Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation.

Many cancers evade immune rejection by suppressing major histocompatibility class I (MHC-I) antigen processing and presentation (AgPP). Such cancers do not respond to immune checkpoint inhibitor therapies (ICIT) such as PD-1/PD-L1 [PD-(L)1] blockade. Certain chemotherapeutic drugs augment tumor control by PD-(L)1 inhibitors through potentiation of T-cell priming but whether and how chemotherapy enhances MHC-I-dependent cancer cell recognition by cytotoxic T cells (CTLs) is not entirely clear. We now show that the lysine acetyl transferases p300/CREB binding protein (CBP) control MHC-I AgPPM expression and neoantigen amounts in human cancers. Moreover, we found that two distinct DNA damaging drugs, the platinoid oxaliplatin and the topoisomerase inhibitor mitoxantrone, strongly up-regulate MHC-I AgPP in a manner dependent on activation of nuclear factor kappa B (NF-κB), p300/CBP, and other transcription factors, but independently of autocrine IFNγ signaling. Accordingly, NF-κB and p300 ablations prevent chemotherapy-induced MHC-I AgPP and abrogate rejection of low MHC-I-expressing tumors by reinvigorated CD8+ CTLs. Drugs like oxaliplatin and mitoxantrone may be used to overcome resistance to PD-(L)1 inhibitors in tumors that had "epigenetically down-regulated," but had not permanently lost MHC-I AgPP activity.

Human health risk assessment based on a total diet study of daily mercury intake in Chengdu, China.

To assess the total daily mercury intake and main exposure sources of residents, six food groups, including marine fish, freshwater fish, poultry, livestock, vegetables, and cereals, were collected from five districts of Chengdu, China. The median concentrations of total mercury (THg) and methylmercury (MeHg) were 12.8 and 6.94 µg kg-1 ww, respectively. Cereals (32.2%), vegetables (30.5%), and livestock (16.2%) contributed to a much larger extent to the total consumption for the participants in Chengdu. All food categories that contributed the most of THg (2.16 µg day-1) and MeHg 1.44 (µg day-1) to the daily intake in Chengdu were cereals and marine fish, respectively. The total Hazard Ratios values below 1 in this study indicate that there is no health risk associated with Hg ingestion from the consumption of these foods for the residents in Chengdu.

Quantum illumination based on cavity-optomagnonics system with Kerr nonlinearity.

Quantum illumination is a quantum optical sensing technique, which employs an entangled source to detect low-reflectivity object immersed in a bright thermal background. Hybrid cavity-optomagnonics system promises to work as quantum illumination because a yttrium iron garnet (YIG) sphere can couple to microwave field and optical field. In this paper, we propose a scheme to enhance the entanglement between the output fields of the microwave and optical cavities by considering the intrinsic Kerr nonlinearity of the YIG. We investigate the difference between intrinsic Kerr nonlinearity and optomagnonical parametric-type coupling on improving entanglement. Our result show that the large value optomagnonical parametric-type coupling does not mean the large entanglement, nevertheless, the large value of Kerr nonlinearity does monotonously improve the entanglement for our group of parameters. Consequently, under feasible parameters of current experiment, the signal-to-noise ratio and probability of detection error can be improved after considering the magnon Kerr nonlinearity.

Comparative Analysis of Endovascular Repair of Single-Branched Stent-Graft and Hybrid Procedure for Patients With Type B Acute Aortic Dissection Involving the Left Subclavian Artery.

PURPOSE: Thoracic endovascular aortic repair (TEVAR) with left subclavian artery (LSA) revascularization has been used in patients with type B aortic dissection (TBAD), with inadequate proximal landing zone (PLZ). The outcomes of comparisons between TEVAR and hybrid procedure on patients with TBAD, with inadequate PLZ, are rarely reported. This study sought to compare and clarify the early and midterm outcomes between TEVAR and hybrid procedure in patients with TBAD, with inadequate PLZ. MATERIALS AND METHODS: Between January 2019 and December 2021, 93 patients with TBAD, with inadequate PLZ, who underwent TEVAR or hybrid procedure, were retrospectively evaluated in Beijing Anzhen hospital. Demographics, comorbidities, preoperative imaging features, periprocedural details, and follow-up outcomes were analyzed. Survival was analyzed according to Kaplan-Meier method. RESULTS: TEVAR procedures were performed on 41 patients (TEVAR group) and hybrid procedures on 52 patients (hybrid group). Early events, 30 day mortality, and all-cause mortality, were not significantly different between the 2 groups. However, patients receiving TEVAR had significantly shorter procedure time (p<0.001), hospital stay (p<0.001), and intensive care unit (ICU) stay (p=0.001) compared with those in the hybrid group. Patients receiving TEVAR had significantly lower midterm events (p=0.014) and re-intervention (p=0.015) compared with those in the hybrid group. CONCLUSION: The study indicated that TEVAR with LSA revascularization for TBAD with inadequate PLZ is associated with a trend toward lower rates of midterm events, while the early and midterm mortalities were comparable with those in hybrid procedure. CLINICAL IMPACT: This study is novel as it compared the outcomes between thoracic endovascular aortic repair (TEVAR) and hybrid procedure in patients with type B aortic dissection (TBAD), with inadequate proximal landing zone, which has been rarely reported previously. We believe that our study makes a significant contribution to the literature because it is clinically relevant as it demonstrated that TEVAR with left subclavian artery (LSA) revascularization for TBAD with inadequate proximal landing zone is associated with a trend toward lower rates of mid-term events, while the early and mid-term mortalities were comparable with those in the hybrid procedure.

Glucagon-Like Peptide-1 Inhibits the Progression of Abdominal Aortic Aneurysm in Mice: The Earlier, the Better.

OBJECTIVES: Glucagon-like peptide-1 (GLP-1) has a cardiovascular protective effect by preventing abdominal aortic aneurysm (AAA) formation. However, it is unclear at what point the agent should be administered to achieve the optimal effect. In this study, we aimed to determine whether administering the GLP-1 receptor agonist liraglutide during the earlier stages would more efficiently inhibit AAA progression in mice. METHODS: Depending on the group, mice were given a daily dose of 300 µg/kg liraglutide for 28 days at 7, 14, and 28 days after aneurysm induction. The morphology of the abdominal aorta was monitored using 7.0 T magnetic resonance imaging (MRI) during the administration of liraglutide. After 28 days of administration, the AAA dilatation ratio was calculated, and histopathological examination was performed. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA) and matrix metalloproteinases (MMPs). The inflammatory response was also evaluated. RESULTS: Liraglutide treatment led to a decrease in AAA formation, including a reduction in abdominal aorta expansion, elastin degradation in the elastic laminae, and vascular inflammation caused by leukocyte infiltration. The expression of MDA and the activity of MMPs (MMP-2, MMP-9) also decreased. Notably, administering liraglutide during the early stages resulted in a significant reduction in the dilatation rate of the aortic wall, as well as in MDA expression, leukocyte infiltration, and MMP activity in the vascular wall. CONCLUSIONS: The GLP-1 receptor agonist liraglutide was found to inhibit AAA progression in mice by exerting anti-inflammatory and antioxidant effects, particularly during the early stages of AAA formation. Therefore, liraglutide may represent a potential pharmacological target for the treatment of AAA.

Unveiling interactions of norfloxacin with microplastic in surface water by 2D FTIR correlation spectroscopy and X-ray photoelectron spectroscopy analyses.

Microplastics (MPs) has shown adsorption of hydrophilic organic matters (HOMs) in aqueous environments. However, it is still difficult to predict the adsorption behaviors of HOMs by different MPs, especially in authentic water systems. In this study, the adsorption behaviors and mechanisms of norfloxacin (NOR) onto polyamide (PA) MPs were investigated in both simulated and real surface water. The results showed that the adsorption equilibrium of NOR by PA in simulated surface water could be achieved within 15 h, while the adsorption rate of NOR in real surface was slowed down, with the equilibrium time of 25 h. Pseudo-second-order model could well describe the adsorption kinetics data. The experimental maximum adsorption capacity of NOR on PA in real surface water (e. g. 132.54 ug/g) was dramatically reduced by 37.5 % compared with that in simulated surface water (e. g. 212.25 ug/g), and the adsorption isotherm would obey Freundlich model. Besides, the leaching of NOR from the surface of PA could occur obviously at acidic environment. Furthermore, the salinity and natural organic matter exhibited significantly adverse effects on the NOR adsorption. Finally, the results of 2D Fourier transform infrared correlation spectroscopy and X-ray photoelectron spectroscopy indicated that the electrostatic, H-bond and van der Waals interactions were involved in the adsorption. More importantly, the sequential functional groups in the adsorption process followed the orders: 1638 (CO) > 1542 amide II (-NH-CO) > 717 (CH2) > 1445 (CO) > 973 amide IV (CONH). This study could provide an insight into the interactions between PA and NOR in different water environments.

Ultrasound-based advanced oxidation processes for landfill leachate treatment: Energy consumption, influences, mechanisms and perspectives.

Advanced oxidation processes (AOPs) based on ultrasound (US) have attracted considerable attention in recent years due to its advantages in the degradation of landfill leachate. The review summarizes the existing treatment methods of leachate from lab-scale, compares their advantages and disadvantages by focusing on the degradation of emerging contaminants (ECs) in the leachate. Then the US-based AOPs are introduced emphatically, including their degradation mechanisms, influencing factors, energy consumption, further optimization methods as well as the possibility of field-scale application are systematically described. Moreover, this review also expounds on the advantages of dual-frequency US (DFUS) technology compared with single-frequency US, and a theoretically feasible DFUS process is proposed to treat ECs in the leachate. Finally, suggestions and prospects for US technologies in treating landfill leachate are put forward to aid future research on landfill leachate treatment. Meaningfully, this manuscript will provide reference values of US-based technologies in landfill leachate treatment for the practical use, facilitating the development of US-based AOPs in landfill leachate management and disposal.

Green remediation of Ni, Zn, and Cu in an electroplating contaminated site by wood vinegar with optimization and risk assessment.

Wood vinegar (WV) is a renewable organic compound, possessing characteristics such as high oxygenated compound content and low negative impact on soil. Based on its weak acid properties and complexing ability to potentially toxic elements (PTEs), WV was used to leach Ni, Zn, and Cu contaminated soil in electroplating sites. In addition, the response surface methodology (RSM) based on the Box-Behnken design (BBD) was established to clarify the interaction between each single factor, and finally completed the risk assessment of the soil. The amounts of PTEs leached from the soil climbed with the increase of WV concentration, liquid-solid ratio, and leaching time, while they surged with the decrease of pH. Under optimal leaching circumstances (the concentration of WV= 100 %; washing time= 919 min; pH= 1.00), the removal rates of Ni, Zn, and Cu could reach 91.7 %, 57.8 %, and 65.0 %, respectively, and the WV-extracted PTEs were mainly from the Fe-Mn oxides fraction. After leaching, the Nemerow integrated pollution index (NIPI) decreased from an initial value of 7.08 (indicating severe pollution) to 0.450 (indicating no pollution). The potential ecological risk index (RI) dropped from 274 (medium level) to 39.1 (low level). Additionally, the potential carcinogenic risk (CR) values reduced by 93.9 % for both adults and children. The results revealed that the washing process significantly reduced the pollution level, potential ecological risk, and health risk. Coupled with FTIR and SEM-EDS analysis, the mechanism of WV removal of PTEs could be explained from three aspects: acid activation, H+ ion exchange, and functional group complexation. In summary, WV is an eco-friendly and high-efficiency leaching material for the remediation of PTEs polluted sites, which will maintain soil function and protect human health.

Immune-based prognostic biomarkers associated with metastasis of osteosarcoma.

This study aimed to identify immune-based prognostic biomarkers associated with metastasis of osteosarcoma. Based on the GEO and TCGA databases, 437 differentially expressed genes were screened between primary and metastatic osteosarcoma. Weighted gene co-expression network analysis (WGCNA) revealed 496 genes in turquoise module which had the highest correlation with osteosarcoma metastasis. Within these two group genes, 122 common genes involved in osteosarcoma metastasis were identified. These genes were enriched in chemokine activity, chemokine receptor binding, TNF signaling pathway, etc. Survival analysis revealed 8 prognostic genes (ANK3, EGR1, FBP1, FOS, KIFC3, MAOB, ISLR and MFAP4) from the 122 genes. RT-qPCR showed that all of these eight genes were differentially expressed between 143B and MNNG/HOS Cl cells. Various infiltrating immune cells showed significant differences between primary and metastatic osteosarcoma. Expression of all the 8 prognostic genes was correlated with infiltration abundance of multiple immune cells, such as follicular helper T cells, activated dendritic cells. In addition, 10 microRNAs and 7 transcription factors that targeted these prognostic genes were predicted. In conclusion, 8 immune-based prognostic genes associated with osteosarcoma metastasis were identified.

An electrochemiluminescence resonance energy transfer biosensor based on CDs/PAMAM/rGO nanocomposites and Au@Ag2S nanoparticles for PML/RARα fusion gene detection.

In recent years, electrochemiluminescence resonance energy transfer (ECL-RET) with low background signal and high specificity has attracted much attention among researchers. Herein, we established a novel ECL-RET biosensor for PML/RARα fusion gene detection. In this ECL-RET system, carbon dots (CDs) with low toxicity and prominent electrochemical activity were used as donor and Au@Ag2S core-shell nanoparticles (Au@Ag2S NPs) were employed as ECL acceptor. The Au@Ag2S NPs possessed a wide ultraviolet-visible (UV-vis) absorption spectrum between 500 nm and 700 nm, which completely overlapped with the ECL spectrum of CDs. Furthermore, the CDs-decorated poly-amidoamine/reduced graphene oxide (CDs/PAMAM/rGO) nanocomposites were prepared to improve the ECL signals and served as a substrate to stably load capture probe deoxyribonucleic acid (DNA). Based on the ECL-RET biosensing strategy, the Au@Ag2S NPs-labeled assistant probes and target DNA could pair with capture probes to form the sandwich-type DNA structure and the distance between donor and accepter was closed, leading to quenching of the ECL signal of CDs. The ECL-RET biosensor represented eminent analytical performance for PML/RARα fusion gene detection with a wide linear relationship from 5 fM to 500 pM and a low detection limit of 0.72 fM, which provided a novel technical means and theoretical basis for detection and diagnosis of acute promyelocytic leukemia.

Rapid changes in chromatin structure during dedifferentiation of primary hepatocytes in vitro.

Primary hepatocytes are widely used in the pharmaceutical industry to screen drug candidates for hepatotoxicity, but hepatocytes quickly dedifferentiate and lose their mature metabolic function in culture. Attempts have been made to better recapitulate the in vivo liver environment in culture, but the full spectrum of signals required to maintain hepatocyte function ex vivo remains elusive. To elucidate molecular changes that accompany, and may contribute to dedifferentiation of hepatocytes ex vivo, we performed lineage tracing and comprehensive profiling of alterations in their gene expression profiles and chromatin landscape during culture. First, using genetically tagged hepatocytes we demonstrate that expression of the fetal gene alpha-fetoprotein in cultured hepatocytes comes from cells that previously expressed the mature gene albumin, and not from a population of albumin-negative precursor cells, proving mature hepatocytes undergo true dedifferentiation in culture. Next we studied the dedifferentiation process in detail through bulk RNA-sequencing of hepatocytes cultured over an extended period. We identified three distinct phases of dedifferentiation: an early phase, where mature hepatocyte genes are rapidly downregulated in a matter of hours; a middle phase, where fetal genes are activated; and a late phase, where initially rare contaminating non-parenchymal cells proliferate, taking over the culture. Lastly, to better understand the signaling events that result in the rapid downregulation of mature genes in hepatocytes, we examined changes in chromatin accessibility in these cells during the first 24 h of culture using Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq). We find that drastic and rapid changes in chromatin accessibility occur immediately upon the start of culture. Using binding motif analysis of the areas of open chromatin sharing similar temporal profiles, we identify several candidate transcription factors potentially involved in the dedifferentiation of primary hepatocytes in culture.

An Improved Mask R-CNN Micro-Crack Detection Model for the Surface of Metal Structural Parts.

Micro-crack detection is an essential task in critical equipment health monitoring. Accurate and timely detection of micro-cracks can ensure the healthy and stable service of equipment. Aiming at improving the low accuracy of the conventional target detection model during the task of detecting micro-cracks on the surface of metal structural parts, this paper built a micro-cracks dataset and explored a detection performance optimization method based on Mask R-CNN. Firstly, we improved the original FPN structure, adding a bottom-up feature fusion path to enhance the information utilization rate of the underlying feature layer. Secondly, we added the methods of deformable convolution kernel and attention mechanism to ResNet, which can improve the efficiency of feature extraction. Lastly, we modified the original loss function to optimize the network training effect and model convergence rate. The ablation comparison experiments shows that all the improvement schemes proposed in this paper have improved the performance of the original Mask R-CNN. The integration of all the improvement schemes can produce the most significant performance improvement effects in recognition, classification, and positioning simultaneously, thus proving the rationality and feasibility of the improved scheme in this paper.

Rape Straw Supported FeS Nanoparticles with Encapsulated Structure as Peroxymonosulfate and Hydrogen Peroxide Activators for Enhanced Oxytetracycline Degradation.

Iron-based catalysts with high load content of iron sulfide (FeS) were commonly peroxymonosulfate (PMS) and hydrogen peroxide (H2O2) activators to degrade organic pollutants but limited catalytic efficiency and increased risk of ferrous ion leaching restricted their use. Meanwhile, various biomass materials such as straw, peel, and branch have been extensively prepared into biochar for mechanical support for iron-based catalysts; however, the preparation process of biochar was energy-intensive. In this study, FeS nanoparticles modified rape straw composites (RS-FeS) encapsulated with ethylenediaminetetraacetic acid (RS-EDTA-FeS) were successfully presented by in-situ synthesis method for efficiently activating PMS and H2O2 to degrade oxytetracycline (OTC), which was economical and environmentally friendly. The results showed that the modified rape straw can remove OTC efficiently, and the addition of EDTA also significantly enhanced the stability and the reusability of the catalyst. In addition, EDTA also promoted the activation of H2O2 at neutral pH. The OTC degradation efficiency of the two catalysts by PMS was faster than that of H2O2, but H2O2 had a stronger ability to remove OTC than PMS. The highest OTC removal efficiency of RS-FeS and RS-EDTA-FeS were 87.51 and 81.15%. O2•- and 1O2 were the major reactive oxidative species (ROS) in the PMS system. Furthermore, compared with RS-FeS, the addition of EDTA inhabited the generation of O2•- in the PMS system. Instead, O2•- and •OH were the major ROS in the H2O2 system, but 1O2 was also identified in RS-FeS/H2O2 system. RS-EDTA-FeS showed a trend of rising first and then decreasing in recycle test. Instead, the removal rate of OTC by RS-FeS decreased significantly with the increase in reuse times. In the actual wastewater test, the TOC removal of two catalysts active by H2O2 was better than PMS, which was consistent with the test results of OTC, indicating that the two catalysts have application value in the removal of organic pollutants in actual wastewater. This study directly used plant materials as catalysts and omits the preparation process of biochar, greatly reduces the preparation cost and secondary pollution of catalysts, and provides theoretical support for the deepening of advanced oxidation technology.

Assessing the risk of human exposure to bioaccessible arsenic from total diet through market food consumption in Chengdu, China.

To assess the daily intake of total arsenic (tAs) and arsenic speciation and their potential health risks, different food groups, including vegetables, rice, meat, viscera, freshwater fish, and seafood from Chengdu, China were analyzed. The concentrations of tAs ranged from 41.3 to 1185 µg kg-1 with a median of 238 µg kg-1, and 26.0% of tAs in the food groups was of inorganic toxic form. The median concentration of As(V) in rice (184 ± 21.6 µg kg-1) was approximately 2 to 6 times higher than those in other food groups. The bioaccessible inorganic arsenic (iAs) concentrations of the food items obtained from the local markets of Chengdu ranged from 1.07 to 24.6 µg kg-1 (mean of 6.04 µg kg-1). Rice contributed toward the largest amount of daily iAs intake (66.2%). The mean daily iAs intake from vegetable, meat and viscera contributed 10.7%, 12.5% and 6.04% of total iAs intake, respectively. The actual concentration of arsenic in the food exposed to the human body depends on oral bioaccessible fraction. The oral bioaccessibility estimated daily intake (µg kg-1 bw d-1) of tAs and iAs for the residents of Chengdu was 0.32 and 0.16. Health risk assessments carried out based on bioaccessible iAs concentrations showed that the food items were safe for consumption from the iAs perspective.

Selenium toxicity and bioaccumulation in selenium-enriched fly (Chrysomya megacephala) maggots.

Selenium (Se) is an essential trace element for human health, and as a potential animal feed, the Chrysomya megacephala (Fabricius) fly is rich in protein and fat. By using different concentrations of sodium selenite (0, 30, 50, 70 mg kg-1), the possibility of biological Se enrichment in C. megacephala (Fabricius) maggots (CMMs) was investigated. The accumulation, Se speciation, enzymatic activity, and concentrations of copper (Cu), zinc (Zn), chromium (Cr), and cadmium (Cd) in the maggots were also determined. Transcriptomics was also used to investigate the mechanism of the Se response to CMM genes. The results showed that the CMMs had a survival rate of > 80% at Se exposure concentrations ranging from 0 to 100 mg kg-1. The optimal concentration of sodium selenite for CMM growth was 50 mg kg-1, and the weight, protein content, and total Se accumulation of the larvae (10.8 g, 53.5%, and 72.6 ± 3.36 mg kg-1 (DW), respectively) were considerably higher than the control and other exposure doses (p < 0.05). In addition, Se improved the ability of maggots to absorb Cu and Zn, decreased malondialdehyde (MDA) and lipid peroxidation, but improved the antioxidant activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Furthermore, Se negatively affected the absorption of Cd and Cr. According to the transcriptomic findings, Se supplementation can boost protein synthesis and control both antioxidant and non-antioxidant enzyme activity in CMMs. Therefore, our findings showed that Se-enriched CMMs may counteract the toxicity of Cd and Cr, and Se is an effective supplement for improving the consumption safety of cultured animals fed containing CMMs.

Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism.

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. RESULTS: We adapted the fitDNM statistical model to work in noncoding regions and tested enhancers for excess of DNVs in families with autism. We found only one enhancer (hs737) with nominal significance in the discovery (p = 0.0172), replication (p = 2.5 × 10-3), and combined dataset (p = 1.1 × 10-4). Each individual with a DNV in hs737 had shared phenotypes including being male, intact cognitive function, and hypotonia or motor delay. Our in vitro assessment of the DNVs showed they all reduce enhancer activity in a neuronal cell line. By epigenomic analyses, we found that hs737 is brain-specific and targets the transcription factor gene EBF3 in human fetal brain. EBF3 is genome-wide significant for coding DNVs in NDDs (missense p = 8.12 × 10-35, loss-of-function p = 2.26 × 10-13) and is widely expressed in the body. Through characterization of promoters bound by EBF3 in neuronal cells, we saw enrichment for binding to NDD genes (p = 7.43 × 10-6, OR = 1.87) involved in gene regulation. Individuals with coding DNVs have greater phenotypic severity (hypotonia, ataxia, and delayed development syndrome [HADDS]) in comparison to individuals with noncoding DNVs that have autism and hypotonia. CONCLUSIONS: In this study, we identify DNVs in the hs737 enhancer in individuals with autism. Through multiple approaches, we find hs737 targets the gene EBF3 that is genome-wide significant in NDDs. By assessment of noncoding variation and the genes they affect, we are beginning to understand their impact on gene regulatory networks in NDDs.

Impacts of Forest Fire Ash on Aquatic Mercury Cycling.

Mercury (Hg) is a ubiquitous contaminant in the environment and its methylated form, methylmercury (MeHg), poses a worldwide health concern for humans and wildlife, primarily through fish consumption. Global production of forest fire ash, derived from wildfires and prescribed burns, is rapidly increasing due to a warming climate, but their interactions with aqueous and sedimentary Hg are poorly understood. Herein, we compared the differences of wildfire ash with activated carbon and biochar on the sorption of aqueous inorganic Hg and sedimentary Hg methylation. Sorption of aqueous inorganic Hg was greatest for wildfire ash materials (up to 0.21 µg g-1 or 2.2 µg g-1 C) among all of the solid sorbents evaluated. A similar Hg adsorption mechanism for activated carbon, biochar made of walnut, and wildfire ash was found that involves the formation of complexes between Hg and oxygen-containing functional groups, especially the -COO group. Notably, increasing dissolved organic matter from 2.4 to 70 mg C L-1 remarkably reduced Hg sorption (up to 40% reduction) and increased the time required to reach Hg-sorbent pseudo-equilibrium. Surprisingly, biochar and wildfire ash, but not activated carbon, stimulated MeHg production during anoxic sediment incubation, possibly due to the release of labile organic matter. Overall, our study indicates that while wildfire ash can sequester aqueous Hg, the leaching of its labile organic matter may promote production of toxic MeHg in anoxic sediments, which has an important implication for potential MeHg contamination in downstream aquatic ecosystems after wildfires.

IκBα Nuclear Export Enables 4-1BB-Induced cRel Activation and IL-2 Production to Promote CD8 T Cell Immunity.

Optimal CD8 T cell immunity is orchestrated by signaling events initiated by TCR recognition of peptide Ag in concert with signals from molecules such as CD28 and 4-1BB. The molecular mechanisms underlying the temporal and spatial signaling dynamics in CD8 T cells remain incompletely understood. In this study, we show that stimulation of naive CD8 T cells with agonistic CD3 and CD28 Abs, mimicking TCR and costimulatory signals, coordinately induces 4-1BB and cRel to enable elevated cytosolic cRel:IκBα complex formation and subsequent 4-1BB-induced IκBα degradation, sustained cRel activation, heightened IL-2 production and T cell expansion. NfkbiaNES/NES CD8 T cells harboring a mutated IκBα nuclear export sequence abnormally accumulate inactive cRel:IκBα complexes in the nucleus following stimulation with agonistic anti-CD3 and anti-CD28 Abs, rendering them resistant to 4-1BB induced signaling and a disrupted chain of events necessary for efficient T cell expansion. Consequently, CD8 T cells in NfkbiaNES/NES mice poorly expand during viral infection, and this can be overcome by exogenous IL-2 administration. Consistent with cell-based data, adoptive transfer experiments demonstrated that the antiviral CD8 T cell defect in NfkbiaNES/NES mice was cell intrinsic. Thus, these results reveal that IκBα, via its unique nuclear export function, enables, rather than inhibits 4-1BB-induced cRel activation and IL-2 production to facilitate optimal CD8 T cell immunity.

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle.

In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu3+ and Gd3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract-fucoidan was extracted from the same brown algae-Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 µg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 µg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized.

Risk factors of lymphovascular invasion in hypopharyngeal squamous cell carcinoma and its influence on prognosis.

PURPOSE: Lymphatic vascular invasion (LVI) is a poor prognostic factor for hypopharyngeal squamous cell carcinoma (HPSCC), but the risk factors of LVI and its relationship with clinicopathological of HPSCC remain unclear. This study aims to explore these issues. METHODS: We retrospectively analyzed the clinicopathological data of 170 patients with HPSCC from January 2011 to December 2015. The relationship between LVI and clinicopathologic was analyzed by Chi-square test or Fisher's exact test. The risk factors of LVI were examined using a logistic regression model, while risk factors of survival rate were carried out using the Cox regression model. RESULTS: LVI occurred in 59 cases (34.7%). In multivariate analysis, T3-4 stage (HR = 2.877; 95% CI: 1.379-6.004; p = 0.005), N2-3 stage (HR = 2.325; 95% CI: 1.120-4.824; p = 0.024), and poor differentiation (HR = 2.983; 95% CI: 1.229-7.242; p = 0.016) were independent risk factors for LVI; positive LVI was an independent risk factor for local recurrence (HR = 2.488; 95% CI: 1.150-5.383; p = 0.021), poor 5-year OS (HR = 0.375; 95% CI: 0.232-0.606; p < 0.000), DSS (HR = 0.374; 95% CI: 0.235-0.595; p < 0.000), and DFS (HR = 0.454; 95% CI:0.254-0.813; p = 0.008). CONCLUSION: T3-4 stage, N2-3 stage and poor differentiation are independent risk factors for LVI of HPSCC; LVI increases the local recurrence and regional recurrence rate, and decreases 5-year OS, DFS and DSS of HPSCC.