Modeling post-implantation stages of human development into early organogenesis with stem-cell-derived peri-gastruloids.

In vitro stem cell models that replicate human gastrulation have been generated, but they lack the essential extraembryonic cells needed for embryonic development, morphogenesis, and patterning. Here, we describe a robust and efficient method that prompts human extended pluripotent stem cells to self-organize into embryo-like structures, termed peri-gastruloids, which encompass both embryonic (epiblast) and extraembryonic (hypoblast) tissues. Although peri-gastruloids are not viable due to the exclusion of trophoblasts, they recapitulate critical stages of human peri-gastrulation development, such as forming amniotic and yolk sac cavities, developing bilaminar and trilaminar embryonic discs, specifying primordial germ cells, initiating gastrulation, and undergoing early neurulation and organogenesis. Single-cell RNA-sequencing unveiled transcriptomic similarities between advanced human peri-gastruloids and primary peri-gastrulation cell types found in humans and non-human primates. This peri-gastruloid platform allows for further exploration beyond gastrulation and may potentially aid in the development of human fetal tissues for use in regenerative medicine.

Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-ß, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.

Ex utero monkey embryogenesis from blastocyst to early organogenesis.

The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However, our understanding of this period is limited due to restricted access to in vivo embryos. To address this gap, we developed an embedded 3D culture system that allows for the extended ex utero culture of cynomolgus monkey embryos for up to 25 days post-fertilization. Morphological, histological, and single-cell RNA-sequencing analyses demonstrate that ex utero cultured monkey embryos largely recapitulated key events of in vivo development. With this platform, we were able to delineate lineage trajectories and genetic programs involved in neural induction, lateral plate mesoderm differentiation, yolk sac hematopoiesis, primitive gut, and primordial germ-cell-like cell development in monkeys. Our embedded 3D culture system provides a robust and reproducible platform for growing monkey embryos from blastocysts to early organogenesis and studying primate embryogenesis ex utero.

Primate gastrulation and early organogenesis at single-cell resolution.

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.

Glycolysis-Mediated Activation of v-ATPase by Nicotinamide Mononucleotide Ameliorates Lipid-Induced Cardiomyopathy by Repressing the CD36-TLR4 Axis.

BACKGROUND: Chronic overconsumption of lipids followed by their excessive accumulation in the heart leads to cardiomyopathy. The cause of lipid-induced cardiomyopathy involves a pivotal role for the proton-pump vacuolar-type H+-ATPase (v-ATPase), which acidifies endosomes, and for lipid-transporter CD36, which is stored in acidified endosomes. During lipid overexposure, an increased influx of lipids into cardiomyocytes is sensed by v-ATPase, which then disassembles, causing endosomal de-acidification and expulsion of stored CD36 from the endosomes toward the sarcolemma. Once at the sarcolemma, CD36 not only increases lipid uptake but also interacts with inflammatory receptor TLR4 (Toll-like receptor 4), together resulting in lipid-induced insulin resistance, inflammation, fibrosis, and cardiac dysfunction. Strategies inducing v-ATPase reassembly, that is, to achieve CD36 reinternalization, may correct these maladaptive alterations. For this, we used NAD+ (nicotinamide adenine dinucleotide)-precursor nicotinamide mononucleotide (NMN), inducing v-ATPase reassembly by stimulating glycolytic enzymes to bind to v-ATPase. METHODS: Rats/mice on cardiomyopathy-inducing high-fat diets were supplemented with NMN and for comparison with a cocktail of lysine/leucine/arginine (mTORC1 [mechanistic target of rapamycin complex 1]-mediated v-ATPase reassembly). We used the following methods: RNA sequencing, mRNA/protein expression analysis, immunofluorescence microscopy, (co)immunoprecipitation/proximity ligation assay (v-ATPase assembly), myocellular uptake of [3H]chloroquine (endosomal pH), and [14C]palmitate, targeted lipidomics, and echocardiography. To confirm the involvement of v-ATPase in the beneficial effects of both supplementations, mTORC1/v-ATPase inhibitors (rapamycin/bafilomycin A1) were administered. Additionally, 2 heart-specific v-ATPase-knockout mouse models (subunits V1G1/V0d2) were subjected to these measurements. Mechanisms were confirmed in pharmacologically/genetically manipulated cardiomyocyte models of lipid overload. RESULTS: NMN successfully preserved endosomal acidification during myocardial lipid overload by maintaining v-ATPase activity and subsequently prevented CD36-mediated lipid accumulation, CD36-TLR4 interaction toward inflammation, fibrosis, cardiac dysfunction, and whole-body insulin resistance. Lipidomics revealed C18:1-enriched diacylglycerols as lipid class prominently increased by high-fat diet and subsequently reversed/preserved by lysine/leucine/arginine/NMN treatment. Studies with mTORC1/v-ATPase inhibitors and heart-specific v-ATPase-knockout mice further confirmed the pivotal roles of v-ATPase in these beneficial actions. CONCLUSION: NMN preserves heart function during lipid overload by preventing v-ATPase disassembly.

Thermally Inducing Viscous Fluids to Generate Co-Based Perovskites Enriched with Active Species for the Removal of VOCs.

Various Co-based perovskites are synthesized through thermally driving viscous fluids. In this process, rare earth salts, cobalt salts, and citric acid do not require homogeneous mixing but only need to be heated until they melt into a molten viscous slurry. The physicochemical properties of cobalt-based perovskites were examined using techniques such as X-ray diffraction (XRD), electron paramagnetic resonance (EPR), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-Mapping-EDS), X-ray photoelectron spectroscopy (XPS), hydrogen temperature-programmed reduction (H2-TPR), oxygen temperature-programmed desorption (O2-TPD), and N2 adsorption-desorption. The results indicate that the surface-active species can be controlled by altering the A-site elements of cobalt-based perovskites. All catalysts synthesized through the thermal treatment of viscous mixtures exhibited a low activation temperature and a low apparent activation energy for the catalytic oxidation of toluene. Among all cobalt-based perovskites, LaCoO3 demonstrated the most outstanding catalytic activity, primarily attributed to its capacity to expose a larger number of surface-active sites and oxygen species, as well as its superior reducibility. Furthermore, the formation process of optimal LaCoO3 was monitored using thermogravimetric analysis-differential scanning calorimetry (TGA-DSC), and the byproducts of the low-temperature catalytic oxidation of toluene by the catalyst were identified using gas chromatography-mass spectrometry (GC-MS). The possible mechanism of toluene oxidation was inferred by in situ diffuse reflection infrared Fourier transform spectroscopy (DRIFTS). Moreover, LaCoO3 exhibits a predominant resistance to high-temperature hydrothermal conditions. This work provides a scalable and innovative approach to fabricating exceptionally effective catalysts for the efficient purification of VOCs.

Parametric delineation uncertainties contouring (PDUC) modeling on CT scans of prostate cancer patients.

PURPOSE: Variability in contouring contributes to large variations in radiation therapy planning and treatment outcomes. The development and testing of tools to automatically detect contouring errors require a source of contours that includes well-understood and realistic errors. The purpose of this work was to develop a simulation algorithm that intentionally injects errors of varying magnitudes into clinically accepted contours and produces realistic contours with different levels of variability. METHODS: We used a dataset of CT scans from 14 prostate cancer patients with clinician-drawn contours of the regions of interest (ROI) of the prostate, bladder, and rectum. Using our newly developed Parametric Delineation Uncertainties Contouring (PDUC) model, we automatically generated alternative, realistic contours. The PDUC model consists of the contrast-based DU generator and a 3D smoothing layer. The DU generator transforms contours (deformation, contraction, and/or expansion) as a function of image contrast. The generated contours undergo 3D smoothing to obtain a realistic look. After model building, the first batch of auto-generated contours was reviewed. Editing feedback from the reviews was then used in a filtering model for the auto-selection of clinically acceptable (minor-editing) DU contours. RESULTS: Overall, C values of 5 and 50 consistently produced high proportions of minor-editing contours across all ROI compared to the other C values (0.936 ± $ \pm \;$ 0.111 and 0.552 ± $ \pm \;$ 0.228, respectively). The model performed best on the bladder, which had the highest proportion of minor-editing contours (0.606) of the three ROI. In addition, the classification AUC for the filtering model across all three ROI is 0.724 ± $ \pm \;$ 0.109. DISCUSSION: The proposed methodology and subsequent results are promising and could have a great impact on treatment planning by generating mathematically simulated alternative structures that are clinically relevant and realistic enough (i.e., similar to clinician-drawn contours) to be used in quality control of radiation therapy.

Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids.

During gastrulation, the pluripotent epiblast self-organizes into the 3 germ layers-endoderm, mesoderm and ectoderm, which eventually form the entire embryo. Decades of research in the mouse embryo have revealed that a signaling cascade involving the Bone Morphogenic Protein (BMP), WNT, and NODAL pathways is necessary for gastrulation. In vivo, WNT and NODAL ligands are expressed near the site of gastrulation in the posterior of the embryo, and knockout of these ligands leads to a failure to gastrulate. These data have led to the prevailing view that a signaling gradient in WNT and NODAL underlies patterning during gastrulation; however, the activities of these pathways in space and time have never been directly observed. In this study, we quantify BMP, WNT, and NODAL signaling dynamics in an in vitro model of human gastrulation. Our data suggest that BMP signaling initiates waves of WNT and NODAL signaling activity that move toward the colony center at a constant rate. Using a simple mathematical model, we show that this wave-like behavior is inconsistent with a reaction-diffusion-based Turing system, indicating that there is no stable signaling gradient of WNT/NODAL. Instead, the final signaling state is homogeneous, and spatial differences arise only from boundary effects. We further show that the durations of WNT and NODAL signaling control mesoderm differentiation, while the duration of BMP signaling controls differentiation of CDX2-positive extra-embryonic cells. The identity of these extra-embryonic cells has been controversial, and we use RNA sequencing (RNA-seq) to obtain their transcriptomes and show that they closely resemble human trophoblast cells in vivo. The domain of BMP signaling is identical to the domain of differentiation of these trophoblast-like cells; however, neither WNT nor NODAL forms a spatial pattern that maps directly to the mesodermal region, suggesting that mesoderm differentiation is controlled dynamically by the combinatorial effect of multiple signals. We synthesize our data into a mathematical model that accurately recapitulates signaling dynamics and predicts cell fate patterning upon chemical and physical perturbations. Taken together, our study shows that the dynamics of signaling events in the BMP, WNT, and NODAL cascade in the absence of a stable signaling gradient control fate patterning of human gastruloids.

Progress on pivotal role and application of exosome in lung cancer carcinogenesis, diagnosis, therapy and prognosis.

Lung cancer is often diagnosed at an advanced stage and has a poor prognosis. Conventional treatments are not effective for metastatic lung cancer therapy. Although some of molecular targets have been identified with favorable response, those targets cannot be exploited due to the lack of suitable drug carriers. Lung cancer cell-derived exosomes (LCCDEs) receive recent interest in its role in carcinogenesis, diagnosis, therapy, and prognosis of lung cancer due to its biological functions and natural ability to carry donor cell biomolecules. LCCDEs can promote cell proliferation and metastasis, affect angiogenesis, modulate antitumor immune responses during lung cancer carcinogenesis, regulate drug resistance in lung cancer therapy, and be now considered an important component in liquid biopsy assessments for detecting lung cancer. Therapeutic deliverable exosomes are emerging as promising drug delivery agents specifically to tumor high precision medicine because of their natural intercellular communication role, excellent biocompatibility, low immunogenicity, low toxicity, long blood circulation ability, biodegradable characteristics, and their ability to cross various biological barriers. Several studies are currently underway to develop novel diagnostic and prognostic modalities using LCCDEs, and to develop methods of exploiting exosomes for use as efficient drug delivery vehicles. Current status of lung cancer and extensive applicability of LCCDEs are illustrated in this review. The promising data and technologies indicate that the approach on LCCDEs implies the potential application of LCCDEs to clinical management of lung cancer patients.

Recovery of cathode materials from spent lithium-ion batteries and their application in preparing multi-metal oxides for the removal of oxygenated VOCs: Effect of synthetic methods.

Due to the sustainable use of wastes, cathode materials of spent lithium-ion batteries are recovered and used as transition metal precursors to prepare metal oxides catalysts for the oxidation of VOCs. In this work, a series of manganese-based and cobalt-based metal oxides are synthesized via different preparation methods. Catalytic activities of the catalysts prepared are investigated through complete oxidation of oxygenated VOCs and the physicochemical properties of optimum samples are characterized. Evaluation results indicate that MnOx (SY) (HT) sample prepared via hydrothermal method and CoOx (GS) (CP) synthesized via co-precipitation method had better performance, because they have higher specific surface area, higher concentration of active oxygen species and high-valence metal ion, as well as better low-temperature reducibility compared to the other multi-metal oxides used in the study. In addition, TD/GC-MS results imply that further oxidation of by-products requires high reaction temperature during VOCs oxidation.

coMethDMR: accurate identification of co-methylated and differentially methylated regions in epigenome-wide association studies with continuous phenotypes.

Recent technology has made it possible to measure DNA methylation profiles in a cost-effective and comprehensive genome-wide manner using array-based technology for epigenome-wide association studies. However, identifying differentially methylated regions (DMRs) remains a challenging task because of the complexities in DNA methylation data. Supervised methods typically focus on the regions that contain consecutive highly significantly differentially methylated CpGs in the genome, but may lack power for detecting small but consistent changes when few CpGs pass stringent significance threshold after multiple comparison. Unsupervised methods group CpGs based on genomic annotations first and then test them against phenotype, but may lack specificity because the regional boundaries of methylation are often not well defined. We present coMethDMR, a flexible, powerful, and accurate tool for identifying DMRs. Instead of testing all CpGs within a genomic region, coMethDMR carries out an additional step that selects co-methylated sub-regions first. Next, coMethDMR tests association between methylation levels within the sub-region and phenotype via a random coefficient mixed effects model that models both variations between CpG sites within the region and differential methylation simultaneously. coMethDMR offers well-controlled Type I error rate, improved specificity, focused testing of targeted genomic regions, and is available as an open-source R package.

PathwayPCA: an R/Bioconductor Package for Pathway Based Integrative Analysis of Multi-Omics Data.

The authors present pathwayPCA, an R/Bioconductor package for integrative pathway analysis that utilizes modern statistical methodology, including supervised and adaptive, elastic-net, sparse principal component analysis. pathwayPCA can be applied to continuous, binary, and survival outcomes in studies with multiple covariates and/or interaction effects. It outperforms several alternative methods at identifying disease-associated pathways in integrative analysis using both simulated and real datasets. In addition, several case studies are provided to illustrate pathwayPCA analysis with gene selection, estimating, and visualizing sample-specific pathway activities, identifying sex-specific pathway effects in kidney cancer, and building integrative models for predicting patient prognosis. pathwayPCA is an open-source R package, freely available through the Bioconductor repository. pathwayPCA is expected to be a useful tool for empowering the wider scientific community to analyze and interpret the wealth of available proteomics data, along with other types of molecular data recently made available by Clinical Proteomic Tumor Analysis Consortium and other large consortiums.

The permissive role of TCTP in PM2.5/NNK-induced epithelial-mesenchymal transition in lung cells.

BACKGROUND: Translationally controlled tumor protein (TCTP) is linked to lung cancer. However, upon lung cancer carcinogens stimulation, there were no reports on the relationship between TCTP and lung cell carcinogenic epithelial-mesenchymal transition (EMT). This study was designed to investigate the molecular mechanism of regulation of TCTP expression and its role in lung carcinogens-induced EMT. METHODS: To study the role of TCTP in lung carcinogens [particulate matter 2.5 (PM2.5) or 4-methylnitrosamino-l-3-pyridyl-butanone (NNK)]-induced EMT, PM2.5/NNK-treated lung epithelial and non-small cell lung cancer (NSCLC) cells were tested. Cell derived xenografts, human lung cancer samples and online survival analysis were used to confirm the results. MassArray assay, Real-time PCR and Reporter assays were performed to elucidate the mechanism of regulation of TCTP expression. All statistical analyses were performed using GraphPad Prism version 6.0 or SPSS version 20.0. RESULTS: Translationally controlled tumor protein and vimentin expression were up-regulated in PM2.5/NNK-treated lung cells and orthotopic implantation tumors. TCTP expression was positively correlated with vimentin in human NSCLC samples. Patients with high expression of TCTP displayed reduced overall and disease-free survival. TCTP overexpression could increase vimentin expression and promote cell metastasis. Furthermore, PM2.5/NNK stimulation brought a synergistic effect on EMT in TCTP-transfected cells. TCTP knockdown blocked PM2.5/NNK carcinogenic effect. Mechanically, PM2.5/NNK-induced TCTP expression was regulated by one microRNA, namely miR-125a-3p, but not by methylation on TCTP gene promoter. The level of TCTP was regulated by its specific microRNA during the process of PM2.5/NNK stimulation, which in turn enhanced vimentin expression and played a permissive role in carcinogenic EMT. CONCLUSIONS: Our results provided new insights into the mechanisms of TCTP regulatory expression in lung carcinogens-induced EMT. TCTP and miR-125a-3p might act as potential prognostic biomarkers and therapeutic targets for NSCLC.

Enhanced Catalytic Oxidation of Chlorobenzene over MnO2 Grafted In Situ by Rare Earth Oxide: Surface Doping Induces Lattice Oxygen Activation.

A series of highly active MnO2@REOx (RE = Gd, Sm, Ce, and La) catalysts were successfully synthesized via in situ growth on the surface of MnO2, wherein the rare earth oxides were planted on the defect sites left by hydrogen peroxide etching of the surface of MnO2. Their physicochemical performance was investigated by scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD), N2 adsorption-desorption, X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction with hydrogen (H2-TPR), and temperature-programmed desorption of oxygen (O2-TPD). The catalytic properties are compared through the catalytic oxidation of chlorobenzene. Among all catalysts, MnO2@GdOx showed better mobility of surface lattice oxygen and higher molar ratios of Mn4+/Mn3+ (1.10) and Oads/Olatt (0.45), which promoted the superior low-temperature catalytic activity for chlorobenzene oxidation. The long-term chlorobenzene oxidation test (18 h) at different temperatures and the experiments with a mixture of VOCs showed that the as-prepared catalyst not only possessed a high stability but also was suitable for the efficient and simultaneous removal of multicomponent VOCs (toluene, benzene, acetone, and chlorobenzene). This work also provided an idea for the further development of high-efficiency catalysts for the purification of VOCs from complex atmosphere environment.

Highly Active Mn3-xFexO4 Spinel with Defects for Toluene Mineralization: Insights into Regulation of the Oxygen Vacancy and Active Metals.

A series of highly defected Mn3-xFexO4 spinels with different amounts of oxygen vacancies and active metals were successfully synthesized by regulating the insertion of Fe ions into the crystal structure of Mn3O4 via self-polymerizable monomer adjustment of the molten Mn-Fe salt dispersion. The characterization of X-ray diffraction, Raman, scanning electron microscopy, X-ray photoelectron spectroscopy, and N2 adsorption-desorption showed that the doping of Fe increased the lattice defects, oxygen vacancy concentration, specific surface area, mesoporosity, and catalytic properties compared to Cu ions doping. Temperature-programmed reduction with hydrogen and oxygen pulse chemisorption tests determined that the doping level of Fe ions had an important influence on the oxygen vacancy content and the dispersion of active metals on the catalysts' surfaces. For the best Mn-dispersed and most active Mn2.4Fe0.6O4 catalyst, a long-term toluene oxidation measurement running for 120 h of uninterrupted reaction, at the low temperature of 240 °C, high humidity (relative humidity = 100%), and high weight hourly space velocity of 60000 mL·g-1·h-1, was also carried out, which indicated that the catalyst possessed high stability and endurability. Moreover, the continuous oxidation route and internal principle for toluene oxidation were also revealed by the in situ diffuse-reflectance infrared Fourier transform spectroscopy and gas chromatography-mass spectrometry techniques and deep dynamics study.

Catalytic Oxidation of VOCs over SmMnO3 Perovskites: Catalyst Synthesis, Change Mechanism of Active Species, and Degradation Path of Toluene.

Highly active samarium manganese perovskite oxides were successfully prepared by employing self-molten-polymerization, coprecipitation, sol-gel, and impregnation methods. The physicochemical properties of perovskite oxides were investigated by XRD, N2 adsorption-desorption, XPS, and H2-TPR. Their catalytic performances were compared via the catalytic oxidation of toluene. The perovskite prepared by self-molten-polymerization possessed the highest catalytic capacity, which can be ascribed to its higher oxygen adspecies concentration (Olatt/Oads = 0.53), higher surface Mn4+/Mn3+ ratio (Mn4+/Mn3+ = 0.95), and best low-temperature reducibility (H2 consumption = 0.27; below 350 °C). The most active catalyst also exhibited good cycling and long-term stability for toluene oxidation. After a multistep cycle reaction and a long-term reaction of 42 h, the toluene conversion maintained above 99.9% at 270 °C. Mechanistic study hinted that lattice oxygen was involved in toluene oxidation. The oxidation reaction was dependent on the synergism of lattice oxygen, adsorbed oxygen, and oxygen vacancies. The degradation pathway of toluene, researched by diffuse reflectance infrared Fourier transform spectroscopy and online mass spectrometry technologies, demonstrated that a series of organic byproducts existed at a relatively low temperature. This work provides an efficient and practical method for selecting highly active catalysts and for exploring the catalytic mechanism for the removal of atmospheric environmental pollution.

O3-BAC-Cl2: A multi-barrier process controlling the regrowth of opportunistic waterborne pathogens in drinking water distribution systems.

Simulated drinking water distribution system (DWDS) treated with O3-BAC-Cl2 (ozone-biological activated carbon-chlorine) was constructed to study its effects on the regrowth of five typical opportunistic pathogens (OPs). It was found that O3-BAC-Cl2 could significantly reduce the regrowth of target OPs in the effluents of DWDS compared with Cl2 and O3-Cl2 with the same residual chlorine levels. However, the effect of O3-BAC-Cl2 on the average numbers of target OPs gene markers in the biofilms of DWDS was not apparent, suggesting that OPs in the biofilms of DWDS were tolerant to the upstream disinfection process. The quantification of target OPs in the BAC-filter column demonstrated that OPs decreased with the increase of depth, which was likely due to the organic nutrient gradient and microbial competition inside the BAC-filter. Increase in the ozone dose could further reduce the OPs at the bottom of the BAC-filter. Spearman correlation analysis demonstrated that some significant correlations existed between target microorganisms, suggesting potential microbial ecological relationships. Overall, our results demonstrated that the BAC-filter may act as a "battlefield" suppressing the OPs through microbial competition. O3-BAC-Cl2 could be an effective multi-barrier process to suppress the proliferation of OPs in the bulk water of DWDS. However, OPs protected by the biofilms of DWDS should receive further attention because OPs may be detached and released from the biofilms.

One-year survey of opportunistic premise plumbing pathogens and free-living amoebae in the tap-water of one northern city of China.

In this study, qPCR was used to quantify opportunistic premise plumbing pathogens (OPPPs) and free-living amoebae in 11 tap water samples collected over four seasons from a city in northern China. Results demonstrated that the average numbers of gene copies of Legionella spp. and Mycobacterium spp. were significantly higher than those of Aeromonas spp. (p < 0.05). Legionella spp. and Mycobacterium spp. were 100% (44/44) positively detected while P. aeruginosa and Aeromonas spp. were 79.54% (35/44) and 77.27% (34/44) positively detected. Legionella pneumophila was only detected in 4 samples (4/44), demonstrating its occasional occurrence. No Mycobacterium avium or Naegleria fowleri was detected in any of the samples. The average gene copy numbers of target OPPPs were the highest in summer, suggesting seasonal prevalence of OPPPs. Average gene copy numbers of OPPPs in the taps of low-use-frequency were higher than in taps of high-use-frequency, but the difference was not significant for some OPPPs (p > 0.05). Moderate negative correlations between the chlorine concentration and the gene copy numbers of OPPPs were observed by Spearman analysis (rs ranged from -0.311 to -0.710, p < 0.05). However, no significant correlations existed between OPPPs and AOC, BDOC, or turbidity. Moderate positive correlations were observed between the target microorganisms, especially for Acanthamoeba spp., through Spearman analysis (p < 0.05). Based on our studies, it is proposed that disinfectant concentration, season, taps with different-use frequency, OPPP species, and potential microbial correlations should be considered for control of OPPPs in tap water.

Direct Molten Polymerization Synthesis of Highly Active Samarium Manganese Perovskites with Different Morphologies for VOC Removal.

A morphology-controlled molten polymerization route was developed to synthesize SmMnO3 (SMO) perovskite catalysts with netlike (SMO-N), granular-like (SMO-G), and bulk (SMO-B) structures. The SMO perovskites were formed directly by a molten polymerization method, and their morphologies were controlled by using the derivative polymers as templates. Among all catalysts, the porous SMO-N exhibited the highest activity, over which the toluene, benzene, and o-xylene were completely oxidized to CO2 at 240, 270, and 300 °C, respectively, which was comparable to that of typical noble-metal catalysts. The apparent activation energies of toluene over SMO-N (56.4 kJ·mol-1) was much lower than that of SMO-G (70.8 kJ·mol-1) and SMO-B (90.1 kJ·mol-1). Based on the results of scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and H2 temperature-programmed reduction characterization, we deduce that the excellent removal efficiency of volatile organic compounds (VOCs) over SMO-N catalyst was attributable to the special structure, high surface Mn4+/Mn3+ and Olatt/Oads molar ratios, and strong reducibility. Due to the high activity, low cost, and simple preparation strategy, the SMO catalyst is a promising catalyst for VOC removal.

A potential nanoparticle-loaded in situ gel for enhanced and sustained ophthalmic delivery of dexamethasone.

Increasing the permeability of drugs across the cornea is key to improving drug absorption by the eye. This study presents a newly developed in situ gel loaded with nanoparticles, which could achieve controlled drug release and high ocular drug bioavailability by avoiding rapid precorneal clearance. The physicochemical parameters of the formulation were investigated and showed uniform size, physical stability, and favorable rheological and gelling properties. Ex vivo permeation studies revealed significantly higher drug release from the in situ gel loaded with nanoparticles compared to the conventional poloxamer in situ gel and the drug solution. When compared with a marketed formulation, the in situ gel loaded with nanoparticles provided slower controlled release and higher ocular bioavailability of dexamethasone. In conclusion, the developed nanoparticle-loaded in situ gel can successfully increase drug ocular bioavailability by enhancing contact time with the ocular surface and permeation through the cornea.