Chromosome-scale genome assemblies of sexually dimorphic male and female Acrossocheilus fasciatus.

Acrossocheilus fasciatus is a stream-dwelling fish species of the Barbinae subfamily. It is valued for its colorfully striped appearance and delicious meat. This species is also characterized by apparent sexual dimorphism and toxic ovum. Biology and aquaculture researches of A. fasciatus are hindered by the lack of a high-quality reference genome. Here, we report chromosome-level genome assemblies of the male and female A. fasciatus. The HiFi-only genome assemblies for both female and male individuals were 899.13 Mb (N50 length of 32.58 Mb) and 885.68 Mb (N50 length of 33.06 Mb), respectively. Notably, a substantial proportion of the assembled sequences, accounting for 96.15% and 98.35% for female and male genomes, respectively, were successfully anchored onto 25 chromosomes utilizing Hi-C data. We annotated the female assembly as a reference genome and identified a total of 400.62 Mb (44.56%) repetitive sequences, 27,392 protein-coding genes, and 35,869 ncRNAs. The high-quality male and female reference genomes will provide genomic resources for developing sex-specific molecular markers, inform single-sex breeding, and elucidate genetic mechanisms of sexual dimorphism.

Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis.

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation (LT) is critical for precise clinical management strategies. Here, we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells (PBMCs) collected from LT patients (with and without acute cellular rejection [ACR]) at 13 time points. Validation was performed in two independent cohorts with additional LT patients and healthy controls. Our study revealed a four-phase recovery process after LT and delineated changes in immune cell composition, expression programs, and interactions along this process. The intensity of the immune response differs between the ACR and non-ACR patients. Notably, the newly identified inflamed NK cells, CD14+RNASE2+ monocytes, and FOS-expressing monocytes emerged as predictive indicators of ACR. This study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery, providing a four-phase framework that aids the clinical management of LT patients.

Dextran sulfate acting as a chaperone-like component on inhibition of amorphous aggregation and enhancing thermal stability of ovotransferrin.

The tendency of ovotransferrin (OVT) to unfold and aggregate under 60 °C severely restricted sterilization temperature during egg processing. Searching for efficient strategies to improve OVT thermal stability is essential for improving egg product quality and processing suitability. Here, we investigated the effect of sulfate polysaccharide (dextran sulfate, DS) on heat-induced aggregation of OVT. We found that DS can effectively suppress amorphous aggregation of OVT at pH 7.0 after heating. Strikingly, the addition of 5 µM DS fully suppressed insoluble aggregates formation of 0.5 mg/mL OVT. Structure analysis confirmed that DS preserves nearly the entire secondary and tertiary structure of OVT during heating. The steric hindrance effect arising from strong electrostatic interactions between OVT and DS, coupled with reduced OVT hydrophobicity, is the underlying mechanism in suppressing protein-protein interactions, thus enhancing thermal stability. These findings suggest DS could act as protein stabilizers and chaperones, enhancing the thermostability of heat-sensitive proteins.

Dynamic monitoring of aboveground biomass in inner Mongolia grasslands over the past 23 Years using GEE and analysis of its driving forces.

Aboveground biomass (AGB) in grasslands directly reflects the net primary productivity, making it a sensitive indicator of grassland resource quality and ecological degradation. Accurately estimating AGB over large regions to reveal long-term AGB evolution trends remains a formidable challenge. In this study, we divided Inner Mongolia Autonomous Region (IMAR) grasslands into three study regions based on their spatial distribution of grassland types. We combined remote sensing data with ground-based sample data collected over the past 19 years from 6114 field plots using the Google Earth Engine platform. We constructed random forest (RF) and traditional regression AGB inversion models for each region and selected the best-performing model through accuracy assessment to estimate IMAR grassland AGB for the period 2000-2022. We also examined the trends in AGB changes and identified the driving forces affecting IMAR grasslands through the application of Theil-Sen estimation, Mann-Kendall trend analysis, and the Geodetector model. The main findings are as follows: (1) Compared with the univariate parametric traditional regression model, the AGB monitoring accuracy of the multivariate non-parametric RF model in the three study regions increased by 5.94%, 5.08% and 19.14%, respectively. (2) The average AGB per unit area of IMAR grasslands from 2000 to 2022 was 731.41 kg/hm2, with alpine meadow having the highest average AGB (1271.70 kg/hm2) and temperate grassland desertification having the lowest (469.06 kg/hm2). IMAR grasslands exhibited an overall increasing trend in AGB over the past 23 years (6.01 kg/hm2•yr), with the increasing trend covering 83.52% of the grassland area and the decreasing trend covering 16.48%. (3) Spatially, IMAR grassland AGB showed a gradual decline from northeast to southwest and exhibited an increasing trend with increasing longitude (45.423 kg/hm2 per degree) and latitude (71.9 kg/hm2 per degree). (4) Meteorological factors were the most significant factors affecting IMAR grassland AGB, with precipitation (five-year average q value of 0.61) being the most prominent. In the western part of IMAR, where precipitation is consistently limited throughout the year, the primary drivers of influence were human activities, with particular emphasis on the number of livestock (with a five-year average q value of 0.44). It is evident that reducing human activity disturbance and pressure in fragile grassland areas or implementing near-natural restoration measures will be beneficial for the sustainable development of grassland ecosystems. The results of this research hold substantial reference importance for the protection and restoration of grasslands, the supervision and administration of grassland resources, as well as the development of policies related to grassland management.

Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections.

The emergence of new coronaviruses poses a significant threat to animal husbandry and human health. Porcine epidemic diarrhea virus (PEDV) is considered a re-emerging porcine enteric coronavirus, which causes fatal watery diarrhea in piglets. Currently, there are no effective drugs to combat PEDV. Drug repurposing screens have emerged as an attractive strategy to accelerate antiviral drug discovery and development. Here, we screened 206 natural products for antiviral activity using live PEDV infection in Vero cells and identified ten candidate antiviral agents. Among them, Tubercidin, a nucleoside analog derived from Streptomyces tubercidicus, showed promising antiviral activity against PEDV infection. Furthermore, we demonstrated that Tubercidin exhibited significant antiviral activity against both classical and variant PEDV. Time of addition assay showed that Tubercidin displayed a significant inhibitory effect on viral post-entry events but not during other periods. Molecular docking analysis indicated that Tubercidin had better docking efficiency and formed hydrophobic interactions with the active pocket of RNA-dependent RNA polymerase (RdRp) of PEDV and other nidoviruses. Additionally, Tubercidin can effectively suppress other porcine nidoviruses, such as SADS-CoV and PRRSV, demonstrating its broad-spectrum antiviral properties. In summary, our findings provide valuable evidence for the antiviral activity of Tubercidin and offer insights into the development of new strategies for the prevention and treatment of coronavirus infections.

The level of sulfate substitution of polysaccharide regulates thermal-induced egg white protein gel properties: The characterization of gel structure and intermolecular forces.

Sulfated polysaccharides exhibit great potential for regulating protein-protein interactions. In the present study, three sulfated microcrystalline cellulose (MCS) with different degrees of sulfate substitution (DSS: 0.33, 0.51, 0.61) were synthesized and the effects of DSS on the regulation of egg white protein (EWP) aggregation and gelation properties were investigated. The results found that the improvement of protein mechanical properties by MCS is closely related to the level of sulfate substitution. The higher the DSS, the more ordered protein aggregates and compact gel network formed during heating as compared to that of pure EWP. Lower DSS (0.33) shows little effect on the mechanical properties of EWP. Furthermore, all the MCSs could significantly destroy the tertiary structure of protein molecules during heating, while for the secondary structure, MCS with higher DSS (0.51 and 0.61) could effectively control the decreasing tendency of α-helix and increasing tendency of ß-sheet. Hydrophobic interactions were recognized as the major intermolecular force in the compact mixed gels (EWP/MCS2 and EWP/MCS3 gels, DSS was 0.51 and 0.61, respectively). These findings provide a vital understanding of the gelling mechanism of the protein-polysaccharide system and the application of sulfated polysaccharides in protein-based food products.

Designation and characterization of cold-set egg white protein/dextran sulfate hydrogel for curcumin entrapment.

This study aimed to design a cold-set hydrogel of egg white protein (EWP) with good mechanical properties for encapsulating curcumin. Dextran sulfate (DS) and transglutaminase (TGase) were used to control the aggregation and gelation behavior of EWP at preheating step and gelation step, respectively. The optimum soluble protein aggregate size was obtained in the EWP/DS mixture at a mass ratio of 10 under 85 °C preheated (HED10). The presence of TGase further enhanced the cross-linking degree between protein aggregates during the gelation step. The highest gel hardness was found in HED10 hydrogel with TGase, which is almost 10 times the pure EWP gel. Besides, the HED hydrogels effectively slowed down the release rate of curcumin in gastrointestinal digestion. This work provides a theoretical basis for the development of cold-set EWP hydrogel with good mechanical strength by sulfated polysaccharide addition and TGase cross-linking as encapsulation delivery systems.

The prognostic value of the GPAT/AGPAT gene family in hepatocellular carcinoma and its role in the tumor immune microenvironment.

Background: Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide. Hepatocellular carcinoma accounts for an estimated 90% of all liver cancers. Many enzymes of the GPAT/AGPAT family are required for the synthesis of triacylglycerol. Expression of AGPAT isoenzymes has been reported to be associated with an increased risk of tumorigenesis or development of aggressive phenotypes in a variety of cancers. However, whether members of the GPAT/AGPAT gene family also influence the pathophysiology of HCC is unknown. Methods: Hepatocellular carcinoma datasets were obtained from the TCGA and ICGC databases. Predictive models related to the GPAT/AGPAT gene family were constructed based on LASSO-Cox regression using the ICGC-LIRI dataset as an external validation cohort. Seven immune cell infiltration algorithms were used to analyze immune cell infiltration patterns in different risk groups. IHC, CCK-8, Transwell assay, and Western blotting were used for in vitro validation. Results: Compared with low-risk patients, high-risk patients had shorter survival and higher risk scores. Multivariate Cox regression analysis showed that risk score was a significant independent predictor of overall survival (OS) after adjustment for confounding clinical factors (p < 0.001). The established nomogram combined risk score and TNM staging to accurately predict survival at 1, 3, and 5 years in patients with HCC with AUC values of 0.807, 0.806, and 0.795, respectively. This risk score improved the reliability of the nomogram and guided clinical decision-making. In addition, we comprehensively analyzed immune cell infiltration (using seven algorithms), response to immune checkpoint blockade, clinical relevance, survival, mutations, mRNA expression-based stemness index, signaling pathways, and interacting proteins related to the three core genes of the prognostic model (AGPAT5, LCLAT1, and LPCAT1). We also performed preliminary validation of the differential expression, oncological phenotype, and potential downstream pathways of the three core genes by IHC, CCK-8, Transwell assay, and Western blotting. Conclusion: These results improve our understanding of the function of GPAT/AGPAT gene family members and provide a reference for prognostic biomarker research and individualized treatment of HCC.

Prognostic factors of hearing outcome in patients with chronic suppurative otitis media following tympanoplasty: a retrospective cohort study.

Background: Research on the factors affecting the functional outcome of tympanoplasty in chronic suppurative otitis media (CSOM) is limited. This study aimed to investigate the prognostic factors of hearing outcome in CSOM patients following tympanoplasty. The multivariate logistic regression analysis is used to evaluate the influence of demographic, audiological, clinical and disease factors on the postoperative prognosis of CSOM. Methods: A total of 179 CSOM patients who received surgery between January 2016 and December 2019 were retrospectively included. The inclusion criteria are mainly based on clinical classification of otitis media and surgical classification guidelines [2012]. These patients were divided into an effective group (n=132) and a non-effective group (n=47) according to their postoperative air-bone gap (ABG) value. Multivariate analysis was performed according to the pure tone hearing results 1 week before operation and 4 weeks after operation. Results: The type of preoperative hearing impairment, middle ear cholesteatoma, ossicular chain status, tympanic perforation site, repair material, tympanum sclerosis, and surgical methods were significantly different between the effective and non-effective groups (all P<0.01). The speech reception threshold (SRT) (36.88±15.54 vs. 27.68±13.75, P<0.001) and ABG (18.53±9.30 vs. 10.89±5.07, P<0.001) values were markedly reduced after surgery in the effective group but not in the non-effective group. Furthermore, the postoperative decreases in the SRT (9.20±9.69 vs. 2.021±7.34, P<0.001) and ABG (7.64±8.57 vs. 0.45±7.322, P<0.001) values were considerably higher in the effective group than the non-effective group. After multivariate logistic regression analysis, we found that the type of preoperative hearing impairment [P=0.031; odds ratio (OR) =2.378], ossicular chain status (P=0.002; OR =4.430). Conclusions: Our research shows that the curative effect of conductive deafness before operation is 2.378 times better than that of mixed deafness, the curative effect of complete and unfixed ossicular chain before operation is 1.080 times better than that of interrupted ossicular chain, and the curative effect of complete ossicular chain but fixed ossicular chain is 4.430 times better than that of interrupted ossicular chain. Our findings may help to predict the postoperative prognosis of patients, thus facilitating the development of corresponding treatment strategies.

Preparation of a Single-Chain Antibody against Nucleocapsid Protein of Porcine Deltacoronavirus by Phage Display Technology.

Porcine deltacoronavirus (PDCoV) mainly causes severe diarrhea and intestinal pathological damage in piglets and poses a serious threat to pig farms. Currently, no effective reagents or vaccines are available to control PDCoV infection. Single-chain fragment variable (scFv) antibodies can effectively inhibit virus infection and may be a potential therapeutic reagent for PDCoV treatment. In this study, a porcine phage display antibody library from the peripheral blood lymphocytes of piglets infected with PDCoV was constructed and used to select PDCoV-specific scFv. The library was screened with four rounds of biopanning using the PDCoV N protein, and the colony with the highest affinity to the PDCoV N protein was obtained (namely, N53). Then, the N53-scFv gene fragment was cloned into plasmid pFUSE-hIgG-Fc2 and expressed in HEK-293T cells. The scFv-Fc antibody N53 (namely, scFv N53) was purified using Protein A-sepharose. The reactive activity of the purified antibody with the PDCoV N protein was confirmed by indirect enzyme-linked immunosorbent assay (ELISA), western blot and indirect immunofluorescence assay (IFA). Finally, the antigenic epitopes that the scFv N53 recognized were identified by a series of truncated PDCoV N proteins. The amino acid residues 82GELPPNDTPATTRVT96 of the PDCoV N protein were verified as the minimal epitope that can be recognized by the scFv-Fc antibody N53. In addition, the interaction between the scFv-Fc antibody N53 and the PDCoV N protein was further analyzed by molecule docking. In conclusion, our research provides some references for the treatment and prevention of PDCoV.

The Correlation Between Detection Value of Distortion-Product Otoacoustic Emissions and the Early Prognosis of Sudden Sensorineural Hearing Loss.

BACKGROUND: To explore the correlation between the detection value of distortion-product otoacoustic emissions and the early prognosis of sudden sensorineural hearing loss. METHODS: Seventy-eight patients with first-onset sudden sensorineural hearing loss (all frequencies) from April 2018 to July 2019 were included in this study. Distortion-product otoacoustic emissions and pure-tone audiometry tests were performed at days 0, 3, and 6 of admission. Repeated measures analysis of variance was performed to evaluate the changes in the signal-to-noise ratio for different distortion-product otoacoustic emissions frequencies over time and the interaction of grouping factors and time factors. RESULTS: The distortion-product otoacoustic emissions evocation rate in the 4 groups was significantly different starting at day 3 of treatment. It was higher in the cured (35.3%) and obviously effective (20.0%) groups than in the other 2 groups (0%, 0%). At the 6 f2 frequencies of 1105 Hz, 1560 Hz, 2211 Hz, 3125 Hz, 4416 Hz, and 8837 Hz, the signal-to-noise ratio was different among the groups (P < .05) and was notably higher in the cured group. The analysis of the signal-to-noise ratio change before and after treatment at the intermediate f2 frequencies of 1105 Hz, 1560 Hz, and 2211 Hz in all patients indicated a linear correlation between the signal-to-noise ratio change and the pure-tone hearing threshold change, with a correlation coefficient of 0.481. CONCLUSION: Distortion-product otoacoustic emissions evocation in the early stage (within 3 days of treatment) or the signal-to-noise ratio trend over time at intermediate frequencies may predict the prognosis of sudden sensorineural hearing loss.

Cell type-specific histone acetylation profiling of Alzheimer's disease subjects and integration with genetics.

We profile genome-wide histone 3 lysine 27 acetylation (H3K27ac) of 3 major brain cell types from hippocampus and dorsolateral prefrontal cortex (dlPFC) of subjects with and without Alzheimer's Disease (AD). We confirm that single nucleotide polymorphisms (SNPs) associated with late onset AD (LOAD) show a strong tendency to reside in microglia-specific gene regulatory elements. Despite this significant colocalization, we find that microglia harbor more acetylation changes associated with age than with amyloid-ß (Aß) load. In contrast, we detect that an oligodendrocyte-enriched glial (OEG) population contains the majority of differentially acetylated peaks associated with Aß load. These differential peaks reside near both early onset risk genes (APP, PSEN1, PSEN2) and late onset AD risk loci (including BIN1, PICALM, CLU, ADAM10, ADAMTS4, SORL1, FERMT2), Aß processing genes (BACE1), as well as genes involved in myelinating and oligodendrocyte development processes. Interestingly, a number of LOAD risk loci associated with differentially acetylated risk genes contain H3K27ac peaks that are specifically enriched in OEG. These findings implicate oligodendrocyte gene regulation as a potential mechanism by which early onset and late onset risk genes mediate their effects, and highlight the deregulation of myelinating processes in AD. More broadly, our dataset serves as a resource for the study of functional effects of genetic variants and cell type specific gene regulation in AD.

Porcine Deltacoronavirus Utilizes Sialic Acid as an Attachment Receptor and Trypsin Can Influence the Binding Activity.

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhea in nursing piglets. Studies showed that PDCoV uses porcine aminopeptidase N (pAPN) as an entry receptor, but the infection of pAPN-knockout cells or pigs with PDCoV revealed that pAPN might be not a critical functional receptor, implying there exists an unidentified receptor involved in PDCoV infection. Herein, we report that sialic acid (SA) can act as an attachment receptor for PDCoV invasion and facilitate its infection. We first demonstrated that the carbohydrates destroyed on the cell membrane using NaIO4 can alleviate the susceptibility of cells to PDCoV. Further study showed that the removal of SA, a typical cell-surface carbohydrate, could influence the PDCoV infectivity to the cells significantly, suggesting that SA was involved in the infection. The results of plaque assay and Western blotting revealed that SA promoted PDCoV infection by increasing the number of viruses binding to SA on the cell surface during the adsorption phase, which was also confirmed by atomic force microscopy at the microscopic level. In in vivo experiments, we found that the distribution levels of PDCoV and SA were closely relevant in the swine intestine, which contains huge amount of trypsin. We further confirmed that SA-binding capacity to PDCoV is related to the pre-treatment of PDCoV with trypsin. In conclusion, SA is a novel attachment receptor for PDCoV infection to enhance its attachment to cells, which is dependent on the pre-treatment of trypsin on PDCoV. This study paves the way for dissecting the mechanisms of PDCoV-host interactions and provides new strategies to control PDCoV infection.

Characteristic Volatile Fingerprints of Four Chrysanthemum Teas Determined by HS-GC-IMS.

Volatile composition is an important feature that determines flavor, which actively affects the overall evaluation of chrysanthemum tea. In this study, HS-GC-IMS (headspace-gas chromatography-ion mobility spectrometry) was performed to characterize the volatile profiles of different chrysanthemum tea subtypes. Forty-seven volatiles of diverse chemical nature were identified and quantified. Partial least squares discriminant analysis (PLS-DA) revealed that four chrysanthemum teas were distinct from each other based on their volatile compounds. Furthermore, this work provides reference methods for detecting novel volatile organic compounds in chrysanthemum tea plants and products.

Task-induced brain functional connectivity as a representation of schema for mediating unsupervised and supervised learning dynamics in language acquisition.

INTRODUCTION: Based on the schema theory advanced by Rumelhart and Norman, we shed light on the individual variability in brain dynamics induced by hybridization of learning methodologies, particularly alternating unsupervised learning and supervised learning in language acquisition. The concept of "schema" implies a latent knowledge structure that a learner holds and updates as intrinsic to his or her cognitive space for guiding the processing of newly arriving information. METHODS: We replicated the cognitive experiment of Onnis and Thiessen on implicit statistical learning ability in language acquisition but included additional factors of prosodic variables and explicit supervised learning. Functional magnetic resonance imaging was performed to identify the functional network connections for schema updating by alternately using unsupervised and supervised artificial grammar learning tasks to segment potential words. RESULTS: Regardless of the quality of task performance, the default mode network represented the first stage of spontaneous unsupervised learning, and the wrap-up accomplishment for successful subjects of the whole hybrid learning in concurrence with the task-related auditory language networks. Furthermore, subjects who could easily "tune" the schema for recording a high task precision rate resorted even at an early stage to a self-supervised learning, or "superlearning," as a set of different learning mechanisms that act in synergy to trigger widespread neuro-transformation with a focus on the cerebellum. CONCLUSIONS: Investigation of the brain dynamics revealed by functional connectivity imaging analysis was able to differentiate the synchronized neural responses with respect to learning methods and the order effect that affects hybrid learning.

Isolation, characterization and transcriptome analysis of porcine deltacoronavirus strain HNZK-02 from Henan Province, China.

Porcine deltacoronavirus (PDCoV), an emerging porcine enteropathogenic coronavirus, causes acute watery diarrhea and vomiting in piglets. Here, we isolated a strain of PDCoV from intestinal content of a piglet with severe watery diarrhea on a farm located in Henan Province, named PDCoV strain HNZK-02. Subsequently, the complete genomes of cell-cultured PDCoV HNZK-02 passage 5 and 15 were sequenced and analyzed. There was a continuous 3-nucleotide deletion and 7 amino acid changes in S genes when compared with the other reported PDCoVs. RNA sequencing (RNA-seq)-based transcriptome analysis was used to quantitatively identify differentially expressed genes after PDCoV infection in ST cells. In total, 523 differentially expressed genes (DEGs) were identified, including 62 upregulated genes and 457 downregulated genes. The 62 upregulated genes were associated with TNF signaling pathway, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, IL-17 signaling, chemokine signaling pathway and NF-κB signaling pathway. The significant expressing changed genes, including three antiviral genes (Mx1, OASL, OAS1) and three inflammatory chemokine related genes (CCL5, CXCL8, CXCL10) were further validated using quantitative real-time RT-PCR (qRT-PCR) assay. It showed the consistent expression patterns of the candidate genes with those from RNA-seq. Our results demonstrated that PDCoV infection activates NF-κB signaling pathway and leads to the expression of inflammatory factors, which may be related to TLRs but TLR2 is not a critical factor.In general, these results can help us to confirm the molecular regulation mechanism and also provide us a comprehensive resource of PDCoV infection.

Melatonin reduces radiation damage in inner ear.

The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P < 0.05). DPOAEs showed radiotherapy-induced hearing loss at 8-12 kHz, and hearing loss was greater on day 7 than day 3. However, hearing loss was less in the melatonin groups (P < 0.05). Histopathological examination showed irradiation resulted in breaks and distortion of the cochlear basement membrane, disruption of the stria vascularis, and swelling of outer hair cells. Melatonin reduced these changes. Radiotherapy upregulated prestin mRNA expression. Radiotherapy-induced upregulation of prestin was decreased in the melatonin groups (P < 0.05), and the decrease was greater in the 50 mg/kg melatonin group (P < 0.05). Melatonin protects against radiation-induced cochlear damage by reducing damage to outer hair cells.

Rhodanine derivative LJ001 inhibits TGEV and PDCoV replication in vitro.

Transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) are members of the family coronaviridae and mainly cause acute diarrhea/vomiting, dehydration and mortality in piglets, which lead to huge economic losses to the swine industry. Rhodanine derivative LJ001 has been verified to be effective against some enveloped virus infections in vitro. In this study, we evaluated the antiviral activity of LJ001 towards TGEV and PDCoV replication on swine testicular(ST) cells. Our results showed the 50 % cellular cytotoxicity (CC50) value of LJ001 was 146.4 µM on ST cell. The virus titers of TGEV and PDCoV were obviously decreased in the presence of LJ001 with the concentrations of 3.125 and 12.5 µM, and LJ001 potently inhibited TGEV and PDCoV infection at the replication stages of viral life cycle. Further study indicated that LJ001 inhibited TGEV and PDCoV replication by inhibition of viral RNA and protein synthesis, and reducing virus yields at 12 and 24 h post-inoculation. These data indicated that LJ001 had antiviral activities on TGEV and PDCoV replications in vitro, which may serve as a new candidate for treatment of coronaviruses infections.

Porcine parvovirus nonstructural protein NS1 activates NF-κB and it involves TLR2 signaling pathway.

BACKGROUND: Porcine parvovirus (PPV) is a single-stranded DNA virus that causes porcine reproductive failure. It is of critical importance to study PPV pathogenesis for the prevention and control of the disease. NS1, a PPV non-structural protein, is participated in viral DNA replication, transcriptional regulation, and cytotoxicity. Our previous research showed that PPV can activate nuclear factor kappa B (NF-κB) signaling pathway and then up-regulate the expression of interleukin (IL)-6. OBJECTIVES: Herein, the purpose of this study is to determine whether the non-structural protein NS1 of PPV also has the same function. METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, western blot, immunofluorescence assay and small interfering RNA (siRNA) were used. RESULTS: Our findings demonstrated that PPV NS1 protein can up-regulate the expression levels of IL-6 and tumor necrosis factor-alpha in a dose-dependent manner. Moreover, PPV NS1 protein was found to induce the phosphorylation of IκBα, then leading to the phosphorylation and nuclear translocation of NF-κB. In addition, the NS1 protein activated the upstream pathways of NF-κB. Meanwhile, TLR2-siRNA assay showed TLR2 plays an important role in the activation of NF-κB signaling pathway induced by PPV-NS1. CONCLUSIONS: These findings indicated that PPV NS1 protein induced the up-regulated of IL-6 expression through activating the TLR2 and NF-κB signaling pathways. In conclusion, these findings provide a new avenue to study the innate immune mechanism of PPV infection.

Robust Physically Linked Double-Network Ionogel as a Flexible Bimodal Sensor.

To date, ionogel sensors have aroused the extensive interest as an alternative to hydrogel sensors, as they are promising materials to solve the problems of easy drying and easy freezing. However, the weak mechanical properties of ionogels have seriously hindered their large-scale application. Herein, a robust physically linked double-network ionogel (DN ionogel) was fabricated via interpenetrating a poly(hydroxyethyl acrylate) network into an agarose network in 1-ethyl-3-methylimidazolium chloride. The DN ionogel possessed good mechanical properties, high transparency, extreme temperature tolerance, and excellent self-adhesion. The superior electromechanical properties render the DN ionogel as a perfect candidate to be utilized as a strain sensor to monitor various human activities. In addition, the DN ionogel exhibited reasonably high sensitivity to temperature. Therefore, it is believed that this high performance strain-temperature bimodal sensor offers a promising prospect in flexible intelligent electronics.