 alleviated steatosis, inflammation, and ER stress in the liver of T2DM mice. Mechanistically, SW033291 decreased the expressions of SREBP-1c and ACC1, and increased the expression of PPARα in T2DM mice. Additionally, SW033291 inhibited NF-κB and eIF2α/CHOP signaling in T2DM mice. Further, we showed that the protective effects of SW033291 on the above-mentioned pathophysiological processes could be hindered by inhibition of the PGE2 receptor EP4. Overall, our study reveals a novel role of SW033291 in alleviating T2DM and suggests its potential as a new therapeutic strategy for T2DM.

The 15-hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates abnormal hepatic glucose metabolism through PGE2-EP4 receptor-AKT signaling in a type 2 diabetes mellitus mouse model.

Type 2 diabetes mellitus (T2DM) is associated with high rates of morbidity and mortality worldwide. Prostaglandin E2 (PGE2) is a lipid signaling molecule that can ameliorate the symptoms of some metabolic diseases, including T2DM, and improve tissue repair and regeneration. Although SW033291 can increase PGE2 levels through its action as a small molecule inhibitor of the PGE2-degrading enzyme 15-hydroxyprostaglandin dehydrogenase, its effects on T2DM remain unclear. In the present study, we evaluated whether SW033291 treatment exerts a protective effect against T2DM and explored the underlying mechanisms. A T2DM mouse model was established using a high-fat diet combined with streptozotocin treatment. Palmitic acid-treated LO2 cells were used as an insulin-resistant cell model. SW033291 treatment reduced body weight and fasting blood glucose levels as well as serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels in vivo. In addition to ameliorating glucose and insulin tolerance, SW033291 treatment reversed the T2DM-induced decrease in glycogen synthesis and increase in gluconeogenesis in the liver. Furthermore, SW033291 administration increased hepatic glycogen synthase kinase 3 beta (GSK3ß) phosphorylation levels to promote glycogen synthesis. SW033291 treatment also inhibited gluconeogenesis by upregulating AKT serine/threonine kinase (AKT) and forkhead box O1 (FOXO1) phosphorylation and reducing glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 expression in the livers of T2DM model mice. Additionally, SW033291 treatment improved abnormal hepatic glucose metabolism through the PGE2-EP4 receptor-AKT-GSK3ß/FOXO1 signaling pathway in vitro. These results suggest a novel role of SW033291 in improving T2DM and support its potential as a novel therapeutic agent.

FTZ promotes islet ß-cell regeneration in T1DM mice via the regulation of nuclear proliferation factors.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang-Zhenzhu-Tiaozhi capsule (FTZ), a Traditional Chinese Medicine (TCM) patent prescription commonly used in clinical practice, has a significant curative effect on hyperglycemia and hyperlipidemia. Previous studies have shown that FTZ can treat diabetes, but the effect of FTZ on ß-cell regeneration needs to be further explored in T1DM mice. AIM OF THE STUDY: The aim is to investigate the role of FTZ in promoting ß-cell regeneration in T1DM mice, and to further explore its mechanism. MATERIALS AND METHODS: C57BL/6 mice were used as control. NOD/LtJ mice were divided into the Model group and FTZ group. Oral glucose tolerance, fasting blood glucose, and fasting insulin level were measured. Immunofluorescence staining was used to detect the level of ß-cell regeneration and the composition of α-cells and ß-cells in islets. Hematoxylin and eosin staining was used to detect the infiltration degree of inflammatory cells. The apoptosis of islet cells was detected by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. Western blotting was used to detect the expression levels of Pancreas/duodenum homeobox protein 1 (PDX-1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA), and Neurogenin-3 (NGN3). RESULTS: FTZ could increase insulin levels and reduce the glucose level of T1DM mice and promote ß-cell regeneration. FTZ also inhibited the invasion of inflammatory cells and the islet cell apoptosis, and maintained the normal composition of islet cells, thus preserving the quantity and quality of ß-cells. Furthermore, FTZ promoting ß-cell regeneration was accompanied by increasing the expression of PDX-1, MAFA, and NGN3. CONCLUSION: FTZ can restore the insulin-secreting function of the impaired pancreatic islet, improve blood glucose level, possibly via the enhancing ß cell regeneration via upregulation of PDX-1, MAFA, and NGN3 in T1DM mice, and may be a potential therapeutic drug for T1DM.

PbO nanoparticles increase the expression of ICAM-1 and VCAM-1 by increasing reactive oxygen species production in choroid plexus.

PbO nanoparticles (nano-PbO) are widely used in the production of electrode materials, but exposure to them can cause brain damage. The first barrier preventing nano-PbO from entering the brain is the choroid plexus. However, the effect of nano-PbO on the choroid plexus remains unclear. Thus, the purpose of this study was to investigate the effect of nano-PbO exposure on lymphocyte cells infiltration, the adhesion protein of the choroid plexus as well as the role of reactive oxygen species (ROS) during the process. Results showed that nano-PbO exposure increased the percentage of lymphocyte cells in the brain and upregulated the expression of surface adhesion proteins, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in choroid plexus. Meanwhile, nano-PbO treatment also resulted in the increase of intercellular ROS production, and significantly decrease glutathione (GSH) content, glutathione peroxidase (GSH-PX) activity, and superoxide dismutase (SOD) activity in Z310 cells beside the increase of ICAM and VCAM-1 expression. Treatment with ROS inhibitor N-acetylcysteine (NAC) significantly downregulated the expression of ICAM-1 and VCAM-1expression. In conclusion, exposure to nano-PbO increases the expression of ICAM-1 and VCAM-1 through oxidative stress, which may contribute to peripheral lymphocyte cells infiltration into the brain.

Pb induces ferroptosis in choroid plexus epithelial cells via Fe metabolism.

Pb can enhance blood-cerebrospinal fluid barrier (BCSFB) permeability and accumulate in brain tissue, leading to central nervous system (CNS) dysfunction. Choroid plexus (CP) epithelial cells are the main components of the BCSFB with crucial functions in BCSFB maintenance. However, the mechanism by which Pb exposure affects CP epithelial cells remains unclear. Here, ferroptosis was identified as the major programmed cell death modality by sophisticated high-throughput sequencing and biochemical investigations in primary cultured CP epithelial cells following Pb exposure. Bioinformatics analysis using the ferroptosis database revealed that 16 ferroptosis-related genes were differentially expressed in primary cultured CP epithelial cells following Pb exposure. Among them, Gpx4, Slc7a11, Tfrc, and Slc40a1 were hub ferroptosis-related genes. In addition, CP epithelial cells can be impaired when the concentration of the Pb2+ reached 2050 µg/L (10 µM PbAc), which included the decrease of cell viability, Gpx4 and Slc7a11 proteins expression, etc. Moreover, inhibition of ferroptosis enhanced CP epithelial cell viability and reduced BCSFB permeability in vitro following Pb exposure. In summary, ferroptosis of CP epithelial cells is involved in BCSFB dysfunction following Pb exposure. Gpx4, Slc7a11, Tfrc, and Slc40a1 are hub ferroptosis-related genes in CP epithelial cells.

Thermally conductive and compliant polyurethane elastomer composites by constructing a tri-branched polymer network.

Most elastomers suffer from poor thermal conductivity, which limits their further applications in various fields, especially for electronic devices. A common method to enhance thermal conductivity is to introduce thermally conductive fillers into elastomers. Unfortunately, thermal conductivity and compliance are often correlated and coupled: large amounts of fillers are required to increase thermal conductivity while damaging the compliance dramatically. In this study, we report thermally conductive and compliant polyurethane elastomer composites by constructing a tri-branched polymer network. The resultant polyurethane elastomer composites exhibit excellent superhigh stretchability (2000%), low Young's modulus (640 kPa), and low thermal resistance (0.11 K cm2 W-1). Experimental rheology and a theoretical tube model are employed to study the nature of the high compliant tri-branched polymer network. Furthermore, the remarkable flexibility of our elastomer composite and heat dissipation act as thermal interface materials in the thermal management of flexible electronics. These findings advance our understanding on the rational design of the polymer frameworks of thermal composites, improving our ability to predict, design, and leverage their unique properties for future applications.

Integration of high-throughput phenotyping, GWAS, and predictive models reveals the genetic architecture of plant height in maize.

Plant height (PH) is an essential trait in maize (Zea mays) that is tightly associated with planting density, biomass, lodging resistance, and grain yield in the field. Dissecting the dynamics of maize plant architecture will be beneficial for ideotype-based maize breeding and prediction, as the genetic basis controlling PH in maize remains largely unknown. In this study, we developed an automated high-throughput phenotyping platform (HTP) to systematically and noninvasively quantify 77 image-based traits (i-traits) and 20 field traits (f-traits) for 228 maize inbred lines across all developmental stages. Time-resolved i-traits with novel digital phenotypes and complex correlations with agronomic traits were characterized to reveal the dynamics of maize growth. An i-trait-based genome-wide association study identified 4945 trait-associated SNPs, 2603 genetic loci, and 1974 corresponding candidate genes. We found that rapid growth of maize plants occurs mainly at two developmental stages, stage 2 (S2) to S3 and S5 to S6, accounting for the final PH indicators. By integrating the PH-association network with the transcriptome profiles of specific internodes, we revealed 13 hub genes that may play vital roles during rapid growth. The candidate genes and novel i-traits identified at multiple growth stages may be used as potential indicators for final PH in maize. One candidate gene, ZmVATE, was functionally validated and shown to regulate PH-related traits in maize using genetic mutation. Furthermore, machine learning was used to build predictive models for final PH based on i-traits, and their performance was assessed across developmental stages. Moderate, strong, and very strong correlations between predictions and experimental datasets were achieved from the early S4 (tenth-leaf) stage. Colletively, our study provides a valuable tool for dissecting the spatiotemporal formation of specific internodes and the genetic architecture of PH, as well as resources and predictive models that are useful for molecular design breeding and predicting maize varieties with ideal plant architectures.

Fufang-zhenzhu-tiaozhi formula protects islet against injury and promotes ß cell regeneration in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang-zhenzhu-tiaozhi formula (FTZ) is a patented preparation of traditional Chinese medicine that has been used to treat hyperglycemia and hyperlipidemia in the clinic for almost 10 years. Our previous study had demonstrated that FTZ can protect islet ß cell injury in vitro. However, the efficacy of FTZ on ß cell regeneration in vivo and the involved anti-diabetic mechanism remains unknown. AIM OF THE STUDY: We aim to investigate the effects of FTZ as a good remedy for islet protection and ß cell regeneration, and to reveal the underlying mechanism. MATERIALS AND METHODS: C57BL/6 mice were fed with high-fat diet for 3 weeks and then intraperitoneally injected with streptozotocin (90 mg/kg/d × 1 d) to establish type 2 diabetes (T2D) models. Mice in each group were divided into three batches that sacrificed after 3, 7 and 28 days of FTZ administration. Body weight, blood glucose, and oral glucose tolerance test were measured at indicated time points. Fasting insulin was determined by enzyme-linked immunosorbent assay (ELISA) kit. Neonatal ß cell was assessed by insulin & PCNA double immunofluorescence staining, and the underlying mechanisms related to ß cell regeneration were further performed by hematoxylin-eosin staining, insulin & glucagon double immunofluorescence staining and Western blot. RESULTS: FTZ and metformin can significantly help with the symptoms of DM, such as alleviating weight loss, reducing blood glucose, improving the level of insulin in vivo, and relieving insulin resistance, suggesting FTZ and metformin treatment maintained the normal morphological function of islet. Notably, ß cell regeneration, which is indicated by insulin and PCNA double-positive cells, was promoted by FTZ, whereas few neonatal ß cells were observed in metformin group. Hematoxylin-eosin staining, and its quantification results showed that FTZ effectively prevented the invasion of inflammatory cells into the islets in diabetic mice. Most ß cells in the islets of diabetic model mice were devoid, and the islets were almost all α cells, while the diabetic mice administered FTZ could still maintain about half of the ß cells in the islet. Furthermore, FTZ upregulated the expression of critical transcription factors during ß cell development and maturation (such as PDX-1, MAFA and NGN3) in diabetic mice. CONCLUSIONS: FTZ can alleviate diabetes symptoms and promote ß cell regeneration in diabetic mice. Moreover, FTZ promotes ß cell regeneration by preserving islet (resisting inflammatory cells invading islets), maintaining the number of ß cells in islets, and increasing the expression of PDX-1, MAFA and NGN3.

Role of prostaglandin E2 in macrophage polarization: Insights into atherosclerosis.

Atherosclerosis, a trigger of cardiovascular disease, poses grave threats to human health. Although atherosclerosis depends on lipid accumulation and vascular wall inflammation, abnormal phenotypic regulation of macrophages is considered the pathological basis of atherosclerosis. Macrophage polarization mainly refers to the transformation of macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, which has recently become a much-discussed topic. Increasing evidence has shown that M2 macrophage polarization can alleviate atherosclerosis progression. PGE2 is a bioactive lipid that has been observed to be elevated in atherosclerosis and to play a pro-inflammatory role, yet recent studies have reported that PGE2 promotes anti-inflammatory M2 macrophage polarization and mitigates atherosclerosis progression. However, the mechanisms by which PGE2 acts remain unclear. This review summarizes current knowledge of PGE2 and macrophages in atherosclerosis. Additionally, we discuss potential PGE2 mechanisms of macrophage polarization, including CREB, NF-κB, and STAT signaling pathways, which may provide important therapeutic strategies based on targeting PGE2 pathways to modulate macrophage polarization for atherosclerosis treatment.