Flare exhaust: An underestimated pollution source in municipal solid waste landfills.

Flares are commonly used in municipal solid waste landfills, and the pollution from flare exhaust is usually underestimated. This study aimed to reveal the odorants, hazardous pollutants, and greenhouse gas emission characteristics of the flare exhaust. Odorants, hazardous pollutants, and greenhouse gases emitted from air-assisted flares and a diffusion flare were analyzed, the priority monitoring pollutants were identified, and the combustion and odorant removal efficiencies of the flares were estimated. The concentrations of most odorants and the sum of odor activity values decreased significantly after combustion, but the odor concentration could still exceed 2,000. The odorants in the flare exhaust were dominated by oxygenated volatile organic compounds (OVOCs), while the major odor contributors were OVOCs and sulfur compounds. Hazardous pollutants, including carcinogens, acute toxic pollutants, endocrine disrupting chemicals, and ozone precursors with the total ozone formation potential up to 75 ppmv, as well as greenhouse gases (methane and nitrous oxide with maximum concentrations of 4,000 and 1.9 ppmv, respectively) were emitted from the flares. Additionally, secondary pollutants, such as acetaldehyde and benzene, were formed during combustion. The combustion performance of the flares varied with landfill gas composition and flare design. The combustion and pollutant removal efficiencies could be lower than 90%, especially for the diffusion flare. Acetaldehyde, benzene, toluene, p-cymene, limonene, hydrogen sulfide, and methane could be priority monitoring pollutants for flare emissions in landfills. Flares are useful for odor and greenhouse gas control in landfills, but they are also potential sources of odor, hazardous pollutants, and greenhouse gases.

Optimizing the Quality of Machine Learning for Identifying the Share of Biogenic and Fossil Carbon in Solid Waste.

Insights into carbon sources (biogenic and fossil carbon) and contents in solid waste are vital for estimating the carbon emissions from incineration plants. However, the traditional methods are time-, labor-, and cost-intensive. Herein, high-quality data sets were established after analyzing the carbon contents and infrared spectra of substantial samples using elemental analysis and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. Then, five classification and eight regression machine learning (ML) models were evaluated to recognize the proportion of biogenic and fossil carbon in solid waste. Using the optimized data preprocessing approach, the random forest (RF) classifier with hyperparameter tuning ranked first in classifying the carbon group with a test accuracy of 0.969, and the carbon contents were successfully predicted by the RF regressor with R2 = 0.926 considering performance-interpretability-computation time competition. The above proposed algorithms were further validated with real environmental samples, which exhibited robust performance with an accuracy of 0.898 for carbon group classification and an R2 value of 0.851 for carbon content prediction. The reliable results indicate that ATR-FTIR coupled with ML algorithms is feasible for rapidly identifying both carbon groups and content, facilitating the calculation and assessment of carbon emissions from solid waste incineration.

A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients.

AML ranks second in the most common types of leukemia diagnosed in both adults and children. Necroptosis is a programmed inflammatory cell death form reported to be an innate immune effector against microbial and viral pathogens and recently has been found to play an eventful role in the oncogenesis, progression, and metastasis of cancer. This study is designed to explore the potential value of necroptosis in predicting prognostic and optimizing the current therapeutic strategies for AML patients. We collected transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases and selected necroptosis-related genes with both differential significance and prognostic value. Six genes (YBX3, ZBP1, CDC37, ALK, BRAF, and BNIP3) were incorporated to generate a risk model with the implementation of multivariate Cox regression. The signature was proven to be an independent prognostic predictor in both training and validation cohorts with hazard ratios (HRs) of 1.51 (95% CI: 1.33-1.72) and 1.57 (95% CI: 1.16-2.12), respectively. Moreover, receiver operating characteristic (ROC) curve was utilized to quantify the predictive performance of the signature and satisfying results were shown with the area under the curve (AUC) up to 0.801 (3-year) and 0.619 (3-year), respectively. In addition, the subtyping of AML patients based on the risk signature demonstrated a significant correlation with the immune cell infiltration and response to immunotherapy. Finally, we incorporated risk signature with the classical clinical features to establish a nomogram which may contribute to the improvement of clinical management. To conclude, this study identified a necroptosis-related signature as a novel biomarker to improve the risk stratification, to inform the immunotherapy efficacy, and to indicate the therapeutic option of targeted therapy.

Targeting matrix metallopeptidase 2 by hydroxyurea selectively kills acute myeloid mixed-lineage leukemia.

Oncogene-induced tumorigenesis results in the variation of epigenetic modifications, and in addition to promoting cell immortalization, cancer cells undergo more intense cellular stress than normal cells and depend on other support genes for survival. Chromosomal translocations of mixed-lineage leukemia (MLL) induce aggressive leukemias with an inferior prognosis. Unfortunately, most MLL-rearranged (MLL-r) leukemias are resistant to conventional chemotherapies. Here, we showed that hydroxyurea (HU) could kill MLL-r acute myeloid leukemia (AML) cells through the necroptosis process. HU target these cells by matrix metallopeptidase 2 (MMP2) deficiency rather than subordinate ribonucleotide reductase regulatory subunit M2 (RRM2) inhibition, where MLL directly regulates MMP2 expression and is decreased in most MLL-r AMLs. Moreover, iron chelation of HU is also indispensable for inducing cell stress, and MMP2 is the support factor to protect cells from death. Our preliminary study indicates that MMP2 might play a role in the nonsense-mediated mRNA decay pathway that prevents activation of unfolding protein response under innocuous endoplasmic reticulum stress. Hence, these results reveal a possible strategy of HU application in MLL-r AML treatment and shed new light upon HU repurposing.

Multifunctional theranostic nanoparticles for multi-modal imaging-guided CAR-T immunotherapy and chemo-photothermal combinational therapy of non-Hodgkin's lymphoma.

Accurate and effective tumor diagnosis, detection, and treatment are key for improving the survival rates of patients. Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable clinical success in eradicating hematologic malignancies. However, the hostile microenvironment in solid tumors severely prevents CAR-T cells from migrating and from infiltrating and killing malignant cells. Tumor microenvironment modulation strategies have attracted much attention in the field of cancer immunotherapy. Multifunctional nanoplatforms that integrate the advantages of different therapeutic techniques can allow for the multimodal synergistic treatment of tumors. In this study, a biocompatible, tumor-targeting, on-demand approach combining CAR-T cell immunotherapy and a chemo-photothermal therapy nanoplatform (FA-Gd-GERTs@Ibrutinib) based on gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) has been developed for multimodal imaging, and it provides a reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction. In our study, folate (FA) receptor targeted molecules are used to improve the accuracy and sensitivity of computed tomography/magnetic resonance/Raman multimodal tumor imaging. The photothermal effect of the nanoprobe can promote the angiogenesis of lymphoma tissue, destroy the extracellular matrix, loosen compact tissue, stimulate chemokine secretion, and effectively enhance the infiltration ability in the case of non-Hodgkin's lymphoma, without dampening the CD19 CAR-T cell activity. The treatment results in tumor-bearing mice proved the existence of excellent synergistic therapy; photothermal therapy improves the accumulation and effector function of CAR-T cells within solid tumors. It is believed that multifunctional nanomaterials with targeted multi-modal imaging capabilities that support combination therapy can provide an efficient route for accurate diagnosis and efficient treatment.

A T-cell independent universal cellular therapy strategy through antigen depletion.

Rationale: T cell therapeutic strategy using CD19-targeting chimeric antigen receptor (CAR) is a revolutionary, novel, and successful treatment for B-cell malignancies. However, the dependency on T-cell mediated cytotoxicity restricts CAR-T therapy as a patient-specific individualized therapy with severe side effects, such as cytokine release syndrome (CRS). Whether a non-T-cell based universal cellular therapy can substitute CAR-T therapy is largely unknown. Methods: Various artificial antigen-recognizing cells were prepared to determine whether non-T-cell-derived CD19-scFv bearing effector cells could cause target cell death. A universal strategy for CRS-free cellular therapeutics was proposed, utilizing artificial antigen-recognizing cells (AARC), which can be manufactured universally and routinely as "off-the-shelf" mesenchymal stromal cells (MSCs) or other types of non-autologous cells expressing anergic CARs. Results: We demonstrated that T-lymphocytic and non-lymphocytic cells could cause CD19 internalization and subsequent depletion when armed with a CD19-recognizing moiety. This CD19 antigen depletion could efficiently induce T-cell independent apoptosis in target cancer cells whose survival depends on CD19 expression, suggesting that CD19 antigen depletion constitutes a crucial tumor destroying mechanism for CD19-CAR-T, especially for its long-term efficacy. Conclusion: Our results uncovered an unrecognized CAR-T cytotoxicity and antigen loss mechanism and provided new insights into a shift from unique patient-specific autologous therapeutics to universal and standardized allogeneic treatment.

Deubiquitinating enzyme inhibitor alleviates cyclin A1-mediated proteasome inhibitor tolerance in mixed-lineage leukemia.

Drug resistance is a significant obstacle to effective cancer treatment. Drug resistance develops from initially reversible drug-tolerant cancer cells, which offer therapeutic opportunities to impede cancer relapse. The mechanisms of resistance to proteasome inhibitor (PI) therapy have been investigated intensively, however the ways by which drug-tolerant cancer cells orchestrate their adaptive responses to drug challenges remain largely unknown. Here, we demonstrated that cyclin A1 suppression elicited the development of transient PI tolerance in mixed-lineage leukemia (MLL) cells. This adaptive process involved reversible downregulation of cyclin A1, which promoted PI resistance through cell-cycle arrest. PI-tolerant MLL cells acquired cyclin A1 dependency, regulated directly by MLL protein. Loss of cyclin A1 function resulted in the emergence of drug tolerance, which was associated with patient relapse and reduced survival. Combination treatment with PI and deubiquitinating enzyme (DUB) inhibitors overcame this drug resistance by restoring cyclin A1 expression through chromatin crosstalk between histone H2B monoubiquitination and MLL-mediated histone H3 lysine 4 methylation. These results reveal the importance of cyclin A1-engaged cell-cycle regulation in PI resistance in MLL cells, and suggest that cell-cycle re-entry by DUB inhibitors may represent a promising epigenetic therapeutic strategy to prevent acquired drug resistance.

Mixed-lineage leukemia protein modulates the loading of let-7a onto AGO1 by recruiting RAN.

Not available.

mTORC1-mediated amino acid signaling is critical for cell fate determination under transplant-induced stress.

Transplantation of in vitro-manipulated cells is widely used in hematology. While transplantation is well recognized to impose severe stress on transplanted cells, the nature of transplant-induced stress remains elusive. Here, we propose that the lack of amino acids in serum is the major cause of transplant-induced stress. Mechanistically, amino acid deficiency decreases protein synthesis and nutrient consummation. However, in cells with overactive AKT and ERK, mTORC1 is not inhibited and protein synthesis remains relatively high. This impaired signaling causes nutrient depletion, cell cycle block, and eventually autophagy and cell death, which can be inhibited by cycloheximide or mTORC1 inhibitors. Thus, mTORC1-mediated amino acid signaling is critical in cell fate determination under transplant-induced stress, and protein synthesis inhibition can improve transplantation efficiency.

Arsenic sulfide induces RAG1-dependent DNA damage for cell killing by inhibiting NFATc3 in gastric cancer cells.

BACKGROUND: Arsenic sulfide was found to have potential anti-cancer activities, especially in gastric cancer. However, the underlying mechanism need to be further explored. This study was aimed to investigate the mechanism of arsenic compounds on gastric cancer. METHODS: Gastric cancer cell lines were infected with lentiviral vector carrying shNFATc3 and/or treated with arsenic sulfide. MTT assay were performed to assess cell growth. Flow cytometer assays were used to detect cell cycle and reactive oxygen species (ROS) level of gastric cancer cells. Western blot was carried out to detect nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3), cell cycle markers, DNA damage pathway protein expression as well as other protein expression in gastric cancer cell lines. The expression of recombination activating gene 1 (RAG1) in gastric cancer cell lines was determined by RNA-sequencing analyses and Real-Time qPCR. The effect of NFATc3 on RAG1 were determined by CHIP-qPCR assay. The effect of arsenic sulfide on AGS cells was evaluated in vivo. RESULTS: We show that arsenic sulfide as well as knockdown of NFATc3 resulted in increased double-strand DNA damage in gastric cancer cells by increasing the expression of RAG1, an endonuclease essential for immunoglobulin V(D) J recombination. Overexpression of NFATc3 blocked the expression of RAG1 expression and DNA damage induced by arsenic sulfide. Arsenic sulfide induced cellular oxidative stress to redistribute NFATc3, thereby inhibiting its transcriptional function, which can be reversed by N-acetyl-L-cysteine (NAC). We show that NFATc3 targets the promoter of RAG1 for transcriptional inhibition. We further showed that NFATc3 upregulation and RAG1 downregulation significantly associated with poor prognosis in patients with gastric cancer. Our in vivo experiments further confirmed that arsenic sulfide exerted cytotoxic activity against gastric cancer cells through inhibiting NFATc3 to activate RAG1 pathway. CONCLUSION: These results demonstrate that arsenic sulfide targets NFATc3 to induce double strand DNA break (DSB) for cell killing through activating RAG1 expression. Our results link arsenic compound to the regulation of DNA damage control and RAG1 expression as a mechanism for its cytotoxic effect.

Transcriptome Analysis Provides a Preliminary Regulation Route of the Ethylene Signal Transduction Component, SlEIN2, during Tomato Ripening.

Ethylene is crucial in climacteric fruit ripening. The ethylene signal pathway regulates several physiological alterations such as softening, carotenoid accumulation and sugar level reduction, and production of volatile compounds. All these physiological processes are controlled by numerous genes and their expression simultaneously changes at the onset of ripening. Ethylene insensitive 2 (EIN2) is a key component for ethylene signal transduction, and its mutation causes ethylene insensitivity. In tomato, silencing SlEIN2 resulted in a non-ripening phenotype and low ethylene production. RNA sequencing of SlEIN2-silenced and wild type tomato, and differential gene expression analyses, indicated that silencing SlEIN2 caused changes in more than 4,000 genes, including those related to photosynthesis, defense, and secondary metabolism. The relative expression level of 28 genes covering ripening-associated transcription factors, ethylene biosynthesis, ethylene signal pathway, chlorophyll binding proteins, lycopene and aroma biosynthesis, and defense pathway, showed that SlEIN2 influences ripening inhibitor (RIN) in a feedback loop, thus controlling the expression of several other genes. SlEIN2 regulates many aspects of fruit ripening, and is a key factor in the ethylene signal transduction pathway. Silencing SlEIN2 ultimately results in lycopene biosynthesis inhibition, which is the reason why tomato does not turn red, and this gene also affects the expression of several defense-associated genes. Although SlEIN2-silenced and green wild type fruits are similar in appearance, their metabolism is significantly different at the molecular level.

Role of the Tomato Non-Ripening Mutation in Regulating Fruit Quality Elucidated Using iTRAQ Protein Profile Analysis.

Natural mutants of the Non-ripening (Nor) gene repress the normal ripening of tomato fruit. The molecular mechanism of fruit ripening regulation by the Nor gene is unclear. To elucidate how the Nor gene can affect ripening and fruit quality at the protein level, we used the fruits of Nor mutants and wild-type Ailsa Craig (AC) to perform iTRAQ (isobaric tags for relative and absolute quantitation) analysis. The Nor mutation altered tomato fruit ripening and affected quality in various respects, including ethylene biosynthesis by down-regulating the abundance of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), pigment biosynthesis by repressing phytoene synthase 1 (PSY1), ζ-carotene isomerase (Z-ISO), chalcone synthase 1 (CHS1) and other proteins, enhancing fruit firmness by increasing the abundance of cellulose synthase protein, while reducing those of polygalacturonase 2 (PG2) and pectate lyase (PL), altering biosynthesis of nutrients such as carbohydrates, amino acids, and anthocyanins. Conversely, Nor mutation also enhanced the fruit's resistance to some pathogens by up-regulating the expression of several genes associated with stress and defense. Therefore, the Nor gene is involved in the regulation of fruit ripening and quality. It is useful in the future as a means to improve fruit quality in tomato.

Efficient Virus-Induced Gene Silencing in Solanum rostratum.

Solanum rostratum is a "super weed" that grows fast, is widespread, and produces the toxin solanine, which is harmful to both humans and other animals. To our knowledge, no study has focused on its molecular biology owing to the lack of available transgenic methods and sequence information for S. rostratum. Virus-induced gene silencing (VIGS) is a powerful tool for the study of gene function in plants; therefore, in the present study, we aimed to establish tobacco rattle virus (TRV)-derived VIGS in S. rostratum. The genes for phytoene desaturase (PDS) and Chlorophyll H subunit (ChlH) of magnesium protoporphyrin chelatase were cloned from S. rostratum and used as reporters of gene silencing. It was shown that high-efficiency VIGS can be achieved in the leaves, flowers, and fruit of S. rostratum. Moreover, based on our comparison of three different types of infection methods, true leaf infection was found to be more efficient than cotyledon and sprout infiltration in long-term VIGS in multiple plant organs. In conclusion, the VIGS technology and tomato genomic sequences can be used in the future to study gene function in S. rostratum.

[3-Dimensional model reconstruction of penis and surrounding tissue].

OBJECTIVE: To evaluate the feasibility of 3-Dimensional (3-D) model reconstruction of penis and surrounding structures based on magnetic resonance images, which may provide the model building method for modeling surgery of individual penoplasty. METHODS: Magnetic resonance (MR) images of penis with different imaging parameters were evaluated. With the surface rendering construction, the 3D virtual model was established by Amira software. RESULTS: The anatomical details imaging is better in T2-weighted fast spin-echo images with 3.0 mm slice thickness. The established model based on the MR images can show the soft-tissue, suspensory ligament of the penis. The suspensory ligament stretches between the pubic symphysis and the corpora cavernosa. The penile roots attach to inferior ramus of pubis. CONCLUSIONS: MR imaging provides enough anatomical information for modeling. It can be used for the development of model surgery system of individual penoplasty.

Three-dimensional virtual model and animation of penile lengthening surgery.

BACKGROUND: Three-dimensional digital models, animations, and simulations have been used in the plastic surgical field for surgical education and training and patient education. In penile lengthening surgery, proper patient selection and well-designed surgical interventions are necessary; however, no such surgical or patient education tool exists. METHODS: Using magnetic resonance images as references, a preliminary three-dimensional digital model of the penis with its adjacent structures was constructed using Amira 5. This preliminary model was imported into Maya 2009, a computer modeling and animation software program, for processing to correct many defects. The refined model was used to create digital animation of penile lengthening surgery, including ordered steps of the procedure, using Maya 2009 and Adobe After Effects CS4. RESULTS: A three-dimensional digital animation was created to illustrate penile lengthening surgery. All major surgical steps were demonstrated, including exposure, transversal incision of the fundiform ligament, partial division and release of the suspensory ligament. CONCLUSIONS: Three-dimensional digital models and animations of penile lengthening surgery may serve as resources for patient education to facilitate patient selection and resident education outside the operating room.

[Study on genetic polymorphisms of 13 SNP loci in Guangxi Zhuang population of China].

OBJECTIVE: The fluorescence labeled multi-PCR system was applied to investigate the allele frequency of the 13 single nucleotide polymorphism (SNP) in 314 Guangxi Zhuang populations, and to evaluate their application value in forensic medicine. METHODS: Thirteen autosomal diallelic SNP loci were selected and the SNP genotyping system of fragment length discrepant allele specific fluorescence labeled multi-PCR technique was applied to investigate their allele frequency distribution in Guangxi Zhuang population. RESULTS: The allele frequencies of the 13 single nucleotide pdymorphism (SNP) in Guangxi Zhuang population were obtained, which shows that the allele frequency distribution is in accordance with Hardy-Weinberg equilibrium. Their heterozygosity was between 0.2166 and 0.5478, the polymorphism information content was between 0.2084 and 0.3750, their cumulate discrimination probability was 99.99%, and the cumulate exclusion power was 87.71%. CONCLUSION: Several SNP loci could be genotyped simultaneously using the fluorescence labeled fragment length discrepant multiplex-PCR technique; the 13 SNP loci have a highly applicable value in the field of forensic personal identification.

[A comparative study on genetic polymorphism and genetic relationship of 13 SNPs in three Chinese populations].

Using the fluorescence labeled capillary electrophoresis of multi-PCR technique, the single nucleotide polymorphism (SNP) typing system of fragment length discrepant allele specific fluorescence labeled multi-PCR technique is established based on the principle of allele-specific PCR. The typing of the 13 SNP loci can be completed simultaneously according to the length of PCR products and the number of product peaks. It appears a single product peak when the SNP is homozygous, and two product peaks with 4 bp differences will appear when it is heterozygous. By using this system, we conducted population census about allele frequencies for 13 autosomal SNP loci in Southern Liaoning Han samples, Mongolian samples in Inner Mongolia and Zhuang samples in Guangxi area, and got the allele frequencies of the 13 SNP loci in the three populations, then preliminarily discussed their genetic relationship by comparing their differences in allelic polymorphism. The results indicate that the allelic distributions of the 13 SNP loci in the three populations are polymorphic, and the difference is significant in some SNP loci (P< or =0.01). The sampling survey shows that the result is consistent with Hardy-Weinberg equilibrium, and Han population in southern Liaoning has relatively closer relationship with Mongolian in Inner Mongolia than with Zhuang population in Guangxi by origin.