Toll-like receptor 4 (TLR4) signal activation of macrophages can lead to endotoxin-induced uveitis (EIU). Previously, our research group has demonstrated a higher expression of TLR4 in vivo during EIU than normal. In this study, we analyzed levels of peritoneal macrophage cytokines from C3H/HeN mice with LPS stimulation in vitro to elucidate the effect of TLR4 on cytokines during EIU.

Phosphorus deficiency is a major limiting factor for crop yield worldwide. Previous studies revealed that PHR1 and it homologues play a key role in regulating the phosphate starvation response in plants. However, the function of PHR homologues in common wheat (Triticum aestivum) is still not fully understood. The aim of the study was to characterize the function of PHR1 genes in regulating phosphate signalling and plant growth in wheat.

The development of alien addition lines is important for transferring useful genes from exotic species into common wheat. A hybrid of common wheat cv. 7182 (2n = 6x = 42, AABBDD) and Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs) via embryo culture produced the novel intergeneric disomic addition line 59-11. The seed morphology of 59-11 resembled the parent 7182 and it exhibited extreme agronomic characteristics, i.e., twin stable spikelets, fertile florets, and multi-kernel clusters. Furthermore, 59-11 produced plump kernels with a high seed-setting percentage during the advanced maturation stage. The line was screened based on genomic in situ hybridization, EST-SSR, EST-STS, and gliadin to identify P. huashanica chromatin in the wheat background. The chromosome number and configuration of 59-11 was 2n = 44 = 22 II and we confirmed the 6Ns disomic chromosome additions based on A-PAGE analysis and molecular markers. The results suggested that the production of twin spikelets and multiple kernels per spike in the wheat-P. huashanica addition line was related to homologous group 6 in the wheat chromosome. This is the first report of the introduction of improved spike traits into common wheat from the alien species P. huashanica and it opens up the possibility of increasing the wheat yield based on this enlarged gene pool.

Cerenkov luminescence tomography (CLT) provides the three-dimensional (3D) radiopharmaceutical biodistribution in small living animals, which is vital to biomedical imaging. However, existing single-spectral and multispectral methods are not very efficient and effective at reconstructing the distribution of the radionuclide tracer. In this paper, we present a semi-quantitative Cerenkov radiation spectral characteristic-based source reconstruction method named the hybrid spectral CLT, to efficiently reconstruct the radionuclide tracer with both encouraging reconstruction results and less acquisition and image reconstruction time.

Through distant crossing, diploid, triploid and tetraploid hybrids of red crucian carp (Carassius auratus red var., RCC♀, Cyprininae, 2n = 100) × topmouth culter (Erythroculter ilishaeformis Bleeker, TC♂, Cultrinae, 2n = 48) were successfully produced. Diploid hybrids possessed 74 chromosomes with one set from RCC and one set from TC; triploid hybrids harbored 124 chromosomes with two sets from RCC and one set from TC; tetraploid hybrids had 148 chromosomes with two sets from RCC and two sets from TC. The 5S rDNA of the three different ploidy-level hybrids and their parents were sequenced and analyzed. There were three monomeric 5S rDNA classes (designated class I: 203 bp; class II: 340 bp; and class III: 477 bp) in RCC and two monomeric 5S rDNA classes (designated class IV: 188 bp, and class V: 286 bp) in TC. In the hybrid offspring, diploid hybrids inherited three 5S rDNA classes from their female parent (RCC) and only class IV from their male parent (TC). Triploid hybrids inherited class II and class III from their female parent (RCC) and class IV from their male parent (TC). Tetraploid hybrids gained class II and class III from their female parent (RCC), and generated a new 5S rDNA sequence (designated class I-N). The specific paternal 5S rDNA sequence of class V was not found in the hybrid offspring. Sequence analysis of 5S rDNA revealed the influence of hybridization and polyploidization on the organization and variation of 5S rDNA in fish. This is the first report on the coexistence in vertebrates of viable diploid, triploid and tetraploid hybrids produced by crossing parents with different chromosome numbers, and these new hybrids are novel specimens for studying the genomic variation in the first generation of interspecific hybrids, which has significance for evolution and fish genetics.

CD24 expression is associated with human colorectal cancer (CRC). Our previous data indicated that CD24 promoted the proliferation and invasion of colorectal cancer cells through the activation of ERK1/2. Since Src family kinases are frequently deregulated in CRC and closely related to the MAPK signaling pathway, we investigated the impact of Lyn, an important member of SFKs, on CD24-induced ERK1/2 activation in CRC.

Degraded fucoidan (F1) was desulfated by DMSO-MeOH. And anion exchange chromatography was performed to fractionate desulfated F1 (ds-F1) into five fractions. Electrospray ionization mass spectrometry (ESI-MS) showed that each fraction contained at least one set of neutral and/or sulfated fucooligosaccharides in the form of methyl glycosides. And the structures of oligomeric fragments were characterized by ESI-CID-MS/MS and ESI-CID-MS/MS/MS. In addition, more structural features were shown by NMR. Therefore, it was concluded that LF1 contained a backbone of (1→3)-linked fucopyranose residues sulfated at C-4 and branched at C-2 by fucopyranose residues and fucoglucuronomannan, fucoglucuronan, galactan and xylan were found in LF-5. Finally, it was concluded that F1 was the middle component, which contained the information of both F0.5 and F2, indicating that the differences between F1 and F0.5, F2 might be derived primarily from the different needs of algae itself.

Stroke is the leading cause of death in China. According to the Chinese Stroke Screening and Prevention Project, 8 main risk factors were assessed and individuals with 3 or more risk factors were identified as high-risk population of stroke. To explore the potential impropriety of counting the risk factors but ignoring the different strength of association of each risk factor, we performed this study.

Serum bilirubin is a potent endogenous antioxidant and has been identified as cardiovascular risk in cohort studies, while the relation to type 2 diabetes (T2D) in the elderly remains unclear. We investigated both cross-sectional and prospective associations between serum bilirubin levels and T2D risk in the Dongfeng-Tongji (DFTJ) cohort, and replicated the prospective findings in a nested case-control study (509 cases and 509 controls) within the Singapore Chinese Health Study (SCHS). In the cross-sectional analysis of DFTJ cohort (15,575 participants with 2,532 diabetes cases), serum bilirubin levels (total, direct and indirect) increased in new on-set diabetes and decreased with the diabetic duration. In the longitudinal analysis of DFTJ cohort (772 incident diabetes cases during 4.5 years of follow-up among 12,530 diabetes-free participants at baseline), positive association was found between direct bilirubin and T2D risk comparing extreme quartiles, similar results were observed in the nested case-control study within SCHS. Total and indirect bilirubin levels were not significantly associated with T2D in either cohort. In conclusion, our findings do not support the protective association between serum bilirubin levels and incident T2D in the middle-aged and elderly adults; instead, direct bilirubin levels were associated with increased risk of T2D.

We detected the mcr-1 gene in 21 (14.8%) Salmonella isolates from pigs at slaughter; 19 were serovar Typhimurium sequence type 34. The gene was located on IncHI2-like plasmids that also harbored IncF replicons and lacked a conjugative transfer region. These findings highlight the need to prevent further spread of colistin resistance in animals and humans.

Rufy3 is a RUN domain-containing protein that has been associated with gastric cancers; however, the role of Rufy3 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that Rufy3 expression was higher in 11/12 fresh CRC tissues than in adjacent normal tissues. Rufy3 induced elevated expression and transactivity of four major oncogenes in CRC. Moreover, siRNA-mediated repression of Rufy3 induced G0/G1 cell cycle arrest, and Rufy3 overexpression enhanced CRC cell proliferation in vitro and in vivo. Furthermore, Rufy3 up-regulation promoted epithelial-mesenchymal transition (EMT) and metastatic phenotypes. Using an established in vitro cell model of 5-fluorouracil-resistant (5-FU) CRC cells, we assessed cellular morphology, molecular changes, and invasion and found that these characteristics were consistent with EMT. Silencing of Rufy3 by siRNA reversed EMT and greatly diminished the invasion of 5-FU-treated cells. In addition, TGF-β1 induced Rufy3 expression in a dose-dependent manner, and Rufy3 knockdown inhibited TGF-β1-induced EMT. In vivo, higher expression of Rufy3 promoted CRC cell invasion and metastasis and induced EMT. Taken together, this work identified that Rufy3 promoted cancer metastasis in CRC cells through EMT induction.

Aquatic mammals, such as cetaceans experience various depths, with accordingly diverse oxygenation, thus, cetaceans have developed adaptations for hypoxia, but mechanisms underlying this tolerance to low oxygen are unclear. Here we analyzed VHL and HIF-2α, in the hypoxia signaling pathway. Variations in VHL are greater than HIF-2α between cetaceans and terrestrial mammals, and beluga whale VHL (BW-VHL) promotes HIF-2α degradation under hypoxia. BW-VHL catalyzes BW-HIF-2α to form K48-linked poly-ubiquitin chains mainly at the lysine 429 of BW-HIF-2α (K429) and induces BW-HIF-2α for proteasomal degradation. W100 within BW-VHL is a key site for BW-VHL functionally and BW-VHL enhances transcriptional activity of BW-HIF-2α under hypoxia. Our data therefore reveal that BW-VHL has a unique function that may contribute to hypoxic adaptation.

iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against bacterial infections, including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the specific iNKT cell ligand α-galactosylceramide or S. pneumoniae infection. In untreated mice, the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae induced CD1d-dependent rapid recruitment of neutrophils out of the vasculature. The neutrophils guided iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell recruitment by blocking CCL17 increased susceptibility to S. pneumoniae infection, suggesting a critical role for the influx of iNKT cells in host defense.

Steady-state visual evoked potentials (SSVEP) based paradigm is a conventional BCI method with the advantages of high information transfer rate, high tolerance to artifacts and the robust performance across users. But the occurrence of mental load and fatigue when users stare at flickering stimuli is a critical problem in implementation of SSVEP-based BCIs. Based on electroencephalography (EEG) power indices α, θ, θ + α, ratio index θ/α and response properties of amplitude and SNR, this study quantitatively evaluated the mental load and fatigue in both of conventional flickering and the novel motion-reversal visual attention tasks. Results over nine subjects revealed significant mental load alleviation in motion-reversal task rather than flickering task. The interaction between factors of "stimulation type" and "fatigue level" also illustrated the motion-reversal stimulation as a superior anti-fatigue solution for long-term BCI operation. Taken together, our work provided an objective method favorable for the design of more practically applicable steady-state evoked potential based BCIs.

Cisplatin is a widely used chemotherapy drug, despite its significant ototoxic side effects. To date, the mechanism of cisplatin-induced ototoxicity remains unclear, and hearing preservation during cisplatin-based chemotherapy in patients is lacking. We found activation of the ATM-Chk2-p53 pathway to be a major determinant of cisplatin ototoxicity. However, prevention of cisplatin-induced ototoxicity is hampered by opposite effects of ATM activation upon sensory hair cells: promoting both outer hair cell death and inner hair cell survival. Encouragingly, however, genetic or pharmacological ablation of p53 substantially attenuated cochlear cell apoptosis, thus preserving hearing. Importantly, systemic administration of a p53 inhibitor in mice bearing patient-derived triple-negative breast cancer protected auditory function, without compromising the anti-tumor efficacy of cisplatin. Altogether, these findings highlight a novel and effective strategy for hearing protection in cisplatin-based chemotherapy.

Gnotobiotic mouse model is generally used to evaluate the efficacy of gut microbiota. Sex differences of gut microbiota are acknowledged, yet the effect of recipient's gender on the bacterial colonization remains unclear. Here we inoculated male and female germ-free C57BL/6J mice with fecal bacteria from a man with short-term vegetarian and inulin-supplemented diet. We sequenced bacterial 16S rRNA genes V3-V4 region from donor's feces and recipient's colonic content. Shannon diversity index showed female recipients have higher bacteria diversity than males. Weighted UniFrac principal coordinates analysis revealed the overall structures of male recipient's gut microbiota were significantly separated from those of females, and closer to the donor. Redundancy analysis identified 46 operational taxonomic units (OTUs) differed between the sexes. The relative abundance of 13 OTUs were higher in males, such as Parabacteroides distasonis and Blautia faecis, while 33 OTUs were overrepresented in females, including Clostridium groups and Escherichia fergusonii/Shigella sonnei. Moreover, the interactions of these differential OTUs were sexually distinct. These findings demonstrated that the intestine of male and female mice preferred to accommodate microbiota differently. Therefore, it is necessary to designate the gender of gnotobiotic mice for complete evaluation of modulatory effects of gut microbiota from human feces upon diseases.

Qishen granules (QSG), a traditional Chinese medicine, have been prescribed widely in the treatment of coronary heart diseases. Previous studies demonstrated that QSG had anti-inflammatory and cardio-protective effects in mice with acute myocardial infarction (AMI). However, the mechanisms by which QSG attenuate inflammation and prevent post-AMI heart failure (HF) are still unclear. In this study, we explored the anti-inflammatory mechanisms of QSG by in vitro and in vivo experiments. A novel inflammatory injury model of H9C2 cells was induced by lipopolysaccharide (LPS)-stimulated macrophage-conditioned media (CM). An animal model of AMI was conducted by ligation of left anterior descending (LAD) coronary artery in mice. We found that QSG inhibited release of cytokines from LPS-stimulated RAW 264.7 macrophages and protected H9C2 cardiac cells against CM-induced injury. In vivo results showed that QSG administration could improve cardiac functions and alter pathological changes in model of AMI. QSG regulated multiple key molecules, including phospholipases A2 (PLA2), cyclooxygenases (COXs) and lipoxygenases (LOXs), in arachidonic acid metabolism pathway. Interestingly, QSG also targeted TNF-α-NF-κB and IL-6-JAK2-STAT3 signaling pathways. Taken together, QSG achieve synergistic effects in mitigating post-AMI HF by regulating multiple targets in inflammatory pathways. This study provides insights into anti-inflammatory therapeutics in managing HF after AMI.

Prolyl oligopeptidase (POP) is a serine endopeptidase that is widely distributed in vivo, particularly in the liver. Significant changes in functional mitochondrial proteins involved with mitochondrial oxidoreductases/transporters and nucleic acid binding proteins were observed after POP inhibition in the liver, which suggested a role of POP in regulating liver energy metabolism. Steatosis in nonalcoholic fatty liver disease (NAFLD) is associated with disturbances in lipid and energy metabolism in hepatocytes. Here, we aimed to study the effect of POP on hepatocyte steatosis.

To investigate brain activity during the reinforcement learning process in social contexts is a topic of increasing research interest. Previous studies have mainly focused on using electroencephalograms (EEGs) for feedback evaluation in reinforcement learning tasks by measuring event-related potentials. Few studies have investigated the time-frequency (TF) profiles of a cue that manifested whether a following feedback is available or not after decision-making. Moreover, it remains unclear whether the TF profiles of the cue interact with different agents to whom the feedback related. In this study we used the TF approach to test EEG oscillations of the cue stimuli in three agents ('Self', 'Other', and 'Computer') conditions separately. The results showed that the increased central-posterior delta power was elicited by the feedback unavailable cues more so than with the feedback available cue within 200-350 ms after the onset of the cue, but only in the self-condition. Moreover, a frontal-central theta oscillation had enhanced power when following the feedback unavailable cue as opposed to the feedback available cue across three agencies. These findings demonstrated that the cue for knowing an outcome produced reward prediction error-like signals, which were mirrored by the delta and theta oscillations during decision-making. More importantly, the present study demonstrated that the theta and delta oscillations reflected separable components of the advanced cue processing before the feedback in decision-making.

Total 25(OH)D levels were determined to assess bone health in elderly populations; however, the bioavailability of 25(OH)D is regulated by the albumin and vitamin D binding protein (DBP) levels and DBP variations. Whether bioavailable 25(OH)D level is a superior biomarker for vitamin D than total 25(OH)D level regarding the BMD and the bone metabolism were not yet fully understood. With a community based cross-sectional study of 967 postmenopausal women, we found that the variant rs7041, but not rs4588, of DBP was significantly associated with the blood DBP level, which was positively correlated with the total 25(OH)D level but negatively associated with bioavailable 25(OH)D levels. Both total and bioavailable 25(OH)D levels were significantly correlated with the BMD value in postmenopausal women; however, only the bioavailable 25(OH)D level was an independent determinant of the BMD values when adjusted for age, body mass index and bone turnover biomarkers (OST and β-CTX). The bioavailable and total 25(OH)D were negatively correlated with bone formation biomarkers (OST, PINP and ALP) and PTH levels, while they were positively correlated with osteoprotegerin (OPG) level; however, the bone resorption biomarker (β-CTX) was not correlated with the 25(OH)D levels. An increment of PTH level, along with reduced bioavailable 25(OH)D levels, was evident when the bioavailable 25(OH)D level was <5ng/mL, which may be the optimal cutpoint for sufficient vitamin D in Chinese elderly women. The blood calcium, magnesium, ALP, TSH, FGF23, and phosphorus levels were not correlated with the total or the bioavailable 25(OH)D levels. These results suggested that high bioavailable 25(OH)D levels were correlated with reduced bone turnover processes and were a biomarker superior to total 25(OH)D for vitamin D in assessing the risks of bone-related diseases. The results indicate that the bioavailable 25(OH)D level should be determined in assessing the bone health.