Quantitative electroencephalography (qEEG), apolipoprotein A-I (APOA-I), and apolipoprotein epsilon 4 (APOE ɛ4) alleles for the diagnosis of mild cognitive impairment and Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is the most common type of dementia. Amnestic mild cognitive impairment (aMCI), a pre-dementia stage is an important stage for early diagnosis and intervention. This study aimed to investigate the diagnostic value of qEEG, APOA-I, and APOE ɛ4 allele in aMCI and AD patients and found the correlation between qEEG (Delta + Theta)/(Alpha + Beta) ratio (DTABR) and different cognitive domains. METHODS: All participants were divided into three groups: normal controls (NCs), aMCI, and AD, and all received quantitative electroencephalography (qEEG), neuropsychological scale assessment, apolipoprotein epsilon 4 (APOE ɛ4) alleles, and various blood lipid indicators. Different statistical methods were used for different data. RESULTS: The cognitive domains except executive ability were all negatively correlated with DTABR in different brain regions while executive ability was positively correlated with DTABR in several brain regions, although without statistical significance. The consequences confirmed that the DTABR of each brain area were related to MMSE, MoCA, instantaneous memory, and the language ability (p < 0.05), and the DTABR in the occipital area was relevant to all cognitive domains (p < 0.01) except executive function (p = 0.272). Also, occipital DTABR was most correlated with language domain when tested by VFT with a moderate level (r = 0.596, p < 0.001). There were significant differences in T3, T5, and P3 DTABR between both AD and NC and aMCI and NCs. As for aMCI diagnosis, the maximum AUC was achieved when using T3 combined with APOA-I and APOE ε4 (0.855) and the maximum AUC was achieved when using T5 combined with APOA-I and APOE ε4 (0.889) for AD diagnosis. CONCLUSION: These findings highlight that APOA-I, APOE ɛ4, and qEEG play an important role in aMCI and AD diagnosis. During AD continuum, qEEG DTABR should be taken into consideration for the early detection of AD risk.

Azide Ionic Liquids for Safe, Green, and Highly-Efficient Azidation Reactions to Produce Azide Polymers.

Azide compounds are widely used and especially, polymers bearing pendant azide groups are highly desired in numerous fields. However, harsh reaction conditions are always mandatory to achieve full azidation, causing severe side reactions and degradation of the polymers. Herein, we report the design and preparation of two azide ionic liquids (AILs) with azide anion and triethylene glycol (E3 )-containing cation, [P444E3 ][N3 ] and [MIME3 ][N3 ]. Compared with the traditional sodium azide (NaN3 ) approach, both AILs showed much higher reaction rates and functional-group tolerance. More importantly, they could act as both reagents and solvents for the quantitative azidation of various polymeric precursors under mild conditions. Theoretical simulations suggested that the outstanding performance of AILs originated from the existence of ion pairs during the reaction, and the E3 moieties played a crucial role. Lastly, after the reaction, the AILs could be easily regenerated, presenting a safer, greener, and highly efficient synthesis route for azide polymers.

Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer's disease: findings based on urine proteomics and machine learning.

BACKGROUND: Alzheimer's disease is a prevalent disease with a heavy global burden. Proteomics is the systematic study of proteins and peptides to provide comprehensive descriptions. Aiming to obtain a more accurate and convenient clinical diagnosis, researchers are working for better biomarkers. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels. METHODS: We firstly enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples, and conducted an LC-MS/MS analysis. In parallel, clinical data were collected, and clinical examinations were performed. After statistical and bioinformatics analyses, significant risk factors and differential urinary proteins were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM. RESULTS: Fifty-seven AD patients, 43 MCI patients, and 62 CN subjects were enrolled. A total of 3366 proteins were identified, and 608 urine proteins were finally included in the analysis. There were 33 significantly differential proteins between the AD and CN groups and 15 significantly differential proteins between the MCI and CN groups. AD diagnostic panel included DDC, CTSC, EHD4, GSTA3, SLC44A4, GNS, GSTA1, ANXA4, PLD3, CTSH, HP, RPS3, CPVL, age, and APOE ε4 with an AUC of 0.9989 in the training test and 0.8824 in the test set while MCI diagnostic panel included TUBB, SUCLG2, PROCR, TCP1, ACE, FLOT2, EHD4, PROZ, C9, SERPINA3, age, and APOE ε4 with an AUC of 0.9985 in the training test and 0.8143 in the test set. Besides, diagnostic proteins were weakly correlated with cognitive functions. CONCLUSIONS: In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN.

Yak-Derived CXCL14 Activates the Pro-Inflammatory Response of Macrophages and Inhibits the Proliferation and Migration of HepG2.

CXCL14 (C-X-C motif chemokine ligand 14) is an important chemokine involved in infection and immunity and plays an important role in a variety of immune-related diseases. The 446 bp cDNA sequence of the CXCL14 gene in yaks was obtained. Additionally, the prokaryotic expression vector of the CXCL14 protein with a molecular weight of 27 kDa was successfully constructed and expressed. The proliferation activities and migration abilities of spleen macrophages were significantly inhibited after treatment with the CXCL14 protein at different concentrations (1, 10 and 20 µg/mL) (p < 0.05). Furthermore, the expressions of pro-inflammatory cytokines interleukin 1 beta (IL-1ß), interleukin 6 (IL6), interleukin 8 (IL8) and interferon-α (TNF-α) were significantly increased (p < 0.05), but the expression of anti-inflammatory factor interleukin 10 (IL10) was significantly decreased (p < 0.05). The contents of inflammatory factors in the supernatant of cells were detected using ELISA, and it was also found that the contents of TNF-α, IL6 and cytochrome c oxidase subunit II (COX2) were significantly increased under different CXCL14 protein concentrations (p < 0.05). Finally, the exogenous addition of CXCL14 inhibited the activity, clonal formation and migration of hepatoma cells (HepG2). Additionally, after HepG2 cells were treated with 20 µg/mL CXCL14 protein for 12 h, 24 h and 36 h, the expression levels of BCL2 homologous antagonist/killer (BAK) and the BCL2-associated X apoptosis regulator (BAX) were increased to varying degrees, while the expression levels of hypoxia-inducible factor 1 subunit alpha (HIF1A), the mechanistic target of rapamycin kinase (mTOR) and cyclin-dependent kinase 1 (CDK1) genes decreased compared to the control group. In conclusion, the CXCL14 protein can inhibit the proliferation and migration of HepG2 cells by inducing the expression of macrophage pro-inflammatory factors and activating apoptosis-related genes to exert innate immunity. These results are helpful to further study the function of the CXCL14 protein and provide research data for the innate immune mechanism of yaks under harsh plateau environments.

Transcriptomic analysis reveals differentially expressed genes and key immune pathways in the spleen of the yak (Bos grunniens) at different growth stage.

Yak is one of the rare and unique cattle species on the Qinghai-Tibetan Plateau, which has strong adaptability to the extreme environment of the plateau. The spleens are important functional organs that enable animals to adapt to their external environment and are vital in the growth and development process. To further investigate changes in immune function during yak development, we compared the transcriptome profiles of spleen tissues among juvenile (1-day old), youth (15-months old), and prime (5-years old) yaks. Immunology of spleen development was evaluated based on histological analyses and global gene expression was examined by using RNA-sequencing (RNA-seq) technology. In this work, we found 6378 genes with significant differences between the spleen of juvenile yak and youth yak, with the largest difference between groups. There were 3144 genes with significant differences between the spleen of young yak and prime yak, with the smallest differences between groups. Further, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for the functional annotation of these genes. GO and KEGG analysis showed that some of them were related to growth, disease, immune, and metabolism. However, the genetic mechanism underlying the adaptability of yak spleens at different ages to harsh plateau environments remains unknown. These findings are important for studying the mechanisms of spleen development in yaks of different age groups.

SiO2 dust induces inflammation and pulmonary fibrosis in rat lungs through activation of ASMase/ceramide pathway.

The role of ASMase/ceramide signaling pathway in the development of silicosis needs to be verified by in vivo experiments. We investigated the role of the ASMase/ceramide signaling pathway in the progression of silicosis and the effect of desipramine (DMI) (1 mg/mL) on the development of silicosis, by establishing a silica (1 mL, 50 mg/mL) dust-contaminated rat silicosis model and administering the ASMase inhibitor, DMI, to the dust-contaminated rats. The results showed that the levels of interleukin (IL)-1ß and IL-6 were increased in the lung tissues of the rats in the dust-contaminated group at the initial stage after dusting; the inflammatory cell aggregation in the lung tissue was increased. With time progression, the hydroxyproline content in the lung tissue increased, and alpha-smooth muscle actin (α-SMA), collagen I, and vimentin substantially increased, suggesting that silicosis was formed in the lung tissue of the rats 28 days after SiO2 dust treatment. Moreover, the levels of ASMase, ceramide, and sphingosine-1-phosphate (S1P) were increased in the lung tissue of rats. The expression of ß-catenin, fibronectin, and caspase-3 protein was increased, and E-cadherin protein expression was decreased in the lung tissue of the rats in the late stage of dust contamination. The ASMase and ceramide in the lung tissues of the rats in the DMI intervention group were reduced, as were the lung tissue inflammation levels, collagen expression, and lung fibrosis. These results suggest that SiO2 dust may activate the ASMase/ceramide signaling pathway in rat lung tissue, promoting pulmonary fibrosis. DMI inhibited this activation, attenuated apoptosis, blocked epithelial-mesenchymal transition, and halted silica dust-induced silicofibrosis.

Synthesis and Properties of Biodegradable Hydrogel Based on Polysaccharide Wound Dressing.

The metabolic disorder of the wound microenvironment can lead to a series of serious symptoms, especially chronic wounds, which result in significant pain in patients. At present, there is no effective and widely used wound dressing. Therefore, it is important to develop new multifunctional wound dressings. Hydrogel is an ideal wound dressing for medical nursing because of its abilities to absorb exudate and maintain wound wetting, its excellent biocompatibility, and its ability to provide a moist environment for wound repair. Because of these features, hydrogel overcomes the shortcomings of traditional dressings. Therefore, hydrogel has high medical value and is widely studied. In this study, a biodegradable hydrogel based on polysaccharide was synthesized and used as a wound dressing. The swelling degree and degradability of hydrogel were characterized as the characteristics of the wound dressing. The results showed that the prepared hydrogel was degraded with trypsin and in the soil environment. Furthermore, the wound dressing can effectively inhibit the bacterial environment, promote the deposition of the collagen structure of the wound tissue, and accelerate the healing of the wound. The proposed hydrogel has value in practical medical nursing application.

A Similarity Measure-Based Approach Using RS-fMRI Data for Autism Spectrum Disorder Diagnosis.

Autism spectrum disorder (ASD) is a lifelong neurological disease, which seriously reduces the patients' life quality. Generally, an early diagnosis is beneficial to improve ASD children's life quality. Current methods based on samples from multiple sites for ASD diagnosis perform poorly in generalization due to the heterogeneity of the data from multiple sites. To address this problem, this paper presents a similarity measure-based approach for ASD diagnosis. Specifically, the few-shot learning strategy is used to measure potential similarities in the RS-fMRI data distributions, and, furthermore, a similarity function for samples from multiple sites is trained to enhance the generalization. On the ABIDE database, the presented approach is compared to some representative methods, such as SVM and random forest, in terms of accuracy, precision, and F1 score. The experimental results show that the experimental indicators of the proposed method are better than those of the comparison methods to varying degrees. For example, the accuracy on the TRINITY site is more than 5% higher than that of the comparison method, which clearly proves that the presented approach achieves a better generalization performance than the compared methods.

Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer's disease.

Introduction: Alzheimer's disease is a prevalent disease with a heavy global burden and is suggested to be a metabolic disease in the brain in recent years. The metabolome is considered to be the most promising phenotype which reflects changes in genetic, transcript, and protein profiles as well as environmental effects. Aiming to obtain a comprehensive understanding and convenient diagnosis of MCI and AD from another perspective, researchers are working on AD metabolomics. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels. Methods: We first enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples and conducted an LC-MS/MS analysis. In parallel, clinical data were collected and clinical examinations were performed. After statistical and bioinformatics analyzes, significant risk factors and differential urinary metabolites were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM. Results: Fifty-seven AD patients, 43 MCI patients and 62 CN subjects were enrolled. A total of 2,140 metabolites were identified among which 125 significantly differed between the AD and CN groups, including 46 upregulated ones and 79 downregulated ones. In parallel, there were 93 significant differential metabolites between the MCI and CN groups, including 23 upregulated ones and 70 downregulated ones. AD diagnostic panel (30 metabolites+ age + APOE) achieved an AUC of 0.9575 in the test set while MCI diagnostic panel (45 metabolites+ age + APOE) achieved an AUC of 0.7333 in the test set. Atropine, S-Methyl-L-cysteine-S-oxide, D-Mannose 6-phosphate (M6P), Spiculisporic Acid, N-Acetyl-L-methionine, 13,14-dihydro-15-keto-tetranor Prostaglandin D2, Pyridoxal 5'-Phosphate (PLP) and 17(S)-HpDHA were considered valuable for both AD and MCI diagnosis and defined as hub metabolites. Besides, diagnostic metabolites were weakly correlated with cognitive functions. Discussion: In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN. Atropine, M6P and PLP were evidence-based hub metabolites in AD.

Dietary carbon loaded with nano-ZnO alters the gut microbiota community to mediate bile acid metabolism and potentiate intestinal immune function in fattening beef cattle.

BACKGROUND: To our knowledge, carbon loaded with nano-ZnO (NZnOC) represents a new nutritional additive for the animal husbandry industry. However, the mechanism by which NZnOC mediates beef cattle growth and intestinal health is not fully understood. This study aimed to investigate the effects of carbon loaded with nano-ZnO (NZnOC) supplementation on growth performance, gut microbiota, bile acid (BAs) metabolism and intestinal immunity in fattening cattle. Twenty cattle (16 ± 0.95 months) were randomly assigned to two dietary groups: CON (control, without feed additive) and NZnOC (diet supplemented with 80 mg NZnOC/kg diet dry matter basic) for 60 d. The colon digesta microbiota composition and BAs concentration were determined by microbiota metagenomics and gas chromatography methods, respectively. RESULTS: The results showed that the NZnOC-supplemented cattle had greater final weight, average daily gain and gain-to-feed ratio than those in the CON group. Cattle fed the NZnOC diet had a higher relative abundance of the secondary BAs synthesizing phyla Firmicutes, Tenericutes and Actinobacteria than those fed the CON diet. Dietary supplementation with NZnOC increased the relative abundance of the secondary BAs synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, and Brevibacillus in colon digesta. Cattle fed the NZnOC diet had increased activities of 3α-hydroxysteroid dehydrogenase (EC: 1.1.1.52) and bile acid-CoA ligase BaiB (EC: 6.2.1.7) in the colon digesta compared with those fed the CON diet. The primary BAs taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid were significantly decreased by dietary NZnOC supplementation, while the secondary BAs deoxycholic acid, taurolithocholic acid, beta-muricholic acid, 12-ketolithocholic acid and ursodeoxycholic acid were significantly increased. Dietary supplementation with NZnOC increased the mRNA abundance of G protein-coupled bile acid receptor 1, protein kinase cAMP-activated catalytic subunit alpha, cyclic-AMP response element binding protein 1 and interleukin (IL)-10 in the colon mucosa of cattle, while the mRNA abundance of tumor necrosis factor and IL-1ß were significantly decreased. CONCLUSIONS: In summary, dietary supplementation with NZnOC can facilitate the growth performance and intestinal immune function of cattle by improving BAs metabolism. NZnOC can be supplemented in the diet as a safe regulator of gut microbiota and as a feed additive in the ruminants industry.

The transmembrane replacement H7N9-VLP vaccine displays high levels of protection in mice.

The incidence of infections caused by the H7N9 subtype of the influenza virus has expanded rapidly in China in recent decades, generating massive economic loss and posing a significant threat to public health. In the absence of specialized antiviral treatments or long-term effective preventative vaccinations, it is critical to constantly enhance vaccines and create effective antiviral drugs to prevent the recurrence of pandemics. In the present study, a transmembrane-substituted (TM) virus-like particle (VLP)-based vaccine was created by replacing the transmembrane region of hemagglutinin (HA) protein with the transmembrane region of the H3 HA protein and then used to immunize BALB/c mice. Sera and T cells were collected from the immunized mice to evaluate the passive immune effects. Our results showed that naïve mice achieved 80-100% protection against homologous and heterologous H7N9 influenza strains after receiving passive serum immunization; the protective effect of the TM VLPs was more evident than that of the wild-type HA VLPs. In contrast, mice immunized with passive T cells achieved only 20 to 80% protection against homologous or heterologous strains. Our findings significantly contribute to understanding the control of the H7N9 virus and the development of a vaccine.

Metal-free visible-light-driven cascade cyclization reaction to synthesize 2-oxindoles via benzoyl and phenylsulfinyl radicals with acrylamide derivatives.

A metal-free visible-light-driven cascade cyclization reaction to synthesize 3-methyl-3-acetophenone-2-oxindoles and 3-methyl-3-(methylsulfonyl)benzene-2-oxindoles in yields up to 96% and 99%, via benzoyl and phenylsulfinyl radicals with acrylamide derivatives is reported, respectively. Extensive studies, including gram-scale, radical capture and isotope experiments, were performed to indicate that the reaction may involve a radical process.

ANXA11 mutations are associated with amyotrophic lateral sclerosis-frontotemporal dementia.

Background: The Annexin A11 (ANXA11) gene has been newly identified as a causative gene of amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). The current study aimed to investigate the ANXA11 mutations in a Chinese ALS-FTD or FTD cohort. Methods: We included ten probands/patients with suspected ALS-FTD or FTD. Mutational analysis of ANXA11 was performed through Next Generation Sequencing (NGS) and Sanger sequencing. We collected and reviewed clinical presentation, neuropsychology test results, brain-imaging findings, and electrophysiological examination findings. Results: In total, six probands presented with ALS-FTD, and four with behavior variant FTD (bv-FTD). We identified a non-synonymous heterozygous mutation (c.119A>G, p.D40G) of ANXA11 in proband 1, which is associated with ALS. However, this is the first report of the mutation causing ALS-FTD. Proband 1 started with abnormal behavior and progressed to classic upper motor nervous disease. Magnetic resonance imaging (MRI) showed significant bilateral temporal lobe atrophy and bilateral hyperintensities along the corticospinal tracts.18F-AV45-PET imaging showed negative amyloid deposits. Conclusion: ANXA11-related diseases have high clinical and genetic heterogeneity. Our study confirmed the contribution of ANXA11 mutations to ALS-FTD. The ANXA11 mutations established a complex genotype-phenotype correlation in ALS-FTD. Our research further elucidated the genetic mechanism of ALS-FTD and contributed to setting the foundation of future targeted therapy.

A moderate static magnetic field promotes C. elegans longevity through cytochrome P450s.

Ageing is co-regulated by genetic and environmental factors. Life on earth lives and evolves in a mild geomagnetic field. Yet, the biological effects of a moderate magnetic field on ageing and the underlying genetic mechanisms remain barely unknown. Here, we report that a moderate static magnetic field (SMF) extends the lifespan of Caenorhabditis elegans, a well-established model organism in ageing research. Consistently, the SMF-treated worms show improved motility and mitochondrial function when aged. We identified from the transcriptomic changes upon SMF treatment that the upregulation of three cytochrome P450 genes are required for SMF-induced longevity. Our findings thus reveal that proper SMF treatment could promote longevity through the well-conserved cytochrome P450 enzymes.

Preparation and Performance Analysis of Bacterial Cellulose-Based Composite Hydrogel Based on Scanning Electron Microscope.

In order to better prepare and analyze bacterial cellulose-based composite hydrogels, an experimental method based on scanning electron microscopy was proposed. The specific content of the method is to observe the hydrogel through scanning electron microscope, to observe the space between molecules through experiments, and to improve the effect of bacterial cellulose preparation of hydrogel. The experimental results show that the gel preparation effect is best when PEG concentration is not more than observed by scanning electron microscope. It is better to prepare bacterial cellulose complex hydrogel by scanning electron microscopy.

Combined intervention with N-acetylcysteine and desipramine alleviated silicosis development by regulating the Nrf2/HO-1 and ASMase/ceramide signaling pathways.

Silicosis is a systemic disease characterized by diffuse fibrosis of the lung tissue caused by long-term inhalation of large amounts of free silica (SiO2) dust. The pathogenesis of silicosis has not been fully elucidated, and there is a lack of effective treatment methods. N-acetylcysteine (NAC) can potentially treat pulmonary fibrosis by exerting antioxidant effects. Desipramine (DMI) can influence pulmonary fibrosis development by inhibiting acid sphingomyelinase (ASMase) activity and regulating ceramide concentrations. Both can interfere with pulmonary fibrosis through different mechanisms, but the intervention effects of NAC combined with DMI on silicosis fibrosis have not been reported. Therefore, this study established a rat silicosis model using a single tracheal drip of SiO2 dust suspension in Wistar rats to investigate the effect of NAC combined with DMI on SiO2 dust-induced silicosis and its related molecular mechanisms. The histopathological examination of the SiO2 dust-induced silicosis rats suggested that NAC and DMI alone or in combination could decrease the severity of pulmonary fibrosis in rats. The combined intervention had a better effect on reducing fibrosis than the individual interventions. NAC and DMI, alone or in combination, decreased the levels of markers related to pulmonary fibrosis in rats (smooth muscle α-actin (α-SMA), collagen (Col) I, Col III, hydroxyproline (HYP), inflammatory factors (transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α (TNF-α)), and lipid peroxidase malondialdehyde (MDA)). The nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme-oxygenase-1 (HO-1) and ASMase/ceramide pathways were inhibited to some extent by increasing the superoxide dismutase (SOD) levels of antioxidant enzymes and 8-iso-prostaglandin F2α (8-iso-PGF2α) levels of lipid peroxides. The combined intervention and NAC alone inhibited the SiO2 dust-induced elevation of matrix metalloproteinase 1 (MMP-1) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1), but the effect was not significant in the DMI-treated group. Combining DMI and NAC inhibited Col I deposition and reduced HO-1, TIMP-1, and ASMase levels in lung tissues compared to individual treatments. In summary, the SiO2 dust could induce oxidative stress and inflammation in rats, resulting in an imbalance in extracellular matrix (ECM) synthesis/catabolism and ASMase/ceramide signaling pathway activation, leading to silicosis development.The combined intervention of DMI and NAC may synergistically regulate the Nrf2/HO-1 pathway, maintain the anabolic balance of the ECM, inhibit ASMase/ceramide signaling pathway activation by suppressing the inflammatory response and effectively delay silicosis fibrosis progression.

Evaluation of the Clinical Effectiveness of Oseltamivir for Influenza Treatment in Children.

Objective: To estimate the clinical effectiveness of oseltamivir in children with different subtypes of influenza virus infection. Methods: A total of 998 children with acute respiratory infection were enrolled from January to March 2018, and were divided into influenza A, influenza B, influenza A + B, and non-influenza infection (IV-negative) groups. Influenza-like symptoms and duration of fever were evaluated and compared between oseltamivir-treated and non-treated groups. Results: There were no significant differences in the reduction in total febrile period and duration of fever from the onset of therapy between the oseltamivir treated and non-treated children infected with influenza A (p = 0.6885 for total febrile period and 0.7904 for the duration of fever from the onset of treatment), influenza B (p = 0.1462 and 0.1966), influenza A + B (p = 0.5568 and 0.9320), and IV-negative (p = 0.7631 and 0.4655). The duration of fever in children received oseltamivir therapy within 48 h was not significantly shorter than that beyond 48 h (p > 0.05). Additionally, percentages and severities of influenza-like symptoms, including headache, myalgia, fatigue, bellyache, vomiting, diarrhea, sore throat, cough, and coryza were not decreased and alleviated after treatment of oseltamivir. Conclusion: Oseltamivir treatment does not significantly shorten the duration of fever, nor does it significantly relieve influenza-like symptoms in children with infection of influenza.

Molecular characterization, expression and anti-tumor function analysis of yak IFITM2 gene.

IFITM2 is interferon-induced transmembrane protein 2, which plays an extremely key role in anti-tumor and anti-virus diseases. In this study, the 602 bp cDNA sequence of the yak (Bos grunniens) IFITM2 (BgIFITM2) gene was obtained. Moreover, the prokaryotic expression vector of BgIFITM2 protein was constructed and expressed successfully, with a molecular weight of 33.680 kDa. The proliferation activities and migration abilities of HepG2 cells were significantly inhibited after treatment with BgIFITM2 protein (0.1 and 1 µg/mL) (P < 0.05). The expressions of B cell lymphoma-2 (BCL2)/BCL2-associated X (BAX) and molecular target of rapamycin (mTOR) genes were significantly decreased, but the expressions of BAX gene were significantly increased after treatment with BgIFITM2 protein (0.1 and 1 µg/mL) (P < 0.05). The expression of BAX protein was also significantly increased after treatment with 1 µg/mL BgIFITM2 protein (P < 0.05). Finally, the addition of BgIFITM2 protein attenuated the formation of tumor lesions in mice, and the pathological damage of the lung was less than that in the model group. The expression of Ki67 protein in the model group was significantly higher than that in the control group (P < 0.05), but the expression of Ki67 protein in the BgIFITM2 group was significantly lower than that in the model group (P < 0.05). Taken together, BgIFITM2 protein could inhibit the proliferative activity of HepG2 cells by regulating apoptosis-related genes, and reduce the invasiveness of HepG2 cells in mice lung tissue. These results facilitate further studies on the function of BgIFITM2 protein.

Comparative proteomic analysis of spleen reveals key immune-related proteins in the yak (Bos grunniens) at different growth stages.

Spleen plays an indispensable role in the immune system as the largest lymphatic organ in the body. The spleens of yaks at three developmental stages (1 day fetal yak, 15 months juvenile yak and 5 years old adult yak) were sampled and the Tandem mass tag (TMT) quantification method was employed in spleen proteomic analysis. The results showed that 6576 proteins and 529 differentially expressed proteins (DEPs) were identified in the yak spleens at three growth stages. Gene ontology (GO) analysis of DEPs indicated that DEPs were enriched in Oxygen transport, Actin filament movement, DNA replication, Cell cycle process, and Cell macromolecule biosynthesis process, which was conducive to high altitude breathing, protein synthesis and organ growth in yaks. These were indispensable for yak spleen growth and cell metabolism, high altitude adaptation. Those DEPs were further analyzed based on Kyoto encyclopedia of genes and genomes (KEGG) pathways, which principally participated in Th1 and Th2 cell differentiation, NF-kappa B signaling pathway, Phagosome, and Glutathione metabolism. Those pathways were associated with some animal life activities in defense against microbial antigens, indicating that with age, the immune function of the yak's spleen continued to increase. Hemoglobin, Tumor necrosis factor receptor associated factor 1 (TRAF1), T cell receptor (TCR), Macrophage receptor, Fc receptors (FcR), and Gamma-glutamyl transferase (GGT) of DEPs played roles in immune function in yak spleen directly or indirectly. The dynamic changes of Toll like receptor 2 (TLR2), TRAF1 and Heat shock protein 27 (HSP27 or HSPB1) detected by Immunohistochemistry were consistent with those obtained from TMT proteomic. In conclusion, this study provides extensive and functional analyses of the spleen proteome at three developmental stages and will offer a new insight into key proteins involved in the immune function of yak spleen.

A pairwise functional connectivity similarity measure method based on few-shot learning for early MCI detection.

Alzheimer's disease is an irreversible neurological disease, therefore prompt diagnosis during its early stage, i.e., early mild cognitive impairment (MCI), is crucial for effective treatment. In this paper, we propose an automatic diagnosis method, a few-shot learning-based pairwise functional connectivity (FC) similarity measure method, to detect early MCI. We first employ a sliding window strategy to generate a dynamic functional connectivity network (FCN) using each subject's rs-fMRI data. Then, normal controls (NCs) and early MCI patients are distinguished by measuring the similarity between the dynamic FC series of corresponding brain regions of interest (ROIs) pairs in different subjects. However, previous studies have shown that FC patterns in different ROI-pairs contribute differently to disease classification. To enable the FCs of different ROI-pairs to make corresponding contributions to disease classification, we adopt a self-attention mechanism to weight the FC features. We evaluated the suggested strategy using rs-fMRI data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and the results point to the viability of our approach for detecting MCI at an early stage.