Two-Phase Electrosynthesis of Dihydroxycoumestans: Discovery of a New Scaffold for Topoisomerase I Poison.

Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9-dihydroxycoumestans via two-electrode constant current electrolysis was developed. The application of a two-phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o-benzoquinone intermediates from over-oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1-targeted antitumor agent.

Trade-off between Pore-Throat Structure and Mineral Composition in Modulating the Stability of Soil Organic Carbon.

The preservation of soil organic carbon (OC) is an effective way to decelerate the emission of CO2 emission. However, the coregulation of pore structure and mineral composition in OC stabilization remains elusive. We employed the in situ nondestructive oxidation of OC by low-temperature ashing (LTA) combined with near edge X-ray absorption fine structure (NEXAFS), high-resolution microtomography (µ-CT), field emission electron probe microanalysis (FE-EPMA) with C-free embedding, and novel Cosine similarity measurement to investigate the C retention in different aggregate fractions of contrasting soils. Pore structure and minerals contributed equally (ca. 50%) to OC accumulation in macroaggregates, while chemical protection played a leading role in C retention with 53.4%-59.2% of residual C associated with minerals in microaggregates. Phyllosilicates were discovered to be more prominent than Fe (hydr)oxides in C stabilization. The proportion of phyllosilicates-associated C (52.0%-61.9%) was higher than that bound with Fe (hydr)oxides (45.6%-55.3%) in all aggregate fractions tested. This study disentangled quantitatively for the first time a trade-off between physical and chemical protection of OC varying with aggregate size and the different contributions of minerals to OC preservation. Incorporating pore structure and mineral composition into C modeling would optimize the C models and improve the soil C content prediction.

Electrochemical Synthesis of Phenothiazinone as Fluorophore and Its Application in Bioimaging.

Phenothiazinone is a promising yet underutilized fluorophore, possibly due to the lack of a general accessibility. This study reports a robust and scalable TEMPO-mediated electrochemical method to access a variety of phenothiazinones from 2-aminothiophenols and quinones. The electrosynthesis proceeds in a simple cell architecture under mild condition, and notably carbon-halogen bond in quinones remains compared to conventional methods, enabling orthogonal downstream functionalization. Mechanistic studies corroborate that TEMPO exerts a protective effect in avoiding product decomposition at the cathode. In particular, benzophenothiazinones show intriguing luminescence in both solid and solution state, and thus their photophysical properties are scrutinized in detail. Further bio-imaging of the lipid droplets in living cells highlights the considerable promise of benzophenothiazinones as fluorescent dye in the biomedical fields.

Recent Advances in Self-Assembly and Application of Para-Aramids.

Poly(p-phenylene terephthalamide) (PPTA) is one kind of lyotropic liquid crystal polymer. Kevlar fibers performed from PPTA are widely used in many fields due to their superior mechanical properties resulting from their highly oriented macromolecular structure. However, the "infusible and insoluble" characteristic of PPTA gives rise to its poor processability, which limits its scope of application. The strong interactions and orientation characteristic of aromatic amide segments make PPTA attractive in the field of self-assembly. Chemical derivation has proved an effective way to modify the molecular structure of PPTA to improve its solubility and amphiphilicity, which resulted in different liquid crystal behaviors or supramolecular aggregates, but the modification of PPTA is usually complex and difficult. Alternatively, higher-order all-PPTA structures have also been realized through the controllable hierarchical self-assembly of PPTA from the polymerization process to the formation of macroscopic products. This review briefly summarizes the self-assembly methods of PPTA-based materials in recent years, and focuses on the polymerization-induced PPTA nanofibers which can be further fabricated into different macroscopic architectures when other self-assembly methods are combined. This monomer-started hierarchical self-assembly strategy evokes the feasible processing of PPTA, and enriches the diversity of product, which is expected to be expanded to other liquid crystal polymers.

Source separation, transportation, pretreatment, and valorization of municipal solid waste: a critical review.

Waste sorting is an effective means of enhancing resource or energy recovery from municipal solid waste (MSW). Waste sorting management system is not limited to source separation, but also involves at least three stages, i.e., collection and transportation (C&T), pretreatment, and resource utilization. This review focuses on the whole process of MSW management strategy based on the waste sorting perspective. Firstly, as the sources of MSW play an essential role in the means of subsequent valorization, the factors affecting the generation of MSW and its prediction methods are introduced. Secondly, a detailed comparison of approaches to source separation across countries is presented. Constructing a top-down management system and incentivizing or constraining residents' sorting behavior from the bottom up is believed to be a practical approach to promote source separation. Then, the current state of C&T techniques and its network optimization are reviewed, facilitated by artificial intelligence (AI) and the Internet of Things technologies. Furthermore, the advances in pretreatment strategies for enhanced sorting and resource recovery are introduced briefly. Finally, appropriate methods to valorize different MSW are proposed. It is worth noting that new technologies, such as AI, show high application potential in waste management. The sharing of (intermediate) products or energy of varying processing units will inject vitality into the waste management network and achieve sustainable development.

Of dilemmas and tensions: a qualitative study of palliative care physicians' positions regarding voluntary active euthanasia in Quebec, Canada.

OBJECTIVES: In 2015, the Province of Quebec, Canada passed a law that allowed voluntary active euthanasia (VAE). Palliative care stakeholders in Canada have been largely opposed to euthanasia, yet there is little research about their views. The research question guiding this study was the following: How do palliative care physicians in Quebec position themselves regarding the practice of VAE in the context of the new provincial legislation? METHODS: We used interpretive description, an inductive methodology to answer research questions about clinical practice. A total of 18 palliative care physicians participated in semistructured interviews at two university-affiliated hospitals in Quebec. RESULTS: Participants positioned themselves in opposition to euthanasia. Their justifications were framed within their professional commitment to not hasten death, which sat in tension with the value of patients' autonomy to choose how to die. Participants described VAE as unacceptable if it impeded opportunities to evaluate and alleviate suffering. Further, they contested government rhetoric that positioned VAE as a way to improve end-of-life care. Participants felt that VAE would diminish the potential of palliative care to relieve suffering. Dilemmas were apparent in their narratives, about reconciling respect for patient autonomy with broader palliative care values, and the value of accompanying and not abandoning patients who make requests for VAE while being committed to neither prolonging nor hastening death. CONCLUSIONS: This study provides insight into nuanced positions of experienced palliative care physicians in Quebec and confirms expected tensions between an important stakeholder and the practice of VAE as guided by the new legislation.

Design Nitrogen (N) and Sulfur (S) Co-Doped 3D Graphene Network Architectures for High-Performance Sodium Storage.

To develop high-performance sodium-ion batteries (NIBs), electrodes should possess well-defined pathways for efficient electronic/ionic transport. In this work, high-performance NIBs are demonstrated by designing a 3D interconnected porous structure that consists of N, S co-doped 3D porous graphene frameworks (3DPGFs-NS). The most typical electrode materials (i.e., Na3 V2 (PO4 )3 (NVP), MoS2 , and TiO2 ) are anchored onto the 3DPGFs-NS matrix (denoted as NVP@C@3DPGFs-NS; MoS2 @C@3DPGFs-NS and TiO2 @C@3DPGFs-NS) to demonstrate its general process to boost the energy density of NIBs. The N, S co-doped porous graphene structure with a large surface area offers fast ionic transport within the electrode and facilitates efficient electron transport, and thus endows the 3DPGFs-NS-based composite electrodes with excellent sodium storage performance. The resulting NVP@C@3DPGFs-NS displays excellent electrochemical performance as both cathode and anode for NIBs. The MoS2 @C@3DPGFs-NS and TiO2 @C@3DPGFs-NS deliver capacities of 317 mAhg-1 at 5 Ag-1 after 1000 cycles and 185 mAhg-1 at 1 Ag-1 after 2000 cycles, respectively. The excellent long cycle life is attributed to the 3D porous structure that could greatly release mechanical stress from repeated Na+ extraction/insertion. The novel structure 3D PGFs-NS provides a general approach to modify electrodes of NIBs and holds great potential applications in other energy storage fields.

iTRAQ protein profile analysis of tomato green-ripe mutant reveals new aspects critical for fruit ripening.

Green-ripe (Gr) tomato carries a dominant mutation and yields a nonripening fruit phenotype. The mutation results from a 334 bp deletion in a gene of unknown function at the Gr locus. The putative influence of Gr gene-deletion mutation on biochemical changes underlying the nonripening phenotype remains largely unknown. Respiration of Gr fruit was found to be reduced at mature green and breaker stage of ripening, while the fruit softening was dramatically prolonged. We studied the proteome of Gr mutant fruit using high-throughput iTRAQ and high-resolution mass spectrometry and identified 43 proteins representing 43 individual genes as potential influence-targets of Gr mutated fruit. The identified proteins are involved in several ripening-related pathways including cell-wall metabolism, photosynthesis, oxidative phosphorylation, carbohydrate and fatty acid metabolism, protein synthesis, and processing. Affected protein levels are correlated with the corresponding gene transcript levels. The modulation in the accumulation levels of PI(U1)P, PGIP, and PG2 supported the delayed softening phenotype of the Gr fruit. Further investigation in GR gene-silencing fruit ascertained the doubtless modulation of these targets by the deletion mutation of GR gene.

Construction of semiconductor nanocomposites for room-temperature gas sensors.

Gas sensors are essential for ensuring public safety and improving quality of life. Room-temperature gas sensors are notable for their potential economic benefits and low energy consumption, and their expected integration with wearable electronics, making them a focal point of contemporary research. Advances in nanomaterials and low-dimensional semiconductors have significantly contributed to the enhancement of room-temperature gas sensors. These advancements have focused on improving sensitivity, selectivity, and response/recovery times, with nanocomposites offering distinct advantages. The discussion here focuses on the use of semiconductor nanocomposites for gas sensing at room temperature, and provides a review of the latest synthesis techniques for these materials. This involves the precise adjustment of chemical compositions, microstructures, and morphologies. In addition, the design principles and potential functional mechanisms are examined. This is crucial for deepening the understanding and enhancing the operational capabilities of sensors. We also highlight the challenges faced in scaling up the production of nanocomposite materials. Looking ahead, semiconductor nanocomposites are expected to drive innovation in gas sensor technology due to their carefully crafted design and construction, paving the way for their extensive use in various sectors.

Solution Blow Spinning of the Benzimidazole-Containing Aramid Nanofibers for Separators of Lithium-Ion Batteries.

Nanofibers based on high-performance polymers are much highlighted in recent studies toward advanced lithium-ion batteries. Herein, we demonstrate one scalable poly(ethylene oxide) (PEO)-assisted solution blow spinning strategy for the preparation of heterocyclic aramid (HA) nanofibers of poly(p-phenylene-benzimidazole-terephthalamide). The incorporation of PEO is essential to improve the spinnability of the HA solution achieved directly through the low-temperature-solution copolymerization process. Additionally, the flexible PEO with a strong H-bonding affinity is also utilized as the molecular zipper to adjust the pore size of the nanofiber membrane during the post-treatment process. The obtained membrane combines the good wettability of PEO to the liquid electrolytes, with outstanding mechanical strength, modulus, toughness, and environmental resistance of HA. The nonwoven separator membranes with a porosity of 83.6% exhibited excellent comprehensive performance, which could be seen not only on the high tensile strength (68.2 MPa), modulus (3.0 GPa), and toughness but also on the high thermal stability (Td > 405 °C) and flame retardancy, as well as the high electrolyte uptake (302.4%). The ion conductivity of the porous separators reached 0.83 mS/cm, with the bulk resistance dropping to 1/4 of the reference polypropylene separator. In the assembly of the Li/LiFePO4 half battery, the HA separators displayed improved discharge specific capacity and high retention in both rate capability and cycling tests, providing the potential industrial preparation for advanced lithium-ion batteries.

A Biterm Topic Model for Sparse Mutation Data.

Mutational signature analysis promises to reveal the processes that shape cancer genomes for applications in diagnosis and therapy. However, most current methods are geared toward rich mutation data that has been extracted from whole-genome or whole-exome sequencing. Methods that process sparse mutation data typically found in practice are only in the earliest stages of development. In particular, we previously developed the Mix model that clusters samples to handle data sparsity. However, the Mix model had two hyper-parameters, including the number of signatures and the number of clusters, that were very costly to learn. Therefore, we devised a new method that was several orders-of-magnitude more efficient for handling sparse data, was based on mutation co-occurrences, and imitated word co-occurrence analyses of Twitter texts. We showed that the model produced significantly improved hyper-parameter estimates that led to higher likelihoods of discovering overlooked data and had better correspondence with known signatures.

Long-term observation on safety and visual quality of implantable collamer lens V4c implantation for myopia correction: a 5-year follow-up.

AIM: To elucidate the safety and visual quality of implantable collamer lens with central hole (ICL V4c) implantation for correcting moderate and high myopia for at least 5y. METHODS: This retrospective study was conducted on 58 patients (114 eyes) who were followed up for at least 5y after ICL V4c implantation. The observation was done before and on 1d, 1mo, 1 and 5y or more after the surgical procedure. The visual acuity, subjective refraction, intraocular pressure, vault, axial length, central hole position, pupil diameter, visual quality, and adverse events were analyzed. The visual quality includes aberration, the modulation transfer function cutoff frequency (MTF cutoff), objective scattering index (OSI), Stroller's ratio (SR), and visual quality questionnaire. RESULTS: The average follow-up period was 69.25±3.80mo (range 60-82mo) and the preoperative spherical equivalent (SE) was -8.66±1.97 D. At 5y after operation, the safety index was 1.01±0.02 and the efficacy index was 0.99±0.42 and SE was -0.65±0.63 D. The 59.6% of the eyes achieved an uncorrected distance visual acuity of 20/20, 76.3% of the eyes had SE within ±1.0 D at the last visit. The axial length increased by 0.29±0.71 mm 5y after the surgery (t=-3.843, P<0.001). The mean vault at the last follow-up was 510.59±245.61 µm. The central hole was on the temporal side in 80 eyes (84.2%). The visual quality questionnaire showed that 98.2% patients were satisfied with the surgical procedure. Adverse events occurred in 4 eyes (3.5%), including the posttraumatic toric ICL rotation (2 eyes), iris incarceration (1 eye), and posttraumatic ICL displacement (1 eye) at the last follow-up. CONCLUSION: Long-term ICL V4c implantation is safe, effective, and stable for correcting moderate and to high myopia, and the visual quality with patients is excellent and satisfactory, but the progression of axial length still needs attention after surgery.

Gene expression network reconstruction by LEP method using microarray data.

Gene expression network reconstruction using microarray data is widely studied aiming to investigate the behavior of a gene cluster simultaneously. Under the Gaussian assumption, the conditional dependence between genes in the network is fully described by the partial correlation coefficient matrix. Due to the high dimensionality and sparsity, we utilize the LEP method to estimate it in this paper. Compared to the existing methods, the LEP reaches the highest PPV with the sensitivity controlled at the satisfactory level. A set of gene expression data from the HapMap project is analyzed for illustration.

Long-term effects of copper nanoparticles on volatile fatty acids production from sludge fermentation: Roles of copper species and bacterial community structure.

The long-term effects of copper nanoparticles (Cu NPs) on volatile fatty acids (VFAs) production during the waste activated sludge (WAS) fermentation, and the underlying mechanisms regarding copper species distribution and bacterial community evolution were explored. The yield of VFAs in the control was 1086 mg COD/L, whereas those were inhibited by 11.1%, 56.0% and 83.1%, with 25, 50, and 100 mg/g-TSS Cu NPs, respectively. Further investigation indicated that Cu NPs severely affected hydrolysis and acidification of WAS in a dose-dependent manner, while had little impact on solubilization. Besides, Cu NPs enriched the acid-consuming anaerobe while reducing the acid-forming bacteria. The metabolic pathways, microbial function, and enzymatic activities involved were inhibited at all tested dosages. Moreover, soluble and acid-extractable fractions dominated the copper speciation, which were also the main factors inhibiting the VFA production. This study provides a new perspective to interpret the long-term impacts of Cu NPs on WAS fermentation.

Propionic acid-rich fermentation (PARF) production from organic wastes: A review.

Nowadays, increasing attention has been drawn to biological valorization of organic wastes. Wherein, propionic acid-rich fermentation (PARF) has become a focal point of research. The objective of this review is to make a thorough investigation on the potential of PARF production and give future outlook. By discussing the key factors affecting PARF including substrate types, pH, temperature, retention time, etc., and various improving methods to enhance PARF including different pretreatments, inoculation optimization and immobilization, a comprehensive summary on how to achieve PARF from organic waste is presented. Then, current application of PARF liquid is concluded, which is found to play an essential role in the efficient denitrification and phosphorus removal of wastewater and preparation of microbial lipids. Finally, the environmental performance of PARF production is reviewed through life cycle assessment studies, and environmentally sensitive sectors are summarized for process optimization, providing a reference for waste management in low carbon scenarios.

A mixture model for signature discovery from sparse mutation data.

Mutational signatures are key to understanding the processes that shape cancer genomes, yet their analysis requires relatively rich whole-genome or whole-exome mutation data. Recently, orders-of-magnitude sparser gene-panel-sequencing data have become increasingly available in the clinic. To deal with such sparse data, we suggest a novel mixture model, Mix. In application to simulated and real gene-panel sequences, Mix is shown to outperform current approaches and yield mutational signatures and patient stratifications that are in higher agreement with the literature. We further demonstrate its utility in several clinical settings, successfully predicting therapy benefit and patient groupings from MSK-IMPACT pan-cancer data. Availability: https://github.com/itaysason/Mix-MMM .

Joint effects of carbon nanotubes and copper oxide nanoparticles on fermentation metabolism towards Saccharofermentans acetigenes: Enhancing environmental adaptability and transcriptional expression.

In this study, the joint effects of widely used copper oxide nanoparticles (CuO NPs) and multi-walled carbon nanotubes (MWCNTs) on the fermentation metabolism of a model acetogenic bacterium Saccharofermentans acetigenes were investigated and the underlying mechanisms were further explored. The presence of sole CuO NPs or MWCNTs severely inhibited the acetate generation, while their co-existences did not further decrease the acetate yield as expected. Further analysis indicated the joint effects facilitated the enhancement of bacterial stimulus response to the environment and interspecies communication, which improved adaptive capacity to the adverse environment involved in nanomaterials. Meanwhile, the co-existence reduced inhibitory effects of sole nanomaterial on the gene expressions and catalytic activities of key enzymes involved in glycolysis and pyruvate metabolism. Therefore, the joint effects could enhance environmental adaptation of S. acetigenes and transcriptional expressions of key enzymes for acetic acid production-related processes, alleviating the inhibition of CuO NPs to acetate production.

A Novel Colon Wall Flattening Model for Computed Tomographic Colonography: Method and Validation.

Computed tomographic colonography (CTC) has been developed for screening of colon cancer. Flattening the three-dimensional (3D) colon wall into two-dimensional (2D) image is believed to (1) provide supplementary information to the endoscopic views and further (2) facilitate colon registration, taniae coli (TC) detection, and haustral fold segmentation. Though the previously-used conformal mapping-based flattening methods can preserve the angular geometry, they have the limitations in providing accurate information of the 3D inner colon wall due to the lack of undulating topography. In this paper, we present a novel colon-wall flattening method using a strategy of 2.5D approach. Coupling with the conformal flattening model, the presented new approach builds an elevation distance map to depict the neighborhood characteristics of the inner colon wall. We validated the new method via two CTC applications: TC detection and haustral fold segmentation. Experimental results demonstrated the effectiveness of our strategy for CTC studies.