HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products via the cGAS-STING pathway.

A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization per se does not completely block reverse transcription. Surprisingly, due to the combined effects of enhanced reverse transcription and defects in nuclear entry, two separate CA mutants that form hyperstable cores induced innate immune sensing more potently than destabilizing CA mutations. At low concentrations that allowed the accumulation of reverse transcription products, CA-targeting compounds GS-CA1 and lenacapavir measurably impacted CA lattice stability in cells and modestly enhanced innate immune sensing of HIV. Interestingly, innate immune activation observed with viruses containing unstable cores was abolished by low doses of lenacapavir. Innate immune activation observed with both hyperstable and unstable CA mutants was dependent on the cGAS-STING DNA-sensing pathway and reverse transcription. Overall, our findings demonstrate that CA lattice stability and reverse transcription are finely balanced to support reverse transcription and minimize cGAS-STING-mediated sensing of the resulting viral DNA. IMPORTANCE: In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.

The role of spleen radiomics model for predicting prognosis in esophageal squamous cell carcinoma patients receiving definitive radiotherapy.

BACKGROUND: The spleen plays an important role in systemic antitumor immune response, but whether spleen imaging features have predictive effect for prognosis and immune status was unknown. The aim of this study was to investigate computed tomography (CT)-based spleen radiomics to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC) underwent definitive radiotherapy (dRT) and to try to find its association with systemic immunity. METHODS: This retrospective study included 201 ESCC patients who received dRT. Patients were randomly divided into training (n = 142) and validation (n = 59) groups. The pre- and delta-radiomic features were extracted from enhanced CT images. LASSO-Cox regression was used to select the radiomics signatures most associated with progression-free survival (PFS) and overall survival (OS). Independent prognostic factors were identified by univariate and multivariate Cox analyses. The ROC curve and C-index were used to evaluate the predictive performance. Finally, the correlation between spleen radiomics and immune-related hematological parameters was analyzed by spearman correlation analysis. RESULTS: Independent prognostic factors involved TNM stage, treatment regimen, tumor location, pre- or delta-Rad-score. The AUC of the delta-radiomics combined model was better than other models in the training and validation groups in predicting PFS (0.829 and 0.875, respectively) and OS (0.857 and 0.835, respectively). Furthermore, some spleen delta-radiomic features are significantly correlated with delta-ALC (absolute lymphocyte count) and delta-NLR (neutrophil-to-lymphocyte ratio). CONCLUSIONS: Spleen radiomics is expected to be a useful noninvasive tool for predicting the prognosis and evaluating systemic immune status for ESCC patients underwent dRT.

The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression.

While CD4+ T cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of "natural" hosts such as sooty mangabeys does not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T cell activation abolishes CARD8 function and increases permissiveness to infection. In humanized mice reconstituted with CARD8-deficient cells, CD4+ depletion is delayed despite high viremia. Finally, we discovered loss-of-function mutations in CARD8 from "natural hosts," which may explain the peculiarly non-pathogenic nature of these infections. Our study suggests that CARD8 drives CD4+ T cell depletion during pathogenic HIV/SIV infections.

PRKCSH serves as a potential immunological and prognostic biomarker in pan-cancer.

Protein kinase C substrate 80K-H (PRKCSH) plays a crucial role in the protein N-terminal glycosylation process, with emerging evidence implicating its involvement in tumorigenesis. To comprehensively assess PRKCSH's significance across cancers, we conducted a pan-cancer analysis using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE). We assessed aberrant PRKCSH mRNA and protein expression, examined its prognostic implications, and identified correlations with clinical features, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immunity across cancer types. We explored PRKCSH gene alterations, DNA methylation, and their impact on patient prognosis. Gene Set Enrichment Analysis (GSEA) and single-cell analysis revealed potential biological roles. Additionally, we investigated drug susceptibility and conducted Connectivity Map (Cmap) analysis. Key findings revealed that PRKCSH exhibited overexpression in most tumors, with a significant association with poor overall survival (OS) in six cancer types. Notably, PRKCSH expression demonstrated variations across disease stages, primarily increasing in advanced stages among eleven tumor types. Moreover, PRKCSH exhibited significant correlations with TMB in five cancer categories, MSI in eight, and displayed associations with immune cell populations in pan-cancer analysis. Genetic variations in PRKCSH were identified across 26 tumor types, suggesting favorable disease-free survival. Furthermore, PRKCSH methylation displayed a significant negative correlation with its expression in 27 tumor types, with a marked decrease compared to normal tissues in ten tumors. Cmap predicted 24 potential therapeutic small molecules in over four cancer types. This study highlights that PRKCSH, as a potential oncogene, may be a promising prognostic marker and therapeutic target of immunotherapy for a range of malignancies.

Ultra-fast supercritically solvothermal polymerization for large single-crystalline covalent organic frameworks.

Crystalline polymer materials, e.g., hyper-crosslinked polystyrene, conjugate microporous polymers and covalent organic frameworks, are used as catalyst carriers, organic electronic devices and molecular sieves. Their properties and applications are highly dependent on their crystallinity. An efficient polymerization strategy for the rapid preparation of highly or single-crystalline materials is beneficial not only to structure-property studies but also to practical applications. However, polymerization usually leads to the formation of amorphous or poorly crystalline products with small grain sizes. It has been a challenging task to efficiently and precisely assemble organic molecules into a single crystal through polymerization. To address this issue, we developed a supercritically solvothermal method that uses supercritical carbon dioxide (sc-CO2) as the reaction medium for polymerization. Sc-CO2 accelerates crystal growth due to its high diffusivity and low viscosity compared with traditional organic solvents. Six covalent organic frameworks with different topologies, linkages and crystal structures are synthesized by this method. The as-synthesized products feature polarized photoluminescence and second-harmonic generation, indicating their high-quality single-crystal nature. This method holds advantages such as rapid growth rate, high productivity, easy accessibility, industrial compatibility and environmental friendliness. In this protocol, we provide a step-by-step procedure including preparation of monomer dispersion, polymerization in sc-CO2, purification and characterization of the single crystals. By following this protocol, it takes 1-5 min to grow sub-mm-sized single crystals by polymerization. The procedure takes ~4 h from preparation of monomer dispersion and polymerization in sc-CO2 to purification and drying of the product.

Alteration of serum bile acids in non-small cell lung cancer identified by a validated LC-MS/MS method.

BACKGROUND: Bile acids (BA) are important metabolites and serve as signaling molecules, which are involve in multiple cancer-related signaling pathways. METHODS: A validated LC-MS/MS approach was applied in a case-control study with 220 non-small cell lung cancer (NSCLC) patients and 244 matched healthy controls. The concentrations of seven common types of BAs in serum were determined and compared. Subgroup analyses based on demographic factor, lifestyle, pathologic types and tumor stage were conducted. Machine learning analysis was performed for NSCLC classification. RESULTS: Serum levels of primary BAs, including cholic acid (CA), taurocholic acid (TCA) and glycocholic acid (GCA), were upregulated, while lithocholic acid (LCA), a type of secondary BA, was downregulated in NSCLC patients compared with healthy controls in overall analysis. Higher level of chenodeoxycholic acid (CDCA) and lower level of ursodeoxycholic acid (UDCA) were observed in female, elder, overweight patients, as well as patients without alcohol use in comparison with controls. CDCA and CA levels were higher only in lung adenocarcinoma (LUAD), and UDCA and DCA levels were lower only in squamous cell carcinoma (LUSC), while the concentrations of TCA, GCA, and LCA were altered prevalently in LUAD and LUSC patients. For discrimination of NSCLC from healthy people, the area under the receiver operating characteristics (ROC) curve of the models through support vector machine (SVM) approach was 0.91 (95% CI 0.88-0.94) in the training set and 0.84 (95% CI 0.78-0.91) in the validation set, respectively. CONCLUSIONS: Serum BAs were altered in NSCLC patients compared with controls, among which primary BAs were elevated and secondary BAs were decreased. Moreover, distinct patterns of BA alterations were revealed between LUAD patients and LUSC patients.

Comprehensive serum N-glycan profiling identifies a biomarker panel for early diagnosis of non-small-cell lung cancer.

Aberrant serum N-glycan profiles have been observed in multiple cancers including non-small-cell lung cancer (NSCLC), yet the potential of N-glycans in the early diagnosis of NSCLC remains to be determined. In this study, serum N-glycan profiles of 275 NSCLC patients and 309 healthy controls were characterized by MALDI-TOF-MS. The levels of serum N-glycans and N-glycosylation patterns were compared between NSCLC and control groups. In addition, a panel of N-glycan biomarkers for NSCLC diagnosis was established and validated using machine learning algorithms. As a result, a total of 54 N-glycan structures were identified in human serum. Compared with healthy controls, 29 serum N-glycans were increased or decreased in NSCLC patients. N-glycan abundance in different histological types or clinical stages of NSCLC presented differentiated changes. Furthermore, an optimal biomarker panel of eight N-glycans was constructed based on logistic regression, with an AUC of 0.86 in the validation set. Notably, this model also showed a desirable capacity in distinguishing early-stage patients from healthy controls (AUC = 0.88). In conclusion, our work highlights the abnormal N-glycan profiles in NSCLC and provides supports potential application of N-glycan biomarker panel in clinical NSCLC detection.

Enhanced natural degradation of cyanide tailings: Integrated application of solar drying system and UV irradiation.

Cyanide tailings are the bulk solid waste generated by the production processes of gold mines. Since the highly toxicity of cyanide affects its disposal and comprehensive utilization, a decyanation treatment is needed. However, wide-ranging industrial uses of the current decyanation methods are restricted due to the treatment effects and costs. Based on the natural degradation method, the cyanide treatment effect was enhanced by raising the treatment temperature, increasing the ultraviolet (UV) irradiation and turning the pile periodically. Using the Arrhenius equation, the activation energies of the cyanide hydrolysis reactions were calculated as 52.22 kJ/mol and 34.59 kJ/mol for heating alone and for heating combined with UV irradiation, respectively. At 60 â„ƒ, the cyanide tailings reached the discharge standard (leachate, total cyanide (CNt)< 5 mg/L) after 8 h of treatment. Moreover, after adding UV irradiation (with an intensity of 120 µW/cm2) and a hydrogen peroxide spray (spraying intensity, 2 mL/kg) to the above conditions and shortening the treatment time to 7 h, the cyanide tailings reached the standard for use in building materials (leachate, CNt <0.5 mg/L). Based on these results, UV irradiation, ventilation, spraying and pile-turning were integrated into the solar drying room to form an enhanced natural degradation system, which was applied in the semi-industrial scale treatment of the cyanide tailings. The results showed that the cyanide tailings consistently met the standards for discharge and use in building materials, successfully verified the conditions and effects of the laboratory treatment, and reduced the treatment cost by more than 50 %.

A Self-attention Graph Convolutional Network for Precision Multi-tumor Early Diagnostics with DNA Methylation Data.

DNA methylation-based precision tumor early diagnostics is emerging as state-of-the-art technology that could capture early cancer signs 3 ~ 5 years in advance, even for clinically homogenous groups. Presently, the sensitivity of early detection for many tumors is ~ 30%, which needs significant improvement. Nevertheless, based on the genome-wide DNA methylation data, one could comprehensively characterize tumors' entire molecular genetic landscape and their subtle differences. Therefore, novel high-performance methods must be modeled by considering unbiased information using excessively available DNA methylation data. To fill this gap, we have designed a computational model involving a self-attention graph convolutional network and multi-class classification support vector machine to identify the 11 most common cancers using DNA methylation data. The self-attention graph convolutional network automatically learns key methylation sites in a data-driven way. Then, multi-tumor early diagnostics is realized by training a multi-class classification support vector machine based on the selected methylation sites. We evaluated our model's performance through several data sets of experiments, and our results demonstrate the effectiveness of the selected key methylation sites, which are highly relevant for blood diagnosis. The pipeline of the self-attention graph convolutional network based computational framework.

Association analysis of melanophilin (MLPH) gene expression and polymorphism with plumage color in quail.

We explore the relationship between the melanophilin (MLPH) gene and quail plumage color and provide a reference for subsequent quail plumage color breeding. In this experiment, real-time quantitative PCR (RT-qPCR) technology was used to analyze the relative mRNA expression levels of Korean quail (maroon) and Beijing white quail embryos at different developmental stages. Two single-nucleotide polymorphisms (SNPs) in the MLPH gene were screened based on the RNA-sequencing (RNA-Seq) data of skin tissues of Korean quail and Beijing white quail during the embryonic stage. Kompetitive allele-specific PCR (KASP) technology was used for genotyping in the resource population, and correlation analysis was carried out with the plumage color traits of quail. Finally, bioinformatics was used to predict the effects of these two SNPs on the structure and function of the encoded protein. The results showed that the expression level of the MLPH gene during embryonic development of Beijing white quail was significantly higher than that of Korean quail ( P < 0.01 ). The frequency distribution of the three genotypes (CC, CA and AA) of the Beijing white quail at the c.1807C  >  A mutation site was significantly different from that of the Korean quail ( P < 0.01 ). The frequency distribution of the three genotypes (GG, GA and AA) of the Beijing white quail at the c.2129G  >  A mutation site was significantly different from that of the Korean quail ( P < 0.01 ). And there was a significant correlation between the c.1807C  >  A mutation site and the white plumage phenotype. Bioinformatics showed that SNP1 (c.1807C  >  A) was a neutral mutation and that SNP2 (c.2129G  >  A) was a deleterious mutation. The prediction of protein conservation showed that the mutation sites of coding proteins R603S and G710D caused by SNP1 (c.1807C  >  A) and SNP2 (c.2129G  >  A) were highly conserved.

The CARD8 inflammasome in HIV infection.

The biggest challenge to immune control of HIV infection is the rapid within-host viral evolution, which allows selection of viral variants that escape from T cell and antibody recognition. Thus, it is impossible to clear HIV infection without targeting "immutable" components of the virus. Unlike the adaptive immune system that recognizes cognate epitopes, the CARD8 inflammasome senses the essential enzymatic activity of the HIV-1 protease, which is immutable for the virus. Hence, all subtypes of HIV clinical isolates can be recognized by CARD8. In HIV-infected cells, the viral protease is expressed as a subunit of the viral Gag-Pol polyprotein and remains functionally inactive prior to viral budding. A class of anti-HIV drugs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs), can promote Gag-pol dimerization and subsequent premature intracellular activation of the viral protease. NNRTI treatment triggers CARD8 inflammasome activation, which leads to pyroptosis of HIV-infected CD4+ T cells and macrophages. Targeting the CARD8 inflammasome can be a potent and broadly effective strategy for HIV eradication.

CARD8 Inflammasome Activation by HIV-1 Protease.

The pattern recognition receptor CARD8 is an inflammasome sensor for intracellular HIV-1 protease activity. Previously, the only method for studying the CARD8 inflammasome has been through utilizing DPP8/DPP9 inhibitors including Val-boroPro (VbP) to modestly and nonspecifically activate the CARD8 inflammasome. The identification of HIV-1 protease as a target for sensing by CARD8 has opened the door for a new method of studying the underlying mechanism of CARD8 inflammasome activation. Additionally, triggering the CARD8 inflammasome offers a promising strategy for reducing HIV-1 latent reservoirs. Here we describe the methods to study CARD8 sensing of HIV-1 protease activity through non-nucleoside reverse transcriptase inhibitor (NNRTI)-mediated pyroptosis of HIV-1-infected immune cells and through an HIV and CARD8 co-transfection model.

Photo-Enhanced Chemo-Transistor Platform for Ultrasensitive Assay of Small Molecules.

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.

Epidemiological Survey and Risk Factor Analysis of 14 Potential Pathogens in Golden Snub-Nosed Monkeys at Shennongjia National Nature Reserve, China.

Golden snub-nosed monkeys (Rhinopithecus roxellanae) belong to Class A, the highest level of endangered primate species. Exploring the infection status of potential pathogens in golden snub-nosed monkeys is important for controlling associated diseases and protecting this species. The objective of this study was to investigate the seroprevalence for a number of potential pathogens and the prevalence of fecal adenovirus and rotavirus. A total of 283 fecal samples were collected from 100 golden snub-nosed monkeys in December 2014, June 2015, and January 2016; 26 blood samples were collected from 26 monkeys in June 2014, June 2015, January 2016 and November 2016 at Shennongjia National Reserve in Hubei, China. The infection of 11 potential viral diseases was examined serologically using an Indirect Enzyme-linked Immunosorbent Assay (iELISA) and Dot Immunobinding Assays (DIA), while the whole blood IFN-γ in vitro release assay was used to test tuberculosis (TB). In addition, fecal Adenovirus and Rotavirus were detected using Polymerase Chain Reaction (PCR). As a result, the Macacine herpesvirus-1 (MaHV-1), Golden snub-nosed monkey cytomegalovirus (GsmCMV), Simian foamy virus (SFV) and Hepatitis A virus (HAV) were detected with the seroprevalence of 57.7% (95% CI: 36.9, 76.6), 38.5% (95% CI: 20.2, 59.4), 26.9% (95% CI: 11.6, 47.8), and 7.7% (95% CI: 0.0, 84.2), respectively. Two fecal samples tested positive for Adenovirus (ADV) by PCR, with a prevalence of 0.7% (95% CI: 0.2, 2.5), and further, the amplification products were sequenced. Phylogenetic analysis revealed that they belonged to the HADV-G group. However, other pathogens, such as Coxsackievirus (CV), Measles virus (MeV), Rotavirus (RV), Simian immunodeficiency virus (SIV), Simian type D retroviruses (SRV), Simian-T-cell lymphotropic virus type 1 (STLV-1), Simian varicella virus (SVV), Simian virus 40 (SV40) and Mycobacterium tuberculosis complex (TB) were negative in all samples. In addition, a risk factor analysis indicated that the seroprevalence of MaHV-1 infection was significantly associated with old age (≥4 years). These results have important implications for understanding the health status and conservation of the endangered golden snub-nosed monkey population at Shennongjia Nature Reserve.

Gut microbiome variations in Rhinopithecus roxellanae caused by changes in the environment.

BACKGROUND: The snub-nosed monkey (Rhinopithecus roxellanae) is an endangered animal species mainly distributed in China and needs to be protected. Gut microbiome is an important determinant of animal health and population survival as it affects the adaptation of the animals to different foods and environments under kinetic changes of intrinsic and extrinsic factors. Therefore, this study aimed to elucidate gut fecal microbiome profiles of snub-nosed monkeys affected by several extrinsic and intrinsic factors, including raising patterns (captive vs. wild), age, sex, and diarrheal status to provide a reference for making protection strategies. RESULTS: The 16S rRNA gene sequencing was firstly used to pre-check clustering of 38 fecal samples from the monkeys including 30 wild and 8 captive (5 healthy and 3 diarrheal) from three Regions of Shennongjia Nature Reserve, Hubei Province, China. Then the 24 samples with high-quality DNA from 18 wild and 6 captive (4 healthy and 2 diarrheal) monkeys were subjected to shotgun metagenomic sequencing to characterize bacterial gut microbial communities. We discovered that the raising pattern (captive and wild) rather than age and sex was the predominant factor attributed to gut microbiome structure and proportionality. Wild monkeys had significantly higher bacterial diversity and lower Bacteroidetes/Firmicutes ratios than captive animals. Moreover, the gut microbiomes in wild healthy monkeys were enriched for the genes involved in fatty acid production, while in captive animals, genes were enriched for vitamin biosynthesis and metabolism and amino acid biosynthesis from carbohydrate intermediates. Additionally, a total of 37 antibiotic resistant genes (ARG) types were detected. Unlike the microbiome diversity, the captive monkeys have a higher diversity of ARG than the wild animals. CONCLUSION: Taken together, we highlight the importance of self-reprogramed metabolism in the snub-nosed monkey gut microbiome to help captive and wild monkeys adapt to different intrinsic and extrinsic environmental change.

Integrated membrane electrochemical reactor-membrane distillation process for enhanced landfill leachate treatment.

Treatment of recalcitrant landfill leachate (LFL) induces huge energy consumption and carbon emissions due to its complex composition. Although membrane distillation (MD) exhibits good potential in LFL treatment with waste heat utilization, membrane fouling and ammonia rejection are still the major problems encountered that hinder its application. Herein, membrane electrochemical reactor (MER) was coupled with MD for simultaneous membrane fouling control and resource recovery. LFL pretreatment with membrane-less electrochemical reactor (EO) and without pretreatment were also purified by MD for comparison. Results showed that the MER-MD system rejected almost all CODCr, total phosphorus, metal salts, and ammonia nitrogen (increased by 33.5%-43.5% without chemical addition), and recovered 31% of ammonia nitrogen and 48% of humic acid in the raw LFL. Owing to the effective removal of hardness (61%) and organics (77%) using MER, the MER-MD system showed higher resistance to the membrane wetting and fouling, with about 61% and 14% higher final vapor flux than those of the MD and EO-MD systems, respectively, and the pure water flux could be fully recovered by alkaline solution cleaning. Moreover, SEM-EDS, ATR-FTIR and XRD characterization further demonstrated the superiority of the MD membrane fouling reversibility of the MER-MD system. Energy consumption and carbon emissions analysis showed that the MER-MD system reduced the total energy consumption/carbon emissions by ∼20% and ∼8% compared to the MD and EO-MD systems, respectively, and the ammonia nitrogen recovered by MER could offset 8.25 kg carbon dioxide equivalent. Therefore, the introduction of MER pretreatment in MD process would be an option to decrease energy consumption and reduce carbon emissions for MD treatment of LFL.

Ammonia-induced oxidative stress triggered proinflammatory response and apoptosis in pig lungs.

Ammonia, a common toxic gas, is not only one of the main causes of haze, but also can enter respiratory tract and directly affect the health of humans and animals. Pig was used as an animal model for exploring the molecular mechanism and dose effect of ammonia toxicity to lung. In this study, the apoptosis of type II alveolar epithelial cells was observed in high ammonia exposure group using transmission electron microscopy. Gene and protein expression analysis using transcriptome sequencing and western blot showed that low ammonia exposure induced T-cell-involved proinflammatory response, but high ammonia exposure repressed the expression of DNA repair-related genes and affected ion transport. Moreover, high ammonia exposure significantly increased 8-hydroxy-2-deoxyguanosine (8-OHdG) level, meaning DNA oxidative damage occurred. In addition, both low and high ammonia exposure caused oxidative stress in pig lungs. Integrated analysis of transcriptome and metabolome revealed that the up-regulation of LDHB and ND2 took part in high ammonia exposure-affected pyruvate metabolism and oxidative phosphorylation progress, respectively. Inclusion, oxidative stress mediated ammonia-induced proinflammatory response and apoptosis of porcine lungs. These findings may provide new insights for understanding the ammonia toxicity to workers in livestock farms and chemical fertilizer plants.

Synergistic detoxification by combined reagents and safe filling utilization of cyanide tailings.

Cyanide tailings are the major hazardous wastes generated in the production process of the gold industry, which not only contain highly toxic cyanide, but also contain heavy metals with recycling value and other substances suitable for building materials or filling. These tailings are in urgent need of purification treatment and safe utilization. In this study, the impacts of treatment methods, types and combinations of reagents on decyanation effect were researched. Gold in cyanide tailings was recovered by flotation, and flotation tailings were used for filling after identifying the properties of solid waste. Results are as follows: (1) INCO method and 5 reagents (sodium sulfite, sodium persulfate, copper sulfate, ferrous sulfate and zinc sulfate) were selected for synergistic decyanation treatment, and cyanide concents in slurry and leaching solution were decreased to the minimum. (2) The gold recovery rate of the tailings through flotation was increased by 27.8% than without detoxification. (3) Flotation tailings were identified as general industrial solid wastes by leaching toxicity and toxic substance content analysis. (4) As filling aggregate, under the conditions of slurry concentration of 63% and cement-sand ratio of 1:6, the strength filling body of flotation tailings reached 1.32 Mpa after 28 days of maintenance. (5) This process and combined reagents were applied to engineering. The cyanide content in the leaching solution and the flotation recovery rate of gold were kept below 0.2 mg/L and above 60% respectively, and the strength of the filling body was stable to meet the requirements of underground filling.