Effects of 90 dB pure tone exposure on auditory and cardio-cerebral system functions in macaque monkeys.

Excessive noise exposure presents significant health risks to humans, affecting not just the auditory system but also the cardiovascular and central nervous systems. This study focused on three male macaque monkeys as subjects. 90 dB sound pressure level (SPL) pure tone exposure (frequency: 500Hz, repetition rate: 40Hz, 1 min per day, continuously exposed for 5 days) was administered. Assessments were performed before exposure, during exposure, immediately after exposure, and at 7-, 14-, and 28-days post-exposure, employing auditory brainstem response (ABR) tests, electrocardiograms (ECG), and electroencephalograms (EEG). The study found that the average threshold for the Ⅴ wave in the right ear increased by around 30 dB SPL right after exposure (P < 0.01) compared to pre-exposure. This elevation returned to normal within 7 days. The ECG results indicated that one of the macaque monkeys exhibited an RS-type QRS wave, and inverted T waves from immediately after exposure to 14 days, which normalized at 28 days. The other two monkeys showed no significant changes in their ECG parameters. Changes in EEG parameters demonstrated that main brain regions exhibited significant activation at 40Hz during noise exposure. After noise exposure, the power spectral density (PSD) in main brain regions, particularly those represented by the temporal lobe, exhibited a decreasing trend across all frequency bands, with no clear recovery over time. In summary, exposure to 90 dB SPL noise results in impaired auditory systems, aberrant brain functionality, and abnormal electrocardiographic indicators, albeit with individual variations. It has implications for establishing noise protection standards, although the precise mechanisms require further exploration by integrating pathological and behavioral indicators.

Quantitative Proteomics Provided Insights into the Protective Effects of Heat Acclimation on the Rat Hypothalamus after Exertional Heatstroke.

BACKGROUND: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. METHODS: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. RESULTS: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1ß, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. CONCLUSIONS: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.

900 MHZ electromagnetic field exposure relieved AD-like symptoms on APP/PS1 mice: A potential non-invasive strategy for AD treatment.

BACKGROUND: Evidence shows that microwaves radiation may have various biological effects on central nervous system. Role of electromagnetic fields in neurodegenerative diseases, especially AD, has been widely studied, but results of these studies are inconsistent. Therefore, the above effects were verified again and the mechanism was preliminarily discussed. METHODS: Amyloid precursor protein (APP/PS1) and WT mice were exposed to long-term microwave radiation for 270 days (900 MHz, SAR: 0.25-1.055 W/kg, 2 h/day, alternately), and related indices were assessed at 90, 180 and 270 days. Cognition was evaluated by Morris water maze, Y maze and new object recognition tests. Congo red staining, immunohistochemistry and ELISA were used to analyze Aß plaques, Aß40 and Aß42 content. Differentially expressed proteins in hippocampus between microwave-exposed and unexposed AD mice were identified by proteomics. RESULTS: Spatial and working memory was improved in AD mice after long-term 900 MHz microwave exposure compared with after sham exposure. Microwave radiation (900 MHz) for 180 or 270 days did not induce Aß plaque formation in WT mice but inhibited Aß accumulation in the cerebral cortex and hippocampus in 2- and 5-month-old APP/PS1 mice. This effect mainly occurred in the late stage of the disease and may have been attributed to downregulation of apolipoprotein family member and SNCA expression and excitatory/inhibitory neurotransmitter rebalance in the hippocampus. CONCLUSIONS: The present results indicated that long-term microwave radiation can retard AD development and exert a beneficial effect against AD, suggesting that 900 MHz microwave exposure may be a potential therapy for AD.

The Crystal Structure of the MHC Class I (MHC-I) Molecule in the Green Anole Lizard Demonstrates the Unique MHC-I System in Reptiles.

The reptile MHC class I (MCH-I) and MHC class II proteins are the key molecules in the immune system; however, their structure has not been investigated. The crystal structure of green anole lizard peptide-MHC-I-ß2m (pMHC-I or pAnca-UA*0101) was determined in the current study. Subsequently, the features of pAnca-UA*0101 were analyzed and compared with the characteristics of pMHC-I of four classes of vertebrates. The amino acid sequence identities between Anca-UA*0101 and MHC-I from other species are <50%; however, the differences between the species were reflected in the topological structure. Significant characteristics of pAnca-UA*0101 include a specific flip of ∼88° and an upward shift adjacent to the C terminus of the α1- and α2-helical regions, respectively. Additionally, the lizard MHC-I molecule has an insertion of 2 aa (VE) at positions 55 and 56. The pushing force from 55-56VE triggers the flip of the α1 helix. Mutagenesis experiments confirmed that the 55-56VE insertion in the α1 helix enhances the stability of pAnca-UA*0101. The peptide presentation profile and motif of pAnca-UA*0101 were confirmed. Based on these results, the proteins of three reptile lizard viruses were used for the screening and confirmation of the candidate epitopes. These data enhance our understanding of the systematic differences between five classes of vertebrates at the gene and protein levels, the formation of the pMHC-I complex, and the evolution of the MHC-I system.

A Newly Recognized Pairing Mechanism of the α- and ß-Chains of the Chicken Peptide-MHC Class II Complex.

MHC class II (MHC-II) molecules play a crucial role in cellular and humoral immunity by forming peptide-MHC-II (pMHC-II) complexes. The three-dimensional structures of pMHC-II complexes have been well resolved in humans and mice. However, there is no structural information for pMHC-II complexes in nonmammals. In chickens, there are two closely related and highly polymorphic ß-chains and one monomorphic α-chain, and the mechanism by which one monomorphic α-chain combines with two polymorphic ß-chains to form a functional heterodimer remains unknown. In this study, we report the crystal structure of a chicken pMHC-II complex (pBL2*019:01) at 1.9-Å resolution as the first nonmammalian structure of a pMHC-II complex. The structure reveals an increase in hydrogen bonding between the α and ß main chains at the central interface that is introduced by the insertion of four residues in the α-chain. The residues in the ß-chain that form hydrogen bonds with the α-chain are conserved among all ß alleles. These structural characteristics explain the phenomenon of only one BLA allele without sequence variation pairing with highly diverse BLB alleles from two loci in the genome. Additionally, the characteristics of the peptide in the peptide-binding groove were confirmed. These results provide a new understanding of the pairing mechanism of the α- and ß-chains in a pMHC-II complex and establish a structural principle to design epitope-related vaccines for the prevention of chicken diseases.

A Glimpse of the Peptide Profile Presentation by Xenopus laevis MHC Class I: Crystal Structure of pXela-UAA Reveals a Distinct Peptide-Binding Groove.

The African clawed frog, Xenopus laevis, is a model species for amphibians. Before metamorphosis, tadpoles do not efficiently express the single classical MHC class I (MHC-I) molecule Xela-UAA, but after metamorphosis, adults express this molecule in abundance. To elucidate the Ag-presenting mechanism of Xela-UAA, in this study, the Xela-UAA structure complex (pXela-UAAg) bound with a peptide from a synthetic random peptide library was determined. The amino acid homology between the Xela-UAA and MHC-I sequences of different species is <45%, and these differences are fully reflected in the three-dimensional structure of pXela-UAAg. Because of polymorphisms and interspecific differences in amino acid sequences, pXela-UAAg forms a distinct peptide-binding groove and presents a unique peptide profile. The most important feature of pXela-UAAg is the two-amino acid insertion in the α2-helical region, which forms a protrusion of ∼3.8 Å that is involved in TCR docking. Comparison of peptide-MHC-I complex (pMHC-I) structures showed that only four amino acids in ß2-microglobulin that were bound to MHC-I are conserved in almost all jawed vertebrates, and the most unique feature in nonmammalian pMHC-I molecules is that the AB loop bound ß2-microglobulin. Additionally, the binding distance between pMHC-I and CD8 molecules in nonmammals is different from that in mammals. These unique features of pXela-UAAg provide enhanced knowledge of T cell immunity and bridge the knowledge gap regarding the coevolutionary progression of the MHC-I complex from aquatic to terrestrial species.

Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope.

Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell-mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I-ß2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV-PA123-130 We determined the structure of the BF2*1501-PA123-130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123-130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123-130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV-PA123-130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123-130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.

Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Structure and Peptidome of the Bat MHC Class I Molecule Reveal a Novel Mechanism Leading to High-Affinity Peptide Binding.

Bats are natural reservoir hosts, harboring more than 100 viruses, some of which are lethal to humans. The asymptomatic coexistence with viruses is thought to be connected to the unique immune system of bats. MHC class I (MHC I) presentation is closely related to cytotoxic lymphocyte immunity, which plays an important role in viral resistance. To investigate the characteristics of MHC I presentation in bats, the crystal structures of peptide-MHC I complexes of Pteropus alecto, Ptal-N*01:01/HEV-1 (DFANTFLP) and Ptal-N*01:01/HEV-2 (DYINTNLVP), and two related mutants, Ptal-N*01:01/HEV-1PΩL (DFANTFLL) and Ptal-N*01:01ΔMDL/HEV-1, were determined. Through structural analysis, we found that Ptal-N*01:01 had a multi-Ala-assembled pocket B and a flexible hydrophobic pocket F, which could accommodate variable anchor residues and allow Ptal-N*01:01 to bind numerous peptides. Three sequential amino acids, Met, Asp, and Leu, absent from the α1 domain of the H chain in other mammals, were present in this domain in the bat. Upon deleting these amino acids and determining the structure in p/Ptal-N*01:01ΔMDL/HEV-1, we found they helped form an extra salt-bridge chain between the H chain and the N-terminal aspartic acid of the peptide. By introducing an MHC I random peptide library for de novo liquid chromatography-tandem mass spectrometry analysis, we found that this insertion module, present in all types of bats, can promote MHC I presentation of peptides with high affinity during the peptide exchange process. This study will help us better understand how bat MHC I presents high-affinity peptides from an extensive binding peptidome and provides a foundation to understand the cellular immunity of bats.

PICK1 attenuates high glucose-induced pancreatic ß-cell death through the PI3K/Akt pathway and is negatively regulated by miR-139-5p.

Diabetes mellitus is a metabolic disease characterized by an increase in blood glucose levels due to lack of insulin secretion. Previous studies have confirmed that PICK1 is critical for both ß-cell function and glucose homeostasis. The aim of this study was to investigate the role of PICK1 in response to high glucose-induced ß-cell dysfunction and the molecular mechanism of regulation of PICK1. We found that overexpression of PICK1 in db/db diabetic mice significantly improved glucose tolerance and increased insulin release. High glucose treatment of Min6 cells inhibited PICK1 expression, and overexpression of PICK1 protected against high glucose-induced pancreatic cell dysfunction. Activation of the PI3K/Akt pathway by PICK1 in Min6 cells resulted in increased GLUT2 expression and this increase was abolished by treatment with a PI3K-specific inhibitor. Further, we showed that expression of PICK1 is negatively regulated by miR-139-5p through directly targeting its 3'UTR. These data suggested that PICK1 may participate in the functional protection of pancreatic ß-cells through PI3K/Akt signaling, promote insulin secretion, and delay the progression of diabetes, and is negatively regulated by miR-139-5p, further clarifying the regulation of pancreatic ß-cell function.

Distribution of ancient α1 and α2 domain lineages between two classical MHC class I genes and their alleles in grass carp.

Major histocompatibility complex (MHC) class I molecules play a crucial role in the immune response by binding and presenting pathogen-derived peptides to specific CD8+ T cells. From cDNA of 20 individuals of wild grass carp (Ctenopharyngodon idellus), we could amplify one or two alleles each of classical MHC class I genes Ctid-UAA and Ctid-UBA. In total, 27 and 22 unique alleles of Ctid-UAA and Ctid-UBA were found. The leader, α1, transmembrane and cytoplasmic regions distinguish between Ctid-UAA and Ctid-UBA, and their encoded α1 domain sequences belong to the ancient lineages α1-V and α1-II, respectively, which separated several hundred million years ago. However, Ctid-UAA and Ctid-UBA share allelic lineage variation in their α2 and α3 sequences, in a pattern suggestive of past interlocus recombination events that transferred α2+α3 fragments. The allelic Ctid-UAA and Ctid-UBA variation involves ancient variation between domain lineages α2-I and α2-II, which in the present study was dated back to before the ancestral separation of teleost fish and spotted gar (> 300 million years ago). This is the first report with compelling evidence that recombination events combining different ancient α1 and α2 domain lineages had a major impact on the allelic variation of two different classical MHC class I genes within the same species.

Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides.

Feline immunodeficiency virus (FIV) infection in domestic cats is the smallest usable natural model for lentiviral infection studies. FLA-E*01801 was applied to FIV AIDS vaccine research. We determined the crystal structure of FLA-E*01801 complexed with a peptide derived from FIV (gag positions 40 to 48; RMANVSTGR [RMA9]). The A pocket of the FLA-E*01801 complex plays a valuable restrictive role in peptide binding. Mutation experiments and circular-dichroism (CD) spectroscopy revealed that peptides with Asp at the first position (P1) could not bind to FLA-E*01801. The crystal structure and in vitro refolding of the mutant FLA-E*01801 complex demonstrated that Glu63 and Trp167 in the A pocket play important roles in restricting P1D. The B pocket of the FLA-E*01801 complex accommodates M/T/A/V/I/L/S residues, whereas the negatively charged F pocket prefers R/K residues. Based on the peptide binding motif, 125 FLA-E*01801-restricted FIV nonapeptides (San Diego isolate) were identified. Our results provide the structural basis for peptide presentation by the FLA-E*01801 molecule, especially A pocket restriction on peptide binding, and identify the potential cytotoxic T lymphocyte (CTL) epitope peptides of FIV presented by FLA-E*01801. These results will benefit both the reasonable design of FLA-E*01801-restricted CTL epitopes and the further development of the AIDS vaccine.IMPORTANCE Feline immunodeficiency virus (FIV) is a viral pathogen in cats, and this infection is the smallest usable natural model for lentivirus infection studies. To examine how FLA I presents FIV epitope peptides, we crystallized and solved the first classic feline major histocompatibility complex class I (MHC-I) molecular structure. Surprisingly, pocket A restricts peptide binding. Trp167 blocks the left side of pocket A, causing P1D to conflict with Glu63 We also identified the FLA-E*01801 binding motif X (except D)-(M/T/A/V/I/L/S)-X-X-X-X-X-X-(R/K) based on structural and biochemical experiments. We identified 125 FLA-E*01801-restricted nonapeptides from FIV. These results are valuable for developing peptide-based FIV and human immunodeficiency virus (HIV) vaccines and for studying how MHC-I molecules present peptides.

Comparative effectiveness of metformin monotherapy in extended release and immediate release formulations for the treatment of type 2 diabetes in treatment-naïve Chinese patients: Analysis of results from the CONSENT trial.

AIMS: Metformin treatment for type 2 diabetes mellitus (T2DM) can be limited by gastrointestinal (GI) adverse events (AEs), resulting in treatment discontinuation. We investigated whether once-daily metformin extended release (XR) is superior in terms of GI tolerability, with non-inferior efficacy, compared with thrice-daily metformin immediate release (IR) in treatment-naïve Chinese patients with T2DM. MATERIALS AND METHODS: This prospective, open-label, randomized, multicentre, phase IV interventional study enrolled Chinese T2DM patients to receive either metformin XR or metformin IR with a 2-week screening period, a 16-week treatment period and a 2-week follow-up period without treatment. Co-primary endpoints were a non-inferiority assessment of metformin XR vs metformin IR in glycated haemoglobin (HbA1c) least squares mean (LSM) change from baseline to week 16 and the superiority of GI tolerability for metformin XR vs metformin IR. RESULTS: Overall, 532 patients were randomized to metformin IR (n = 267) or metformin XR (n = 265). The HbA1c LSM change was -1.61% and -1.58% in each group, respectively (LSM difference, 0.03; 95% confidence interval [CI], -0.10, 0.17). Incidences of drug-related AEs were 26.5% (n = 66) in the metformin IR-only group and 32.2% (n = 85) in the metformin XR-only group, and GI AEs were 23.8% and 22.3% in each group, respectively (difference, -1.52; 95% CI, -8.60, 5.56). The treatment difference met the predefined non-inferiority upper CI margin of 0.4% in HbA1c. CONCLUSIONS: Metformin XR was non-inferior to metformin IR for the LSM change in HbA1c from baseline to week 16 and not superior to metformin IR for overall GI AE incidence during treatment of Chinese T2DM patients.

Lesch-Nyhan Syndrome in a Chinese Family with Mutation in the Hypoxanthine-Guanine Phosphoribosyltransferase Gene.

BACKGROUND: Lesch-Nyhan syndrome (LNS) is a congenital X-linked recessive neurogenetic disorder caused by mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene. The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis, and neurological developmental disorders. Studies have reported more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low. METHODS: Here we report a 16-year-old male patient who suffered neurological dysfunction at an early age and gouty arthritis in his youth. RESULTS: No activity of the HPRT enzyme was detected in the erythrocytes. Furthermore, we found a mutation on exon 3 of the HPRT gene in the patient and his mother (exon 3: c.143G>A), which resulted in arginine to histidine (p.R48H) substitution in the encoded protein. The same mutation was reported in several European families, but was found for the first time in a Chinese family. CONCLUSIONS: Clinicians in China have poor experience in diagnosing LNS cases due to the low incidence in China. Therefore, LNS screening for infants or adolescents with hyperuricemia, gouty arthritis, and neurological dysfunction should be performed.

High prevalence and diversity of viruses of the subfamily Gammaherpesvirinae, family Herpesviridae, in fecal specimens from bats of different species in southern China.

Several studies have reported the detection of herpesviruses (HVs) in bats. However, the prevalence and phylogenetic characteristics of HVs in bats are still poorly understood. To elucidate the epidemiological characteristics of bat HVs in southern China, 520 fecal samples from eight bat species were collected in four geographic regions of southern China. Of these samples, 73 (14.0 %) tested positive for HVs using nested polymerase chain reaction assay. Phylogenetic analysis revealed a high degree of molecular diversity of HVs in bats of different species from different geographic regions. Our study provides evidence for co-evolution of bats and HVs.

Combined 17α-hydroxylase/17,20-lyase deficiency with short stature: case study.

BACKGROUNDS: 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is an uncommon form of congenital adrenal hyperplasia. Most patients are tall owing to delayed closure of epiphyses as a result of deficiency of sex hormones. METHODS: We present a 17-OHD case with unusual short stature and reviewed related literature. RESULTS: A 17-year-old female patient presented with primary amenorrhea, hypertension, hypokalemia and hypergonadotropic hypogonadism (HH). Sequencing of the CYP17A1 gene identified a homozygous c.985_987delTACinsAA in exon 6 that confirmed the diagnosis of 17-OHD. However, her height (148 cm, height standard deviation score [HSDS] -2.28) was unusually low compared with that of other 17-OHD patients. Levels of growth hormone (GH) and insulin-like growth factor (IGF)-1 were normal, and the GH provocation test excluded the possibility of GH deficiency. She underwent glucocorticoid and sex-hormone replacement therapy, reaching a final height of 152 cm (HSDS -1.59). These data suggest that tall stature is not a requisite characteristic of 17-OHD. Further studies are needed to clarify the effects of sex hormone on linear bone growth (LBG) in 17-OHD patients.

[Detection of High Molecular Weight Polycyclic Aromatic Hydrocarbons in Mixed Colloid Solution of Spherical Au and Urchin-Like Au-Ag Alloy with Surface-Enhanced Raman Scattering].

In this paper, Au nanosphere and Au-Ag alloy nanourchin were prepared by reducing the chloroauric acid. The mixed colloid solutions of Au nanosphere and Au-Ag alloy nanourchin were used as surface-enhanced Raman scattering (SERS) substrate to detect polycyclic aromatic hydrocarbons (PAHs) in aqueous solution. The size of Au-Ag alloy nanourchin particle was about 300~400 nm and the thorn-like bulge covered on it was about 40~100 nm. The mixed colloid solutions of Au nanosphere and Au-Ag alloy nanourchin which were optimized pH values and other parameters presented a better enhancement than Au nanosphere. The enhancement effect was about three times that of Au nanosphere colloid solution. Three kinds of high molecular weight PAHs, pyrene(4 rings), benzoanthracene(4 rings) and benzo[a]pyrene(5 rings), were detected. The results showed that there were good linear relationships between Raman intensity and concentration in the low concentration range and the mixed SERS substrate had a good reproducibility and stability. Their limits of detection (LODs) were 0.44, 2.92 and 1.64 nmol·L-1, respectively. The innovation of this paper was that the mixed colloid solutions of Au nanosphere and Au-Ag alloy nanourchin are prepared as SERS substrate and the trace-level high molecular weight PAHs are detected. The results show that the detection of trace-level high molecular weight PAHs in aqueous can be realized using the mixed SERS substrate prepared in this study, which proposed an in-situ method for detecting the high molecular weight PAHs in aqueous.

Comparison of genomic and amino acid sequences of eight Japanese encephalitis virus isolates from bats.

We compared nucleotide and deduced amino acid sequences of eight Japanese encephalitis virus (JEV) isolates derived from bats in China. We also compared the bat JEV isolates with other JEV isolates available from GenBank to determine their genetic similarity. We found a high genetic homogeneity among the bat JEVs isolated in different geographical areas from various bat species at different time periods. All eight bat JEV isolates belonged to genotype III. The mean evolutionary rate of bat JEV isolates was lower than those of isolates of other origin, but this difference was not statistically significant. Based on these results, we presume that the bat JEV isolates might be evolutionarily conserved. The eight bat JEV isolates were phylogenetically similar to mosquito BN19 and human Liyujie isolates of JEV. These results indicate that bats might be involved in natural cycle of JEV.

Update on Nonhuman Primate Models of Brain Disease and Related Research Tools.

The aging of the population is an increasingly serious issue, and many age-related illnesses are on the rise. These illnesses pose a serious threat to the health and safety of elderly individuals and create a serious economic and social burden. Despite substantial research into the pathogenesis of these diseases, their etiology and pathogenesis remain unclear. In recent decades, rodent models have been used in attempts to elucidate these disorders, but such models fail to simulate the full range of symptoms. Nonhuman primates (NHPs) are the most ideal neuroscientific models for studying the human brain and are more functionally similar to humans because of their high genetic similarities and phenotypic characteristics in comparison with humans. Here, we review the literature examining typical NHP brain disease models, focusing on NHP models of common diseases such as dementia, Parkinson's disease, and epilepsy. We also explore the application of electroencephalography (EEG), magnetic resonance imaging (MRI), and optogenetic study methods on NHPs and neural circuits associated with cognitive impairment.

Neural Oscillation Disorder in the Hippocampal CA1 Region of Different Alzheimer's Disease Mice.

BACKGROUND: Alzheimer's disease (AD) is a well-known neurodegenerative disease that gradually induces neural network dysfunction and progressive memory deficits. Neural network activity is represented by rhythmic oscillations that influence local field potentials (LFPs). However, changes in hippocampal neural rhythmic oscillations in the early stage of AD remain largely unexplored. OBJECTIVE: This study investigated neural rhythmic oscillations in 3-month-old APP/PS1 and 5x- FAD mice to assess early neural connectivity in AD. METHODS: LFPs were recorded from the hippocampal CA1 region with implanted microelectrode arrays while the mice were in the awake resting stage. Welch fast Fourier transforms, continuous wavelet transforms, and phase-amplitude coupling analyses were used to compute the power density of different frequency bands and phase-amplitude modulation indices in the LFPs. RESULTS: Our results showed impaired theta, low gamma, and high gamma frequency band power in APP/PS1 and 5xFAD mice during the awake resting stage. AD mice also showed decreased delta, alpha, and beta frequency band power. Impaired theta-low gamma and theta-high gamma phaseamplitude coupling were observed in 5xFAD mice. CONCLUSION: This study revealed neural network activity differences in oscillation power and cross-frequency coupling in the early stage of AD, providing a new perspective for developing biomarkers for early AD diagnosis.