Efficient hydrogen production from wastewater remediation by piezoelectricity coupling advanced oxidation processes.

Efficient H2 harvesting from wastewater instead of pure water can minimize fresh water consumption, which is expected to solve the problem of water shortage in H2 production process and contribute to carbon neutrality in the environmental remediation, but the inevitable electron depletion caused by electron-consuming pollutants will result in an exhausted H2 evolution reaction (HER) performance. In this paper, by coupling piezocatalysis and advanced oxidation processes (AOPs) by a MoS2/Fe0/peroxymonosulfate (PMS) ternary system, extensive types of wastewater achieved considerable H2 generation, which exceeded the yield in pure water with synchronous advanced degradation of organic pollutants. In addition, profiting from the crucial bridging role of PMS, the H2 yield in nitrobenzene wastewater after the introduction of PMS-based AOPs increased 3.37-fold from 267.7 µmol·g-1·h-1 to 901.0 µmol·g-1·h-1 because the presence of PMS both thermodynamically benefited MoS2 piezocatalytic H2 evolution and eliminated the electron depletion caused by organic pollutants. By this way, the original repressed H2 evolution performance in substrate of wastewater not only was regained but even showed a significant enhancement than that in pure water (505.7 µmol·g-1·h-1). Additionally, the cyclonic piezoelectric reactor was preliminarily designed for future industrialization. This strategy provided a valuable path for the recycling of actual wastewater by fuel production and synchronous advanced treatment.

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.

Day and Night Reversed Feeding Aggravates High-Fat Diet-Induced Abnormalities in Intestinal Flora and Lipid Metabolism in Adipose Tissue of Mice.

BACKGROUND: The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic disorders. The intestinal microflora engages in regulating various physiological functions of the host through its metabolites. OBJECTIVES: This study aimed to investigate the impact of reversed feeding schedules during the day and night on intestinal flora and lipid metabolism in high-fat diet-induced obese mice. METHODS: Mice aged 8-10 wk were subjected to either daytime or nighttime feeding and were administered a control or high-fat diet for 18 wk. At the end of the experiment, various assessments were conducted, including analysis of serum biochemic indices, histologic examination, evaluation of gene and protein expression in adipose tissue, and scrutiny of changes in intestinal microbial composition. RESULTS: The results showed that day-night reversed feeding caused an increase in fasting blood glucose and exacerbated the high-fat diet-induced weight gain and lipid abnormalities. The mRNA expression levels of Leptin and Dgat1 were increased by day-night reversed feeding, which also reduced the expression level of adiponectin under the high-fat diet. Additionally, there was a significant increase in the protein concentrations of PPARγ, SREBP1c, and CD36. Inverted feeding schedules led to a reduction in intestinal microbial diversity, an increase in the abundance of inflammation-related bacteria, such as Coriobacteriaceae_UCG-002, and a suppression of beneficial bacteria, including Akkermansia, Candidatus_Saccharimonas, Anaeroplasma, Bifidobacterium, Carnobacterium, and Odoribacter. Acinetobacter exhibited a significant negative correlation with Leptin and Fasn, suggesting potential involvement in the regulation of lipid metabolism. CONCLUSIONS: The results elucidated the abnormalities of lipid metabolism and intestinal flora caused by day-night reversed feeding, which exacerbates the adverse effects of a high-fat diet on lipid metabolism and intestinal microflora. This reversal in feeding patterns may disrupt both intestinal and lipid metabolism homeostasis by altering the composition and abundance of intestinal microflora in mice.

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.

The association of gestational age and birthweight with blood pressure, cardiac structure, and function in 4 years old: a prospective birth cohort study.

BACKGROUND: Current evidence relating birthweight and gestational age to cardiovascular risk is conflicting. Whether these factors have independent or interactive impacts on cardiovascular parameters during early childhood remains unclear. The goal of this study was to explore whether there were any independent and interactive effects of gestational age and birthweight on blood pressure, left ventricle (LV) structure, and function in 4 years old. METHODS: This study included 1194 children in the Shanghai Birth Cohort from 2013 to 2016. Information about the mothers and children was recorded at time of birth using a questionnaire. Follow-up measurements, including anthropometric, blood pressure, and echocardiography, were taken between 2018 and 2021, when the children were 4 years old. Multiple linear or logistic regressions and restricted cubic spline were used to explore the association of birthweight and gestational age with cardiovascular measurements. RESULTS: Gestational age had a significant negative correlation with both systolic blood pressure [ß = - 0.41, 95% CI: (- 0.76, - 0.07)] and mean arterial pressure [ß = - 0.36, 95%CI: (- 0.66, - 0.07)]. The risk of prehypertension decreased with increased gestational age [OR = 0.54, 95% CI: (0.32, 0.93)]. The relationship between birthweight with blood pressure was U-shape (P for non-linear < 0.001). The wall thickness, volume, mass, and cardiac output of LV increased with birthweight, though the ejection fraction [ß = - 1.02, 95% CI: (- 1.76, - 0.27)] and shorten fraction [ß = 0.72, 95% CI: (- 1.31, - 0.14)] decreased with birthweight. The risk of LV hypertrophy was not associated with birthweight [OR = 1.59, 95% CI: (0.68, 3.73)]. CONCLUSIONS: In this study, we found different associations of birthweight and gestational age with cardiovascular measurements in the offspring at 4 years old. Gestational age influenced blood pressure independent of birthweight. Heart size and function at 4 years old was influenced mostly by birthweight and not by gestational age.

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.

Exosomal ncRNAs profiling of mycobacterial infection identified miRNA-185-5p as a novel biomarker for tuberculosis.

BACKGROUND: There are ever increasing researches implying that noncoded RNAs (ncRNAs) specifically circular RNAs (circRNAs) and microRNAs (miRNAs) in exosomes play vital roles in respiratory disease. However, the detailed mechanisms persist to be unclear in mycobacterial infection. METHODS: In order to detect circRNAs and miRNAs expression pattern and potential biological function in tuberculosis, we performed immense parallel sequencing for exosomal ncRNAs from THP-1-derived macrophages infected by Mycobacterium tuberculosis H37Ra, Mycobacterium bovis BCG and control Streptococcus pneumonia, respectively and uninfected normal cells. Besides, THP-1-derived macrophages were used to verify the validation of differential miRNAs, and monocytes from PBMCs and clinical plasma samples were used to further validate differentially expressed miR-185-5p. RESULTS: Many exosomal circRNAs and miRNAs associated with tuberculosis infection were recognized. Extensive enrichment analyses were performed to illustrate the major effects of altered ncRNAs expression. Moreover, the miRNA-mRNA and circRNA-miRNA networks were created and expected to reveal their interrelationship. Further, significant differentially expressed miRNAs based on Exo-BCG, Exo-Ra and Exo-Control, were evaluated, and the potential target mRNAs and function were analyzed. Eventually, miR-185-5p was collected as a promising potential biomarker for tuberculosis. CONCLUSION: Our findings provide a new vision for exploring biological functions of ncRNAs in mycobacterial infection and screening novel potential biomarkers. To sum up, exosomal ncRNAs might represent useful functional biomarkers in tuberculosis pathogenesis and diagnosis.

SFTS bunyavirus NSs protein sequestrates mTOR into inclusion bodies and deregulates mTOR-ULK1 signaling, provoking pro-viral autophagy.

Autophagy is emerging as a critical player in host defense against diverse infections, in addition to its conserved function to maintain cellular homeostasis. Strikingly, some pathogens have evolved strategies to evade, subvert or exploit different steps of the autophagy pathway for their lifecycles. Here, we present a new viral mechanism of manipulating autophagy for its own benefit with severe fever with thrombocytopenia syndrome bunyavirus (SFTSV, an emerging high-pathogenic virus) as a model. SFTSV infection triggers autophagy, leading to complete autophagic flux. Mechanistically, we show that the nonstructural protein of SFTSV (NSs) interacts with mTOR, the pivotal regulator of autophagy, by targeting its kinase domain and captures mTOR into viral inclusion bodies (IBs) induced by NSs itself. Furthermore, NSsimpairs mTOR-mediated phosphorylation of unc-51-like kinase 1 (ULK1) at Ser757, disrupting the inhibitory effect of mTOR on ULK1 activity and thus contributing to autophagy induction. Pharmacologic treatment and Beclin-1 knockout experimental results establish that, in turn, autophagy enhances SFTSV infection and propagation. Moreover, the minigenome reporter system reveals that SFTSV ribonucleoprotein (the transcription and replication machinery) activity can be bolstered by autophagy. Additionally, we found that the NSs proteins of SFTSV-related bunyaviruses have a conserved function of targeting mTOR. Taken together, we unravel a viral strategy of inducing pro-viral autophagy by interacting with mTOR, sequestering mTOR into IBs and hence provoking the downstream ULK1 pathway, which presents a new paradigm for viral manipulation of autophagy and may help inform future development of specific antiviral therapies against SFTSV and related pathogens.

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.

Estimating the Mass of Pharmaceuticals Harbored in Municipal Solid Waste Landfills by Analyzing Refuse Samples at Various Ages and Depths.

Pharmaceuticals have been detected at high concentrations in municipal solid waste (MSW) landfill leachates, which are recognized as an underestimated source of pharmaceutical residues in the environment. However, limited efforts have been made to characterize pharmaceuticals in MSW landfill refuse, which is also of significant concern given the potential long-term environmental impact. Herein, we excavated landfill refuse from six cells with landfill ages of 7-27 years in the largest MSW landfill in Shanghai (in each cell, landfill refuse was collected from different depths of 2-8 m) and analyzed samples for the presence of 55 pharmaceuticals, including antibiotics and non-antibiotics. The results reveal the presence of 42 pharmaceuticals in landfill refuse, with median concentrations ranging from 0.30 to 116 µg/kg. Antibiotic and non-antibiotic pharmaceuticals exhibited diverse concentration trends with age, related to changes in policy intervention and consumption over time. Different concentration variations of individual pharmaceuticals were observed in refuse samples excavated at different depths and positively correlated to their sorption ability. The mass of pharmaceuticals in the investigated landfill was estimated from the obtained concentrations to be 80-220 tons with 95% probability, based on Monte Carlo analysis. To the best of our knowledge, this study provides the first estimate of pharmaceutical mass in an MSW landfill. The results will be helpful for understanding the potential long-term environmental impact of pharmaceuticals in landfills.

Spatial distribution, contamination characteristics and ecological-health risk assessment of toxic heavy metals in soils near a smelting area.

Soil heavy metals (HMs) contamination stemming from smelting and mining activities is becoming a global concern due to its devastating impacts on the environment and human health. In this study, 128 soil samples were investigated to assess the spatial distribution, contamination characteristics, ecological and human health risk of HMs in soils near a smelting area by using BP artificial neural network (BP-ANN) and Monte Carlo simulation. The results showed that the concentrations of all five HMs in the soil greatly exceeded the background value of study area with a basic trend: Pb > As > Cr > Cd > Hg, indicating a high pollution level. Arsenic and lead were the major pollutants in the study area with an exceedance rate of 78.95% and 28.95%, respectively. The toxic fume and dust emitted during the smelting process were identified as the major sources of HMs pollution in soil, while Cd pollution was mainly caused by agricultural activities near the study area. The probabilistic risk assessment suggested that the average HQ values of five HMs for children and adults exceeded the acceptable threshold with a trend: As > Pb > Cr > Cd > Hg. The average CR values of As, Cr and Pb for all population were greatly larger than the acceptable threshold (CR ≥ 1), indicating a high cancer risk. However, the CR values of Cd for adults and children were within the acceptable threshold (CR < 1), implying no cancer risk. The results of the present study can provide some insight into the contamination characteristics, ecological and human health risk of HMs in contaminated soils by mining and smelting activities, which can help prevent and control soil pollution and environmental risk.

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.

Interlayer Structure Manipulation of Iron Oxychloride by Potassium Cation Intercalation to Steer H2O2 Activation Pathway.

Structural regulation of the active centers is often pivotal in controlling the catalytic functions, especially in iron-based oxidation systems. Here, we discovered a significantly altered catalytic oxidation pathway via a simple cation intercalation into a layered iron oxychloride (FeOCl) scaffold. Upon intercalation of FeOCl with potassium iodide (KI), a new stable phase of K+-intercalated FeOCl (K-FeOCl) was formed with slided layers, distorted coordination, and formed high-spin Fe(II) species compared to the pristine FeOCl precursor. This structural manipulation steers the catalytic H2O2 activation from a traditional Fenton-like pathway on FeOCl to a nonradical ferryl (Fe(IV)═O) pathway. Consequently, the K-FeOCl catalyst can efficiently remove various organic pollutants with almost 2 orders of magnitude faster reaction kinetics than other Fe-based materials via an oxidative coupling or polymerization pathway. A reaction-filtration coupled process based on K-FeOCl was finally demonstrated and could potentially reduce the energy consumption by almost 50%, holding great promise in sustainable pollutant removal technologies.

Host restriction of emerging high-pathogenic bunyaviruses via MOV10 by targeting viral nucleoprotein and blocking ribonucleoprotein assembly.

Bunyavirus ribonucleoprotein (RNP) that is assembled by polymerized nucleoproteins (N) coating a viral RNA and associating with a viral polymerase can be both the RNA synthesis machinery and the structural core of virions. Bunyaviral N and RNP thus could be assailable targets for host antiviral defense; however, it remains unclear which and how host factors target N/RNP to restrict bunyaviral infection. By mass spectrometry and protein-interaction analyses, we here show that host protein MOV10 targets the N proteins encoded by a group of emerging high-pathogenic representatives of bunyaviruses including severe fever with thrombocytopenia syndrome virus (SFTSV), one of the most dangerous pathogens listed by World Health Organization, in RNA-independent manner. MOV10 that was further shown to be induced specifically by SFTSV and related bunyaviruses in turn inhibits the bunyaviral replication in infected cells in series of loss/gain-of-function assays. Moreover, animal infection experiments with MOV10 knockdown corroborated the role of MOV10 in restricting SFTSV infection and pathogenicity in vivo. Minigenome assays and additional functional and mechanistic investigations demonstrate that the anti-bunyavirus activity of MOV10 is likely achieved by direct impact on viral RNP machinery but independent of its helicase activity and the cellular interferon pathway. Indeed, by its N-terminus, MOV10 binds to a protruding N-arm domain of N consisting of only 34 amino acids but proving important for N function and blocks N polymerization, N-RNA binding, and N-polymerase interaction, disabling RNP assembly. This study not only advances the understanding of bunyaviral replication and host restriction mechanisms but also presents novel paradigms for both direct antiviral action of MOV10 and host targeting of viral RNP machinery.

Antitumor efficacy of CRISPR/Cas9-engineered ICP6 mutant herpes simplex viruses in a mouse xenograft model for lung adenocarcinoma.

Oncolytic viruses (OVs), including oncolytic herpes simplex viruses (oHSVs), are promising therapeutics against cancer. Here, we report two ICP6-mutated HSVs (type I) generated by CRISPR/Cas9, rHSV1/∆RR (with ICP6 ribonucleotide reductase [RR] domain deleted) and rHSV1/∆ICP6 (with a complete deletion of ICP6), exhibiting potent antitumor efficacy against lung adenocarcinoma. Both the mutants showed strong cytotoxicity in vitro, comparable with the control viruses expressing intact ICP6, but in relatively lower titers. Moreover, these mutant viruses exhibited preferential killing ability against lung tumor cells rather than normal lung fibroblast cells. Further, unlike the control HSV-1 causing severe illness or death in the mouse model, the ICP6-mutated viruses did not induce significant pathogenicity but instead effectively reduced tumor burden in vivo and led to 100% survival of the animals, indicating notable antitumor activity and attenuated virulence. In addition, rHSV1/∆RR seemed to have even better antitumor efficacy than rHSV1/∆ICP6, albeit no statistical significance in inhibition of tumor volume. Histopathologically, rHSV1/∆RR induced massive neutrophil infiltration to the tumor microenvironment and consistently, triggered more antitumor immune and neutrophil chemotactic cytokines or higher expression levels of them (indicated by quantitative polymerase chain reaction and transcriptome analyses). These results demonstrate the anti-adenocarcinoma potential of the CRISPR/Cas9-engineered ICP6 mutant HSV1, especially the rHSV1/∆RR, which likely induces stronger innate antitumor immune response. Together, these findings may provide new valuable clues for further development of OV-based therapeutics against lung adenocarcinoma or other types of tumors.

Bioavailability and health risk of toxic heavy metals (As, Hg, Pb and Cd) in urban soils: A Monte Carlo simulation approach.

Toxic heavy metals pollution in urban soil has become a major global issue due to its adverse effects on the environment and human health. In this paper, 26 soil samples were analyzed to assess the speciation, bioavailability and human health risk of Arsenic (As), Mercury (Hg), Lead (Pb) and Cadmium (Cd) in urban soils of a heavy industrial city in NE China by using a Monte Carlo simulation approach. The results showed that As, Hg, Pb and Cd concentrations in the soil all exceed the corresponding background value of study area. Mercury displays the highest value of geo-accumulation index (Igeo), followed by Cd, Pb and As. The pollution load index (PLI) value (>2) indicates a moderate pollution level in the study area. The chemical speciation of HMs mainly exists in residual fraction except Cd. The probabilistic health risk assessment demonstrated that the mean values of Total Carcinogenic Risk (TCR) and Hazard Index (HI) calculated with total concentration are at the unacceptable level, with a higher risk to children than adults. However, the mean values calculated with bioavailable fraction are all within the acceptable level. The mean value of TCR and HI obtained by bioavailable fraction is about 96% and 95% lower than that obtained by total concentration, respectively. Thus, this study suggested that the bioavailable fraction of HMs is a more reliable parameter for health risk assessment, while the total concentration of HMs can overestimate the true risk. The results of this study provide some insight into the speciation, bioavailability and health risks of toxic heavy metals in urban soils in those heavy industrial cities.

Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice.

Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of Per1/Per2 Double knockout (DKO) reduced the reproductive capacity of elderly male mice. The sperm motility and spermatogenic capacity of male DKO mice were weak. Hormone-targeted metabolomics showed reduced plasma levels of free testosterone in DKO male mice compared with WT male mice. Transcriptomic analysis of testicular tissue showed the down-regulation of testosterone synthesis-related enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, and Star) in the steroid hormone synthesis pathway. Spermatogenesis genes, Tubd1 and Pafah1b were down-regulated, influencing tubulin dynamics and leading to impaired motility. Seleno-compound metabolic loci, Scly and Sephs2, were up-regulated and Slc7a11 and Selenop were down-regulated. Western-blotting showed that steroid acute regulatory protein (StAR) and p-CREB, PKA and AC1 were reduced in testicular tissue of DKO mice compared to WT. Therefore, Per1/Per2 disruption reduced testosterone synthesis and sperm motility by affecting the PKA-StAR pathway, leading to decreased fertility.

Cooperative physical separation of oil and suspended solids from methanol-to-olefin wastewater: A pilot study.

Methanol-to-olefin (MTO) is an important non-petroleum chemical process for the preparation of light olefins. However, the MTO process consumes copious amounts of water and produces large amounts of untreated effluent. Therefore, the realization of efficient wastewater treatment and recycling is key to the green low-carbon development of MTO. Here, a cooperative process combining swirl regenerating micro-channel separation (SRMS) and combined fibrous coalescence (CFC) technologies was proposed to separate high contents of oil and suspended matter in MTO wastewater. Using a pilot device with a treatment capacity of 1 m3/h, the average oil content in MTO wastewater decreased from 750 mg/L to <30 mg/L, while the average content of suspended matter decreased from 108 mg/L to <15 mg/L. Compared with a commercial MTO wastewater treatment process (olefin production capacity of 0.6 million tons per annum), the proposed method could reduce wastewater discharges and costs by 57% and US$ 0.23 million per annum respectively. Equipment costs and operational energy consumption were also reduced by 30% and >95% respectively. The combined process may provide the basis for the green and sustainable treatment of MTO wastewater and its recycling.