Immunopotentiating effect of lentinan on chicks and its inhibitory effect on Marek's disease virus infection.

Marek's disease virus (MDV) is a significant tumorigenic virus that causes severe immunosuppression in chickens. Lentinan (LNT) is an immunomodulator containing ß-glucans and is widely used in areas such as antiviral, anticancer, and immune regulation. To investigate the immunomodulatory effects of LNT on specific pathogen-free (SPF) chicks and its potential to inhibit MDV infection, we conducted an MDV challenge experiment and observed the immune-enhancing effect of LNT on SPF chicks. The results showed that LNT promoted the growth and development of SPF chicks and induced the upregulation of cytokines such as Mx protein, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The specific gravity of CD4+ T-lymphocytes and CD8+ T-lymphocytes and their ratios were also significantly upregulated. Prophylactic use of LNT inhibited MDV replication in lymphocytes, liver, and spleen. It also alleviated MDV-induced weight loss and hepatosplenomegaly in SPF chicks. The present study confirms that LNT can enhance the levels of innate and cellular immunity in SPF chicks and contributes to the inhibition of MDV replication in vivo and mitigation of immune organ damage in chicks due to MDV infection. This provides an adjunctive measure for better control of MDV infection.

DDAH1 promotes neurogenesis and neural repair in cerebral ischemia.

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

Deep Reinforcement Learning for Autonomous Driving with an Auxiliary Actor Discriminator.

In the research of robot systems, path planning and obstacle avoidance are important research directions, especially in unknown dynamic environments where flexibility and rapid decision makings are required. In this paper, a state attention network (SAN) was developed to extract features to represent the interaction between an intelligent robot and its obstacles. An auxiliary actor discriminator (AAD) was developed to calculate the probability of a collision. Goal-directed and gap-based navigation strategies were proposed to guide robotic exploration. The proposed policy was trained through simulated scenarios and updated by the Soft Actor-Critic (SAC) algorithm. The robot executed the action depending on the AAD output. Heuristic knowledge (HK) was developed to prevent blind exploration of the robot. Compared to other methods, adopting our approach in robot systems can help robots converge towards an optimal action strategy. Furthermore, it enables them to explore paths in unknown environments with fewer moving steps (showing a decrease of 33.9%) and achieve higher average rewards (showning an increase of 29.15%).

Maxillary gingival neurolemmoma: a case report and literature review.

OBJECTIVE: To explore and summarize the clinical features, differential diagnosis and treatment of the oral maxillofacial schwandoma. CASE PRESENTATION: This is a report of a case of a 46-year-old female patients with neurolemmoma in the maxillary gingiva. The clinical features, pathological features, differential diagnosis and treatment were analyzed. Literature review was conducted in search of domestic and overseas journal full-text database from 1986 ~ 2017. 39 reports on the oral and maxillofacial Neurolemmoma from 1986 to 2017 in the database of China hospital knowledge database and the PubMed database, there were 405 patients. There were 23 cases of gingival mucosa, 17 in foreign literature and only 6 in the domestic literature. CONCLUSIONS: The incidence of gingival Neurolemmoma is extremely low, the predilection age is similar to other parts, it is middle-aged and young, and there is no obvious gender tendency. About 25-45% of schwannomas are found in the head and neck, and rarely in the mouth (only 1%). The most common internal location of the mouth is the tongue, followed by the floor of the mouth, buccal mucosa, palate, gums, and lips. Schwannomas are slow-growing benign tumors that are rare in the gums. Gingival schwannoma is usually a single occurrence, and the clinical manifestations are mostly painless gum mass, tooth loosening and displacement, without peripheral bone changes and regional lymph node metastasis. It is difficult to diagnose this tumor according to clinical manifestations, and pathological diagnosis is still the basis for the diagnosis of gingival schwannoma. So far, surgical resection is the preferred treatment for this disease, and the prognosis is good.

Combined inhibitory effect of interferon and antiserum on avian hepatitis E virus.

Epidemiologic investigations in recent years have shown that the detection rate of avian hepatitis E virus (HEV) in chicken flocks is increasing in China. Nevertheless, effective prevention and control measures are still lacking. In this study, specific pathogen-free (SPF) chicken serum against HEV was prepared using recombinant HEV open reading frames (ORF2 and ORF3) proteins as immunogens. An SPF chicken infection model was established by intravenous inoculation of chick embryos. Swab samples were collected at 7, 14, 21, and 28 d of age and used to detect avian HEV load, along with other indicators, by fluorescence quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) assay. The therapeutic effects on blocking vertical HEV transmission were observed, by using the methods of antibody application alone, mixed, or combined application of each of the 2 antibodies with type I interferon. The results showed that type I interferon alone or in combination with antiserum reduced the positive rate of HEV from 100 to 62.5% and 25%, respectively. However, the avian HEV-positivity rate was reduced to 75, 50, and 37.5% after type I interferon was used alone or in combination with antisera against ORF2 and ORF3, respectively. The inhibitory effect of type I interferon alone or in combination with an antiserum, on HEV replication was more significant in cells than in vivo. In this study, the inhibitory effect of type I interferon alone or in combination with an antiserum on avian HEV replication was observed in vitro and in vivo, providing the necessary technical reserve for disease prevention and control.

Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis.

As well as their ion transportation function, the voltage-dependent potassium channels could act as the cell signal inducer in a variety of pathogenic processes. However, their roles in neurogenesis after stroke insults have not been clearly illustrated. In our preliminary study, the expressions of voltage-dependent potassium channels Kv4.2 was significantly decreased after stroke in cortex, striatum and hippocampus by real-time quantitative PCR assay. To underlie the neuroprotection of Kv4.2 in stroke rehabilitation, recombinant plasmids encoding the cDNAs of mouse Kv4.2 was constructed. Behavioral tests showed that the increased Kv4.2 could be beneficial to the recovery of the sensory, the motor functions and the cognitive deficits after stroke. Temozolomide (TMZ), an inhibitor of neurogenesis, could partially abolish the mentioned protections of Kv4.2. The immunocytochemical staining showed that Kv4.2 could promote the proliferations of neural stem cells and induce the neural stem cells to differentiate into neurons in vitro and in vivo. And Kv4.2 could up-regulate the expressions of ERK1/2, p-ERK1/2, p-STAT3, NGF, p-TrkA, and BDNF, CAMKII and the concentration of intracellular Ca2+. Namely, we concluded that Kv4.2 promoted neurogenesis through ERK1/2/STAT3, NGF/TrkA, Ca2+/CAMKII signal pathways and rescued the ischemic impairments. Kv4.2 might be a potential drug target for ischemic stroke intervention.

MdPR4, a pathogenesis-related protein in apple, is involved in chitin recognition and resistance response to apple replant disease pathogens.

To maximize breeding and exploitation of disease resistance traits for managing apple replant disease (ARD), it is of great importance to understand the mechanisms of apple root resistance. Currently, little is known about the functions of the specific genes that confer resistance traits in apple root. In this study, molecular, biochemical, and genetic approaches allowed an in-depth understanding of the role of the MdPR4 gene in the defense response of apple root. The MdPR4 encoding gene showed upregulation following ARD pathogen inoculation in our previous transcriptome data. Subcellular localization analyses revealed that MdPR4 is localized on the plasma membrane, endoplasmic reticulum, and apoplast, which is mainly determined by its signal peptide. Molecular docking analysis between MdPR4 protein with chitin molecule and in vitro MdPR4 chitin affinity assay proved its chitin-binding ability, which provided evidence for its role in chitin-mediated immune responses. Purified MdPR4 protein and MdPR4 overexpressed apple callus inhibited spore germination and mycelial growth of ARD-related Fusarium spp. pathogens. These data support the conclusion that MdPR4 is a chitin-binding protein in apple vegetative tissues that may play an important role in defense activation in response to ARD pathogen infection.

Transcriptome analysis of transgenic apple fruit overexpressing microRNA172 reveals candidate transcription factors regulating apple fruit development at early stages.

BACKGROUND: MicroRNA172 (miR172) has been proven to be critical for fruit growth, since elevated miR172 activity blocks the growth of apple (Malus x domestica Borkh.) fruit. However, it is not clear how overexpression of miR172 affects apple fruit developmental processes. METHODS: To answer this question, the present study, analyzed global transcriptional changes in miR172-overexpressing (miR172OX) and nongenetically modified wild-type (WT) apple fruit at two developmental stages and in different fruit tissues via RNA-seq. In addition, two cultivars, 'Hanfu' and 'M9', which have naturally fruit size variation, were included to identify miR172-dependent DEGs. qRT-PCRwas used to verify the reliability of our RNA-seq data. RESULTS: Overexpression of miR172 altered the expression levels of many cell proliferation- and cell expansion-related genes. Twenty-four libraries were generated, and 10,338 differentially expressed genes (DEGs) were detected between miR172OX and WT fruit tissues. 'Hanfu' and 'M9' are two common cultivars that bear fruit of different sizes (250 g and 75 g, respectively). Six libraries were generated, and 3,627 DEGs were detected between 'Hanfu' and 'M9'. After merging the two datasets, 6,888 candidate miR172-specific DEGs were identified. The potential networks associated with fruit size triggered traits were defined among genes belonging to the families of hormone synthesis, signaling pathways, and transcription factors. Our comparative transcriptome analysis provides insights into transcriptome responses to miR172 overexpression in apple fruit and a valuable database for future studies to validate functional genes and elucidate the fruit developmental mechanisms in apple.

A dual-functional nanovehicle with fluorescent tracking and its targeted killing effects on hepatocellular carcinoma cells.

All-in-one drug delivery nanovehicles with low cytotoxicity, high clinical imaging tracking capability, and targeted- and controlled-releasing performances are regarded as promising nanoplatforms for tumor theranostics. Recently, the design of these novel nanovehicles by low molecular weight amphiphilic chitosan (CS) was proposed. Based on fluorescent gold nanoclusters (AuNCs), a tumor-targeting nanovehicle (i.e. AuNCs-CS-AS1411) was prepared via electrostatic attraction between AuNC-conjugated chitosan (i.e. AuNCs-CS) and the anti-nucleolin aptamer, AS1411. After that, the anticancer drug methotrexate (MTX) was encapsulated into the nanovehicles and then the dual-functional nano-drug (i.e. MTX@AuNCs-CS-AS1411) was comparatively supplied to the human hepatocellular carcinoma cell line HepG2 and the human normal liver cell line LO2, to exhibit its "all in one" behavior. Under the conditions of the same concentration of MTX, MTX@AuNCs-CS-AS1411 demonstrates more intensive cytotoxicity and apoptosis-inducing activity against HepG2 cells than those against normal LO2 cells, mainly due to the targeting effect of AS1411 on the nucleolins that were found at high levels on the surface of tumor cells, but are at low levels or absent on normal cells. On the other hand, the MTX release from the MTX@AuNCs-CS-AS1411 was much faster in mildly acidic solution than that in neutral pH. Thus, it may provide a possibility to more significantly release MTX in intracellular lysosome of tumor cells, rather than let loose MTX during transport of the drug from blood vessels to tumor tissue. In conclusion, our dual-functional nanovehicle possesses high fluorescence efficiency and photostability, low cytotoxicity, pH-dependent controlled release, high sensitivity and target-specificity to cancer cells which allowed concurrent targeted imaging and delivery in cancer chemotherapies.

[Spectrometric determination of trace elements in 'Jinguang' prunus mume var. bungo of different growth periods].

A study was carried out on the content of trace elements such as Ca, Fe, Zn, Mn and Cu of prunus mume var. bungo in different growth periods by WFX-110 atomic absorption spectrometry. The results indicated that the linear relationships of different elements within the limits of working curves are good and the range of the recovery is 98% -105%, hence showing that the results are satisfactory. The total content of these five trace elements increases as the fruit grows, but the concentration is related to the growth of fruit and fruit core, which provides us with valuable data. The contents of the trace elements essential to human body are relatively high, which shows that this fruit breed has a relatively high nutritive value.