Sorted-Cell Sequencing on HCC Specimens Reveals EPS8L3 as a Key Player in CD24/CD13/EpCAM-Triple Positive, Stemness-Related HCC Cells.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs and identify their regulatory mechanisms in stemness-related cells. METHODS: We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients' resected specimens. Knockdown approach was used, and relevant functional assays were conducted on the identified targets of interest. RESULTS: Flow cytometry on a total of 60 HCC resected specimens showed significant heterogeneity in the expression of LCSC markers, with CD24, CD13, and EpCAM mainly contributing to this heterogeneity. Concomitant expression of CD24, CD13, and EpCAM was detected in 32 HCC samples, and this was associated with advanced tumor stages. Transcriptomic sequencing on the HCC cells sorted for these individual markers identified epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8L3) as a common gene associated with the 3 markers and was functionally validated in HCC cells. Knocking down EPS8L3 suppressed the expression of all 3 markers. To search for the upstream regulation of EPS8L3, we found SP1 bound to EPS8L3 promoter to drive EPS8L3 expression. Furthermore, using Akt inhibitor MK2206, we showed that Akt signaling-driven SP1 drove the expression of the 3 LCSC markers. CONCLUSIONS: Our findings suggest that Akt signaling-driven SP1 promotes EPS8L3 expression, which is critical in maintaining the downstream expression of CD24, CD13, and EpCAM. The findings provide insight into potential LCSC-targeting therapeutic strategies.

Regulating charge transfer for enhanced PAA activation over sulfur-doped magnetic CoFe2O4: A novel strategy for simultaneous micropollutants degradation and bacteria inactivation.

Micropollutants and bacteria are prevalent pollutants in wastewater, posing significant risks to ecosystems and human health. As peracetic acid (PAA) is being increasingly used as a disinfectant, activation of PAA by low-cost and high-performance activators is a promising strategy for wastewater treatment. In this study, the sulfur-doped magnetic CoFe2O4 (SCFO) is successfully developed for efficient PAA activation to simultaneously decontaminate and disinfect wastewater. PAA/SCFO-0.3 exhibits exceptional performance, degrading 100 % of 8 µM sulfamethoxazole (SMX) with a first-pseudo reaction rate of 1.275 min-1, and achieving 5.3-log inactivation of Escherichia coli (E. coli) within 3 min at a PAA dosage of 0.2 mM and catalyst dosage of 0.025 g/L (initial pH 6.5). Scavenging experiments and electron paramagnetic resonance (EPR) analysis identify CH3C(O)O• and CH3C(O)OO• as the dominant reactive species for SMX degradation. The sulfur species in SCFO-0.3 facilitate Co2+ regeneration and regulate charge transfer, promoting PAA activation for SMX degradation. Moreover, the PAA/SCFO-0.3 system demonstrates operational feasibility over a broad range of water matrices and has excellent stability and reusability (maintaining 93 % removal of SMX after 5 cycles), demonstrating its potential for industrial applications. This study provides insights into enhancing PAA activation through sulfur doping in transition metal catalysts and highlights the practical applicability of the PAA/SCFO-0.3 system as an advanced alternative to conventional disinfection for simultaneous decontamination and disinfection in wastewater.

Metagenomic analysis of gut microbiome illuminates the mechanisms and evolution of lignocellulose degradation in mangrove herbivorous crabs.

BACKGROUND: Sesarmid crabs dominate mangrove habitats as the major primary consumers, which facilitates the trophic link and nutrient recycling in the ecosystem. Therefore, the adaptations and mechanisms of sesarmid crabs to herbivory are not only crucial to terrestrialization and its evolutionary success, but also to the healthy functioning of mangrove ecosystems. Although endogenous cellulase expressions were reported in crabs, it remains unknown if endogenous enzymes alone can complete the whole lignocellulolytic pathway, or if they also depend on the contribution from the intestinal microbiome. We attempt to investigate the role of gut symbiotic microbes of mangrove-feeding sesarmid crabs in plant digestion using a comparative metagenomic approach. RESULTS: Metagenomics analyses on 43 crab gut samples from 23 species of mangrove crabs with different dietary preferences revealed a wide coverage of 127 CAZy families and nine KOs targeting lignocellulose and their derivatives in all species analyzed, including predominantly carnivorous species, suggesting the crab gut microbiomes have lignocellulolytic capacity regardless of dietary preference. Microbial cellulase, hemicellulase and pectinase genes in herbivorous and detritivorous crabs were differentially more abundant when compared to omnivorous and carnivorous crabs, indicating the importance of gut symbionts in lignocellulose degradation and the enrichment of lignocellulolytic microbes in response to diet with higher lignocellulose content. Herbivorous and detritivorous crabs showed highly similar CAZyme composition despite dissimilarities in taxonomic profiles observed in both groups, suggesting a stronger selection force on gut microbiota by functional capacity than by taxonomy. The gut microbiota in herbivorous sesarmid crabs were also enriched with nitrogen reduction and fixation genes, implying possible roles of gut microbiota in supplementing nitrogen that is deficient in plant diet. CONCLUSIONS: Endosymbiotic microbes play an important role in lignocellulose degradation in most crab species. Their abundance is strongly correlated with dietary preference, and they are highly enriched in herbivorous sesarmids, thus enhancing their capacity in digesting mangrove leaves. Dietary preference is a stronger driver in determining the microbial CAZyme composition and taxonomic profile in the crab microbiome, resulting in functional redundancy of endosymbiotic microbes. Our results showed that crabs implement a mixed mode of digestion utilizing both endogenous and microbial enzymes in lignocellulose degradation, as observed in most of the more advanced herbivorous invertebrates.

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma.

Background: The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients. The heterogeneity of the malignant cells in pathway functions, transcription factors (TFs) regulation, overall survival, stemness, as well as ligand-receptor-based intercellular communication with macrophages were characterized. The aggressive and stemness feature for the target tumor subclone was validated by the conduction of in vitro assays including sphere formation, proliferation, Annexin V apoptosis, flow cytometry, siRNA library screening assays, and multiple in vivo preclinical mouse models including mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection. Results: Our analysis yielded a comprehensive atlas of 31,664 cells, revealing a diverse array of malignant cell subpopulations. Notably, we identified a stemness-related subclone of HCC cells with concurrent upregulation of CD24, CD47, and ICAM1 expression that correlated with poorer overall survival. Functional characterization both in vitro and in vivo validated S100A11 as one of the top downstream mediators for tumor initiation and stemness maintenance of this subclone. Further investigation of cell-cell communication within the tumor microenvironment revealed a propensity for bi-directional crosstalk between this stemness-related subclone and tumor-associated macrophages (TAMs). Co-culture study showed that this interaction resulted in the maintenance of the expression of cancer stem cell markers and driving M2-like TAM polarization towards a pro-tumorigenic niche. We also consolidated an inverse relationship between the proportions of TAMs and tumor-infiltrating T cells. Conclusions: Our study highlighted the critical role of stemness-related cancer cell populations in driving an immunosuppressive tumor microenvironment and identified the S100A11 gene as a key mediator for stemness maintenance in HCC. Moreover, our study provides support that the maintenance of cancer stemness is more attributed to M2 polarization than the recruitment of the TAMs.

Selective electrocatalytic transformation of highly toxic phenols in wastewater to para-benzoquinone at ambient conditions.

The selective transformation of organics from wastewater to value-added chemicals is considered an upcycling process beneficial for carbon neutrality. Herein, we present an innovative electrocatalytic oxidation (ECO) system aimed at achieving the selective conversion of phenols in wastewater to para-benzoquinone (p-BQ), a valuable chemical widely utilized in the manufacturing and chemical industries. Notably, 96.4% of phenol abatement and 78.9% of p-BQ yield are synchronously obtained over a preferred carbon cloth-supported ruthenium nanoparticles (Ru/C) anode. Such unprecedented results stem from the weak Ru-O bond between the Ru active sites and generated p-BQ, which facilitates the desorption of p-BQ from the anode surface. This property not only prevents the excessive oxidation of the generated p-BQ but also reinstates the Ru active sites essential for the rapid ECO of phenol. Furthermore, this ECO system operates at ambient conditions and obviates the need for potent chemical oxidants, establishing a sustainable avenue for p-BQ production. Importantly, the system efficacy can be adaptable in actual phenol-containing coking wastewater, highlighting its potential practical application prospect. As a proof of concept, we construct an electrified Ru/C membrane for ECO of phenol, attaining phenol removal of 95.8% coupled with p-BQ selectivity of 73.1%, which demonstrates the feasibility of the ECO system in a scalable flow-through operation mode. This work provides a promising ECO strategy for realizing both phenols removal and valuable organics recovery from phenolic wastewater.

A freshwater algae classification system based on machine learning with StyleGAN2-ADA augmentation for limited and imbalanced datasets.

Automated algae classification using machine learning is a more efficient and effective solution compared to manual classification, which can be tedious and time-consuming. However, the practical application of such a classification approach is restricted by the scarcity of labeled freshwater algae datasets, especially for rarer algae. To overcome these challenges, this study proposes to generate artificial algal images with StyleGAN2-ADA and use both the generated and real images to train machine-learning-driven algae classification models. This approach significantly enhances the performance of classification models, particularly in their ability to identify rare algae. Overall, the proposed approach improves the F1-score of lightweight MobileNetV3 classification models covering all 20 freshwater algae covered in this research from 88.4% to 96.2%, while for the models that cover only the rarer algae, the experiments show an improvement from 80% to 96.5% in terms of F1-score. The results show that the approach enables the trained algae classification systems to effectively cover algae with limited image data.

Directional Separation of Highly Reductive Electrons to the Reactive Center in a Magnetic S-Scheme ZnFe2O4/A-MoS2 Heterojunction for Enhanced Peroxymonosulfate Activation toward Pharmaceuticals and Personal Care Product Removal.

Pharmaceuticals and personal care products (PPCPs) are ubiquitous in sewage, adversely affecting ecosystems and human health. In this study, an S-scheme magnetic ZnFe2O4/ammoniated MoS2 (ZnFe2O4/A-MoS2) heterojunction as a visible-light-driven PMS activator for PPCP degradation was developed. ZnFe2O4/A-MoS2 achieves improved photocatalytic activity because the construction of S-scheme heterojunction promotes the separation of the highly reductive photogenerated electrons. The optimized photocatalyst (10%-ZnFe2O4/A-MoS2, 0.2 g/L) achieved 100% removal of 2 ppm carbamazepine (CBZ) within 2.5 min at a PMS dosage of 0.5 mM (initial pH 7.0). Mechanistic investigation revealed that the separated electrons to the ZnFe2O4 reactive center of the heterojunction facilitated PMS activation and generated SO4·- as the dominant reactive species for CBZ degradation. The system exhibited excellent practicability in various samples of actual sewage, where most sewage components negatively impacted CBZ degradation. Further, the chloride ions in high-salinity sewage could be activated to generate additional reactive chlorine species for PPCP degradation. The heterojunction possesses outstanding reusability and stability in treating various water conditions. This work provides mechanistic and practical perspectives in developing novel S-type heterojunctions for recalcitrant pollutant treatment.

Solar-driven photocatalytic chlorine activation for the simultaneous degradation of pharmaceuticals and personal care products and the inactivation of Escherichia coli in drinking water.

Removal of pharmaceuticals and personal care products (PPCPs) is often inefficient during conventional water treatment, posing threats to human health. Herein, we have developed a novel solar/TiO2/chlorine system upgraded from chlorine disinfection for the simultaneous degradation of PPCPs and the inactivation of Escherichia coli from drinking water. The addition of 100 µM of chlorine to the photocatalytic process considerably enhanced the degradation efficiency of PPCPs and demonstrated excellent disinfecting abilities, as confirmed by a 4.7 × increase in the carbamazepine degradation rate constant coupled with a 3.2-log (99.94%) reduction of E. coli cells within 1 min. Photoinduced charge pairs (hVB+ and eCB-) were identified for reactive species generation, and HO• and ClO• were the primary contributors to PPCPs degradation. The process exhibited satisfactory carbamazepine degradation efficiency in different water matrices and the cycling tests showed the TiO2 photocatalyst to be highly stable and reusable. Overall, our solar/TiO2/chlorine system is a potentially effective alternative to conventional drinking water treatment using chlorination.

Integrating Reactive Chlorine Species Generation with H2 Evolution in a Multifunctional Photoelectrochemical System for Low Operational Carbon Emissions Saline Sewage Treatment.

Conventional wastewater treatment plants (WWTPs) suffer from high carbon emissions and are inefficient in removing emerging organic pollutants (EOPs). Consequently, we have developed a low operational carbon emissions multifunctional photoelectrochemical (PEC) system for saline sewage treatment to simultaneously remove organic pollutants, ammonia, and bacteria, coupled with H2 evolution. A reduced BiVO4 (r-BiVO4) photoanode with enhanced PEC properties, ascribed to constructing sufficient oxygen vacancies and V4+ species, was synthesized for the aforementioned technique. The PEC/r-BiVO4 process could treat saline sewage to meet local WWTPs' discharge standard in 40 min at 2.0 V vs Ag/AgCl and completely degrade carbamazepine (one of EOPs), coupled with 633 µmol of H2 production; 93.29% reduction in operational carbon emissions and 77.82% decrease in direct emissions were achieved by the PEC/r-BiVO4 process compared with large-scale WWTPs, attributed to the restrained generation of CH4 and N2O. The PEC system activated chloride ions in sewage to generate numerous reactive chlorine species and facilitate •OH production, promoting contaminants removal. The PEC system exhibited operational feasibility at varying pH and total suspended solids concentrations and has outstanding reusability and stability, confirming its promising practical potential. This study proposed a novel PEC reaction for reducing operational carbon emissions from saline sewage treatment.

Two-Dimensional Modeling of Nano Zero-Valent Iron Transport and Retention before and after Phosphate Adsorption.

The mobility of nano zero-valent iron (nZVI) will greatly affect its practical application as a remediation material for contaminated groundwater. One-dimensional (1D) column tests are commonly used in previous work to study its migration behavior, but the two-dimensional (2D) test is still very limited. This study reports a novel research system to study the 2D transport and retention behavior of colloids and solutes, which includes a 2D model test setup and the corresponding image analysis method. The transport behaviors of methyl orange (MO), nZVI, and phosphate-loaded nZVI (PnZVI) are studied using this system. The results show that the research system can reasonably describe the tempo-spatial concentration distribution of colloids and solutes. After phosphate adsorption, the mobility of nZVI is enhanced due to the increase in negative surface charge, which implies a potential environmental risk of nZVI to facilitate contaminant transport. The migration of PnZVI is not significantly influenced by its density, which is faster than MO in the longitudinal direction. The range of the plume of PnZVI in the longitudinal direction is larger than that of MO, which implies that PnZVI has a stronger longitudinal dispersion than MO.

Post-Global Pandemic Challenges and improvements in advanced detection and removal processes of toxic pollutants: Editorial.

Every two years, the Pollutant Toxic Ions and Molecules Conference, PTIM, meets the environmentalist, biologist, chemists and health researchers in Costa de Caparica, Portugal, to showcase the latest technologies, methodologies and research advances in pollution detection, contamination control, remediation, and related health issues, as well as policy implications.

Dual-function hydrogel composite for post-electroplating cationic and anionic metal removal: A practicality study.

Metals produced as by-products of the electroplating process pose threats to both human and environmental health, so it is important that they are removed from electroplating effluents. In this study, a dual-function hydrogel composite, prepared from a pair of cationic and anionic hydrogel composites via a facile method, was tested in batch and in a fluidized-bed column to treat a simulated electroplating effluent. For the batch treatment, both adsorption and desorption reached equilibrium within 30 min, showing the dual-function composite's fast adsorption capacity. Additionally, the removal efficiency was found to be pH-independent, and insignificant effect was found in the co-presence of monovalent ions (up to 10 meq L-1). Reusability of the dual-function composite was tested for six cycles, where the treated effluent consistently met discharge standards, and the reused adsorbent was confirmed by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy to be highly stable. The fast settling by gravity of the dual-function composite in batch motivated further studies of the material in a fluidized-bed column. Process variables such as feed flow, airflow, and adsorbent's bed depth were optimized using response surface methodology (RSM). Using an optimal solution, the model predicted a treatable cationic volume of 1045 mL and an anionic volume of 1695 mL; their corresponding experimental values were 1028 and 1680 mL. Therefore, in terms of practicality (fast removal, pH-independence, high stability, and gravity-driven settling), the application of the dual-function composite in a fluidized-bed reactor has shown much promise for the simultaneous removal of post-electroplating cationic and anionic metals.

Different responses of gram-negative and gram-positive bacteria to photocatalytic disinfection using solar-light-driven magnetic TiO2-based material, and disinfection of real sewage.

A solar-light-driven magnetic photocatalyst, reduced-graphene-oxide/Fe,N-TiO2/Fe3O4@SiO2 (RGOFeNTFS), was developed for the photocatalytic disinfection of different strains of bacteria: gram-negative Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), and gram-positive Enterococcus faecalis (E. faecalis). The different responses of the bacteria during the reaction were investigated. Gram-positive E. faecalis was found to be more susceptible to photocatalytic disinfection and exhibited a higher leakage of intracellular components than the two gram-negative bacteria. The interactions between the bacteria and RGOFeNTFS were analyzed for Zeta potential, hydrophilicity and SEM. Under the experimental conditions, the opposite surface charges of the bacteria (negative Zeta potential) and RGOFeNTFS (positive Zeta potential) contribute to their interactions. With a more negative Zeta potential (than E. coli and E. faecalis), S. typhimurium interacts more strongly with RGOFeNTFS and is mainly attacked by •OH near the photocatalyst surface. E. coli and E. faecalis (with less negative Zeta potentials) interact less strongly with RGOFeNTFS, and compete for the dominant reactive species (•O2-) in the bulk solution. Therefore, the co-existence of bacteria significantly inhibits the photocatalytic disinfection of E. coli and E. faecalis, but insignificantly for S. typhimurium. Moreover, photocatalytic disinfection using RGOFeNTFS show potential for treating real sewage, which meets the local discharge standard (of E. coli) after a 60-min reaction. In real sewage, different bacteria are disinfected simultaneously.

N-doped graphitic C3N4 nanosheets decorated with CoP nanoparticles: A highly efficient activator in singlet oxygen dominated visible-light-driven peroxymonosulfate activation for degradation of pharmaceuticals and personal care products.

CoP nanoparticle-loaded N-doped graphitic C3N4 nanosheets (CoP/N-g-C3N4) were fabricated via a facile three-step method to degrade pharmaceuticals and personal care products (PPCPs) via a visible-light-driven (VLD) peroxymonosulfate (PMS) activation system. 2 ppm carbamazepine (CBZ) can be removed completely within 10 min by the VLD-PMS system with a kinetic constant of k = 0.29128 min-1, as 25.8 times compared to that under dark conditions (k = 0.01128 min-1). The experimental and theoretical results showed that the doped graphitic N atoms could modulate the electronic properties of the g-C3N4 nanosheets. Subsequently, the Density Functional Theory (DFT) explained that CoP showed preference to bonding with the nitrogen atoms involved in the newly formed NË­N bond, and the Co‒N bond dramatically enhanced the transfer of photo-generated electrons from the N-g-C3N4 nanosheets. Electron paramagnetic resonance (EPR) tests show that singlet oxygen (1O2) plays a leading role in this case. Moreover, PMS molecules are also tended to be absorbed onto the electron-deficient carbon atoms near the newly formed NË­N bonds for PMS reduction, synergistically enhancing the degradation efficiency for CBZ and benzophenone-3 (BZP). The newly established VLD-PMS activation system was shown to treat the actual sewage in Hong Kong sewage treatment plants (STPs) very well. This work supplements the fundamental theory of radical and non-radical pathways in the sulfate radical (SO4•-)-based advanced oxidation process (SR-AOP) for environmental cleanup purposes.

Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma.

Interaction between tumor cells and immune cells in the tumor microenvironment is important in cancer development. Immune cells interact with the tumor cells to shape this process. Here, we use single-cell RNA sequencing analysis to delineate the immune landscape and tumor heterogeneity in a cohort of patients with HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress tumor T cell infiltration and TIGIT-NECTIN2 interaction regulates the immunosuppressive environment. The cell state transition of immune cells towards a more immunosuppressive and exhaustive status exemplifies the overall cancer-promoting immunocellular landscape. Furthermore, the heterogeneity of global molecular profiles reveals co-existence of intra-tumoral and inter-tumoral heterogeneity, but is more apparent in the latter. This analysis of the immunosuppressive landscape and intercellular interactions provides mechanistic information for the design of efficacious immune-oncology treatments in hepatocellular carcinoma.

Scaled-up development of magnetically recyclable Fe3O4/La(OH)3 composite for river water phosphate removal: From bench-scale to pilot-scale study.

The use of magnetic lanthanum-based materials for phosphate removal from river water has gained increasing attention. However, challenges to produce and use lanthanum-based materials in large-scale or pilot-scale studies remain. In this work, a kilogram-scale Fe3O4/La(OH)3 magnetically recyclable composite for removing phosphate from river water was developed through a low-temperature precipitation route. The composite was used to remove phosphate from river water at both bench- and pilot-scales. Based on the bench-scale tests, the developed Fe3O4/La(OH)3 composite was found to have excellent magnetic particle separation efficiency (>98%) and a sorption capacity of 11.77 mg/g for phosphate. A 1.0 g/L dosage of the composite in the river water sample was able to selectively reduce the phosphate level from 0.089 to 0.005 mg/L in 60 min over five consecutive adsorption cycles. At the pilot-scale, the Fe3O4/La(OH)3 composite only achieved 36.0% phosphate removal efficiency, which is considerably different from the bench-scale results over an operational time of five months and a total treatment volume of 300 m3. This significantly reduced removal efficiency is mainly attributable to turbidity, suspended solids, and organic matter in the river water and the deteriorated magnetic separation efficiency. This study revealed potential challenges and shed new insights on moving magnetic nanocomposite-based technology from the bench-scale to the pilot-scale, which can inspire new designs for the application of similar technology.

Visible-light-driven peroxymonosulfate activation in photo-electrocatalytic system using hollow-structured Pt@CeO2@MoS2 photoanode for the degradation of pharmaceuticals and personal care products.

In this study, we constructed an innovative photo-electrocatalysis-assisted peroxymonosulfate (PEC/PMS) system to degrade pharmaceuticals and personal care products (PPCPs). A hollow-structured photoanode (i.e., Pt@CeO2@MoS2) was specifically synthesized as a photoanode to activate PMS in the PEC system. As proof of concept, the Pt@CeO2@MoS2 photoanode exhibited superior degradation performance toward carbamazepine (CBZ) with PMS assistance. Specifically, the kinetic constant of PEC/PMS (k = 0.13202 min-1) could be enhanced about 87.4 times compared to that of the PEC system (0.00151 min-1) alone. The PMS activation mechanism revealed that the synergistic effect between the hollow material and the change of surface valence states (Ce3+ to Ce4+) and (Mo4+ to Mo6+) contribute to enhancing the degradation efficiency of the visible-light-driven PEC/PMS process. The scavenger testing and EPR showed that 1O2, O2•-, SO4•- and •OH play dominant roles in the SR-AOPs. Furthermore, the applicability of Pt@CeO2@MoS2 used in SR-AOPs was systematically investigated regarding of the reaction parameters and identification of intermediates and dominant radicals as well as the mineralization rate and stability. The outcomes of this study can provide a new platform for environmental remediation.

Critical review of photocatalytic disinfection of bacteria: from noble metals- and carbon nanomaterials-TiO2 composites to challenges of water characteristics and strategic solutions.

This critical review covers ways to improve TiO2-based photocatalysts, how water characteristics may affect photocatalytic disinfection, and strategies to tackle the challenges arising from water characteristics. Photocatalysis has shown much promise in the disinfection of water/wastewater, because photocatalysis does not produce toxic by-products, and is driven by green solar energy. There are however several drawbacks that are curbing the prevalence of photocatalytic disinfection applications: one, the efficiency of photocatalysts may limit popular utilization; two, the water characteristics may present some challenges to the process. TiO2-based photocatalysts may be readily improved if composited with noble metals or carbon nanomaterials. Noble metals give TiO2-based composites a higher affinity for dissolved oxygen, and induce plasmonic and Schottky effects in the TiO2; carbon nanomaterials with a tunable structure, on the other hand, give the composites an improved charge carrier separation performance. Other than photocatalyst materials, the characteristics of water/wastewater is another crucial factor in the photocatalysis process. Also examined in this review are the crucial impacts that water characteristics have on photocatalysts and their interaction with bacteria. Accordingly, strategies to address the challenge of water characteristics on photocatalytic disinfection are explored: one, to modify the semiconductor conduction band to generate long-lifetime reactive species; two, to improve the interaction between bacteria and photocatalysts.

Hepatitis B Virus-Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear. APPROACH AND RESULTS: We adopted a targeted sequencing strategy to survey HBV integrations in human HBV-associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients' HCCs. Furthermore, we performed array-based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis-activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere-forming ability in HCC cells. CONCLUSIONS: Our results reveal a cis-activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV-integrated HCCs may achieve TERT activation in hepatocarcinogenesis.