The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation.

Auditory neuropathy spectrum disorder (ANSD) is a form of hearing loss in which auditory signal transmission from the inner ear to the auditory nerve and brain stem is distorted, giving rise to speech perception difficulties beyond that expected for the observed degree of hearing loss. For many cases of ANSD, the underlying molecular pathology and the site of lesion remain unclear. The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.3, although the causative gene has yet to be identified.

ROOT UV-B SENSITIVE (RUS) genes exist in most eukaryotic organisms, and encode proteins that contain a DUF647 (domain of unknown function 647). Although the RUS genes are known to play essential roles in Arabidopsis seedling development, their precise functions are not well understood in other plants, including rice.

The CD34+CD38- subset of AML cells is enriched for resistance to current chemotherapeutic agents and considered to contribute to disease progression and relapse in Acute Myeloid Leukaemia (AML) patients following initial treatment.

Cisplatin is one of the most active cytotoxic agents for non-small cell lung cancer (NSCLC) treatment. However, the development of cisplatin resistance is common. Bu-Zhong-Yi-Qi decoction (BZYQD), a Chinese traditional herbal medicine, is widely used for the enhancement of antitumor effect in other medications. In this study, we evaluated the effect and drug-resistance reversal mechanism of BZYQD combined with cisplatin on cisplatin-resistant A549/DDP cells. Our results showed that BZYQD exhibited direct cytotoxic and chemosensitizing effects. Cotreatment with BZYQD and cisplatin induced intrinsic apoptotic pathways which were measured by condensed nuclear chromatin, Annexin V/PI apoptosis assay, and apoptosis related proteins expression. In addition, cotreatment with BZYQD and cisplatin also activated autophagy, as indicated by an increase in LC3 puncta, classical autophagosomes and/or autolysosomes, and an accumulation of LC3-II and ATG7 protein. Finally, cotreatment with BZYQD and cisplatin resulted in the generation of ROS and scavenging ROS by NAC almost completely suppressing cell death. These results suggest that cotreatment with BZYQD and cisplatin might reverse cisplatin resistance by inducing ROS accumulation, which activates apoptosis and autophagy by oxidative stress. The combination of BZYQD and cisplatin may represent a novel approach in treatment for NSCLC and thus offer a new target for chemotherapy.

The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma membrane, like WT P2X2, but exhibit a significantly reduced response to ATP stimulation. Both mutants reduced the channel conductance, but G353R mutation also altered the voltage dependency. Co-expression with WT P2X2 could restore the response to ATP. As the ratio of WT P2X2 vs. mutants increased, the response to ATP was also increased. Computer modeling confirmed that both V60L and G353R dominant-deafness mutant subunits do not have any negative effect on WT P2X2 subunit, when assembled as a heterotrimer. Improper docking or defective gating is the more likely mechanism for impaired channel function by these P2X2 deafness mutations. These results suggest that P2X2 dominant deafness mutations do not have negative effects on WT P2X2 isoforms, and that adding additional WT P2X2 could rescue the lost channel function caused by the deafness mutations. These P2X2 dominant deafness mutations may have negative-effects on other partners leading to hearing loss.

The chloroplast genomic information was obtained from three wild Solanum and four hybrids by chloroplast genome sequencing. The chloroplast genomes of the seven samples comprise of a circular structure and sizes from 155,581 to 155,612 bp and composed of 130 genes. The genome structures of the two hybrids were identical, while the other two hybrids showed 2 bp differences in the LSC when compared with their maternal parent. The total sites of SNP and InDel were 39-344 and 54-90, respectively. With the exception of one hybrid with two additional sites, the other hybrids were identical to their maternal.

Background: Although there have been many epidemiological studies, research focusing on psoriasis' health burden on a global scale is still lacking. Trends and variations in the global health burden of psoriasis are evaluated by time, age, gender, geographical location, and socioeconomic status, using disability-adjusted life years (DALYs) from the Global Burden of Disease Study. Methods: The health burden of psoriasis was evaluated by DALYs, which combined years lost to disability (a morbidity component) with years of life lost (a mortality component). The global and national DALYs number, crude DALYs rate, and age-standardized DALYs rate were obtained from the GBD 2017 study database. The corresponding human development index (HDI) was collected from the United Nations Development Programme. Results: From 1990 to 2017, the DALYs number and crude DALYs rate due to psoriasis increased by 73 and 22%, respectively. In comparison, the age-standardized DALYs rate showed a slight increase. Patients in the age range of 65-69 years bear a more significant psoriasis burden. Both males and females showed an increasing trend in burden caused by psoriasis over the past 27 years, with females bearing a more significant psoriasis burden than males. The health burden of psoriasis was substantially unequal in geography with a Gini coefficient of 0.27. The concentration indexes indicated a socioeconomic associated inequality in psoriasis burden with values of 0.22, accounting for 48.64% variance across countries (R2 = 0.4864, p < 0.001). Between-nation inequality in the distribution of psoriasis burden continued to decline throughout the past 27 years. Gini coefficients of psoriasis burden decreased from 0.280 in 1990 to 0.265 in 2017. The concentration indexes indicated the same trend with 0.236 in the 1990s and 0.223 in 2017. Conclusions: Global health progress in psoriasis together with inequality in the past few decades. Although the inequality of psoriasis burden has shown some improvement during the past 27 years, disparities still exist in age, gender, geographical location, as well as socioeconomic status. The findings of this study highlight the global importance of psoriasis and is important in policy planning for psoriasis services on a global scale.

Moderate leaf rolling helps to form the ideotype of rice. In this study, six independent OsRUS1-GFP overexpression (OsRUS1-OX) transgenic rice lines with rapid and dynamic leaf rolling phenotype in response to sunlight were constructed. However, the mechanism is unknown. Here, RNA-Seq approach was utilized to identify differentially expressed genes between flag leaves of OsRUS1-OX and wildtype under sunlight. 2920 genes were differentially expressed between OsRUS1-OX and WT, of which 1660 upregulated and 1260 downregulated. Six of the 16 genes in GO: 0009415 (response to water stimulus) were significantly upregulated in OsRUS1-OX. The differentially expressed genes between WT and OsRUS1-OX were assigned to 110 KEGG pathways. 42 of the 222 genes in KEGG pathway dosa04075 (Plant hormone signal transduction) were differentially expressed between WT and OsRUS1-OX. The identified genes in GO:0009415 and KEGG pathway dosa04075 were good candidates to explain the leaf rolling phenotype of OsRUS1-OX. The expression patterns of the 15 genes identified by RNA-Seq were verified by qRT-PCR. Based on transcriptomic and qRT-PCR analysis, a mechanism for the leaf rolling phenotype of OsRUS1-OX was proposed. The differential expression profiles between WT and OsRUS1-OX established by this study provide important insights into the molecular mechanism behind the leaf rolling phenotype of OsRUS1-OX.

In order to perfect the design strategy of messenger RNA (mRNA) vaccines against the H5N1 influenza virus, we investigated whether different antigen designs and the use of adjuvants could improve the immune effect of mRNA vaccines. We designed three different forms of antigen genes, including Flu [H1/H3/H5/B-HA2(aa90~105)-M2e(24aa)], Flu-Fe (Fe, ferritin), and CD5-Flu-Fe (CD5, a secretion signal peptide). Meanwhile, R848 (Requimod) was selected as the adjuvant of the mRNA vaccine. We prepared cationic lipid nanoparticles for mRNA delivery, named LNP-Man (mannose-modified lipid nanoparticles). Cell transfection results showed that Flu-Fe/CD5-Flu-Fe containing ferritin could express the target antigens HA2 and M2e more efficiently than Flu. In the mice immune experiment, five immune groups (LNP-Man/Flu, LNP-Man/Flu-Fe, LNP-Man/CD5-Flu-Fe, LNP-Man/Flu-Fe+R848, and LNP-Man/CD5-Flu-Fe+R848) and two control groups (LNP-Man, PBS) were set up. After being infected with the 1×LD50 H5N1 avian influenza virus, the survival rate of the mice in the LNP-Man/CD5-Flu-Fe, LNP-Man/Flu-Fe+R848, and LNP-Man/CD5-Flu-Fe+R848 were 100%. More importantly, in LNP-Man/Flu-Fe+R848 and LNP-Man/CD5-Flu-Fe+R848 groups, there was no residual virus detected in the mice lung tissue on the 5th day postchallenge. Overall, this study provides a new idea for the design of H5N1 avian influenza virus mRNA vaccines in terms of antigen designs and adjuvant selection.

The tumor suppressor p53 plays a pivotal role in tumor prevention. The activity of p53 is mainly restrained by the ubiquitin E3 ligase Mdm2. However, it is not well understood how the Mdm2-p53 pathway is intricately regulated. Here we report that the RNA binding protein RALY functions as an oncogenic factor in lung cancer. RALY simultaneously binds to Mdm2 and the deubiquitinating enzyme USP7. Via these interactions, RALY not only stabilizes Mdm2 by stimulating the deubiquitinating activity of USP7 toward Mdm2 but also increases the trans-E3 ligase activity of Mdm2 toward p53. Consequently, RALY enhances Mdm2-mediated ubiquitination and degradation of p53. Functionally, RALY promotes lung tumorigenesis, at least partially, via negative regulation of p53. These findings suggest that RALY destabilizes p53 by modulating the function of Mdm2 at multiple levels. Our study also indicates a critical role for RALY in promoting lung tumorigenesis via p53 inhibition.

Pyocyanin, a secreted virulence factor, plays an essential role during Pseudomonas aeruginosa infection. Infection of the central nervous system by this bacterium results in high mortality, but the studies on its mechanism are still rather limited. In this study, we first evaluate the neuronal damage caused by pyocyanin exposure in neuronal HT22 cells. Pyocyanin leads to mitochondrial syndrome and antioxidant defense disruption, therefore increasing intercellular reactive oxygen species (ROS) production. Several typical superior antioxidant polyphenols effectively protect against pyocyanin-induced neuronal cell damage. These findings suggest the neuronal protective activity more or less relies on the structure, rather than the residues. Pre-incubation of catechin activates the essential pathway, indicating inverse correlation of ERK and AMPK phosphorylation participates in this process. These data outline a novel strategy to eliminate intracellular generated ROS. The investigated candidates could be potentially used as therapeutic agents against various ROS-related neurological diseases.

The aim of this study was to determine the diagnostic values of kidney shear wave velocity (SWV) and bone morphogenetic protein-7 (BMP-7), and their correlation in the diagnosis of early diabetic kidney disease.

To investigate the influence of the mitochondrial calcium uniporter on the mitochondrial permeability transition pore, the present study observed mitochondrial morphology in cortical neurons isolated from adult rats using transmission electron microscopy, and confirmed the morphology and activity of isolated mitochondria by detecting succinic dehydrogenase and monoamine oxidase, two mitochondrial enzymes. Isolated mitochondria were treated with either ruthenium red, an inhibitor of the uniporter, spermine, an activator of the uniporter, or in combination with cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. Results showed that ruthenium red inhibited CaCl2-induced mitochondrial permeability transition pore opening, spermine enhanced opening, and cyclosporin A attenuated the effects of spermine. Results demonstrated that the mitochondrial calcium uniporter plays a role in regulating the mitochondrial permeability transition pore in mitochondria isolated from the rat brain cortex.

Connexin26 (Cx26) and Cx30 are predominant isoforms of gap junction channels in the cochlea and play a critical role in hearing. In this study, the cellular distributions of Cx26 and Cx30 in the cochlear sensory epithelium of guinea pigs were examined by immunofluorescent staining and confocal microscopy in whole mounts of the cochlear sensory epithelium and dissociated cell preparations. The expression of Cx26 and Cx30 demonstrated a longitudinal gradient distribution in the epithelium and was reduced threefold from the cochlear apex to base. The reduction was more pronounced in the Deiters cells and pillar cells than in the Hensen cells. Cx26 was expressed in all types of supporting cells, but little Cx30 labeling was seen in the Hensen cells. Cx26 expression in the Hensen cells was concentrated mainly in the second and third rows, forming a distinct band along the sensory epithelium at its outer region. In the dissociated Deiters cells and pillar cells, Cx30 showed dense labeling at the cell bodies and processes in the reticular lamina. Cx26 labeling largely overlapped that of Cx30 in these regions. Cx26 and Cx30 were also coexpressed in the gap junctional plaques between Claudius cells. Neither Cx26 nor Cx30 labeling was seen in the hair cells and spiral ganglion neurons. These observations demonstrate that Cx26 and Cx30 have a longitudinal gradient distribution and distinct cellular expression in the auditory sensory epithelium. This further supports our previous reports that Cx26 and Cx30 can solely and concertedly perform different functions in the cochlea.

Chronic tinnitus and hyperacusis often develop with age-related hearing loss presumably due to aberrant neural activity in the central auditory system (CAS) induced by cochlear pathologies. However, the full spectrum of physiological changes that occur in the CAS as a result age-related hearing loss are still poorly understood. To address this issue, neurophysiological measures were obtained from the cochlea and the inferior colliculus (IC) of 2, 6 and 12 month old C57BL/6J mice, a mouse model for early age-related hearing loss. Thresholds of the compound action potentials (CAP) in 6 and 12 month old mice were significantly higher than in 2 month old mice. The sound driven and spontaneous firing rates of IC neurons, recorded with 16 channel electrodes, revealed mean IC thresholds of 22.8 ± 6.5 dB (n = 167) at 2 months, 37.9 ± 6.2 dB (n = 132) at 6 months and 47.1 ± 15.3 dB (n = 151) at 12 months of age consistent with the rise in CAP thresholds. The characteristic frequencies (CF) of IC neurons ranged from 3 to 32 kHz in 2 month old mice; the upper CF ranged decreased to 26 kHz and 16 kHz in 6 and 12 month old mice respectively. The percentage of IC neurons with CFs between 8 and 12 kHz increased from 36.5% in 2 month old mice, to 48.8% and 76.2% in 6 and 12 month old mice, respectively, suggesting a downshift of IC CFs due to the high-frequency hearing loss. The average spontaneous firing rate (SFRs) of all recorded neurons in 2 month old mice was 3.2 ± 2.5 Hz (n = 167). For 6 and 12 month old mice, the SFRs of low CF neurons (<8 kHz) was maintained at 3-6 spikes/s; whereas SFRs of IC neurons with CFs > 8 kHz increased to 13.0 ± 15.4 (n = 68) Hz at 6 months of age and then declined to 4.8 ± 7.4 (n = 110) spikes/s at 12 months of age. In addition, sound-evoked activity at suprathreshold levels at 6 months of age was much higher than at 2 and 12 months of age. To evaluate the behavioral consequences of sound evoked hyperactivity in the IC, the amplitude of the acoustic startle reflex was measured at 4, 8 and 16 kHz using narrow band noise bursts. Acoustic startle reflex amplitudes in 6 and 12 month old mice (n = 4) were significantly larger than 2 month old mice (n = 4) at 4 and 8 kHz, but not 16 kHz. The enhanced reflex amplitudes suggest that high-intensity, low-frequency sounds are perceived as louder than normal in 6 and 12 month old mice compared to 2 month olds. The increased spontaneous activity, particularly at 6 months, may be related to tinnitus whereas the increase in sound-evoked activity and startle reflex amplitudes may be related to hyperacusis.

Apoptosis and autophagy are known to play important roles in cancer development. It has been reported that HVJ-E induces apoptosis in cancer cells, thereby inhibiting the development of tumors. To define the mechanism by which HVJ-E induces cell death, we examined whether HVJ-E activates autophagic and apoptotic signaling pathways in HeLa cells.

While non-alcoholic fatty liver disease (NAFLD) has been widely studied, the pathophysiology of lean NAFLD, the critical NAFLD subgroup, remains elusive. This study aimed to clarify the association between polymorphisms of GCKR, waist circumference, and the odds of lean NAFLD in the elderly Chinese Han population who live in the Zhangjiang community center of Shanghai, China. Three single nucleotide polymorphisms (SNPs), including rs1260326, rs780093, and rs780094, were genotyped in MassARRAY Analyzer. The association between SNPs with waist circumference in five genetic models was analyzed and rechecked by the logistic regression analysis. Mediation models were established to evaluate whether the waist circumstance can mediate the association between SNPs and lean NAFLD. In this study, the frequency of the C allele of rs1260326, rs780093, and rs780094 was significantly lower in lean NAFLD individuals than in lean non-NAFLD ones. The association between rs1260326 in GCKR and the odds of lean NAFLD was mediated via waist circumference after adjusting gender and age in the elderly Chinese Han population (β = 1.196, R2 = 0.043, p = 0.020). For the first time, this study examined the mediating effect of waist circumference on the association between rs1260326 in GCKR and the odds of lean NAFLD (β = 0.0515, 95% CI 0.0107-0.0900, p = 0.004). It may contribute to illustrating the pathogenesis of lean NAFLD and indicate that waist circumference management might improve lean NAFLD control.

The risk factors of chronic kidney disease were analyzed by using the region of interest quantitative technology of color Doppler combined with QLab software, and a Nomogram was established to conduct an individualized assessment of patients with chronic kidney disease.

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.