Heparanase Stimulation of Physiological Cardiac Hypertrophy is Suppressed Following Chronic Diabetes Resulting in Cardiac Remodeling and Dysfunction.

Although endothelial cells control smooth muscle tone in coronary vessels, these cells also influence subjacent cardiomyocyte growth. As heparanase, with exclusive expression in endothelial cells, enables extracellular matrix remodeling, angiogenesis, metabolic reprogramming, and cell survival, it is conceivable that it could also encourage development of cardiac hypertrophy. Global heparanase overexpression resulted in physiological cardiac hypertrophy, likely an outcome of HSPG clustering and activation of hypertrophic signaling. The autocrine effect of heparanase to release neuregulin-1 may have also contributed to this effect. Hyperglycemia induced by streptozotocin-diabetes sensitized the heart to flow-induced release of heparanase and neuregulin-1. Despite this excess secretion, progression of diabetes caused significant gene expression changes related to mitochondrial metabolism and cell death that led to development of pathological hypertrophy and heart dysfunction. Physiological cardiac hypertrophy was also observed in rats with cardiomyocyte-specific VEGFB overexpression. When perfused, hearts from these animals released significantly higher amounts of both heparanase and neuregulin-1. However, subjecting these animals to diabetes triggered robust transcriptome changes related to metabolism, and a transition to pathological hypertrophy. Our data suggest that in the absence of mechanisms that support cardiac energy generation and prevention of cell death, as seen following diabetes, there is a transition from physiological to pathological cardiac hypertrophy and a decline in cardiac function.

Pathogenesis and virulence of Heartland virus.

Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution, and high pathogenicity in the United States. Infection from HRTV results in fever, thrombocytopenia, and leucopenia in humans, and in some cases, symptoms can progress to severe outcomes, including haemorrhagic disease, multi-organ failure, and even death. Currently, no vaccines or antiviral drugs are available for treatment of the HRTV disease. Moreover, little is known about HRTV-host interactions, viral replication mechanisms, pathogenesis and virulence, further hampering the development of vaccines and antiviral interventions. Here, we aimed to provide a brief review of HRTV epidemiology, molecular biology, pathogenesis and virulence on the basis of published article data to better understand this virus and provide clues for further study.

Exploring the impact of prenatal perfluoroalkyl and polyfluoroalkyl substances exposure on blood pressure in early childhood: A longitudinal analysis.

Previous research investigating the correlation between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and subsequent blood pressure (BP) in offspring has yielded limited and contradictory findings. This study was conducted to investigate the potential relationship between maternal PFAS levels during pregnancy and subsequent BP in early childhood. A total of 129 expectant mothers from the Shanghai Birth Cohort were included in the study. Using high-performance liquid chromatography/tandem mass spectrometry, we measured ten PFAS compounds in maternal plasma throughout the pregnancy. When the children reached the age of 4, we examined their systolic BP (SBP) and diastolic BP (DBP), along with mean arterial pressure (MAP) and pulse pressure (PP). Data interpretation employed multiple linear and logistic regression models, complemented by Bayesian kernel machine regression (BKMR).We found that the majority of PFAS concentrations remained stable during pregnancy. The linear and BKMR models indicated a positive relationship between the PFAS mixture in maternal plasma and offspring's DBP and MAP, with perfluorohexanesulphonic acid (PFHxS) having the most significant influence (PFHxS and DBP [first trimester:ß=3.03, 95%CI: (1.01,5.05); second trimester: ß=2.35, 95%CI: (0.94,3.75); third trimester: ß=2.57, 95%CI:(0.80,4.34)]; MAP [first trimester:ß=2.55, 95%CI: (0.64,4.45); second trimester: ß=2.28, 95%CI: (0.95,3.61); third trimester: ß=2.35, 95%CI:(0.68,4.01)]). Logistic regression highlighted an increased risk of prehypertension and hypertension in offspring with higher maternal PFHxS concentrations during all three trimesters [first trimester: OR=2.53, 95%CI:(1.11,5.79), second trimester: OR=2.05, 95%CI:(1.11,3.78), third trimester: OR=3.08, 95%CI:(1.40,6.79)]. A positive correlation was identified between the half-lives of PFAS and the odds ratio (OR) of prehypertension and hypertension in childhood (ß=0.139, P=0.010). In conclusion, this research found maternal plasma PFAS concentrations to be positively associated with BP in offspring, with PFHxS showing the most significant influence. This correlation remained consistent throughout pregnancy, and this effect was proportional to the half-lives of PFAS.

Active cellulose acetate/purple sweet potato anthocyanins@cyclodextrin metal-organic framework/eugenol colorimetric film for pork preservation.

As a natural pH-sensing colorant, purple sweet potato anthocyanins (PSPAs) have demonstrated great potential in colorimetric film for freshness monitoring. However, the photothermal instability of PSPAs is still a challengeable issue. Herein, γ-cyclodextrin metal-organic framework (CD-MOF) loaded with PSPAs (PSPAs@CD-MOF, i.e., PM) and eugenol (EUG) were incorporated in cellulose acetate (CA) matrix for developing a smart active colorimetric film of CA/PM/EUG, where PM and EUG were hydrogen-bonded with CA. Attentions were focused on the photothermal colorimetric stability, colorimetric response, and antibacterial activity of the films. The presence of PM and EUG endowed the film outstanding UV-blocking performance and enhanced the barrier against water vapor and oxygen. Target film of CA/PM15/EUG10 had good photothermal colorimetric stability due to the protection of CD-MOF on PSPAs and the color changes with pH-stimuli were sensitive and reversible. In addition to antioxidant activity, CA/PM15/EUG10 had antibacterial activity against Escherichia coli and Staphylococcus aureus. The application trial results indicated that the CA/PM15/EUG10 was valid to indicate pork freshness and extended the shelf-life by 100 % at 25 °C, which has demonstrated a good perspective on smart active packaging for freshness monitoring and shelf-life extension.

Antimicrobial photodynamic inactivation pH-responsive films based on gelatin/chitosan incorporated with aloe-emodin.

Using novel active food packaging has gradually become a daily necessity in terms of impeding microbial contamination. Here, an antimicrobial photodynamic inactivation (PDI) pH-responsive film is developed by incorporating aloe-emodin (AE) into a vehicle of gelatin/chitosan (GC). Besides enhancement in hydrophobicity, the well-dispersed crystals of AE in the GC matrix by hydrogen bonding can upgrade the film's mechanical strength and barrier. The matrix is capable of regulating the release of AE in response to acidic stimuli by a combination mechanism of diffusion and polymer relaxation. Being benefitted from the inherent bioactivity of AE and the PDI activity under visible light irradiation (i.e., 456 nm), the target film of GC-AE2 has excellent antibacterial effect towards Staphylococcus aureus and Escherichia coli, showing bacterial viability of 9.93 ± 1.33 % and 14.85 ± 1.16 %, respectively. Furthermore, the film can effectively thwart Botrytis cinerea infection in cherry tomatoes, demonstrating its potential in preventing the microbial spoilage of postharvest fruits.

Photocatalytic chitosan-based bactericidal films incorporated with WO3/AgBr/Ag and activated carbon for ethylene removal and application to banana preservation.

Ethylene (C2H4) and pathogenic microorganisms are the two major causes of the deterioration of postharvest fruits and vegetables (F&V). Hence, the development of active packaging with C2H4 scavenging and bactericidal activities is urgently desirable. Herein, a novel photocatalytic active film (CS-PC-AC) is developed for banana preservation by incorporating WO3/AgBr/Ag photocatalyst (PC) and activated carbon (AC) into chitosan (CS). The fabricated PC is a ternary Z-scheme heterojunction and its high photocatalytic activity is achieved by the bridge of Ag between WO3 and AgBr through rapid transfer and separation of photogenerated electrons and holes. AC plays an indispensable role in the photocatalytic reaction through molecule adsorption and transport. PC and AC are hydrogen bonded with chitosan and their incorporation has slight effect on film's thermal stability but decreases the film's mechanical and barrier properties to some extent. CS-PC-AC exhibits strong bactericidal activity (killing ~100 % of Escherichia coli and Staphylococcus aureus within 3 h) and good C2H4 scavenging activity (C2H4 scavenging rate of 49 ± 2 %) under visible light irradiation, which can extend the banana shelf-life by at least 50 % at 25 °C. These results indicate the good perspective of CS-PC-AC in the delay of the deterioration of postharvest F&V.

Host factor MxA restricts Dabie bandavirus infection by targeting the viral NP protein to inhibit NP-RdRp interaction and ribonucleoprotein activity.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case mortality rates, which is caused by Dabie bandavirus (DBV), a novel pathogen also termed as SFTS virus (SFTSV). Currently, no specific therapeutic drugs or vaccines are available for SFTS. Myxovirus resistance protein A (MxA) has been shown to inhibit multiple viral pathogens; however, the role of MxA in DBV infection is unknown. Here, we demonstrated that DBV stimulates MxA expression which, in turn, restricts DBV infection. Mechanistic target analysis revealed that MxA specifically interacts with the viral nucleocapsid protein (NP) in a manner independent of RNA. Minigenome reporter assay showed that in agreement with its targeting of NP, MxA inhibits DBV ribonucleoprotein (RNP) activity. In detail, MxA interacts with the NP N-terminal and disrupts the interaction of NP with the viral RNA-dependent RNA polymerase (RdRp) but not NP multimerization, the critical activities of NP for RNP formation and function. Furthermore, MxA N-terminal domain was identified as the functional domain inhibiting DBV infection, and, consistently, then was shown to interact with NP and obstruct the NP-RdRp interaction. Additionally, threonine 103 within the N-terminal domain is important for MxA inhibition to DBV, and its mutation (T103A) attenuates MxA binding to NP and obstruction of the NP-RdRp interaction. This study uncovers MxA inhibition of DBV with a series of functional and mechanistical analyses, providing insights into the virus-host interactions and probably helping inform the development of antiviral agents in the future.IMPORTANCEDBV/SFTSV is an emerging high-pathogenic virus. Since its first identification in China in 2009, cases of DBV infection have been reported in many other countries, posing a significant threat to public health. Uncovering the mechanisms of DBV-host interactions is necessary to understand the viral pathogenesis and host response and may advance the development of antiviral therapeutics. Here, we found that host factor MxA whose expression is induced by DBV restricts the virus infection. Mechanistically, MxA specifically interacts with the viral NP and blocks the NP-RdRp interaction, inhibiting the viral RNP activity. Further studies identified the key domain and amino acid residue required for MxA inhibition to DBV. Consistently, they were then shown to be important for MxA targeting of NP and obstruction of the NP-RdRp association. These findings unravel the restrictive role of MxA in DBV infection and the underlying mechanism, expanding our knowledge of the virus-host interactions.

Reduction in Insulin Uncovers a Novel Effect of VEGFB on Cardiac Substrate Utilization.

BACKGROUND: The heart relies heavily on external fatty acid (FA) for energy production. VEGFB (vascular endothelial growth factor B) has been shown to promote endothelial FA uptake by upregulating FA transporters. However, its impact on LPL (lipoprotein lipase)-mediated lipolysis of lipoproteins, a major source of FA for cardiac use, is unknown. METHODS: VEGFB transgenic (Tg) rats were generated by using the α-myosin heavy chain promoter to drive cardiomyocyte-specific overexpression. To measure coronary LPL activity, Langendorff hearts were perfused with heparin. In vivo positron emission tomography imaging with [18F]-triglyceride-fluoro-6-thia-heptadecanoic acid and [11C]-palmitate was used to determine cardiac FA uptake. Mitochondrial FA oxidation was evaluated by high-resolution respirometry. Streptozotocin was used to induce diabetes, and cardiac function was monitored using echocardiography. RESULTS: In Tg hearts, the vectorial transfer of LPL to the vascular lumen is obstructed, resulting in LPL buildup within cardiomyocytes, an effect likely due to coronary vascular development with its associated augmentation of insulin action. With insulin insufficiency following fasting, VEGFB acted unimpeded to facilitate LPL movement and increase its activity at the coronary lumen. In vivo PET imaging following fasting confirmed that VEGFB induced a greater FA uptake to the heart from circulating lipoproteins as compared with plasma-free FAs. As this was associated with augmented mitochondrial oxidation, lipid accumulation in the heart was prevented. We further examined whether this property of VEGFB on cardiac metabolism could be useful following diabetes and its associated cardiac dysfunction, with attendant loss of metabolic flexibility. In Tg hearts, diabetes inhibited myocyte VEGFB gene expression and protein secretion together with its downstream receptor signaling, effects that could explain its lack of cardioprotection. CONCLUSIONS: Our study highlights the novel role of VEGFB in LPL-derived FA supply and utilization. In diabetes, loss of VEGFB action may contribute toward metabolic inflexibility, lipotoxicity, and development of diabetic cardiomyopathy.

Preliminary Investigation of Thermoelectric Electromotive Force Oscillation of NiCr/NiSi Thin Film Thermocouple in Dynamic Calibration.

In order to reveal the dynamic response characteristic of thin film thermocouples (TFTCs), the nichrome/nisil (NiCr/NiSi) TFTCs are prepared onto the glass substrate. With short pulse infrared laser system, NiCr/NiSi TFTCs are dynamically calibrated. The thermoelectric electromotive force (TEF) curves of NiCr/NiSi TFTCs are recorded by the memory hicorder system, which could reflect TEF signals with resolution ratio in nanosecond and microvolt, simultaneously. With increasing laser energy from 15.49 to 29.59 mJ, TEF curves display more and more violent oscillation, even negative value. The results show that the bounce of thermal energy happens between two interfaces of TFTCs because the thermal conductivity of glass and air is significantly lower than that of NiSi/NiCr TFTCs. The bounce of thermal energy results in the obvious decrease of nNiCr and nNiSi , as well as oscillation of TEF. For laser energy in 29.59 mJ, the bounce of thermal energy in NiCr film could result in nNiCr < nNiSi . Then, TEF value appears abnormal negative value. Based on the results, the complex thermal energy transport process in TFTCs dynamic calibration is revealed, which results in the oscillation of thermal energy and TEF signal.

The Identity of Nickel Peroxide as a Nickel Superoxyhydroxide for Enhanced Electrocatalysis.

Nickel peroxides are a class of stoichiometric oxidants that can selectively oxidize various organic compounds, but their molecular level structure remained elusive until now. Herein, we utilized structural prediction using the Stochastic Surface Walking method based on a neural network potential energy surface and advanced characterization using the as-synthesized nickel peroxide to unravel its chemical identity as the bridging superoxide containing nickel hydroxide, or nickel superoxyhydroxide. Superoxide incorporation tunes the local chemical environment of nickel and oxygen beyond the conventional Bode plot, offering a 6.4-fold increase in the electrocatalytic activity of urea oxidation. A volcanic dependence of the activity on the oxygen equivalents leads to the proposed active site of the Ni(OO)(OH)Ni five-membered ring. This work not only unveils the possible structures of nickel peroxides but also emphasizes the significance of tailoring the oxygen environment for advanced catalysis.

Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in multiple cellular biological processes potentially associated with the physiological actions of the viral glycoproteins. Then, we elucidated the role of a representative cellular protein, HAX1. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is required for functional glycoprotein-mediated progeny virion packaging. Consistently, the inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections in cellular and animal models. Together, the findings provide a systematic CCHFV Gn/Gc-cell protein-protein interaction map, but also unravel a HAX1/mitochondrion-associated host antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.

The Neutralizing Monoclonal Antibodies against SFTS Group Bandaviruses Suggest New Targets of Specific or Broad-Spectrum Antivirals.

Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV) and Guertu virus (GTV) belong to the severe fever with thrombocytopenia syndrome/Heartland group of genus Bandavirus in the family Phenuiviridae of order Bunyavirales. Severe fever with thrombocytopenia syndrome virus and HRTV, identified from ticks from Asia and America, respectively, are important pathogens causing severe febrile diseases in humans. Guertu virus, closely related to these two viruses, is a potential pathogen, but no confirmed infection has been identified. So far, human-derived neutralizing monoclonal antibodies (mAbs) against SFTSV have been identified as having a great potential to be developed as antivirals; however, there is still a lack of neutralizing mAbs to GTV and HRTV. In this study, five neutralizing the mAbs against GTV and HRTV were obtained by hybridoma screening technology, four of which (14B4, 14D8, and 20D4 derived from GTV, and 27C8 derived from HRTV) showed cross reactivity and neutralization to all three viruses, and one derived from HRTV (10D6) neutralized HRTV specifically. The possible mechanisms of mAbs cross neutralization among the three viruses are discussed by analyzing their glycoprotein (GP) sequences and structures. Generating these neutralizing mAbs provides important antiviral candidates against GTV, HRTV, and SFTSV despite their differential activities, and their protective effect could be further evaluated in virus-infected mice. Their differential neutralizing efficiency and specificity further suggested that the three viruses share common mechanisms on the basis of GP functioning, and that HRTV poses a unique mechanism that differs from the other viruses. These findings shed light on developing broad-spectrum antiviral strategies against bandaviruses and promoting an understanding of the bandavirus infection process.

Perfluoroalkyl substances in umbilical cord blood and blood pressure in offspring: a prospective cohort study.

BACKGROUND: Humans are widely exposed to perfluoroalkyl substances (PFAS), which have been found to be associated with various adverse birth outcomes. As blood pressure (BP) is an important parameter reflecting cardiovascular health in early life, it is necessary to investigate the association of PFAS exposure during early lifetime and BP in childhood. Therefore, we investigated the potential association between PFAS levels in umbilical cord blood and BP of the offspring at 4 years of age in a prospective cohort study. METHODS: PFAS in umbilical cord blood samples after birth were measured with high-performance liquid chromatography/tandem mass spectrometry in the Shanghai Birth Cohort. BP was measured at 4 years of age in the offspring. Multiple linear regression model was used to investigate the association between individual PFAS level and BP of the offspring. Bayesian kernel machine regression (BKMR) was used to analyze the relationship between the PFAS mixture and BP of the offspring, while weighted quantile sum (WQS) regression was utilized for sensitivity analysis. RESULTS: A total of 129 mother-child pairs were included in our analysis. In multiple linear regressions, we observed that long-chain PFAS, mainly including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUA), was negatively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP). BKMR showed that an increase in umbilical cord blood PFAS mixture levels was significantly associated with a decrease in SBP, DBP and MAP [Estimated differences (SD): -0.433 (0.161); -0.437 (0.176); -0.382 (0.179), respectively]. The most important component in the association with SBP, DBP, and MAP was PFUA. PFDoA was found to be positively associated with SBP, DBP and MAP in both models. Sensitivity analysis with WQS regression showed consistent results. CONCLUSION: Our findings suggested that umbilical blood PFAS exposure was negatively associated with BP in offspring at 4 years of age, including SBP, DBP, and MAP.

Internal reuse of methanol-to-olefin wastewater based on micro-channel separation coupling hydrocyclone regeneration.

Methanol-to-olefin (MTO) is a typical new coal chemical industry example. Due to the large volume of generated wastewater, complex composition including catalysts, aromatics and various oxygen-containing compounds, and serious environmental hazard, wastewater recycling is critical for sustainable industrial development and ecological protection. Herein, a swirl regenerating micro-channel separation (SRMS) technology was proposed to integrate deep filtration and hydrocyclone-enhanced regeneration. A small-scale experimental investigation was first conducted to verify the feasibility of the MTO wastewater treatment. A pilot SRMS device with a treatment capacity of 20 m3/h was constructed, and the device's continuous operation effect and stability were comprehensively evaluated. The separation performance of the SRMS device at different solution pH values and the impact of the hydrocyclone-enhanced regeneration of separation media were discussed in detail. At low solution pH values (<7), the SRMS device exhibits an average separation efficiency of 92.0% for fine particulate matter in wastewater, and the median particle size, d50, decreases from 1.55 to 0.6 µm. As the solution pH increases, the repulsive energy barrier for the medium-contaminant and contaminant-contaminant increases, inhibiting the deposition behavior of particulate pollutants. In addition, hydrocyclone desorbs contaminants deposited on the separation media and the average contaminant residual rate decreases from 3.3 to 0.2 wt%. We propose an industrial application for treating and reusing MTO wastewater (200 m3/h) using the SRMS technology based on the experimental results. The costs of the wastewater treatment process are as low as 0.25 CNY/m3, and the wastewater reuse rate is over 97% without chemical consumption. This work can provide an environmentally friendly and economically sustainable approach to the source management of MTO wastewater.

Modified sphenoidotomy for isolated sphenoid sinus disease: A series of 117 cases.

BACKGROUND: The atresia rate of sphenoid ostium after endoscopic sphenoidotomy for isolated sphenoid disease is 9.4%-10.2%. AIMS: To reduce sphenoid sinus ostium atresia rate after sphenoidotomy surgery. MATERIALS AND METHODS: The data of patients with isolated sphenoid sinus disease at our hospital between 2015 and 2022 were retrospectively analyzed. The age, gender, disease course, pathology, postoperative follow-up time, anatomy data of sphenoid sinus and postoperative sinus ostium atresia rate were compared between the two groups of patients with traditional sphenoidotomy and modified sphenoidotomy. RESULTS: A total of 117 patients with isolated sphenoid sinus disease underwent endoscopic sphenoidotomy. There were 76 cases in the traditional sphenoidotomy group, fungus ball in 59.2% of patients, the postoperative sinus ostium atresia rate was 14.5%. There were 41 cases in the modified sphenoidotomy group, fungus ball in 53.6% of patients, and 0 case of sinus ostium atresia. Statistical analysis showed significant differences in postoperative sinus ostium atresia rate. There was no significant difference in age, pathology, postoperative follow-up time, anatomy data of sphenoid, and other data. CONCLUSIONS AND SIGNIFICANCE: The modified endoscopic sphenoidotomy may reduce the rate of postoperative sinus ostium atresia.

Active colorimetric bilayer polycaprolactone-eucalyptus oil@silk fibroin-bayberry anthocyanins (PCL-EO@SF-BAs) membrane with directional water transport (DWT) for food packaging.

Currently, designing smart membranes with multifunctional effectiveness is crucial to food freshness monitoring and retention. Herein, an active colorimetric Janus bilayer membrane with directional water transport (DWT) performance is constructed by electrospinning, which comprises a hydrophilic layer of silk fibroin-bayberry anthocyanins (SF-BAs) and a hydrophobic layer of polycaprolactone-eucalyptus oil (PCL-EO). The entities of BAs and EO are well dispersed in the fiber matrix by hydrogen bonds and physical interactions, respectively. BAs endow the membrane colorimetric response and antioxidant activity, and EO contributes to the antibacterial activity while DWT performance is generated from the asymmetric wettability of the two layers. The bilayer membrane has an accumulative one-way transport index of 1077%, an overall moisture management capacity of 0.76 and a water evaporation rate of 0.48 g h-1. Moreover, the release of BAs and EO was predominantly controlled by Fickian diffusion. As a pH-sensing indicator, PCL-EO@SF-BAs is highly sensitive to external pH stimuli and the response is reversible. In addition to freshness monitoring, PCL-EO@SF-BAs can extend the shelf-life of pork beyond 100% at 4 °C. Also, it can extend the shelf life of shrimp by approximately 70% at 25 °C with the synergistic effect of antibacterial activity and the DWT performance.

Enhancement of the classification and recovery process of fine mineral particles via a newly developed volute feed hydrocyclone.

Ore resources in the mining process form a large number of unmanageable tailings, mostly inhalable fine mineral particles, into the environment will cause serious pollution, and recycling is a precious resource. The cyclone classification provides the possibility for the recovery and exploitation of fine particles, but the recovery and utilization rate of conventional cyclone separation is seriously low, and the performance urgently should be optimized. In the present study, a new type of volute feed was proposed to strengthen the classification and recovery process of fine mineral particles. Combined with numerical simulation and experimental research, the effects of various structural parameters and operating parameters on the flow field distribution, particle motion, and classification performance were systematically examined. The obtained results reveal that the new volute feed structure can effectively reduce the internal turbulence and improve the flow field stability and particle classification efficiency. Compared with the traditional hydrocyclone, the classification efficiency of fine particles with new feed structure increases by 10-18%. Increasing underflow diameter and feed pressure and reducing overflow diameter and feed concentration are also beneficial to lessening classification particle size and enhancing classification performance. The currently achieved outcomes can provide valuable guidelines for further development of novel hydrocyclones.

SARS-CoV-2 NSP13 interacts with host IRF3, blocking antiviral immune responses.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to human health since late 2019. Notably, the progression of the disease is associated with impaired antiviral interferon (IFN) responses. Although multiple viral proteins were identified as potential IFN antagonists, the underlying molecular mechanisms remain to be fully elucidated. In this study, we firstly demonstrate that SARS-CoV-2 NSP13 protein robustly antagonizes IFN response induced by the constitutively active form of transcription factor IRF3 (IRF3/5D). This induction of IFN response by IRF3/5D is independent of the upstream kinase, TBK1, a previously reported NSP13 target, thus indicating that NSP13 can act at the level of IRF3 to antagonize IFN production. Consistently, NSP13 exhibits a specific, TBK1-independent interaction with IRF3, which, moreover, is much stronger than that of NSP13 with TBK1. Furthermore, the NSP13-IRF3 interaction was shown to occur between the NSP13 1B domain and IRF3 IRF association domain (IAD). In agreement with the strong targeting of IRF3 by NSP13, we then found that NSP13 blocks IRF3-directed signal transduction and antiviral gene expression, counteracting IRF3-driven anti-SARS-CoV-2 activity. These data suggest that IRF3 is likely to be a major target of NSP13 in antagonizing antiviral IFN responses and provide new insights into the SARS-CoV-2-host interactions that lead to viral immune evasion.

Developing and characterizing monoclonal antibodies of Guertu bandavirus nucleoprotein for developing methods of Guertu bandavirus and severe fever with thrombocytopenia syndrome virus detection.

Belonging to genus Bandavirus in Phenuiviridae family, Guertu bandavirus (GTV) is a potential pathogen closely related to severe fever with thrombocytopenia syndrome virus (SFTSV) and heartland virus (HRTV) associated with human diseases. Although the medical significance of GTV is not clear, there was serological evidence suggesting past infection with this virus has occurred, indicating its potential threat to human health. So, it is important to prepare for detection of GTV infection so as to control virus transmission and promote disease diagnosis and treatment. This study is aimed at obtaining monoclonal antibodies (mAbs) against GTV nucleoprotein (NP) and evaluating their activities in recognizing viral antigens from genetic-related bandaviruses, SFTSV and HRTV. Eight mAbs were obtained and four of them (22G1, 25C2, 25E2, and 26F8) recognize linear epitopes of GTV NP. The four mAbs showed cross-reactivity to SFTSV but were unable to react with HRTV. Two fine epitopes were identified by the four mAbs, ENP1 (194YNSFRDPLHAAV205) and ENP2 (226GPDGLP231), which are highly conserved in the NPs of GTV and SFTSV but are distinct in HRTV NP. The features of epitopes, including their hydrophilicity, antibody accessibility, flexibility, antigenicity, and spatial locations, were predicted and analyzed, and their potential functional impacts on virus infection and replication and their use for virus detection were discussed. Our results promote the understanding of the molecular basis of GTV and SFTSV NP in inducing antibody responses. The NP-specific mAbs generated in this study are promising fundamental materials for developing viral antigen detection methods for GTV and SFTSV.

Development of a new cellular immunological detection method for tuberculosis based on HupB protein induced IL-6 release test.

Objective: As a virulence factor, HupB plays important roles in the survival of MTB after infection and modulates the host immune response. In the current study, we aim to explore a new cellular immunological detection method for tuberculosis infection detection based on HupB protein. Methods: HupB was used to stimulate PBMCs extracted from pulmonary tuberculosis (PTB) patients, and secreted cytokines was examined. Then, we constructed a single center and a multi-center clinical trials to collect PBMCs from PTB patients, nPTB patients, or healthy volunteers to verify our findings. Results: Cytokine's screening illustrated that IL-6 was the only cytokine released after HupB stimulation. Single-center and multi-center clinical trials showed that HupB stimulation significantly increased the level of IL-6 in the supernatant of PBMCs from PTB patients. Then we compared the specificity and sensitivity of HupB induced IL-6 release assay with ESAT-6 and CFP10 induced interferon γ release assay (IGRA), and found in smear positive PTB patients, the specificity and sensitivity of HupB induced IL-6 release assay was better than IGRA, and in smear negative PTB patients, the sensitivity was better. Combination of both assays provided an improved specificity and sensitivity for tuberculosis diagnosis. Conclusion: This study explored an immunological detection method for tuberculosis infection cells based on HupB protein-induced IL-6 release test, which can be used to enhance the diagnosis diagnostic accuracy of TB.