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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

ABSTRACT The relation between the spin period ( Ps) and the orbital period ( Po) in high-mass X-ray binaries is investigated. Be/X-ray binaries and SG/X-ray binaries occupy different areas in the Corbet diagram. The supergiant fast X-ray transients, IGR J18483-0311 and IGR J11215-5952, however, fall into the area occupied by Be/X-ray binaries. After excluding the other evolution scenarios, we find that the positions of the two supergiant fast X-ray transients in the diagram can be interpreted by being the descendants of O-emission X-ray binaries, i.e. the supergiant stars in these systems formed from O-type emission line stars instead of normal main-sequence stars. Therefore, we suggest that there are two types of SG/X-ray binaries: the first one is directly evolved from OB-type main-sequence star and neutron star systems without accretion history, and the other evolved from Be/X-ray binaries with accretion history. [ABSTRACT FROM AUTHOR]

SUMMARY The prognosis of esophageal squamous cell carcinoma (ESCC) is poor. It is urgent to improve this situation. Epidermal growth factor receptor (EGFR)-targeted therapy possesses a promising clinical efficacy. Mutations of EGFR and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified in esophageal carcinoma, but corresponding Chinese data are limited. So we investigated the mutation status of EGFR and KRAS in Chinese patients with ESCC, and explored their correlations with clinicopathological features. Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 50 randomly selected Chinese patients with ESCC. EGFR mutations in exons 18-21 were detected by Scorpions amplification refractory mutation system technology. KRAS mutations in codons 12, 13 were detected by direct sequencing of polymerase chain reaction products. The correlations between clinicopathological features and the mutation status of EGFR and KRAS were analyzed using the Statistical Package for the Social Sciences. In the present study, EGFR mutations were found in 7 (14%) out of 50 patients, including G719X missense mutation ( n= 1), in-frame deletion ( n= 2), and L858R missense mutation ( n= 5). Six (12%) out of 50 patients had KRAS mutations in codon 12. Concurrent EGFR and KRAS mutations were detected in one sample. The presences of EGFR and KRAS mutations were not associated with gender, age, smoking history, cell differentiation, or cancer stage. In conclusion, the incidence of EGFR mutations in Chinese patients with ESCC was higher than that of previous reports, and the incidence of KRAS mutations was not low. EGFR and KRAS mutations were mainly located in exons 19 and 21 and codon 12, respectively. Unlike in NSCLC, concurrent EGFR and KRAS mutations existed. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the radiation exposure levels in victims of a 60Co radiation accident using chromosome aberration analysis and the micronucleus assay. Peripheral blood samples were collected from three victims exposed to 60Co 10 days after the accident and were used for the chromosome aberration and micronucleus assays. After in vitro culture of the lymphocytes, the frequencies of dicentric chromosomes and rings (dic+r) and the numbers of cytokinesis blocking micronuclei (CBMN) in the first mitotic division were determined and used to estimate radiation dosimetry. The Poisson distribution of the frequency of dic+r in lymphocytes was used to assess the uniformity of the exposure to 60Co radiation. Based on the frequency of dic+r in lymphocytes, estimates of radiation exposure of the three victims were 5.61 Gy (A), 2.48 Gy (B) and 2.68 Gy (C). The values were estimated based on the frequencies of CBMN, which were 5.45 Gy (A), 2.78 Gy (B) and 2.84 Gy (C). The estimated radiation dosimetry demonstrated a critical role in estimating the radiation dose and facilitating an accurate clinical diagnosis. Furthermore, the frequencies of dir+r in victims A and B deviated significantly froma normal Poisson distribution. Chromosome aberration analysis offers a reliable means for estimating biological exposure to radiation. In the present study, the micronucleus assay demonstrated a high correlation with the chromosome aberration analysis in determining the radiation dosimetry 10 days after radiation exposure. [ABSTRACT FROM AUTHOR]

We use deep Hubble Space Telescope photometry of the rich, young (∼20- to 45-Myr old) star cluster NGC 1818 in the Large Magellanic Cloud to derive its stellar mass function (MF) down to . This represents the deepest robust MF thus far obtained for a stellar system in an extragalactic, low-metallicity environment. Combining our results with the published MF for masses above , we obtain a complete present-day MF. This is a good representation of the cluster's initial MF (IMF), particularly at low masses, because our observations are centred on the cluster's uncrowded half-mass radius. Therefore, stellar and dynamical evolution of the cluster will not have affected the low-mass stars significantly. The NGC 1818 IMF is well described by both a lognormal and a broken power-law distribution with slopes of and (Salpeter-like) for masses in the range from 0.15 to and greater than , respectively. Within the uncertainties, the NGC 1818 IMF is fully consistent with both the Kroupa solar neighbourhood and the Chabrier lognormal mass distributions. [ABSTRACT FROM AUTHOR]

In this paper, the numerical simulation of the 3D seepage flow with fractional derivatives in porous media is considered under two special cases: non-continued seepage flow in uniform media (NCSF-UM) and continued seepage flow in non-uniform media (CSF-NUM). A fractional alternating direction implicit scheme (FADIS) for the NCSF-UM and a modified Douglas scheme (MDS) for the CSF-NUM are proposed. The stability, consistency and convergence of both FADIS and MDS in a bounded domain are discussed. A method for improving the speed of convergence by Richardson extrapolation for the MDS is also presented. Finally, numerical results are presented to support our theoretical analysis. [ABSTRACT FROM PUBLISHER]

Aims: To investigate VP37 [WSV 254 of White spot syndrome virus (WSSV) genome] interacting with shrimp cells and protecting shrimp against WSSV infection. Methods and Results: VP37 was expressed in Escherichia coli and was confirmed by Western blotting. Virus overlay protein binding assay (VOPBA) technique was used to analyse the rVP37 interaction with shrimp and the results showed that rVP37 interacted with shrimp cell membrane. Binding assay of recombinant VP37 with shrimp cell membrane by ELISA confirmed that purified rVP37 had a high-binding activity with shrimp cell membrane. Binding of rVP37 to shrimp cell membrane was a dose-dependent. Competition ELISA result showed that the envelope protein VP37 could compete with WSSV to bind to shrimp cells. In vivo inhibition experiment showed that rVP37 provided 40% protection. Inhibition of virus infection by rVP37 in primary cell culture revealed that rVP37 counterparted virus infection within the experiment period. Conclusions: VP37 has been successfully expressed in E. coli. VP37 interacted with shrimp cells. Significance and Impact of the Study: The results suggest that rVP37 has a potential application in prevention of virus infection. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) class I antigen-processing machinery components defects are found in many tumors, which may have a negative impact on the outcome of T-cell based immunotherapy. Scant information is available about antigen-processing machinery component expression in esophageal squamous cell carcinoma (ESCC). Here, we investigated that HLA class I, β2-microglobulin (β2m), and transporter associated with antigen processing subunit (TAP1) expression in 160 formalin-fixed and paraffin-embedded esophageal lesions (120 primary ESCC and 40 matched lymph node metastases) in a tissue microarray by immunohistochemical staining. A synchronous downregulation of HLA class I, β2m, and TAP1 was observed in 57.3% of primary and 64.7% of metastatic lesions. And at least one of these three molecules exhibited an impaired expression in all metastatic and 95% of primary ESCC lesions. Only TAP1 expression was more frequently (P < 0.001) downregulated in metastatic than in primary ESCC lesions, and significantly (P < 0.05) associated with tumor grade. HLA class I, β2m, and TAP1 expression was more frequently downregulated in primary ESCC lesions with lymph node metastasis than those without lymph node metastasis (HLA class I: P = 0.003, β2m: P = 0.034, and TAP1: P = 0.028). Our findings suggest that abnormalities of HLA class I, β2m, and TAP-1 expression is a frequent event in ESCC, which might provide ESCC cells with a mechanism to escape from cytotoxic T lymphocyte recognition. The present study emphasizes the need to evaluate the antigen-processing pathway in ESCC patients, particularly in those selected for T-cell based immunotherapies. [ABSTRACT FROM AUTHOR]

This stroke experiment was designed to define the mismatch between perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in MRI by applying early or instantly acquired PWI. Eight rats were induced with stroke through photothrombotic occlusion of the middle cerebral artery and scanned serially between 1 h and day 3 after induction using DWI and PWI with a 1.5 T MR scanner. The relative lesion volumes (rLV) on MRI and triphenyl tetrazolium chloride-stained specimens were defined as the proportion of lesion volume over brain volume. Discrepancies in the rLV between PWI- and DWI-derived apparent diffusion coefficient (ADC) maps were expressed by subtraction of the ADC from PWI, resulting in three possible patterns: (i) (PWI-ADC > 10% of PWI) denoting a mismatch; (ii) (-(10% of PWI) ⩽ PWI-ADC ⩽ 10% of PWI) denoting a match; and (iii) (PWI-ADC < -(10% of PWI)) denoting a reverse mismatch. The differences were compared with the minuend being either early PWI (ePWI) or instant PWI (iPWI) and the subtrahend being instant ADC (iADC). The occurrence and evolution of PWI-ADC patterns were analysed. Over time, PWI-ADC discrepancies evolved from mismatch, through to match, to reversed mismatch. The PWI-ADC mismatch still existed 3 days after MCA occlusion in one to three of the eight cases. The rLVs and mismatch incidences between the ePWI-iADC and iPWI-iADC models were linear correlated. A higher mismatch rate occurred in iPWI-iADC within day 1 and in ePWI-iADC at day 3. Both ePWI and iPWI proved useful to define PWI-ADC patterns within day 1. At day 3, iPWI appeared more adequate. [ABSTRACT FROM AUTHOR]

Background Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. Objectives To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. Methods Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. Results The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. Conclusions The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus. [ABSTRACT FROM AUTHOR]

Aims: To characterize the luxO gene in fish pathogen Vibrio alginolyticus MVP01 and investigate its roles in regulation of extracellular products (ECP) and siderophore production. Methods and Results: The luxO gene was cloned from V. alginolyticus MVP01. Genetic analysis revealed that it encoded a protein with high similarity to other LuxO homologues. The luxO in-frame deletion mutant and rpoN null mutant were constructed with suicide plasmids. We demonstrated that sole deletion in LuxO increased the secretion of extracellular protease and haemolytic products, but decreased siderophore production for V. alginolyticus MVP01. Mutants with null rpoN displayed significantly enhanced protease level and siderophore production while notable reduction in haemolytic activities of ECP. Conclusions: Vibrio alginolyticus harbours functional luxO gene that regulates the secretion of extracellular protease and haemolytic materials as well as siderophore production in either σ54 dependent or independent manners. Significance and Impact of the Study: The current study demonstrated that V. alginolyticus MVP01 produces extracellular protease and haemolytic activity material as well as siderophore, which may be characteristics of the virulence of the strain. Revelations that secretion of these products is under the regulation of LuxO and σ54 as well as the potential quorum sensing systems in V. alginolyticus MVP01 will expedite the understanding of vibriosis pathogenesis. [ABSTRACT FROM AUTHOR]

Background Dyschromatosis symmetrica hereditaria (DSH, MIM 127400) is a dominantly inherited skin disease associated with mutations in ADAR, the gene that encodes a double-stranded RNA-specific adenosine deaminase. We previously reported two novel ADAR mutations (p.Q513X and p.R916W) and confirmed the role of ADAR in Chinese patients with DSH. Both haploinsufficiency and a dominant-negative effect have been suggested as the potential mechanism by which ADAR mutations cause DSH. Objectives To identify ADAR mutations in two additional Chinese DSH families and to obtain insight into the pathogenic mechanism of heterozygous ADAR mutations. Methods For mutation detection, all ADAR exons and their flanking intronic sequences were amplified and sequenced. Mutations were further confirmed by restriction analysis. Direct sequencing of cDNA fragments produced by reverse transcription–polymerase chain reaction (RT–PCR) and real-time quantitative RT–PCR were used to examine the expression of ADAR in peripheral lymphocytes isolated from affected individuals. Results A small deletion, c.1555delT (p.C519fs), and a missense mutation, c.3116A>G (p.K1039R), were found in families A and B, respectively. In individuals carrying p.Q513X or p.C519fs, sequencing of cDNA fragments indicated almost total loss of mRNA expression from the mutant alleles, and real-time quantitative RT–PCR showed an approximately 50% reduction of ADAR expression. However, equal abundance of the wild-type and mutant cDNA sequences without reduction of ADAR expression was found in a patient with the missense p.R916W mutation. These results suggest that both the nonsense p.Q513X and frameshift p.C519fs mutations have generated null alleles probably by nonsense-mediated mRNA decay. Conclusions Two novel ADAR mutations were found in Chinese patients with DSH. Evidence for ADAR haploinsufficiency as a mechanism underlying the molecular pathogenesis of DSH was obtained. [ABSTRACT FROM AUTHOR]

s.-f. yang, q.-s. liu, j.-h. tay and y. liu. 2004. This paper attempts to develop a kinetic model to describe the growth of aerobic granules developed under different operation conditions. A series of experiments were conducted by using four-column sequencing batch reactors to study the formation of aerobic granules under different conditions, e.g. organic loading rates, hydrodynamic shear forces and substrate N/COD ratios. A simple kinetic model based on the Linear Phenomenological Equation was successfully derived to describe the growth of aerobic granules. It was found that the growth of aerobic granules in terms of equilibrium size and size-dependent growth rate were inversely related to shear force imposed to microbial community, while a high organic loading favoured the growth of aerobic granules, leading to a large size granule. The effect of substrate N/COD ratio on the growth kinetics of aerobic granules was realized through change in microbial populations, and enriched nitrifying population in aerobic granules developed at high substrate N/COD ratio resulted in a low overall growth rate of aerobic granules. The proposed model can provide good prediction for the growth of aerobic granules indicated by the correlation coefficient >0·95. The kinetic model proposed could offer a useful tool for studying the growth kinetics of cell-to-cell immobilization process. The study confirmed that the growth of aerobic granules and biofilms are subject to a similar kinetic pattern. This work would also be helpful for better understanding the mechanism of aerobic granulation. [ABSTRACT FROM AUTHOR]

Aims: This paper attempts to investigate the role of cellular polysaccharides in the formation and stability of aerobic granules. Methods and Results: Three column sequential aerobic sludge blanket reactors (R1, R2 and R3) were operated at a superficial air upflow velocity of 0·3 cm s–1, 1·2 cm s–1 and 2·4 cm s–1, respectively. Aerobic granules appeared at cycle 42 in R2 and R3 with a mean size of 0·37 mm in R2 and 0·35 mm in R3, however, aerobic granulation was not observed in R1. After the formation of aerobic granules, the sludge volume index (SVI) decreased to 55 ml g–1 in R2 and 46 ml g–1 in R3. Aerobic granulation was concurrent with a sharp increase of cellular polysaccharides normalized to cellular proteins, which increased from 5·7 to 13·0 mg per mg proteins in R2, and 7·5–13·9 mg per mg protein in R3. The content of polysaccharides in aerobic granules was 2–3 times higher than that in the bioflocci cultivated in R1. The disappearance of aerobic granules in R2 was tightly coupled to a drop in cellular polysaccharides. After the reappearance of bioflocci in R2, the content of cellular polysaccharides were found to be restored to the level observed in R1. Conclusions: It appears that the production of cellular polysaccharides could be stimulated by hydrodynamic shear force and contributes to the formation and stability of aerobic granules. Significance and Impact of the Study: It is expected that this study would provide useful information for better understanding the mechanisms of aerobic granulation. [ABSTRACT FROM AUTHOR]

Aims: This paper attempts to provide visual evidence of how aerobic granulation evolves in sequential aerobic sludge blanket reactors. Methods and Results: A series of experiments were conducted in two column-type sequential aerobic sludge reactors fed with glucose and acetate as sole carbon source, respectively. The evolution of aerobic granulation was monitored using image analysis and optical and scanning electron microscopy. The results indicated that the formation of aerobic granules was a gradual process from seed sludge to compact aggregates, further to granular sludge and finally to mature granules with the sequential operation proceeding. Glucose- and acetate-fed granules have comparable characteristics in terms of settling velocity, size, shape, biomass density and microbial activity. However, the microbial diversity of the granules was associated with the carbon source supplied. In this work, an important aerobic starvation phase was identified during sequential operation cycles. It was found that periodical aerobic starvation was an effective trigger for microbial aggregation in the reactor and further strengthened cell–cell interaction to form dense aggregates, which was an essential step of granulation. The periodical starvation-induced aggregates would finally be shaped to granules by hydrodynamic shear and flow. Conclusions: Aerobic granules can be formed within 3 weeks in the systems. The periodical starvation and hydrodynamic conditions would play a crucial role in the granulation process. Significance and Impact of the Study: Aerobic granules have excellent physical characteristics as compared with conventional activated sludge flocs. This research could be helpful for the development of an aerobic granule-based novel type of reactor for handling high strength organic wastewater. [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]

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]

A response from the authors of the article "Novel Clinical and Molecular Findings in Chinese Families With Hailey-Hailey Disease" in a previous issue is presented.

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]

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]

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]

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]

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]

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]

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]

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]

Background: Radiofrequency ablation (RFA) is a relatively new treatment for hypersplenism. The results of a randomized clinical trial comparing RFA and splenectomy with 5 years of follow-up are reported. Methods: Fifty-seven patients with hypersplenism due to liver cirrhosis were assigned randomly (in a 1 : 2 ratio) to splenectomy (19 patients) or RFA (38). The RFA group was subdivided according to the percentage of the spleen ablated: less than 50 per cent (9 patients), 50-70 per cent (18) or over 70 per cent (11). Routine blood tests were performed before and after operation, and total spleen volume and ablated volume were measured by contrast-enhanced computed tomography. The primary endpoint of the trial was recurrence of hypersplenism, assessed as platelet and white cell counts, at 5 years after surgery. Results: White cell and platelet counts increased rapidly after intervention in both groups. By 36 months after operation peripheral platelet and white cell counts had decreased significantly in the RFA group compared with the splenectomy group, and declined to baseline levels by 48 months. Hypersplenism recurred after 6 months in patients with less than 50 per cent of the spleen ablated. Blood cell count in the splenectomy group and in patients with more than 50 per cent of the spleen ablated decreased with time after operation, but to levels that remained significantly higher than those before operation (P < 0.050). Splenic volume reached its nadir 12 months after RFA and then increased with time. Conclusion: Splenic RFA represents an attractive alternative treatment for hypersplenism induced by liver cirrhosis, particularly when more than 50 per cent of the spleen is ablated. [ABSTRACT FROM AUTHOR]

P and S receiver functions obtained from a portable array of 34 broad-band stations in east central China provide a detailed image of the crust–mantle and lithosphere–asthenosphere boundaries (LAB) in the Dabie Shan and its adjacent areas. Clear S-to- P converted waves produced at the LAB show a thin lithosphere beneath the whole study area. Based on our results, the thickest lithosphere of 72 km is observed beneath the southern part of the area within the Yangtze craton, whereas beneath the North-China platform, the lithosphere is only 60 km thick. S receiver functions also reveal, in good agreement with P receiver functions, a maximum depth of the Moho beneath the Dabie Shan orogen at approximately 40 km. Furthermore, we interpret the structural difference at 32° latitude as the probable location of the mantle suture formed between the Yangtze and the Sino-Korean cratons. [ABSTRACT FROM AUTHOR]

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]

Darier disease (DD) is a rare autosomal dominant skin disorder with characteristic abnormal keratinization and acantholysis. The causative gene, ATP2A2, is located on chromosome 12, and encodes a sarco/endoplasmic reticulum calcium pump ATPase (SERCA2). Two Chinese patients with sporadic DD participated in this study. Genomic sequence analysis identified two novel missense mutations (c.742C>A and c.2098A>G) in the ATP2A2 gene. Our findings provide an additional ATP2A2 mutation causative for DD development, and new lines of evidences for the understanding of genotype-phenotype correlations. [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]

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]

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]

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]