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Rabbit hemorrhagic disease virus (RHDV) is a member of the Caliciviridae family and cannot be propagated in vitro, which has impeded the progress of investigating its replication mechanism. Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells. Here, aided by this replicon system and using two-step affinity purification, we purified the RHDV replicase and identified its associated host factors. We identified rabbit nucleolin (NCL) as a physical link, which mediating the interaction between other RNA-dependent RNA polymerase (RdRp)-related host proteins and the viral replicase RdRp. We found that the overexpression or knockdown of NCL significantly increased or severely impaired RHDV replication in RK-13 ​cells, respectively. NCL was identified to directly interact with RHDV RdRp, p16, and p23. Furthermore, NCL knockdown severely impaired the binding of RdRp to RdRp-related host factors. Collectively, these results indicate that the host protein NCL is essential for RHDV replication and acts as a physical link between viral replicase and host proteins.

An improved in vacuo in situ quantitative analytical method for the deposited impurities on the inner-wall of tokamak device is reported.

This work reports on the plasmonic properties of a symmetry-breaking system consisting of rhodium dual broken nanorings, in the ultraviolet-visibleregime. In the structure, two rhodium broken rings are located with a separation on the scale of nanometers. As the separation, the light polarization,and the relative orientation of the broken angles are respectively varied, theplasmonic scattering efficiency of the system is investigated, using the finite difference time domain method. Multiple plasmonic resonances are revealed,and the associated asymmetry-induced Fano-like lineshapes are fitted to amodel that employs multiple Fano lineshape functions. The resonance wave-lengths, the spectral widths, and the characteristic q values are determinedfrom the best fit parameters, and the plasmonic characteristics of the sys-tem are quantitatively probed. The results in this work may be beneficial indesigns of plasmonic devices that operates at ultraviolet-visible wavelengths.

This work reports on the plasmonic properties of a symmetry-breaking system consisting of rhodium dual broken nanorings, in the ultraviolet-visible regime. In the structure, two rhodium broken rings are located with a separation on the scale of nanometers. As the separation, the light polarization, and the relative orientation of the broken angles are respectively varied, the plasmonic scattering efficiency of the system is investigated, using the finite difference time domain method. Multiple plasmonic resonances are revealed, and the associated asymmetry-induced Fano-like lineshapes are fitted to a model that employs multiple Fano lineshape functions. The resonance wavelengths, the spectral widths, and the characteristic q values are determined from the best fit parameters, and the plasmonic characteristics of the system are quantitatively probed. The results in this work may be beneficial in designs of plasmonic devices that operates at ultraviolet-visible wavelengths.

Simultaneously manipulating adsorption thermodynamics/kinetics and site density to realize the efficient adsorption capability of single-atom materials was important for adsorption-related catalysis, separation or purification, but remained challenging. Taking adsorptive desulfurization as a model, we reported a simple protonation of pyridinic-N strategy that notably improved the adsorption capability of Cu-N-C for dibenzothiophene via the cation-π and Cu-S interaction. The pyridinic-NH+ both acted as adsorption site and modulated the N-ligand field to elongate Cu-N bond to enhance the bonding strength of single-atom Cu site for organosulfur via upshifting the d-band center, thereby causing a higher desulfurization capacity of Cu-N-C than its counterparts. Moreover, the protonation reconstructed the surface electric field of Cu-N-C to weaken the repulsion effect between Cu-N-C and dibenzothiophene, which along with the abundant porous channel accelerated mass transfer and accumulation of dibenzothiophene around adsorption sites. This endowed Cu-N-C with a 2.4~310-fold higher adsorption kinetics than most reported adsorbents, thus achieving a ultrafast decrease of sulfur level (

In this work, the optical properties of a rhodium I-shaped nanomaterial are studied. In the UV-visible regime, the scattering efficiency and the electric field are calculated via the finite-difference time-domain method, with the parameters varying including the height, the length ratio, and the polarization of the incident light. The results show that multiple resonance peaks are observed in the scattering spectrum in the ultraviolet region, corresponding to different electromagnetic modes. It is also revealed that the peak strength of the nanostructure can be effectively tuned by adjusting the structural parameters. The proposed rhodium nanomaterial may provide a theoretical basis for the design of optical devices in the ultraviolet regime. The obtained results provide useful guidance for the implementation of nanoantenna and fluorescence enhancement, etc.

With the proliferation of modern integrated electronic and telecommunication systems, high-performance electromagnetic interference (EMI) shielding materials with flexibility, outstanding thermal conductive properties and superior EMI shielding performances are designed to solve the problems of electromagnetic radiation and heat accumulation. Herein, flexible asymmetric trilaminar architecture film with good mechanical properties is prepared via the facile three-step vacuum-assisted filtration (VAF) followed by hot-pressing approach, which is composed of silver-plated aramid nanofibers (ANF-Ag), ANF- Fe3O4&CNT (ANF-FC) and ANF-reduced graphene oxide (ANF-rGO) layers. The conductive ANF-Ag and ANF-rGO layers acted as the EMI shielding, thermal conductive layers, and supporting substrate layers. The magnetic ANF-FC layer played the role in synergistically enhancing the EMI shielding performance. The resultant flexible and asymmetric trilaminar hybrid membrane exhibited maximum thermal conductivity of 8.5 W·m-1K-1 and EMI SE of 67.5 dB, but also maintained a high tensile strength of 75.5 MPa and superb electrical conductivity of 2.46×106 S/m. This asymmetric trilaminar structures film holds great promise to addresses issues of electromagnetic radiation and heat accumulation for personal smart electronic devices, wearable electronics, electronic telecommunication systems.

Covalently bonded carbon nitride (CN) has stimulated extensive attention as a metal-free semiconductor. However, because of the complexity of polymeric structures, the acquisition of critical roles of each molecular constituent in CN for photocatalysis remains elusive. Herein, we clarify the fundamental active units of CN in photocatalysis by synthesizing CN with more detailed molecular structures. Enabled by microwave synthesis, the as-prepared CN consists of distinguishable melem (M1) and its incomplete condensed form (M2). We disclose rather than the traditional opinion of being involved in the whole photocatalytic processes, M1 and M2 make primary contributions in light absorption and charge separation, respectively. Meanwhile, oxygen molecules are unusually observed to be activated by participating in the photoexcited processes via electronic coupling mainly to M2. As a result, such CN has a higher activity, which was up to 8 times that of traditional bulk CN for photocatalytic oxidation of tetracycline in water., The acquisition of critical roles of each molecular constituent in carbon nitrides for photocatalysis remains elusive. Here the authors synthesize carbon nitrides with distinguishable units and reveal the roles of the different units in light absorption and charge separation.

In this work a graphene-photonic crystal composite structure is proposed, in which graphene nanoribbons are placed on top of a photonic crystal that is composed of two alternating dielectric materials. The optical properties of the composite structure are investigated in the infrared regime, by varying the Fermi energy, the layer number of the graphene, as well as the polarization angle of the incident light. Plasmonic resonance effects are revealed and the resonance wavelength, the peak width, and the peak intensity are determined. Quantitatively, the polarization-angle dependent peak intensity is well fitted to a trigonometric function. It is demonstrated that the resonance peak is quite sensitive to the dielectric material that is adjacent to the graphene. It is also shown that the structure has a high sensitivity of 7660 nm/RIU to the refractive index of the surrounding environment, with a figure of merit of 6.38. Based on the results, the graphene-photonic crystal composite structure proposed in this work may have potential applications in designing of plasmonic devices, such as ones that can be used to detect subtle variations in the refractive index of surrounding environments.

The magnetic field is the most common element in the universe, and high static magnetic field (HiSMF) has been reported to act as an inhibited factor for osteoclasts differentiation. Although many studies have indicated the negative role of HiSMF on osteoclastogenesis of RANKL-induced RAW264.7 cells, the molecular mechanism is still elusive. In this study, the HiSMF-retarded cycle and weakened differentiation of RAW264.7 cells was identified. Through RNA-seq analysis, RANKL-induced RAW264.7 cells under HiSMF were analysed, and a total number of 197 differentially expressed genes (DEGs) were discovered. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that regulators of cell cycle and cell division such as Bub1b, Rbl1, Ube2c, Kif11, and Nusap1 were highly expressed, and CtsK, the marker gene of osteoclastogenesis was downregulated in HiSMF group. In addition, pathways related to DNA replication, cell cycle, and metabolic pathways were significantly inhibited in the HiSMF group compared to the Control group. Collectively, this study describes the negative changes occurring throughout osteoclastogenesis under 16 T HiSMF treatment from the morphological and molecular perspectives. Our study provides information that may be utilized in improving magnetotherapy on bone disease.

Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants that is caused by peste des petits ruminants virus (PPRV). To date, the molecular mechanism of PPRV infection is still unclear. It is well known that host proteins might be involved in the pathogenesis process for many viruses. In this study, we first proved that nucleolin (NCL), a highly conserved host factor, interacts with the core domain of PPRV N protein through its C terminus and co-locates with the N protein in the nucleus of cells. To investigate the role of NCL in PPRV infection, the expression level of NCL was inhibited with small interfering RNAs of NCL, and the results showed that PPRV growth was improved. However, the proliferation of PPRV was inhibited when the expression level of NCL was improved. Further analysis indicated that the inhibitory effect of NCL on the PPRV was caused by stimulating the interferon (IFN) pathways in host cells. In summary, our results will help us to understand the mechanism of PPRV infection.

To investigate the influence of organic cation transporter 3 (OCT3) expression on the effect of the combination regimen of 5-fluorouracil, folinic acid and oxaliplatin ((m)FOLFOX6) in colorectal cancer (CRC) patients. This is a retrospective study conducted at a single centre (Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, China). Patients with stage IIb-IV resectable CRC who were being postoperatively treated with (m)FOLFOX6 as a first-line adjuvant chemotherapy regimen for at least 5 cycles and had resected primary tumour samples available were eligible for the study. Patients who preoperatively received chemotherapy and/or radiotherapy or were treated with targeted drugs or other anticancer drugs were excluded from the study. Immunohistochemical staining and digital image analysis were used to assess OCT3 expression in tumour samples. According to OCT3 expression level, the receiver operating characteristic curve (ROC curve) was used to divide the patients into two groups. Cox proportional risk regression was performed with the forward LR (forward stepwise regression based on maximum likelihood estimation) method using SPSS17.0 software. The primary endpoint was the 2-year progression-free survival. In total, 57 patients were included between 2014 and 2016 according to the inclusion and exclusion criteria (22 had low OCT3 expression, and 35 had high OCT3 expression). The mean age was 55.7 (30–74) years, and 37 of the total patients were male. According to TNM stage, 5 patients had stage IV disease, 44 patients had stage III disease, and 8 patients had stage II disease. Through Cox regression analysis, we found that among patients receiving the (m)FOLFOX6 regimen, those with higher OCT3 expression had a higher two-year progression-free survival rate than those with lower OCT3 expression (P = 0.038). The hazard ratio of patients with high OCT3 expression compared with patients with low OCT3 expression was 0.247. Besides, it was found that the age of patients was negatively correlated with expression level of OCT3, which can explain why patients over 70 years do not benefit from oxaliplatin-containing chemotherapy. High OCT3 expression in CRC tissues may be a protective factor for CRC patients treated with (m)FOLFOX6.

High static magnetic fields (HiSMFs) are usually defined as those SMFs with intensities ≥1 T. Although many studies have indicated that SMFs have positive effects on bone tissue, there were limited studies that investigate the effects of cells, including osteoclasts, to illustrate the effect of HiSMF on osteoclast differentiation, and whether iron involve in the altered osteoclast formation and resorption ability under HiSMF. 16 T HiSMF generated from a superconducting magnet was used. Osteoclastogenesis, bone resorption, acting ring formation, messenger ribonucleic acid expression, and protein expression were determined by tartrate-resistant acid phosphatase staining, pits formation assay, rhodamine-conjugated phalloidine staining, quantitative real-time polymerase chain reaction, and western blot, respectively. The changes induced by HiSMF in the level of iron and the concentration of mitochondrial protein, adenosine triphosphate, reactive oxygen species, malonaldehyde, and glutathione were examined by atomic absorption spectrometry and corresponding commercial kits, respectively. The results showed that HiSMF significantly inhibited osteoclastic formation and resorption ability and reduced cellular iron content during osteoclast differentiation. Mitochondrial concentration and oxidative stress levels in osteoclasts were decreased under HiSMF. Mechanistically, HiSMF markedly blocked the expression of osteoclast-associated transcription factors and osteoclast marker genes and inhibited iron absorption and iron storage-related protein expression. These findings demonstrated that the effect of HiSMF on iron metabolism of osteoclasts was involved in the inhibition of HiSMF on osteoclast differentiation.

Exposure to microgravity during long-term habitation in space results in numerous physiological alterations in the human body. Among them, reduction in bone mineral density is well known as one of the most important changes, which limits further space exploration by humans. Although numerous studies have been conducted on microgravity-induced bone loss, the explicit mechanism behind its occurrence has not been fully elucidated. Even though mechanical unloading has been generally accepted as a dominant cause of microgravity-induced bone loss, the risks of iron-loading and oxidative damage due to increased iron stores and dietary iron intake during spaceflight have attracted much attention, especially in bone. Indeed, excessive iron accumulation has been found in astronauts exposed to microgravity during spaceflight. Moreover, a great deal of evidence from clinical, animal, and cellular studies indicates that iron-loading has direct adverse effects on bone metabolism. This review summarizes the latest findings on bone loss and iron status in microgravity conditions, as well as the association between iron-loading and bone abnormalities. We discuss the possible mechanisms of iron overload-induced skeletal involution. Finally, we hypothesize that, in addition to mechanical unloading, iron overload due to long-term spaceflight missions is a high risk factor for microgravity-induced bone loss. The underlying mechanism by which it occurs is iron-loading that leads to an imbalance in bone remodeling, involving bone formation and bone resorption, mediated by oxidative stress via the Fenton reaction.

The important role of osteoclast-derived exosomes in bone remodeling of microgravity-induced osteoporosis has been validated. However, the underlying mechanism remains unclear. A set of total miRNAs expressed in osteoclast-derived exosomes may configure the specific signature of the bone tissue in the microgravity condition. This study aimed to investigate the miRNA expression profile of osteoclast-derived exosomes in simulated microgravity using next-generation sequencing. Cell culture supernatant of osteoclasts under normal gravity conditions and simulated microgravity conditions were harvested for the extraction of exosomes and exosomal miRNAs. Our results revealed that 116 aberrantly expressed exosomal miRNAs including 29 up-regulated miRNAs and 87 down-regulated miRNAs were found in the simulated microgravity group compared to the normal gravity control group. The candidate target genes and signaling pathways of 15 selected differentially expressed miRNAs were identified via target genes prediction, GO and KEGG analyses. Furthermore, miRNA qPCR assay was performed to validate the RNA sequencing results. Collectively, these analyses provide insight regarding the effects of microgravity in modulating the extracellular miRNA profile through exosomes released from osteoclasts. The selective packaging of miRNA cargo in exosomes under microgravity could facilitate the development of promising and effective targets for the diagnosis, prevention, and treatment of microgravity-induced osteoporosis.

This study presents the effects of nanoscale zero valent iron (nZVI) concentration on the biomethanation of gaseous CO2. During anaerobic batch experiment with 9 times injection of CO2, the CO2 concentration in the headspace rapidly decreased by dissolution. Then, when nZVI was added at 6.25 and 12.5 g/L, the dissolved CO2 was biochemically transformed into CH4 at a maximum production rate of 2.38 and 3.93 μmol/hr, respectively. Biomethanation at these two nZVI concentrations continued until the end of experiment. In spite of more H2 evolution by nZVI at 25 g/L, biomethanation did not occur, due to the significant inhibition of methanogenesis by nZVI. As the nZVI concentration increased, relative abundance of the hydrogenotrophic methanogens, especially Methanobacteriales, increased. However, at 25 g/L of nZVI concentration, acetic acid was accumulated and the relative abundance of Clostridium became predominant, indicating that homoacetogenesis was superior over methanogenesis.

In the microgravity environment of space, astronauts undergo osteoporosis due to an imbalance in bone remodeling. Recent studies have shown that exosomes derived from osteoclasts could mediate cell-to-cell communication in bone remodeling. However, the role of osteoclast-derived exosomes in bone remodeling in microgravity remains a mystery. Our objective is to investigate the cellular processes modulated by exosomes from RAW264.7 cell-derived osteoclasts and the underlying mechanism of action for the exosomes-mediated osteogenesis of osteoblast-like MC3T3-E1 cells in simulated microgravity. We took advantage of the random positioning machine (RPM) to simulate microgravity for the model and investigated the role of exosomes from RAW264.7 cell-derived osteoclasts in osteoclast-osteoblast communication. The results showed that this type of mature osteoclast-derived exosomes (OC-Exos) in the RPM evidently inhibited the cellular proliferation of osteoblasts via inducing cellular apoptosis and altering their cell cycle distribution. Alkaline phosphatase and mineralization activity of MC3T3-E1 cells were significantly lower after treatment with OC-Exos from RPM and mRNA expression of osteoblast-specific genes were down-regulated. Further study confirmed that OC-Exos in RPM obstructed the differentiation of MC3T3-E1 cells by interfering with Wnt/β-catenin signaling pathway. Together, these observations demonstrated that OC-Exos played an essential role in the regulation of bone remodeling in the microgravity environment. These results shed light on a novel pathway of cross-talk between osteoclasts and osteoblasts, which will be helpful to explain the possible mechanisms underlying osteoporosis in microgravity.

In this work, a double-deck structure consisting of graphene nanoribbons is proposed, and the plasmonic properties of the system is investigated at mid-infrared wavelengths. In the structure, two graphene nanoribbon arrays with different parameters are coated on both sides of a glass substrate. With respectively varying the Fermi energies, the layer numbers of the graphenes, and the widths of the ribbons, the light transmittance is studied in the wavelength region from 5 to 30 $$\mu$$ m, via the finite difference time domain method. Multiple plasmonic resonances are revealed in the double-deck graphenes. It is shown that the plasmonic resonance properties including the resonance wavelengths, the peak intensities, and the peak widths can be adjusted by changing the parameters of the graphenes. The double-deck graphene nanoribbon structure proposed in this work may be implemented in designs of plasmonic devices in mid-infrared regime.

ObjectivesCeftazidime/avibactam is not active against MBL-producing bacteria. Combining ceftazidime/avibactam or avibactam with aztreonam can counter the resistance of MBL-producing Enterobacterales. The aim of this study was to evaluate whether the addition of avibactam could reduce or close the mutant selection window (MSW) of aztreonam in Escherichia coli and Klebsiella pneumoniae harbouring MBLs; MSW is a pharmacodynamic (PD) parameter for the selection of emergent resistant mutants.MethodsIn vitro susceptibility of 19 clinical isolates to ceftazidime/avibactam, aztreonam alone, and in co-administration (aztreonam/ceftazidime/avibactam and aztreonam/avibactam) was determined, as well as the mutant prevention concentration (MPC). The fraction of time within 24 h that the free drug concentration was within the MSW (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) in both plasma and epithelial lining fluid (ELF) were determined from simulations of 10 000 profiles. The joint PTA was used to derive a joint cumulative fraction of response (CFR).ResultsAll isolates were resistant to ceftazidime/avibactam or aztreonam. Combining aztreonam and avibactam or ceftazidime/avibactam resulted in synergistic bactericidal activities against all isolates. Synergism was primarily due to the aztreonam/avibactam combination. For aztreonam/avibactam dosing regimens evaluated in clinical trials, fT>MPC values were >90% and >80%, whereas fTMSW measures were ConclusionsEffective antimicrobial combination optimized the PD parameters measuring selection for emergent mutants by increasing fT>MPC and reducing fTMSW.

Ovarian cancer (OC) is the fifth most common female malignant tumor and the leading cause of cancer-related death in women worldwide. Epithelial ovarian cancer (EOC) is the predominant type of OC. Investigating the mechanism underlying tumorigenesis and progression of EOC is urgent. Our previous research has shown that long non-coding RNAs (lncRNAs) CDKN2A-AS1 is upregulated in EOC tissues and cells. Furthermore, we have predicted that CDKN2A-AS1 is associated with the bone morphogenetic protein (BMP)-SMAD signaling pathway, which is negatively regulated by the sclerostin domain containing 1 (SOSTDC1). Therefore, we conjecture that the CDKN2A-AS1 regulate BMP-SMAD signaling pathway via interacting with SOSTDC1, which need more investigation. Moreover, the functions of the BMP-SMAD signaling pathway and the SOSTDC1 on EOC are still unclear. Herein, we unearthed that CDKN2A-AS1, BMP2/4/7, SMAD1/5/9 and phosphorylation of SMAD1/5/9 (p-SMAD1/5/9) were upregulated in EOC tissues and cells, whereas SOSTDC1 was downregulated in EOC tissues and cells. We firstly demonstrated that CDKN2A-AS1 bound directly with the SOSTDC1. CDKN2A-AS1 downregulated the expression of SOSTDC1, but upregulated the expression of BMP2/4/7, SMAD1/5/9, and p-SMAD1/5/9. CDKN2A-AS1 promoted the proliferation, migration, invasion of EOC cells and tumor growth in vivo, whereas SOSTDC1 inhibited the proliferation, migration, invasion of EOC cells. Knockdown SOSTDC1 rescued the inhibitory effect of si-lncRNA CDKN2A-AS1 on the EOC cells proliferation, migration and invasion. These results demonstrated that CDKN2A-AS1activated the BMP-SMAD signaling pathway by directly bind with SOSTDC1 to promote EOC tumor growth. CDKN2A-AS1/SOSTDC1 axis may provide a novel therapeutic strategy for EOC treatment.

ObjectiveAlthough Polymerase-epsilon (POLE)-mutated and mismatch repair (MMR)-deficient endometrial cancers (ECs) are considered as promising candidates for anti-PD-1/PD-L1 therapy, selecting only these patients may exclude other patients who could potentially respond to this treatment strategy, highlighting the need of additional biomarkers for better patient selection. This study aims to evaluate potential predictive biomarkers for anti-PD-1/PD-L1 therapy in addition to POLE mutation (POLEm) and MMR deficiency (MMRd).MethodsWe performed next generation sequencing for POLE from 202 ECs, and immunohistochemistry for MLH1, MSH2, MSH6, PMS2, CD3, CD8, PD-1 and PD-L1 on full-section slides from these ECs. We assessed the association of POLEm and MMRd with clinicopathologic features, expression of check point proteins, and density of tumor-infiltrating lymphocytes (TILs). Prognostic impact of these immune markers was also evaluated.ResultsPOLEm, MMRd and high-grade tumors exhibited elevated level of TILs. Increased expression of PD-1 and PD-L1 was observed in MMRd and high-grade ECs. A subgroup of MMR proficient ECs also harbored increased density of TILs, and positive expression of PD-1 and PD-L1. In addition, negative expression of checkpoint proteins and high density of TILs in combination was associated with good prognosis.ConclusionsCandidates for PD-1 blockade may extend beyond POLEm and MMRd ECs, additional factors such as tumor grade, and combination of TILs levels and expression of checkpoint proteins may need to be considered for better patient selection.

The mitochondrial antiviral-signaling protein (MAVS, also known as VISA, IPS-1, or CARDIF) plays an essential role in the type I interferon (IFN) response and in retinoic acid-inducible gene I (RIG-I) mediated antiviral innate immunity in mammals. In this study, the caprine MAVS gene (caMAVS, 1566 bp) was identified and cloned. The caMAVS shares the highest amino acid similarity (98.1%) with the predicted sheep MAVS. Confocal microscopy analysis of partial deletion mutants of caMAVS revealed that the transmembrane and the so-called Non-Characterized domains are indispensable for intracellular localization to mitochondria. Overexpression of caMAVS in caprine endometrial epithelial cells up-regulated the mRNA levels of caprine interferon-stimulated genes. We concluded that caprine MAVS mediates the activation of the type I IFN pathway. We further demonstrated that both the CARD-like domain and the transmembrane domain of caMAVS were essential for the activation of the IFN-β promotor. The interaction between caMAVS and caprine RIG-I and the vital role of the CARD and NC domain in this interaction was demonstrated by co-immunoprecipitation. Upon infection with the Peste des Petits Ruminants Virus (PPRV, genus Morbillivirus), the level of MAVS was greatly reduced. This reduction was prevented by the addition of the proteasome inhibitor MG132. Moreover, we found that viral protein V could interact and colocalize with MAVS. Together, we identified caMAVS as a RIG-I interactive protein involved in the activation of type I IFN pathways in caprine cells and as a target for PPRV immune evasion.

In recent years, public health emergencies have occurred frequently, posing a serious threat to the regional economy and the safety of people's lives and property. In particular, the outbreak of the COVID-19 novel coronavirus this year has caused serious losses to the global economy. On this basis, this article attempts to use modern advanced artificial intelligence technology and modern social science and technology to provide technical assistance and support for the prevention and control of major public health incidents, in order to improve the Chinese government's public relations capabilities and response to public health emergencies. Ability and level. This article attempts to use 3S technology closely related to artificial intelligence technology to design and establish a public health emergency response system, so as to improve the government's response and decision-making ability to respond to and deal with public health emergencies, and reduce the occurrence of emergencies. The results showed that among the 298 respondents, 145 believed that public health emergencies depend on human-to-human transmission. Most event information is acceptable, while 169 people who rely on mobile phones for information think that most of them are acceptable, and 89 people who rely on TV media for information think that most of them are acceptable. It shows that the use of artificial intelligence technology can effectively solve and prevent the further development of the situation, and at the same time improve the government's ability and level to respond to major public health emergencies, and increase the government's prestige in the eyes of the public.

COVID-19 is an emerging infectious disease that is extremely contagious and can cause serious consequences and even death.Convalescent plasma, an unregistered therapy, from which the antibodies mig...

Rabbit hemorrhagic disease virus (RHDV) is an important member of the Caliciviridae family and cannot be propagated in vitro, which has greatly impeded progress of investigating its replication mechanism. Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells. Here, aided by this replicon system and using two-step affinity purification, we purified the RHDV replicase and identified its associated host factors. We identified rabbit nucleolin (NCL) as a physical link required for the formation of RHDV replication complexes (RCs), by mediating the interaction between other host proteins and the viral RNA replicase, RNA-dependent RNA polymerase (RdRp). We found that RHDV RdRp uses an amino acid (aa) region spanning residues 448–478 to directly interact with NCL’s RNA-recognition motif 2. We also found that the viral p16 protein uses a highly conserved region (35Cys–Ile–Arg–Ala38 or CIRA motif) to specifically bind the N-terminal region of NCL (aa 1–110) and that RHDV p23 uses a specific domain (aa 90–145) to bind NCL’s RNA-recognition motif 1. Disrupting these protein–protein interactions severely weakened viral replication. Furthermore, NCL overexpression or knockdown significantly increased or severely impaired, respectively, RHDV replication. Collectively, these results indicate that the host protein NCL is essential for RHDV replication and plays a key role in the formation of RHDV RCs. The mechanisms by which NCL promotes viral replicase assembly reported here shed light on viral RC biogenesis and may inform antiviral therapies.Author summaryRabbit hemorrhagic disease virus (RHDV) is the causative agent of highly contagious and lethal hemorrhagic disease in the European rabbit, but the host factors involved in RHDV replication remain poorly understood. In the present study, we isolated RHDV replication complex (RC) for the first time and identified its main components. We found that nucleolin (NCL) plays a key role in the formation of the RHDV RC. NCL not only interacts with viral replicase (RdRp), it also specifically binds to other important host factors. In addition, we proved that NCL is necessary for RHDV replication because the level of RHDV replication is significantly affected by knocking down the NCL gene in cells. Together, our data suggest that RHDV completes its replication by hijacking NCL to recruit other viral proteins and host factors, thereby assembling the RC of RHDV.

Reports of human-pathogenic C. braakii strains, especially of strains showing resistance to carbapenems, are rare. To the best of our knowledge, our results represent the first detection of carbapenemase gene blaKPC-2 in C. braakii strains. In addition, we have studied detailed genetic characteristics of the novel IncR/IncP6 hybrid plasmid pCRE3-KPC, which was isolated from a clinical multidrug-resistant Citrobacter braakii CRE3 strain. Our results may provide further insight into the horizontal transfer of multidrug resistance genes in bacteria and into the genomic diversity and molecular evolution of plasmids., Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become widespread in hospitals and the environment. Here, we describe a blaKPC-2-carrying plasmid called pCRE3-KPC, which was recovered from a clinical multidrug-resistant Citrobacter braakii CRE3 strain in China. The complete nucleotide sequence of pCRE3-KPC was determined by combining MiSeq and MinION sequencing and then compared with those of three related plasmids. Plasmid conjugal transfer and electroporation tests, modified carbapenem inactivation method, and bacterial antimicrobial susceptibility test were carried out. We compared this plasmid with three related plasmids to verify that the backbone of pCRE3-KPC was composed of the backbones of the IncR plasmid and IncP6 plasmid. Further bioinformatics analysis showed that pCRE3-KPC carried two resistance-related regions (the blaKPC-2 gene cluster and the aacC2-tmrB-related region). The aacC2-tmrB-related region included two novel insertion sequences (ISCfr28 and ISCfr16). IMPORTANCE Reports of human-pathogenic C. braakii strains, especially of strains showing resistance to carbapenems, are rare. To the best of our knowledge, our results represent the first detection of carbapenemase gene blaKPC-2 in C. braakii strains. In addition, we have studied detailed genetic characteristics of the novel IncR/IncP6 hybrid plasmid pCRE3-KPC, which was isolated from a clinical multidrug-resistant Citrobacter braakii CRE3 strain. Our results may provide further insight into the horizontal transfer of multidrug resistance genes in bacteria and into the genomic diversity and molecular evolution of plasmids.

Rabbit hemorrhagic disease (RHD) is an acute, inflammatory, septic, and devastating infectious disease caused by Rabbit hemorrhagic disease virus (RHDV), which poses a serious threat to the rabbit industry. RHDV2 (GI.2/RHDVb), a recently reported new variant could cause RHD in wild populations, but also RHDV-vaccinated rabbits. For now, both RHDV and RHDV2 are the main causes of RHD. To develop a new subunit vaccine that could protect rabbits against both classic RHDV and RHDV2 infections, we constructed a recombinant baculovirus (Bac-classic RHDV VP60-RHDV2 VP60) containing the VP60 genes of classic RHDV and RHDV2. Both VP60 genes were well expressed simultaneously in Spodoptera frugiperda cells (Sf9) after infection with the recombinant baculovirus. Transmission electron microscopy showed that the recombinant VP60 self-assembled into virus-like particles (VLPs). The antigenicity and immunogenicity of the bivalent VLPs vaccine were examined with animal experiments. Our results demonstrated that both the humoral and cellular immune responses were efficiently induced in rabbits by a subunit vaccine based on the recombinant baculovirus. In addition, all rabbits immunized with the bivalent VLPs vaccine survived after challenged with classic RHDV, and showed no clinical signs of RHD, whereas all the rabbits in the negative control group died from classic RHDV infection and showed typical clinical signs of RHD. In summary, our results indicated that the recombinant baculovirus carrying two VP60 genes is a candidate construct from which to develop a bivalent VLPs vaccine against both classic RHDV and RHDV2 infections.

Both zero valent iron (ZVI) and nano-scaled ZVI (nZVI) have the potential for biomethanation of CO2 under anaerobic condition, but when they were continuously added to a semi-continuous anaerobic bioreactor, exhibited different effects on the microbial mechanisms and system performances. When ZVI and nZVI were continuously added, 33.40 and 11.52 % of the dissolved input CO2 were transformed into CH4, respectively. The abiotic corrosion rate and H2 evolution rate by ZVI were 27 times lower than those by nZVI. Active biomethanation occurred earlier in the period of operation with nZVI, and later with ZVI. As nZVI accumulated in the bioreactor, biomethanation stopped, without utilization of both the H2 and VFAs generated. Based on microbial community analysis, biomethanation by using both irons depended on hydrogenotrophic methanogenesis, but in the case of ZVI, direct use of electron from ZVI by methanogens was also significant. Based on the estimation of CO2 conversion, ZVI could be more effectively and stably used for biomethanation compared to nZVI, with less loss in the form of chemical precipitates

By coupling P450 enzyme-like single-atom Fe-N center and graphitic N into N-doped carbon matrix, we precisely fabricated a robust Fe-N-C adsorbent for efficient, stable and reversible desulfurization, notably exceeding the counterparts of commercial carbon black, iron porphyrin and its hybrid. Our results disclosed that the adsorptive desulfurization mainly occurred in the atomic Fe-N and graphitic N sites via the formation of Fe-S bond between Fe3d and S3p orbitals, and N/S electrostatic interaction, respectively. The excellent desulfurization capability (34.03 mg S/g) of Fe-N-C not only originated from its effective adsorption sites, large surface area and abundant porosity, but also relied on the moderate binding strength between adsorption sites and organosulfur, which could be well optimized by modulating the pyrrolic/pyridinic N and graphitization structure, enabling its outstanding recyclability via a feasible cleavage of formed Fe-S and N-S bonds without obvious loss of activity. Moreover, Fe-N-C still maintained the 91.20% and 84.56% desulfurization selectivity, even in the presence of the interfacing substrates such as thiophene and 4,6-dimethyldibenzothiophene, respectively. This work would provide a new opportunity to metal-N-C with tunable site configuration and density for various selective adsorption and separation.

Iron is an essential micronutrient in mammalian cells for basic processes such as DNA synthesis, cell cycle progression, and mitochondrial activity. Macrophages play a vital role in iron metabolism, which is tightly linked to their phagocytosis of senescent and death erythrocytes. It is now recognized that the polarization process of macrophages determines the expression profile of genes associated with iron metabolism. Although iron metabolism is strictly controlled by physiology, cancer has recently been connected with disordered iron metabolism. Moreover, in the environment of cancer, tumor-associated macrophages (TAMs) exhibit an iron release phenotype, which stimulates tumor cell survival and growth. Usually, the abundance of TAMs in the tumor is implicated in poor disease prognosis. Therefore, important attention has been drawn toward the development of tumor immunotherapies targeting these TAMs focussing on iron metabolism and reprogramming polarized phenotypes. Although further systematic research is still required, these efforts are almost certainly valuable in the search for new and effective cancer treatments.

Objective The role of mismatch repair (MMR) deficiency in ovarian cancer (OC) pathogenesis and its association with other clinicopathologic features, such as microsatellite instability (MSI) and expression of checkpoint proteins, remain largely elusive. Methods We performed Immunohistochemistry (IHC) for MLH1, MSH2, MSH6 and PMS2 on full-section slides from 419 OCs to assess the MMR status. The clinical relevance of MMR deficiency was analyzed in combination with clinical data. The MSI status (by MSI assay) and expression of CD3, CD8, PD-1 and PD-L1 (by IHC) were compared in OCs with different MMR status. Results We found that 2.6% OCs were MMR-negative, 4.3% OCs were MMR-low, and 63.6% of MMR-negative OCs were of endometrioid subtype. A significantly higher proportion of MMR-negative OCs were diagnosed at stage I or II compared to MMR-proficient OCs (p=0.0041). MSI was observed in all tested MMR-negative OCs, 14.3% of tested MMR-low OCs and 3.2% of tested MMR-proficient OCs. In addition, MMR-negative OCs had better progression free survival compared to MMR-proficient and MMR-low OCs (p=0.0046). Furthermore, the majority of OCs were PD-1-positive in intratumoral lymphocytes regardless of MMR status; while MMR-negative OCs exhibited significantly increased CD3+ and CD8+ tumor-infiltrating lymphocytes, and PD-L1+ intratumoral immune cells compared to MMR-proficient OCs. Conclusion Our data suggests that MMR deficient OC is a unique molecular subgroup, characterized by early stage of diagnosis, MSI phenotype, and increased tumor-infiltrating lymphocytes. These patients may be good candidates for anti-PD-1/PD-L1 therapy.

It has been widely accepted that spherical periodicity generally dominates liquid and amorphous structure formation, where atoms tend to gather near spherically periodic shells according to Friedel oscillation. Here it is revealed that the same order is just hidden in the atomic global packing modes of the crystalline phases relevant to bulk metallic glasses. Among the multiple nearest-neighbor clusters developed from all the non-equivalent atomic sites in a given phase, there always exists a principal cluster, centered by which the spherical periodicity, both topologically and chemically, is the most distinct. Then the principal clusters plus specific glue atoms just constitute the cluster-plus-glue-atom structural units shared by both metallic glasses and the corresponding crystalline phases. It is further pointed out that the spherical periodicity order represents the common structural homology of crystalline and amorphous states in the medium-range through scrutinizing all binary bulk-glass-relevant phases in Cu-(Zr, Hf), Ni-(Nb, Ta), Al-Ca, and Pd-Si systems.

Infrared and visible images (multi-sensor or multi-band images) have many complementary features which can effectively boost the performance of object detection. Recently, convolutional neural networks (CNNs) have seen frequent use to perform object detection in multi-band images. However, it is very difficult for CNNs to extract complementary features from infrared and visible images. In order to solve this problem, a difference maximum loss function is proposed in this paper. The loss function can guide the learning directions of two base CNNs and maximize the difference between features from the two base CNNs, so as to extract complementary and diverse features. In addition, we design a focused feature-enhancement module to make features in the shallow convolutional layer more significant. In this way, the detection performance of small objects can be effectively improved while not increasing the computational cost in the testing stage. Furthermore, since the actual receptive field is usually much smaller than the theoretical receptive field, the deep convolutional layer would not have sufficient semantic features for accurate detection of large objects. To overcome this drawback, a cascaded semantic extension module is added to the deep layer. Through simple multi-branch convolutional layers and dilated convolutions with different dilation rates, the cascaded semantic extension module can effectively enlarge the actual receptive field and increase the detection accuracy of large objects. We compare our detection network with five other state-of-the-art infrared and visible image object detection networks. Qualitative and quantitative experimental results prove the superiority of the proposed detection network.

Efficient cooling system is an essential part of heavy duty extrusion pelleting line which plays an important role in production engineering of megaton polyolefin. In this paper, a new cooling system based on two-phase closed thermosyphon (TPCT) used in heavy duty extrusion pelleting line was presented. Comparative experimental results show that thermal performance of TPCT is more efficient, and the temperature uniformity is much better than traditional extruder (similar to coiled heat exchanger) in preheating process and extrusion reaction process. The effects of different operation conditions: filling ratio (0.2, 0.35, 0.5, 0.65 and 0.8), flow rate of cooling water (120 L/h, 180 L/h, 240 L/h, 300 L/h and 360 L/h) and heating power (7 kW, 9 kW and 11 kW) on thermal characteristics were experimental investigated, respectively. The results show that temperature of barrel inner wall increased significantly as filling ratio increased and evaporator appeared dry out when filling ratio is 0.2. The flow rate of cooling water affected the condenser section obviously, but had little influence on evaporation section. With increase of heating power, the start-up time decreases and the heat transfer coefficient increased. An ideal cooling scheme was concluded: the liquid filling ratio was 0.35, the cooling water flow rate was 180 L/h and the heating power was 11 kW when working medium was water.

Groundwater contaminated with inorganic arsenic (iAs) is the main source of human exposure to arsenic and generates a global health issue. In this study, the urinary excretion, as well as the time-course distributions of various arsenic species in murine tissues, especially in different brain regions were determined after a single oral administration of 2.5, 5, 10 and 20mg/kg sodium arsenite (NaAsO2). Our data showed that the peak times of urinary, hepatic and nephritic total arsenic (TAs) were happened at about 1h, then TAs levels decreased gradually and almost could not be observed after 72h. On contrast, the time course of TAs in lung, urinary bladder and different brain regions exhibited an obvious process of accumulation and elimination,and the peak times were nearly at 6h to 9h. TAs levels of 10 and 20mg/kg NaAsO2 groups were significantly higher than 2.5 and 5mg/kg groups, and the amounts of TAs in 5mg/kg groups were in the order of liver>lung>kidney>urinary bladder>hippocampus>cerebral cortex>cerebellum. In addition, iAs was the most abundant species in liver and kidney, while lung and urinary bladder accumulated the highest concentrations of dimethylated arsenicals (DMA). What's more, the distributions of arsenic species were not homogeneous among different brain regions, as DMA was the sole species in cerebral cortex and cerebellum, while extremely high concentrations and percentages of monomethylated arsenicals (MMA) were found in hippocampus. These results demonstrated that distributions of iAs and its methylated metabolites were tissue-specific and even not homogeneous among different brain regions, which must be considered as to the tissue- and region-specific toxicity of iAs exposure. Our results thus provide useful information for clarifying and reducing the uncertainty in the risk assessment for this metalloid.

Efficient cooling system is an essential part of heavy duty extrusion pelleting line which plays an important role in 300 kt/a production engineering of polyolefin. In this paper, a wickless gravity-assisted two-phase cooling system (WGATPCS) used in heavy duty extrusion pelleting line was presented. The volume of the fluid (VOF) model in FLUENT was used to simulate the two-phase flow and heat transfer characteristic during the operation of WGATPCS by solving the equations of continuity, momentum and energy. The vapor velocity and temperature distribution of cooling system were obtained. The operating conditions applied in this paper are the followings: the filling ratio is 0.3, cooling water flow rate is 180 L/h, and heating power is 11 kW. The predicted temperature profile showed a good agreement with experimental data and the maximum relative error was below 0.99%. Therefore, it was concluded that the CFD model successfully reproduced the heat and mass transfer processes in proposed cooling system. The variation of liquid film thickness, the characteristics of liquid film and vapor-liquid interface were also analyzed. The maximum liquid film thickness was 0.017 mm at the bottom of condenser pipe, the velocity of vapor and liquid at vapor-liquid interface were 0.00785 m/s and 0.09 m/s respectively. The average condensation and evaporation heat transfer coefficients were 68083 W/(m 2 K) and 3929 W/(m 2 K), respectively.

It is known that bulk metallic glass compositions can be well interpreted by cluster formulas for stable liquids [cluster](glue atom) 1 or 3 , where the clusters are derived from relevant devitrification phases. In the present work, the glass forming composition formulas in Ni-Nb and Ni-Ta systems are fully examined. The procedures include choosing the appropriate eutectic crystalline phases, selecting the principal clusters via the criteria such as spherical periodicity and cluster isolation degree, and determining the glue atoms. After strictly following these procedures, the best glass forming compositions Ni 62 Nb 38 in Ni-Nb system and the range 59–62 at.% Ni in Ni-Ta system are explained by formulas [Ni-Nb 4 Ni 8 ]Nb 2 Ni and [M-Ni 6 Ta 6 ]Ni 3 (M is a random mixture of Ni and Ta) respectively.

This study suggests a method for the recovery of nitrogen in waste or wastewater as ammonium phosphate crystals. Recovered crystals were a mixture of mono-ammonium phosphate (MAP) and di-ammonium phosphate (DAP), which are valuable fertilizers. A lab-scale system was constructed with an ammonia stripper and absorber with phosphoric acid solution. Formation of ammonium phosphate crystals was dependent on the concentration and volume of phosphoric acid in the absorber. The absorption efficiency of ammonia in the absorber increased as the concentration and volume of phosphoric acid increased. However, the crystals formed better in a smaller volume of absorbing solution. When the N/P ratio in the ammonia absorbed solution reached 0.38 in a continuous stripping condition, crystals could not be formed in the absorber, but could be formed in a crystallizer maintained at 10 °C, the optimal temperature for crystallization. The N/P ratio of the recovered crystals was 1.47, indicating that the crystals were a mixture of MAP and DAP. Analyses of SEM and XRD revealed that the recovered crystals were composed of MAP and DAP.