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Detection of free precession is very important for analysing the internal structure of neutron stars. So far, because of the interference of the accretion process, no feasible method has been proposed to detect the precession of accreting neutron stars in both theory and observations. Based on the analysis of archive data from Chandra and the Neutron Star Interior Composition ExploreR (NICER) of the ultra-compact X-ray binary system 4U 1820–30, we find that the energy spectra have a stable sinusoidal bi-directional oscillation period near 1000 s, no matter which state the X-ray binary system is in. After we fit the energy spectra and carry out Fourier decomposition of the fitting parameters, we find that this period is more steadily emitted from the neutron star. We discuss the possible origin of this period and conclude that the period is most likely the free precession period of the neutron star in 4U 1820–30. Its nutation can result in the seesaw-like periodical bi-directional oscillation we find in this paper. [ABSTRACT FROM AUTHOR]

Fast transitions between different types of power density spectra (PDS) happening over time-scales of several tens of seconds are rare phenomena in black hole X-ray binaries. In this paper, we report a broad-band spectral-timing analysis of the fast transitions observed in the 2021 outburst of GX 339−4 using NICER and Insight -HXMT observations. We observe transitions between band-limited noise-dominated PDS and type-B quasi-periodic oscillations (QPOs), and their rapid appearance or disappearance. We also make a detailed comparison between the fast transitions in GX 339−4 with those seen in MAXI J1820+070 and MAXI J1348−630. By comparing the spectra of the periods with and without type-B QPOs, we find that the spectral ratios above 10 keV are nearly constant or slightly decreasing, and the values are different between sources. Below 10 keV, the flux change of the Comptonization component is inversely proportional to the flux change of the thermal component, suggesting that the appearance of type-B QPOs is associated with a redistribution of the accretion power between the disc and the Comptonizing emission region. The spectral ratios between the periods with type-B QPO and those with broad-band noise are significantly different from that with type-B QPO and without type-B QPO, where the ratios (type-B QPO/broad-band noise) show a maximum at around 4 keV and then decrease gradually towards high energies. Finally, we discuss the possible change of the geometry of the inner accretion flow and/or jet during the transitions. [ABSTRACT FROM AUTHOR]

We present the results of the neutron star X-ray binary system Cen X-3 performed by Insight -HXMT with two observations during 2017 and 2018. During these two observations, the source reached a X-ray luminosity of ∼1038 erg s−1 from 2–105 keV. The analysis of the broadband X-ray spectrum reports the presence of two cyclotron resonance scattering features (CRSFs) with the fundamental line at ∼ 28 keV and the harmonic line at ∼47 keV. The multiple lines exist by fittings with different continuum models, like the absorbed negative and positive power-law with an exponential cutoff (NPEX) model and a power-law with high energy exponential cutoff model. This is the first time that both fundamental and harmonic lines are detected in Cen X-3. We also show evidence of two cyclotron lines in the phase-resolved spectrum of Cen X-3. The CRSF and continuum spectral parameters show evolution with the pulse profile, and the two line centroid energy ratio does not change significantly and locates in a narrow value range of 1.6−1.7 over the pulse phase. The implications of the discovering two cyclotron absorption features and phase-resolved spectral properties are discussed. [ABSTRACT FROM AUTHOR]

Using wavelet analysis and power density spectrum, we investigate two transient quasi-periodic oscillations (QPOs) observed in MAXI J1535−571 observed with Insight - HXMT. The transient QPOs have a centroid frequency of ∼10 Hz with an FWHM ∼0.6 Hz, and an rms amplitude |$\sim 14{{\ \rm per\ cent}}$|⁠. Energy spectra of QPO and non-QPO regimes are also separated and analysed, and the spectra become softer with higher E cut in the non-QPO regime compared to the QPO regime. Our results suggest that the transient QPOs detected in MJD 58016 and 58017 are still the type-C QPO, and the source remains in its HIMS. The duration of all type-C QPO signals based on wavelet is positively correlated with the mean count rate above ∼10 keV, implying appearance of QPOs in different time-scales should be coupled with the corona. The transient QPO properties could be related to the jet or flares, perhaps the partial ejection of the corona is responsible for the disappearance of the type-C QPO. [ABSTRACT FROM AUTHOR]

We investigated the quasi-periodic oscillation (QPO) features in the accretion-powered X-ray pulsar Cen X-3 observed by Insight-HXMT. For two observations in 2020 when Cen X-3 was in an extremely soft state, the power density spectrum revealed the presence of obvious QPO features at ∼40 mHz with an averaged fractional rms amplitude of ∼9 per cent. We study the mHz QPO frequency and rms amplitude over orbital phases, and find that the QPO frequency is ∼33–39 mHz at the orbital phase of 0.1–0.4, increasing to ∼37–43 mHz in the orbital phase of 0.4–0.8, but has no strong dependence on X-ray intensity. We also carried out an energy-dependent QPO analysis, the rms amplitude of the mHz QPOs have a decreasing trend as the energy increases from 2 to 20 keV. In addition, the QPO time-lag analysis shows that the time-delay is ∼20 ms (a hard lag) in the range of ∼5–10 keV, and becomes negative [time-lag of −(20–70) ms] above ∼10 keV. The different QPO theoretical models are summarized and discussed. In the end, we suggest that these energy-dependent timing features as well as the origin of mHz QPOs in Cen X-3 may be ascribed to an instability when the accretion disc is truncated near the corotation radius. [ABSTRACT FROM AUTHOR]

Heavy metal pollution is a global concern. Targeting at the surface sediments in western Chaohu Lake and using metagenome sequencing, we probed into the mechanism of how microbes adapted to heavy metal‐polluted sediments under natural conditions. It was found the heavy metal pollution intensity of the three typical sampling places ranked as estuary of Nanfeihe River (NFH) > Zhongmiao Town (HZ) > Hongshizui (HSZ). Totally 129 phyla, 2631 genera and 12 989 species were detected in the sediment samples, and HSZ, HZ and NFH had 35, 51 and 67 exclusive genera, respectively. The bacterial biomass and virus quantity from NFH accounted for 22·84 and 70·69% of total quantities, respectively, and the microbial community compositions in NFH were also different from those in HSZ and HZ. Metagenomics sequencing and functional gene annotation showed NFH contained many functional genes related to nucleic acid transport and metabolism, ribosome structures and biological origin, replication recombining and repair and inorganic ion transport and metabolism. Kyoto Encyclopedia of Genes and Genomes analysis suggested the sediments from NFH were rich in enzymes correlated with heavy metal transport and reduction. Our findings offer some scientific basis for Chaohu Lake control and microbe resource utilization. [ABSTRACT FROM AUTHOR]

We present a detailed study of the high-mass X-ray binary Vela X-1, using observations performed by Insight-HXMT in 2019 and 2020, concentrating on timing analysis and spectral studies including pulse phase-resolved spectroscopy. The cyclotron line energy is found to be ∼21–27 and 43–50 keV for the fundamental and first harmonic, respectively. We present the evolution of spectral parameters and find that the two line centroid energy ratio E 2/ E 1 evolved from ∼2 before MJD 58900 to ∼1.7 after that. The harmonic cyclotron line energy has no relation to the luminosity but the fundamental line energy shows a positive correlation with X-ray luminosity, suggesting that Vela X-1 is located in the sub-critical accreting regime. In addition, the pulse phase-resolved spectroscopy in Vela X-1 is performed. Both the cyclotron resonant scattering feature and continuum parameters show strong variability over the pulse phase with the ratio of two line energies about 2 near the peak phases and down to ∼1.6 around off-peak phases. Long-term significant variations of the absorption column density and its evolution over the pulse phase may imply the existence of the clumpy wind structure near the neutron star. [ABSTRACT FROM AUTHOR]

In this paper, wavelet analysis is used to study the spectral-timing properties of MAXI J1535–571 observed by the Hard X-ray Modulation Telescope (Insight -HXMT). Low-frequency quasi-periodic oscillations (QPOs) are detected in nine observations. Based on wavelet analysis, the time intervals with QPOs and non-QPOs are isolated, and the corresponding spectra with QPOs and non-QPOs are analysed. We find that the spectra with QPOs (hereafter QPO spectra) are softer than those without QPOs (hereafter non-QPO spectra) in the hard intermediate state (HIMS), while in the soft intermediate state (SIMS), the QPO spectra are slightly harder. The disc temperature of the QPO regime is slightly lower during the HIMS, but becomes higher during the SIMS. The cutoff energies of QPO spectra and non-QPO spectra do not show significant differences. The flux ratio of the disc to total flux is higher for the time intervals with non-QPOs than that in the QPO regime. We propose that these differences in the spectral properties between QPO and non-QPO regimes could be explained through the scenario of Lense–Thirring precession, and the reversal of the QPO/non-QPO behaviour between the HIMS and SIMS may be associated with the appearance/disappearance of a type-B QPO, which might originate in the precession of the jet. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab is an antibody against interleukin‐4 receptor α, used in the treatment of atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate‐to‐severe AD. Methods: In this randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0–1 and a reduction from baseline of ≥ 2 points at week 16. Results: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37–32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75–55·97; P < 0·001) and had ≥ 3‐point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26–55·34; P < 0·001) and ≥ 4‐point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69–45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment‐emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. Conclusions: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile. What is already known about this topic?Two randomized, placebo‐controlled phase III trials (SOLO 1 and SOLO 2) have demonstrated that dupilumab is effective and safe when used in the treatment of atopic dermatitis in adults.However, very few Chinese participants were included and, therefore, the efficacy and safety of dupilumab in this population is unclear. What does this study add?The findings of this randomized, placebo‐controlled phase III trial show that dupilumab is effective in improving the signs and symptoms of atopic dermatitis in adult Chinese patients and has a favourable safety profile in this population. Plain language summary available online [ABSTRACT FROM AUTHOR]

We report the orbital X-ray variability of the high-mass X-ray binary (HMXB) GX 301−2. GX 301−2 underwent a spin-up process in 2018–2020 with the period evolving from ∼685–670 s. The energy-resolved pulse profiles of the pulsar at 1–60 keV varied from single-peaked and sinusoidal shapes to multipeaked ones across different orbital phases. Pulse fractions evolving over the orbit had negative correlations with the X-ray flux. The broad-band X-ray energy spectrum of the pulsar can be described with a partially covered negative–positive cut-off power-law continuum model. Near the periastron passage of the pulsar we found strong variation in the additional column density (⁠|$N_{\mathrm{H}_{2}}$|⁠), which correlated with variation of the flux. Curves of growth for both Fe Kα and Fe Kβ lines were plotted to investigate the distribution of matter around the neutron star. We also found evidence for two cyclotron absorption lines in the phase-averaged spectra in GX 301−2, with one line of 30–42 keV and the other line varying over 48–56 keV. The centroid energies of both lines show a similar relationship with X-ray luminosity: positive correlation in the lower luminosity range, and a negative relation above a critical luminosity of |$10^{37}\, \rm erg\, s^{-1}$|⁠. We estimate the surface magnetic field of the neutron star in GX 301−2 to be ∼(0.5–2) × 1013 G. The two cyclotron line energies have a nearly fixed ratio of ∼1.63 while having a low strength ratio (∼0.05), suggesting that these two features may actually be one line. [ABSTRACT FROM AUTHOR]

Introduction Takotsubo syndrome (TTS) is a clinical syndrome characterized by an acute and transient left ventricular dysfunction that is always triggered by an emotional or physical stimulation.[1] TTS is often be misdiagnosed as acute coronary syndrome (ACS). Learning point for cliniciansTakotsubo syndrome is a type of reversible acute cardiac dysfunction triggered by psychological or physical stress, mainly present with chest pain and dyspnea. [Extracted from the article]

An integrated multi-trophic aquaculture (IMTA) system, with one fish cage model surrounded by an island and shellfish rafts, was used in the current study. Planktonic and sediment bacterial communities in the IMTA system were monitored over four seasons in 2019. In both plankton and sediment samples, the most dominant phyla were Proteobacteria and Bacteroidota. Sediment bacterial samples were more similar and had higher levels of biodiversity than planktonic bacterial samples. Obvious seasonal variations were found in plankton samples, but not in sediment samples. No obvious inter-site variations in planktonic and sediment bacteria (fish cages, shellfish rafts and control sites) were found and the results suggested that no obvious impact of feeding operations in fish culture cage model on bacterial communities in the IMTA system was observed in this study. Based on the sequence data, some faecal indicator bacteria and potentially pathogenic bacterial species were detected. According to the results, the bacterial water quality in the IMTA system was acceptable. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) analysis revealed that the primary difference in potential functional roles of planktonic and sediment bacteria was amino acid transport and metabolism, which was active in different seasons. [ABSTRACT FROM AUTHOR]

Summary: Food allergy is related to increasing risk of the development of allergic asthma, but the precise interplay between sensitization to different allergens in different compartments of the body is not fully understood. The aim of this study was to develop a novel humanized murine model of mixed food and respiratory allergy that recapitulates the human anaphylactic response and to more clearly understand the impact of food allergies on asthma. Immunodeficient mice transferred with peripheral blood mononuclear cells (PBMCs) from donors with peanut and house dust mite (HDM) allergy were exposed and challenged to peanut. Between peanut exposure and challenge, mice were intranasally treated to HDM. Allergic parameters were analyzed. Allergen‐specific immunoglobulin (Ig)E in sera could only be measured in mice treated with peripheral blood mononuclear cells (PBMCs) plus allergen. A preceding peanut exposure increased IgE levels, histamine release, bronchial hyper‐responsiveness and lung inflammation. Recruitment of inflammatory cells to the airways was aggravated associated with an enhanced T helper type 2 (Th2)/Th17 cytokine secretion when the two allergies were present. A preceding peanut exposure amplifies allergic asthma in this humanized model, which may contribute to the understanding of underlying immunological mechanism of polysensitization occurring in allergic individuals and evaluation of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background Patients on dialysis were susceptible to coronavirus disease 2019 (COVID-19) and were prone to severe clinical characteristics after infection; acute kidney injury was related to mortality in COVID-19 cases. Limited is known about the characteristics of COVID-19 patients with end-stage renal disease not requiring renal replacement therapy (RRT). Aim Evaluate clinical characteristics, course and outcomes of COVID-19 patients with chronic kidney disease (CKD) who did not require RRT and those on dialysis. Design A two-center retrospective study. Methods A total of 836 adult patients with COVID-19 (24 CKD not on dialysis; 15 dialysis-dependent CKD) were included. The study includes no patients with renal transplantation. Risk factors were explored. Results CKD not requiring RRT is an independent risk factor for in-hospital death [adjusted odds ratio (aOR) 7.35 (95% CI 2.41–22.44)] and poor prognosis [aOR 3.01 (95% CI 1.23–7.33)]. Compared with COVID-19 cases without CKD, those with CKD not requiring RRT showed similar percentage of initial moderate cases (75.00% vs. 73.65%) but higher incidence of in-hospital neutrophilia (50.00% vs. 27.30%) or death (50.00% vs. 9.03%). The odds ratio of dialysis associated to mortality in CKD patients was 2.00 (95% CI 0.52–7.63), suggesting COVID-19 patients with dialysis-dependent CKD were at greater risk of in-hospital death. For COVID-19 patients with CKD not requiring RRT, statins reduced the risk of neutrophilia [OR 0.10 (95% CI 0.01–0.69)] while diuretics increased the risk of neutrophilia [OR 15.4 (95% CI 1.47–160.97)], although both showed no association to mortality. Conclusion COVID-19 patients with CKD presented high incidence of neutrophilia, poor prognosis and in-hospital death, with dialysis patients being more vulnerable. [ABSTRACT FROM AUTHOR]

Summary: Although the pathogenesis of acute myeloid leukemia (AML) is still unknown, accumulating evidence has revealed that immune response plays a vital part in the pathogenesis. Here, we investigated the involvement of 21 single nucleotide polymorphisms (SNPs) of immunorelated genes, including cytokines [interleukin (IL)‐2, IL‐4, IL‐9, IL‐12A, IL‐22, interferon (IFN‐α) and transforming growth factor (TGF)‐β1], transcriptional regulatory genes (TBX21, STAT1, STAT3, STAT5B, STAT6, GATA3, FOXP3 and IRF4) and others (IL2RA, IL6R, NFKBIA) in 269 AML in‐patients and 200 healthy controls. Furthermore, we analyzed the relationship between the SNPs and clinical characteristics. Immunorelated SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. All the SNPs in healthy controls were consistent with Hardy–Weinberg equilibrium. All final P‐values were adjusted by Bonferroni multiple testing. Our results showed that IL‐22 (rs2227491) was significantly associated with the white blood cell (WBC) counts. Signal transducer and activator of transcription 5B (STAT‐5B) (rs6503691) showed a close relationship with the recurrent genetic abnormalities in patients with AML. We verified the negatively independent effect of age and risk of cytogenetics on overall survival (OS). More importantly, the GG genotype of IL‐12A (rs6887695) showed a negative impact on AML prognosis independently. Furthermore, the relative expression of IL‐12 was decreased in GG genotype, no matter under a co‐dominant or recessive model. However, no correlation was observed between the SNPs mentioned above and disease susceptibility, risk stratification and survival. Our findings suggest that immunorelated gene polymorphisms are associated with prognosis in AML, which may perform as novel inspection targets for AML patients. [ABSTRACT FROM AUTHOR]

Summary: Tumor necrosis factor (TNF)‐like weak inducer of apoptosis (TWEAK) acts through its receptor fibroblast growth factor inducible 14 (Fn14), and participates in skin inflammation. Both TWEAK and Fn14 are highly expressed in skin lesions of patients with atopic dermatitis. The purpose of this study was to further explore the effect of Fn14 inhibition on experimental atopic dermatitis. Experimental atopic dermatitis was induced in the wild‐type and Fn14 knock‐out BALB/c mice. The effect of TWEAK/Fn14 interaction on keratinocytes was studied in an in‐vitro model of atopic dermatitis. Fn14 deficiency ameliorates skin lesions in the mice model, accompanied by less infiltration of inflammatory cells and lower local levels of proinflammatory cytokines, including TWEAK, TNF‐α and interleukin (IL)‐17. Fn14 deficiency also attenuates the up‐regulation of TNFR1 in skin lesions of atopic dermatitis. Moreover, topical TWEAK exacerbates skin lesion in the wild‐type but not in the Fn14 knock‐out mice. In vitro, TWEAK enhances the expressions of IL‐17, IL‐18 and IFN‐γ in keratinocytes under atopic dermatitis‐like inflammation. These results suggest that Fn14 deficiency protects mice from experimental atopic dermatitis, involving the attenuation of inflammatory responses and keratinocyte apoptosis. In the context of atopic dermatitis‐like inflammation, TWEAK modulates keratinocytes via a TNFR1‐mediated pathway. [ABSTRACT FROM AUTHOR]

In 2015, the Asian Radiation Dosimetry Group established a regional network of biological dosimetry laboratories known as the ARADOS-WG03 (Working Group 03; Biological Dosimetry). A survey was conducted in 2017 to evaluate the capabilities and capacities of the participating laboratories for emergency preparedness and responses in large-scale nuclear and/or radiological incidents. The results of this survey were identified and assessed. The data provide important information on the current state of emergency cytogenetic biological dosimetry capabilities in the Asian region. [ABSTRACT FROM AUTHOR]

Aims: Genotype VII Newcastle disease (ND) is one of the most epidemic and serious infectious diseases in the poultry industry. A novel vaccine targeting VII Newcastle disease virus (NDV) is still proving elusive. Methods and Results: In this study, we constructed regulated delayed lysis Salmonella strains expressing either a fusion protein (F) alone under an eukaryotic CMV promoter or together with chicken IL‐18 (chIL‐18) as a molecular adjuvant under prokaryotic Ptrc promoter, named pYL1 and pYL23 respectively. Oral immunization with recombinant strains induced NDV‐specific serum IgG antibodies in both pYL1‐ and pYL23‐immunized chickens. The presence of chIL‐18 significantly increased lymphocyte proliferation in immunized chickens, as well as the percentages of CD3+CD4+ and CD3+CD8+ T cells in serum, even if a statistically significant difference did not exist. After a virulent challenge, pYL23 immunization provided about 80% protection at day 10 postinfection, compared with 60% of protection offered by pYL1 immunization and 100% protection in the inactivated vaccine group, indicating the enhanced immune response provided by chIL‐18, which was also confirmed by histochemical analysis. Conclusions: Recombinant lysis Salmonella‐vectored DNA vaccine could provide us a novel potential option for controlling NDV infection. Significance and Impact of the Study: This study took use of a regulated delayed lysis Salmonella vector for the design of an orally administrated vaccine against NDV. [ABSTRACT FROM AUTHOR]

Study Question: Can follicle survival in frozen-thawed human ovarian tissue be quantified in situ using the dye Neutral Red (NR) to stain viable follicles specifically?Summary Answer: A follicle survival rate within ovarian tissue can be calculated using NR followed by histological evaluation and evidence for a consistently high follicle survival in a series of ovarian tissue from 25 Danish girls and women undergoing ovarian tissue cryopreservation (OTC) was obtained.What Is Known Already: Securing follicle survival in cryopreserved ovarian tissue is crucial for proper quality control when centers wish to implement OTC. The only established technique for validation of follicle survival is xenografting of thawed ovarian tissue to immunodeficient mice. However, this functional test is expensive, time consuming, requires animal facilities and only provides a qualitative-not quantitative-measure for follicle survival.Study Design Size, Duration: Quantification of follicle survival in human ovarian tissue donated from 30 girls and women having tissue cryopreserved for fertility preservation from 2000 to 2015 at the Laboratory of Reproductive Biology in Copenhagen, Denmark.Participants/materials, Setting, Methods: Cryopreserved ovarian cortex was donated from 25 girls and young women aged 10-36 years (mean age: 25 years) and the average storage time in liquid nitrogen was 9.1 ± 5.6 years, ranging from 1.6 to 17.9 years. In 12 of the cases, the ovarian tissue was collected from the local hospital and in the other 13 cases the ovarian tissue was transported on ice up to 6 h prior to freezing. Donated fresh ovarian surplus tissue was obtained from five women aged 23-34 years (mean age: 27 years). Ovarian tissues were chopped into small fragments and incubated in culture medium containing 50 mg/ml NR for 3-4 h. Fragments of ovarian tissue containing clearly NR-stained follicles were selected for counting, encapsulated in 4% agar and were processed for histology to calculate a follicular survival rate.Main Results and the Role Of Chance: The mean follicle survival rate in the 25 patients after freezing and thawing was 84% ± 11 (mean ±SD), ranging from 50% to 98%. The high follicle survival rate in this clinical series of patients reflects a constant high-quality service performed in our center and confirms the robustness of the slow freezing protocol. No significant association between follicle survival rates and storage time was found using linear regression analysis, suggesting that storage in liquid nitrogen does not affect viability of the tissue. No significant association in follicle survival rates was found between ovarian tissues collected at the local hospital compared to tissues transported on ice prior to freezing, supporting that prolonged cooling does not seem to greatly affect the follicle survival. For the fresh ovarian tissue, the average follicle survival rate was 91% ± 5 (mean ± SD) in five patients, ranging from 81% to 95%.Limitations, Reasons For Caution: Even though the NR staining requires active incorporation of the dye, the test is merely a short in situ test that cannot completely replace the functional value of xenografting studies in which the integrity and developmental potential of the ovarian follicles are assessed.Wider Implications Of the Findings: OTC is now being employed around the world but to date it has been difficult for centers to evaluate the effectiveness of their program and perform proper quality control. NR staining combined with histological evaluation is the first quantitative method to provide a survival rate for follicles in frozen-thawed human ovarian tissue and offer a valuable and easily applicable tool to validate the cryopreservation procedure when implementing OTC or as routine quality control for the overall freezing performance within tissue banking facilities.Study Funding/competing Interest(s): The Research Pools of Rigshospitalet, the Danish Cancer Foundation, Dagmar Marshalls Foundation, and the Novo Nordic Foundation are thanked for having funded this study. The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Abstract: The isobaric tags for relative and absolute quantitation (iTRAQ) were applied to identify differentially expressed proteins (DEPs) in Litopenaeus vannamei in response to different virulence white spot syndrome virus infection. A total of 2780 unique peptides corresponding to 754 proteins were identified. The number of significant differentially expressed proteins was 161, including 38 up‐regulated ones and 123 down‐regulated ones in low‐virulence infection library compared with normal‐virulence infection library. Gene Ontology function annotation indicated that the differentially expressed proteins mainly participated in the biological process. Subcellular location classification showed that the largest distribution of differentially expressed proteins was found in the cytoplasm in both down‐regulated and up‐regulated proteins. Kyoto encyclopaedia of genes and genomes analysis revealed that most of the differentially expressed proteins were involved in carbon metabolism. Moreover, three metabolic pathways, including carbon metabolism, inositol phosphate metabolism, and fructose and mannose metabolism, were significantly affected. Our findings offered a better understanding of the host response to different virulence white spot syndrome virus infection. Significance and Impact of the Study: White spot syndrome virus (WSSV) is one of the most harmful pathogens in shrimp farming. Previous studies have shown that genetic variations of white spot syndrome virus cause the strains of different virulence. The hosts also show different self‐regulation when infected by different viruses. A better understanding of host response to white spot syndrome virus will help elucidate the virulence and pathogenesis of this unique pathogen. [ABSTRACT FROM AUTHOR]

Dear Editor, During the outbreak of coronavirus disease 2019 (COVID-19), healthcare workers (HCWs) caring for patients with COVID-19 have to wear personal protective equipment (PPE) and are therefore susceptible to PPE-related adverse skin reactions. Limitations of this study include response bias, as HCWs with adverse skin reactions were more likely to respond. [Extracted from the article]

Aims Study the response of microbial communities and selected petroleum hydrocarbon ( PH)-degrading genes on simulated PH spills in soils/sediments from different geographic locations. Methods and Results A microcosm experiment was conducted by spiking mixtures of petroleum hydrocarbons (PHs) to soils/sediments collected from four different regions of China, including the Dagang Oilfield ( DG), Sand of Bohai Sea ( SS), Northeast China ( NE) and Xiamen ( XM). Changes in bacterial community and the abundance of PH-degrading genes ( alkB, nah and phe) were analysed by denaturing gradient electrophoresis ( DGGE) and qPCR, respectively. Degradation of alkanes and PAHs in SS and NE materials were greater ( P < 0·05) than those in DG and XM. Clay content was negatively correlated with the degradation of total alkanes by 112 days and PAHs by 56 days, while total organic carbon content was negatively correlated with initial degradation of total alkanes as well as PAHs. Abundances of alkB, nah and phe genes increased 10- to 100-fold and varied by soil type over the incubation period. DGGE fingerprints identified the dominance of α-, β- and γ- Proteobacteria (Gram −ve) and Actinobacteria (Gram +ve) bacteria associated with degradation of PHs in the materials studied. Conclusion The geographic divergence resulting from the heterogeneity of physicochemical properties of soils/sediments appeared to influence the abundance of metabolic genes and community structure of microbes capable of degrading PHs. Significance and Impact of the Study When developing practical in-situ bioremediation approaches for PHs contamination of soils/sediment, appropriate microbial community structures and the abundance of PH-degrading genes appear to be influenced by geographic location. [ABSTRACT FROM AUTHOR]

Neutron stars are observed to undergo small, abrupt rotational speed-up. This phenomenon is known as glitch. In pulsar timing observations, detection of a neutron star glitch is constrained by the time of occurrence of the event relative to entire observing span and observing cadences, time of occurrence of preceding/subsequent glitches relative to observing cadences and the strength of timing noise. Using the Yu et al. data sets, in this paper, we analyse the observational selection in terms of detection probability. We define partial probabilities for the constraints and use the Monte Carlo method with assuming glitches distribute uniformly to solve the complete probability formula for both group case involving 157 pulsars and individual cases for each of the seven pulsars with glitch numbers ≥5. In the simulations, numerical Bayesian inference is used for glitch identification. With the derived detection probability density and observed results, we uncover glitch size probability distribution embedded in the data for both the group and individual cases. We find the most prominent correction occurred for PSR J1341–6220, in which the exponent of the power-law model varies from the observed +0.7+1.4-0.7 to -0.4+1.0-0.4. We suggest observers determine the detection probability for glitch theories, e.g. the self-organized criticality. [ABSTRACT FROM AUTHOR]

The correlations of murine double minute 2 ( MDM2) T309 G and esophageal cancer were elucidated because the association between MDM2 expression states and clinicopathological parameters of esophageal squamous cell carcinoma ( ESCC) is controversial. We conducted a meta-analysis on studies screened from Pub Med, Web of Science, Embase, the Cochrane Library, and the Chinese Biomedical Literature Databases that were published before October 2014. All studies describing the association between MDM2 and ESCC were traced. Meta-analysis was performed using the STATA software ( Stata Corp., College Station, TX, USA). A total of 9 studies with 707 cases and 324 controls were included. MDM2 expression was higher in ESCC than in normal esophageal epithelium (odds ratio [ OR] 10.38, 95% confidence interval [ CI] 6.42-16.78, P < 0.001). High MDM2 expression was associated with early primary tumor stage ( T1/ T2 vs. T3/ T4, OR 0.59, 95% CI 0.38-0.92, P = 0.018) and increased risk of regional lymph node metastasis ( N0 vs. N1, OR 1.66, 95% CI 1.03-2.67, P = 0.039). However, no relationship was observed between MDM2 expression and the risk of distant metastasis ( OR = 2.09, 95% CI 1.00-4.36, P = 0.050), and MDM2 was not significantly correlated with TP53 expression ( OR 1.22, 95% CI 0.53-2.77, P = 0.643). Our analysis suggests that MDM2 acts as a potent marker of early primary tumor stage but higher risk of regional lymph node metastasis in ESCC. However, because of the limited number of studies included, the result should be further clarified by well-designed prospective studies. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 45-year-old Chinese man with bilateral reddish, palmoplantar hyperkeratotic lesions on his hands and feet. Topics covered include the results of his physical examination, the diagnosis of Nagashima-type palmoplantar keratosis (PPK) with underlying SERPINB7 mutation and the distribution of SERPINB7 in the stratum granulosum.

A new genotype of yellow head virus (YHV), designated as YHV-8, was found in farmed shrimp Fenneropenaeus chinensis suffering suspectedly from EMS/AHPNS (early mortality disease/acute hepatopancreatic necrosis disease) in China in 2012. In this study, a one-step, real-time reverse-transcription loop-mediated isothermal amplification (rRT-LAMP) assay was developed for better detection of both genotypes of YHV-1 and YHV-8. A set of six specific primers was successfully designed targeting a conserved region of the YHV genome. The LAMP reaction was optimized to contain 8 mmol l−1 Mg2+ and 1·4 mmol l−1 dNTPs, and to be performed at 58°C for 60 min. The detection sensitivity of the rRT-LAMP method was as low as 7 × 100 copies per reaction. The specificity of the method was validated by the absence of any cross-reaction with the RNA samples extracted from other shrimp viruses (Taura syndrome virus, white spot syndrome virus, infectious hypodermal and haematopoietic necrosis virus, hepatopancreatic parvovirus) and specific pathogen-free (SPF) shrimp. The resulting standard curves showed high correlation coefficient values. Furthermore, the test of farm samples showed that YHV was detected in three of 111 Litopenaeus vannamei, six of eight Fenneropenaeus chinensis, five of 19 Macrobrachium rosenbergii and none of the nine Marsupenaeus japonicus. These results suggest that this assay is applicable widely as a new rapid and sensitive detection method in the research of YHV. Significance and Impact of the Study In this study, we designate a new genotype of yellow head virus (YHV) as YHV genotype 8 (YHV-8) which was detected in diseased shrimp in China. A rapid, sensitive and specific rRT-LAMP detecting method for both YHV-8 and YHV-1 has been established. It is anticipated that this novel assay will be instrumental for diagnosis and surveillance of the virulent genotypes of YHV. [ABSTRACT FROM AUTHOR]

SIPI-8294, as an erythromycin derivative, has only weak antibacterial effects on MRSA and MSSA. Interestingly, synergistic effect of SIPI-8294 with oxacillin was observed both in vitro and in vivo. Western blot and RT-PCR results demonstrate that mecA expressions were suppressed by SIPI-8294 in MRSA. Furthermore, the knock out of mecA in ATCC 43300 led to the loss of synergy of the combinations while mecA complemented strain showed almost the same synergistic capability compared to the wild type strain. However, the knock out of mecR1 and mecI in MRSA displayed no impact on the synergy of the combinations and the ability of SIPI-8294 to suppress mecA expression. In summary, our study has demonstrated that SIPI-8294 could dramatically reverse MRSA resistance to β-lactams both in vitro and in vivo owing to inhibiting mecA expression. However, mecR1 and mecI, as the pivotal regulatory genes of mecA, do not participate in SIPI-8294- mecA pathway. The research indicates that it may be a promising strategy for combating MRSA infections with the combinations of SIPI-8294 and β-lactam antibiotics. The research of the mechanism is important for structure modification and new drug development. Significance and Impact of the Study This study is the first report on the mechanism of synergy between SIPI-8294 and β-lactams against MRSA on the molecular level. In this study, SIPI-8294 showed strong synergistic effects on β-lactam antibiotics both in vitro and in vivo owing to inhibiting mecA expression. As pivotal regulatory genes of mecA, mecR1 and mecI do not participate in SIPI-8294- mecA pathway and are not involved in the synergism of SIPI-8294 and β-lactams. The research indicates that it may be a promising strategy for combating MRSA infections with the combinations of SIPI-8294 and β-lactams. The research is important for structure modification and new drug development. [ABSTRACT FROM AUTHOR]

Oxygen deficiency is a critical limiting factor for nosiheptide production in Streptomyces actuosus during fermentation. To alleviate oxygen limitation and enhance the yield of nosiheptide, haemoprotein from Sinorhizobium meliloti (SmHb) was overexpressed in S. actuosus with overexpression of haemoglobin from Vitreoscilla ( VHb) as a positive control. The expression of SmHb and VHb in S. actuosus was confirmed by SDS- PAGE and CO-difference spectra analysis. The results showed that S. actuosus recombinant strain with SmHb expression had higher nosiheptide production (increased by 151%) than the wild strain ( WT) under the low aeration conditions, which was similar with S. actuosus mutant strain with VHb expression. Furthermore, two copies of SmfHb gene were integrated in S. actuosus, which further increased the nosiheptide production by approx. 1·9-fold compared with original strain, and final nosiheptide yield was up to 2352 μg ml−1. These results suggested that engineering of SmHb expression could be used as an efficient method for constructing a high nosiheptide-accumulating strain. Significance and Impact of the Study The significant improvement of nosiheptide production was found in recombinant strain with overexpressed sm gene. And further improvement was obtained in the two copies of sm overexpressing strain. These results suggested that engineering of SmHb expression could be used as an efficient method for constructing a high nosiheptide-accumulating strain. [ABSTRACT FROM AUTHOR]

Two new species--Stigmaeopsis temporalis n. sp. collected in Kochi, Japan, and S. tegmentalis n. sp. collected in Fuzhou, China--both from bamboo plants, are described. In addition, four new life types (WN-p, WN-h, WN-n, and CW-g) in five species--S. temporalis, Stigmaeopsis tenuinidus Zhang et Zhang, S. tegmentalis, Neonidulus tereotus Beard et Walter, and Eotetranychus asiaticus Ehara--are documented in relation to their supposed functions. [ABSTRACT FROM AUTHOR]

Flavivirus envelope protein locates at the outermost surface of viral particle and mediates virus entry and fusion infection, and plays an important role in eliciting neutralizing antibody. In this study, goose tembusu virus ( GTV) E protein was expressed and purified from Escherichia coli. The immunological changes and protection efficiency of this protein serving as recombinant subunit vaccine were then tested. In ducks, recombinant E protein markedly elicited specific neutralizing antibody, stimulated the secretion of IL-2, TNF- α and IFN-γ cytokines and promoted the proliferation of lymphocytes. Additionally, population of soluble CD4 and soluble CD8 molecules in sera significantly increased in response to this antigen. Moreover, virus challenge revealed that recombinant E protein contributed to protection against GTV challenge. Taken together, the data indicate that recombinant GTV E protein could induce significant humoral and cell-mediated responses and that recombinant E protein can serve as a potential subunit vaccine candidate against GTV. Significance and Impact of the Study The sudden outbreak and quick spread of newly emerging goose tembusu virus ( GTV) have resulted in serious economic loss. There is no effective commercial vaccine or reasonably available control measure so far. In this study, GTV E protein was expressed and purified from Escherichia coli, and it was found that recombinant E protein could induce significant humoral and cell-mediated responses. It indicated that recombinant E protein can serve as a potential subunit vaccine candidate against GTV. [ABSTRACT FROM AUTHOR]

Essential oils have been found to exert antibacterial, antifungal, spasmolytic, and antiplasmodial activity and therapeutic effect in cancer treatment. In this study, the antibacterial activities of four main essential oils' components (thymol (Thy), eugenol (Eug), berberine (Ber), and cinnamaldehyde (Cin)) were evaluated against two food-borne pathogens, Listeria monocytogenes and Salmonella Typhimurium, either alone or in combination with streptomycin. Checkerboard assay demonstrated that Thy and Cin elicited a synergistic effect with streptomycin against L. monocytogenes, while a synergy existed between Cin or Eug and streptomycin against Salm. Typhimurium. Further experiments showed that this synergy was sufficient to eradicate biofilms formed by these two bacteria. Thus, our data highlighted that the combinations of specific components from essential oils and streptomycin were useful for the treatment of food-borne pathogens, which might help prevent the spread of antibiotic resistance through improving antibiotic effectiveness. Significance and Impact of the Study This study has shown the synergistic effect of four components of essential oil (thymol, eugenol, berberine and cinnamaldehyde) combined with streptomycin on planktonic and biofilm-associated food-borne pathogens Listeria monocytogenes and Salmonella Typhimurium. These findings indicate that combination of specific components of essential oils with streptomycin may provide alternative methods to overcome the problem of food-borne bacteria both in suspension and in biofilm. [ABSTRACT FROM AUTHOR]

Globular clusters (GCs) are the oldest stellar systems in the Galaxy, in which millisecond pulsars are widely believed to be the only steady γ-ray emitters. So far, nine γ-ray GCs have been identified and a few candidates, such as 2MS-GC01 and IC 1257, have been suggested. In this work, after analysing the publicly available Fermi Large Area Telescope data, we confirm the significant γ-ray emission from 2MS-GC01 and IC 1257 and report the discovery of γ-ray emission from NGC 5904 and 6656 within their tidal radii. Also, strong evidence of significant γ-ray emission is found from FSR 1735. From the observed γ-ray luminosities, we estimate the numbers of millisecond pulsars that are expected to be present in these GCs. [ABSTRACT FROM AUTHOR]

The evpP gene in fish pathogen Edwardsiella tarda, coding the T6 SS secretory protein Evp P and carrying an evpA-evpO independent promoter region, was crucial for host cell invasion. The transcription of evpP was positively regulated by either the two-component system Esr A- Esr B or iron concentration, and its overexpression was known to enhance the invasion ability in our previous study. This work demonstrated that the H- NS protein, a pleiotropic regulator of gene expression, was a new transcriptional modulator of evpP gene. The results showed that in vivo the transcriptional level of evpP was downregulated by H- NS and in vitro this global regulator interacted directly with evpP promoter region. Moreover, DNase I footprinting experiments mapping the interaction regions of H- NS and evpP revealed that this global regulator bound to evpP promoter and neighbouring areas at multiple sites. We provided a new insight into evpP regulation network and demonstrated the repression of H- NS to the transcription of evpP gene. Significance and Impact of the Study Recently, the devastating fish disease edwardsiellosis caused by Edwardsiella tarda has been widely concerned. The xenogeneic silencing of the classic regulator H-NS to the T6SS secretory protein EvpP, which played an important role in the virulence of Edw. tarda, was firstly reported in this study. It raised a better understanding of the virulence regulation of EvpP and provided more information about the complex infection mechanism of this pathogen. Our findings would contribute to the development of live attenuated vaccines against edwardsiellosis thus reducing the economic losses caused by this bacterium. [ABSTRACT FROM AUTHOR]

Preoperative elevations in the levels of serum amyloid A ( SAA) or C-reactive protein ( CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma ( ESCC). In total, 252 patients with ESCC who had undergone surgery with curative-intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic ( ROC) curve ( AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1-, 3-, and 5-year overall survival ( OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant ( r2 = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels ( AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III ( P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor ( P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis. [ABSTRACT FROM AUTHOR]

Background: Etoposide, an inhibitor of the normal religation activity of the nuclear enzyme topoisomerase II, can induce a secondary acute myeloid leukemia characterized by site-specific DNA rearrangements. The schedule of drug administration appears to be a clinical risk factor for this devastating treatment complication.Purpose: We tested the hypothesis that prolonged exposure of leukemia cells in vitro to low concentrations of etoposide, compared with short exposures to high concentrations, could produce equivalent or greater desired cytotoxic effects, with decreased occurrence of undesired site-specific double-stranded DNA recombinational events (i.e., recombinogenesis).Methods: We used the frequency of V(D)J (variable-diversity-joining) recombinase-mediated deletions of exons 2 and 3 of the hypoxanthine phosphoribosyltransferase (HPRT) gene as a biomarker of etoposide-induced, nonhomologous, site-specific DNA rearrangement. A polymerase chain reaction-based technique was used to measure exon 2 + 3 deletions in human lymphoid leukemia CCRF-CEM cells 6 days after either 4-hour or 24-hour treatment with etoposide at clinically relevant concentrations. Cytotoxic effects of etoposide (determined by the number of viable cells present in the treated compared with the control [i.e., untreated] cells) were measured 6 days after treatment of the cells. The frequency of the exon 2 + 3 deletion following the two treatment-duration conditions was compared by use of the Mantel-Haenszel statistic. All P values resulted from two-sided tests.Results: Cytotoxicity increased with increasing etoposide concentration and exposure duration, as expected. By day 6, the frequency of exon 2 + 3 deletions was significantly higher (global P value = .0003) after the 4-hour treatment than after the 24-hour treatment, regardless of whether the frequency was assessed at etoposide concentrations achieving equivalent (e.g., 95%) cytotoxicity (14.2 x 10(-7) versus 4.1 x 10(-7) or at equivalent etoposide concentrations (e.g., 1 microM) (10.8 x 10(-7) versus 1.3 x 10(-7). Thus, the ratio of desired cytotoxic to undesired recombinogenic effects was higher with the 24-hour schedule. After the treated cells were subcloned at limiting dilutions, the frequency of the exon 2 + 3 deletion increased from 16.3 x 10(-7) to 4.33 x 10(-3), indicating that the recombinational event is not necessarily lethal.Conclusion: For all drug concentrations and levels of cytotoxicity studied in CCRF-CEM cells, there was a greater ratio of cytotoxicity to genetic recombination following prolonged exposure to etoposide than following brief exposure.Implication: These data suggest that recombinogenesis is not inextricably linked to cytotoxicity. If confirmed in the clinical setting, the use of prolonged dosage schedules may provide a means to decrease the risk of etoposide-induced acute myeloid leukemia without compromising treatment efficacy. [ABSTRACT FROM AUTHOR]

MicroRNA-155 (mi R155) is required for antibody production after vaccination with attenuated Salmonella. mi R155-deficient B cells generated reduced germinal centre responses and failed to produce high-affinity immunoglobulin ( Ig)G1 antibodies. In this study, we observed up-regulation of mi R155 in the peripheral blood mononuclear cells ( PBMCs) of patients with myasthenia gravis ( MG), and mi R155 was also up-regulated in torpedo acetylcholine receptor ( T- AChR)-stimulated B cells. We used an inhibitor of mi R155 conjugated to anti- CD20 single-chain antibody to treat both the cultured B cells and the experimental autoimmune MG ( EAMG) mice. Our results demonstrated that silencing of mi R155 by its inhibitor impaired the B cell-activating factor ( BAFF)- R-related signalling pathway and reduced the translocation of nuclear factor ( NF)-κ B into the nucleus. Additionally, AChR-specific autoantibodies were reduced, which may be related to the altered amounts of marginal zone B cells and memory B cells in the spleens of EAMG mice. Our study suggests that mi R155 may be a promising target for the clinical therapy of MG. [ABSTRACT FROM AUTHOR]

Stress waves, known as acoustic emissions (AEs), are released by localized inelastic deformation events during the progressive failure of brittle rocks. Although several numerical models have been developed to simulate the deformation and damage processes of rocks, such as non-linear stress–strain behaviour and localization of failure, only a limited number have been capable of providing quantitative information regarding the associated seismicity. Moreover, the majority of these studies have adopted a pseudo-static approach based on elastic strain energy dissipation that completely disregards elastodynamic effects. This paper describes a new AE modelling technique based on the combined finite-discrete element method (FEM/DEM), a numerical tool that simulates material failure by explicitly considering fracture nucleation and propagation in the modelling domain. Given the explicit time integration scheme of the solver, stress wave propagation and the effect of radiated seismic energy can be directly captured. Quasi-dynamic seismic information is extracted from a FEM/DEM model with a newly developed algorithm based on the monitoring of internal variables (e.g. relative displacements and kinetic energy) in proximity to propagating cracks. The AE of a wing crack propagation model based on this algorithm are cross-analysed by traveltime inversion and energy estimation from seismic recordings. Results indicate a good correlation of AE initiation times and locations, and scaling of energies, independently calculated with the two methods. Finally, the modelling technique is validated by simulating a laboratory compression test on a granite sample. The micromechanical parameters of the heterogeneous model are first calibrated to reproduce the macroscopic stress–strain response measured during standard laboratory tests. Subsequently, AE frequency–magnitude statistics, spatial clustering of source locations and the evolution of AE rate are investigated. The distribution of event magnitude tends to decay as power law while the spatial distribution of sources exhibits a fractal character, in agreement with experimental observations. Moreover, the model can capture the decrease of seismic b value associated with the macrorupture of the rock sample and the transition of AE spatial distribution from diffuse, in the pre-peak stage, to strongly localized at the peak and post-peak stages, as reported in a number of published laboratory studies. In future studies, the validated FEM/DEM-AE modelling technique will be used to obtain further insights into the micromechanics of rock failure with potential applications ranging from laboratory-scale microcracking to engineering-scale processes (e.g. excavations within mines, tunnels and caverns, petroleum and geothermal reservoirs) to tectonic earthquakes triggering. [ABSTRACT FROM AUTHOR]

S100 A9 belongs to the S100 family of calcium-binding proteins and plays a key role in many inflammatory conditions. Recent studies have found that S100 A9 was elevated significantly in the bronchoalveolar lavage fluid of idiopathic pulmonary fibrosis patients, and might be a biomarker for fibrotic interstitial lung diseases. However, the exact function of S100 A9 in pulmonary fibrosis needs further studies. We performed this study to investigate the effect of S100 A9 on human embryo lung fibroblast ( HLF) proliferation and production of cytokines and collagen, providing new insights into the possible mechanism. S100 A9 promoted proliferation of fibroblasts and up-regulated expression of both proinflammatory cytokines interleukin ( IL)-6, IL-8, IL-1β and collagen type III. S100 A9 also induced HLF cells to produce α-smooth muscle actin (α- SMA) and receptor for advanced glycation end-product ( RAGE). In addition, S100 A9 caused a significant increase in extracellular-regulated kinase ( ERK)1/2 mitogen-activated protein kinase ( MAPK) phosphorylation, while the status of p38 and c-Jun N-terminal kinase ( JNK) phosphorylation remained unchanged. Treatment of cells with S100 A9 also enhanced nuclear factor kappa B ( NF-κ B) activation. RAGE blocking antibody pretreatment inhibited the S100 A9-induced cell proliferation, cytokine production and pathway phosphorylation. S100 A9-mediated cell activation was suppressed significantly by ERK1/2 MAPK inhibitor and NF-κ B inhibitor. In conclusion, S100 A9 promoted HLF cell growth and induced cells to secret proinflammatory cytokines and collagen through RAGE signalling and activation of ERK1/2 MAPK and NF-κ B pathways. [ABSTRACT FROM AUTHOR]

The objective of this study was to char-acterize variation and identify SNP and chromosomal regions associated with mineral concentrations in LM of Angus beef cattle. Samples of LM from 2,285 Angus cattle were obtained, and concentrations of 7 minerals, including iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc, were quantified. Genomic DNA extracted from the ground beef sample used for mineral composition was genotyped with the Bovine SNP50 Infinium II BeadChip, and effects of SNP on each trait were estimated using the Bayes-CΠ module of GenSel software. Pedigree-based estimates of heri-tabilities and corresponding genetic variances indicate iron was the only mineral concentration that could be considered a good candidate for manipulation by genomic selection. The amount of variation that could be accounted for by SNP genotypes was concordant with pedigree-based heritabilities and varied from very low for potassium and sodium (<0.09) to medium high (0.37) for iron. Although significant chromosomal regions were identified for all minerals analyzed in this study, further study focused on iron. Seven regions on 6 chromosomes (1, 2, 7, 10, 15, and 28) were identi-fied to have a major effect on the iron content of LM in Angus cattle. The accuracy of direct genomic values (DGV) for iron concentration was estimated using a 5-fold cross-validation strategy. The accuracy of DGV estimated as the genetic correlation between DGV and the phenotype (iron concentration) adjusted for con-temporary groups was 0.59. A bivariate animal model was used to estimate genetic correlations between iron concentrations and a reduced set of economically important carcass traits: HCW, rib eye area, calculated USDA yield grade, percent KPH, and marbling score. The genetic correlations between iron concentration and HCW, percentage KPH, marbling score, and rib eye area were small (-0.19 to 0.15) and nonsignificant. Although still weak (0.22), a positive significant genet-ic correlation was identified between iron content and USDA calculated yield grade. Beef is a major contribu-tor of iron and zinc in the human diet, and this study found that iron content might be effectively manipulat-ed through marker-assisted selection programs, without compromising other carcass and palatability traits. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of bowtie filtration on dedicated cone beam CT (CBCT) of the head and neck. Methods: A validated hybrid simulation technique was used to model a commercial CBCT system with offset scanning geometry, 90kV tube potential and 145x75mm imaging field of view. Three bowtie filters were formulated to produce uniform flux intensity in the projection image of cylindrical objects of diameter 14, 16 and 18 cm. The influence of these simulated filters was compared with the original flat filtration in terms of the output radiation field, the dose delivered to the object, the scatter distribution in projections and the quality of the reconstructed image. Results: Compared against flat filtration, dose reduction for the bowtie case, examined as a function of radial distance within a 16-cm-diameter water cylinder, varied from 8.7% at the centre to 53.8% at the periphery. Scatter reduction, quantified using scatter-to-primary ratio in projection images, was up to 37.6% for a 14-cm-diameter cylindrical contrast phantom. Using the supplied routine image reconstruction, bowtie filtration resulted in comparable noise appearance, contrast resolution and artefact pattern for computational anatomical phantoms, with <5% difference in contrast-to-noise ratio. Conclusion: Bowtie filtration can effectively reduce the dose and scatter in CBCT of the head and neck. For better image quality, corresponding modification to the image pre-processing and reconstruction is needed. Advances in knowledge: The hybrid simulation approach can usefully explore the impact of proposed system component and design changes. [ABSTRACT FROM AUTHOR]

Background Ichthyosis vulgaris (IV; OMIM 146700) is a very common inherited skin disorder. Loss-of-function mutations in the filaggrin gene ( FLG) have been identified as the cause of IV. In a previous study, we found that the percentage of FLG null mutations was lower in IV associated with atopic dermatitis (AD) than in IV not associated with AD (isolated IV). We speculated that some clinical manifestations of IV in patients with AD are not induced by FLG mutations. Objectives In order to clarify this issue, we collected 21 IV pedigrees, 33 patients with sporadic isolated IV and 116 patients with AD-associated IV to analyse FLG mutation frequency and filaggrin expression in isolated IV and AD-associated IV. Methods A comprehensive sequencing of the FLG gene in all patients was performed using an overlapping polymerase chain reaction (PCR) strategy. We also studied the immunohistochemistry of profilaggrin/filaggrin protein expression in the skin and measured the mRNA expression using real-time PCR in seven patients, including one patient with IV harbouring the mutation c.3321delA, two patients with AD-associated IV harbouring c.3321delA and c.6834del5, and four patients with AD-associated IV without FLG mutations. Results The percentage of mutations in the FLG gene was 74% and 43% in patients with isolated IV and patients with AD-associated IV, respectively. Immunohistochemical staining revealed that profilaggrin/filaggrin peptides were remarkably reduced in the epidermis of all the patients. All the patients with either AD or IV showed lower FLG mRNA expression compared with the normal control. Conclusions These results indicate that factors other than FLG gene mutations can downregulate profilaggrin/filaggrin expression, leading to the ichthyosiform phenotype in the context of AD. [ABSTRACT FROM AUTHOR]

After 2010, three outbursts of H1743−322 were detected by RXTE. We have carried out timing and spectral analysis of the data, emphasizing on the two with relatively complete evolution history presented in the RXTE/Proportional Counter Array observations. We then constitute an enlarged outburst sample for H1743−322 which allows us to investigate the spectral transitions in more details. We find that the spectral transitions to high-soft state constrain a region for four outbursts in hardness–intensity diagram. An extension of the region locates in the vicinity of the failed outburst in 2008, and excludes it from a successful group. We therefore suggest that the failed outburst in 2008 may present the first almost successful outburst sample, which is important for modelling the outburst, especially upon the conditions required for transition to high-soft state. [ABSTRACT FROM AUTHOR]

The objective of this study was to estimate genetic parameters for concentrations of minerals in LM and to evaluate their associations with beef palatabil-ity traits. Samples of LM from 2,285 Angus cattle were obtained and fabricated into steaks for analysis of mineral concentrations and for trained sensory panel assessments. Nine minerals, including calcium, copper, iron, magne-sium, manganese, phosphorus, potassium, sodium, and zinc, were quantified. Restricted maximum likelihood procedures were used to obtain estimates of variance and covariance components under a multiple-trait animal model. Estimates of heritability for mineral concentrations in LM varied from 0.01 to 0.54. Iron and sodium were highly and moderately heritable, respectively, whereas the other minerals were lowly heritable except for calcium, copper, and manganese, which exhibited no genetic varia-tion. Strong positive genetic correlations existed between iron and zinc (0.49, P < 0.05), between magnesium and phosphorus (0.88, P < 0.05), between magnesium and sodium (0.68, P < 0.05), and between phosphorus and potassium (0.69, P < 0.05). Overall tenderness assessed by trained sensory panelists was positively associated with manganese, potassium, and sodium and negatively associated with phosphorus and zinc concentrations (P < 0.05). Juiciness assessed by trained sensory panelists was negatively associated with magnesium and positively associated with manganese and sodium concentrations [P < 0.05). Livery or metallic flavor was not associated with any of the minerals (P > 0.05). Beefy flavor was positive-ly associated with calcium, iron, and zinc and negatively associated with sodium concentration, whereas a painty or fishy flavor was positively associated with sodium and negatively associated with calcium and potassium con-centrations (P < 0.05). Beef is a major contributor of iron and zinc in the human diet, and these results demonstrate sufficient genetic variation for these traits to be improved through marker-assisted selection programs without com-promising beef palatability. [ABSTRACT FROM AUTHOR]

SUMMARY The goal of this study was to explore the molecular mechanism of hypoxia inducible factor-1 alpha (HIF-1 alpha) action on migration and invasion of esophageal carcinoma cells. We used cobalt chloride (CoCl2) to mimic tumor hypoxic microenvironment and analyzed the expressions of E-cadherin, matrix metalloproteinase-2 (MMP-2), and HIF-1 alpha in esophageal carcinoma cells under hypoxia by reverse transcription polymerase chain reaction and Western blotting. To analyze the function of HIF-1 alpha in Eca109 and TE1 cells, we established stable HIF-1 alpha knockdown cells using small interfering RNA. Blocking effect was detected by Western blotting. The concentrations of MMP-2 protein in the conditioned medium were also determined by enzyme-linked immunosorbent assay. Wound-healing and cell invasion assay were used to evaluate the migration and invasion of esophageal carcinoma cells. After exposure to hypoxia, expressions of HIF-1 alpha protein in Eca109 and TE1 cells were upregulated, both mRNA and protein levels of E-cadherin were downregulated, and MMP-2 were upregulated ( P < 0.05), whereas HIF-1 alpha mRNA had no significant change ( P > 0.05). Small interfering RNA could block HIF-1 alpha effectively under hypoxia, then enhanced E-cadherin expression and inhibited MMP-2 expression, respectively. Furthermore, expression of HIF-1 alpha protein was stable even though MMP-2 repressed by BB2516. Compared with that in normoxia, Snail expression was enhanced when Eca109 or TE1 cells exposed to hypoxia. Once HIF-1 alpha blocked, Snail expressions were inhibited accordingly. Wound recovery and the number of invading cells decreased ( P < 0.05) after HIF-1 alpha blocked. The hypoxia suppresses E-cadherin expression and enhances MMP-2 expression favoring esophageal carcinoma migration and invasion via HIF-1 alpha activation. Our observations suggest that HIF-1 alpha inhibition might be an effective strategy to weaken the migration and invasion of esophageal carcinoma cells. [ABSTRACT FROM AUTHOR]

Background: Elevated levels of antibodies against antigens in the Epstein-Barr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence.Methods: We conducted a case-control study using data from male case patients (n = 1316) and control subjects (n = 1571) living in Guangdong Province, an area in China at high risk for NPC, to study potential NPC risk factors and EBV inducers. Two independent healthy male populations from a second high-risk area (n = 1657) and a low-risk area (n = 1961) were also included in the analysis of potential EBV inducers using logistic regression models. In vitro assays were performed to investigate the effect of cigarette smoke extract on EBV activation in two EBV-positive cell lines. All statistical tests were two-sided.Results: Smoking was associated with an increased risk of NPC among the Guangdong participants with 20-40 and 40 or more pack-years vs never smokers (OR = 1.52, 95% CI = 1.22 to 1.88 and OR = 1.76, 95% CI = 1.34 to 2.32, respectively; P (trend) < .001). Smoking was the only factor linked to EBV seropositivity among the expanded control group and the independent low-risk population. In vitro experiments showed that cigarette smoke extract promoted EBV replication, induced the expression of the immediate-early transcriptional activators Zta and Rta, and increased transcriptional expression levels of BFRF3 and gp350 in the lytic phase.Conclusion: Smoking is not only associated with NPC risk in individuals from China but is also associated with EBV seropositivity in healthy males and is involved in EBV activation. [ABSTRACT FROM AUTHOR]

Aims: Daptomycin, one of the A21978C factors produced by Streptomyces roseosporus, is an acidic cyclic lipopeptide antibiotic with potent activity against a variety of Gram-positive pathogens. To increase the titre of this extensively used and clinically important antibiotic, we applied a reported-guided rpsL mutation selection system to generate strains producing high levels of A21978C. Methods and Results: In the reporter design, dptE was chosen as the overexpressing target, and neo-encoding neomycin phosphotransferase as the reporter. Using this reporter-guided selection system, 20% of the selected, streptomycin-resistant mutants produced greater amounts of A21978C than the starting strain. The selection system increased the screening efficiency about 10-fold with a frequency of 1·7% A21978C overproducing strains among str r mutants. A21978C production was increased approximately 2·2-fold in the rpsL K43N mutant. Conclusions: The combination of ribosome engineering and reporter-guided mutant selection generated an A21978C overproducing strain that produced about twice as much A21978C as the parental strain. Significance and Impact of the Study: The strategies presented here, which integrated the advantages of both ribosome engineering and reporter-guided mutation selection, could be applied to other bacteria to improve their yield of secondary metabolites. [ABSTRACT FROM AUTHOR]

Aims: Subcellullar localizations and cross-immunities of GAPDHs from six common pathogenic bacteria in aquaculture were investigated. Methods and Results: Subcellullar localizations of GAPDHs of Edwardsiella tarda EIB202, Edwardsiella ictaluri ATCC33202, Aeromonas hydrophila LSA34, Vibrio anguillarum MVM425, Vibrio alginolyticus EPGS020401 and Vibrio harveyi VIB647 were analysed with Western blotting, indirect immunofluorescence and flow cytometry examinations. Immunoprotections of different recombinant GAPDHs against these pathogens were investigated with zebrafish model. Western blotting of subcellular extractions showed that all GAPDHs were secreted into extracellular medium and periplasmic space. In addition, GAPDHs were demonstrated to distribute in the outer membranes except MVM425 and VIB647. And, GAPDHs were confirmed to be present on the surface of these bacteria with indirect immunofluorescence and flow cytometry examinations. The remarkable cross-protective immunities of these recombinant GAPDHs were induced in zebrafish, and the relative protective survivals were almost over 60%. Conclusions: Localizations of GAPDHs from these pathogenic bacteria were similar to many other causative agents. And, GAPDHs could be important protective antigens and give remarkable cross-immunity against different pathogens. Significance and Impact of the Study: Recombinant GAPDH could be designed as a broad spectrum vaccine candidate against multiple microbial infections in aquaculture. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a fatal disease with great public health impact worldwide. Heme oxygenase (HO)-1 has recently been reported as an important player in tumor angiogenesis and metastasis. However, the role of HO-1 in liver cancer metastasis is unclear. In this study, we explored genetic differences and downstream signal transduction pathways of HO-1 in liver cancer cell lines. HO-1 wild-type and mutant cell lines were generated from human liver cancer cell line HepG2. The overexpression of wild-type HO-1 decreased the migration of HepG2 cells. In contrast, the overexpression of mutant HO-1G143H increased the migration of the cancer cells. Interleukin (IL)-6 is one of the major downstream molecules that mediated this process because IL-6 expression and migration are suppressed by HO-1 and increased when HO-1 is knocked down by shRNA. In addition, we demonstrated carbon monoxide (CO) and p38MAPK are the cofactors in this signal pathway. In vivo animal model demonstrated HO-1 inhibited the tumor growth. In conclusion, in vitro and in vivo data show HO-1 inhibits the human HCC cells migration and tumor growth by suppressing the expression of IL-6. The heme degradation product CO is a cofactor in this process and inhibits p38MAPK phosphorylation. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to classify Edwardsiella strains isolated from China aquaculture based on biochemical and molecular methods. Methods and Results: In this study, biochemical characterization of 19 Edwardsiella tarda isolates and two Edwardsiella ictaluri isolates was performed with API 20E system. Other pathogenicity-related phenotypes such as haemagglutination, haemolytic activities and lethality to fish were also examined in these strains. As it was difficult to categorize the subgroups of Edw. tarda according to their origins or phenotypic properties, three PCR-based methods, i.e. PCR amplification of virulence genes, Enterobacterial repetitive intergenic consensus-PCR and BOX-PCR, were carried out to further resolve the relatedness of the Edw. tarda isolates. As a result, all Edw. tarda isolates could be generally grouped into pathogenic and nonpathogenic branches before being classified into strain-specific or origin-specific clades. Conclusions: Biochemical characterization was sensitive for interspecific typing, while PCR-based approaches permitted a more accurate discrimination for intraspecific typing resulting in pathogenic and nonpathogenic clusters and further more delicate clades for Edwardsiella. Significance and Impact of the Study: PCR-based genomic fingerprinting to study the relatedness and trace the pathogenicity of the Edwardsiella strains will be helpful in investigating the virulence factors of Edwardsiella and in the development of vaccines and diagnostics for edwardsiellosis. [ABSTRACT FROM AUTHOR]