Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis.

Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.

A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).

Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC.

BACKGROUND AND AIMS: Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the hypoxic TME of HCC remains to be elucidated. APPROACH AND RESULTS: We analyzed the immune landscapes of hypoxia-low and hypoxia-high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses. The mechanisms of immunosuppression in immune subsets of interest were further explored using in vitro hypoxia assays. Regulatory T cells (Tregs) and a number of immunosuppressive myeloid subsets, including M2 macrophages and human leukocyte antigen-DR isotype (HLA-DRlo ) type 2 conventional dendritic cell (cDC2), were found to be significantly enriched in hypoxia-high tumor regions. On the other hand, the abundance of active granzyme Bhi PD-1lo CD8+ T cells in hypoxia-low tumor regions implied a relatively active immune landscape compared with hypoxia-high regions. The up-regulation of cancer-associated genes in the tumor tissues and immunosuppressive genes in the tumor-infiltrating leukocytes supported a highly pro-tumorigenic network in hypoxic HCC. Chemokine genes such as CCL20 (C-C motif chemokine ligand 20) and CXCL5 (C-X-C motif chemokine ligand 5) were associated with recruitment of both Tregs and HLA-DRlo cDC2 to hypoxia-high microenvironments. The interaction between Tregs and cDC2 under a hypoxic TME resulted in a loss of antigen-presenting HLA-DR on cDC2. CONCLUSIONS: We uncovered the unique immunosuppressive landscapes and identified key immune subsets enriched in hypoxic HCC. In particular, we identified a potential Treg-mediated immunosuppression through interaction with a cDC2 subset in HCC that could be exploited for immunotherapies.

Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma.

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

Ancient co-option of an amino acid ABC transporter locus in Pseudomonas syringae for host signal-dependent virulence gene regulation.

Pathogenic bacteria frequently acquire virulence traits via horizontal gene transfer, yet additional evolutionary innovations may be necessary to integrate newly acquired genes into existing regulatory pathways. The plant bacterial pathogen Pseudomonas syringae relies on a horizontally acquired type III secretion system (T3SS) to cause disease. T3SS-encoding genes are induced by plant-derived metabolites, yet how this regulation occurs, and how it evolved, is poorly understood. Here we report that the two-component system AauS-AauR and substrate-binding protein AatJ, proteins encoded by an acidic amino acid-transport (aat) and -utilization (aau) locus in P. syringae, directly regulate T3SS-encoding genes in response to host aspartate and glutamate signals. Mutants of P. syringae strain DC3000 lacking aauS, aauR or aatJ expressed lower levels of T3SS genes in response to aspartate and glutamate, and had decreased T3SS deployment and virulence during infection of Arabidopsis. We identified an AauR-binding motif (Rbm) upstream of genes encoding T3SS regulators HrpR and HrpS, and demonstrated that this Rbm is required for maximal T3SS deployment and virulence of DC3000. The Rbm upstream of hrpRS is conserved in all P. syringae strains with a canonical T3SS, suggesting AauR regulation of hrpRS is ancient. Consistent with a model of conserved function, an aauR deletion mutant of P. syringae strain B728a, a bean pathogen, had decreased T3SS expression and growth in host plants. Together, our data suggest that, upon acquisition of T3SS-encoding genes, a strain ancestral to P. syringae co-opted an existing AatJ-AauS-AauR pathway to regulate T3SS deployment in response to specific host metabolite signals.

A DeoR-Type Transcription Regulator Is Required for Sugar-Induced Expression of Type III Secretion-Encoding Genes in Pseudomonas syringae pv. tomato DC3000.

The type III secretion system (T3SS) of plant-pathogenic Pseudomonas syringae is essential for virulence. Genes encoding the T3SS are not constitutively expressed and must be induced upon infection. Plant-derived metabolites, including sugars such as fructose and sucrose, are inducers of T3SS-encoding genes, yet the molecular mechanisms underlying perception of these host signals by P. syringae are unknown. Here, we report that sugar-induced expression of type III secretion A (setA), predicted to encode a DeoR-type transcription factor, is required for maximal sugar-induced expression of T3SS-associated genes in P. syringae DC3000. From a Tn5 transposon mutagenesis screen, we identified two independent mutants with insertions in setA. When both setA::Tn5 mutants were cultured in minimal medium containing fructose, genes encoding the T3SS master regulator HrpL and effector AvrRpm1 were expressed at lower levels relative to that of a wild-type strain. Decreased hrpL and avrRpm1 expression also occurred in a setA::Tn5 mutant in response to glucose, sucrose, galactose, and mannitol, demonstrating that setA is genetically required for T3SS induction by many different sugars. Expression of upstream regulators hrpR/S and rpoN was not altered in setA::Tn5, indicating that SetA positively regulates hrpL expression independently of increased transcription of these genes. In addition to decreased response to defined sugar signals, a setA::Tn5 mutant had decreased T3SS deployment during infection and was compromised in its ability to grow in planta and cause disease. These data suggest that SetA is necessary for P. syringae to effectively respond to T3SS-inducing sugar signals encountered during infection.

Extraction of intra-biliary hepatocellular carcinoma by endoscopic retrograde cholangiopancreatography.

BACKGROUND: Hepatocellular carcinoma with biliary ductal invasion is rare and associated with a significantly lower survival rate. CASE PRESENTATION: We present an unusual case of a patient with hepatocellular carcinoma and biliary invasion, who had his diagnosis confirmed by histological analysis from tissue extracted by endoscopic retrograde cholangiopancreatography. An 87-year-old male presented with a 1-day history of right upper quadrant pain and jaundice. His past medical history included recurrent gallstone cholangitis and a previous cholecystectomy. An abdominal CT demonstrated a dilated intrahepatic biliary tree with left proximal intrahepatic hyperdensities, as well as a 3 cm hepatocellular carcinoma. He was initially suspected to have concurrent gallstone cholangitis and a newly diagnosed hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography and balloon trawling of the intraductal lesions extracted necrotic tumour-like tissue which was histologically consistent with hepatocellular carcinoma. The extraction of the intra-biliary portion of HCC resulted in complete resolution of his jaundice, enabling further treatment with nivolumab, which would not have been possible if the obstruction was not cleared. The patient is currently well and has completed his 6th cycle of nivolumab. CONCLUSION: Obstructive jaundice is an uncommon presentation for patients with HCC. it is key for clinicians to be aware of the possibility of intrabiliary invasion in order obtain an early diagnosis and to reduce any delay in treatment.

Temperature determination of superheated water vapor by rotational-vibrational Raman spectroscopy.

We present a novel non-invasive laser-based tool for tracer-free spatially resolved temperature measurement in superheated water vapor at atmospheric pressure. The technique exploits the temperature sensitivity of the rotational-vibrational Raman spectrum of the v1 stretching vibration. This Letter demonstrates the Raman sensor, its application to a steam gasification reactor, and four methods to analyze the Raman spectra in order to obtain the temperature: an equal intensity point approach, a pseudo-isosbestic point approach, and two approaches based on the reconstruction of the Raman band by Gaussian/Lorentzian profiles. The evaluated water vapor temperatures inside a reactor for plasma-assisted gasification are compared to data acquired by supercontinuum absorption spectroscopy.

Primary Renal Hybrid Low-grade Fibromyxoid Sarcoma-Sclerosing Epithelioid Fibrosarcoma: An Unusual Pediatric Case With EWSR1-CREB3L1 Fusion.

Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity. Tumors exhibiting features of both entities are considered hybrid LGFMS-SEF lesions. While the majority of LGFMS cases are characterized by FUS-CREB3L2 gene fusions, most cases of pure SEF show EWSR1 gene rearrangements. In the largest study of hybrid LGFMS-SEF tumors to date, all cases exhibited FUS rearrangements, a similar genetic profile to LGFMS. We herein describe the clinicopathological features and genetic findings of a case of primary renal hybrid LGFMS-SEF occurring in a 10-year-old child, with disseminated metastases. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was performed on both the primary renal tumor that showed the morphology of a LGFMS, and a cervical metastasis that showed the morphology of SEF. An EWSR1-CREB3L1 gene fusion occurring between exon 11 of EWSR1 and exon 6 of CREB3L1 was present in both the LGFMS and SEF components. This unusual case provides evidence that a subset of hybrid LGFMS-SEF harbor EWSR1-CREB3L1 gene fusions. In this case, these features were associated with an aggressive clinical course, with disease-associated mortality occurring within 12 months of diagnosis.

Fha interaction with phosphothreonine of TssL activates type VI secretion in Agrobacterium tumefaciens.

The type VI secretion system (T6SS) is a widespread protein secretion system found in many Gram-negative bacteria. T6SSs are highly regulated by various regulatory systems at multiple levels, including post-translational regulation via threonine (Thr) phosphorylation. The Ser/Thr protein kinase PpkA is responsible for this Thr phosphorylation regulation, and the forkhead-associated (FHA) domain-containing Fha-family protein is the sole T6SS phosphorylation substrate identified to date. Here we discovered that TssL, the T6SS inner-membrane core component, is phosphorylated and the phosphorylated TssL (p-TssL) activates type VI subassembly and secretion in a plant pathogenic bacterium, Agrobacterium tumefaciens. Combining genetic and biochemical approaches, we demonstrate that TssL is phosphorylated at Thr 14 in a PpkA-dependent manner. Further analysis revealed that the PpkA kinase activity is responsible for the Thr 14 phosphorylation, which is critical for the secretion of the T6SS hallmark protein Hcp and the putative toxin effector Atu4347. TssL phosphorylation is not required for the formation of the TssM-TssL inner-membrane complex but is critical for TssM conformational change and binding to Hcp and Atu4347. Importantly, Fha specifically interacts with phosphothreonine of TssL via its pThr-binding motif in vivo and in vitro and this interaction is crucial for TssL interaction with Hcp and Atu4347 and activation of type VI secretion. In contrast, pThr-binding ability of Fha is dispensable for TssM structural transition. In conclusion, we discover a novel Thr phosphorylation event, in which PpkA phosphorylates TssL to activate type VI secretion via its direct binding to Fha in A. tumefaciens. A model depicting an ordered TssL phosphorylation-induced T6SS assembly pathway is proposed.

Validation of a HPLC-ESI MS/MS method for the determination of clonidine in human plasma and its application in a bioequivalence study in Chinese healthy volunteers.

A rapid and sensitive liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to determine clonidine in human plasma was developed and fully validated. Sample preparation was involved an one-step extraction with diethyl ether. Donepezil was employed as the internal standard (IS). Chromatographic separation was performed on a Hypersil BDS C18 column (i.d. 2.1 × 50 mm, particle size 3µm) with a mobile phase of methanol-water (containing 0.1% formic acid; 60:40, v/v) at a flow rate of 200 µL/min. The peaks were detected by mass spectrometry using the electrospray ion source in selected reaction monitoring mode. The extraction recovery was 72.53-85.25%. The method was found to be linear in a concentration range of 0.02-6.00 ng/mL and the lower limit of quantification was 0.02 ng/mL. The within- and between-batch precisions at three concentrations were 4.33-16.47 and 7.24-17.24% with accuracies of -2.47-10.91 and 1.86-10.19%, respectively. This validated method was successfully used for a bioequivalence study of two clonidine transdermal patches on healthy volunteers. The results suggested that the test formulation of clonidine patch met the regulatory criterion for bioequivalence to the reference formulation, but a larger sample size should be needed for the estimation of bioequivalence.

Fine-needle aspiration of a pancreas with squamoid cyst of pancreatic duct and pancreatic duct stones: A case report of a rare pancreatic lesion and an unusual concurrent finding of stone-related crystals.

Squamoid cyst of pancreatic duct is a rare benign pancreatic lesion that is rarely encountered in fine-needle aspiration (FNA) and surgical resection specimens. Pancreatic stones can be seen in chronic pancreatitis, but stone-related crystals have previously not been described in pancreatic cytology. Presented here is a case report of a squamoid cyst of pancreatic duct with concurrent pancreatic duct stones. We describe the cytomorphology of this benign cyst, as well as the remarkable finding of polymorphous crystals on cyst fluid aspirate. We also describe the histology of the surgically resected cystic lesion. With the increase in detection of incidental pancreatic cysts on imaging, this case highlights the importance of awareness and recognition of benign non-neoplastic epithelial cysts on FNA sampling to avoid overtreatment. The presence of crystals on pancreatic FNA is an unusual finding, likely representing calcium carbonate crystals related to the formation of pancreatic duct stones.

Transporter-mediated depletion of extracellular proline directly contributes to plant pattern-triggered immunity against a bacterial pathogen.

Plants possess cell surface-localized immune receptors that detect microbe-associated molecular patterns (MAMPs) and initiate defenses that provide effective resistance against microbial pathogens. Many MAMP-induced signaling pathways and cellular responses are known, yet how pattern-triggered immunity (PTI) limits pathogen growth in plants is poorly understood. Through a combined metabolomics and genetics approach, we discovered that plant-exuded proline is a virulence-inducing signal and nutrient for the bacterial pathogen Pseudomonas syringae, and that MAMP-induced depletion of proline from the extracellular spaces of Arabidopsis leaves directly contributes to PTI against P. syringae. We further show that MAMP-induced depletion of extracellular proline requires the amino acid transporter Lysine Histidine Transporter 1 (LHT1). This study demonstrates that depletion of a single extracellular metabolite is an effective component of plant induced immunity. Given the important role for amino acids as nutrients for microbial growth, their depletion at sites of infection may be a broadly effective means for defense against many pathogens.

GATA4 downregulation enhances CCL20-mediated immunosuppression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a deadly cancer with a high global mortality rate, and the downregulation of GATA binding protein 4 (GATA4) has been implicated in HCC progression. In this study, we investigated the role of GATA4 in shaping the immune landscape of HCC. METHODS: HCC tumor samples were classified into "low" or "normal/high" based on GATA4 RNA expression relative to adjacent non-tumor liver tissues. The immune landscapes of GATA4-low and GATA4-normal/high tumors were analyzed using cytometry by time-of-flight, bulk/spatial transcriptomic analyses and validated by multiplex immunofluorescence. RESULTS: GATA4-low tumors displayed enrichment in exhausted programmed cell death protein 1+ T cells, immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and macrophages, highlighting the impact of GATA4 downregulation on immunosuppression. Spatial and bulk transcriptomic analyses revealed a negative correlation between GATA4 and C-C Motif Chemokine Ligand 20 (CCL20) expression in HCC. Overexpressing GATA4 confirmed CCL20 as a downstream target, contributing to an immunosuppressive tumor microenvironment, as evidenced by increased regulatory T cells and myeloid-derived suppressor cells in CCL20-high tumors. Lastly, the reduced expression of GATA4 and higher expression of CCL20 were associated with poorer overall survival in patients with HCC, implicating their roles in tumor progression. CONCLUSIONS: Our study reveals that GATA4 downregulation contributes to an immunosuppressive microenvironment, driven by CCL20-mediated enrichment of regulatory T cells and myeloid-derived suppressor cells in HCC. These findings underscore the critical role of GATA4 reduction in promoting immunosuppression and HCC progression.

IFNγ-IL-17+ CD8 T cells contribute to immunosuppression and tumor progression in human hepatocellular carcinoma.

IL-17-producing CD8 (Tc17) T cells have been shown to play an important role in infection and chronic inflammation, however their implications in hepatocellular carcinoma (HCC) remain elusive. In this study, we performed cytometry by time-of-flight (CyTOF) and revealed the distinctive immunological phenotypes of two IFNγ+ and IFNγ- Tc17 subsets that were preferentially enriched in human HCC. Single-cell RNA-sequencing analysis further revealed regulatory circuits governing the different phenotypes of these Tc17 subsets. In particular, we discovered that IFNγ- Tc17 subset demonstrated pro-tumoral characteristics and expressed higher levels of CCL20. This corresponded to increased tumor infiltration of T regulatory cells (Treg) validated by immunohistochemistry in another independent HCC cohort, demonstrating the immunosuppressive functions of IFNγ- Tc17 subset. Most importantly, higher intra-tumoral proportions of IFNγ- Tc17 were associated with poorer prognosis in patients with HCC and this was further validated in The Cancer Genome Atlas (TCGA) HCC cohort. Taken together, this compendium of transcriptomic and proteomic data of Tc17 subsets sheds light on the immunosuppressive phenotypes of IFNγ- Tc17 and its implications in HCC progression.

A genomic enhancer signature associates with hepatocellular carcinoma prognosis.

Background & Aims: Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC. Methods: We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis. Results: We observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients' tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis. Conclusions: We report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC. Impact and Implications: Lifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients' RNA-seq and clinical data, we found the signature genes - with epigenetic and transcriptomic dysregulation - associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.

Intracellular sequestration of the NKG2D ligand ULBP3 by human cytomegalovirus.

Human CMV (HCMV) encodes multiple genes that control NK cell activation and cytotoxicity. Some of these HCMV-encoded gene products modulate NK cell activity as ligands expressed at the cell surface that engage inhibitory NK cell receptors, whereas others prevent the infected cell from upregulating ligands that bind to activating NK cell receptors. A major activating NKR is the homodimeric NKG2D receptor, which has eight distinct natural ligands in humans. It was shown that HCMV is able to prevent the surface expression of five of these ligands (MIC A/B and ULBP1, 2, and 6). In this article, we show that the HCMV gene product UL142 can prevent cell surface expression of ULBP3 during infection. We further show that UL142 interacts with ULBP3 and mediates its intracellular retention in a compartment that colocalizes with markers of the cis-Golgi complex. In doing so, UL142 prevents ULBP3 trafficking to the surface and protects transfected cells from NK-mediated cytotoxicity. This is the first description of a viral gene able to mediate downregulation of ULBP3.

Cadmium adsorption performance and mechanism from aqueous solution using red mud modified with amorphous MnO2.

In this study, red mud modified by manganese dioxide(MRM) was utilized as an adsorbent to effectively remove Cd2+ from aqueous solution. The characteristics were analysed by SEM-EDS, XRD, BET, FTIR and XPS. Different factors that affected the Cd2+ removal on MRM, such as dosage, initial pH, initial Cd2+ concentration, were investigated using batch adsorption experiments. Simultaneously, the adsorption kinetics, adsorption isotherms and adsorption thermodynamics of Cd2+ were also investigated using adsorption experiments data. The characterization results showed that MRM had a rougher, larger specific surface area and pore volume (38.91 m2 g-1, 0.02 cm3 g-1) than RM (10.22 m2 g-1, 0.73 cm3 g-1). The adsorption experiments found that the equilibrium adsorption capacity of MRM for Cd2+ was significantly increased to 46.36 mg g-1, which was almost three times that of RM. According to the fitting results, the pseudo-second-order kinetic model described the adsorption process better than the pseudo-first-order kinetic model. The Langmuir model fitted the adsorption isotherms well, indicating that the adsorption process was unimolecular layer adsorption and the maximum capacity was 103.59 mg g-1. The thermodynamic parameters indicated that the adsorption process was heat-trapping and spontaneous. Finally, combined XPS and FTIR studies, it was speculated that the adsorption mechanisms should be electrostatic attachment, specific adsorption (i.e., Cd-O or hydroxyl binding) and ion exchange. Therefore, manganese dioxide modified red mud can be an effective and economical alternative to the removal of Cd2+ in the wastewater treatment process.

Activation of bisulfite by LaFeO3 loaded on red mud for degradation of organic dye.

In this study, red mud (RM) was used as a support for LaFeO3 to prepare LaFeO3-RM via the ultrasonic-assisted sol-gel method for the removal of methylene blue (MB) assisted with bisulfite (BS) in the aqueous solution. Characterization by scanning electron microscopy and the Brunauer-Emmett-Teller method indicated that LaFeO3-RM exhibited a large surface area and porous structure with a higher pore volume (i.e. 10 times) compared with the bulk LaFeO3. The XRD, XPS and FTIR results revealed that the support of porous RM not only dispersed LaFeO3 particles but also increased Fe oxidation capability, oxygen-containing functional groups and chemically adsorbed oxygen (from 44.3% to 90.3%) of LaFeO3-RM, which improved the catalytic performance in structure and chemical composition. MB was removed through the synergistic effect of adsorption and catalysis, with MB molecules first absorbed on the surface and then degraded. The removal efficiency was 88.19% in the LaFeO3-RM/BS system under neutral conditions but only 27.09% in the LaFeO3/BS system. The pseudo-first-order kinetic constant of LaFeO3-RM was six times higher than that of LaFeO3. Fe(III) in LaFeO3-RM played a key role in the activation of BS to produce SO 4 ⋅ - by the redox cycle of Fe(III)/Fe(II). Dissolved oxygen was an essential factor for the generation of SO 4 ⋅ - . This work provides both a new approach for using porous industrial waste to improve the catalytic performance of LaFeO3 and guidance for resource utilization of RM in wastewater treatment.