PTPN2 copper-sensing rapidly relays copper level fluctuations into EGFR/CREB activation and associated CTR1 transcriptional repression.

Fluxes in human intra- and extracellular copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate (cAMP). We herein applied an unbiased temporal evaluation of the whole-genome transcriptional activities modulated by fluctuations in copper levels to identify the copper sensor proteins responsible for driving these activities. We found that fluctuations in physiologically-relevant copper levels rapidly modulate EGFR/MAPK/ERK signal transduction and activation of the transcription factor cAMP response element-binding protein (CREB). Both intracellular and extracellular assays support Cu 1+ inhibition of the EGFR-phosphatase PTPN2 (and potentially the homologous PTPN1)-via direct ligation to the PTPN2 active site cysteine side chain-as the underlying mechanism of copper-stimulated EGFR signal transduction activation. Depletion of copper represses this signaling pathway. We additionally show i ) copper supplementation drives transcriptional repression of the copper importer CTR1 and ii ) CREB activity is inversely correlated with CTR1 expression. In summary, our study reveals PTPN2 as a physiological copper sensor and defines a regulatory mechanism linking feedback control of copper-stimulated MAPK/ERK/CREB-signaling and CTR1 expression, thereby uncovering a previously unrecognized link between copper levels and cellular signal transduction.

The gut-brain axis: Effect of electroacupuncture pretreatment on learning, memory, and JNK signaling in D-galactose-induced AD-like rats.

Objectives: To examine the effect and potential mechanism of electroacupuncture (EA) pretreatment in spatial learning, memory, gut microbiota, and JNK signaling in D-galactose-induced AD-like rats. Materials and Methods: The AD-like rat model was generated by intraperitoneal injection of D-galactose. Morris water maze was used to determine spatial learning and memory ability, Real-time PCR to determine intestinal flora levels, ELISA to determine tryptophan (Trp) and 5-HT levels in the colon and hippocampal tissues, immunofluorescence to determine 5-HT levels in enterochromaffin cells (ECs), and immunoblotting to determine JNK signaling protein levels in hippocampal tissues. Results: Electroacupuncture pretreatment significantly reduced escape latency and prolonged exploration time in the target quadrant, and significantly increased the relative DNA abundance of Lactobacillus and Bifidobacterium. Meanwhile, electroacupuncture pretreatment also reduced colonic 5-HT levels and increased hippocampal 5-HT levels. Moreover, electroacupuncture pretreatment significantly inhibited hippocampal JNK pathway-related protein expression, including 5-HT6R, JNK, p-JUNK, c-JUN, and p-c-Jun. And the combination of GV20 and ST36 was more effective than single acupoints. Conclusion: Electroacupuncture pretreatment improved the learning and memory ability of D-galactose-induced AD-like model rats, changed the gut microbiota composition, and the mechanism may be related to the gut-brain axis and the JNK signaling pathway. In addition, the combination of GV20 and ST36 could further enhance the efficacy.

[Effects of Earthworm, Straw, and Citric Acid on the Remediation of Zn, Pb, and Cd Contaminated Soil by Solanum photeinocarpum and Pterocypsela indica].

Regulation of exogenous substances and intercropping are effective methods to improve the efficiency of phytoremediation of heavy metal contaminated soil. A pot experiment was used to study the effects of earthworms, straw, and citric acid on the remediation of Zn, Pb, and Cd contaminated soil by monocropping and intercropping of Solanum photeinocarpum and Pterocypsela indica. The results showed that the bioaccumulation factors (BCF) of earthworms for Zn, Pb, and Cd were 0.07-0.13, 0.10-0.26, and 5.64-15.52, respectively. The addition of straw in the soil increased the biomass of earthworms by 22.29%-223.87% but reduced the heavy metal concentrations by 8.15%-62.58%. Straw and citric acid showed passivation and activation effects, respectively, but earthworms had no significant effect on the available concentrations of heavy metals in the soil. Earthworms had no significant effect on the heavy metal concentrations of P. indica but reduced the heavy metal concentrations of S. photeinocarpum. Straw showed an inhibitory effect on the concentrations of heavy metals in P. indica but promoted the concentrations of Cd in S. photeinocarpum. Citric acid had no significant effect on the heavy metal concentrations in S. photeinocarpum but significantly increased the Pb concentrations in P. indica. Intercropping significantly reduced the soil available heavy metal concentrations and increased the heavy metal concentrations in plant roots; however, it had no significant effect on heavy metal concentrations in plant shoots. The total extraction amounts of Zn, Pb, and Cd by plants were mainly manifested as P. indica>intercropping>S. photeinocarpum. The addition of earthworms increased the total extraction amounts of Zn, Pb, and Cd by 12.49%, 35.89%, and 29.01%, respectively, and the addition of straw+earthworms increased the total extraction amounts of Pb by 87.21%. The results indicated that straw significantly promoted the growth of earthworms and reduced their accumulation of heavy metals, and the addition of earthworms alone or in combination with straw can effectively improve the remediation potential of P. indica of Zn, Pb, and Cd contaminated soil.

Plasticity of neuronal excitability and synaptic balance in the anterior nucleus of paraventricular thalamus after nerve injury.

The anterior nucleus of the paraventricular thalamus (aPVT) integrates various synaptic inputs and conveys information to the downstream brain regions for arousal and pain regulation. Recent studies have indicated that the PVT plays a crucial role in the regulation of chronic pain, but the plasticity mechanism of neuronal excitability and synaptic inputs for aPVT neurons in neuropathic pain remains unclear. Here, we report that spinal nerve ligation (SNL) significantly increased the neuronal excitability and reset the excitatory/inhibitory (E/I) synaptic inputs ratio of aPVT neurons in mice. SNL significantly increased the membrane input resistance, firing frequency, and the half-width of action potential. Additionally, SNL enlarged the area of afterdepolarization and prolonged the rebound low-threshold spike following a hyperpolarized current injection. Further results indicate that an inwardly rectifying current density was decreased in SNL animals. SNL also decreased the amplitude, but not the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), nor the amplitude or frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) of aPVT neurons. Moreover, SNL disrupted the E/I synaptic ratio, caused a decrease in weighted tau and half-width of averaged sIPSCs, but did not change these physiological properties of averaged sEPSCs. Finally, pharmacological activation of the GABAA receptor at aPVT could effective relieve SNL-induced mechanical allodynia in mice. These results reveal the plasticity of intrinsic neuronal excitability and E/I synaptic balance in the aPVT neurons after nerve injury and it may play an important role in the development of pain sensitization.

Crocetin alleviates the caerulein-induced apoptosis and inflammation in AR42J cells by activating SIRT1 via NF-κB.

The anti-inflammatory and anti-apoptotic properties of crocetin have been widely demonstrated in numerous diseases. However, the exact role and mechanism of crocetin in acute pancreatitis have not been elucidated. Thus, this paper aims at exploring whether crocetin could be used to alleviate acute pancreatitis and further demonstrating the underlying mechanisms. Cell viability of caerulein-induced pancreatic exocrine cell line AR42J treated with crocetin was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT). Apoptosis and inflammation of these treated cells were detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), western blot and enzyme linked immunosorbent assay (ELISA). The expression of sirtuin-1 (SIRT1) was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. After knockdown of SIRT1, cell viability, apoptosis and inflammation were measured again by corresponding kits. Finally, the NF-κB nuclear translocation and proteins in the NF-κB signaling were examined. Crocetin remarkably suppressed the apoptosis and inflammation of caerulein-induced AR42J cells. The decreased expression of SIRT1 was increased in caerulein-induced AR42J cells after exposure to crocetin. After knockdown of SIRT1, the alleviative effects of crocetin were found to be canceled in these cells. Furthermore, SIRT1 knockdown promoted the NF-κB signal transduction. On the whole, we presented the first evidence for the importance of SIRT1-NF-κB axis in acute pancreatitis and proposed that crocetin alleviates the caerulein-induced apoptosis and inflammation in AR42J cells by activating SIRT1 via NF-κB.

RNA demethylation increases the yield and biomass of rice and potato plants in field trials.

RNA N6-methyladenosine (m6A) modifications are essential in plants. Here, we show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. We demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial m6A demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of m6A in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA m6A methylation is a promising strategy to dramatically improve plant growth and crop yield.

Preventive electroacupuncture ameliorates D-galactose-induced Alzheimer's disease-like inflammation and memory deficits, probably via modulating the microbiota-gut-brain axis.

OBJECTIVES: We aimed to observe the effects of preventive electroacupuncture (EA) on the microbiota-gut-brain axis and spatial learning and memory deficits and to investigate the possible mechanism using D-galactose (D-gal)-induced aging rats. MATERIALS AND METHODS: D-gal was intraperitoneally injected to establish the aging model. We used Morris water maze to detect spatial learning and memory function of rats. RT-PCR was applied to test targeted gut microbes. The expression of zonula occludens-1 (ZO-1) and Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway proteins were detected by Western blotting. ELISA was employed to evaluate the level of lipopolysaccharides (LPS), diamine oxidase (DAO) and S-100ß. Additionally, we observed ionized calcium-binding adapter molecule-1 (Iba-1) expression in the hippocampal CA1 area by immunofluorescence. RESULTS: Morris water maze test showed decreased mean escape latency and increased target quadrant time after EA treatment. The gut microbiota composition has been modified in EA treated rats. Molecular examination indicated that expression of ZO-1 was improved and the the concentration of LPS in blood and hippocampus were reduced in EA treated rats. Further, we observed an inhibition of activated microglia and TLR4/NF-κB pathway in EA groups. CONCLUSION: Preventive EA may alleviate the impairments of the microbiota-gut-brain axis and spatial learning and memory in aging, and the mechanism may be related to the inhibition of TLR4/NF-kB signaling pathway. The combination of acupoints GV20 and ST36 can enhance the therapeutic effect in aging rats.

Acupuncture and Related Therapies for the Cognitive Function of Alzheimer's Disease: A Network Meta-Analysis.

Background: Acupuncture and acupuncture-related therapies are effective for Alzheimer's disease (AD), therefore, we aimed to compare and rank the interventions that mainly focus on acupuncture-related therapies in the treatment of patients with mild to moderate AD. Methods: We used network meta-analysis to evaluate the direct and indirect evidence shown in randomized controlled trials of AD. The data were analyzed using RavMan manager, Stata, and WinBUGS software after two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Results: We analyzed a total of 36 eligible studies, including 2712 patients, involving 14 types of acupuncture-related therapies and comprehensive therapies. For Mini-Mental State Examination (MMSE), acupuncture (ACU) combined with cognitive and memory training (Training) was more effective than ACU, ACU+Chinese herb (CH), ACU+Donepezil (DON), CH, DON, DON+Nimodipine (NIM), Music therapy (Music), NIM, Placebo, and Training (P<0.05), while ACU+CH was batter than CH (P<0.05), and ACU+DON+NIM was better than DON+NIM (P<0.05). For Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog), ACU was more effective than DON and placebo (P<0.05). For Activities of Daily Living (ADL), ACU+DON was better than CH, DON, NIM, and Placebo (P<0.05). For the clinical effectiveness rate, ACU, ACU+CH, ACU+CH+DON, ACU+CH+DON+NIM, ACU+DON, CH, NIM were all more effective than DON+NIM (P<0.05), while ACU and ACU+CH were better than DON (P<0.05). The comprehensive ranking results show that ACU+training and ACU have the highest ranking probability. Conclusion: ACU+Training and ACU may be the best therapies to improve the cognitive function of patients with mild to moderate AD, while the combination of acupuncture-related therapies and other therapies has a higher overall benefit.

Preventive electroacupuncture reduces cognitive deficits in a rat model of D-galactose-induced aging.

Acupuncture can reduce cognitive deficits in Alzheimer's disease. However, whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood. Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline. Therefore, we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications. A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks. Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration. Preventive electroacupuncture alleviated memory impairment, decreased tau hyperphosphorylation, and reduced glycogen synthase kinase-3ß protein and mRNA expression levels in the brainstem dorsal raphe nucleus, where intracellular neurofibrillary tangle lesions first occur. In addition, the DNA methylation level in the promoter region of the glycogen synthase kinase-3ß gene was increased. The effects of preventive electroacupuncture were stronger than those of preventive acupuncture. Intraperitoneal injection of 0.4 mg/kg 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferase that blocks epigenetic modifications, antagonized the effects of preventive electroacupuncture. Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3ß gene in the dorsal raphe nucleus. This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine, China (approval No. HUCMS201712001) on November 28, 2017.

Acupuncture and related therapies for hyperlipidemia: A protocol for systematic review and network meta-analysis.

OBJECTIVE: To compare and rank the clinical effects of different acupuncture and acupuncture-related therapies on patients with hyperlipidemia. METHODS: We used Network Meta-Analysis (NMA) to evaluate the direct and indirect evidence from relevant studies. Three English and 4 Chinese databases were searched to collect randomized controlled trials (RCT) of acupuncture and related therapies in the treatment of hyperlipidemia. The data were analyzed using Stata15.0 and WinBUGS1.4.3 software after 2 researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. RESULTS: Based on the current evidence, we comprehensively compare the pros and cons of various acupuncture-related therapies, rank the efficacy of various acupuncture-related therapies compared with statins in the treatment of hyperlipidemia, and summarize the best acupuncture intervention methods or combinations. CONCLUSION: This study will provide new evidence for the safety and effectiveness of acupuncture-related therapies in the treatment of hyperlipidemia, and may be helpful for clinicians, hyperlipidemia patients, and clinical guideline makers to choose the optimal combination of acupuncture for the treatment of hyperlipidemia. REGISTRATION NUMBER: INPLASY2020100100.

Reaction of BCl3 with H- and Cl-terminated Si(1 0 0) as a pathway for selective, monolayer doping through wet chemistry.

The reaction of boron trichloride with the H and Cl-terminated Si(100) surfaces was investigated to understand the interaction of this molecule with the surface for designing wet-chemistry based silicon surface doping processes using a carbon- and oxygen-free precursor. The process was followed with X-ray photoelectron spectroscopy (XPS). Within the reaction conditions investigated, the reaction is highly effective on Cl-Si(100) for temperatures below 70°C, at which point both surfaces react with BCl3. The XPS investigation followed the formation of a B 1s peak at 193.5 eV corresponding to (B-O)x species. Even the briefest exposure to ambient conditions lead to hydroxylation of surface borochloride species. However, the Si 2p signature at 102 eV allowed for a confirmation of the formation of a direct Si-B bond. Density functional theory was utilized to supplement the analysis and identify possible major surface species resulting from these reactions. This work provides a new pathway to obtain a functionalized silicon surface with a direct Si-B bond that can potentially be exploited as a means of selective, ultra-shallow, and supersaturated doping.

[Effect of pretreatment of acupuncture on learning-memory ability and related protein of NLRP3 inflammasome in hippocampus in Alzheimer's disease like rats].

OBJECTIVE: To observe the effect of pretreatment of acupuncture on the expression of nucleotide-binding oligomerization domain-like receptor 3(NLRP3), Caspase-1, interleukin1ß(IL-1ß) and the number of activated microglia (MG) in the hippocampus in Alzheimer's disease (AD) like rats, so as to explore the mechanism of pretreatment of acupuncture in preventing and treating AD. METHODS: A total of 36 SD rats were randomly divided into a blank group, a model group and an electroacupuncture (EA) group, 12 rats in each group. The AD like rat model was established by 8-week continuous intraperitoneal injection of D-galactose (120 mg·kg-1·d-1) in the model group and the EA group. The rats in the EA group were intervened with EA at "Baihui" (GV 20) and "Zusanli" (ST 36), continuous wave, 5 Hz in frequency, 1 mA in intensity, 20 min each intervention, once a day, for 8 weeks. After the intervention, the spatial learning-memory ability was evaluated by the Morris water maze test. The expression levels of NLRP3, Caspase-1 and IL-1ß protein in hippocampus were detected by Western blot method. The number of activated MG in hippocampus was detected by immunofluorescence labeling method. RESULTS: Compared with the blank group, the average escape latency was prolonged (P<0.01), the number of platform crossing was reduced (P<0.01), and the exploration time of target quadrant was shortened (P<0.01) in the model group. Compared with the model group, the average escape latency was shortened (P<0.01), the number of platform crossing was increased (P<0.01), and the exploration time of target quadrant was prolonged (P<0.01) in the EA group. Compared with the blank group, the expression levels of NLRP3, Caspase-1, IL-1ß protein in hippocampus were increased (P<0.01), and the number of activated MG was increased (P<0.01) in the model group. Compared with the model group, the expression levels of NLRP3, Caspase-1, IL-1ß protein in hippocampus were decreased (P<0.01), and the number of activated MG was decreased (P<0.05) in the EA group. CONCLUSION: Pretreatment of acupuncture could prevent and treat the learning-memory dysfunction in AD like rats, and its mechanism may be related to the inhibition of NLRP3 inflammatsome related protein and MG activation.

Efficacy of microsurgery for dural arteriovenous fistula: A systematic review protocol.

BACKGROUND: Microsurgery is a treatment option for dural arteriovenous fistula (DAF), but its efficacy is still unclear. This study aims to assess the efficacy and safety of microsurgery for the treatment of patients with DAF. METHODS: We will carry out this study assessing the use of microsurgery in patients with DAF from the following electronic databases: PUBMED, EMBASE, Cochrane Library, CINAHL, PsycINFO, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All those databases will be searched from inception to the present without language limitations. Two independent authors will perform study selection, data extraction, and methodological quality assessment. RevMan 5.3 Software will be applied for statistical analysis. RESULTS: This study will assess the efficacy and safety of microsurgery for the treatment of patients with DAF through measuring initial treatment failure, late recurrence, neurological improvement, quality of life, and complications. CONCLUSION: This study will provide most recent evidence of microsurgery for the treatment of patients with DAF. DISSEMINATION AND ETHICS: The findings of this systematic review will be published in peer-reviewed journals. This systematic review dose not needs ethic approval, because it just analyzes the published data without individual information involvement. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019144851.

Aerobic removal of iodinated contrast medium by nano-sized zero-valent iron: A combination of oxidation and reduction.

The removal performance and mechanisms of diatrizoate (DTA), a typical iodinated contrast medium, from water by nano-sized zero-valent iron (nZVI) under aerobic conditions were investigated in this study. Reactive oxygen species (ROS) and transformation products were detected with electron spin resonance and liquid chromatography electrospray ionization tandem mass spectrometry, respectively. Furthermore, the effects of several operational parameters on DTA removal were illustrated. The results showed that nZVI had a much higher DTA removal ability compared to microscale zero-valent iron (mZVI) in the presence of oxygen. Moreover, the detection of ROS and I- as well as the analysis of intermediate products suggested a combination of oxidation and reduction pathways for DTA removal by nZVI under aerobic conditions. Additionally, a high dosage of nZVI and acidic conditions led to the enhancement of DTA removal, while nZVI aging, as well as chloride and nitrate ions in the solution, had negative effects on the degradation of DTA by nZVI in the presence of oxygen.

29,31- H Phthalocyanine Covalently Bonded Directly to a Si(111) Surface Retains Its Metalation Ability.

The reaction of metal-free phthalocyanine molecules with a chlorine-terminated Si(111) surface is investigated to produce a phthalocyanine functionality directly attached to a semiconductor surface, without additional linkers or layers. The carefully prepared Cl-Si(111) surface provides an oxygen-free substrate that is reacted with 29,31- H phthalocyanine (H2Pc) in a wet-chemistry process resulting in HCl elimination. The in situ metalation of this H2Pc-modified silicon surface with cobalt is confirmed, suggesting that the produced functionality is chemically active. These processes are investigated by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and time-of-flight secondary ion mass spectrometry supplemented by density functional theory calculations. The morphology of the surface is monitored by atomic force microscopy. The combined spectroscopic, microscopic, and theoretical investigations demonstrate that additional linkers are not required for phthalocyanine attachment to occur, as the direct attachment can take place by forming Si-N bonds, and that the resulting surface species can participate in a metalation process.

RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide.

RIP1 and RIP3 are necroptosis initiators, but their roles in regulation of glycolysis remain elusive. In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA. Moreover, shikonin also triggered accumulation of intracellular H2O2 and depletion of GSH and cysteine. Mitigation of intracellular H2O2 via supplement of GSH reversed shikonin-induced glycolysis suppression. The role of intracellular H2O2 in regulation of glycolysis suppression was further confirmed in the cells treated with exogenous H2O2. Notably, inhibition of RIP1 or RIP3 prevented intracellular H2O2 accumulation, which was correlated with preventing shikonin-induced downregulation of x-CT and depletion of GSH and cysteine. In addition, supplement of pyruvate effectively inhibited shikonin- or exogenous H2O2-induced accumulation of intracellular H2O2 and glioma cell death. Taken together, we demonstrated in this study that RIP1 and RIP3 contributed to shikonin-induced glycolysis suppression via increasing intracellular H2O2.

Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT.

Ferroptosis is a form of programmed cell death decided by iron-dependent lipid peroxidation, but its role in glioma cell death remains unclear. In this study, we found Pseudolaric acid B (PAB) inhibited the viabilities of glioma cells in vitro and in vivo, which was accompanied by abnormal increases of intracellular ferrous iron, H2O2 and lipid peroxidation, as well as depletion of GSH and cysteine. In vitro studies revealed that the lipid peroxidation and the cell death caused by PAB were both inhibited by iron chelator deferoxamine, but exacerbated by supplement of ferric ammonium citrate. Inhibition of lipid peroxidation with ferrostatin-1 or GSH rescued PAB-induced cell death. Morphologically, the cells treated with PAB presented intact membrane, shrunken mitochondria with increased membrane density, and normal-sized nucleus without chromatin condensation. Mechanistically, PAB improved intracellular iron by upregulation of transferrin receptor. The increased iron activated Nox4, which resulted in overproduction of H2O2 and lipid peroxides. Moreover, PAB depleted intracellular GSH via p53-mediated xCT pathway, which further exacerbated accumulation of H2O2 and lipid peroxides. Thus, PAB triggers ferroptosis in glioma cells and is a potential medicine for glioma treatment.

Characteristics of Organic Acid Secretion Associated with the Interaction between Burkholderia multivorans WS-FJ9 and Poplar Root System.

The objective of this study was to investigate whether plant-bacteria interaction affects the secretion of organic acids by both organisms and to assess whether the production of IAA by the bacterium increases the secretion of organic acids by root exudates, and if the stress produced by low available phosphorus (P) affects the production of organic acids by bacteria, by roots, or by root exudates in presence of bacterial cultures. With this purpose, we used as a biological model poplar plants and one strain of Burkholderia multivorans able to solubilize P. High performance liquid chromatography was utilized to measure organic acids. The tests, the inductive effects of exogenous indole-3-acetic acid (IAA) on secretion of organic acids, the 2 × 4 × 2 factorial design experiment, and the ability of organic acids to solubilize tricalcium phosphate were performed to investigate the interactive effects. The results showed that, after B. multivorans WS-FJ9 interacted with the poplar root system, the key phosphate-solubilizing driving force was gluconic acid (GA) which was produced in three ways: (1) secreted by the root system in the presence of IAA produced by B. multivorans WS-FJ9; (2) secreted by B. multivorans WS-FJ9; and (3) secreted by the poplar root system in the presence of phosphorus stress. When phosphorus stress was absent, the GA was produced as outlined in (1) and (2) above. These results demonstrated that inoculating B. multivorans WS-FJ9 into the poplar root system could increase the amount of GA secretion and implied that the interaction between B. multivorans WS-FJ9 and the poplar root system could contribute to the increase of P available fraction for poplar plants.

N6-Allyladenosine: A New Small Molecule for RNA Labeling Identified by Mutation Assay.

RNA labeling is crucial for the study of RNA structure and metabolism. Herein we report N6-allyladenosine (a6A) as a new small molecule for RNA labeling through both metabolic and enzyme-assisted manners. a6A behaves like A and can be metabolically incorporated into newly synthesized RNAs inside mammalian cells. We also show that human RNA N6-methyladenosine (m6A) methyltransferases METTL3/METTL14 can work with a synthetic cofactor, namely allyl-SAM (S-adenosyl methionine with methyl replaced by allyl) in order to site-specifically install an allyl group to the N6-position of A within specific sequence to generate a6A-labeled RNAs. The iodination of N6-allyl group of a6A under mild buffer conditions spontaneously induces the formation of N1,N6-cyclized adenosine and creates mutations at its opposite site during complementary DNA synthesis of reverse transcription. The existing m6A in RNA is inert to methyltransferase-assisted allyl labeling, which offers a chance to differentiate m6A from A at individual RNA sites. Our work demonstrates a new method for RNA labeling, which could find applications in developing sequencing methods for nascent RNAs and RNA modifications.

High dose of maternal folic acid supplementation is associated to infant asthma.

Maternal folic acid supplementation had a positive effect on preventing neural tube defects (NTDs), but its effects in infant asthma remained unclear. A hospital-based case-control study was conducted with outpatients between March 2010 and March 2011 including 150 onset infant asthma cases and 212 controls, together with a meta-analysis involving 14,438 participants, was performed. The association between maternal folic acid supplementation and the risk of infant asthma was not significant either in the meta-analysis (OR = 1.06, 95% CI =0.99-1.14) or in the case-control study (OR = 0.72, 95% CI =0.37-1.39). However, quantitative analysis of the supplementation dose demonstrated that the risk of infant asthma significantly increased for the infants whose mother were with high-dose supplementation (>72,000 µg•d; OR = 3.16, 95% CI =1.15-8.71) after adjusting for confounding factors in the case-control study. Meanwhile, the risk of infant asthma significantly decreased for the infants whose mother were with low-dose supplementation (<36,000 µg•d; OR = 0.36, 95% CI =0.17-0.77). A high dose of folic acid supplementation for mother during pregnancy was associated with an increased risk of infant asthma, whereas supplementation with a relatively low-dose was associated with a decreased risk of infant asthma. These findings should be further investigated in a large population.