Clinical characteristics and outcomes of acute liver failure in neonates: a retrospective cohort in China.

Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28 days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48 days; 26 days for hypoxic/ischemic injury and 43 days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018).   Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: • Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. • Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. • There are no reliable biochemical markers to predict the outcome of NALF. What is New: • In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. • The overall prognosis of NALF is poor, and its etiology determines the short-term outcome.

Diagnostic Performance and Clinical Impact of Metagenomic Next-Generation Sequencing for Pediatric Infectious Diseases.

Metagenomic next-generation sequencing (mNGS) has shown promise in the diagnosis of infectious diseases in adults, while its efficacy in pediatric infections remains uncertain. We performed a retrospective analysis of 1,493 mNGS samples from pediatric patients with blood, central nervous system, and lower respiratory tract infections. The positive percent agreement (PPA) and the negative percent agreement (NPA) of mNGS were compared to conventional microbiological tests (CMT) based on clinical diagnosis. The agreement of mNGS compared to CMT, as well as the clinical impact of mNGS, were valuated. Using the clinical diagnosis as a reference, mNGS demonstrated a significantly higher overall PPA compared to CMT (53.1% [95% CI = 49.7 to 56.6%] versus 25.8% [95% CI = 22.8 to 28.9%]), while maintaining a comparable overall NPA (93.2% [95% CI = 91.3 to 95.1%] versus 97.2% [95% CI = 95.9 to 98.4%]). In septic patients under 6 years of age or with immunosuppressive status, mNGS showed a higher PPA and a comparable NPA compared to CMT. The overall PPA and NPA of mNGS compared to CMT were 75.3 and 75.0%, respectively. The majority of cases of Streptococcus pneumoniae, Streptococcus agalactiae, Mycobacterium tuberculosis complex, and Pneumocystis jirovecii infections were identified by mNGS. A positive clinical impact of 14.0% (206/1,473), a negative impact of 0.8% (11/1,473), a nonimpact of 84.7% (1,248/1,473), and an unknown impact of 0.5% (8/1,473) were observed in the mNGS results. Notably, the positive impact was greater among immunosuppressed patients than among nonimmunosuppressed individuals (67/247, 27.1% versus 139/1,226, 11.3%; P < 0.001). mNGS is valuable for pathogen detection, diagnosis, and clinical management of infections among pediatric patients. mNGS was thus effective for the diagnosis of pediatric infections, which may guide clinical management. Patients with immunosuppressive conditions benefited more from mNGS testing.

Rational design of MXene-based single atom catalysts for Na-Se batteries from sabatier principle.

Na-Se batteries have attracted great attention because of their high-energy density and low cost, though the shuttle effect of polyselenides and sluggish reaction dynamics still limit their practical applications. Herein, MXenes were decorated with single zinc atom as selenium hosts, and the effect of interfacial electrochemical reaction was studied via first-principles simulation. The embedding of single zinc atom into MXenes was found to enhance the anchoring ability to inhibit the shuttle effect. However, Zn-MXenes as single atom catalysts had different effects on interfacial electrochemical reactions, which can be attributed to the increased interaction strengths between Zn-MXenes and polyselenides. For Ti-based MXenes, the enhanced interaction was found to be beneficial for the electrochemical reaction, whereas the overly strong anchoring strength of Zn-Cr2CO2 would inhibit charging-discharging kinetics. Therefore, the matching of MXenes and metal atoms should be considered to adjust the anchoring ability based on the Sabatier principle. This work provides new insights into the design of SACs and high-performance Na-Se batteries.

GridAttackAnalyzer: A Cyber Attack Analysis Framework for Smart Grids.

The smart grid is one of the core technologies that enable sustainable economic and social developments. In recent years, various cyber attacks have targeted smart grid systems, which have led to severe, harmful consequences. It would be challenging to build a real smart grid system for cybersecurity experimentation and validation purposes. Hence, analytical techniques, with simulations, can be considered as a practical solution to make smart grid cybersecurity experimentation possible. This paper first provides a literature review on the current state-of-the-art in smart grid attack analysis. We then apply graphical security modeling techniques to design and implement a Cyber Attack Analysis Framework for Smart Grids, named GridAttackAnalyzer. A case study with various attack scenarios involving Internet of Things (IoT) devices is conducted to validate the proposed framework and demonstrate its use. The functionality and user evaluations of GridAttackAnalyzer are also carried out, and the evaluation results show that users have a satisfying experience with the usability of GridAttackAnalyzer. Our modular and extensible framework can serve multiple purposes for research, cybersecurity training, and security evaluation in smart grids.

Relationship between phenotype and genotype of 102 Chinese newborns with Prader-Willi syndrome.

High rates of misdiagnosis and delayed intervention in neonatal PWS are leading to poor prognoses. To determine the clinical and image characteristics of newborns with Prader-Willi syndrome (PWS). A total of 102 cases of newborns definitively diagnosed with PWS at the Children's Hospital of Fudan University from 02/2014 to 12/2017 were retrospectively analyzed. We analyzed the modulated voxel-based morphology (VBM) of gray matter in PWS by T2 weighted imaging. Of 102 cases, 75 (73.5%) have paternal deletion of 15q11.2-q13, whereas 27 (26.5%) have maternal uniparental disomy (UPD). Of the 75 deletion cases, 75 (100%) week crying, 71 (94.7%) hypotonia, 70 (93.3%) poor feeding, 46 (61.3%) hypopigmentation, 43 (57.3%) male cryptorchidism, 10 (13.3%) female labia minora, 48 (64%) characteristic facial features. Of 27 UPD cases, 27 (100%) week crying and hypotonia, 25 (92.6%) hypophagia, 20 (74.1%) male cryptorchidism, 1 (3.7%) female labia minora, 19 (70.4%) characteristic facial features, 12 (44.4%) hypopigmentation. The modulated VBM analysis shows that the middle frontal gyrus, orbitofrontal cortex (middle), and inferior frontal gyrus are the most variable brain regions that determine the endo-phenotype difference between the two genotypes. Hypotonia, hypophagia, and maldevelopment of sexual organs are general characteristics of newborns with PWS in Chinese population. In UPD cases, the proportions of premature newborns, elderly parturient women and congenital malformations were higher than for paternal deletion cases. The differences in the gray matter volume of these three regions between the two genotypes may explain the differences in maladaptive behaviors and emotions.

A functional mammalian target of rapamycin complex 1 signaling is indispensable for c-Myc-driven hepatocarcinogenesis.

Amplification and/or activation of the c-Myc proto-oncogene is one of the leading genetic events along hepatocarcinogenesis. The oncogenic potential of c-Myc has been proven experimentally by the finding that its overexpression in the mouse liver triggers tumor formation. However, the molecular mechanism whereby c-Myc exerts its oncogenic activity in the liver remains poorly understood. Here, we demonstrate that the mammalian target of rapamycin complex 1 (mTORC1) cascade is activated and necessary for c-Myc-dependent hepatocarcinogenesis. Specifically, we found that ablation of Raptor, the unique member of mTORC1, strongly inhibits c-Myc liver tumor formation. Also, the p70 ribosomal S6 kinase/ribosomal protein S6 and eukaryotic translation initiation factor 4E-binding protein 1/eukaryotic translation initiation factor 4E signaling cascades downstream of mTORC1 are required for c-Myc-driven tumorigenesis. Intriguingly, microarray expression analysis revealed up-regulation of multiple amino acid transporters, including solute carrier family 1 member A5 (SLC1A5) and SLC7A6, leading to robust uptake of amino acids, including glutamine, into c-Myc tumor cells. Subsequent functional studies showed that amino acids are critical for activation of mTORC1 as their inhibition suppressed mTORC1 in c-Myc tumor cells. In human hepatocellular carcinoma specimens, levels of c-Myc directly correlate with those of mTORC1 activation as well as of SLC1A5 and SLC7A6. CONCLUSION: Our current study indicates that an intact mTORC1 axis is required for c-Myc-driven hepatocarcinogenesis; thus, targeting the mTOR pathway or amino acid transporters may be an effective and novel therapeutic option for the treatment of hepatocellular carcinoma with activated c-Myc signaling. (Hepatology 2017;66:167-181).

Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity.

Zoledronate is a bisphosphonate that is widely used in the treatment of metabolic bone diseases. However, zoledronate induces significant nephrotoxicity associated with acute tubular necrosis and renal fibrosis when administered intravenously. There is speculation that zoledronate-induced nephrotoxicity may result from its pharmacological activity as an inhibitor of the mevalonate pathway but the molecular mechanisms are not fully understood. In this report, human proximal tubular HK-2 cells and mouse models were combined to dissect the molecular pathways underlying nephropathy caused by zoledronate treatments. Metabolomic and proteomic assays revealed that multiple cellular processes were significantly disrupted, including the TGFß pathway, fatty acid metabolism and small GTPase signaling in zoledronate-treated HK-2 cells (50 µM) as compared with those in controls. Zoledronate treatments in cells (50 µM) and mice (3 mg/kg) increased TGFß/Smad3 pathway activation to induce fibrosis and kidney injury, and specifically elevated lipid accumulation and expression of fibrotic proteins. Conversely, fatty acid transport protein Slc27a2 deficiency or co-administration of PPARA agonist fenofibrate (20 mg/kg) prevented zoledronate-induced lipid accumulation and kidney fibrosis in mice, indicating that over-expression of fatty acid transporter SLC27A2 and defective fatty acid ß-oxidation following zoledronate treatments were significant factors contributing to its nephrotoxicity. These pharmacological and genetic studies provide an important mechanistic insight into zoledronate-associated kidney toxicity that will aid in development of therapeutic prevention and treatment options for this nephropathy.

Effects of lead exposure on dendrite and spine development in hippocampal dentate gyrus areas of rats.

Lead exposure has been implicated in the impairment of synaptic plasticity in the hippocampal dentate gyrus (DG) areas of rats. However, whether the degradation of physiological properties is based on the morphological alteration of granule neurons in DG areas remains elusive. Here, we examined the dendritic branch extension and spine formation of granule neurons after lead exposure during development in rats. Dendritic morphology was studied using Golgi-Cox stain method, which was followed by Sholl analysis at postnatal days 14 and 21. Our results indicated that, for both ages, lead exposure significantly decreased the total dendritic length and spine density of granule neurons in the DG of the rat hippocampus. Further branch order analysis revealed that the decrease of dendritic length was observed only at the second branch order. Moreover, there were obvious deficits in the proportion and size of mushroom-type spines. These deficits in spine formation and maturity were accompanied by a decrease in Arc/Arg3.1 expression. Our present findings are the first to show that developmental lead exposure disturbs branch and spine formation in hippocampal DG areas. Arc/Arg3.1 may have a critical role in the disruption of neuronal morphology and synaptic plasticity in lead-exposed rats.

Experimental and numerical study on the shear performance of stainless steel-GFRP connectors for use in precast concrete sandwich panels.

Precast Concrete Sandwich Panel (PCSP) is composed of concrete load-bearing panels, thermal insulation panels, and decorative panels, which are assembled through connectors, integrating load-bearing, thermal insulation, and decorative functions. The connector bears the main shear force between the wall panels, and the shear resistance and insulation performance of the connector largely determine the mechanical stability and insulation effect of the wall panels, which is a key component in PCSPs. The current common practice is to cross assemble stainless steel insulation (SSI) connectors and Glass-Fiber-Reinforced Plastic (GFRP) connectors into PCSPs, which can reduce building energy consumption and save resources while meeting strength and insulation requirements. A large-scale pull-out test on a PCSP with intersecting SSI-GFRP connectors was conducted in this paper. The damage process and damage pattern of PCSP were observed and the shear performance of SSI-GFRP connectors was analyzed. Secondly, a numerical analysis model of the test PCSP was built using ABAQUS finite element software and its validity was verified through the test data. In addition, parameters such as connector diameter, connector number ratio and concrete strength were analyzed for their effect on the shear performance of SSI-GFRP connectors and it was found that connector diameter and connector number ratio had a significant effect. Finally, it is found that there are some differences between the classical theory for calculating the shear performance of SSI-GFRP connectors and the actual results. A theoretical correction factor (ζ) is given to improve the accuracy of the calculation of the classical theory, and its influencing factors and changing rules are investigated.

Self-Supervised 3-D Semantic Representation Learning for Vision-and-Language Navigation.

In vision-and-language navigation (VLN) tasks, most current methods primarily utilize RGB images, overlooking the rich 3-D semantic data inherent to environments. To rectify this, we introduce a novel VLN framework that integrates 3-D semantic information into the navigation process. Our approach features a self-supervised training scheme that incorporates voxel-level 3-D semantic reconstruction to create a detailed 3-D semantic representation. A key component of this framework is a pretext task focused on region queries, which determines the presence of objects in specific 3-D areas. Following this, we devise an long short-term memory (LSTM)-based navigation model that is trained using our 3-D semantic representations. To maximize the utility of these 3-D semantic representations, we implement a cross-modal distillation strategy. This strategy encourages the RGB model's outputs to emulate those from the 3-D semantic feature network, enabling the concurrent training of both branches to merge RGB and 3-D semantic data effectively. Comprehensive evaluations on both the R2R and R4R datasets reveal that our method significantly enhances performance in VLN tasks.

Neurosonography: Shaping the future of neuroprotection strategies in extremely preterm infants.

This review aims to explore the current application of Cranial Ultrasound Screening (CUS) in the diagnosis and treatment of brain diseases in extremely preterm infants. It also discusses the potential role of emerging ultrasound-derived technologies such as Super Microvascular Structure Imaging (SMI), Shear Wave Elastography (SWE), Ultrafast Doppler Ultrasound (UfD), and 3D ventricular volume assessment and automated segmentation techniques in clinical practice. A systematic search of medical databases was conducted using the keywords "(preterm OR extremely preterm OR extremely low birth weight) AND (ultrasound OR ultrasound imaging) AND (neurodevelopment OR brain development OR brain diseases OR brain injury OR neuro*)" to identify relevant literature. The titles, abstracts, and full texts of the identified articles were carefully reviewed to determine their relevance to the research topic. CUS offers unique advantages in early screening and monitoring of brain diseases in extremely preterm infants, as it can be performed at the bedside without the need for anesthesia or special monitoring. This technique facilitates early detection and intervention of conditions such as intraventricular hemorrhage, white matter injury, hydrocephalus, and hypoxic-ischemic injury in critically ill preterm infants. Continuous refinement of the screening and follow-up processes provides reliable clinical decision-making support for healthcare professionals and parents. Emerging ultrasound technologies, such as SWE, SMI, and UfD, are being explored to provide more accurate and in-depth understanding of brain diseases in extremely preterm infants. SWE has demonstrated its effectiveness in assessing the elasticity of neonatal brain tissue, aiding in the localization and quantification of potential brain injuries. SMI can successfully identify microvascular structures in the brain, offering a new perspective on neurologic diseases. UfD provides a high-sensitivity and quantitative imaging method for the prevention and treatment of neonatal brain diseases by detecting subtle changes in red blood cell movement and accurately assessing the status and progression of brain diseases. CUS and its emerging technologies have significant applications in the diagnosis and treatment of brain diseases in extremely preterm infants. Future research aims to address current technical challenges, optimize and enhance the clinical decision-making capabilities related to brain development, and improve the prevention and treatment outcomes of brain diseases in extremely preterm infants.

Brain development in newborns and infants after ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies. DATA SOURCES: A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature. RESULTS: About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%-23% of neonates within the first 24 hours, and bleeding events occur in 27%-60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects. CONCLUSIONS: The impact of ECMO on an infant's nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants.

Knowledge-Based Embodied Question Answering.

In this paper, we propose a novel Knowledge-based Embodied Question Answering (K-EQA) task, in which the agent intelligently explores the environment to answer various questions with the knowledge. Different from explicitly specifying the target object in the question as existing EQA work, the agent can resort to external knowledge to understand more complicated question such as "Please tell me what are objects used to cut food in the room?", in which the agent must know the knowledge such as "knife is used for cutting food". To address this K-EQA problem, a novel framework based on neural program synthesis reasoning is proposed, where the joint reasoning of the external knowledge and 3D scene graph is performed to realize navigation and question answering. Especially, the 3D scene graph can provide the memory to store the visual information of visited scenes, which significantly improves the efficiency for the multi-turn question answering. Experimental results have demonstrated that the proposed framework is capable of answering more complicated and realistic questions in the embodied environment. The proposed method is also applicable to multi-agent scenarios.

A Spacetime Odyssey of Neural Progenitors to Generate Neuronal Diversity.

To understand how the nervous system develops from a small pool of progenitors during early embryonic development, it is fundamentally important to identify the diversity of neuronal subtypes, decode the origin of neuronal diversity, and uncover the principles governing neuronal specification across different regions. Recent single-cell analyses have systematically identified neuronal diversity at unprecedented scale and speed, leaving the deconstruction of spatiotemporal mechanisms for generating neuronal diversity an imperative and paramount challenge. In this review, we highlight three distinct strategies deployed by neural progenitors to produce diverse neuronal subtypes, including predetermined, stochastic, and cascade diversifying models, and elaborate how these strategies are implemented in distinct regions such as the neocortex, spinal cord, retina, and hypothalamus. Importantly, the identity of neural progenitors is defined by their spatial position and temporal patterning factors, and each type of progenitor cell gives rise to distinguishable cohorts of neuronal subtypes. Microenvironmental cues, spontaneous activity, and connectional pattern further reshape and diversify the fate of unspecialized neurons in particular regions. The illumination of how neuronal diversity is generated will pave the way for producing specific brain organoids to model human disease and desired neuronal subtypes for cell therapy, as well as understanding the organization of functional neural circuits and the evolution of the nervous system.

Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.

Humans have long been combating chronic pain. In clinical practice, opioids are first- choice analgesics, but long-term use of these drugs can lead to serious adverse reactions. Finding new, safe and effective pain relievers that are useful treatments for chronic pain is an urgent medical need. Based on accumulating evidence from numerous studies, excess reactive oxygen species (ROS) contribute to the development and maintenance of chronic pain. Some antioxidants are potentially beneficial analgesics in the clinic, but ROS-dependent pathways are completely inhibited only by scavenging ROS directly targeting cellular or subcellular sites. Unfortunately, current antioxidant treatments donot achieve this effect. Furthermore, some antioxidants interfere with physiological redox signaling pathways and fail to reverse oxidative damage. Therefore, the key upstream processes and mechanisms of ROS production that lead to chronic pain in vivo must be identified to discover potential therapeutic targets related to the pathways that control ROS production in vivo. In this review, we summarize the sites and pathways involved in analgesia based on the three main mechanisms by which ROS are generated in vivo, discuss the preclinical evidence for the therapeutic potential of targeting these pathways in chronic pain, note the shortcomings of current research and highlight possible future research directions to provide new targets and evidence for the development of clinical analgesics.

Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development.

Cell competition acts as a quality-control mechanism that eliminates cells less fit than their neighbors to optimize organ development. Whether and how competitive interactions occur between neural progenitor cells (NPCs) in the developing brain remains unknown. Here, we show that endogenous cell competition occurs and intrinsically correlates with the Axin2 expression level during normal brain development. Induction of genetic mosaicism predisposes Axin2-deficient NPCs to behave as "losers" in mice and undergo apoptotic elimination, but homogeneous ablation of Axin2 does not promote cell death. Mechanistically, Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain cell fitness, and Axin2-deficient cell elimination requires p53-dependent signaling. Furthermore, mosaic Trp53 deletion confers a "winner" status to p53-deficient cells that outcompete their neighbors. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness, suggesting that the Axin2-p53 axis may coordinate to survey cell fitness, regulate natural cell competition, and optimize brain size during neurodevelopment.

Galectin-3 in Microglia-Mediated Neuroinflammation: Implications for Central Nervous System Diseases.

Microglial activation is one of the common hallmarks shared by various central nervous system (CNS) diseases. Based on surrounding circumstances, activated microglia play either detrimental or neuroprotective effects. Galectin-3 (Gal-3), a group of ß-galactoside-binding proteins, has been cumulatively revealed to be a crucial biomarker for microglial activation after injuries or diseases. In consideration of the important role of Gal-3 in the regulation of microglial activation, it might be a potential target for the treatment of CNS diseases. Recently, Gal-3 expression has been extensively investigated in numerous pathological processes as a mediator of neuroinflammation, as well as in cell proliferation. However, the underlying mechanisms of Gal-3 involved in microgliamediated neuroinflammation in various CNS diseases remain to be further investigated. Moreover, several clinical studies support that the levels of Gal-3 are increased in the serum or cerebrospinal fluid of patients with CNS diseases. Thus, we summarized the roles and underlying mechanisms of Gal-3 in activated microglia, thus providing a better insight into its complexity expression pattern, and contrasting functions in CNS diseases.

Insight into the dual effect of water on lignin dissolution in ionic liquids.

The dual regulation of water on lignin in ionic liquids was studied at the molecular level by molecular dynamics simulation. The simulation results show that a small amount of water will destroy the ion association in ionic liquids, that is, it will produce more free anions and cations. The free ions around lignin are conducive to the dissolution of lignin. On the contrary, excess water will seriously solvate anions and cations. By changing the number of lignin clusters, it is more intuitive to observe that the dissolution of lignin in ILs containing a small amount of water is stronger than that in pure IL, however, the dissolution ability of lignin is reduced after adding a large amount of water in ILs. It is concluded that with the increase of water content, water changes from co-solvent to anti-solvent in the dissolution process. This study provides ideas for the design of IL-water system for economic pretreatment of biomass.

Dysfunction of the Brain-derived Neurotrophic Factor-Tyrosine Kinase B Signaling Pathway Contributes to Learning and Memory Impairments Induced by Neuroinflammation in Mice.

Accumulating evidence suggests that neuroinflammation is the main mechanism in cognitive dysfunction and that brain-derived neurotrophic factor (BDNF) is involved in learning and memory by binding to tyrosine kinase B (TrkB) receptors. Herein, we tested the roles of the BDNF-TrkB signaling pathway and its downstream cascade in lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Mice were treated with LPS (0.25 mg/kg) for 7 days, and learning and memory function was evaluated by the novel object recognition test (NORT). Western blotting was performed to elucidate roles of the BDNF-TrkB signaling pathway and its downstream cascades in LPS mice. The NORT showed that LPS induced learning and memory deficits in mice. The levels of IL-1ß, IL-6, and TNF-α in the serum and central nervous system decreased in LPS mice. In addition, LPS reduced the protein levels of BDNF, p-TrkB, Bcl-2, p-ERK1/2, p-CaMK2, p-CREB and p-GluR1 and increased the expression of Bax in the hippocampus and medial prefrontal cortex regions. In the entorhinal cortex, the protein levels of BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB were decreased, and the protein level of Bax was increased in LPS mice. Interestingly, 7,8-DHF alleviated these disorders in LPS mice and improved learning and memory function; however, the TrkB antagonist ANA12 effectively reversed effects of 7,8-DHF. Therefore, we conclude that the BDNF-TrkB signaling pathway and its downstream cascades disorders in different regions are main mechanisms of cognitive dysfunction, and 7,8-DHF maybe useful as a new treatment for preventing or treating cognitive dysfunction induced by neuroinflammation in neurodegenerative diseases.