CKAP5 stabilizes CENP-E at kinetochores by regulating microtubule-chromosome attachments.

Stabilization of microtubule plus end-directed kinesin CENP-E at the metaphase kinetochores is important for chromosome alignment, but its mechanism remains unclear. Here, we show that CKAP5, a conserved microtubule plus tip protein, regulates CENP-E at kinetochores in human cells. Depletion of CKAP5 impairs CENP-E localization at kinetochores at the metaphase plate and results in increased kinetochore-microtubule stability and attachment errors. Erroneous attachments are also supported by computational modeling. Analysis of CKAP5 knockout cancer cells of multiple tissue origins shows that CKAP5 is preferentially essential in aneuploid, chromosomally unstable cells, and the sensitivity to CKAP5 depletion is correlated to that of CENP-E depletion. CKAP5 depletion leads to reduction in CENP-E-BubR1 interaction and the interaction is rescued by TOG4-TOG5 domain of CKAP5. The same domain can rescue CKAP5 depletion-induced CENP-E removal from the kinetochores. Interestingly, CKAP5 depletion facilitates recruitment of PP1 to the kinetochores and furthermore, a PP1 target site-specific CENP-E phospho-mimicking mutant gets stabilized at kinetochores in the CKAP5-depleted cells. Together, the results support a model in which CKAP5 controls mitotic chromosome attachment errors by stabilizing CENP-E at kinetochores and by regulating stability of the kinetochore-attached microtubules.

Negligible radiological impact of Indian nuclear power plants on the environment and the public: Findings from a 20-year study.

Nuclear power plants, recognized for their extended operational life, minimal greenhouse gas emissions, and high-power density, are deemed as reliable energy sources. Nonetheless, concerns persist regarding the radioactive discharges from these plants and their potential impact on health and the environment. To comprehend the radiological implications of such releases, this study presents, for the first time, an analysis of radiological data from 7 Indian nuclear power plants (NPPs), collected by Indian environmental survey laboratories (ESL) over the past two decades (2000-2020). This dataset encompasses radioactivity concentrations in the atmospheric, aquatic, and terrestrial environments within a 30 km radius of each NPP, as well as the annual cumulative external gamma doses recorded by environmental thermoluminescence dosimeters (TLDs). The analysis yielded several key findings: (i) Radioactivity concentrations around the NPPs were low and comparable to values measured at other nuclear power plant sites worldwide; (ii) Tritium concentrations in receiving water bodies were <1 % of the internationally recommended limit of 10,000 Bq/l; (iii) The estimated total radiation doses to the public were at most 10 % of the stipulated regulatory dose limit of 1000 µSv and consistently decreased over the study period and (iv) Variations in doses among the NPP sites were primarily attributed to legacy technology used in specific reactors. These results indicate efficient and secure reactor operations and the minimal contribution of Indian nuclear power plants to anthropogenic doses in the country. The findings hold potential significance for reinforcing India's commitment to advancing its nuclear power program.

E3-ubiquitin ligase, FBXW7 regulates mitotic progression by targeting BubR1 for ubiquitin-mediated degradation.

Faithful chromosome segregation requires correct attachment of kinetochores with the spindle microtubules. Erroneously-attached kinetochores recruit proteins to activate Spindle assembly checkpoint (SAC), which senses the errors and signals cells to delay anaphase progression for error correction. Temporal control of the levels of SAC activating-proteins is critical for checkpoint activation and silencing, but its mechanism is not fully understood. Here, we show that E3 ubiquitin ligase, SCF-FBXW7 targets BubR1 for ubiquitin-mediated degradation and thereby controls SAC in human cells. Depletion of FBXW7 results in prolonged metaphase arrest with increased stabilization of BubR1 at kinetochores. Similar kinetochore stabilization is also observed for BubR1-interacting protein, CENP-E. FBXW7 induced ubiquitination of both BubR1 and the BubR1-interacting kinetochore-targeting domain of CENP-E, but CENP-E domain degradation is dependent on BubR1. Interestingly, Cdk1 inhibition disrupts FBXW7-mediated BubR1 targeting and further, phospho-resistant mutation of Cdk1-targeted phosphorylation site, Thr 620 impairs BubR1-FBXW7 interaction and FBXW7-mediated BubR1 ubiquitination, supporting its role as a phosphodegron for FBXW7. The results demonstrate SCF-FBXW7 as a key regulator of spindle assembly checkpoint that controls stability of BubR1 and its associated CENP-E at kinetochores. They also support that upstream Cdk1 specific BubR1 phosphorylation signals the ligase to activate the process.

MassSpecPreppy-An end-to-end solution for automated protein concentration determination and flexible sample digestion for proteomics applications.

In proteomics, fast, efficient, and highly reproducible sample preparation is of utmost importance, particularly in view of fast scanning mass spectrometers enabling analyses of large sample series. To address this need, we have developed the web application MassSpecPreppy that operates on the open science OT-2 liquid handling robot from Opentrons. This platform can prepare up to 96 samples at once, performing tasks like BCA protein concentration determination, sample digestion with normalization, reduction/alkylation and peptide elution into vials or loading specified peptide amounts onto Evotips in an automated and flexible manner. The performance of the developed workflows using MassSpecPreppy was compared with standard manual sample preparation workflows. The BCA assay experiments revealed an average recovery of 101.3% (SD: ± 7.82%) for the MassSpecPreppy workflow, while the manual workflow had a recovery of 96.3% (SD: ± 9.73%). The species mix used in the evaluation experiments showed that 94.5% of protein groups for OT-2 digestion and 95% for manual digestion passed the significance thresholds with comparable peptide level coefficient of variations. These results demonstrate that MassSpecPreppy is a versatile and scalable platform for automated sample preparation, producing injection-ready samples for proteomics research.

The role of point-of-care testing in cardiac arrest patients.

BACKGROUND: Point-of-care testing (POCT) provides real time information to the clinical team, leading to early diagnosis and treatment. Whether POCT plays a role in improving outcomes in patients with out of hospital cardiac arrest (OHCA) remains unknown. The objective of this study was to describe use of POCT in OHCA and to explore its association with outcomes. METHODS: We conducted a retrospective chart review on patients transferred by emergency medical services (EMS) to the ED for out-of-hospital cardiac arrest (OHCA) in 2019. Data collected from patient charts included baseline information, the Utstein criteria for cardiac arrest, whether POCT was used, whether POCT was abnormal, and what treatment was given, if any, as a result of the abnormal POCT. Outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge. Outcomes in patients with and without POCT were compared using chi-square and t-tests. RESULTS: There were 119 study patients. Their mean (SD) age was 65 (18) years and 65% were male. Cardiac arrest was witnessed in 48% and initial rhythm was asystole in 66%. The rates of ROSC and survival were 22.7% (95%CI, 16.1-31.1) and 3.4% (95%CI, 1.3-8.3). POCT was used in 66 patients (55.4%; 95%CI, 46.5-64.1) all of whom had at least one abnormality. The results of POCT led to administration of a therapy in 60 patients (91.0%; 95%CI, 81.6-95.8). The rates of ROSC in patients with and without POCT were 22.6% vs 22.7% respectively. The rates of survival to discharge in patients with and without POCT were 0% vs 3.8% respectively. CONCLUSIONS: POCT is commonly used in the ED for patients with OHCA and its results often lead to changes in therapies. However, use of POCT was not associated with ROSC or survival to discharge.

SigB modulates expression of novel SigB regulon members via Bc1009 in non-stressed and heat-stressed cells revealing its alternative roles in Bacillus cereus.

BACKGROUND: The Bacillus cereus Sigma B (SigB) dependent general stress response is activated via the two-component RsbKY system, which involves a phosphate transfer from RsbK to RsbY. It has been hypothesized that the Hpr-like phosphocarrier protein (Bc1009) encoded by bc1009 in the SigB gene cluster may play a role in this transfer, thereby acting as a regulator of SigB activation. Alternatively, Bc1009 may be involved in the activation of a subset of SigB regulon members. RESULTS: We first investigated the potential role of bc1009 to act as a SigB regulator but ruled out this possibility as the deletion of bc1009 did not affect the expression of sigB and other SigB gene cluster members. The SigB-dependent functions of Bc1009 were further examined in B. cereus ATCC14579 via comparative proteome profiling (backed up by transcriptomics) of wt, Δbc1009 and ΔsigB deletion mutants under heat stress at 42 °C. This revealed 284 proteins displaying SigB-dependent alterations in protein expression levels in heat-stressed cells, including a subgroup of 138 proteins for which alterations were also Bc1009-dependent. Next to proteins with roles in stress defense, newly identified SigB and Bc1009-dependent proteins have roles in cell motility, signal transduction, transcription, cell wall biogenesis, and amino acid transport and metabolism. Analysis of lethal stress survival at 50 °C after pre-adaptation at 42 °C showed intermediate survival efficacy of Δbc1009 cells, highest survival of wt, and lowest survival of ΔsigB cells, respectively. Additional comparative proteome analysis of non-stressed wt and mutant cells at 30 °C revealed 96 proteins with SigB and Bc1009-dependent differences in levels: 51 were also identified under heat stress, and 45 showed significant differential expression at 30 °C. This includes proteins with roles in carbohydrate/ion transport and metabolism. Overlapping functions at 30 °C and 42 °C included proteins involved in motility, and ΔsigB and Δbc1009 cells showed reduced motility compared to wt cells in swimming assays at both temperatures. CONCLUSION: Our results extend the B. cereus SigB regulon to > 300 members, with a novel role of SigB-dependent Bc1009 in the activation of a subregulon of  > 180 members, conceivably via interactions with other transcriptional regulatory networks.

Kinetochore-microtubule attachment in human cells is regulated by the interaction of a conserved motif of Ska1 with EB1.

The kinetochore establishes the linkage between chromosomes and the spindle microtubule plus ends during mitosis. In vertebrates, the spindle-kinetochore-associated (Ska1,2,3) complex stabilizes kinetochore attachment with the microtubule plus ends, but how Ska is recruited to and stabilized at the kinetochore-microtubule interface is not understood. Here, our results show that interaction of Ska1 with the general microtubule plus end-associated protein EB1 through a conserved motif regulates Ska recruitment to kinetochores in human cells. Ska1 forms a stable complex with EB1 via interaction with the motif in its N-terminal disordered loop region. Disruption of this interaction either by deleting or mutating the motif disrupts Ska complex recruitment to kinetochores and induces chromosome alignment defects, but it does not affect Ska complex assembly. Atomic-force microscopy imaging revealed that Ska1 is anchored to the C-terminal region of the EB1 dimer through its loop and thereby promotes formation of extended structures. Furthermore, our NMR data showed that the Ska1 motif binds to the residues in EB1 that are the binding sites of other plus end targeting proteins that are recruited to microtubules by EB1 through a similar conserved motif. Collectively, our results demonstrate that EB1-mediated Ska1 recruitment onto the microtubule serves as a general mechanism for the formation of vertebrate kinetochore-microtubule attachments and metaphase chromosome alignment.

Exploration of a library of piperonylic acid-derived hydrazones possessing variable aryl functionalities as potent dual cholinesterase and monoamine oxidase inhibitors.

A library of piperonylic acid-derived hydrazones possessing variable aryl moiety was synthesized and investigated for their multifunctional properties against cholinesterases (ChEs) and monoamine oxidases (MAOs). The in vitro enzymatic assay results revealed that the tested hydrazones have exhibited excellent cholinesterase inhibition profile. Compound 4i, (E)-N'-(2,3-dichlorobenzylidene)benzo[d][1,3]dioxole-5-carbohydrazide showed promising dual inhibitory profile against AChE (0.048 ± 0.007 µM), BChE (0.89 ± 0.018 µM), and MAO-B (0.95 ± 0.12 µM) enzymes. SAR exploration revealed that the truncation of the linker connecting both the aryl binding sites of the semicarbazone scaffold, by one atom, has relatively suppressed the AChE inhibitory potential. Kinetic studies disclosed that the compound 4i reversibly inhibited AChE enzyme in a competitive manner (Ki = 8.0 ± 0.076 nM), while it displayed a non-competitive and reversible inhibition profile against MAO-B (Ki = 9.6 ± 0.021 µM). Moreover, molecular docking studies of synthesized compounds against ChEs and MAOs provided the crucial molecular features that enable their close association and interaction with the target enzymes. All atomistic simulation studies confirmed the stable association of compound 4i within the active sites of AChE and MAO-B. In addition, theoretical ADMET prediction studies demonstrated the acceptable pharmacokinetic profile of the dual inhibitors. In summary, the attempted lead simplification study afforded a potent dual ChE-MAO-B inhibitor compound that merits further investigation.

Predicting Antiviral Resistance Mutations in SARS-CoV-2 Main Protease with Computational and Experimental Screening.

The main protease (Mpro) of SARS-CoV-2 is essential for viral replication and has been the focus of many drug discovery efforts since the start of the COVID-19 pandemic. Nirmatrelvir (NTV) is an inhibitor of SARS-CoV-2 Mpro that is used in the combination drug Paxlovid for the treatment of mild to moderate COVID-19. However, with increased use of NTV across the globe, there is a possibility that future SARS-CoV-2 lineages will evolve resistance to NTV. Early prediction and monitoring of resistance mutations could allow for measures to slow the spread of resistance and for the development of new compounds with activity against resistant strains. In this work, we have used in silico mutational scanning and inhibitor docking of Mpro to identify potential resistance mutations. Subsequent in vitro experiments revealed five mutations (N142L, E166M, Q189E, Q189I, and Q192T) that reduce the potency of NTV and of a previously identified non-covalent cyclic peptide inhibitor of Mpro. The E166M mutation reduced the half-maximal inhibitory concentration (IC50) of NTV 24-fold and 118-fold for the non-covalent peptide inhibitor. Our findings inform the ongoing genomic surveillance of emerging SARS-CoV-2 lineages.

Mechanical aspiration thrombectomy for the treatment of pulmonary embolism: A systematic review and meta-analysis.

INTRODUCTION: There are no randomized trials studying the outcomes of mechanical aspiration thrombectomy (MAT) for management of pulmonary embolism (PE). METHODS: We performed a systematic review and meta-analysis of existing literature to evaluate the safety and efficacy of MAT in the setting of PE. Inclusion criteria were as follows: studies reporting more than five patients, study involved MAT, and reported clinical outcomes and pulmonary artery pressures. Studies were excluded if they failed to separate thrombectomy data from catheter-directed thrombolysis data. Databases searched include PubMed, EMBASE, Web of Science until April, 2021. RESULTS: Fourteen case series were identified, consisting of 516 total patients (mean age 58.4 ± 13.6 years). Three studies had only high-risk PE, two studies had only intermediate-risk PE, and the remaining nine studies had a combination of both high-risk and intermediate-risk PE. Six studies used the Inari FlowTriever device, five studies used the Indigo Aspiration system, and the remaining three studies used the Rotarex or Aspirex suction thrombectomy system. Four total studies employed thrombolytics in a patient-specific manner, with seven receiving local lysis and 17 receiving systemic lysis, and 40 receiving both. A random-effects meta-analyses of proportions of in-hospital mortality, major bleeding, technical success, and clinical success were calculated, which yielded estimate pooled percentages [95% CI] of 3.6% [0.7%, 7.9%], 0.5% [0.0%, 1.8%], 97.1% [94.8%, 98.4%], and 90.7% [85.5%, 94.3%]. CONCLUSION: There is significant heterogeneity in clinical, physiologic, and angiographic data in the currently available data on MAT. RCTs with consistent parameters and outcomes measures are still needed.

Genetic evaluation of Jatropha backcross hybrid clones (BC4F1) for yield and oil quality.

Jatropha curcas is a tropical species that has been recognized as a promising biodiesel plant. During 2018-2021, researchers at Forest College and Research Institute, Mettupalayam, elicited information on Jatropha's biochemical characteristics, growth performance, variability, and association studies for biometric variables using five backcross (BC4F1) hybrid clones of Jatropha with a control variety TNMC 7. In terms of seed yield, two hybrid clones, CJH 13 (1,218.60 g) and CJH 12 (1,034.40 g), outperformed the other hybrid clones. The seed oil content was higher in CJH 5 (34.19%). The seed oil content had moderate PCV (16.49%) and GCV (16.39%) values, as well as high heritability (99%) and genetic advance (33.56%) as a percentage of the mean. The number of fruits per bunch (0.845 and 0.850) and the number of bunches per branch (0.771 and 0.788) had significant positive phenotypic and genotypic correlations with seed yield, respectively. The iodine numbers, cetane numbers, and saponification values of all hybrid clones were acceptable and satisfactory and were in good compliance with Indian and international biodiesel standards.

Predicting antiviral resistance mutations in SARS-CoV-2 main protease with computational and experimental screening

The main protease (Mpro) of SARS-CoV-2 is essential for viral replication and has been the focus of many drug discovery efforts since the start of the COVID-19 pandemic. Nirmatrelvir (NTV) is an inhibitor of SARS-CoV-2 Mpro that is used in the combination drug Paxlovid for the treatment of mild to moderate COVID-19. However, with increased use of NTV across the globe, there is a possibility that future SARS-CoV-2 lineages will evolve resistance to NTV. Early prediction and monitoring of resistance mutations could allow for measures to slow the spread of resistance and for the development of new compounds with activity against resistant strains. In this work, we have used in silico mutational scanning and inhibitor docking of Mpro to identify potential resistance mutations. Subsequent in vitro experiments revealed five mutations (N142L, E166M, Q189E, Q189I, and Q192T) that reduce the potency of NTV and of a previously identified non-covalent cyclic peptide inhibitor of Mpro. The E166M mutation reduced the half-maximal inhibitory concentration (IC50) of NTV 24-fold, and 118-fold for the non-covalent peptide inhibitor. Our findings inform the ongoing genomic surveillance of emerging SARS-CoV-2 lineages. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/505060v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@14f0713org.highwire.dtl.DTLVardef@15995feorg.highwire.dtl.DTLVardef@8689a7org.highwire.dtl.DTLVardef@b73a64_HPS_FORMAT_FIGEXP M_FIG C_FIG

Variation in biochemical, physiological and ecophysiological traits among the teak (Tectona grandis Linn. f) seed sources of India.

Teak being an iconic timber species the studies on its physiological and biochemical traits are very limited in India and worldwide. As a result, the current study aimed to assess biochemical parameters such as chlorophyll a, chlorophyll b, total chlorophyll, carotenoids, chlorophyll ab ratio, proline content, and peroxidase activity, along with physiological parameters such as Chlorophyll stability index, relative water content, and leaf area, as well as ecophysiological traits such as net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (Tr), Leaf temperature, intrinsic water-use efficiency (iWUE), instantaneous water use efficiency and intrinsic carboxylation efficiency of thirty teak seed sources collected from different states of India. FCRITK 19, FCRITK 21, FCRITK 25, FCRITK 29, and FCRITK 05 were reported to have a greater photosynthetic rate (> 17 µmol m-2 s-1) coupled with a relative water content of more than 50% and a chlorophyll stability index of more than 60%, which could be used in a future genetic improvement programme. Correlation analysis indicated that water use efficiency was found to be strongly but negatively correlated with transpiration rate (-0.601) and stomatal conductance (-0.910). The proline content had a substantial positive correlation with the chlorophyll stability index (0.890), signifying that they are associated with abiotic stress conditions. Cluster analysis was attempted to discriminate the sources based on biochemical, physiological and ecophysiological traits. Eleven sources (FCRITK 25, FCRITK 27, FCRITK 29, FCRITK 14, FCRITK 30, FCRITK 16, FCRITK 05, FCRITK 13, FCRITK 02, FCRITK 17 and FCRITK 15) exhibited superior performance compared to rest of the sources.

Animal Models of Hepatocellular Carcinoma for Local-Regional Intraarterial Therapies.

Animal models play a crucial role in developing and testing new therapies for hepatocellular carcinoma (HCC), providing preclinical evidence prior to exploring human safety and efficacy outcomes. The interventional radiologist must weigh the advantages and disadvantages of various animal models available when testing a new local-regional therapy. This review highlights the currently available animal models for testing local-regional therapies for HCC and details the importance of considering animal genetics, tumor biology, and molecular mechanisms when ultimately choosing an animal model. Keywords: Animal Studies, Interventional-Vascular, Molecular Imaging-Clinical Translation, Molecular Imaging-Cancer, Chemoembolization, Liver © RSNA, 2022.

The Vibrio vulnificus stressosome is an oxygen-sensor involved in regulating iron metabolism.

Stressosomes are stress-sensing protein complexes widely conserved among bacteria. Although a role in the regulation of the general stress response is well documented in Gram-positive bacteria, the activating signals are still unclear, and little is known about the physiological function of stressosomes in the Gram-negative bacteria. Here we investigated the stressosome of the Gram-negative marine pathogen Vibrio vulnificus. We demonstrate that it senses oxygen and identified its role in modulating iron-metabolism. We determined a cryo-electron microscopy structure of the VvRsbR:VvRsbS stressosome complex, the first solved from a Gram-negative bacterium. The structure points to a variation in the VvRsbR and VvRsbS stoichiometry and a symmetry breach in the oxygen sensing domain of VvRsbR, suggesting how signal-sensing elicits a stress response. The findings provide a link between ligand-dependent signaling and an output - regulation of iron metabolism - for a stressosome complex.

Riociguat attenuates the changes in left ventricular proteome and microRNA profile after experimental aortic stenosis in mice.

BACKGROUND AND PURPOSE: Development and progression of heart failure involve endothelial and myocardial dysfunction as well as a dysregulation of the NO-sGC-cGMP signalling pathway. Recently, we reported that the sGC stimulator riociguat has beneficial effects on cardiac remodelling and progression of heart failure in response to chronic pressure overload. Here, we examined if these beneficial effects of riociguat were also reflected in alterations of the myocardial proteome and microRNA profiles. EXPERIMENTAL APPROACH: Male C57BL/6N mice underwent transverse aortic constriction (TAC) and sham-operated mice served as controls. TAC and sham animals were randomised and treated with either riociguat or vehicle for 5 weeks, starting 3 weeks after surgery, when cardiac hypertrophy was established. Afterwards, we performed mass spectrometric proteome analyses and microRNA sequencing of proteins and RNAs, respectively, isolated from left ventricles (LVs). KEY RESULTS: TAC-induced changes of the LV proteome were significantly reduced by treatment with riociguat. Bioinformatics analyses revealed that riociguat improved TAC-induced cardiovascular disease-related pathways, metabolism and energy production, for example, reversed alterations in the levels of myosin heavy chain 7, cardiac phospholamban and ankyrin repeat domain-containing protein 1. Riociguat also attenuated TAC-induced changes of microRNA levels in the LV. CONCLUSION AND IMPLICATIONS: The sGC stimulator riociguat exerted beneficial effects on cardiac structure and function during pressure overload, which was accompanied by a reversal of TAC-induced changes of the cardiac proteome and microRNA profile. Our data support the potential of riociguat as a novel therapeutic agent for heart failure.

Antiviral cyclic peptides targeting the main protease of SARS-CoV-2.

Antivirals that specifically target SARS-CoV-2 are needed to control the COVID-19 pandemic. The main protease (Mpro) is essential for SARS-CoV-2 replication and is an attractive target for antiviral development. Here we report the use of the Random nonstandard Peptide Integrated Discovery (RaPID) mRNA display on a chemically cross-linked SARS-CoV-2 Mpro dimer, which yielded several high-affinity thioether-linked cyclic peptide inhibitors of the protease. Structural analysis of Mpro complexed with a selenoether analogue of the highest-affinity peptide revealed key binding interactions, including glutamine and leucine residues in sites S1 and S2, respectively, and a binding epitope straddling both protein chains in the physiological dimer. Several of these Mpro peptide inhibitors possessed antiviral activity against SARS-CoV-2 in vitro with EC50 values in the low micromolar range. These cyclic peptides serve as a foundation for the development of much needed antivirals that specifically target SARS-CoV-2.

Insights on synthesis and applications of graphene-based materials in wastewater treatment: A review.

Graphene has excellent unique thermal, chemical, optical, and mechanical properties such as high thermal conductivity, high chemical stability, optical transmittance, high current density, higher surface area, etc. Due to their outstanding properties, the attention towards graphene-based materials and their derivatives in wastewater treatment has been increased in recent times. Different graphene-based materials such as graphene oxides, graphene quantum dots, graphene nanoplatelets, graphene nanoribbons and other graphene-based nanocomposites are synthesized through chemical vapor deposition, mechanical and electrochemical exfoliation of graphite. In this review, the specifics about the graphenes and their derivatives, the synthesis strategy of graphene-based materials are described. This review critically explained the applications of graphene-based materials in wastewater treatment. Graphene-based materials were utilized as adsorbents, electrodes, and photocatalysts for the efficient removal of toxic pollutants such as heavy metals, dyes, pharmaceutics, antibiotics, phenols, polycyclic aromatic hydrocarbons have been highlighted and discussed. Herein, the potential scope of graphene-based material in the field of wastewater treatment is critically reviewed. In addition, a brief perspective on future research directions and difficulties in the synthesis of graphene-based material are summarized.

Deep Generative Medical Image Harmonization for Improving Cross-Site Generalization in Deep Learning Predictors.

BACKGROUND: In the medical imaging domain, deep learning-based methods have yet to see widespread clinical adoption, in part due to limited generalization performance across different imaging devices and acquisition protocols. The deviation between estimated brain age and biological age is an established biomarker of brain health and such models may benefit from increased cross-site generalizability. PURPOSE: To develop and evaluate a deep learning-based image harmonization method to improve cross-site generalizability of deep learning age prediction. STUDY TYPE: Retrospective. POPULATION: Eight thousand eight hundred and seventy-six subjects from six sites. Harmonization models were trained using all subjects. Age prediction models were trained using 2739 subjects from a single site and tested using the remaining 6137 subjects from various other sites. FIELD STRENGTH/SEQUENCE: Brain imaging with magnetization prepared rapid acquisition with gradient echo or spoiled gradient echo sequences at 1.5 T and 3 T. ASSESSMENT: StarGAN v2, was used to perform a canonical mapping from diverse datasets to a reference domain to reduce site-based variation while preserving semantic information. Generalization performance of deep learning age prediction was evaluated using harmonized, histogram matched, and unharmonized data. STATISTICAL TESTS: Mean absolute error (MAE) and Pearson correlation between estimated age and biological age quantified the performance of the age prediction model. RESULTS: Our results indicated a substantial improvement in age prediction in out-of-sample data, with the overall MAE improving from 15.81 (±0.21) years to 11.86 (±0.11) with histogram matching to 7.21 (±0.22) years with generative adversarial network (GAN)-based harmonization. In the multisite case, across the 5 out-of-sample sites, MAE improved from 9.78 (±6.69) years to 7.74 (±3.03) years with histogram normalization to 5.32 (±4.07) years with GAN-based harmonization. DATA CONCLUSION: While further research is needed, GAN-based medical image harmonization appears to be a promising tool for improving cross-site deep learning generalization. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.