RESUMEN

Purpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC. Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal. Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10-1.48) and 0.77 (0.66-0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (P trend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells. Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.

RESUMEN

Neuroligin-3 (Nlgn3) is an autism-associated cell-adhesion molecule that interacts with neurexins and is robustly expressed in both neurons and astrocytes. Neuronal Nlgn3 is an essential regulator of synaptic transmission but the function of astrocytic Nlgn3 is largely unknown. Given the high penetrance of Nlgn3 mutations in autism and the emerging role of astrocytes in neuropsychiatric disorders, we here asked whether astrocytic Nlgn3 might shape neural circuit properties in the cerebellum similar to neuronal Nlgn3. Imaging of tagged Nlgn3 protein produced by CRISPR/Cas9-mediated genome editing showed that Nlgn3 is enriched in the cell body but not the fine processes of cerebellar astrocytes (Bergmann glia). Astrocyte-specific knockout of Nlgn3 did not detectably alter the number of synapses, synaptic transmission, or astrocyte morphology in mouse cerebellum. However, spatial transcriptomic analyses revealed a significant shift in gene expression among multiple cerebellar cell types after the deletion of astrocytic Nlgn3. Hence, in contrast to neuronal Nlgn3, astrocytic Nlgn3 in the cerebellum is not involved in shaping synapses but may modulate gene expression in specific brain areas.

RESUMEN

BACKGROUND: Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)-related HCC. METHODS: In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway-related genes and overall survival (OS) of 866 patients with HBV-related HCC. RESULTS: It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV-related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose-response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3-year and 5-year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10-3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10-5 and 0.033, respectively). CONCLUSIONS: Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV-related HCC.

Asunto(s)

RESUMEN

BACKGROUND: Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis-related genes on survival in hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) patients remains unknown. METHODS: We used two-stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosis-related genes and overall survival (OS) of 866 HBV-HCC patients. RESULTS: We identified that two potentially functional SNPs (CREB3 rs10814274 C > T and GALNT14 rs17010547 T > C) were significantly independently associated with the OS of HBV-HCC patients (CT + TT verse CC, hazards ratio (HR) = 0.77, 95% confidence interval (CI) = 0.67-0.89, p < 0.001 for rs10814274 and TC + CC verse TT, HR = 0.66, 95% CI = 0.53-0.82, p < 0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1-2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR = 0.56, 95% CI = 0.45-0.70, p < 0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival-associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells. CONCLUSION: These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV-HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings.

Asunto(s)

RESUMEN

Background: Although the sphingolipid metabolism pathway is known to play a significant role in tumor progression, there have been few studies on how genetic variants in the sphingolipid metabolism pathway genes affect the survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: We utilized available genotyping data to conduct multivariate Cox proportional hazards regression model analysis, examining the associations of 12,188 single nucleotide polymorphisms (SNPs) in 86 sphingolipid metabolism pathway genes on the survival of 866 HBV-HCC patients, and the model was also used in additive interaction analysis. We used bioinformatics functional prediction and expression quantitative trait locus (eQTL) analysis to explore the potential functions of SNPs and to evaluate the association of SNPs with the corresponding mRNA expression, respectively. We also used the online database TIMER2.0 (http://timer.comp-genomics.org/) to analyze the relationship between the corresponding mRNA expression levels and immune cell infiltration. Results: Our study found that GBA2 rs1570247 G>A was significantly associated with elevated survival of HBV-HCC patients [(hazards ratio (HR)=0.74, 95% confidence interval (CI)=0.64-0.86, P<0.001)]. And on an additive scale, a synergistic effect was observed between the GG genotype of rs1570247 and advanced BCLC stage. Among HBV-HCC patients with advanced BCLC stage, those carrying the GBA2 rs1570247 GG genotype exhibited a significantly elevated risk of mortality (HR=3.32, 95%CI=2.45-4.50). Further functional prediction and eQTL analysis revealed that rs1570247 were located in the 5' untranslated region of the GBA2, the A allele of SNP rs1570247 was associated with higher mRNA expression levels of GBA2 in normal liver tissues (P=0.009). Moreover, we observed a positive correlation between GBA2 mRNA expression and the infiltration level of B lymphocytes cell (R=0.331, P<0.001), while a negative correlation was noted between GBA2 mRNA expression and the infiltration level of macrophage M2 in HCC (R=-0.383, P<0.001). Conclusion: Our findings suggest that GBA2 rs1570247 G>A in sphingolipid metabolism pathway may be a key factor for survival of HBV-HCC patients by regulating the expression of corresponding genes and affecting the infiltration level of immune cells.

RESUMEN

The subsynaptic organization of postsynaptic neurotransmitter receptors into nanoclusters that are aligned with presynaptic release sites is essential for the high fidelity of synaptic transmission. However, the mechanisms controlling the nanoscale organization of neurotransmitter receptors in vivo remain incompletely understood. Here, we deconstructed the role of neuroligin-3 (Nlgn3), a postsynaptic adhesion molecule linked to autism, in organizing AMPA-type glutamate receptors in the calyx of Held synapse. Deletion of Nlgn3 lowered the amplitude and slowed the kinetics of AMPA receptor-mediated synaptic responses. Super-resolution microscopy revealed that, unexpectedly, these impairments in synaptic transmission were associated with an increase in the size of postsynaptic PSD-95 and AMPA receptor nanoclusters but a decrease of the densities in these clusters. Modeling showed that a dilution of AMPA receptors into larger nanocluster volumes decreases synaptic strength. Nlgn3, likely by binding to presynaptic neurexins, thus is a key organizer of AMPA receptor nanoclusters that likely acts via PSD-95 adaptors to optimize the fidelity of synaptic transmission.

RESUMEN

We have previously used surface chemistry analysis techniques to optimize the functionalization of carbonate rocks with a silylated polyacrylamide-based relative permeability modifier (RPM). The RPM is expected to selectively reduce the permeability to water in a hydrocarbon reservoir setting, resulting in a reduction in the amount of produced water while maintaining the production of oil/gas. This study will focus on using core flooding techniques with brine/crude oil under reservoir conditions (i.e., 1500 psi pore pressure and 60 °C temperature) to understand the impact of a silylated polyacrylamide-based RPM on the fluid transport properties in carbonate rocks. The effects of RPM concentration, brine salinity, rock permeability, and pore structure on permeability characteristics were studied. Scanning electron microscopy (SEM) combined with energy dispersive spectroscopy (EDX) provided visual images of the polymer adsorbed onto the rock surfaces and confirmed the attachment of the polymer on the surface of the rock pore space after treatment. The relative percentage of Si increased from 1.65 to 13.55%, and the relative percentage of N increased to 4.54%. Core flooding showed that increasing the PAM-co-AA (poly acrylamide-co-acrylic acid partial sodium salt) concentration resulted in residual resistance factors for oil (RRFoil) and brine (RRFbrine) that were greater than 1. However, there was a modest decrease in the disproportionate permeability reduction (DRP) ratio (RRFbrine/RRFoil) from 1.75 to 1.60 when the polymer concentration was increased from 0.05 to 0.1 wt %. Furthermore, the RRFbrine values decreased slightly from 120 to 62 with increasing salinity (i.e., 1-10% NaCl) because of electrostatic shielding caused by charged ions in brine and the RPM. The cross-over points of relative permeability in these four samples shifted to the right because of the larger decrease in relative water permeability compared with relative oil permeability. End-point relative permeability to water in sample C-5 decreased by 80%, showing a reduction greater than that in the sample C-2 (i.e., 74%). Kr curves indicated a stronger formation damage in sample C-1, C-2, and C-4 than in sample C-5. Rock samples with a higher initial permeability exhibited a higher RRFbrine to RRFoil ratio (i.e., 3.05) under similar test conditions. This can be attributed to a larger pore radius, which was verified by nuclear magnetic resonance (NMR) measurements. Furthermore, a detailed mechanism has been proposed to understand the effects of the RPM on fluid transport in porous carbonate cores. In this study, SEM-EDX and NMR measurements combined with core flooding tests provide insights into the performance of silylated polyacrylamide-based RPMs and benefit its future implementation in carbonate reservoirs.

RESUMEN

Astrocytes respond to and regulate neuronal activity, yet their role in mammalian behavior remains incompletely understood. Especially unclear is whether, and if so how, astrocyte activity regulates contextual fear memory, the dysregulation of which leads to pathological fear-related disorders. We generated GFAP-ChR2-EYFP rats to allow the specific activation of astrocytes in vivo by optogenetics. We found that after memory acquisition within a temporal window, astrocyte activation disrupted memory consolidation and persistently decreased contextual but not cued fear memory accompanied by reduced fear-related anxiety behavior. In vivo microdialysis experiments showed astrocyte photoactivation increased extracellular ATP and adenosine concentrations. Intracerebral blockade of adenosine A1 receptors (A1Rs) reversed the attenuation of fear memory. Furthermore, intracerebral or intraperitoneal injection of A1R agonist mimicked the effects of astrocyte activation. Therefore, our findings provide a deeper understanding of the astrocyte-mediated regulation of fear memory and suggest a new and important therapeutic strategy against pathological fear-related disorders.

Memory is the record of what we learn over time and is essential to our survival. But not all memories are helpful. Repeatedly recalling a traumatic event ­ such as an assault ­ can be harmful. About 1 in 3 people who experience severe trauma go on to develop post-traumatic stress disorder (PTSD), in which they re-live the traumatic event in the form of flashbacks and nightmares. Others develop panic disorder, phobias or depression. Preventing this chain of events is challenging because fear memories form rapidly and last a long time. Current treatments involve re-exposing individuals to the traumatic event. This could be real-life exposure in the case of a phobia. Or it could involve visualizing the event, in the case of PTSD. Controlled re-exposure can help individuals learn new coping strategies. But it does not erase the initial fear memory. A better approach might be to take advantage of the fact that new memories are unstable. To form a long-lasting memory trace, newly acquired information must go through a process called consolidation to stabilize it. This process takes place in an area of the brain called the hippocampus. If consolidation does not occur, new memory traces can fade away. Li, Li et al. now show that preventing consolidation in the rat brain stops the animals from forming lasting memories of a stressful event, namely a foot shock. In the study, the rats first learned to associate a foot shock with a tone. This training took place inside a specific chamber. After learning the association, the rats began to freeze ­ a sign of fear ­ whenever they entered the chamber. This happened even if the tone was not played. But Li, Li et al. showed that they could reduce this fear response by activating cells in the hippocampus known as astrocytes, shortly after the learning episode. Activating the astrocytes made them release a substance called adenosine. Molecules of adenosine then bound to and activated proteins called adenosine A₁ receptors. Administering a drug that activated these receptors directly had the same effect as activating the astrocytes themselves. This suggests that drugs of this type could one day help patients with fear-related disorders such as PTSD and phobias. For this to become a reality, new studies must test different drugs and find the best ways of administering them. After testing in animal models, the next step will be preliminary clinical trials in people.

Asunto(s)

RESUMEN

PURPOSE: The aim of this study was to demonstrate the viability of the transverse circumflex scapular artery perforator flap (TCSAPF) in children with soft tissue defects of the lower limb. METHODS: In an anatomic study, 25 fresh cadavers were injected with lead oxide-gelatin for spiral computed tomography and 3-dimensional image reconstruction. In a 3-year clinical application study, children with soft tissue defects and exposed tendons and/or bones in the lower limb underwent free-TCSAPF repair of the defect. RESULTS: Perforators from the transverse branch of the circumflex scapular artery were identified in both anatomical and clinical studies. The average external diameter was 0.9 ± 0.3 mm. Each perforator supplied an average area of 63.5 ± 16.8 cm in anatomical. Twenty-one children were included in this group (9 boys, 12 girls, mean age, 6.6 ± 2.7 years). The size of the flaps ranged from 6 to 17 cm × 4.5 to 7 cm (average, 65.3 ± 22.6 cm). The average flap harvesting time was 30.1 ± 8.5 minutes, average operation time was 138.6 ± 31.5 minutes, and average blood loss was 89.5 ± 21.9 mL. The average length of the vessel pedicle was 8.2 ± 2.4 cm. Arterial congestion occurred in one child, 18 hours postoperatively; subsequent re-exploration and great saphenous vein transplantation were successful. Of the 3 children who had bulky flaps, 1 patient underwent defatting. Satisfactory outcomes included good appearance and function of the recipient and donor areas. CONCLUSIONS: The TCSAPF provides high-quality skin and vessel flexibility, providing a reliable blood supply in children. The flap has potential benefits over existing perforator flaps.

Asunto(s)

RESUMEN

Complex brain circuitry with feedforward and feedback systems regulates neuronal activity, enabling neural networks to process and drive the entire spectrum of cognitive, behavioral, sensory, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits is underpinned by hundreds of synaptic adhesion molecules that span synaptic junctions. Dysfunction of a single molecule or molecular interaction at synapses can lead to disrupted circuit activity and brain disorders. Neuroligins, a family of cell adhesion molecules, were first identified as postsynaptic-binding partners of presynaptic neurexins and are essential for synapse specification and maturation. Here, we review recent advances in our understanding of how this family of adhesion molecules controls neuronal circuit assembly by acting in a synapse-specific manner.

Asunto(s)

RESUMEN

Particulate matter is one of the main pollutants, causing hazy days, and it has been serious concern for public health worldwide, particularly in China recently. Quality of outdoor atmosphere with a pollutant emission of PM2.5 is hard to be controlled; but the quality of indoor air could be achieved by using fibrous membrane-based air-filtering devices. Herein, we introduce nanofiber membranes for both indoor and outdoor air protection by electrospun synthesized polyacrylonitrile:TiO2 and developed polyacrylonitrile-co-polyacrylate:TiO2 composite nanofiber membranes. In this study, we design both polyacrylonitrile:TiO2 and polyacrylonitrile-co-polyacrylate:TiO2 nanofiber membranes with controlling the nanofiber diameter and membrane thickness and enable strong particulate matter adhesion to increase the absorptive performance and by synthesizing the specific microstructure of different layers of nanofiber membranes. Our study shows that the developed polyacrylonitrile-co-polyacrylate:TiO2 nanofiber membrane achieves highly effective (99.95% removal of PM2.5) under extreme hazy air-quality conditions (PM2.5 mass concentration 1 mg/m3). Moreover, the experimental simulation of the test in 1 cm3 air storehouse shows that the polyacrylonitrile-co-polyacrylate:TiO2 nanofiber membrane (1 g/m2) has the excellent PM 2.5 removal efficiency of 99.99% in 30 min.

RESUMEN

Presynaptic endosomes reportedly participate in synaptic vesicle (SV) recycling. However, it remains unclear whether they differentially regulate SV biogenesis and synaptic transmission in different types of synapses and how they are implicated in diseases. Using cryo-electron tomography and endocytic tracing, we uncover different endocytic modes and dynamics associated with distinct SV morphology between glutamatergic and GABAergic synapses. We further find that cathepsin D (CatD), a lysosomal storage disease (LSD) protein, is selectively located in GABAergic presynaptic endosomes. Inactivation of CatD results in enlarged presynaptic endosomes, reduces the readily releasable pool, and impairs synaptic transmission in GABAergic, but not glutamatergic, synapses. Moreover, CatD-deficient mice exhibit hyperactivity and increased sensitivity to seizure, mimicking epileptic behavior in CatD-related LSD patients. These data reveal an important role for presynaptic endosomal CatD in regulating GABAergic SV biogenesis and provide mechanistic insights for understanding the synaptic pathology and behavioral defects in CatD-associated LSD.

Asunto(s)

RESUMEN

Self-healability is a crucial feature for developing artificial superhydrophobic surfaces. Although self-healing of microscopic defects has been reported, the restoration of severely damaged superhydrophobic surfaces remains a technological challenge. Here, we report a robust superhydrophobic surface possessing ultrafast recoverability after catastrophic damage. The surface is fabricated via integrating its hierarchical texture comprised of Super P (a conductive carbon black) and TiO2 nanoparticles into a poly(dimethylsiloxane) network cross-linked by dynamic pyrogallol-Fe coordination. In the presence of an electrical trigger, the surface restores its macroscopic configuration, hierarchical texture, mechanical properties, and wettability within 1 min after being cut or plasma etching. The restoration is attributed to the reconstruction of the multiscale structures through dynamic coordination. Application of the self-healable surface is demonstrated by a fast de-icing process. The present investigation offers a novel insight into the durability and reliability of artificial superhydrophobic surfaces against catastrophic damage, which has potential application in the fields including self-cleaning, anti-icing, advanced electronics, and so on.

RESUMEN

Self-healability is an attractive feature for next-generation energy-storage devices aiming at flexible/wearable electronics. However, realizing self-healability usually involves complicated molecular design and synthetic processes. Here, we demonstrate that sodium hyaluronate (SH), a kind of natural polysaccharide, can be used as a versatile polymer to facile fabricate intrinsically self-healable energy-storage devices. Self-healable sodium ion batteries and asymmetric capacitors are fabricated by integrating their electroactive components into dynamic SH networks cross-linked via borate ester bonding. The devices autonomously recover their configuration integrity, microstructure, and mechanical and electrochemical properties even after nine cycles of breaking/healing, exhibiting excellent reliability, easy maintenance, and superior safety. The electrochemical performances and self-healability are estimated to be the best among those of the existing self-healable energy-storage devices. This facile and versatile strategy might greatly accelerate the design and fabrication of smart and robust energy-storage devices applicable for advanced flexible electronics or soft robot, and so on.

RESUMEN

A sample treatment technique based on a duel frequency ultrasonic device for enzymatic digestion of rice is reported. The ultrasonic device combines a high intensity ultrasonic probe and the temperature control function of ultrasonic water bath, which can effectively extract cadmium from rice within only 160 s under the optimized conditions. Compared with the traditional ultrasonic assisted enzymatic digestion, the new method not only shortens the time significantly (e.g., from the 90 min of ultrasonic water bath to the present few minutes), but also increases the extraction efficiency of cadmium (such as ~ 75% from ultrasonic probe to app. 100%). Through the optimization of ultrasonic mode, ultrasonic frequency, power and the type of enzyme, we found that enzyme played a dominant role in ultrasound assisted enzymatic digestion. Compared with a-amylase and pepsin, trypsin is more suitable for the extraction of cadmium from rice. Furthermore, ultrasound energy is beneficial to enzymatic hydrolysis of bimolecular, and this promotion is related to the frequency of ultrasound. The reliability of this method was evaluated by analyzing the content of cadmium in the certified reference materials (CRMs, GBW10045, GBW08510, GBW08511 and GBW08512) based on atomic fluorescence spectrometry combined with a modified chemical vapor generation. The proposed method has been applied satisfactorily in the determination of Cd in several rice samples.

RESUMEN

Smart miniaturized aquatic devices have many important applications, but their locomotion at different interfaces remains a challenge. Here, we report a smart miniaturized submarine moving at various air/liquid or oil/water interfaces. The microsubmarine is fabricated by a CO2-responsive superhydrophobic copper mesh and is driven by the Marangoni effect. The microsubmarine can not only transfer among different interfaces reversibly but also move horizontally at the interfaces freely. The unique locomotion of the device is attributed to a CO2-triggered switch between superhydrophobicity and underwater superoleophobicity. Moreover, the microsubmarine exhibits good stability and excellent oil repellence at the oil/water interface. Our study provides a strategy for fabricating smart aquatic devices that have potential applications in environment monitoring, water purification, channel-free microfluidics, and so on.

RESUMEN

A gold particle deposited glassy carbon electrode (Au/GCE) was first used in electrochemical vapor generation (ECVG) technology and demonstrated to have excellent catalytic property for the electrochemical conversion process of aqueous mercury, especially for methylmercury (CH3Hg+), to gaseous mercury. Systematical research has shown that the highly consistent or distinct difference between the atomic fluorescence spectroscopy signals of CH3Hg+ and Hg2+ can be achieved by controlling the electrolytic parameters of ECVG. Hereby, a new green and accurate method for mercury speciation analysis based on the distinguishing electrochemical reaction behavior of Hg2+ and CH3Hg+ on the modified electrode was firstly established. Furthermore, electrochemical impedance spectra and the square wave voltammetry displayed that the ECVG reaction of CH3Hg+ may belong to the electrocatalytic mechanism. Under the selected conditions, the limits of detection of Hg2+ and CH3Hg+ are 5.3 ng L-1 and 4.4 ng L-1 for liquid samples and 0.53 pg mg-1 and 0.44 pg mg-1 for solid samples, respectively. The precision of the 5 measurements is less than 6% within the concentration of Hg2+ and CH3Hg+ ranging from 0.2 to 15.0 µg L-1. The accuracy and practicability of the proposed method was verified by analyzing the mercury content in the certified reference material and several fish as well as water samples.

Asunto(s)

RESUMEN

Excellent self-healability and cold resistance are attractive properties for a portable/wearable energy-storage device. However, achieving the features is fundamentally dependent on an intrinsically self-healable electrolyte with high ionic conduction at low temperature. Here we report such a hydrogel electrolyte comprising sodium alginate cross-linked by dynamic catechol-borate ester bonding. Since its dynamically cross-linked alginate network can tolerate high-content inorganic salts, the electrolyte possesses excellent healing efficiency/cyclability but also high ionic conduction at both room temperature and low temperature. A supercapacitor with the multifunctional hydrogel electrolyte completely restores its capacitive properties even after breaking/healing for 10 cycles without external stimulus. At a low temperature of -10 °C, the capacitor is even able to maintain at least 80% of its room-temperature capacitance. Our investigations offer a strategy to assemble self-healable and cold-resistant energy storage devices by using a multifunctional hydrogel electrolyte with rationally designed polymeric networks, which has potential application in portable/wearable electronics, intelligent apparel or flexible robot, and so on.

RESUMEN

Selective elimination of unwanted synapses is vital for the precise formation of neuronal circuits during development, but the underlying mechanisms remain unclear. Using inositol 1,4,5-trisphosphate receptor type 2 knockout (Itpr2(-/-)) mice to specifically disturb somatic Ca(2+) signaling in astrocytes, we showed that developmental elimination of the ventral posteromedial nucleus relay synapse was impaired. Interestingly, intracerebroventricular injection of ATP, but not adenosine, rescued the deficit in synapse elimination in Itpr2(-/-) mice. Further studies showed that developmental synapse elimination was also impaired in P2ry1(-/-) mice and was not rescued by ATP, indicating a possible role of purinergic signaling. This hypothesis was confirmed by MRS-2365, a selective P2Y1 agonist, could also rescue the deficient of synapse elimination in Itpr2(-/-) mice. Our results uncovered a novel mechanism suggesting that astrocytes release ATP in an IP3R2-dependent manner to regulate synapse elimination.

Asunto(s)

RESUMEN

MicroRNAs (miRNAs) are a new class of prognostic and diagnostic biomarkers for many cancers. Recent studies have shown that miRNAs are highly stable in plasma/serum. The aim of this study was to investigate the role of miR-421 in osteosarcoma. We found that the serum expression levels of miR-421 were significantly higher in osteosarcoma patients than those in healthy volunteers. Moreover, miR-421 expression was significantly higher in osteosarcoma tissues compared with that in the adjacent normal tissues. Meanwhile, the expression of miR-421 was upregulated in 90 % (36/40) osteosarcoma tissues compared to non-tumor tissues. More importantly, the expression levels of miR-421 in osteosarcoma tissues were correlated with those in patients' serum. In addition, patients with high miR-421 expression had shorter overall survival (OS) than those with low expressions. We also found that overexpression of miR-421 promoted osteosarcoma cell line MG-63 proliferation, migration, and invasion. In conclusion, miR-421 expression levels were upregulated in osteosarcoma tissue and serum and it may be a useful marker for diagnosis of osteosarcoma.

Asunto(s)