LSM12 and ME31B/DDX6 Define Distinct Modes of Posttranscriptional Regulation by ATAXIN-2 Protein Complex in Drosophila Circadian Pacemaker Neurons.

ATAXIN-2 (ATX2) has been implicated in human neurodegenerative diseases, yet it remains elusive how ATX2 assembles specific protein complexes to execute its physiological roles. Here we employ the posttranscriptional co-activator function of Drosophila ATX2 to demonstrate that LSM12 and ME31B/DDX6 are two ATX2-associating factors crucial for sustaining circadian rhythms. LSM12 acts as a molecular adaptor for the recruitment of TWENTY-FOUR (TYF) to ATX2. The ATX2-LSM12-TYF complex thereby stimulates TYF-dependent translation of the rate-limiting clock gene period (per) to maintain 24 hr periodicity in circadian behaviors. In contrast, ATX2 contributes to NOT1-mediated gene silencing and associates with NOT1 in a ME31B/DDX6-dependent manner. The ME31B/DDX6-NOT1 complex does not affect PER translation but supports high-amplitude behavioral rhythms along with ATX2, indicating a PER-independent clock function of ATX2. Taken together, these data suggest that the ATX2 complex may switch distinct modes of posttranscriptional regulation through its associating factors to control circadian clocks and ATX2-related physiology.

Development of an indirect ELISA system for diagnosis of porcine edema disease using recombinant modified Stx2e antigen.

AIM: This study aimed to develop a sensitive and specific recombinant antigen protein indirect enzyme-linked immunosorbent assay (ELISA) kit to detect the Shiga toxin (Stx)-producing Escherichia coli (STEC) antibodies against porcine edema disease (ED). METHODS AND RESULTS: The recombinant antigen was co-expressed with the STEC-derived Stx2e A2-fragment and Stx2e B protein in E. coli BL21(DE3) pLysS cells and purified using maltose-binding protein open columns. We used a Shiga-like toxin 2 antibody to test the specificity of the recombinant antigen in an indirect ELISA, which was detected in antigen-coated wells but not in uncoated wells. We tested the indirect ELISA system using samples from the STEC-immunized pig group, the commercial swine farm group, and healthy aborted fetal pleural effusion group; five and twenty samples, respectively, were positive for STEC in the former, whereas all three samples were negative for STEC in the latter. CONCLUSIONS: This newly developed indirect ELISA may be a specific method for diagnosing STEC infections in pigs.

Temperature-Dependent Molecular Evolution of Biochar-Derived Dissolved Black Carbon and Its Interaction Mechanism with Polyvinyl Chloride Microplastics.

Biochar-derived dissolved black carbon (DBC) molecules are dependent on the BC formation temperature and affect the fate of emerging contaminants in waters, such as polyvinyl chloride microplastic (MPPVC). However, the temperature-dependent evolution and MPPVC-interaction of DBC molecules remain unclear. Herein, we propose a novel DBC-MPPVC interaction mechanism by systematically interpreting heterogeneous correlations, sequential responses, and synergistic relationships of thousands of molecules and their linking functional groups. Two-dimensional correlation spectroscopy was proposed to combine Fourier transform-ion cyclotron resonance mass spectrometry and spectroscopic datasets. Increased temperature caused diverse DBC molecules and fluorophores, accompanied by molecular transformation from saturation/reduction to unsaturation/oxidation with high carbon oxidation states, especially for molecules with acidic functional groups. The temperature response of DBC molecules detected via negative-/positive-ion electrospray ionization sequentially occurred in unsaturated hydrocarbons → lignin-like → condensed aromatic → lipid-/aliphatic-/peptide-like → tannin-like → carbohydrate-like molecules. DBC molecular changes induced by temperature and MPPVC interaction were closely coordinated, with lignin-like molecules contributing the most to the interaction. Functional groups in DBC molecules with m/z < 500 showed a sequential MPPVC-interaction response of phenol/aromatic ether C-O, alkene C═C/amide C═O → polysaccharides C-O → alcohol/ether/carbohydrate C-O groups. These findings help to elucidate the critical role of DBCs in MP environmental behaviors.

TonEBP recognizes R-loops and initiates m6A RNA methylation for R-loop resolution.

R-loops are three-stranded, RNA-DNA hybrid, nucleic acid structures produced due to inappropriate processing of newly transcribed RNA or transcription-replication collision (TRC). Although R-loops are important for many cellular processes, their accumulation causes genomic instability and malignant diseases, so these structures are tightly regulated. It was recently reported that R-loop accumulation is resolved by methyltransferase-like 3 (METTL3)-mediated m6A RNA methylation under physiological conditions. However, it remains unclear how R-loops in the genome are recognized and induce resolution signals. Here, we demonstrate that tonicity-responsive enhancer binding protein (TonEBP) recognizes R-loops generated by DNA damaging agents such as ultraviolet (UV) or camptothecin (CPT). Single-molecule imaging and biochemical assays reveal that TonEBP preferentially binds a R-loop via both 3D collision and 1D diffusion along DNA in vitro. In addition, we find that TonEBP recruits METTL3 to R-loops through the Rel homology domain (RHD) for m6A RNA methylation. We also show that TonEBP recruits RNaseH1 to R-loops through a METTL3 interaction. Consistent with this, TonEBP or METTL3 depletion increases R-loops and reduces cell survival in the presence of UV or CPT. Collectively, our results reveal an R-loop resolution pathway by TonEBP and m6A RNA methylation by METTL3 and provide new insights into R-loop resolution processes.

Recent advances in g-C3N4-based photocatalysis for water treatment: Magnetic and floating photocatalysts, and applications of machine-learning techniques.

Over the past decade, there has been a substantial increase in research investigating the potential of graphitic carbon nitride (g-C3N4) for various environmental remediations. Renowned for its photocatalytic activity under visible light, g-C3N4 offers a promising solution for treating water pollutants. However, traditional g-C3N4-based photocatalysts have inherent drawbacks, creating a disparity between laboratory efficacy and real-world applications. A primary practical challenge is their fine-powdered form, which hinders separation and recycling processes. A promising approach to address these challenges involves integrating magnetic or floating materials into conventional photocatalysts, a strategy gaining traction within the g-C3N4-based photocatalyst arena. Another emerging solution to enhance practical applications entails merging experimental results with contemporary computational methods. This synergy seeks to optimize the synthesis of more efficient photocatalysts and pinpoint optimal conditions for pollutant removal. While numerous review articles discuss the laboratory-based photocatalytic applications of g-C3N4-based materials, there is a conspicuous absence of comprehensive coverage regarding state-of-the-art research on improved g-C3N4-based photocatalysts for practical applications. This review fills this void, spotlighting three pivotal domains: magnetic g-C3N4 photocatalysts, floating g-C3N4 photocatalysts, and the application of machine learning to g-C3N4 photocatalysis. Accompanied by a thorough analysis, this review also provides perspectives on future directions to enhance the efficacy of g-C3N4-based photocatalysts in water purification.

Oxoglaucine Suppresses Hepatic Fibrosis by Inhibiting TGFß-Induced Smad2 Phosphorylation and ROS Generation.

Hepatic fibrosis is the first stage of liver disease, and can progress to a chronic status, such as cirrhosis or hepatocellular carcinoma. Excessive production of extracellular matrix (ECM) components plays an important role in the development of fibrosis. Mechanistically, transforming growth factor beta (TGFß)-induced phosphorylation of Smad is thought to be a key signaling pathway in the development of liver fibrosis. Although the natural isoquinoline alkaloid oxoglaucine (1,2,9,10-tetramethoxy-7H-dibenzo(de,g)quinolin-7-one) exerts numerous beneficial effects, including anti-cancer, anti-inflammatory, and anti-osteoarthritic effects in diverse cell types, the effects of oxoglaucine on liver fibrosis and fibrogenic gene expression have not been fully elucidated. The aim of this study is to evaluate the signaling pathway and antifibrotic activity of isoquinoline alkaloid oxoglaucine in TFGß-induced hepatic fibrosis in vitro. Using Hepa1c1c7 cells and primary hepatocytes, we demonstrated that oxoglaucine treatment resulted in inhibition of the expression of fibrosis markers such as collagen, fibronectin, and alpha-SMA. Subsequent experiments showed that oxoglaucine suppressed TGFß-induced phosphorylation of Smad2 and reactive oxygen species (ROS) generation, without altering cell proliferation. We further determined that the increase in Smad7 by oxoglaucine treatment is responsible for the inhibition of Smad2 phosphorylation and the anti-fibrogenic effects. These findings indicate that oxoglaucine plays a crucial role in suppression of fibrosis in hepatocytes, thereby making it a potential drug candidate for treatment of liver fibrosis.

Effects of HAT-CN Layer Thickness on Molecular Orientation and Energy-Level Alignment with ZnPc.

Efficient energy-level alignment is crucial for achieving high performance in organic electronic devices. Because the electronic structure of an organic semiconductor is significantly influenced by its molecular orientation, comprehensively understanding the molecular orientation and electronic structure of the organic layer is essential. In this study, we investigated the interface between a 1,4,5,8,9,11-hexaazatriphenylene hexacarbonitrile (HAT-CN) hole injection layer and a zinc-phthalocyanine (ZnPc) p-type organic semiconductor. To determine the energy-level alignment and molecular orientation, we conducted in situ ultraviolet and X-ray photoelectron spectroscopies, as well as angle-resolved X-ray absorption spectroscopy. We found that the HAT-CN molecules were oriented relatively face-on (40°) in the thin (5 nm) layer, whereas they were oriented relatively edge-on (62°) in the thick (100 nm) layer. By contrast, ZnPc orientation was not significantly altered by the underlying HAT-CN orientation. The highest occupied molecular orbital (HOMO) level of ZnPc was closer to the Fermi level on the 100 nm thick HAT-CN layer than on the 5 nm thick HAT-CN layer because of the higher work function. Consequently, a considerably low energy gap between the lowest unoccupied molecular orbital level of HAT-CN and the HOMO level of ZnPc was formed in the 100 nm thick HAT-CN case. This may improve the hole injection ability of the anode system, which can be utilized in various electronic devices.

White-light emission in Yb3+/Er3+/Tm3+- and Yb3+/Er3+/Tm3+/Ho3+-dopedα-NiMoO4nanoparticles.

Yb3+/Er3+/Tm3+- and Yb3+/Er3+/Tm3+/Ho3+-dopedα-NiMoO4nanoparticles were synthesized using a microwave hydrothermal method and studied for white-light emission under 980 nm laser diode excitation. White upconversion (UC) light was successfully obtained with the appropriate control of blue, green, and red emissions by successfully tuning the Er3+and Ho3+concentrations in Yb3+/Er3+/Tm3+- and Yb3+/Er3+/Tm3+/Ho3+-dopedα-NiMoO4, respectively. In addition, the white color emission was shown by the CIE chromaticity coordinates of samples. The energy transfer mechanisms are explained in detail based on the emission spectra and pump power density-dependent UC luminescence intensity in rare earth (Yb3+/Er3+/Tm3+and Yb3+/Er3+/Tm3+/Ho3+)-dopedα-NiMoO4nanoparticles. The results indicate that Yb3+/Er3+/Tm3+- and Yb3+/Er3+/Tm3+/Ho3+-dopedα-NiMoO4nanoparticles can be good candidates for white-light devices.

Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening.

Endocrine-disrupting potential was evaluated during the sewage treatment process using in vitro bioassays. Aryl hydrocarbon receptor (AhR)-, androgen receptor (AR)-, glucocorticoid receptor (GR)-, and estrogen receptor (ER)-mediated activities were assessed over five steps of the treatment process. Bioassays of organic extracts showed that AhR, AR, and GR potencies tended to decrease through the sewage treatment process, whereas ER potencies did not significantly decrease. Bioassays on reverse-phase high-performance liquid chromatography fractions showed that F5 (log KOW 2.5-3.0) had great ER potencies. Full-scan screening of these fractions detected two novel ER agonists, arenobufagin and loratadine, which are used pharmaceuticals. These compounds accounted for 3.3-25% of the total ER potencies and 4% of the ER potencies in the final effluent. The well-known ER agonists, estrone and 17ß-estradiol, accounted for 60 and 17% of the ER potencies in F5 of the influent and primary treatment, respectively. Fourier transform ion cyclotron resonance mass spectrometry analysis showed that various molecules were generated during the treatment process, especially CHO and CHOS (C: carbon, H: hydrogen, O: oxygen, and S: sulfur). This study documented that widely used pharmaceuticals are introduced into the aquatic environments without being removed during the sewage treatment process.

The Efficacy of Atelocollagen to Inhibit Fibrotic Proliferation in Tenon Tissue: in vitro study.

INTRODUCTION: To evaluate the safety and efficacy of atelocollagen in preventing the fibrotic change of human tenon tissue induced by transforming growth factor ß1 (TGFß1) Methods: Primary cultured human Tenon's fibroblasts (HTFs) were incubated with TGFß1 alone, and with a various concentrations of atelocollagen respectively. Cell viability was measured by cell counting kit-8 (CCK8). The mRNA levels of α-smooth muscle actin (α-SMA), vimentin, fibronectin, zonular occludens scaffolding protein (ZO-1), cellular communication network factor 2 (CCN2) and interleukin-6 (IL-6) were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR), western blot and immunofluorescence analysis. Wound healing assay and collagen contraction assay were additionally evaluated for identifying the inhibitory effect of atelocollagen in HTFs. To elucidate the mechanism by which atelocollagen affects HTFs proliferation, the phospho-extracellular-signal-regulated kinases (pERK)/total-extracellular-signal-regulated kinases (tERK), phospho-focal adhesion kinase (pFAK)/total-focal adhesion kinase (tFAK), and pSmad3/tSmad3 protein expression ratios were measured by Western blot. RESULTS: The safety of atelocollagen in HTF was identified by CCK8 analysis. The expression of α-SMA and vimentin in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased at both mRNA and protein levels, while that of ZO-1 in 0.046% atelocollagen increased compared with TGFß1-treated cells. The protein expression of fibronectin, CCN2, and IL-6 in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased. Immunofluorescence microscopy of α-SMA and ZO-1 showed results similar to those of the western blot. In the wound scratch assays, cell migration was significantly attenuated in HTFs treated with 0.005% atelocollagen. Atelocollagen at 0.005, 0.011, and 0.023% significantly inhibited the gel contraction induced by TGFß1 at both 24 h and 48 h. The increase in pERK/tERK and pSmad3/tSmad3 protein expression ratios in TGFß1-treated HTFs significantly decreased after treatment with 0.023 and 0.046% atelocollagen. CONCLUSION: Since atelocollagen gel effectively suppresses the proliferation of HTFs in TGFß1 - induced transdifferentiation, it may be a potential therapeutic agent in glaucoma surgery.

Coronary CT Angiography CAD-RADS versus Coronary Artery Calcium Score in Patients with Acute Chest Pain.

Background The Coronary Artery Disease Reporting and Data System (CAD-RADS) was established in 2016 to standardize the reporting of coronary artery disease at coronary CT angiography (CCTA). Purpose To assess the prognostic value of CAD-RADS at CCTA for major adverse cardiovascular events (MACEs) in patients presenting to the emergency department with chest pain. Materials and Methods This multicenter retrospective observational cohort study was conducted at four qualifying university teaching hospitals. Patients presenting to the emergency department with acute chest pain underwent CCTA between January 2010 and December 2017. Multivariable Cox regression analysis was used to evaluate risk factors for MACEs, including clinical factors, coronary artery calcium score (CACS), and CAD-RADS categories. The prognostic value compared with clinical risk factors and CACS was also assessed. Results A total of 1492 patients were evaluated (mean age, 58 years ± 14 years [standard deviation]; 759 men). During a median follow-up period of 31.5 months, 103 of the 1492 patients (7%) experienced MACEs. Multivariable Cox regression analysis showed that a moderate to severe CACS was associated with MACEs after adjusting for clinical risk factors (hazard ratio [HR] range, 2.3-4.4; P value range, <.001 to <.01). CAD-RADS categories from 3 to 4 or 5 (HR range, 3.2-8.5; P < .001) and high-risk plaques (HR = 3.6, P < .001) were also associated with MACEs. The C statistics revealed that the CAD-RADS score improved risk stratification more than that using clinical risk factors alone or combined with CACS (C-index, 0.85 vs 0.63 [P < .001] and 0.76 [P < .01], respectively). Conclusion The Coronary Artery Disease Reporting and Data System classification had an incremental prognostic value compared with the coronary artery calcium score in the prediction of major adverse cardiovascular events in patients presenting to the emergency department with acute chest pain. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vliegenthart in this issue.

Interferon-γ inhibits retinal neovascularization in a mouse model of ischemic retinopathy.

Interferon-γ (IFNG) is one of the key cytokines that regulates both innate and adaptive immune responses in the body. However, the role of IFNG in the regulation of vascularization, especially in the context of Vascular endothelial growth factor A (VEGFa)-induced angiogenesis is not clarified. Here, we report that IFNG shows potent anti-angiogenic potential against VEGFa-induced angiogenesis. IFNG significantly inhibited proliferation, migration, and tube formation of Human umbilical vein endothelial cells (HUVECs) both under basal and VEGFa-treated conditions. Intriguingly, Knockdown (KD) of STAT1 abolished the inhibitory effect of IFNG on VEGFa-induced angiogenic processes in HUVECs. Furthermore, IFNG exhibited potent anti-angiogenic efficacy in the mouse model of oxygen-induced retinopathy (OIR), an in vivo model for hypoxia-induced retinal neovascularization, without induction of functional side effects. Taken together, these results show that IFNG plays a crucial role in the regulation of VEGFa-dependent angiogenesis, suggesting its potential therapeutic applicability in neovascular diseases.

Ultrahigh-field cardiovascular magnetic resonance T1 and T2 mapping for the assessment of anthracycline-induced cardiotoxicity in rat models: validation against histopathologic changes.

BACKGROUND: Chemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity. METHODS: Rat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed. RESULTS: Five control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01).  Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores) CONCLUSIONS: Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.

Serial T1 mapping of right ventricle in pulmonary hypertension: comparison with histology in an animal study.

BACKGROUND: Right ventricular (RV) free wall fibrosis is an important component of adverse remodeling with RV dysfunction in pulmonary hypertension (PH). However, no previous reports have compared cardiovascular magnetic resonance (CMR) findings and histological analysis for RV free wall fibrosis in PH. We aimed to assess the feasibility of CMR T1 mapping with extracellular volume fraction (ECV) for evaluating the progression of RV free wall fibrosis in PH, and compared imaging findings to histological collagen density through an animal study. METHODS: Among 42 6-week-old Wistar male rats, 30 were classified according to disease duration (baseline before monocrotaline injection, and 2, 4, 6 and 8 weeks after injection) and 12 were used to control for aging (4 and 8 weeks after the baseline). We obtained pre and post-contrast T1 maps for native T1 and ECV of RV and left ventricular (LV) free wall for six animals in each disease-duration group. Collagen density of RV free wall was calculated with Masson's trichrome staining. The Kruskall-Wallis test was performed to compare the groups. Native T1 and ECV to collagen density were analyzed with Spearman's correlation. RESULTS: The mean values of native T1, ECV and collagen density of the RV free wall at baseline were 1541 ± 33 ms, 17.2 ± 1.3%, and 4.7 ± 0.5%, respectively. The values of RV free wall did not differ according to aging (P = 0.244, 0.504 and 0.331, respectively). However, the values significantly increased according to disease duration (P < 0.001 for all). Significant correlations were observed between native T1 and collagen density (r = 0.770, P < 0.001), and between ECV and collagen density for the RV free wall (r = 0.815, P < 0.001) in PH. However, there was no significant difference in native T1 and ECV values for the LV free wall according to the disease duration from the baseline (P = 0.349 and 0.240, respectively). CONCLUSIONS: We observed significantly increased values for native T1 and ECV of the RV free wall without significant increase of the LV free wall according to the disease duration of PH, and findings were well correlated with histological collagen density.

Prognostic Value of Coronary Artery Disease-Reporting and Data System Score for Major Adverse Cardiac Events in Patients Attending the Emergency Department With Acute Chest Pain.

OBJECTIVE: This study aimed to compare the prognostic performance of Coronary Artery Disease (CAD)-Reporting and Data System (CAD-RADS) score with those of clinical risk factors and the extent of CAD classification for predicting major adverse cardiac events in emergency department patients. METHODS: A total of 779 patients with acute chest pain at low to intermediate risk for CAD underwent cardiac computed tomography angiography. The primary end point was early and late major adverse cardiac events. We developed the following models: model 1, clinical risk factors; model 2, clinical risk factors and CAD-RADS scores; model 3, clinical risk factors and extent of CAD. RESULTS: The C-statistics revealed that both CAD-RADS score and CAD extent improved risk stratification over the clinical risk factors (C-index for early events: C-index: 0.901 vs 0.814 and 0.911 vs 0.814; C-index for late events: 0.897 vs 0.808 and 0.905 vs 0.808; all P < 0.05). CONCLUSIONS: The CAD-RADS score had additional risk prediction benefits over clinical risk factors for emergency department patients.

Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans.

Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels. Our analysis revealed a mechanism of Orai gating by STIM binding to the intracellular 2-3 loop of Orai in C. elegans that is radically different from Orai gating by STIM binding to the N and C termini of Orai in mammals. In addition, we found that the conserved hydrophobic amino acids in the 2-3 loop of Orai1 are important for the oligomerization and gating of channels and are regulated via an intramolecular interaction mechanism mediated by the N and C termini of Orai1. This study identifies a previously unknown SOCE mechanism in C. elegans and suggests that, while the STIM-Orai interaction is conserved between invertebrates and mammals, the gating mechanism for Orai channels differs considerably.

Synergism of AZD6738, an ATR Inhibitor, in Combination with Belotecan, a Camptothecin Analogue, in Chemotherapy-Resistant Ovarian Cancer.

Epithelial ovarian cancer remains the leading cause of mortality among all gynecologic malignancies owing to recurrence and ultimate development of chemotherapy resistance in the majority of patients. In the chemotherapy-resistant ovarian cancer preclinical model, we investigated whether AZD6738 (an ataxia telangiectasia and Rad3-related (ATR) inhibitor) could synergize with belotecan (a camptothecin analog and topoisomerase I inhibitor). In vitro, both chemotherapy-resistant and chemotherapy-sensitive ovarian cancer cell lines showed synergistic anti-proliferative activity with a combination treatment of belotecan and AZD6738. The combination also demonstrated synergistic tumor inhibition in mice with a chemotherapy-resistant cell line xenograft. Mechanistically, belotecan, a DNA-damaging agent, increased phospho-ATR (pATR) and phospho-Chk1 (pChk1) in consecutive order, indicating the activation of the DNA repair system. This consequently induced G2/M arrest in the cell cycle analysis. However, when AZD6738 was added to belotecan, pATR and pChk1 induced by belotecan alone were suppressed again. A cell cycle analysis in betotecan showed a sub-G1 increase as well as a G2/M decrease, representing the release of G2/M arrest and the induction of apoptosis. In ascites-derived primary cancer cells from both chemotherapy-sensitive and -resistant ovarian cancer patients, this combination was also synergistic, providing further support for our hypothesis. The combined administration of ATR inhibitor and belotecan proved to be synergistic in our preclinical model. This combination warrants further investigation in a clinical trial, with a particular aim of overcoming chemotherapy resistance in ovarian cancer.

A critical review on modulation of NiMoO4-based materials for photocatalytic applications.

Semiconductor photocatalysis has been widely utilized to solve the problems of energy shortage and environmental pollution. Among the explored photocatalysts, nickel molybdate (NiMoO4) has revealed many advantages for photocatalytic applications, which include visible light absorption, low cost, environment-friendly, large surface area, good electrical conductivities, and tailorable band structure. However, the recombination of photogenerated carriers, which diminishes photocatalytic efficiency, has been held as a major hurdle to the widespread application of this material. To overcome this limitation, various surface modulations such as morphology control, doping of heteroatom, deposition of noble metal nanoparticles, and fabrication of composite structures have been explored in many published studies. This article comprehensively reviews the recent progress in the modulations of NiMoO4-based materials to improve the photocatalytic efficiency. The enhanced photocatalytic capabilities of NiMoO4-based materials are reviewed in terms of such applications as pollutant removal, disinfection of bacteria, and water splitting. The current challenges and possible future direction of research in this field are also highlighted. This comprehensive review is expected to advance the design of highly efficient NiMoO4-based materials for photocatalytic applications.

A critical review on strategies for improving efficiency of BaTiO3-based photocatalysts for wastewater treatment.

Barium titanate (BaTiO3) photocatalysts with perovskite structures are promising candidates for the effective removal of hazardous organic pollutants from water/wastewater owing to several advantages, including low cost, non-toxicity, high stability, environmental friendliness, favorable band positions, high oxygen vacancies, multiple crystal phases, rapid migration of charge carriers at the surface, band bending, spontaneous polarization, and easy tailoring of the sizes and morphologies. However, this high dielectric/ferroelectric material is only active in UV light (band gap: 3.2 eV), which reduces the photocatalytic degradation performance. To make barium titanate more suitable for photocatalysis, the surfaces of the powders can be modified to broaden the absorption band. In this paper, various strategies for improving photocatalysis of barium titanate for removing organic pollutants (mostly dyes and drugs) from water/wastewater are critically reviewed. They include modifying the sizes and morphologies of the particles by varying the reaction times and synthesis temperatures, doping with metals/non-metals, loading with noble metal NPs (Ag and Au), and fabrication of heterojunction photocatalysts (conventional type II and Z-scheme). The current challenges and possible future directions of BaTiO3-based materials are also discussed. This comprehensive review is expected to advance the design of highly efficient BaTiO3-based materials for photocatalytic applications in water/wastewater treatment.

Combined dual-size foam glass media filtration process with micro-flocculation for simultaneous removal of particulate and dissolved contaminants in urban road runoff.

In this study, a combined media filtration process with micro-flocculation (CMF) was developed, to simultaneously treat particulate and dissolved contaminants in urban road runoff. Dual-size foam glass media with stone and sand layers were applied and the efficiency of road runoff treatment was investigated according to filtration and micro-flocculation under various experimental conditions (stone/sand layer ratio, linear velocity, and coagulant types). Moreover, the removal efficiencies of suspended solids (SS), phosphorus, organic carbon, and heavy metals (Zn, Cu, Pb, Cd) by CMF were evaluated. The removal rate of SS was maintained to be above 84.1% for 1 h filtration by the dual-size foam glass, regardless of increasing pressure. The removal of phosphorus by micro-flocculation was more suitable in alum than ferric due to a higher initial floc growth rate and an increased particle size. The performance of the CMF was significantly improved over media filtration only process (MF) in removing both particulate and dissolved contaminants. The removal efficiency of all particulate pollutants by CMF was found to be more than 90%, and notably, the dissolved phosphorus, which was mostly not removed by MF, was also removed by 97.4%. Meanwhile, the backwash efficiency of CMF was half that of MF. Physical removal mechanisms, such as internal diffusion, dominated MF, whereas chemical removal mechanisms, such as adsorption and surface precipitation, dominated CMF. These results show the potential of the CMF process for the treatment of urban road runoff and identify the removal mechanisms of the filtration process that use micro-flocculation with dual-size foam glass.