Mechanisms of surface groups regulating developmental toxicity of graphene-based nanomaterials via glycerophospholipid metabolic pathway.

Surface modification of graphene-based nanomaterials (GBNs) may occur in aquatic environment and during intentional preparation. However, the influence of the surface groups on the developmental toxicity of GBNs has not been determined. In this study, we evaluated the developmental toxicity of three GBNs including GO (graphene oxide), RGO (reduced GO) and RGO-N (aminated RGO) by employing zebrafish embryos at environmentally relevant concentrations (1-100 µg/L), and the underlying metabolic mechanisms were explored. The results showed that both GO and RGO-N disturbed the development of zebrafish embryos, and the adverse effect of GO was greater than that of RGO-N. Furthermore, the oxygen-containing groups of GBNs play a more important role in inducing developmental toxicity compared to size, defects and nitrogen-containing groups. Specifically, the epoxide and hydroxyl groups of GBNs increased their intrinsic oxidative potential, promoted the generation of ROS, and caused lipid peroxidation. Moreover, a significant decrease in guanosine and abnormal metabolism of multiple glycerophospholipids were observed in all three GBN-treated groups. Nevertheless, GO exposure triggered more metabolic activities related to lipid peroxidation than RGO or RGO-N exposure, and the disturbance intensity of the same metabolite was greater than that of the other two agents. These findings reveal underlying metabolic mechanisms of GBN-induced developmental toxicity.

Analysis of Potential Risks in Abnormal Physical Development Due to Dietary Habits in Preschool Children.

Background: The prevalence of abnormal physical development in preschool children is often linked to their dietary habits, necessitating a comprehensive investigation. Understanding the intricacies of these habits is crucial for formulating targeted interventions to enhance the overall health and well-being of this vulnerable population. Objective: This study aims to explore the dietary habits of preschool children in Shijiazhuang and evaluate their impact on abnormal physical development. The primary objective is to identify key dietary issues, particularly focusing on picky eating, and assess their association with undernutrition and obesity in this age group. Methods: Utilizing a stratified sampling approach, the study involves preschool children and their caregivers from various kindergartens in Shijiazhuang. On-site medical examinations are conducted to measure height and weight and calculate body mass index (BMI). Additionally, parents were surveyed to gather information on the general aspects and dietary habits of their children. Binary logistic regression analysis was employed to ascertain the correlation between picky eating and the risk of undernutrition and obesity. Results: The findings indicate that approximately 70% of preschool children maintain a normal BMI, while 16.67% experience undernutrition, and 13.33% face issues of being overweight or obese. Picky eating emerges as the predominant dietary habit issue, affecting 51.33% of the participants. Binary logistic regression analysis identifies picky eating as a significant risk factor for undernutrition and obesity among children. Conclusions: Picky eating stands out as the primary dietary habit concern for preschool children, concurrently posing a substantial risk for abnormal physical development. Urgent measures are warranted to rectify children's suboptimal dietary habits, elevate nutritional standards, and foster their overall health and development. These findings underscore the imperative need for interventions targeting dietary improvement in preschoolers, contributing to improving their well-being and long-term health outcomes.

Mutation of OsNRAMP5 reduces cadmium xylem and phloem transport in rice plants and its physiological mechanism.

Natural resistance associated macrophage protein 5 (NRAMP5) is a key transporter for cadmium (Cd) uptake by rice roots; however, the effect of OsNRAMP5 on Cd translocation and redistribution in rice plants remains unknown. In this study, an extremely low Cd-accumulation mutant (lcd1) and wild type (WT) plants were utilized to investigate the effect of OsNRAMP5 mutation on Cd translocation and redistribution via the xylem and phloem and its possible physiological mechanism using field, hydroponic and isotope-labelling experiments. The results showed that OsNRAMP5 mutation reduced xylem and phloem transport of Cd, due to remarkably lower Cd translocation from roots to shoots and from the leaves Ⅰ-Ⅲ to their corresponding nodes, as well as lower Cd concentrations in xylem and phloem sap of lcd1 compared to WT plants. Mutation of OsNRAMP5 reduced Cd translocation from roots to shoots in lcd1 plants by increasing Cd deposition in cellulose of root cell walls and reducing OsHMA2-and OsCCX2-mediated xylem loading of Cd, and the citric acid- and tartaric acid-mediated long-distance xylem transport of Cd. Moreover, OsNRAMP5 mutation inhibited Cd redistribution from flag leaves to nodes and panicles in lcd1 plants by increasing Cd sequestration in cellulose and vacuoles, and decreasing OsLCT1-mediated Cd phloem transport in flag leaves.

Bupleurum exerts antiarrhythmic effects by inhibiting L-type calcium channels in mouse ventricular myocytes.

BACKGROUND: Bupleurum (Bup), is a traditional effective medicine to treat colds and fevers in clinics. Multiple studies have demonstrated that Bup exhibites various biological activities, including cardioprotective effects, anti-inflammatory, anticancer, antipyretic, antimicrobial, and antiviral effects, etc. Currently, the effects of Bup on cardiac electrophysiology have not been reported yet. METHODS: Electrocardiogram recordings were used to investigate the effects of Bup on aconitine-induced arrhythmias. Patch-clamp techniques were used to explore the effects of Bup on APs and ion currents. RESULTS: Bup reduced the incidence of ventricular fibrillation (VF) and delayed the onset time of ventricular tachycardia (VT) in mice. Additionally, Bup (40 mg/mL) suppressed DADs induced by high-Ca2+ and shortened action potential duration at 50 % completion of repolarization (APD50) and action potential duration at 90 % completion of repolarization (APD90) to 60.89 % ± 8.40 % and 68.94 % ± 3.24 % of the control, respectively. Moreover, Bup inhibited L-type calcium currents (ICa.L) in a dose-dependent manner, with an IC50 value of 25.36 mg/mL. Furthermore, Bup affected the gated kinetics of L-type calcium channels by slowing down steady-state activation, accelerating the steady-state inactivation, and delaying the inactivation-recovery process. However, Bup had no effects on the Transient sodium current (INa.T), ATX II-increased late sodium current (INa.L), transient outward current (Ito), delayed rectifier potassium current (IK), or inward rectifier potassium current (IK1). CONCLUSION: Bup is an antiarrhythmic agent that may exert its antiarrhythmic effects by inhibiting L-type calcium channels.

Spatial and variety distributions, risk assessment, and prediction model for heavy metals in rice grains in China.

In this study, 6229 brown rice grains from three major rice-producing regions were collected to investigate the spatial and variety distributions of heavy metals in rice grains in China. The potential sources of heavy metals in rice grains were identified using the Pearson correlation matrix and principal component analysis, and the health risks of dietary exposure to heavy metals via rice consumption were assessed using the hazard index (HI) and total carcinogenic risk (TCR) method, respectively. Moreover, 48 paired soil and rice samples from 11 cities were collected to construct a predicting model for Cd accumulation in rice grains using the multiple linear stepwise regression analysis. The results indicated that Cd and Ni were the main heavy metal pollutants in rice grains in China, with approximately 10% of samples exceeding their corresponding maximum allowable limits. The Yangtze River basin had heavier pollution of heavy metals than the Southeast Coastal Region and Northeast Plain, and the indica rice varieties had higher heavy metal accumulation abilities compared with the japonica rice. The Cu, Pb, and Cd mainly originated from anthropogenic sources, while As, Hg, Cr, and Ni originated from both natural and anthropogenic sources. The mean HI and TCR values of dietary exposure to heavy metals via rice consumption ranged from 2.92 to 4.31 and 9.74 × 10-3 to 1.44 × 10-2, respectively, much higher than the acceptable range, and As and Ni were the main contributor to the HI and TCR for Chinese adults and children, respectively. The available Si (ASi), total Cd (TCd), available Mo (AMo), and available S (AS) were the main soil factors determining grain Cd accumulation. A multiple linear stepwise regression model was constructed based on ASi, TCd, AMo, and AS in soils with good accuracy and precision, which could be applied to predict Cd accumulation in rice grains and guide safe rice production in contaminated paddy fields.

Circulating tumor cells in gastric cancer: developments and clinical applications.

Circulating tumor cells (CTCs), which are shed from primary tumor or metastatic sites into the bloodstream and subsequently seed into distant tissues, are considered as the precursors of metastases. Gastric cancer (GC) is a highly heterogeneous malignant tumor. With regard to the diagnosis of GC, secondary pathological biopsy is difficult, while invasive examination is harmful to patients. In recent years, CTCs have made great progress in tumor diagnosis, prognosis prediction, efficacy detection and treatment guidance, but the research on the role of CTCs in GC remains limited. The following sections review the landmark studies demonstrating the technical approaches of CTCs monitoring in the field of GC. Moreover, we highlight the clinical application of CTCs numbers and phenotypes in monitoring the therapeutic efficacy and judging patient prognosis by sequential blood analyses.

Naringin exerts antiarrhythmic effects by inhibiting channel currents in mouse cardiomyocytes.

INTRODUCTION: Naringin, a flavonoid extracted from citrus plants, has a variety of biological effects. Studies have shown that increasing the consumption of flavonoid-rich foods can reduce the incidence of cardiac arrhythmia. Naringin has been reported to have beneficial cardiovascular effects and thus can be used to prevent cardiovascular diseases, but the electrophysiological mechanism through which it prevents arrhythmias has not been elucidated. This study was conducted to investigate the effect of naringin on the transmembrane ion channel currents in mouse ventricular myocytes and the antiarrhythmic effect of this compound on Langendorff-perfused mouse hearts. METHODS: Action potentials (APs) and ionic currents were recorded in isolated ventricular myocytes using the whole-cell patch-clamp technique. Anemone toxin II (ATX II) and CaCl2 were used to induce early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), respectively. Electrocardiogram (ECG) recordings were conducted in Langendorff-perfused mouse hearts with a BL-420F biological signal acquisition and analysis system. RESULTS: At the cellular level, naringin shortened the action potential duration (APD) of ventricular myocytes and decreased the maximum depolarization velocity (Vmax) of APs.Naringin inhibited the L-type calcium current (ICa.L) and ATX II enhanced the late sodium current (INa.L) in a concentration-dependent manner with IC50 values of 508.5 µmol/L (n = 9) and 311.6 µmol/L (n = 10), respectively. In addition, naringin also inhibited the peak sodium current (INa·P) and delayed the rectifier potassium current (IK) and the transient outward potassium current (Ito). Moreover, naringin reduced ATX II-induced APD prolongation and EADs and had a significant inhibitory effect on CaCl2-induced DADs as well. At the organ level, naringin reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by ATX II and shortened the duration of both in isolated hearts. CONCLUSION: Naringin can inhibit the occurrence of EADs and DADs at the cellular level; furthermore, it can inhibit INa.L, ICa.L, INa·P, IK, and Ito in ventricular myocytes. Naringin also inhibits arrhythmias induced by ATX II in hearts. By investigating naringin with this electrophysiological method for the first time, we determined that this flavonoid may be a multichannel blocker with antiarrhythmic effects.

Reduction of oil uptake in vacuum fried Pleurotus eryngii chips via ultrasound assisted pretreatment.

The reduction of oil uptake in vacuum-fried Pleurotus eryngii chips by ultrasound assisted pretreatment was investigated regarding the pore structure changes. Pore structure of P. eryngii chips with four pretreatments, such as blanching, blanching + osmosis, blanching + ultrasound and blanching + ultrasound assisted osmosis was determined by mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). In addition, the quality parameters of vacuum-fried P. eryngii chips such as hardness, rehydration ratio, reducing sugar, protein and oil content were also measured. The results showed that the oil absorption of vacuum fried P. eryngii chips was affected by the porous structure. The oil content of vacuum fried P. eryngii chips was significantly and positively correlated with the pores with diameters above 50, 5-50, and 0.5-5 µm in the samples both before and after vacuum frying, while negatively correlated with the pores with diameters below 0.5 µm. Ultrasound pretreatment changed the microporous structure of P. eryngii chips, effectively hindering the oil absorption of samples. In particular, ultrasound assisted osmosis pretreatment induced the formation of more micropores. It was concluded that blanching + ultrasound assisted osmosis pretreatment is a promising method to reduce oil absorption and improve the quality of vacuum fried foods.

Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review.

Esophageal cancer is of high importance to occurrence, development, and treatment resistance. As evidenced by recent studies, pathways (e.g., Wnt/ß-catenin, AMPK, and Hippo) are critical to the proliferation, differentiation, and self-renewal of esophageal cancer. In addition, the above pathways play a certain role in regulating esophageal cancer and act as potential therapeutic targets. Over the past few years, the function of lipid metabolism in controlling tumor cells and immune cells has aroused extensive attention. It has been reported that there are intricate interactions between lipid metabolism reprogramming between immune and esophageal cancer cells, whereas molecular mechanisms should be studied in depth. Immune cells have been commonly recognized as a vital player in the esophageal cancer microenvironment, having complex crosstalk with cancer cells. It is increasingly evidenced that the function of immune cells in the tumor microenvironment (TME) is significantly correlated with abnormal lipid metabolism. In this review, the latest findings in lipid metabolism reprogramming in TME are summarized, and the above findings are linked to esophageal cancer progression. Aberrant lipid metabolism and associated signaling pathways are likely to serve as a novel strategy to treat esophageal cancer through lipid metabolism reprogramming.

Potential Progression Mechanism and Key Genes in Early Stage of mTBI.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive mild traumatic brain injury (rmTBI), and the lack of sensitive diagnostic and prognostic biomarkers for rmTBI leads to long-term sequelae after injury. The purpose of this study is to identify key genes of rmTBI and find the potential progression mechanism in early stage of mTBI. We downloaded the gene expression profiles of GSE2871 from Gene Expression Omnibus (GEO) datasets. Differentially expressed genes (DEGs) were screened from the cerebral cortex of rats 24 hours after smTBI, and these DEGs were then subjected to GO enrichment analysis, KEGG pathway analysis, PPI analysis, and hub analysis. Key genes were identified as the most significantly expressed genes and had a higher degree of connectivity from hub genes. By using homemade metal pendulum impact equipment and a multiple regression discriminant equation to assess the severity of rats after injury, smTBI and rmTBI rat models were established in batches, and q-PCR analyses were performed to verify the key genes. The main KEGG pathways were cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction. SPP1 and C3 were the most significant DEGs, and their connectivity degree was the highest 24 hours after smTBI (logFC > 4; connectivity degree ＞15). The q-PCR analyses were performed 24 hours and 14 days after mTBI. The results showed that SPP1 and C3 were significantly upregulated in smTBI and in rmTBI at 24 hours after injury compared with their levels in sham-injured rats, and the phenomenon persisted 14 days after injury. Notably, 14 days after injury, both of these genes were significantly upregulated in the rmTBI group compared with the smTBI. These pathways and genes identified could help understanding the development in mTBI.

Crosstalk of pyroptosis, ferroptosis, and mitochondrial aldehyde dehydrogenase 2-related mechanisms in sepsis-induced lung injury in a mouse model.

Acute lung injury (ALI) is a common complication of sepsis. Mitochondrial aldehyde dehydrogenase 2 (ALDH2), an enzyme involved in aldehyde metabolism, exerts a protective effect against sepsis. This study investigated the possible mechanisms underlying the roles of ALDH2, pyroptosis, and ferroptosis in sepsis-induced lung injury. A mouse model of sepsis-induced lung injury was established by cecal ligation and puncture (CLP); lung morphology was evaluated by calculation of lung coefficient, hematoxylin-eosin staining, and electron microscopy. Malondialdehyde (MDA), reactive oxygen species (ROS), and 4-hydroxy-2-nonenal (4-HNE) protein expression levels were used to detect the level of lipid oxidative stress. In addition, total iron was detected using an iron detection kit, and the expression of ferroptosis-related proteins (PTGS2, GPX4), pyroptosis-related proteins, and ALDH2 was examined using western blotting. To further examine the likely mechanisms, the ferroptosis inhibitor ferrostatin 1 (Fer-1), NLRP3 inflammasome inhibitor MCC950, and ALDH2 activator Alda-1 were added. CLP-treated mice exhibited destruction of lung tissue morphology, lipid peroxidation injury, iron content, and increased lung PTGS2 protein expression, accompanied by a decrease in GPX4 protein expression. CLP also downregulated ALDH2 expression and increased the expression of the NLRP3 inflammasome and pyroptosis-related proteins. These adverse effects of CLP were relieved by Alda-1, Fer-1, and MCC950 treatment. In conclusion, both pyroptosis and ferroptosis participate in CLP-induced ALI, and ALDH2 plays a protective role by reducing pyroptosis and ferroptosis. This study provides a scientific basis for the treatment of lung injury in sepsis.

The potential role of plasma membrane proteins in response to Zn stress in rice roots based on iTRAQ and PRM under low Cd condition.

Cd pollution had already caused serious threats to crop growth and development, food safety and human health, and become a potential agricultural and global environmental problem. Zn had been used to reduce Cd accumulation in soil and plants. Proteins located in plasma membrane (PM) played important roles in transferring stress signals in plants. To further elucidate how PM proteins modulated Zn/Cd transport under low-Cd condition, quantitative proteomics was employed to identify and verify the differentially expressed proteins (DEPs) and their biological functions at proteome level. A total of 4008 proteins were identified, and 332 DEPs (192 up and 140 down, fold >1.50 or <0.66, p < 0.01) were screened. Functional analysis showed that DEPs were mainly catalytic active and binding proteins, involved in glutathione metabolism, phenylpropanoid biosynthesis, etc. DEPs involved in ion transport played key roles in regulating transmembrane transport, resisting stress and alleviating toxicity of heavy metals to rice roots. DEPs were as the marker proteins in rice root responding to heavy metal stress. This study had important guiding significances for metal ions transport mechanism and screening of biomarkers responding to abiotic stress, and provided references for further researches underlying abiotic stress and detoxication in rice and other plants.

Mapping and functional analysis of high-copper accumulation mutant oshc1 in rice.

Copper (Cu) is an essential but potentially toxic element in rice. Little is known about the mechanism of rice grain Cu accumulation. In this study, we identified a high copper accumulation in grain 1 (oshc1) mutant from the wild type indica rice cultivar 9311 (WT) mutant bank. Compared with those in WT, more Cu was shown to accumulate in the shoots of seedlings and the above-ground tissues except nodes although less total Cu content in oshc1. Further analysis showed that the mutant had an accelerated Cu transport ratio from roots to shoots and higher Cu concentration in xylem sap than WT. This phenomenon in oshc1 was controlled by a single recessive gene, which was identified as BGIOSGA007732, and named OsHMA4. The eight base frame-shift from 1021 to 1028 bp in the coding sequence of OsHMA4 led to a modification after the 341st amino acid and resulted in premature translation termination of OsHMA4 at the 377th amino acid. This may change the function of OsHMA4. Furthermore, the up-regulated OsCOPT7 and OsATX1 and down-regulated OsHMA4 probably decrease Cu compartmentalization in roots of oshc1. In summary, the frame-shift in OsHMA4 changes the function of OsHMA4 and the expression of genes relative to Cu transport in the mutant, which leads to more Cu transport upward and higher Cu accumulation in the rice grains. Moreover, oshc1 was more tolerance to Cu-shortage than WT, while more sensitive to Cu excess exposure than WT. However, RNA-Seq analysis shown that changes in transcription levels of genes in oshc1 involving in molecular function of ions binding and biological processes of cell wall organization and defense response to bio-stress. Which indicates that oshc1 is advantage to Cu limited condition than WT. This work reveals the mechanism of high Cu accumulation in the grains of oshc1 and provides a material to breed new cultivars with optimum levels of Cu in brown rice by crossing with other dominant varieties, which can be planted in different soils to ensure the yield and quality of rice.

Salicylic acid reduces cadmium (Cd) accumulation in rice (Oryza sativa L.) by regulating root cell wall composition via nitric oxide signaling.

The effects of salicylic acid (SA) on cadmium (Cd) accumulation, Cd subcellular distribution, cell wall composition and Cd adsorption in Cd-stressed rice seedlings were examined. The interaction between SA and nitric oxide (NO) signaling in regulating cell wall composition under Cd exposure was also investigated. Our results showed that 5 µmol·L-1 Cd treatment significantly decreased plant height, root length and plant dry weight by 40.1%, 46.1% and 21.3% (p < 0.05), respectively, and the inhibitory effects of Cd on the growth parameters were alleviated by exogenous SA. Application of SA remarkably decreased Cd concentrations in roots and shoots of rice seedlings by 48.0% and 19.6%, respectively, and increased the distribution ratio of Cd in the root cell wall fraction (from 35.7% to 40.6%) compared with Cd treatment alone. The reduced Cd accumulation in rice plants could be attributed to that SA application promoted pectin synthesis and demethylesterification, thereby increasing Cd deposition in the root cell wall. Moreover, SA application promoted lignin biosynthesis to strengthen the cell wall and prevent Cd from entering the root cells. In addition, NO might be involved in SA-induced pectin synthesis, pectin demethylesterification and lignin biosynthesis as a downstream signaling molecule, contributing to reduced Cd accumulation in Cd-stressed rice seedlings. The results provide deep insights into the mechanisms of exogenous SA action in reducing Cd accumulation in rice plants.

NRT2.1, a major contributor to cadmium uptake controlled by high-affinity nitrate transporters.

Management of nitrogen fertilizer is a good strategy for controlling cadmium (Cd) accumulation in plants. Some progress has already been made but much remains to be done. Here, we show that mutants with loss of function of nitrate transporter1.1 (NRT1.1) or nitrate transporter2.1 (NRT2.1) had lower Cd concentrations than wild-type plants under low-nitrate conditions. However, this was eliminated when plants were cultivated in nitrate-free medium or supplied with Cd and nitrate alternately. These findings indicate that inhibition of NRT1.1 or NRT2.1 activity reduces Cd accumulation in plants, and depends on the presence of nitrate. The results showing that nrt2.1-2 mutants had the lowest Cd concentrations compared with Col-0, nrt1.1 and nrt2.4 plants, proves that NRT2.1 is the major contributor to Cd uptake controlled by nitrate high-affinity transporters. NRT2.1 acts as the major contributor to nitrate uptake under Cd stress in low-nitrate conditions, and contributes about 50% to nitrate uptake, while NRT1.1 contributes only 10%, and little is known regarding the role of NRT2.2 and NRT2.4 on nitrate uptake in medium with 200 µM nitrate. Positive correlations between nitrate uptake and Cd concentration in plants were also observed. Collectively, NRT2.1 acts as the major contributor to Cd uptake by controlling nitrate uptake in nitrate high-affinity systems.

Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury.

To observe the changes in NLR family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of diabetes-induced lung injury, and investigate the effect of low-dose ethanol on the production of NLRP3 inflammasome. The type I diabetic mellitus (DM) rat model was established, and the rats were divided into four groups: normal control group (CON group), low-dose ethanol group (EtOH group), diabetes group (DM group) and DM+EtOH group. The rats were fed for 6 and 12 weeks, respectively. The ratio of lung wet weight/body weight (lung/body coefficient) was calculated, and the changes of pulmonary morphology and fibrosis were observed by HE and Masson staining. The changes in pulmonary ultra-structure were examined by electron microscopy. The expressions of mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) and NLRP3 inflammasome key factors, NLRP3, ASC and caspase-1 proteins were detected by western blot. Compared with the CON group, the lung/body coefficient was increased (P<0.05), lung fibrosis occurred, ALDH2 protein expression was decreased, and NLRP3, ASC and caspase-1 protein expressions were increased in the DM rats (P<0.05). Compared with the DM group, the lung/body coefficient and fibrosis degree were decreased, ALDH2 protein expression was increased (P<0.05), and NLRP3, ASC and caspase-1 protein expressions were decreased in the DM+EtOH group (P<0.05). Hence, low-dose ethanol increased ALDH2 protein expression and alleviated diabetes-induced lung injury by inhibiting the production of NLRP3 inflammasome.

Functional plasticity abnormalities over the lifespan of first-episode patients with major depressive disorder: a resting state fMRI study.

BACKGROUND: Neurodevelopmental and neurodegenerative theories of depression suggest that patients with major depressive disorder (MDD) may follow abnormal developmental, maturational, and aging processes. However, a lack of lifespan studies has precluded verification of these theories. Herein, we analyzed functional magnetic resonance imaging (fMRI) data to comprehensively characterize age-related functional trajectories, as measured by the fractional amplitude of low frequency fluctuations (fALFF), over the course of MDD. METHODS: In total, 235 MDD patients with age-differentiated onsets and 235 age- and sex-matched healthy controls (HC) were included in this study. We determined the pattern of age-related fALFF changes by cross-sectionally establishing the general linear model (GLM) between fALFF and age over a lifespan. Furthermore, the subjects were divided into four age groups to assess age-related neural changes in detail. Inter-group fALFF comparison (MDD vs. HC) was conducted in each age group and Granger causal analysis (GCA) was applied to investigate effective connectivity between regions. RESULTS: Compared with the HC, no significant quadratic or linear age effects were found in MDD over the entire lifespan, suggesting that depression affects the normal developmental, maturational, and degenerative process. Inter-group differences in fALFF values varied significantly at different ages of onset. This implies that MDD may impact brain functions in a highly dynamic way, with different patterns of alterations at different stages of life. Moreover, the GCA analysis results indicated that MDD followed a distinct pattern of effective connectivity relative to HC, and this may be the neural basis of MDD with age-differentiated onsets. CONCLUSIONS: Our findings provide evidence that normal developmental, maturational, and ageing processes were affected by MDD. Most strikingly, functional plasticity changes in MDD with different ages of onset involved dynamic interactions between neuropathological processes in a tract-specific manner.

Z-scheme TiO2@Ti3C2/Cd0.5Zn0.5S nanocomposites with efficient photocatalytic performance via one-step hydrothermal route.

Photocatalytic degradation of pollutants has been proved to be an effective strategy for wastewater treatment. Herein, TiO2 nanoparticles were synthesized on a Ti3C2 matrix by in situ growth, forming Z-scheme TiO2@Ti3C2/Cd0.5Zn0.5S (TO/CZS) multilevel structured nanocomposites via one-step hydrothermal route. The effects of hydrothermal temperature and Cd0.5Zn0.5S content on microstructure and properties of composites were assessed. TO/CZS nanocomposites were probed into phase composition, morphological and optical properties with x-ray diffractometer, infrared radiation, scanning electron microscope and UV-vis reflective spectra. Following the hydrothermal reaction at 160 °C for 12 h, TiO2 nanoparticles of 30 nm in diameter were generated in situ on Ti3C2 lamina and Cd0.5Zn0.5S particles were evenly distributed on the Ti3C2 matrix. The photocatalytic activity of TO/CZS composites were evaluated, which found that degradation rate constant (k = 0.028 min-1) of TO/CZS-40 on Rhodamine B was 5.19 times that of pure TiO2 and 4.48 times that of Cd0.5Zn0.5S. Through anchoring Ti3C2 as an electron transition mediator and combination with TiO2 and Cd0.5Zn0.5S, the new Z-scheme between TiO2 oxidized by Ti3C2 and Cd0.5Zn0.5S establishes a multilevel structure of separating electron-hole pairs. This work demonstrates a valid way to control electrons and hole transfer directions efficiently through designing multilevel semiconductor structural designs.

Eleutheroside B, a selective late sodium current inhibitor, suppresses atrial fibrillation induced by sea anemone toxin II in rabbit hearts.

Eleutheroside B (EB) is the main active constituent derived from the Chinese herb Acanthopanax senticosus (AS) that has been reported to possess cardioprotective effects. In this study we investigated the effects of EB on cardiac electrophysiology and its suppression on atrial fibrillation (AF). Whole-cell recording was conducted in isolated rabbit atrial myocytes. The intracellular calcium ([Ca2+]i) concentration was measured using calcium indicator Fura-2/AM fluorescence. Monophasic action potential (MAP) and electrocardiogram (ECG) synchronous recordings were conducted in Langendorff-perfused rabbit hearts using ECG signal sampling and analysis system. We showed that EB dose-dependently inhibited late sodium current (INaL), transient sodium current (INaT), and sea anemone toxin II (ATX II)-increased INaL with IC50 values of 167, 1582, and 181 µM, respectively. On the other hand, EB (800 µM) did not affect L-type calcium current (ICaL), inward rectifier potassium channel current (IK), and action potential duration (APD). Furthermore, EB (300 µM) markedly decreased ATX II-prolonged the APD at 90% repolarization (APD90) and eliminated ATX II-induced early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and triggered activities (TAs). Moreover, EB (200 µM) significantly suppressed ATX II-induced Na+-dependent [Ca2+]i overload in atrial myocytes. In the Langendorff-perfused rabbit hearts, application of EB (200 µM) or TTX (2 µM) substantially decreased ATX II-induced incidences of atrial fibrillation (AF), ventricular fibrillation (VF), and heart death. These results suggest that augmented INaL alone is sufficient to induce AF, and EB exerts anti-AF actions mainly via blocking INaL, which put forward the basis of pharmacology for new clinical application of EB.

Isoliensinine Eliminates Afterdepolarizations Through Inhibiting Late Sodium Current and L-Type Calcium Current.

Isoliensinine (IL) extracted from lotus seed has a good therapeutic effect on cardiovascular diseases. However, its effect on ion channels of ventricular myocytes is still unclear. We used whole-cell patch-clamp techniques to detect the effects of IL on transmembrane ion currents and action potential (AP) in isolated rabbit left ventricular myocytes. IL inhibited the transient sodium current (INaT), late sodium current (INaL) enlarged by sea anemone toxin (ATX II) and L-type calcium current (ICaL) in a concentration-dependent manner without affecting inward rectifier potassium current (IK1) and delayed rectifier potassium current (IK). These inhibitory effects are mainly manifested as reduced the AP amplitude (APA) and maximum depolarization velocity (Vmax) and shortened the action potential duration (APD), but had no significant effect on the resting membrane potential (RMP). Moreover, IL significantly eliminated ATX II-induced early afterdepolarizations (EADs) and high extracellular calcium-induced delayed afterdepolarizations (DADs). These results revealed that IL effectively eliminated EADs and DADs through inhibiting INaL and ICaL in ventricular myocytes, which indicates it has potential antiarrhythmic action.