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Interspecies blastocyst complementation holds great potential to address the global shortage of transplantable organs by growing human organs in animals. However, a major challenge in this approach is the limited chimerism of human cells in evolutionarily distant animal hosts due to various xenogeneic barriers. Here, we reveal that human pluripotent stem cells (PSCs) struggle to adhere to animal PSCs. To overcome this barrier, we developed a synthetic biology strategy that leverages nanobody-antigen interactions to enhance interspecies cell adhesion. We engineered cells to express nanobodies and their corresponding antigens on their outer membranes, significantly improving adhesion between different species' PSCs during in vitro assays and increasing the chimerism of human PSCs in mouse embryos. Studying and manipulating interspecies pluripotent cell adhesion will provide valuable insights into cell interaction dynamics during chimera formation and early embryogenesis., Competing Interests: Declaration of interests E.B., J.H., and J.W. are inventors on provisional patent application 63/488,889 entitled “A synthetic nanobody-mediated cell adhesion system to improve chimerism” arising from this work. J.W. is a member of the Cell Stem Cell advisory board., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 [ 3 H]chloroquine (endosomal pH), and [ 14 C]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 V 1 G1/V 0 d2) 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., Competing Interests: Disclosures None.

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-β, 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., Competing Interests: Declaration of interests Y.W., L.Y., T.T., and J.W. are inventors on a patent application (applied through the Board of Regents of The University of Texas System, application number 63/488,401) entitled “Methods For the Derivation Culture Of Embryonic and Extra-Embryonic Stem Cells” arising from this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 (H 2 -TPR), oxygen temperature-programmed desorption (O 2 -TPD), and N 2 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, LaCoO 3 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 LaCoO 3 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, LaCoO 3 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.

Recent advances in human blastoids have opened new avenues for modeling early human development and implantation. One limitation of our first protocol for human blastoid generation was relatively low efficiency. We now report an optimized protocol for the efficient generation of large quantities of high-fidelity human blastoids from naive pluripotent stem cells. This enabled proteomics analysis that identified phosphosite-specific signatures potentially involved in the derivation and/or maintenance of the signaling states in human blastoids. Additionally, we uncovered endometrial stromal effects in promoting trophoblast cell survival, proliferation, and syncytialization during co-culture with blastoids and blastocysts. Side-by-side single-cell RNA sequencing revealed similarities and differences in transcriptome profiles between pre-implantation blastoids and blastocysts, as well as post-implantation cultures, and uncovered a population resembling early migratory trophoblasts during co-culture with endometrial stromal cells. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, and tractable model for human blastocysts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of interests J.W. and L.L. are named inventors on a patent application (applied through the Board of Regents of The University of Texas System, application number 63/510,612; status of application pending) entitled “SYSTEM AND METHODS FOR GENERATION OF HUMAN FETAL PROGENITORS, TISSUES, AND ORGANS FROM CULTURED STEM CELLS” arising from this work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Photocatalytic CO 2 conversion for hydrocarbon fuel production has been known as one of the most promising strategies for achieving carbon neutrality. Yet, its conversion efficiency remains unsatisfactory mainly due to its severe charge-transfer resistance and slow charge kinetics. Herein, a tunable interfacial charge transfer on an oxygen-vacancies-modified bismuth molybdate nanoflower assembled by 2D nanosheets (BMOVs) and 2D bismuthene composite (Bi/BMOVs) is demonstrated for photocatalytic CO 2 conversion. Specifically, the meticulous design of the Ohmic contact formed between BMOVs and bismuthene can allow the modulation of the interfacial charge-transfer resistance. According to density functional theory (DFT) simulations, it is ascertained that such exceptional charge kinetics is attributed to the tunable built-in electric field (IEF) of the Ohmic contact. As such, the photocatalytic CO 2 reduction performance of the optimized Bi/BMOVs (CO and CH 4 productions rate of 169.93 and 4.65 µmol g -1 h -1 , respectively) is ca. 10 times higher than that of the pristine BMO (CO and CH 4 production rates of 16.06 and 0.51 µmol g -1 h -1 , respectively). The tunable interfacial resistance of the Ohmic contact reported in this work can shed some important light on the design of highly efficient photocatalysts for both energy and environmental applications., (© 2023 Wiley-VCH GmbH.)

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Understanding the mechanisms of blastocyst formation and implantation is critical for improving farm animal reproduction but is hampered by a limited supply of embryos. Here, we developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via assembling bovine trophoblast stem cells and expanded potential stem cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, in vitro growth, and the ability to elicit maternal recognition of pregnancy following transfer to recipient cows. Bovine blastoids represent an accessible in vitro model for studying embryogenesis and improving reproductive efficiency in livestock species., Competing Interests: Declaration of interests C.A.P.-A., Y. Wang., Y. Wei., Z.J., and J.W. are co-inventors on US provisional patent application 63/370,068 relating to bovine-blastocyst-like structures and uses thereof., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Procrastination (the intentional delay of action despite knowing that one will be worse off due to the delay) is a widespread phenomenon with various negative consequences, especially among adolescents. Based on relevant evidence, this study examined the relation between negative life events and adolescents' procrastination, as well as the underlying mechanisms-specifically, the effects of negative emotions and rumination, as well as the potential gender differences. A total of 780 adolescents (M age = 12.92 years old; 52.2% females) were recruited to complete a set of questionnaires assessing negative life events, procrastination, depression-anxiety-stress symptoms and rumination. Results showed that negative life events were positively associated with procrastination, and negative emotions significantly mediated the relation; rumination played a moderating role in this mediation model, specifically, both the direct and indirect effects in this mediation model were stronger for adolescents with higher rumination. Besides this, gender differences in this moderated mediation model were also found-the indirect effect of negative emotions was stronger for girls, and this mediating effect could be moderated by rumination only for boys. These results expanded our understanding of how negative life events influence procrastination and when (or for whom) negative life events influence procrastination the most. The findings also have significant implications for the prevention and intervention of adolescents' procrastination.

In the current information age, SNSs (Social Network Sites) have been popular among young adolescents, and have also become a main manner to maintain social relationships. Against this background, based on relevant evidence, the present study aimed to examine the association between positive self-disclosure on SNSs and adolescents' friendship quality, as well as the underlying mechanism-the potential mediating role of perceived positive feedback and the moderating role of social anxiety. A sample of 1713 adolescents aged 11 to 19 was recruited to participate in this study, to complete a set of scales. Results indicated that positive self-disclosure on SNSs was positively associated with adolescents' friendship quality, and positive feedback significantly mediated the association between self-disclosure positivity and friendship quality. This mediating effect, moderated by social anxiety, could significantly moderate the mediating effect of positive feedback; specifically, compared with higher social anxiety adolescents, the association between positive self-disclosure and positive feedback was stronger among individuals with lower social anxiety. These findings may expand previous studies, with several theoretical and practical implications.

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., (© 2022. The Author(s).)

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Although ectopic expression in model organisms suggests that morphogen gradients form through diffusion, little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis due to the combined difficulties of measuring endogenous morphogen levels and observing development in utero. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells, during specification of germ layers. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a paradigm for tissue patterning by an activator-inhibitor pair., (© 2022. The Author(s).)

A series of Sm-Mn perovskite@mullite composites with different amounts of acid sites were successfully synthesized by regulating the level of in situ etched-surface modification. X-ray diffraction (XRD) test showed that the crystal structure of catalyst gradually changed from perovskite to perovskite@mullite composites and mullite. The characterization of temperature programmed desorption with ammonia (NH 3 -TPD) confirmed the acid sites on the surface of catalyst can be deployed by the in-situ modification. The temperature-programmed reduction with hydrogen (H 2 -TPR), and N 2 adsorption-desorption showed that the surface modification also increased the reducibility, surface area, and mesoporosity of catalyst. The catalytic activities were compared by a long-term catalytic oxidation of chlorobenzene evaluation for 20 h of uninterrupted reaction at a relatively low temperature of 300 °C, and the Sm-Mn perovskite@mullite composite (SMPM-1.2) possessed the best catalytic stability. The X-ray photoelectron spectroscopy (XPS) measurement determined that the high ratios of lattice oxygen and tetravalent manganese did not improve the stability of catalyst in the catalytic oxidation of chlorobenzene, but the activities trends of samples were consistent with the change of surface (Mn 4+ +Mn 3+ )/Mn 2+ ratios. Meanwhile, the catalytic experiments for benzene, toluene, o-xylene and acetone showed that the as-prepared catalyst was also suitable for the efficient removal of the different types of VOCs. This work supplied a method for the further development of high activity catalysts for the removal of VOCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Low redox ability and severe photocorrosion limit the photocatalytic activity of metal sulfides. Herein, step-scheme (S-scheme) heterojunction composited by diethylenetriamine (DETA) ammoniated MnS (α-MnS) and Bi 2 MoO 6 with Bi surface plasmon resonance (SPR) was successfully fabricated (Bi-5 %M/BMO). This special electron transport structure effectively suppresses the photocorrosion of α-MnS and makes photocatalysts with high redox ability. DETA was protonated to form positively charged ammonium ions and they are easy to combine with acid gas CO 2 , reducing the activation energy of CO 2 , building an efficient catalytic reaction system, and improving CO 2 reduction efficiency. The CO evolution rate of Bi-5 %M/BMO (61.11 μmol g -1 h -1 ) is 2.42, 7.89 and 5.01 times greater than that of 5 %M/BMO, pure α-MnS hollow spheres and Bi 2 MoO 6 , respectively. This indicates that Bi SPR effect can promote the separation of photon-generated electron-hole pairs dramatically. The ammoniated S-scheme heterostructure decorated with the SPR effect may provide a new perspective to design heterojunction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The spent ternary lithium-ion batteries were utilized as the precursors to prepare Sm-Mn and Sm-Co perovskite oxides (SmMnO 3 -spent ternary lithium-ion battery [STLIB] and SmCoO 3 -STLIB) for the first time. Their catalytic activities were evaluated by catalytic oxidation of propylene glycol methyl ether. Compared with that of the catalysts synthesized by analytical reagents, the catalytic activities of SmMnO 3 -STLIB and SmCoO 3 -STLIB had been significantly enhanced. The analysis of X-ray photoelectron spectroscopy (XPS) showed that the molar ratios of Mn 4+ /Mn 3+ and O ads /O latt of SmMnO 3 -STLIB were higher than that of pure SmMnO 3 and the Co 3+ /Co 2+ ratios of SmCoO 3 -STLIB was much larger than that of pure SmCoO 3 . The hydrogen temperature-programmed reduction (H 2 -TPR) and N 2 adsorption-desorption tests determined that the reducibilities and specific surface areas of SmMnO 3 -STLIB and SmCoO 3 -STLIB were also superior to pure catalysts. Ultimately, the by-products of the catalytic oxidation of propylene glycol methyl ether over SmMnO 3 -STLIB were also detected by gas chromatography-mass spectrometry (GC-MS). This work will provide a demonstration for the resource utilization of spent lithium ions batteries and the analysis of the increased activity obtained by using spent lithium ions batteries as the precursors to prepare catalysts., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study analyzed the effect of lipid peroxidation using 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) and acrolein on the in vitro and in vivo allergenicity of α-lactalbumin (α-La). The structure of oxidized α-La was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, fluorescence spectroscopy, and circular dichroism, whereas the changes in the allergenic properties were evaluated. Lipid peroxidation induced changes to the structural properties that might destroy and/or mask α-La epitopes. In comparison to native α-La, oxidation complexes caused a decrease in the immunoglobulin E (IgE) binding capacity, as observed via immunoblotting. Moreover, the capacity to release mediators and cytokines from KU812 cells was also greatly reduced. In vivo , oxidation with AAPH and acrolein caused a significant reduction in IgE, IgG, IgG1, mast cell protease 1, and plasma histamine, along with the reduction of mast surface c-Kit + and FcεRI + expression. Therefore, these results indicate that oxidation via AAPH and acrolein can potentially reduce the allergenicity of α-La, which can help with the better understanding of the changes in allergenicity of milk allergen by lipid peroxidation.

Mammalian embryonic development is a complex process driven by self-organization. Understanding how a fertilized egg develops into an embryo composed of more than 200 cell types in precise spatial patterns remains one of the fundamental challenges in biology. Pluripotent stem cells have been used as in vitro models for investigating mammalian development, and represent promising building blocks for regenerative therapies. Recently, sophisticated stem cell-based models that recapitulate early embryonic fate patterning and morphogenesis have been developed. In this article, we review recent advances in stem cell models of embryos in particular focusing on signaling activities underpinning cell fate decisions in space and time., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In this work, manganese is selectively and efficiently recovered from spent lithium-ion batteries via advanced oxidation by using potassium permanganate and ozone, and the transition metal-doped α-MnO 2 and β-MnO 2 are one-step prepared for catalytic oxidation of VOCs. The recovery rate of manganese can be approximately 100% while the recovery efficiency of cobalt, nickel, and lithium is less than 15%, 2%, and 1%, respectively. Compared with pure α-MnO 2 and β-MnO 2 , transition metal-doped α-MnO 2 and β-MnO 2 exhibit better catalytic performance in toluene and formaldehyde removal attributed to their lower crystallinity, more defects, larger specific surface area, more oxygen vacancies, and better low-temperature redox ability. Besides, the introduction of the appropriate proportion of cobalt or nickel into MnO 2 can significantly improve its catalytic activity. Furthermore, the TD/GC-MS result indicates that toluene may be oxidized in the sequence of toluene - benzyl alcohol - benzaldehyde-benzoic acid - acetic acid, 2-cyclohexen-1-one, 4-hydroxy-, cyclopent-4-ene-1,3-dione - carbon dioxide. This method provides a route for the resource utilization of spent LIBs and the synthesis of MnO 2 ., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Porous Mn-based mullite SmMn 2 O 5 was synthesized by the in-situ dismutation of solid state Mn 3+ in bulk SmMnO 3 perovskite to catalytic oxidation of benzene and chrolobenznen. The physicochemical property of catalyst was acquired by XRD, SEM, N 2 adsorption-desorption, XPS, O 2 -TPD and H 2 -TPR. Compared with that of bulk SmMnO 3 and bulk SmMn 2 O 5 , the porous SmMn 2 O 5 mullite (SmMn 2 O 5 -ID) displayed higher molar ratios of Mn 4+ /Mn 3+ and O latt /O ads , and better active oxygen desorption capacity, reducibility and larger specific surface, which promoted the preferable low-temperature catalytic oxidation of VOC. The increase in the content of Mn 4+ on the surface of the Sm-Mn mullite reduced the surface defects and increased the proportion of its surface lattice oxygen, thereby promoting the attack of VOC molecules by more lattice oxygen. Combined with the analysis of reactant intermediate for benzene oxidation by in situ diffuse reflectance infrared Fourier transform spectroscopy, the catalytic mechanism of the catalyst was also explored. Moreover, SmMn 2 O 5 -ID also showed the excellent stability and the superior removal of mixed VOCs with different concentration ratios. This finding provides an efficient and practical method for exploiting highly active Mn-based mullite with a high efficiency and stability for the purification of air pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/objective: SSS07, a humanized rabbit monoclonal antibody, can selectively block human tumor necrosis factor-α (TNF-α). The objective of this study was to assess the safety, tolerability, and relative immunogenicity of SSS07 after multiple single subcutaneous (SC) doses in healthy volunteers., Methods: A total of 71 healthy volunteers were randomized to six sequential ascending-dose groups (5, 15, 30, 50, 75, and 100 mg), and except for the 100 mg group that only had one subject who received a placebo, all of the other groups included two placebo-control subjects. Safety, tolerability, and immunogenicity were assessed by physical examinations, vital signs, electrocardiography (ECG), clinical laboratory tests, and plasma anti-drug antibody (ADA) over 28 days for each group. Their concentrations of TNF-α were also analyzed. Only after safety and tolerance were determined in the lower-dose groups was the next dose group initiated. The dose increments did not exceed 100 mg., Results: No serious adverse events or dose-limited toxicity (DLT) were observed, so 100 mg was defined as the maximum tolerated dose (MTD). Overall, 71 AEs and 59 treatment-related adverse events (TRAEs) were reported in 36 (60.0%) and 30 (50.0%) volunteers, respectively, who received SSS07. All AEs and TRAEs were mild or moderate and expected based on previous results with similar types of drugs, without new safety concerns. Except for infections and administration site reactions, the frequency and intensity of the other TRAEs were similar for SSS07 and placebo. No severe acute immune reactions occurred. The lower dose's immunogenicity was stronger than the higher doses. The highest ADA titer was observed 3 to 6 months after administration., Conclusion: SSS07 was generally safe and well tolerated in healthy Chinese volunteers. Higher immunogenicity was observed at low SSS07 concentration levels. The infections and administration site conditions might have been related to the immunogenicity and the degree of inhibition of TNF-α. However, the existence of ADA did not appear to affect the safety of the subjects throughout the follow-up period. These findings could support further investigations of treatments with humanized monoclonal antibodies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of highly active MnO 2 @REO x (RE = Gd, Sm, Ce, and La) catalysts were successfully synthesized via in situ growth on the surface of MnO 2 , wherein the rare earth oxides were planted on the defect sites left by hydrogen peroxide etching of the surface of MnO 2 . Their physicochemical performance was investigated by scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD), N 2 adsorption-desorption, X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction with hydrogen (H 2 -TPR), and temperature-programmed desorption of oxygen (O 2 -TPD). The catalytic properties are compared through the catalytic oxidation of chlorobenzene. Among all catalysts, MnO 2 @GdO x showed better mobility of surface lattice oxygen and higher molar ratios of Mn 4+ /Mn 3+ (1.10) and O ads /O latt (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.

Cytosine base editors (CBEs) enable efficient cytidine-to-thymidine (C-to-T) substitutions at targeted loci without double-stranded breaks. However, current CBEs edit all Cs within their activity windows, generating undesired bystander mutations. In the most challenging circumstance, when a bystander C is adjacent to the targeted C, existing base editors fail to discriminate them and edit both Cs. To improve the precision of CBE, we identified and engineered the human APOBEC3G (A3G) deaminase; when fused to the Cas9 nickase, the resulting A3G-BEs exhibit selective editing of the second C in the 5'-CC-3' motif in human cells. Our A3G-BEs could install a single disease-associated C-to-T substitution with high precision. The percentage of perfectly modified alleles is more than 6000-fold for disease correction and more than 600-fold for disease modeling compared with BE4max. On the basis of the two-cell embryo injection method and RNA sequencing analysis, our A3G-BEs showed minimum genome- and transcriptome-wide off-target effects, achieving high targeting fidelity., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The selectivity of a facile reductive and extractive desulfurization process was studied. In this desulfurization method, polyethylene glycol was used as the extractant, and sodium borohydride was used as the reductant. Several different simulated fuels were prepared by dissolving thiophenic sulfides, methylbenzene and hexylene in octane. The results showed that methylbenzene and olefins had different effects on different sulfur compounds during this desulfurization process. The extraction and reduction mechanisms were also explained. Four factors could affect the desulfurization performance: (1) intermolecular hydrogen bonding: (a) active O bonding with aromatic H or (b) S bonding with H atoms in hydroxide radicals, (2) "like-dissolves-like" interactions between polyethylene glycol and thiophenic sulfides, (3) the methyl steric hindrance effect and the electron density of sulfur atoms, and (4) the combination of S atoms with produced nickel boride to form active desulfurization centres. The desulfurization reaction path was also deduced according to the GC/MS results.

Objective: This meta-analysis was performed to investigate hyperlipidemia in patients with carcinoma treated with vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors., Methods: We searched for eligible phase II and III studies using PubMed and Embase databases. We then summarized reported occurrences of hyperlipidemia in patients with different cancers. Relative risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by Revman 5 software in meta-analysis., Results: Eleven trials (4760 subjects) were included in this meta-analysis. Overall, VEGF/VEGFR inhibitors had similar incidence of hypertriglyceridemia (RR = 0.56, 95% CI = 0.24%-1.32%, P = .19), hypercholesterolemia (RR = 1.15, 95% CI = 0.42%-3.16%, P = .78), and LDL elevation (RR = 4.58, 95% CI = 0.80%-26.25%, P = .09) than control drugs, under high heterogeneity. Moreover, subgroup analyses found VEGF/VEGFR inhibitors had higher incidence of hypertriglyceridemia (RR = 1.86, 95% CI = 1.37%-2.52%, P < .001) and hypercholesterolemia (RR = 2.95, 95% CI = 2.02%-4.30%, P = .006) than blank control or placebo control drugs (placebo-controlled-group), although with lower incidence of hypertriglyceridemia (RR = 0.29, 95% CI = 0.12%-0.69%, P < .001) and hypercholesterolemia (RR = 0.39, 95% CI = 0.28%-0.56%, P < .001) than positive control drugs (positive-controlled-groups)., Conclusion: The use of VEGF/VEGFR inhibitors, especially the multitargeted VEGFR tyrosine kinase inhibitors (VEGFR-TKIs), was associated with higher risk of hyperlipidemia than the use of placebo, but this risk was less than that associated with mTOR or FGFR inhibitors. It indicated that clinicians need to pay close attention to the occurrence of hyperlipidemia in VEGFR-TKIs therapies., (Copyright © 2020 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital. Published by Elsevier Inc. All rights reserved.)

Valuable metals such as manganese, cobalt, nickel and copper are recycled from spent ternary lithium-ions batteries (LiBs) and are considered as the active metal precursor to prepare based-manganese multi oxide for VOCs oxidation. The results of characterization analysis indicate that the catalyst from spent LiBs shows larger specific surface area of 26.80 m 2 /g as well as abundant mesoporous structures on the surface, higher molar ratio of Mn 4+ /Mn 3+ (0.70) and O latt /O ads (1.68), better low-temperature reductivity and stronger intensity of weak acid sites in comparison with those of pure manganese oxides. The evaluation experiments show that the catalyst from waste exhibits more excellent catalytic performance of toluene combustion in comparison with pure manganese oxides. Furthermore, the presence of considerable amount of lithium and aluminum ions can severely weaken the catalytic activity while the co-existence of nickel, cobalt and copper ions contribute a lot to facilitate the catalytic behavior. In-situ DRIFT study implies that the introduction of lithium, aluminum, nickel, copper and cobalt into pure manganese oxides can facilitate toluene conversion to various extents, following the consecutive steps via benzyl species, benzoyl oxide species, benzaldehyde species, benzoate species and the primary intermediates are benzoate species., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: 2-HP-β-cyclodextrin-PLGA nanoparticle complexes were prepared to enhance the aqueous humour delivery of Triamcinolone acetonide. Materials & methods: Drug-loaded 2-HP-β-CD/PLGA nanoparticle complexes prepared by adapting a quasi-emulsion solvent evaporation technique. In vitro drug release, in vitro transcorneal permeation study, histopathological study and in vivo transcorneal penetration of PLGA nanoparticles and 2-HP-β-CD/PLGA nanoparticle complexes were evaluated. Results: Particle size distributions of 2-HP-β-CD/PLGA nanoparticle complexes were 149.4 ± 3.7 nm and presented stable system. Corneal penetration studies revealed steady sustained drug release (First-order); 2-HP-β-CD/PLGA nanoparticle complexes increased ocular bioavailability by increasing dispersion in the tear film and improving drug release. Conclusion: 2-HP-β-CD/PLGA nanoparticle complex formulation is a promising alternative to conventional eye drops.

We investigated the allergenicity, digestibility and functional properties of whey protein isolate (WPI) after covalent conjugation with chlorogenic acid (CHA). The covalent conjugation of CHA may cause an unfolded protein structure. The WPI-CHA conjugate showed lower IgE binding capacity but higher intestinal digestibility than unmodified WPI. Furthermore, after digestion, the IgE binding capacity of β-lactoglobulin and α-lactoalbumin was lower in the digested WPI-CHA conjugate than digested WPI. Moreover, the solubility, emulsifying activity, foaming properties and antioxidant capacity of WPI were enhanced by covalent conjugation of CHA. Covalent conjugation with CHA might reduce the allergenicity in vitro of WPI by improving the functional properties of the protein., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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, N 2 adsorption-desorption, XPS, and H 2 -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 (O latt /O ads = 0.53), higher surface Mn 4+ /Mn 3+ ratio (Mn 4+ /Mn 3+ = 0.95), and best low-temperature reducibility (H 2 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.

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., Competing Interests: The authors have declared that no competing interests exist.

A series of highly defected Mn 3- x Fe x O 4 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 Mn 3 O 4 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 N 2 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 Mn 2.4 Fe 0.6 O 4 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.

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Anthraquinones, a class of naturally occurring polyphenolic compounds, exhibit a wide range of bioactivities. However, most free anthraquinones are lipophilic bioactive compounds. Bovine β-lactoglobulin (βLG), a major whey protein, has a high affinity for small hydrophobic compounds. In this study, the interactions between anthraquinones (rhein, emodin, and chrysophanol) and βLG were investigated by using fluorescence, circular dichroism (CD), Fourier-transform infrared spectroscopy (FTIR), and docking studies. These anthraquinones bound to the site near Trp19-Arg124 on βLG with a binding constant (Ka) between 10 3 and 10 5  L mol -1 to form complexes, which changed the secondary structure of βLG, inducing an α-helix to β-sheet structure transition. The order of binding increased with an increasing polarity in the order of rhein > emodin > chrysophanol. In addition, the degree of radical scavenging capacity masking increased with an increasing binding affinity. Complexation with βLG significantly increases the hydrosolubility of anthraquinones., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

During embryonic development, diffusible signaling molecules called morphogens are thought to determine cell fates in a concentration-dependent way. Yet, in mammalian embryos, concentrations change rapidly compared to the time for making cell fate decisions. Here, we use human embryonic stem cells (hESCs) to address how changing morphogen levels influence differentiation, focusing on how BMP4 and Nodal signaling govern the cell-fate decisions associated with gastrulation. We show that BMP4 response is concentration dependent, but that expression of many Nodal targets depends on rate of concentration change. Moreover, in a self-organized stem cell model for human gastrulation, expression of these genes follows rapid changes in endogenous Nodal signaling. Our study shows a striking contrast between the specific ways ligand dynamics are interpreted by two closely related signaling pathways, highlighting both the subtlety and importance of morphogen dynamics for understanding mammalian embryogenesis and designing optimized protocols for directed stem cell differentiation., Editorial Note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)., Competing Interests: IH, KB, MM, SC, MG, LL, AW No competing interests declared, (© 2019, Heemskerk et al.)

Drinking water distribution systems (DWDS) may be a "Trojan Horse" for some waterborne diseases caused by opportunistic pathogens (OPs). In this study, two simulated DWDS inoculated with groundwater were treated with chlorine (Cl 2 ) and ultraviolet/chlorine (UV/Cl 2 ) respectively to compare their effects on the OPs distributed in four different phases (bulk water, biofilms, corrosion products, and loose deposits) of DWDS. 16S rRNA genes sequencing and qPCR were used to profile microbial community and quantify target genes of OPs, respectively. Results showed that UV/Cl 2 was more effective than single Cl 2 to control the regrowth of OPs in the water with the same residual chlorine concentration. However, the OPs inhabiting the biofilms, corrosion products, and loose deposits seemed to be tolerant to UV/Cl 2 and Cl 2 , demonstrating that OPs residing in these phases were resistant to the disinfection processes. Some significant microbial correlations between OPs and Acanthamoeba were found by Spearman correlative analysis (p < 0.05), demonstrating that the ecological interactions may exist in the DWDS. 16S rRNA genes sequencing of water samples revealed a significant different microbial community structure between UV/Cl 2 and Cl 2 . This study may give some implications for controlling the OPs in the DWDS disinfected with UV/Cl 2 ., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 (r s 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., (Copyright © 2018. Published by Elsevier B.V.)

Simulated drinking water distribution system (DWDS) treated with O 3 -BAC-Cl 2 (ozone-biological activated carbon-chlorine) was constructed to study its effects on the regrowth of five typical opportunistic pathogens (OPs). It was found that O 3 -BAC-Cl 2 could significantly reduce the regrowth of target OPs in the effluents of DWDS compared with Cl 2 and O 3 -Cl 2 with the same residual chlorine levels. However, the effect of O 3 -BAC-Cl 2 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. O 3 -BAC-Cl 2 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., (Copyright © 2018. Published by Elsevier B.V.)

γ-MnO 2 , SmMnO 3 , and γ-MnO 2 /SmMnO 3 catalysts were prepared by facile methods, wherein the SmMnO 3 (SMO) perovskite was synthesized through one-step calcination and the γ-MnO 2 /SmMnO 3 was formed by an in situ growth of γ-MnO 2 on the surface of SMO. These materials ware characterized by XRD, SEM-mapping, N 2 -adsorption, XPS and H 2 -TPR to investigate their textural properties. Compared with that of SMO and γ-MnO 2 , the γ-MnO 2 /SMO shows better performance for catalytic oxidation of aromatic VOCs in wet air (10 vol.%), which may be attributed to its higher surface molar ratio of lattice oxygen to adsorbed oxygen (O latt /O ads ) and better low-temperature reducibility. Besides, for γ-MnO 2 /SMO catalyst, a successive oxidation route and the inner principle of BETX (benzene, ethylbenzene, toluene, and o-xylene) oxidation were also revealed via various tests and a comprehension of dynamics investigation. Meanwhile, the experiments under simulated realistic exhaust conditions displayed that the γ-MnO 2 /SmMnO 3 is also a good catalyst with high stability for aromatic VOCs oxidation, and fulfilled endurability to high humidity (20 vol.%)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The effects of O 3 /Cl 2 disinfection on corrosion and the growth of opportunistic pathogens in drinking water distribution systems were studied using annular reactors (ARs). The corrosion process and most probable number (MPN) analysis indicated that the higher content of iron-oxidizing bacteria and iron-reducing bacteria in biofilms of the AR treated with O 3 /Cl 2 induced higher Fe 3 O 4 formation in corrosion scales. These corrosion scales became more stable than the ones that formed in the AR treated with Cl 2 alone. O 3 /Cl 2 disinfection inhibited corrosion and iron release efficiently by changing the content of corrosion-related bacteria. Moreover, ozone disinfection inactivated or damaged the opportunistic pathogens due to its strong oxidizing properties. The damaged bacteria resulting from initial ozone treatment were inactivated by the subsequent chlorine disinfection. Compared with the AR treated with Cl 2 alone, the opportunistic pathogens M. avium and L. pneumophila were not detectable in effluents of the AR treated with O 3 /Cl 2 , and decreased to (4.60±0.14) and (3.09±0.12) log 10 (gene copies/g corrosion scales) in biofilms, respectively. The amoeba counts were also lower in the AR treated with O 3 /Cl 2 . Therefore, O 3 /Cl 2 disinfection can effectively control opportunistic pathogens in effluents and biofilms of an AR used as a model for a drinking water distribution system., (Copyright © 2018. Published by Elsevier B.V.)

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.

Insulin-degrading enzyme (IDE) plays a critical role in both the proteolytic degradation and inactivation of insulin. The exploration of novel IDE inhibitors could aid in the study of novel therapeutics for type-2 diabetes. Herein, we report a hypothesized stabilized β-hairpin peptide that can efficiently inhibit the enzymatic activity of IDE. The resulting stabilized peptide B35 is demonstrated to activate the AKT phosphorylation pathway in skeletal muscle cells and is shown to slow insulin degradation. An 80 mg kg -1 intraperitoneal (i.p.) injection of the stabilized β-hairpin peptide B35 is demonstrated to improve glucose tolerance during an oral glucose tolerance test in obese mouse model. We note that this stabilized peptide exhibited negligible cytotoxicity in both in vitro and in vivo assays, even at high concentrations (300 μM). This study suggests that IDE peptide inhibitors could function as potentially meaningful candidates for the development of type-2 diabetes therapeutics.

The effects of ozone-biologically activated carbon (O 3 -BAC) treatment with various phosphate doses (0, 0.3 or 0.6 mg/L) were investigated on the formation of disinfection by-products (DBPs) and occurrence of opportunistic pathogens (OPs) in drinking water distribution systems (DWDSs) simulated by annular reactors (ARs). It was found that the lowest DBPs and the highest inactivation of OPs such as Mycobacterium spp., Mycobacterium avium, Aeromonas spp., Pseudomonas aeruginosa and Hartmanella vermiformis, occurred in the effluent of the AR with 0.6 mg/L phosphate addition. Based on the results of different characterization techniques, for the AR with 0.6 mg/L phosphate-enhanced O 3 -BAC treatment, dissolved organic carbon in the influent exhibited the lowest concentration and most stable fraction due to the improved biodegradation effect. Moreover, the total amount of suspended extracellular polymeric substances (EPS) in the bulk water of the AR decreased greatly, resulting in the lowest chlorine consumption and DBPs formation in the AR. In Fourier transform infrared spectra of the suspended EPS, the amide II band (1600-1500 cm -1 ) disappeared and the protein/polysaccharide ratio decreased remarkably, indicating the destruction of protein and a decrease in hydrophobicity. Moreover, β-sheets and α-helices in the protein secondary structures were degraded while the random coils increased sharply as phosphate addition increased to 0.6 mg/L, inhibiting microbial aggregation and hence weakening the chlorine-resistance capability. Thus, most of the OPs in suspended biofilms were more easily inactivated by residual chlorine, resulting in the lowest OPs occurrence in the effluent of the AR. Our findings indicated that enhancing the efficiency of the BAC filter by adding phosphate is a promising method for improving water quality in DWDSs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To help produce hypoallergenic food, this study investigated reducing the allergenicity and improving the functional properties of bovine β-lactoglobulin (βLG) by covalent conjugation with (-)-epigallo-catechin 3-gallate (EGCG) and chlorogenic acid (CA). The covalent bond between the polyphenols and the amino acid side-chains in βLG was confirmed by MALDI-TOF-MS and SDS-PAGE. Structural analysis by fluorescence spectroscopy, circular dichroism (CD) and Fourier transform infrared (FTIR) indicated that the covalent conjugate of EGCG and CA led to the changed protein structure of βLG. Western blot analysis and enzyme-linked immunosorbent assay indicated that conjugation of βLG with these polyphenols was effective in reducing the IgE-binding capacity of βLG. The conjugates maintained the retinol-binding activity without denaturation the protein and enhanced the thermal stability with high antioxidant activity. The study provides an innovative approach to producing hypoallergenic food., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A morphology-controlled molten polymerization route was developed to synthesize SmMnO 3 (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 CO 2 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 H 2 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 Mn 4+ /Mn 3+ and O latt /O ads 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.

Bacterial community structure and iron corrosion were investigated for simulated drinking water distribution systems (DWDSs) composed of annular reactors incorporating three different treatments: ozone, biologically activated carbon and chlorination (O 3 -BAC-Cl 2 ); ozone and chlorination (O 3 -Cl 2 ); or chlorination alone (Cl 2 ). The lowest corrosion rate and iron release, along with more Fe 3 O 4 formation, occurred in DWDSs with O 3 -BAC-Cl 2 compared to those without a BAC filter. It was verified that O 3 -BAC influenced the bacterial community greatly to promote the relative advantage of nitrate-reducing bacteria (NRB) in DWDSs. Moreover, the advantaged NRB induced active Fe(III) reduction coupled to Fe(II) oxidation, enhancing Fe 3 O 4 formation and inhibiting corrosion. In addition, O 3 -BAC pretreatment could reduce high-molecular-weight fractions of dissolved organic carbon effectively to promote iron particle aggregation and inhibit further iron release. Our findings indicated that the O 3 -BAC treatment, besides removing organic pollutants in water, was also a good approach for controlling cast iron corrosion and iron release in DWDSs., (Copyright © 2017. Published by Elsevier B.V.)

In this paper, the microstructure and mechanical properties that distribute regulation along the rolling direction of tailor rolled blanks (TRB) were investigated. A tensile specimen with equal probability in yield (EYS) was first designed considering variation both in thickness and in material strength. The uniaxial tension test was carried out with a digital image correlation method to analyze the mechanical behaviors. The results showed that the strain distribution of EYS was homogeneous. From the results, it can be known that a new design philosophy for a TRB tensile specimen is reasonable and EYS is suitable to characterize the mechanical behavior of TRB. The true stress-strain curves of metal in different cross sections of TRB were calculated. On the basis of the true stress-strain curves, a material model of TRB was constructed and then implemented into finite element simulations of TRB uniaxial tensile tests. The strain distribution of numerical and experimental results was similar and the error between the elongation of the specimen after fracture obtained by experiment and FE ranged from 9.51% to 13.06%. Therefore, the simulation results match well with the experimental results and the material model has high accuracy and as well as practicability.