Artificial Retina Based on Organic Heterojunction Transistors for Mobile Recognition.

The flicker frequency of incident light constitutes a critical determinant in biology. Nevertheless, the exploration of methods to simulate external light stimuli with varying frequencies and develop artificial retinal neurons capable of responsive behavior remains an open question. This study presents an artificial neuron comprising organic phototransistors. The triggering properties of neurons are modulated by optical input, enabling them to execute rudimentary synaptic functions, emulating the biological characteristics of retinal neurons. The artificial retinal neuron exhibits varying responses to incoming light frequencies, allowing it to replicate the persistent visual behavior of the human eye and facilitating image discrimination. Additionally, through seamless integration with circuitry, it can execute motion recognition on a machine cart, preventing collisions with high-speed obstacles. The artificial retinal neuron offers a cost-effective and energy-efficient route for future mobile robot processors.

Optically Readable Organic Electrochemical Synaptic Transistors for Neuromorphic Photonic Image Processing.

Optically readable organic synaptic devices have great potential in both artificial intelligence and photonic neuromorphic computing. Herein, a novel optically readable organic electrochemical synaptic transistor (OR-OEST) strategy is first proposed. The electrochemical doping mechanism of the device was systematically investigated, and the basic biological synaptic behaviors that can be read by optical means are successfully achieved. Furthermore, the flexible OR-OESTs are capable of electrically switching the transparency of semiconductor channel materials in a nonvolatile manner, and thus the multilevel memory can be achieved through optical readout. Finally, the OR-OESTs are developed for the preprocessing of photonic images, such as contrast enhancement and denoising, and feeding the processed images into an artificial neural network, achieving a recognition rate of over 90%. Overall, this work provides a new strategy for the implementation of photonic neuromorphic systems.

Artificial Vision Adaption Mimicked by an Optoelectrical In2O3 Transistor Array.

Simulation of biological visual perception has gained considerable attention. In this paper, an optoelectrical In2O3 transistor array with a negative photoconductivity behavior is designed using a side-gate structure and a screen-printed ion-gel as the gate insulator. This paper is the first to observe a negative photoconductivity in electrolyte-gated oxide devices. Furthermore, an artificial visual perception system capable of self-adapting to environmental lightness is mimicked using the proposed device array. The transistor device array shows a self-adaptive behavior of light under different levels of light intensity, successfully demonstrating the visual adaption with an adjustable threshold range to the external environment. This study provides a new way to create an environmentally adaptive artificial visual perception system and has far-reaching significance for the future of neuromorphic electronics.

Lactobacillus plantarum-derived extracellular vesicles protect against ischemic brain injury via the microRNA-101a-3p/c-Fos/TGF-ß axis.

Currently, the reported source of extracellular vesicles (EVs) for the treatment of ischemic stroke（IS）is limited to mammals. Moreover, these EVs are restricted to clinical translation by the high cost of cell culture. In this respect, Lactobacillus plantarum culture is advantaged by low cost and high yield. However, it is poorly understood whether Lactobacillus plantarum-derived EVs (LEVs) are applicable for the treatment of IS. Here, our results demonstrated that LEVs reduced apoptosis in ischemic neuron both in vivo and in vitro. As revealed by high-throughput sequencing, miR-101a-3p expression was significantly elevated by LEV treatment in OGD/R-induced neurons, as confirmed in the tMCAO mice treated with LEVs. Mechanistically, c-Fos was directly targeted by miR-101a-3p. In addition, c-Fos determined ischemia-induced neuron apoptosis in vivo and in vitro through the TGF-ß1 pathway, miR-101a-3p inhibition aggravated ischemia-induced neuron apoptosis in vitro and in vivo, and miR-101a-3p overexpression produced the opposite results. Hsa-miR-101-3p was downregulated in the plasma of patients with IS but upregulated in the patients with neurological recovery after rt-PA intravenous thrombolysis. In conclusion, Our results demonstrated for the first time that LEVs might inhibit neuron apoptosis via the miR-101a-3p/c-Fos/TGF-ß axis, and has-miR-101-3p is a potential marker of neurological recovery in IS patients.

A Smart Patch with On-Demand Detachable Adhesion for Bioelectronics.

A smart ionic skin patch with on-demand detachable adhesion has been developed as human-machine interface for physiological signal monitoring. In spite of the multifunctions demonstrated by existing ionic skin, it is still difficult to distinguish different signals simultaneously. Moreover, the secondary damages to the tissues are often overlooked when the adhesive materials are removing from the wound. Herein, a multifunctional biomimetic hydrogel with temperature, mechanical, electrical, and pH response is developed. This hydrogel is designed by in situ polymerizing of hydrophilic anion monomers in a natural cationic polysaccharide to construct multifunctional biomimetic ionic channel. Due to the reversible physical cross-linked network and thermosensitivity, the mechanical properties, adhesion, and visual effect of the hydrogel can be tuned by changing hydrogen bonding density via phase transition, thus making it an excellent biosafe material for wearable device. The hydrogel is utilized as skin patch intended for monitoring physiological signals stimulated by physical and chemical changes involving pressure, temperature, pH value, and electrocardiograph. Especially, this ionic skin patch can recognize temperature change signals precisely either in broad or extremely narrow temperature range. This smart skin patch can even recognize the pressure and temperature signals in real time and differentiate the signals simultaneously.

Oxygen uptake is more efficient in idiopathic pulmonary arterial hypertension than in chronic thromboembolic pulmonary hypertension.

BACKGROUND AND OBJECTIVE: The responses of oxygen uptake efficiency (OUE) during cardiopulmonary exercise training (CPET) have not been reported in patients with pulmonary hypertension. We aimed to investigate the differences in OUE between patients with idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Forty-four patients with IPAH and 29 patients with CTEPH were retrospectively enrolled into our study. All patients underwent right-heart catheterization, pulmonary function test and performed the 6-min walk test and CPET. RESULTS: We found that oxygen uptake efficiency plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold (OUE@AT) was significantly higher in IPAH than that in CTEPH (both P = 0.002). However, patients with CTEPH had lower mean pulmonary artery pressure, pulmonary vascular resistance and transpulmonary gradient (all P < 0.05). The correlation between OUEP and heart rate at anaerobic threshold (HR_AT) was significant (r = 0.376, P < 0.05); however, no statistically significant correlation was found with ventilation at anaerobic threshold (VE_AT) (r = -0.074, P > 0.05) in patients with IPAH. In patients with CTEPH, both anaerobic threshold (r = 0.307, P > 0.05) and VE_AT (r = -0.709, P < 0.0001) were reduced. OUEP were higher in WHO functional class I/II patients than in WHO functional class III/IV patients (all P < 0.05). CONCLUSIONS: OUEP and OUE@AT are higher in IPAH than that in CTEPH not in proportion to haemodynamics, probably due to differences in cardiac function and pulmonary vascular occlusion. OUEP correlates well with the exercise capacity and the severity of the disease.

[Correlation between oxygen uptake efficiency and exercise capacity in pulmonary hypertension patients].

OBJECTIVE: To explore the characteristics of oxygen uptake efficiency (OUE) in patients with pulmonary hypertension (PH) and analyze the correlation between OUE and exercise capacity. METHODS: A total of 76 PH patients and 29 healthy controls at Shanghai Pulmonary Hospital between October 2010 and January 2014 were evaluated. All PH patients were classified into 4 groups according to the World Health Organization functional class (WHO-FC). Pulmonary function and cardiopulmonary exercise tests were performed in all subjects. RESULTS: Compared with health control, the PH patients had lower forced vital capacity (FVC) of expected value (%pre), forced expiratory volume in one second (FEV(1))%pre and FEV(1)/FVC ((81.9 ± 15.5)% vs (88.6 ± 14.1)%, (75.0 ± 16.4)% vs (85.2 ± 17.2)% and (78.3 ± 9.3)% vs (88.3 ± 7.3)%, all P < 0.05). Compared with control group, there were also significant reductions in oxygen uptake efficiency slope (OUES), oxygen uptake efficiency plateau (OUEP) and OUE at the anaerobic threshold ((1.14 ± 0.42) vs (2.32 ± 0.34) (L/min)/lg (L/min), (27 ± 5) vs (37 ± 4) ml/L, (24 ± 6) vs (34 ± 5) ml/L, all P < 0.05). No significant differences existed in OUES, OUEP and OUE at the anaerobic threshold in PH patients between WHO-FC Iand WHO-FC II groups. There were significant differences in OUE among other groups (all P < 0.05). And OUES, OUEP and OUE at the anaerobic threshold were correlated positively with exercise tolerance in PH patients. CONCLUSION: OUE significantly declines in PH patients compared with normal subjects and it is correlated positively with exercise capacity.

Protein 4.1R attenuates autoreactivity in experimental autoimmune encephalomyelitis by suppressing CD4(+) T cell activation.

Immune synapse components contribute to multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) pathogenesis as they play important role in autoreactive T cell activation. Protein 4.1R, a red cell membrane cytoskeletal protein, recently was identified as an important component of immunological synapse (IS) and acted as the negative regulator of CD4(+) T cell activation. However, the pathological role of 4.1R in the MS/EAE pathogenesis is still not elucidated. In this study, we investigated the potential role of protein 4.1R in pathologic processes of EAE by using 4.1R knockout mouse model. Our results suggest that 4.1R can prevent pathogenic autoimmunity in MS/EAE progression by suppressing the CD4(+) T cell activation.

[Correlation between submaximal exercise measurements and peak oxygen uptake in patients with pulmonary arterial hypertension].

OBJECTIVE: To explore the correlation between submaximal exercise measurements and peak oxygen uptake in patients with pulmonary arterial hypertension (PAH). METHODS: The clinical data were retrospectively analyzed for 106 patients with PAH from Affiliated Shanghai Pulmonary Hospital, Tongji University from October 2010 to October 2013. The examinations included routine pulmonary function test, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk test, right heart catheterization and cardiopulmonary exercise testing. And within the same period, matched 20 healthy subjects without smoking and cardiopulmonary diseases were selected as control group. RESULTS: Peak oxygen uptake (P-VO2), anaerobic threshold (AT), oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) were significantly lower in patients with PAH than control group ((841 ± 257) vs (1 682 ± 284) ml/min, (661 ± 171) vs (1 041 ± 243) ml/min, 1.1 ± 0.4 vs 2.3 ± 0.4, 25.8 ± 5.2 vs 35.5 ± 4.0, respectively) (all P < 0.001). And the predicted parametric values (%pred) were also lower in PAH group than control group (all P < 0.001). While the lowest ventilation (VE)/CO2 output (VCO2) (L-VE/VCO2) and VE/VCO2 slope were significantly higher in PAH group than control group (50.5 ± 15.9 vs 30.5 ± 3.0 and 57.2 ± 23.2 vs 25.6 ± 2.8, both P < 0.001). Pearson correlation analysis showed, except for VE/VCO2 slope%pred, AT%pred, L-VE/VCO2%pred, OUES%pred and OUEP%pred were correlated with P-VO2 (all P < 0.001). According to multiple linear regression analysis, only AT%pred and OUES%pred were the independent predictors of P-VO2 (ß = 0.394, 0.384, both P < 0.001) and OUES%pred might be better than AT%pred (the adjusted ß = 0.674). When AT%pred < 58.0% or OUES%pred < 65.0%, exercise capacity in PAH declined obviously with the sensitivity was 92.3% and 96.2% and the specificity 81.2% and 75.5% respectively. CONCLUSIONS: Exercise capacity in patients with PAH is significantly lower than healthy subjects. OUES%pred and AT%pred may be used as an independent predictor of exercise capacity. And OUES%pred may be more powerful.

Childhood asthma was associated with the presence of cardio-cerebrovascular diseases in US middle-aged and elderly.

Background: Asthma and cardio-cerebrovascular diseases (CVDs) share a common etiology of chronic systemic inflammation. Our manuscript was to investigate the association between childhood asthma and CVDs in middle-aged and elderly. Methods: A total of 12,070 US middle-aged and elder were enrolled in the National Health and Nutrition Examination Survey. Childhood asthma was defined as a previous diagnosis of asthma at <18 years of age. Associations between childhood asthma and overall and cause-specific CVDs were evaluated using multivariable logistic regression models and subgroup analyses, including coronary artery disease (CAD), angina, and stroke. Results: The prevalence of CVDs, including CAD (p = 0.031) and angina (p < 0.001), was significantly higher in patients with asthma (p = 0.008). Asthma was independently associated with a higher risk of CVDs (odds ratio [OR]:1.50, 95 % confidence interval [CI]: 1.22-1.84, p < 0.001), CAD (OR: 1.55, 95 %CI: 1.17-2.02, p = 0.002), and angina (OR: 1.93, 95 %CI: 1.42-2.58, p < 0.001) while not related to stroke (p = 0.233). Subgroup analysis suggested that the association was consistent across sex, race, and the presence of obesity, chronic obstructive pulmonary disease, and diabetes. Conclusions: Childhood asthma was significantly associated with the presence of cardiocerebrovascular diseases, including CAD and angina in middle-aged and elderly. These findings underscore the importance of addressing childhood asthma as a potential risk factor for cardiovascular morbidity in middle-aged and elderly populations.

From agricultural waste residue to wealth support: A magnetically N-heterocyclic carbene functionalized corn cob cellulose as a new stabilizer for Pd catalyst in Suzuki reaction.

Because of eco-friendliness, biodegradability and ease of modification, cellulose is deemed as alternative to unrenewable petroleum resources. Nonetheless, it is more indispensable to exploit corn cob cellulose produced from agricultural waste residue as supportive materials in green catalysis. In this study, a new magnetically benzimidazole functionalized cellulose/Fe3O4 derived from corn cob cellulose as a stabilizer agent (Fe3O4@CL-NHC) was prepared, and palladium was immobilized on this stabilizer (Fe3O4@CL-NHC-Pd). The catalyst was fully characterized by different techniques including TEM, SEM, and XPS analyses, etc. The abundant hydroxyl groups of cellulose provided uniform dispersion and high stability of palladium, while Fe3O4 as a support offered simple magnetic separation. High efficiency (up to 99 %) was demonstrated by this biocatalyst under green conditions in relatively short reaction times towards Suzuki reactions. Due to collaborative interactions of N-heterocyclic carbene and hydroxyl groups with palladium, the synthesized complex prevented metal leaching effectively (<1 %). Moreover, the magnetic property of this catalyst (43.0 emu g-1) provides facile recovery of this composite from the reaction mixture with great ease for several times, which overcomes issues of complicated work-up separation. This work offers a promising avenue to enriching the application of biopolymer from agricultural residue in the potential organic transformations.

A guanosine/konjac glucomannan supramolecular hydrogel with antioxidant, antibacterial and immunoregulatory properties for cutaneous wound treatment.

Developing naturally-derived wound dressing materials with intrinsic therapeutic effects is desirable for the clinical applications. Recently, guanosine-based supramolecular G-quadruplex (G4) hydrogel exhibited great potential in preparing biological materials due to its simple fabrication method and responsive gel networks. However, the weak mechanical properties and the consequent burst release of bioactive molecules restrict its clinical applications. Herein, we found that konjac glucomannan (KGM) with immunoregulatory effect did not affect the self-assembly of G-quadruplexes and thus effectively enhancing the mechanical properties of G4 hydrogel. Aloin, as a model drug, was in situ loaded into gel networks, finally obtaining the G4/Aloin-KGM hydrogel. This hydrogel exhibited porous morphology, swelling ability and hemostatic capability. Boronate bonds in G4 networks and aloin collectively endowed the hydrogel with excellent antioxidant performance. Meanwhile, aloin also provided outstanding in vitro and in vivo bactericidal ability. The wounds treated with this biocompatible hydrogel demonstrated faster regeneration of epithelial and dermal tissues, and the whole wound healing stages were accelerated by promoting collagen deposition, facilitating macrophage polarization towards M2 phenotype, down-regulating the expression level of IL-6, and up-regulating the expression level of IL-10, CD31 and α-SMA.

Species pool and soil properties in mangrove habitats influence the species-immigration process of diazotrophic communities across southern China.

Microbial immigration is an ecological process in natural environments; however, the ecological trade-off mechanisms that govern the balance between species extinction and migration are still lacking. In this study, we investigated the mechanisms underlying the migration of diazotrophic communities from soil to leaves across six natural mangrove habitats in southern China. The results showed that the diazotrophic alpha and beta diversity exhibited significant regional and locational variations. The diazotrophic species pool gradually increased from the leaves to nonrhizosphere soil at each site, exhibiting a vertical distribution pattern. Mantel test analyses suggested that climate factors, particularly mean annual temperature, significantly influenced the structure of the diazotrophic community. The diazotrophic community assembly was mainly governed by dispersal limitation in soil and root samples, whereas dispersal limitation and ecological drift were dominant in leaves. Partial least squares path modeling revealed that the species pool and soil properties, particularly the oxidation-reduction potential and pH, were closely linked to the species-immigration ratio of diazotrophic communities. Our study provides novel insights for understanding the ecological trait diversity patterns and spread pathways of functional microbial communities between below- and aboveground habitats in natural ecosystems.IMPORTANCEEnvironmental selection plays key roles in microbial transmission. In this study, we have provided a comprehensive framework to elucidate the driving patterns of the ecological trade-offs in diazotrophic communities across large-scale mangrove habitats. Our research revealed that Bradyrhizobium japonicum, Marinobacterium lutimaris, and Agrobacterium tumefaciens were more abundant in root-associated soil than in leaves by internal and external pathways. The nonrhizospheric and rhizospheric soil samples harbored the most core amplicon sequence variants, indicating that these dominant diazotrophs could adapt to broader ecological niches. Correlation analysis indicated that the diversities of the diazotrophic community were regulated by biotic and abiotic factors. Furthermore, this study found a lower species immigration ratio in the soil than in the leaves. Both species pool and soil properties regulate the species-immigration mechanisms of the diazotrophic community. These results suggest that substantial species immigration is a widespread ecological process, leading to alterations in local community diversity across diverse host environments.

Regulation of mTOR complexes in long-lived growth hormone receptor knockout and Snell dwarf mice.

Downregulation of mTOR (mechanistic target of rapamycin) can extend lifespan in multiple species, including mice. Growth hormone receptor knockout mice (GHRKO) and Snell dwarf mice have 40% or greater lifespan increase, and have lower mTORC1 function, which might reflect alteration in mTORC1 components or alteration of upstream proteins that modulate mTOR activity. Here we report reduction of mTORC components DEPTOR and PRAS40 in liver of these long-lived mice; these changes are opposite in direction to those that would be expected to lead to lower mTORC1 function. In contrast, levels of the upstream regulators TSC1 and TSC2 are elevated in GHRKO and Snell liver, kidney and skeletal muscle, and the ratio of phosphorylated TSC2 to total TSC2 is lower in the tissues of the long-lived mutant mice. In addition, knocking down TSC2 in GHRKO fibroblasts reversed the effects of the GHRKO mutation on mTORC1 function. Thus increased amounts of unphosphorylated, active, inhibitory TSC may contribute to lower mTORC1 function in these mice.

miR-155-5p in Extracellular Vesicles Derived from Choroid Plexus Epithelial Cells Promotes Autophagy and Inflammation to Aggravate Ischemic Brain Injury in Mice.

Ischemic stroke is a common disease of the central nervous system, and ischemic brain injury (IBI) is its main manifestation. Recently, extracellular vesicles (EVs) have been strongly related to the diagnosis and treatment of IBI. However, the underlying mechanism of their effects remains enigmatic. In the present study, we aimed to study how miR-155-5p plays a role in choroid plexus epithelial (CPE) cell-derived EVs in IBI pathology. We found that miR-155-5p expression was enriched in CPE cell-derived EVs, which were subsequently internalized by neurons, enabling the delivery of miR-155-5p into neurons. An inducible oxygen and glucose deprivation and reoxygenation (OGD/R) cell model was developed to mimic ischemic neuronal injury in vitro. miR-155-5p overexpression led to reduced neuron viability, promoted apoptosis, elevated autophagic proteins' expression, and activated NLR family pyrin domain-containing 3- (NLRP3-) related inflammasomes, thereby aggravating OGD-induced neuronal injury. A dual-luciferase reporter assay exhibited that miR-155-5p could inhibit the Ras homolog enriched in brain (Rheb) expression, a mechanism critical for miR-155-5p-mediated neuronal injury. Furthermore, a mouse IBI model was developed using the transient middle cerebral artery occlusion (tMCAO) method. Animal experiments verified that miR-155p delivery via CPE cell-derived EVs aggravated IBI by suppressing Rheb expression. In conclusion, miR-155-5p in CPE-derived EVs can aggravate IBI pathology by suppressing Rheb expression and promoting NLRP3-mediated inflammasomes, suggesting its role as a potential therapeutic target in IBI.

Mimic enzymatic preparation of conductive supramolecular-polymeric hydrogels with antibacterial and antioxidant properties for accelerating wound healing.

Supramolecular-polymeric hydrogels by combining low-molecular-weight gelators (LMWGs) with polymers have attracted great attention due to their unique double networks. Polymers are generally introduced into an LMWG matrix, thus enhancing the mechanical performance and broadening of the application fields of supramolecular hydrogels. Herein, a series of supramolecular-polymer hydrogels with inherent multiple properties were fabricated as wound dressings. An enzyme-like supramolecular H/G4 hydrogel co-assembled by hemin and guanosine-quartet motifs was successively integrated with hyaluronic acid (HA) and polyaniline (PANI), yielding a supramolecular-polymeric composite hydrogel (namely H/G4-HA(Cu)/PANI). The introduction of Cu2+-crosslinked hydrazide-grafted HA polymeric networks not only enhanced the viscoelasticity of the H/G4 supramolecular hydrogel but also endowed composite hydrogels with bioactive properties as wound healing dressings. The enzyme-like nanofibril H/G4 hydrogel could catalyse the oxidative polymerization of aniline, thus introducing PANI into gel networks. The porous H/G4-HA(Cu)/PANI exhibited a certain degree of swelling ratio under physiological conditions. H/G4-HA(Cu)/PANI also showed degradability, conductivity and appropriate mechanical properties. Through a full-thickness skin defect model of mice, this haemostatic, antioxidant, antibacterial and drug-free H/G4-HA(Cu)/PANI could accelerate wound healing processes by promoting wound closure, collagen deposition and upregulation of the CD31 expression level, which indicates that H/G4-HA(Cu)/PANI could be a promising wound dressing material.

Research on the insurance of swimming crab temperature and salinity index insurance based on Copula function.

Under climate change, the sea surface temperature and salinity change greatly, which poses a considerable threat to sustainable food security. Sea surface temperature and salinity (SST/SSS) are selected to examine the annual output of swimming crab in 24 cities along the eastern China. The Copula-based function was used to construct the probability distribution model of the swimming crab yield with SST and SSS. The pure premium rate of the swimming crab production in these 24 cities are also examined. The results show that 1) There is significant positive correlations between the yield of swimming crab with temperature and salinity over the study area. The only exception is that the correlation between yield of swimming crab and salinity is not significant in the south of study area. 2) The span of the pure insurance premium rate of swimming crab in 24 cities increases rapidly with the increase of the protection level, the maximum span up to 2.04%, and the minimum span is only 1.6%. 3) The distribution of the swimming crab insurance premium rate is various in space. The insurance premium rate of 8 cities in the south of Taizhou is low with the highest premium rate at 5.6%. The insurance premium rate of 16 cities in north of Taizhou is relatively high with the rate between 6%-22%. The research can provide a theoretical basis for the pricing of insurance products for swimming crab in 24 cities in the typical aquaculture areas in eastern China.

Cap-independent translation of GPLD1 enhances markers of brain health in long-lived mutant and drug-treated mice.

Glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1) hydrolyzes inositol phosphate linkages in proteins anchored to the cell membrane. Mice overexpressing GPLD1 show enhanced neurogenesis and cognition. Snell dwarf (DW) and growth hormone receptor knockout (GKO) mice show delays in age-dependent cognitive decline. We hypothesized that augmented GPLD1 might contribute to retained cognitive function in these mice. We report that DW and GKO show higher GPLD1 levels in the liver and plasma. These mice also have elevated levels of hippocampal brain-derived neurotrophic factor (BDNF) and of doublecortin (DCX), suggesting a mechanism for maintenance of cognitive function at older ages. GPLD1 was not increased in the hippocampus of DW or GKO mice, suggesting that plasma GPLD1 increases elevated these brain proteins. Alteration of the liver and plasma GPLD1 was unaltered in mice with liver-specific GHR deletion, suggesting that the GH effect was not intrinsic to the liver. GPLD1 was also induced by caloric restriction and by each of four drugs that extend lifespan. The proteome of DW and GKO mice is molded by selective translation of mRNAs, involving cap-independent translation (CIT) of mRNAs marked by N6 methyladenosine. Because GPLD1 protein increases were independent of the mRNA level, we tested the idea that GPLD1 might be regulated by CIT. 4EGI-1, which enhances CIT, increased GPLD1 protein without changes in GPLD1 mRNA in cultured fibroblasts and mice. Furthermore, transgenic overexpression of YTHDF1, which promotes CIT by reading m6A signals, also led to increased GPLD1 protein, showing that elevation of GPLD1 reflects selective mRNA translation.

Microstructure and properties evolution of Mg-2Y-0.6Nd-0.6Zr alloy rolled at room and liquid nitrogen temperature.

The microstructure evolution, texture, mechanical behavior and twin deformation of the ECAPed Mg-2Y-0.6Nd-0.6Zr alloy at room and liquid nitrogen temperature were investigated by rolling samples. The ECAP processed material appeared the texture of 45° to the extrusion direction and its yield strength reached 93.6 MPa. The results showed that cryorolling encourages twinning in Mg-2Y-0.6Nd-0.6Zr alloy, enhancing the tensile strength and texture. Activation of {10-12} twinning during rolling was found to be more pronounced in the cryorolled samples than in the cold rolled samples owing to a lower temperature. As a result, the cryorolled samples had more twins than and cold rolled ones, the proportion of twin areas of room temperature rolling and ultra-low temperature rolling were: 2.45% and 4.23%.

Disrupting phosphorylation of Tyr-1070 at GluN2B selectively produces resilience to depression-like behaviors.

Drugs targeting N-methyl-D-aspartate receptors (NMDARs) have been approved to treat major depressive disorder (MDD); however, the presence of undesirable psychotomimetic and cognitive side effects may limit their utility. In this study, we show that the phosphorylation levels of the GluN2B subunit at tyrosine (Y) 1070 increase in mice after both acute and chronic restraint stress (CRS) exposure. Preventing GluN2B-Y1070 phosphorylation via Y1070F mutation knockin produces effects similar to those of antidepressants but does not affect cognitive or anxiety-related behaviors in subject mice. Mechanistically, the Y1070F mutation selectively reduces non-synaptic NMDAR currents and increases the number of excitatory synapses in the layer 5 pyramidal neurons of medial prefrontal cortex (mPFC) but not in the hippocampus. Altogether, our study identifies phosphorylation levels of GluN2B-Y1070 in the mPFC as a dynamic, master switch guarding depressive behaviors, suggesting that disrupting the Y1070 phosphorylation of GluN2B subunit has the potential for developing new antidepressants.