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Image-to-image translation models have shown remarkable ability on transferring images among different domains. Most of existing work follows the setting that the source domain and target domain keep the same at training and inference phases, which cannot be generalized to the scenarios for translating an image from an unseen domain to another unseen domain. In this work, we propose the Unsupervised Zero-Shot Image-to-image Translation (UZSIT) problem, which aims to learn a model that can translate samples from image domains that are not observed during training. Accordingly, we propose a framework called ZstGAN: By introducing an adversarial training scheme, ZstGAN learns to model each domain with domain-specific feature distribution that is semantically consistent on vision and attribute modalities. Then the domain-invariant features are disentangled with an shared encoder for image generation. We carry out extensive experiments on CUB and FLO datasets, and the results demonstrate the effectiveness of proposed method on UZSIT task. Moreover, ZstGAN shows significant accuracy improvements over state-of-the-art zero-shot learning methods on CUB and FLO., Comment: Accepted by Nuerocomputing

Aristolactam I (AL-I) is the main active ingredient in the Aristolochia plant species, which have been associated with severe nephrotoxicity. In order to investigate the mechanism of AL-I induced renal epithelial-mesenchymal transition (EMT), we established an AL-I induced EMT model in human proximal tubular epithelial cells (HK-2 cells). Biochemical analysis experiment including Morphological examination, 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay, and Western blot analysis were performed. The results showed that AL-I accumulates in the cytosol causing cytotoxicity and inhibition of proliferation in a concentration- and time-dependent manner. Morphological examination showed that with the increasing concentration of AL-I, the tendency of HK-2 cells transform form epithelial cell to fibroblast cells was stronger. In the Western blot analysis, the expression of α-Smooth muscle actin (α-SMA) and Transforming Growth Factor β1 (TGF-β1) were significantly up-regulated, the expression of E-cadherin was significantly down-regulated after administrating. The ratio of the expression of P-Smad2/3 and Smad2/3 was significantly up-regulated, suggested that TGF-β/Smad-dependent signaling pathway was activated in this process. With presence of TGF-β receptor inhibitor (LY364947), we found that the expressions of three EMT related proteins (E-cadherin, α-SMA and TGF-β1) were obviously reversed. In conclusion, we acknowledge that AL-I can induce renal EMT process in HK-2 cell, which is triggered by the activation of TGF-β/Smad-dependent signaling pathway.

In Alzheimer's disease and related dementias, amyloid beta (Aβ) and amyloid plaques can disrupt long-term synaptic plasticity, learning and memory and cognitive function. Plaque accumulation can disrupt corticocortical circuitry leading to abnormalities in sensory, motor, and cognitive processing. In this study, using 5xFAD (five Familial Alzheimer's Disease -FAD- mutations) mice, we evaluated amyloid plaque formation in different cortical areas, and whether differential amyloid accumulation across cortical fields correlates with changes in dendritic complexity of layer 3 corticocortical projection neurons and functional responses in the primary somatosensory cortex following whisker stimulation. We focused on three cortical areas: the primary somatosensory cortex (S1), the primary motor cortex (M1), and the prefrontal cortex (PFC including the anterior cingulate, prelimbic, and infralimbic subdivisions). We found that Aβ and amyloid plaque accumulation is not uniform across 5xFAD cortical areas, while there is no expression in littermate controls . We also found that there are differential layer 3 pyramidal cell dendritic complexity changes across the three areas in 5xFAD mice, compared to same age controls, with no apparent relation to differential amyloid accumulation. We used voltage-sensitive dye imaging (VSDi) to visualize neural activity in S1, M1 and PFC following whisker activation. Control mice show normal physiological responses in all three cortical areas, whereas 5xFAD mice only display physiological responses in S1. Taken together our results show that 5xFAD mutation affects the overall dendritic morphology of layer 3 pyramidal cells across sensory-motor and association cortex irrespective of the density and distribution of the Aβ amyloid proteins. Corticocortical circuitry between the sensory and motor/association areas is most likely disrupted in 5xFAD mice as cortical responses to whisker stimulation are altered.

In eukaryotic cells, changes in chromatin accessibility are necessary for chromatin to maintain its highly dynamic nature at different times during the cell cycle. Histone chaperones interact with histones and regulate chromatin dynamics. Facilitates chromatin transcription (FACT) is an important histone chaperone that plays crucial roles during various cellular processes. Here, we analyze the structural characteristics of FACT, discuss how FACT regulates nucleosome/chromatin reorganization and summarize possible functions of FACT in transcription, replication, and DNA repair. The possible involvement of FACT in cell fate determination is also discussed. Abbreviations: FACT: facilitates chromatin transcription, Spt16: suppressor of Ty16, SSRP1: structure-specific recognition protein-1, NTD: N-terminal domain, DD: dimerization domain, MD: middle domain, CTD: C-terminus domain, IDD: internal intrinsically disordered domain, HMG: high mobility group, CID: C-terminal intrinsically disordered domain, Nhp6: non-histone chromosomal protein 6, RNAPII: RNA polymerase II, CK2: casein kinase 2, AID: acidic inner disorder, PIC: pre-initiation complex, IR: ionizing radiation, DDSB: DNA double-strand break, PARlation: poly ADP-ribosylation, BER: base-excision repair, UVSSA: UV-stimulated scaffold protein A, HR: homologous recombination, CAF-1: chromatin assembly factor 1, Asf1: anti-silencing factor 1, Rtt106: regulator of Ty1 transposition protein 106, H3K56ac: H3K56 acetylation, KD: knock down, SETD2: SET domain containing 2, H3K36me3: trimethylation of lysine36 in histone H3, H2Bub: H2B ubiquitination, iPSCs: induced pluripotent stem cells, ESC: embryonic stem cell, H3K4me3: trimethylation of lysine 4 on histone H3 protein subunit, CHD1: chromodomain protein

Sepsis is a type of systemic inflammation response syndrome that leads to organ function disorders. Currently, there is no specific medicine for sepsis in clinical practice. Lipopolysaccharide (LPS) is an important endotoxin that causes sepsis. Here, we report an effective two-drug combination therapy to treat LPS-induced liver and kidney injury in endotoxic rats. Ulinastatin (UTI) and Thrombomodulin (TM) are biological macromolecules extracted from urine. In our study, combination therapy significantly improved LPS-induced liver and kidney pathological structure and functional injury, and significantly improved the survival rate of endotoxic rats. Results of TUNEL staining and Western blot showed that UTI combined with TM inhibited the excessive apoptosis of liver and kidney cells caused by LPS. The drug combination also promoted the proliferation of liver and kidney cells, reduced the levels of pro-inflammatory factors interleukin (IL)-6, IL-1β, tumor or necrosis factor (TNF)-α and nitric oxide, and down-regulated the expression of High Mobility Group Box 1 (HMGB1), Toll-like receptor (TLR) 4 and Nuclear Factor (NF)-κB phosphorylation to inhibit inflammation. In addition, the combination of UTI and TM also promoted the production of a variety of antioxidant enzymes in the tissues and inhibited the production of lipid peroxidation malondialdehyde (MDA) to enhance antioxidant defenses. Our experiments also proved that UTI combined with TM did not reduce the anticoagulant effect of TM. These results suggested that UTI combined with TM can improve endotoxin-induced liver and kidney damage and mortality by inhibiting liver and kidney cell apoptosis, promoting proliferation, and inhibiting inflammation and oxidative injury.

Background: Sepsis, a systemic inflammatory disease that leads to life-threatening organ functions disorders, such as liver and kidney injury. Ulinastatin (UTI) and Thrombomodulin (TM) are active macromolecules isolated from human urine. UTI and TM have been found to have therapeutic effects on inflammatory diseases. In this study, we verified protective effect of UTI combined with TM on liver and kidney injury caused by sepsis, and further explored the mechanisms.Methods: The sepsis model was established by intravenous injection of LPS into the tail vein of rats. Blood, liver and kidney tissues were collected after injection of UTI or TM. ELISA was used to measure serum levels of pro-inflammatory cytokines. The characteristic functional indexes of liver and kidney in serum and multiple coagulation function indexes of rats were detected via corresponding kits. Histological changes of liver and kidney tissues were investigated by HE staining. Apoptosis in liver and kidney tissues were examined by TUNEL staining, and the expression levels of apoptosis-related proteins were also analyzed. HMGB1/TLR4/NF-κB pathway in liver and kidney tissues were examined by Western Blot. PCNA-positive cells were detected by immunohistochemistry. The survival rate of rats in each group was statistically analyzed.Results: UTI combined with TM reduced LPS-induced secretion of IL-6 and TNF-α in the serum. The drug combination reduced the liver and kidney functional indicators ALT, AST, BUN and Cr, and ameliorated liver and kidney pathology injury of rats. It inhibited apoptosis of liver and kidney cells via down-regulating the expression of apoptotic protein Bax, Cleaved caspase-3, up-regulating the expression of anti-apoptotic protein bcl-2, and promoted the proliferation of liver and kidney cells. The drug combination reversed the up-regulation of HMGB1, TLR4, and phosphorylated NF-κB protein mediated by LPS. Anticoagulation test indicated UTI does not affect the anticoagulant effect of TM when they are used in combination. Moreover, the drug combination significantly improved the survival rate of septic rats. Conclusions: These results indicate that UTI combined with TM plays a key role in protecting liver and kidney injury in septic rats, which will suggest a promising treatment for sepsis-induced organ injury.

God class refers to a class that undertakes too many responsibilities for tasks that should more appropriately be handled by multiple classes. The existence of god classes seriously affects the maintainability and understandability of software. To eliminate god class, we first need to identify them. Researchers have proposed traditional methods using code metrics and deep learning methods using code metrics and text information to detect god classes. However, the relationship existing in metrics and text information is often ignored; moreover, deep learning methods require a large number of reliable datasets, while authentic god class datasets are scarce. To solve the above problems, we propose a novel god class detection method based on multi-aspect interactions and dataset fine-tuning. First, we use proposed model to extract multi-aspect interaction information, including three parts: (i) the interaction information existing in code metrics; (ii) the interaction information existing in texts; (iii) the interaction information existing in texts and code metrics. In this way, we can not only make use of code metrics and text information, but also fully exploit the multi-aspect interaction information. Second, we train with large-scale synthetic datasets to obtain a pre-trained model, then fine-tune the pre-trained model parameters with high-quality authentic datasets. Using the training method of pre-training and fine-tuning, we can solve the problem of low-reliability synthetic datasets and scarce authentic datasets. Finally, evaluation results on open-source applications suggest that the proposed approach improves on the state-of-the-art.

This study examined over 48,000 eighth-grade Chinese students’ mathematics performance and use of learning strategies. In particular, this study explored how the use of learning strategies and their combinations are related to students’ mathematics performance in Chinese context. This study examined three kinds of learning strategies derived from the Programme for International Student Assessment (PISA) 2012: memorization, elaboration, and control. The findings indicate that few students chose the memorization strategy as their predominant way of learning mathematics. Instead, students usually chose a combination of learning strategies. The choice of combinations of learning strategies was highly correlated with students’ mathematics performance. Students who chose control strategies outperformed those who chose memorization strategies or elaboration strategies. This study also examined the relationship between learning strategy use and mathematics performance of students who were only children (students with no siblings, born under the “one child” policy) and students living in nonagricultural residential locations (hukou status), both of which are background variables unique to Chinese context. The findings indicate that only-child and nonagricultural students outperformed non-only-child and agricultural students when choosing the same learning strategies. However, those who chose control-dominant strategies performed better than those who chose memorization-dominant strategies, regardless of their background. This study provides a new lens for considering the relationship between learning strategy use and mathematics performance, demonstrating that various learning strategies should be considered together rather than separately.

An efficient biomass and high-value bioactive substances production strategy was developed for unicellular microalgae Porphyridium purpureum. We studied the optimal culture method and metabolites accumulation under different C/N conditions, and further proposed methods to increase the yield under high C/N ratio. The highest biomass reached 16.24 g/L with ASW medium by mixotrophy. High C/N ratio and mediate C/N can significantly promote the synthesis and secretion of polysaccharides, as well as the accumulation of ω-6 PUFAs; however, inhibit the growth, resulting in lower yield. With the significant increase of C/N ratio, protein degradation was accelerated, providing sufficient nitrogen source for efficient accumulation of carbohydrates (1.66 g/L EPS) and PUFAs (231.24 mg/L ARA). Finally, we reduced the growth inhibition, shortened the culture cycle, and doubled the final biomass to 9.34 g/L under nitrogen deficiency condition. Our exploitation of a cost-effective and feasible culture method for red algae is particularly significant.

Sunlight enhanced peel color and significantly up-regulated the expression of PyMYB10 and PybHLH genes. MYB-bHLH-WD40 transcriptional complex forms in the light and is involved in regulating anthocyanin accumulation in the peel. Anthocyanin is the major pigment in the peel of Yunnan red pear (Pyrus pyrifolia (Burm.) Nak.). A transcriptional activation protein complex, involving members of the transcription factor classes of MYB, bHLH and WD40, regulates anthocyanin biosynthesis. This complex was examined in the peel of red pear. In order to clarify the interaction of PyMYB10, PybHLH and PyWD40, fruit were bagged then peel samples collected 0, 3, 5, and 7 days after bag removal. Samples were used for Western blotting and protein interaction analysis. The results showed that sunlight enhanced peel color and significantly up-regulated the expression of both PyMYB10 and PybHLH genes. Co-immunoprecipitation (Co-IP) analysis showed that PybHLH interacted with PyMYB10 or PyWD40, and PyMYB10 interacted with PyWD40. Using onion cells as a model system, bimolecular fluorescence complementation (BiFC) confirmed these interactions and showed that the interaction localized to the nuclei. GST Pull down and Far-Western blotting assays demonstrated that PybHLH interacted with PyMYB10 or PyWD40, respectively, and PyMYB10 interacted with PyWD40 in vitro. In addition, EMSA assay showed that PyMYB10 can directly bind to the promoter of the gene encoding the anthocyanin biosynthesis enzyme anthocyanidin synthase (PyANS). Taken together, these results showed that the ternary complex of PyMYB10, PybHLH and PyWD40 transcription factors forms to regulate anthocyanin biosynthesis and accumulation in Yunnan red pear.

β-Amyloid (Aβ) species probably exert neurotoxic effects in Alzheimer's disease. In the present study, the effect of antioxidant plumbagin was tested against Aβ25-35-induced neurotoxicity in the SH-SY5Y cell line. Cell viability was determined using an MTT assay. Antioxidant status was analyzed through antioxidant enzyme activities, nuclear factor erythroid 2-related factor 2 (Nrf-2), and its downstream protein expressions. Inflammatory response was determined through nuclear factor-κB (NF-κB) pathway and cytokine expressions. Aβ25-35 showed a decrease in cell viability in a concentration-dependent manner. The IC50 value was found to be 17 µM. Pretreatment with plumbagin prevented Aβ25-35-induced toxicity by improving the cell viability up to 96%. Plumbagin inhibited Aβ25-35-induced oxidative stress by decreasing reactive oxygen species and lipid peroxidation. Aβ25-35-induced redox imbalance caused decreased Nrf-2 expression, with downregulation Nrf-2 target proteins heme oxygenase 1 and NAD(P)H dehydrogenase (quinone 1) during Aβ25-35 treatment. However, plumbagin improved the antioxidant defense system by increasing Nrf-2 expression with concomitant upregulation in heme oxygenase 1 and NAD(P)H dehydrogenase (quinone 1). Aβ25-35 induced inflammatory response through upregulated NF-κB, cyclooxygenase-2, and inducible nitric oxide synthase levels. Plumbagin exerted anti-inflammatory effects by decreasing NF-κB, cyclooxygenase-2, and inducible nitric oxide synthase levels. Aβ25-35-induced increases in proinflammatory cytokine (interleukin-8, interleukin-6, and monocyte chemoattractant protein-1) expressions were suppressed by plumbagin pretreatment. Altogether, the present study indicates that plumbagin prevents redox status and inflammatory activation during Aβ25-35-induced toxicity by modulating the antioxidant defense system and Nrf-2 signaling.

There are a lot of middle-class or small-class high-performance computing clusters at universities and research institutes, etc. Large volumes of job logs have been accumulated after many years of operation. In this paper, on the basis of accumulated job logs on a high-performance computing cluster, we examine and analyze the job logs. Then, we study machine learning based performance analysis and prediction methods for parallel jobs. Various machine learning methods such as multivariate linear fitting, artificial neural network are used to build performance prediction models. We compare the errors of each model, and select the optimal prediction model for different users. The experimental results show that we can obtain reasonable prediction accuracy using the selected machine learning algorithms.

Phosphoenolpyruvate carboxylase (PEPC) catalyzes the carboxylation of phosphoenolpyruvate (PEP) in the presence of bicarbonate to form oxaloacetate (OAA), and it plays an important role in high-efficient production of OAA-derived metabolites such as lysine, glutamate and succinate. However, PEPCs often suffered from serious feedback inhibition by various metabolic effectors like aspartate. Here, the feedback inhibition of PEPC from Corynebacterium glutamicum was removed by adding a short terminal peptide like His-tag. The effect of His-tag location on the structure and important properties such as activity, thermostability and feedback inhibition of PEPC has been investigated. The purified untagged PEPC, Nterminal His-tagged PEPC (PEPC-N-His) and C-terminal His-tagged PEPC (PEPC-C-His) were characterized. PEPCN- His (439.71/sec/mM) showed a 1.26 and 186-fold higher catalytic efficiency than untagged PEPC (348.59/sec/mM) and PEPC-C-His (2.36/sec/mM), respectively. Both PEPCN- His and untagged PEPC were significantly inhibited by aspartate at the concentrations above 4 mM (residual activities < 10%), while PEPC-C-His was almost desensitized to aspartate within 10 mM (around 90% of residual activity). Structural analysis showed that the extension of C-terminus may cause steric hindrance for aspartate binding with enzymes, leading to the deregulation of feedback inhibition of PEPC-C-His. This study provides a deeper understanding of the effect of terminal fragments on the structure and function of PEPCs, and helps to engineer the feedback inhibition of PEPCs and structurally similar enzymes.

There is plenty of human-machine joint decision-making scenarios in the real world applications, such as driving assistant, suspect identification, medical diagnosis, etc. Existing algorithms propose that machine should give a rejection option when having a high risk or uncertainty score so that the input can be passed to human to make the decision. This is an interesting algorithmic model of human-machine collaboration, but implicitly assumes that humans are more trustworthy than machines. Such an assumption ignores the bias and inconsistency of human, especially in scenarios where machines have superior recognition ability than humans. In this work, we investigate the human-machine joint decision-making problem in distorted surveillance videos, where machines experimentally prove to be comparable to human beings in tolerance to distortion, sometimes even stronger. We propose a new human-machine joint decision-making framework by considering both the confidences of machine and human. To obtain the confidence of human, we build a real-life human decision-making database and propose a deep neural network to estimate human's confidence. Then, confidence alignment method and decision rule are proposed to further output the final decision. Experiments demonstrate that the proposed framework can make less human intervention and more accurate decisions in several human-machine joint decision-making scenarios.

RATIONALE Although distal nerves located at sites prone to compression are susceptible to autoimmune attack, Guillain-Barre' syndrome (GBS) with exclusive hand muscle involvement is rarely found in clinics. All reported patients presented with a special variant - finger extensor weakness, especially claw hand caused by predominant ulnar extensor involvement. Similar to typical GBS, these patients showed bilateral symmetric onset with rapid clinical progression. PATIENT CONCERNS A 62-year-old man with GBS was admitted to our hospital with unilateral onset of claw hand. He showed relatively slow progression and did not develop bilateral symmetric claw hands until 6 weeks later. DIAGNOSES Eventually the patient was diagnosed as having a regional variant of GBS by neuronal electrophysiology and cerebrospinal fluid examinations. INTERVENTIONS This patient was treated with intravenous thrombolysis within 4.5 hours of onset. Eventually he was diagnosed as having a regional variant of GBS and was treated with gamma-globulin (400 mg/kg/d) for 5 consecutive days via intravenous infusion. OUTCOMES The patient had a slow recovery with persistent mild finger extensor weakness. LESSONS This patient presented with unilateral onset of claw hand, and the diagnosis of acute ischemic stroke could not be excluded because of a short time window; hence, he was treated with intravenous thrombolysis within 4.5 hours of onset. Eventually he was diagnosed as having a regional variant of GBS. It is important that GBS should also be considered in patients with unilateral hand weakness and unknown aetiology in the early stages of disease.

Semantic information is important in video encryption. However, existing image quality assessment (IQA) methods, such as the peak signal to noise ratio (PSNR), are still widely applied to measure the encryption security. Generally, these traditional IQA methods aim to evaluate the image quality from the perspective of visual signal rather than semantic information. In this paper, we propose a novel semantic-level full-reference image quality assessment (FR-IQA) method named Semantic Distortion Measurement (SDM) to measure the degree of semantic distortion for video encryption. Then, based on a semantic saliency dataset, we verify that the proposed SDM method outperforms state-of-the-art algorithms. Furthermore, we construct a Region Of Semantic Saliency (ROSS) video encryption system to demonstrate the effectiveness of our proposed SDM method in the practical application.

Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l -glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l -glutamate exporter, MscCG, was discovered in an industrial l -glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l -glutamate exporter and an osmotic safety valve in C. glutamicum . Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l -glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l -glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l -glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to product excretion as well as product reuptake, making transporter engineering a useful strategy for strain improvement. The significance of our research is in identifying and characterizing a novel l -glutamate exporter from the industrial workhorse Corynebacterium glutamicum , which will enrich the understanding of l -glutamate excretion and provide a new target for studying bacterial amino acid transport and engineering transport reactions.

Immobilization of enzymes is important and widely applied in biocatalysis. Streptomyces platensis gene gox, encoding an extracellular L-glutamate oxidase (Gox), was fused to cellulose binding domain (CBDcex) from Cellulomonas fimi and the recombinant protein Gox-CBD was expressed in Escherichia coli. The fusion protein (Gox-CBD) was immobilized onto microcrystalline cellulose. The preparation conditions, binding capacity, properties and stability of the immobilized enzyme were studied. Under the condition of 4 ℃, for 1 hour, the fusion protein Gox-CBD was able to bind microcrystalline cellulose at a ratio of 9.0 mg of protein per gram of microcrystalline cellulose. Enzymatic properties of free and immobilized L-glutamic oxidase (Gox-CBD) were compared. The specific activity of the immobilized enzyme decreased, but its thermal stability increased a lot compared with that of the free Gox-CBD. After incubation at 60 ℃ for 30 min, 70% of the total activity remained whereas the free recombinant Gox completely lost its activity. The immobilized protein was tightly bound to microcrystalline cellulose at pH below 10 or more than 5 mmol/L NaCl. The fusion protein of Gox-CBD can be specifically immobilized on the microcrystalline cellulose on a single step. Therefore, our findings can provide a novel strategy for protein purification and enzyme immobilization.酶的固定化作为一种重要的技术，已在生物催化领域得到了广泛的应用。现将来源于普拉特链霉菌3304 (Streptomyces platensis NTU3304) 产生的胞外L-谷氨酸氧化酶 (L-glutamate oxidase，Gox) 基因gox 融合到来源于粪碱纤维单胞菌Cellulomonas fimi 的纤维素结合域 (CBDcex) 的基因上， 构建表达载体pETM10-Gox-CBD，并在大肠杆菌中表达。通过蛋白纯化获得融合蛋白，并命名为Gox-CBD。利用CBD 对微晶纤维素特异性吸附的特性将其固定在微晶纤维素上，并对固定化酶的制备条件、结合量、酶学性质及其微晶纤维素结合稳定性等进行了研究。在4 ℃条件下结合约1 h，融合蛋白Gox-CBD 结合在纤维素上的结合量即可达到9.0 mg/g。通过对重组型、融合表达游离的以及固定化在微晶纤维素上的谷氨酸氧化酶的酶学性质进行比较发现，固定化酶的比酶活有所降低；但固定化酶的热稳定性相对于游离酶有了很大的提高，在60 ℃孵育30 min 后还保留有约70%的活性，而游离的重组Gox 在相同条件下几乎完全失去活性。当固定化结合蛋白在pH10 或者盐浓度5 mmol/L 的NaCl 条件下可以牢固结合。并且可以通过一步纯化方法固定化融合蛋白Gox-CBD 于微晶纤维素上。因此，L-谷氨酸氧化酶与纤维素结合域融合表达的研究为蛋白的纯化及酶的固定化提供了一种新策略。.

NMDARs play a major role in patterning of topographic sensory maps in the brain. Genetic knock-out of the essential subunit of NMDARs in excitatory cortical neurons prevents whisker-specific neural pattern formation in the barrel cortex. To determine the role of NMDARs en route to the cortex, we generated sensory thalamus-specific NR1 (Grin1)-null mice (ThNR1KO). A multipronged approach, using histology, electrophysiology, optical imaging, and behavioral testing revealed that, in these mice, whisker patterns develop in the trigeminal brainstem but do not develop in the somatosensory thalamus. Subsequently, there is no barrel formation in the neocortex yet a partial afferent patterning develops. Whisker stimulation evokes weak cortical activity and presynaptic neurotransmitter release probability is also affected. We found several behavioral deficits in tasks, ranging from sensorimotor to social and cognitive. Collectively, these results show that thalamic NMDARs play a critical role in the patterning of the somatosensory thalamic and cortical maps and their impairment may lead to pronounced behavioral defects.

Infraorbital nerve (ION) transection in neonatal rats leads to disruption of whisker-specific neural patterns (barrelettes), conversion of functional synapses into silent synapses, and reactive gliosis in the brain stem trigeminal principal nucleus (PrV). Here we tested the hypothesis that neonatal peripheral nerve crush injuries permit better functional recovery of associated central nervous system (CNS) synaptic circuitry compared with nerve transection. We developed an in vitro whisker pad-trigeminal ganglion (TG)-brain stem preparation in neonatal rats and tested functional recovery in the PrV following ION crush. Intracellular recordings revealed that 68% of TG cells innervate the whisker pad. We used the proportion of whisker pad-innervating TG cells as an index of ION function. The ION function was blocked by ∼64%, immediately after mechanical crush, then it recovered beginning after 3 days postinjury and was complete by 7 days. We used this reversible nerve-injury model to study peripheral nerve injury-induced CNS synaptic plasticity. In the PrV, the incidence of silent synapses increased to ∼3.5 times of control value by 2–3 days postinjury and decreased to control levels by 5–7 days postinjury. Peripheral nerve injury-induced reaction of astrocytes and microglia in the PrV was also reversible. Neonatal ION crush disrupted barrelette formation, and functional recovery was not accompanied by de novo barrelette formation, most likely due to occurrence of recovery postcritical period (P3) for pattern formation. Our results suggest that nerve crush is more permissive for successful regeneration and reconnection (collectively referred to as “recovery” here) of the sensory inputs between the periphery and the brain stem.