Abscisic acid employs NRP-dependent PIN2 vacuolar degradation to suppress auxin-mediated primary root elongation in Arabidopsis.

How plants balance growth and stress adaptation is a long-standing topic in plant biology. Abscisic acid (ABA) induces the expression of the stress-responsive Asparagine Rich Protein (NRP), which promotes the vacuolar degradation of PP6 phosphatase FyPP3, releasing ABI5 transcription factor to initiate transcription. Whether NRP is required for growth remains unknown. We generated an nrp1 nrp2 double mutant, which had a dwarf phenotype that can be rescued by inhibiting auxin transport. Insufficient auxin in the transition zone and over-accumulation of auxin at the root tip was responsible for the short elongation zone and short-root phenotype of nrp1 nrp2. The auxin efflux carrier PIN2 over-accumulated in nrp1 nrp2 and became de-polarized at the plasma membrane, leading to slower root basipetal auxin transport. Knock-out of PIN2 suppressed the dwarf phenotype of nrp1 nrp2. Furthermore, ABA can induce NRP-dependent vacuolar degradation of PIN2 to inhibit primary root elongation. FyPP3 also is required for NRP-mediated PIN2 turnover. In summary, in growth condition, NRP promotes PIN2 vacuolar degradation to help maintain PIN2 protein concentration and polarity, facilitating the establishment of the elongation zone and primary root elongation. When stressed, ABA employs this pathway to inhibit root elongation for stress adaptation.

Effects of aquatic high-intensity interval training and moderate-intensity continuous training on central hemodynamic parameters, endothelial function and aerobic fitness in inactive adults.

Objective: The effects of land-based high-intensity interval training (HIIT) on the cardiovascular system have already been demonstrated. However, the water environment is different from that on land. Therefore, we investigated the effects of 6-week aquatic HIIT and moderate-intensity continuous training (MICT) on central hemodynamic parameters, endothelial function, and aerobic fitness in inactive adults. Methods: Thirty-one inactive adults were randomly assigned to HIIT or MICT group. HIIT group performed twelve 30-s swimming exercise bouts with the intensity of 95% HRmax and 15-18/20 RPE with a 60-s rest period between each bout. MICT group performed a 30-min uninterrupted swimming exercise with the intensity of 70%-75% HRmax and 12-14/20 RPE. Training frequency for both groups was three times a week. The pulse wave analysis and flow-mediated dilation (FMD) were measured by non-invasive equipments. Results: The aerobic fitness significantly increased after HIIT, but no change was seen after MICT. Augmentation pressure (AP) and augmentation index normalized at 75 bpm (AIx@HR75) significantly decreased after HIIT but not MICT, whereas MICT rather than HIIT improved subendocardial viability ratio (SEVR), central and peripheral blood pressure, and resting HR. Only HIIT significantly increased brachial endothelial function. Conclusion: A six-week aquatic HIIT and MICT had no differences in hemodynamic parameters, endothelial function, and aerobic fitness, however 6 weeks of aquatic HIIT reduced arterial stiffness, increased endothelial function and aerobic fitness, while 6 weeks of aquatic MICT reduced arterial blood pressure and resting HR and increased the coronary blood flow reserve.

Asymmetric signal amplification for simultaneous SERS detection of multiple cancer markers with significantly different levels.

Simultaneous detection of cancer biomarkers holds great promise for the early diagnosis of different cancers. However, in the presence of high-concentration biomarkers, the signals of lower-expression biomarkers are overlapped. Existing techniques are not suitable for simultaneously detecting multiple biomarkers at concentrations with significantly different orders of magnitude. Here, we propose an asymmetric signal amplification method for simultaneously detecting multiple biomarkers with significantly different levels. Using the bifunctional probe, a linear amplification mode responds to high-concentration markers, and quadratic amplification mode responds to low-concentration markers. With the combined biobarcode probe and hybridization chain reaction (HCR) amplification method, the detection limits of microRNA (miRNA) and ATP via surface-enhanced Raman scattering (SERS) detection are 0.15 fM and 20 nM, respectively, with a breakthrough of detection concentration difference over 11 orders of magnitude. Furthermore, successful determination of miRNA and ATP in cancer cells supports the practicability of the assay. This methodology promises to open an exciting new avenue for the detection of various types of biomolecules.

CircHIPK3/miR-124 affects angiogenesis in early-onset preeclampsia via CPT1A-mediated fatty acid oxidation.

Multiple theories have been proposed to explain the pathogenesis of early-onset preeclampsia (EOPE), and angiogenic dysfunction is an important part of this pathogenesis. Carnitine palmitoyltransferase (CPT1A) is a key rate-limiting enzyme in the metabolic process of fatty acid oxidation (FAO). FAO regulates endothelial cell (EC) proliferation during vascular germination and is also essential for ab initio deoxyribonucleotide synthesis, but its role in EOPE needs to be further elucidated. In the present study, we investigated its functional role in EOPE by targeting the circHIPK3/miR-124-3p/CPT1A axis. In our study, reduced expression of circHIPK3 and CPT1A and increased expression of miR-124-3p in placental tissues from patients with EOPE were associated with EC dysfunction. Here, we confirmed that CPT1A regulates fatty acid oxidative activity, cell proliferation, and tube formation in ECs by regulating FAO. Functionally, knockdown of circHIPK3 suppressed EC angiogenesis by inhibiting CPT1A-mediated fatty acid oxidative activity, which was ameliorated by CPT1A overexpression. In addition, circHIPK3 regulates CPT1A expression by sponging miR-124-3p. Hence, circHIPK3 knockdown reduced fatty acid oxidation in ECs by sponging miR-124-3p in a CPT1A-dependent manner and inhibited EC proliferation and tube formation, which may have led to aberrant angiogenesis in EOPE. Thus, strategies targeting CPT1A-driven FAO may be promising approaches for the treatment of EOPE. KEY MESSAGES: Decreased Carnitine palmitoyltransferase (CPT1A) expression in preeclampsia(PE). CPT1A overexpression promotes FAO activity and tube formation in ECs. CircHIPK3 can affect CPT1A expression and impaire angiogenesis of EOPE. CircHIPK3 regulates CPT1A expression by acting as a ceRNA of miR-124-3p in HUVECs. Confirming the effect of circHIPK3/miR-124-3p/CPT1A axis on EOPE.

Effect of Bakri balloon tamponade combined with different suture methods on preventing postpartum hemorrhage in women with pregnancy-induced hypertension undergoing cesarean delivery.

OBJECTIVE: To investigate the effect of Bakri balloon tamponade (BBT) combined with different suture methods on preventing postpartum hemorrhage in women with pregnancy-induced hypertension (PIH) undergoing cesarean delivery (CD). METHODS: This randomized, double-blind, controlled trial was conducted at The First Affiliated Hospital of Xingtai Medical College from October 2020 to June 2023. Patients with PIH who had persistent bleeding after CD and were unresponsive to uterine contractions, sutures, or uterine disconnection procedures were eligible participants. Eligible participants were randomly assigned to control and study groups, with 50 patients in each group. The control group used BBT combined with B-lynch uterine compression sutures, while the study group used BBT combined with modified Hayman suture. Intraoperative and postoperative bleeding and changes in vital signs were compared between the 2 groups. Moreover, changes in inflammation levels, coagulation function, and sex hormone levels were compared between the 2 groups before and after surgery. RESULTS: A total of 122 patients with persistent bleeding after CD were recruited, of whom 22 were excluded (16 cases of uterine contractions and/or local uterine myometrial sutures for hemostasis, 4 cases of preoperative uterine artery embolization, and 2 cases of uterine malformations). The intraoperative blood loss, postoperative blood loss at 2 hours, postoperative blood loss at 24 hours, and decrease in red blood cell and hemoglobin in the study group were significantly lower than those in the control group (P < .05). After surgery, the levels of inflammation, coagulation function, and sex hormone in both groups improved compared to before surgery, and the study group was significantly better than the control group (P < .05). In addition, the incidence of postoperative adverse events in the study group was significantly lower than that in the control group (P < .05). CONCLUSIONS: The hemostatic effect of BBT combined with B-lynch uterine compression sutures is comparable to that of BBT combined with modified Hayman suture for postpartum hemorrhage in pregnant women with PIH undergoing CD, but the latter has less blood loss, attenuated inflammatory response, reduced impact on coagulation function and ovarian function, and a lower incidence of adverse events.

A GABAergic inhibitory neural circuit regulates visual reversal learning in Drosophila.

Inflexible cognition and behavior are prominent features of prefrontal cortex damage and several neuropsychiatric disorders. The ability to flexibly adapt cognitive processing and behavior to dynamically changing environmental contingencies has been studied using the reversal learning paradigm in mammals, but the complexity of the brain circuits precludes a detailed analysis of the underlying neural mechanism. Here we study the neural circuitry mechanism supporting flexible behavior in a genetically tractable model organism, Drosophila melanogaster. Combining quantitative behavior analysis and genetic manipulation, we found that inhibition from a single pair of giant GABAergic neurons, the anterior paired lateral (APL) neurons, onto the mushroom bodies (MBs) selectively facilitates behavioral flexibility during visual reversal learning. This effect was mediated by ionotropic GABA(A) receptors in the MB. Moreover, flies with perturbed MB output recapitulated the poor reversal performance of flies with dysfunctional APL neurons. Importantly, we observed that flies with dysfunctional APL-MB circuit performed normally in simple forms of visual learning, including initial learning, extinction, and differential conditioning. Finally, we showed that acute disruption of the APL-MB circuit is sufficient to impair visual reversal learning. Together, these data suggest that the APL-MB circuit plays an essential role in the resolution of conflicting reinforcement contingencies and reveals an inhibitory neural mechanism underlying flexible behavior in Drosophila.

A dopamine sensor based on a methoxypolyethylene glycol polymer covalently modified glassy carbon electrode.

A dopamine (DA) sensor based on a methoxypolyethylene glycol (MPEG) polymer covalently modified glass carbon electrode (GCE) was fabricated by an electroadsorption method. The electrochemical behavior of the sensor towards the catalytic oxidation of DA in pH 5.0 phosphate buffer solution (PBS) was investigated by cyclic voltammetry. The modified electrode obviously enhanced the current response and decreased the overpotentials for the oxidation of DA. Using differential pulse voltammetry, the sensor gave a linear response to DA over the concentration range of 2.0-140 µM with a detection limit (S/N = 3) of 4.68 × 10(-8) M. It was found that MPEG can complex DA through hydrogen bonding interaction between ethylene oxide units of the polymer and the protonated dopamine in acidic PBS and preconcentrate it in the film, which improved the detection limit and sensitivity of DA. The DA sensor exhibits good sensitivity, selectivity and stability, and has been applied for the determination of DA in dopamine hydrochloride injection solution.

A novel cobalt tetranitrophthalocyanine/graphene composite assembled by an in situ solvothermal synthesis method as a highly efficient electrocatalyst for the oxygen reduction reaction in alkaline medium.

A novel micro/nano-composite, based on cobalt(II) tetranitrophthalocyanine (CoTNPc) grown on poly(sodium-p-styrenesulfonate) modified graphene (PGr), as a non-noble-metal catalyst for the oxygen reduction reaction (ORR), is fabricated by an in situ solvothermal synthesis method. The CoTNPc/PGr is characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), respectively. The electrocatalytic activity of the CoTNPc/PGr composite toward the ORR is evaluated using cyclic voltammetry and linear sweep voltammetry methods. The CoTNPc/PGr composite exhibits an unexpected, surprisingly high ORR activity compared to CoTNPc or PGr. The onset potential for ORR on CoTNPc/PGr is found to be around -0.10 V vs. SCE in 0.1 M NaOH solution, which is 30 mV and 70 mV more positive than that on PGr and CoTNPc, respectively. The peak current density on CoTNPc/PGr is about 2 times than that on PGr and CoTNPc, respectively. Rotating disk electrode (RDE) measurements reveal that the ORR mechanism is nearly via a four-electron pathway on CoTNPc/PGr. The current density for ORR on CoTNPc/PGr still remains 69.9% of its initial value after chronoamperometric measurements for 24 h. Pt/C catalyst, on the other hand, only retains 13.3% of its initial current. The peak potential shifts slightly and current barely changes when 3 M methanol is added. The fabricated composite catalyst for ORR displays high activity, good stability and excellent tolerance to the crossover effect, which may be used as a promising Pt-free catalyst in alkaline direct methanol fuel cells (DMFCs).

The GABAergic anterior paired lateral neurons facilitate olfactory reversal learning in Drosophila.

Reversal learning has been widely used to probe the implementation of cognitive flexibility in the brain. Previous studies in monkeys identified an essential role of the orbitofrontal cortex (OFC) in reversal learning. However, the underlying circuits and molecular mechanisms are poorly understood. Here, we use the T-maze to investigate the neural mechanism of olfactory reversal learning in Drosophila. By adding a reversal training cycle to the classical learning protocol, we show that wild-type flies are able to reverse their choice according to the alteration of conditioned stimulus (CS)-unconditioned stimulus (US) contingency. The reversal protocol induced a specific suppression of the initial memory, an effect distinct from memory decay or extinction. GABA down-regulation in the anterior paired lateral (APL) neurons, which innervate the mushroom bodies (MBs), eliminates this suppression effect and impairs normal reversal. These findings reveal that inhibitory regulation from the GABAergic APL neurons facilitates olfactory reversal learning by suppressing initial memory in Drosophila.

Establishment and assessment of a nomogram for predicting prognosis in bone-metastatic prostate cancer.

OBJECTIVE: For the purposes of patients' consultation, condition assessments, and guidance for clinicians' choices, we developed a prognostic predictive model to evaluate the 1-, 3-, and 5-year overall survival (OS) rates of bone-metastatic prostate cancer (PCa) patients. METHODS: We gathered data from 5522 patients with bone metastatic PCa registered in the Surveillance, Epidemiology, and End Results (SEER) database to develop a nomogram. A total of 359 bone metastatic PCas were collected from 2 hospitals to validate the nomogram and assess its discriminatory ability. In addition, we plotted the actual survival against the predicted risk to assess the calibration accuracy. Moreover, we designed a web calculator to quickly obtain accurate survival probability outcomes. RESULTS: Univariate and multivariate Cox hazard regression analyses suggested that age, marital status, prostate-specific antigen (PSA) level, Gleason score, clinical T stage, N stage, surgery, and chemotherapy were closely associated with OS rates. The calibration charts of the training and validation groups showed a high accuracy and reliability. The decision curve analysis (DCA) suggested a favorable clinical net benefit. CONCLUSION: Based on demography and clinical pathology, we developed a reliable nomogram to help clinicians more accurately predict the 1-, 3-, and 5-year OS rates of patients with bone metastatic PCa to guide evaluation and treatment.

Asparagine-rich protein (NRP) mediates stress response by regulating biosynthesis of plant secondary metabolites in Arabidopsis.

The plant-specific stress response protein NRP (asparagine-rich protein) is characterized by an asparagine-rich domain at its N-terminus and a conserved development and cell death (DCD) domain at its C-terminus. Previous transcriptional studies and phenotypic analyses have demonstrated the involvement of NRP in response to severe stress conditions, such as high salt and ER Endoplasmic reticulum-stress. We have recently identified distinct roles for NRP in biotic- and abiotic-stress signaling pathways, in which NRP interacts with different signaling proteins to change their subcellular localizations and stability. Here, to further explore the function of NRP, a transcriptome analysis was carried out on nrp1nrp2 knock-out lines at different life stages or under different growing conditions. The most significant changes in the transcriptome at both stages and conditions turned out to be the induction of the synthesis of secondary metabolites (SMs). Such an observation implicates that NRP is a general stress-responsive protein involved in various challenges faced by plants during their life cycle, which might involve a broad alteration in the distribution of SMs.

Butterfly-Shaped Dibenz[a,j]anthracenes: Synthesis and Photophysical Properties.

A strategy for the synthesis of dibenz[a,j]anthracenes (DBAs) from cyclohexa-2,5-diene-1-carboxylic acids is presented. Our approach involves sequential C-H olefination, cycloaddition, and decarboxylative aromatization. In the key step for DBA skeleton construction, the bis-C-H olefination products, 1,3-dienes, are utilized as substrates for [4 + 2] cycloaddition with benzyne. This concise synthetic route allows for regioselective ring formation and functional group introduction. The structural features and photophysical properties of the resulting DBA molecules are discussed.

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration.

Parkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and Drosophila ortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+ DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1ß as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.

MicroRNA-142-3p facilitates inflammatory response by targeting ZEB2 and activating NF-κB signaling in gouty arthritis.

Gouty arthritis (GA) is caused by monosodium urate (MSU) crystal accumulation in the joints. MSU-mediated inflammation is an important inducing factor in gouty arthritis (GA). Recent studies have demonstrated that microRNAs can influence GA progression. Herein, the role and mechanism of miRNA-142-3p in GA were explored. To establish the in vitro and in vivo GA models, MSU was used to induce inflammatory response in human monocyte cell line THP-1 and male C57BL/6 mice. Protein levels, gene expression and proinflammatory cytokine secretion were respectively tested by Western blotting, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Pathological changes in sagittal sections of ankle tissues were exhibited by hematoxylin-eosin (HE) staining. Binding relationship between miRNA-142-3p and zinc finger E-box binding homeobox 2 (ZEB2) was predicted and confirmed by bioinformatics analysis and luciferase reporter assay. In this study, MSU induced inflammatory response and upregulated miRNA-142-3p in THP-1 cells. Functionally, miRNA-142-3p knockdown inhibited inflammatory response in MSU-stimulated THP-1 cells and alleviated pathological symptoms of GA mice. Mechanically, miRNA-142-3p targeted ZEB2 in THP-1 cells. ZEB2 expression was elevated in MSU-administrated THP-1 cells and GA mice. ZEB2 downregulation reserved the inhibitory effect of miRNA-142-3p deficiency on inflammatory response in MSU-treated THP-1 cells. In addition, miRNA-142-3p activated NF-κB signaling by binding with ZEB2 in THP-1 cells upon MSU stimulation. Overall, miRNA-142-3p facilitates inflammatory response by targeting ZEB2 and activating NF-κB signaling in GA.

MicroRNA-486-5p suppresses inflammatory response by targeting FOXO1 in MSU-treated macrophages.

Gouty arthritis (GA) is mainly caused by the precipitation of monosodium urate (MSU) crystals in the joint. Recently, different regulatory roles of microRNAs (miRNAs) in arthritis have been widely verified. Nevertheless, the specific function of microRNA-486-5p (miR-486-5p) in GA is still unclear. GA cell models in vitro were established by the treatment of 250 µg/mL MSU crystals into THP-1 cells or J774A.1 cells. Then, the accumulation of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-ß was estimated by ELISA. The mRNA levels of TNF-α, IL-8, and IL-ß were measured through RT-qPCR. The protein level of forkhead box protein O1 (FOXO1) was tested via western blot. Furthermore, the interplay of miR-486-5p and FOXO1 was evaluated via the luciferase reporter assay. In this study, MSU treatment successfully stimulated the inflammatory response in macrophage cells. MiR-486-5p downregulation was observed in THP-1 and J774A.1 cells treated with MSU, and its upregulation markedly decreased the concentration and mRNA levels of TNF-α, IL-8, and IL-ß. Furthermore, FOXO1 was demonstrated to be negatively modulated by miR-486-5p. The rescue assay indicated that overexpressing FOXO1 reversed the effects of overexpressing miR-486-5p on inflammatory cytokines. Overall, this study proves that miR-486-5p inhibits GA inflammatory response via modulating FOXO1.

CMTr cap-adjacent 2'-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses.

Cap-adjacent nucleotides of animal, protist and viral mRNAs can be O-methylated at the 2' position of the ribose (cOMe). The functions of cOMe in animals, however, remain largely unknown. Here we show that the two cap methyltransferases (CMTr1 and CMTr2) of Drosophila can methylate the ribose of the first nucleotide in mRNA. Double-mutant flies lack cOMe but are viable. Consistent with prominent neuronal expression, they have a reward learning defect that can be rescued by conditional expression in mushroom body neurons before training. Among CMTr targets are cell adhesion and signaling molecules. Many are relevant for learning, and are also targets of Fragile X Mental Retardation Protein (FMRP). Like FMRP, cOMe is required for localization of untranslated mRNAs to synapses and enhances binding of the cap binding complex in the nucleus. Hence, our study reveals a mechanism to co-transcriptionally prime mRNAs by cOMe for localized protein synthesis at synapses.

Long noncoding RNA SNHG8 accelerates acute gouty arthritis development by upregulating AP3D1 in mice.

Gout can affect the quality of life of patients due to monosodium urate monohydrate (MSU) crystals. Numerous studies have proposed that long noncoding RNAs (lncRNAs) regulate gout. We aimed to reveal the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in acute gouty arthritis (GA). A GA mouse model was established by injection of MSU into footpads. The levels of SNHG8, miR-542-3p and adaptor-related protein complex 3 subunit delta 1 (AP3D1) in footpads were detected via polymerase chain reaction analysis. Hematoxylin-eosin staining revealed the paw swelling in mice. Enzyme-linked immunosorbent assay and western blot analysis were applied to determine the concentrations of proinflammatory cytokines. SNHG8 expression was identified to be upregulated after MSU treatment. Ablation of SNHG8 decreased the MSU-induced enhancement of paw swelling and foot thickness. In addition, SNHG8 depletion decreased the protein levels of proinflammatory factors in GA mice. Mechanically, SNHG8 was verified to be a sponge of miR-542-3p, and miR-542-3p targeted AP3D1 3' untranslated region. SNHG8 competitively bound with miR-542-3p to upregulate AP3D1 expression. Finally, results of rescue assays illustrated that AP3D1 upregulation offset the SNHG8-mediated inhibition on paw swelling and protein levels of proinflammatory factors in GA mice. In conclusion, SNHG8 accelerates acute GA development by upregulating AP3D1 in an miR-542-3p-dependent way in mice, providing an effective therapeutic approach to treat acute GA.

Seeking for potential pathogenic genes of major depressive disorder in the Gene Expression Omnibus database.

INTRODUCTION: Major depressive disorder (MDD) is one of the most common mental disorders worldwide. The aim of this study was to identify potential pathological genes in MDD. METHODS: We searched and downloaded gene expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in MDD. Then, Kyoto Encyclopedia of Genes and Genomes pathway, Gene Ontology analysis, and protein-protein interaction (PPI) network were applied to investigate the biological function of identified DEGs. The quantitative real-time polymerase chain reaction and a published dataset were used to validate the result of bioinformatics analysis. RESULTS: A total of 514 DEGs were identified in MDD. In the PPI network, some hub genes with high degrees were identified, such as EEF2, RPL26L1, RPLP0, PRPF8, LSM3, DHX9, RSRC1, and AP2B1. The result of in vitro validation of RPL26L1, RSRC1, TOMM20L, RPLPO, PRPF8, AP2B1, STIP1, and C5orf45 was consistent with the bioinformatics analysis. Electronic validation of C5orf45, STIP1, PRPF8, AP2B1, and SLC35E1 was consistent with the bioinformatics analysis. DISCUSSION: The deregulated genes could be used as potential pathological factors of MDD. In addition, EEF2, RPL26L1, RPLP0, PRPF8, LSM3, DHX9, RSRC1, and AP2B1 might be therapeutic targets for MDD.

Magnesium efflux from Drosophila Kenyon cells is critical for normal and diet-enhanced long-term memory.

Dietary magnesium (Mg2+) supplementation can enhance memory in young and aged rats. Memory-enhancing capacity was largely ascribed to increases in hippocampal synaptic density and elevated expression of the NR2B subunit of the NMDA-type glutamate receptor. Here we show that Mg2+ feeding also enhances long-term memory in Drosophila. Normal and Mg2+-enhanced fly memory appears independent of NMDA receptors in the mushroom body and instead requires expression of a conserved CNNM-type Mg2+-efflux transporter encoded by the unextended (uex) gene. UEX contains a putative cyclic nucleotide-binding homology domain and its mutation separates a vital role for uex from a function in memory. Moreover, UEX localization in mushroom body Kenyon cells (KCs) is altered in memory-defective flies harboring mutations in cAMP-related genes. Functional imaging suggests that UEX-dependent efflux is required for slow rhythmic maintenance of KC Mg2+. We propose that regulated neuronal Mg2+ efflux is critical for normal and Mg2+-enhanced memory.

The proverbial saying 'you are what you eat' perfectly summarizes the concept that our diet can influence both our mental and physical health. We know that foods that are good for the heart, such as nuts, oily fish and berries, are also good for the brain. We know too that vitamins and minerals are essential for overall good health. But is there any evidence that increasing your intake of specific vitamins or minerals could help boost your brain power? While it might sound almost too good to be true, there is some evidence that this is the case for at least one mineral, magnesium. Studies in rodents have shown that adding magnesium supplements to food improves how well the animals perform on memory tasks. Both young and old animals benefit from additional magnesium. Even elderly rodents with a condition similar to Alzheimer's disease show less memory loss when given magnesium supplements. But what about other species? Wu et al. now show that magnesium supplements also boost memory performance in fruit flies. One group of flies was fed with standard cornmeal for several days, while the other group received cornmeal supplemented with magnesium. Both groups were then trained to associate an odor with a food reward. Flies that had received the extra magnesium showed better memory for the odor when tested 24 hours after training. Wu et al. show that magnesium improves memory in the flies via a different mechanism to that reported previously for rodents. In rodents, magnesium increased levels of a receptor protein for a brain chemical called glutamate. In fruit flies, by contrast, the memory boost depended on a protein that transports magnesium out of neurons. Mutant flies that lacked this transporter showed memory impairments. Unlike normal flies, those without the transporter showed no memory improvement after eating magnesium-enriched food. The results suggest that the transporter may help adjust magnesium levels inside brain cells in response to neural activity. Humans produce four variants of this magnesium transporter, each encoded by a different gene. One of these transporters has already been implicated in brain development. The findings of Wu et al. suggest that the transporters may also act in the adult brain to influence cognition. Further studies are needed to test whether targeting the magnesium transporter could ultimately hold promise for treating memory impairments.

Effect of Electroacupuncture at Different Acupoints on the Expression of NMDA Receptors in ACC and Colon in IBS Rats.

OBJECTIVE: To observe the effects of electroacupuncture (EA) at different acupoints on the expression of N-methyl-D-aspartate receptor (NMDA receptor ) and behaviors in irritable bowel syndrome (IBS) rats. METHODS: Wistar rats were randomly divided into blank control group (blank group, n=10) and model preparation group (n=50); experimental rat model of IBS was established by the "neonatal maternal separation and acetic acid enema" combined with "colorectal distension stimulation" method. A total of 50 IBS rats were randomly assigned to five groups of 10 each: model group, Yintang (GV29) group, Neiguan (PC6) group, Tianshu (ST25) group, and Zusanli (ST36) group. Rats in four treatment groups, aged 9 weeks old, were treated with EA by HANS with a sparse-dense wave with a frequency of 2/100 Hz, current of 0.1-0.3mA, and 20 min/stimulation, every other day for a total of 5 sessions. After treatment, the abdominal visceral sensitivity was evaluated by abdominal withdrawal reflex (AWR), and the psychological and emotional behavior of rats were evaluated by the open-field test (OFT). The expression of NMDA receptors in anterior cingulate cortex (ACC) was detected by Quantitative Real-time PCR, and the positive expression of NMDA receptors in colon was detected by immunohistochemistry. RESULTS: The IBS rat's abdomen is more sensitive and irritable; NR1, NR2A, and NR2B in ACC and NR1 and NR2B in colon of rats significantly increased in the model group versus the normal group (P<0.01) and were inhibited in all treatment groups (P<0.01, P<0.05). Additionally, NR2A and NR2B in ACC reduced more in GV29 group (P<0.01) than in other treatment groups (P all<0.05) compared with the model group. The expression of NR2B in colon was significantly inhibited in ST36 group (P<0.01) and inhibited in GV29 group and ST25 group (P all <0.05) compared with the model group. And the expression of NR2B in colon was more inhibited in ST36 group than in PC6 group (P<0.01). CONCLUSIONS: EA at different acupoints could obviously relieve abdominal pain and abnormal behaviors in IBS rats in different degrees of effects. The effect of abdominal pain-relief, from greatest to least, is ST25, ST36, GV29, and PC6, while the effect of relieving abnormal behaviors caused by IBS, from greatest to least, is GV29, PC6, ST36, and ST25. There are significant differences in the expressions of NMDA receptors in ACC and colon among different acupoints. This difference should be related to the location distribution and indications of acupoints.