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Understanding the association of pyroptosis with tumor progression, prognosis and effect on immunotherapeutic response in breast cancer (BC) is limited. This study analysed forty pyroptosis-related genes to construct the pyroptosis score. Association of the pyroptosis score with the overall survival, clinical features, tumor mutation load, immune cell infiltration, and treatment sensitivity of patients with BC was analysed. Out of 983 BC samples, 304 (30.93%) had genetic alterations with the highest TP53 frequency. We identified three separate subtypes associated with pyroptosis action. These subtypes correlate with the clinicopathological characteristics, TME immune cell infiltration, and disease prognosis. Based on the expression levels of the pyroptosis genes, we divided the pyroptosis score into a high group and a low group. The immune-activated pyroptosis subtype had a higher score with a better prognosis. We also observed that the pyroptosis score correlates with the tumor mutation burden. The pyroptosis score and disease prognosis were directly proportional. A higher pyroptosis score indicated a better prognosis. Results suggest that the pyroptosis-related gene prognosis model is closely related to the immune cell infiltration of BC. The three pyroptosis subtypes associated with BC assist in accurately identifying the tumor subtype, the prognosis of immunotherapy drugs and the patient's therapeutic response. [ABSTRACT FROM AUTHOR]

Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. However, there are few reports on the comparison of efficacy between LEF alone and combined with other csDMARDs. Here, the efficacy and safety of LEF monotherapy (88) and combination (361) therapy groups were evaluated. After 3 months, there were no significant differences in 28-joint disease activity score (DAS28), health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the monotherapy and combination groups (all P > 0.05). According to the European League Against Rheumatism (EULAR) response criteria, it was found that the DAS28 response rates were similar in the two groups (P > 0.05). Besides, the two groups presented similar safety profiles. Subgroup analysis found that there was no difference in efficacy among the three combined therapies (LEF + methotrexate (MTX), LEF + hydroxychloroquine (HCQ), and LEF + MTX + HCQ) and LEF monotherapy. Furthermore, when the dose of LEF was less than 40 mg/day, no significant difference in efficacy was observed between low and high doses. Overall, these results indicated that low dose LEF monotherapy was not inferior to the combination therapy. [ABSTRACT FROM AUTHOR]

Approximately 20% of aged captive giant pandas (Ailuropoda melanoleuca) have cataracts that impair their quality of life. To identify potential biomarkers of cataract formation, we carried out a quantitative proteomics analysis of 10 giant pandas to find proteins differing in abundance between healthy and cataract-bearing animals. We identified almost 150 proteins exceeding our threshold for differential abundance, most of which were associated with GO categories related to extracellular localization. The most significant differential abundance was associated with components of the proteasome and other proteins with a role in proteolysis or its regulation, most of which were depleted in pandas with cataracts. Other modulated proteins included components of the extracellular matrix or cytoskeleton, as well as associated signaling proteins and regulators, but we did not find any differentially expressed transcription factors. These results indicate that the formation of cataracts involves a complex post-transcriptional network of signaling inside and outside lens cells to drive stress responses as a means to address the accumulation of protein aggregates triggered by oxidative damage. The modulated proteins also indicate that it should be possible to predict the onset of cataracts in captive pandas by taking blood samples and testing them for the presence or absence of specific protein markers. [ABSTRACT FROM AUTHOR]

Air quality issue such as particulate matter pollution (PM2.5 and PM10) has become one of the biggest environmental problem in China. As one of the most important industrial base and economic core regions of China, Northeast China is facing serious air pollution problems in recent years, which has a profound impact on the health of local residents and atmospheric environment in some part of East Asia. Therefore, it is urgent to understand temporal-spatial characteristics of particles and analyze the causality factors. The results demonstrated that variation trend of particles was almost similar, the annual, monthly and daily distribution had their own characteristics. Particles decreased gradually from south to north, from west to east. Correlation analysis showed that wind speed was the most important factor affecting particles, and temperature, air pressure and relative humidity were key factors in some seasons. Path analysis showed that there was complex unidirectional causal relationship between particles and individual or combined effects, and NO2 and CO were key factors affecting PM2.5. The hot and cold areas changed little with the seasons. All the above results suggests that planning the industrial layout, adjusting industrial structure, joint prevention and control were necessary measure to reduce particles concentration. [ABSTRACT FROM AUTHOR]

The diversity of pathogens associated with acute respiratory infection (ARI) makes diagnosis challenging. Traditional pathogen screening tests have a limited detection range and provide little additional information. We used total RNA sequencing ("meta-transcriptomics") to reveal the full spectrum of microbes associated with paediatric ARI. Throat swabs were collected from 48 paediatric ARI patients and 7 healthy controls. Samples were subjected to meta-transcriptomics to determine the presence and abundance of viral, bacterial, and eukaryotic pathogens, and to reveal mixed infections, pathogen genotypes/subtypes, evolutionary origins, epidemiological history, and antimicrobial resistance. We identified 11 RNA viruses, 4 DNA viruses, 4 species of bacteria, and 1 fungus. While most are known to cause ARIs, others, such as echovirus 6, are rarely associated with respiratory disease. Co-infection of viruses and bacteria and of multiple viruses were commonplace (9/48), with one patient harboring 5 different pathogens, and genome sequence data revealed large intra-species diversity. Expressed resistance against eight classes of antibiotic was detected, with those for MLS, Bla, Tet, Phe at relatively high abundance. In summary, we used a simple total RNA sequencing approach to reveal the complex polymicrobial infectome in ARI. This provided comprehensive and clinically informative information relevant to understanding respiratory disease. [ABSTRACT FROM AUTHOR]

Seeking better surface plasmon polariton (SPP) waveguides is of critical importance to construct the frequency-agile terahertz (THz) front-end circuits. We propose and investigate here a new class of semiconductor-based slot plasmonic waveguides for subwavelength THz transport. Optimizations of the key geometrical parameters demonstrate its better guiding properties for simultaneous realization of long propagation lengths (up to several millimeters) and ultra-tight mode confinement (~λ2/530) in the THz spectral range. The feasibility of the waveguide for compact THz components is also studied to lay the foundations for its practical implementations. Importantly, the waveguide is compatible with the current complementary metal-oxide-semiconductor (CMOS) fabrication technique. We believe the proposed waveguide configuration could offer a potential for developing a CMOS plasmonic platform and can be designed into various components for future integrated THz circuits (ITCs). [ABSTRACT FROM AUTHOR]

Microsecond pulsed electric fields (PEF) have previously been used for various tumour therapies, such as gene therapy, electrochemotherapy and irreversible electroporation (IRE), due to its demonstrated ability. However, recently nanosecond pulsed electric fields (nsPEF) have also been used as a potential tumor therapy via inducing cell apoptosis or immunogenic cell death to prevent recurrence and metastasis by interacting with intracellular organelles. A large proportion of the existing in-vitro studies of nsPEF on cells also suggests cell necrosis and swelling/blebbing can be induced, but the replicability and potential for other effects on cells suggesting a complicated process which requires further investigation. Therefore, this study investigated the effects of pulse width and intensity of nsPEF on the murine melanoma cells (B16) and normal murine fibroblast cells (L929) through electromagnetic simulation and in-vitro experiments. Through examining the evolution patterns of potential difference and electric fields on the intracellular compartments, the simulation has shown a differential effect of nsPEF on normal and cancerous skin cells, which explains well the results observed in the reported experiments. In addition, the modelling has provided a clear evidence that a few hundreds of ns PEF may have caused a mixed mode of effects, i.e. a 'cocktail effect', including cell electroporation and IRE due to an over their threshold voltage induced on the plasma membrane, as well as cell apoptosis and other biological effects caused by its interaction with the intracellular compartments. The in-vitro experiments in the pulse range of the hundreds of nanoseconds showed a possible differential cytotoxicity threshold of electric field intensity between B16 cells and L929 cells. [ABSTRACT FROM AUTHOR]

Circular saw blades are widely used in stone processing. The circular saw blade cutting hard rock numerical simulation model based on ANSYS/LS-DYNA was established to investigate the complex dynamic problem in rock cutting. The failure mechanism of the rock and the influence of cutting parameters on the cutting force and rock fragments were studied by numerical simulation. The results demonstrated that the failure modes of the rock were mainly tensile failure with some shear failure and compressive failure. The cutting force and the number of fragments increased with the feed speed. With the increasing circular saw blade rotational speed, the cutting force and the number of fragments decreased and tended to stabilize. With the distance between the circular saw blades increasing, the cutting force and rock fragments number increase and then maintain basic stability, and when the distance between double circular saw blades reaches 25 mm, it will form a completed rock plate and the interaction of circular saw blades will decrease. The numerical simulation can accurately simulate rock breakage and force when a circular saw blade cuts rock. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that aquaporins (AQPs) may facilitate tumor development. The molecular pathways connecting the pathological functions of AQPs are unclear and need to be better defined. This study aimed to investigate whether AQP3, one of the AQPs expressed highly in breast cancer, had any clinical implication in estrogen-receptor (ER) positive breast cancer, and explore the regulatory mechanisms of AQP3 in estrogen-related breast cancer progression. Here we show that AQP3 is an important enforcer of migration and invasion in breast cancer. We, for the first time, reported that ER-positive breast cancer tissues obtained from premenopausal patients had higher AQP3 expression when compared to those obtained from postmenopausal patients. Estrogen directly upregulates AQP3 by activating ERE in the promoter of the AQP3 gene. The upregulation of AQP3 can influence the expression of molecules related to epithelial-mesenchymal transition and the reorganization of actin-cytoskeleton, resulting in enhancement of cell migration and invasion in ER-positive breast cancer cells. [ABSTRACT FROM AUTHOR]

Here we reported the phase formation of MxMg2Al4+xSi5−xO18:Eu2+ (M = K, Rb) solid solution phosphors, where M+ ions were introduced into the void channels of Mg2Al4Si5O18 via Al3+/Si4+ substitution to keep the charge balance. XRD results revealed that the as-prepared phosphors with different M+ contents were iso-structural with Mg2Al4Si5O18 phase. The combined analysis of the Rietveld refinement and high resolution transmission electron microscopy (HRTEM) results proved that M+ ions were surely introduced into the intrinsic channels in Mg2Al4Si5O18. The emission peaks of MxMg2Al4+xSi5−xO18:Eu2+ (M = K, Rb) phosphors with various x values performed a systematic red-shift tendency, which was ascribed to the elongation of [MgO6] octahedra. The temperature stable photoluminescence and internal quantum efficiency (QE) of MxMg2Al4+xSi5−xO18:Eu2+ (M = K, Rb) phosphors were enhanced owing to the filling of M+ in the void channels suggesting a new insight to design the solid solution phosphors with improved photoluminescence properties. [ABSTRACT FROM AUTHOR]

To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS. [ABSTRACT FROM AUTHOR]

Nitrate is an important precursor of tobacco-specific nitrosamines (TSNAs) and a remarkable difference in nitrate accumulation between lamina and midrib of flue-cured tobacco has long been observed. However, the physiological and molecular mechanisms underpinning this difference remain poorly understood. In this study, physiological and genetic factors impacting nitrate accumulation were identified in pot experiments using flue-cured tobacco K326 with contrasting nitrate content between lamina and midrib. The results showed that three times higher NO3-N content was observed in midrib than that in the lamina, along with lower pigment, NH4-N content, nitrate reductase activity (NRA), sucrose synthetase activity (SSA), and glutamine synthetase activity (GSA) in midrib. Transcriptome analysis revealed that expression of genes involved in porphyrin and chlorophyll metabolism, carotenoid biosynthesis, photosynthesis-antenna proteins, photosynthesis, carbon fixation in photosynthetic organisms, starch and sucrose metabolism, nitrogen metabolism, and biosynthesis of amino acids were significantly lower in midrib than in lamina. qRT-PCR results showed that the expression level of nitrate transporter genes LOC107782967, LOC107806749, LOC107775674, LOC107829632, LOC107799198, LOC107768465 decreased by 2.74, 1.81, 49.5, 3.5, 2.64 and 2.96-folds while LOC107789301 increased by 8.23-folds in midrib but not in lamina. Reduced chlorophyll content might result in low carbohydrate formation which is the source of energy and carbon skeleton supply, then the low capacity of nitrogen reduction, assimilation and transportation, and the poor ability of nitrate reallocation but the high capacity of accumulation might lead to nitrate accumulation in midrib. The results laid the foundation for reducing nitrate content and TSNA formation in tobacco midribs and their products. [ABSTRACT FROM AUTHOR]

Giant magnetostrictive injector using giant magnetostrictive material acting an electronic controlled injector may be one new promising injector to acquire adjustable injection rates while maintaining large injection quantity. An electronic controlled injector driven by a giant magnetostrictive actuator was designed through combining the driving requirement and output characteristics of the material. To promote responding speed of the coil current, the driving voltage with open-hold-fall type waveform was employed just like using in an electromagnetic injector. Simulation model for the injection characteristic of the injector was established using AMEsim software and verified using experimental results collected by the single injection meter. From simulation and experimental results, designed giant magnetostrictive injector showed good performances as maximum spray rate of 4.5 L/min and minimum spray pulse width of 0.21 ms, and realized the boot shape injection when generated by the designed voltage wave. Furthermore, duration time and amplitude of the pilot spray part in a boot shape injection were respectively adjusted through changing the dwell time and opening time. The boot shape injection reached by the giant magnetostrictive injector can reach quite accurate control of fuel injection and then promote fuel efficiency effectively. [ABSTRACT FROM AUTHOR]

Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas. [ABSTRACT FROM AUTHOR]

Crosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling plays an important role in regulation of plant senescence. Our previous work found that SA could delay methyl jasmonate (MeJA)-induced leaf senescence in a concentration-dependent manner. Here, the effect of low concentration of SA (LCSA) application on MeJA-induced leaf senescence was further assessed. High-throughput sequencing (RNA-Seq) results showed that LCSA did not have dominant effects on the genetic regulatory pathways of basal metabolism like nitrogen metabolism, photosynthesis and glycolysis. The ClusterONE was applied to identify discrete gene modules based on protein–protein interaction (PPI) network. Interestingly, an autophagy-related (ATG) module was identified in the differentially expressed genes (DEGs) that exclusively induced by MeJA together with LCSA. RT-qPCR confirmed that the expression of most of the determined ATG genes were upregulated by LCSA. Remarkably, in contrast to wild type (Col-0), LCSA cannot alleviate the leaf yellowing phenotype in autophagy defective mutants (atg5-1 and atg7-2) upon MeJA treatment. Confocal results showed that LCSA increased the number of autophagic bodies accumulated in the vacuole during MeJA-induced leaf senescence. Collectively, our work revealed up-regulation of autophagy by LCSA as a key regulator to alleviate MeJA-induced leaf senescence. [ABSTRACT FROM AUTHOR]

α-SiAlON ceramics have been in use as engineering ceramics in the most arduous industrial environments such as molten metal handling, cutting tools, gas turbine engines, extrusion molds, thermocouple sheaths, protective cover for high-temperature sensors, etc., owing to their outstanding mechanical, thermal and chemical stability. Taking advantage of the intrinsic properties of α-SiAlONs, we investigate, in this paper, the possibility of using the Er-doped α-SiAlON (Er-α-SiAlON) ceramic as a high-temperature sensing material via its unique near-infrared to visible upconversion property. We first use neutron diffraction and density functional theory calculations to study the electronic structure and thermodynamic stability of Er-α-SiAlON. It is found that the interstitial doping of Er stabilizes the α-SiAlON structure via chemical bonds with O-atoms with N:O ratio of 5:2 in the seven-fold coordination sites of the Er3+ ion. Temperature-dependent upconversion emissions are then studied under 980 and 793 nm excitations over a temperature range of 298–1373 K and the fluorescence intensity ratio (FIR) technique has been employed to investigate the temperature sensing behavior. Temperature-dependent Raman behavior is also investigated. We demonstrate that using Er-α-SiAlON as a sensing material, the limit of temperature measurement via the FIR technique can be pushed well beyond 1200 K. [ABSTRACT FROM AUTHOR]

We present a 2.2 GHz modulated, 1.27 kW output power, monolithic fiber amplifier based on pseudo-random binary sequence (PRBS) phase modulation. The spectral line spacing of maximizing the threshold enhancement factor (plateau of trend) was found by theoretical simulation. The spectral line spacing was adjusted to 12.7 MHz by a pattern length of n = 9, which is close to the plateau of trend in the proposed architecture. A 2.2 GHz low-pass radio frequency filter was used to control the FWHM of the seed. A four-stage Yb-doped fiber amplifier chain was established to boost a distributed Bragg reflector (DBR) laser and a distributed feedback (DFB) diode laser to 1.2 kW and 1.27 kW with a backward reflectively of <1‰, which shows a good suppression of SBS effect. [ABSTRACT FROM AUTHOR]

An all-fiber Raman fiber oscillator operating at 2118 nm pumped by homemade thulium-doped fiber laser with continuous output power of 4.2 W has been demonstrated in this paper. By means of 26 m ultrahigh-numerical-aperture fibers, the average slope efficiency can be up to 23.6%. Because of the Raman spectrum broadening of the first Stokes light, the intensity of high order Raman Stokes has been suppressed. The mechanism of Raman spectrum broadening has been analyzed by group-velocity dispersion and Four-Wave Mixing frequency theories in detail. Two mode field adaptors have been used to reduce the intracavity loss and thermal deposition, which indicates that the proposed architecture is robust and has significant power scaling potential. [ABSTRACT FROM AUTHOR]

This research is to develop a new tool to improve the performance of predicting prostate cancer (PCa) and reducing unnecessary biopsies. The clinical data of patients who were definitely diagnosed by prostate biopsy were retrospectively analyzed. PCa risks that include age, prostate-specific antigen (PSA), PSA density (PSAD), free-PSA (fPSA), the ratio of fPSA to PSA (%fPSA), prostate volume (PV), digital rectal examination (DRE) and multi-parametric magnetic resonance imaging (MP-MRI) were selected by univariate and multivariate analysis. The satisfactory risks were used to establish predictor (Prostate Biopsy Rating Scale, PBRS). The total score (TS) that was obtained from PBRS was performed to forecast PCa. The areas under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI) were used to compare the predictive ability. A total of 1078 cases were recruited. The mean values of TS in PCa and non-PCa were 15.94 ± 3.26 and 10.49 ± 3.36 points respectively. The AUC of PBRS was higher than PSA, PSAD and MP-MRI (0.87 vs. 0.75, 0.78, 0.80, respectively). PBRS can reduce unnecessary biopsies compared with PSA, PSAD and MP-MRI by up to 63%, 54% and 44%, respectively. In brief, PBRS is a promising predictor of forecasting PCa. [ABSTRACT FROM AUTHOR]

In this paper, we design a type of switchable metasurfaces by employing vanadium dioxide (VO2), which possess tunable and diversified functionalities in the terahertz (THz) frequencies. The properly designed homogeneous metasurface can be dynamically tuned from a broadband absorber to a reflecting surface due to the insulator-to-metal transition of VO2. When VO2 is in its insulating state, the metasurface can efficiently absorb the normally incident THz wave in the frequency range of 0.535–1.3 THz with the average absorption of ~97.2%. Once the VO2 is heated up and switched to its fully metallic state, the designed metasurface exhibits broadband and efficient reflection (>80%) in the frequency range from 0.5 to 1.3 THz. Capitalizing on such meta-atom design, we further extend the functionalities by introducing phase-gradients when VO2 is in its fully metallic state and consequently achieve polarization-insensitive beam-steering and polarization-splitting, while maintaining broadband absorption when VO2 is in insulating state. [ABSTRACT FROM AUTHOR]

The ATP binding cassette (ABC) transporters superfamily is one of the largest classes of membrane proteins. The core of the ABC transporter protein is composed of transmembrane domains (TMDs) and nucleotide binding domains (NBD). Eukaryotes ABC transporters are classified into seven main families (ABCA to ABCG) based on sequence similarity and domain organizations. With different domain number and domain organizations, eukaryote ABC transporters show diverse structures: the single structure (NBD or TMD), the ABC2 structure (NBD-NBD), the half structure (TMD-NBD or NBD-TMD) and the full structure (TMD-NBD-TMD-NBD or NBD-TMD-NBD-TMD). However, studies on how various ABC transporter gene structures evolved is still absent. Therefore, in this study, we comprehensively investigated the structural evolution of eukaryotic ABC transporters. The seven eukaryote ABC transporter families (A to G) fell into three groups: A&G group, B,C&D group and E&F group. There were at least four times the number of NBD and TMD fusion events in the origin of the half structure transporter. Two fusion modes were found in the full and ABC2 structure origination. Based on these findings, we present a putative structural evolutionary path of eukaryote ABC transporters that will increase our understanding on their origin, divergence and function. [ABSTRACT FROM AUTHOR]

The post-translational modifications (PTMs) occurring on microtubules have been implicated in the regulation of microtubule properties and functions. Acetylated K40 of α-tubulin, a hallmark of long-lived stable microtubules, is known to be negatively controlled by histone deacetylase 6 (HDAC6). However, the vital roles of HDAC6 in microtubule-related processes such as cell motility and cell division cannot be fully explained by the only known target site on tubulin. Here, we attempt to comprehensively map lysine acetylation sites on tubulin purified from mouse brain tissues. Furthermore, mass spectrometry-based quantitative comparison of acetylated peptides from wild-type vs HDAC6 knockout mice allowed us to identify six new deacetylation sites possibly mediated by HDAC6. Thus, adding new sites to the repertoire of HDAC6-mediated tubulin deacetylation events would further our understanding of the multi-faceted roles of HDAC6 in regulating microtubule stability and cellular functions. [ABSTRACT FROM AUTHOR]

CCAAT/enhancer-binding protein α (C/ebpα) is a transcription factor that plays important roles in the regulation of hepatogenesis, adipogenesis and hematopoiesis. Disruption of the C/EBPα gene in mice leads to disturbed liver architecture and neonatal death due to hypoglycemia. However, the precise stages of liver development affected by C/ebpα loss are poorly studied. Using the zebrafish embryo as a model organism, we show that inactivation of the cebpa gene by TALENs results in a small liver phenotype. Further studies reveal that C/ebpα is distinctively required for hepatic outgrowth but not for hepatoblast specification. Lack of C/ebpα leads to enhanced hepatic cell proliferation and subsequent increased cell apoptosis. Additional loss of p53 can largely rescue the hepatic defect in cebpa mutants, suggesting that C/ebpα plays a role in liver growth regulation via the p53 pathway. Thus, our findings for the first time demonstrate a stage-specific role for C/ebpα during liver organogenesis. [ABSTRACT FROM AUTHOR]

Cilia play important roles in sensing extracellular signals and directing fluid flow. Ciliary dysfunction is associated with a variety of diseases known as ciliopathies. Histone deacetylase 6 (HDAC6) has recently emerged as a major driver of ciliary disassembly, but little is known about the downstream players. Here we provide the first evidence that HDAC6-mediated deacetylation of α-tubulin and cortactin is critical for its induction of ciliary disassembly. HDAC6 is localized in the cytoplasm and enriched at the centrosome and basal body. Overexpression of HDAC6 decreases the levels of acetylated α-tubulin and cortactin without affecting the expression or localization of known ciliary regulators. We also find that overexpression of α-tubulin or cortactin or their acetylation-deficient mutants enhances the ability of HDAC6 to induce ciliary disassembly. In addition, acetylation-mimicking mutants of α-tubulin and cortactin counteract HDAC6-induced ciliary disassembly. Furthermore, HDAC6 stimulates actin polymerization, and inhibition of actin polymerization abolishes the activity of HDAC6 to trigger ciliary disassembly. These findings provide mechanistic insight into the ciliary role of HDAC6 and underscore the importance of reversible acetylation in regulating ciliary homeostasis. [ABSTRACT FROM AUTHOR]

Although aberrant microRNA (miRNA) expression has frequently been observed in inflammatory bowel disease (IBD), its biological functions and targets remain largely unknown. Present study found that miR-19b was significantly downregulated in active Crohn's disease (CD). Using bioinformatics analysis, suppressor of cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive immunity that controls several immuno-inflammatory diseases, was predicted to be a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3 protein levels, but not mRNA, was identified in active-CD intestinal tissue samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29 cells, it was experimentally validated that miR-19b is a direct regulator of SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly recognizes the 3'-untranslated region (3'-UTR) of SOCS3. Furthermore, overexpression of miR-19b decreased SOCS3 expression, leading to increased production of macrophage-inflammatory protein-3α (MIP-3α) in Caco2 cells. In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3α. Finally, intracolonically delivered miR-19b decreased the severity of colitis induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our findings suggest that miR-19b suppresses the inflammatory response by inhibiting SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and thereby prevents the pathogenesis of CD. [ABSTRACT FROM AUTHOR]

The small ubiquitin-related modifier (SUMO) participates in various cellular processes, including maintenance of genome integrity, nuclear transport, transcription and signal transduction. However, the biological function of sumoylation in hematopoiesis has not been fully explored. We show here that definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO-deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent. Critically, a SUMO-C/ebpα fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in part through restored runx1 expression. While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis. [ABSTRACT FROM AUTHOR]

Following the first human infection with the influenza A (H10N8) virus in Nanchang, China in December 2013, we identified two additional patients on January 19 and February 9, 2014. The epidemiologic, clinical, and virological data from the patients and the environmental specimen collected from 23 local live poultry markets (LPMs) were analyzed. The three H10N8 cases had a history of poultry exposure and presented with high fever (>38°C), rapidly progressive pneumonia and lymphopenia. Substantial high levels of cytokines and chemokines were observed. The sequences from an isolate (A/Environment/Jiangxi/03489/2013 [H10N8]) in an epidemiologically linked LPM showed highly identity with human H10N8 virus, evidencing LPM as the source of human infection. The HA and NA of human and environmental H10N8 isolates showed high identity (99.1-99.9%) while six genotypes with internal genes derived from H9N2, H7N3 and H7N9 subtype viruses were detected in environmental H10N8 isolates. The genotype of the virus causing human infection, Jiangxi/346, possessed a whole internal gene set of the A/Environment/Jiangxi/10618/2014(H9N2)-like virus. Thus, our findings support the notion that LPMs can act as both a gene pool for the generation of novel reassortants and a source for human infection, and intensive surveillance and management should therefore be conducted. [ABSTRACT FROM AUTHOR]