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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.

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 (NH3-TPD) confirmed the acid sites on the surface of catalyst can be deployed by the in-situ modification. The temperature-programmed reduction with hydrogen (H2-TPR), and N2 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 (Mn4++Mn3+)/Mn2+ 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.

Interspecies chimera formation with human pluripotent stem cells (PSCs) holds great promise to generate humanized animal models and provide donor organs for transplant. However, the approach is currently limited by low levels of human cells ultimately represented in chimeric embryos. Different strategies have been developed to improve chimerism by genetically editing donor human PSCs. To date, however, it remains unexplored if human chimerism can be enhanced in animals through modifying the host embryos. Leveraging the interspecies PSC competition model, here we discovered retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling, an RNA sensor, in “winner” cells plays an important role in the competitive interactions between co-cultured mouse and human PSCs. We found that genetic inactivation ofDdx58/Ifih1-Mavs-Irf7axis compromised the “winner” status of mouse PSCs and their ability to outcompete PSCs from evolutionarily distant species during co-culture. Furthermore, by usingMavs-deficient mouse embryos we substantially improved unmodified donor human cell survival. Comparative transcriptome analyses based on species-specific sequences suggest contact-dependent human-to-mouse transfer of RNAs likely plays a part in mediating the cross-species interactions. Taken together, these findings establish a previously unrecognized role of RNA sensing and innate immunity in “winner” cells during cell competition and provides a proof-of-concept for modifying host embryos, rather than donor PSCs, to enhance interspecies chimerism.

High-fat environment facilitates the metastasis of lung adenocarcinoma (LUAD) with unknown mechanism. This work aims to reveal the role of fatty acid transporter CD36 in LUAD cell metastasis upon fatty acid oversupply. In human LUAD cells, palmitic acid (PA) treatment promoted CD36 sarcolemmal translocation, where it activated Rac1 and upregulated MMP-9 through Src-Akt/ERK pathway, resulting in redistribution of cortactin, N-WASP and Arp2/3, and finally led to occurrence of finger-like protrusions of actin on cell surface to enhance cell metastasis. Nude mice fed with normal-chew diet (NCD) and high-fat diet (HFD) were subcutaneously injected with scramble/CD36-shRNA stable tranfected-A549 cells respectively. Compared with NCD mice, the HFD group exhibited higher level of blood free fatty acid (FFA) and cholesterol (TC), developed larger xenograft LUAD tumors and enhanced tumor cell metastatic potential in a CD36-dependent manner, which accompanied by obvious sarcolemmal actin remodeling. Consistently, xenografted and tail vein-injected scramble RNA-A549 cells but not CD36-shRNA-A549 in HFD mice formed metastatic LUAD tumors on the lung. Collectively, our finding demonstrates that CD36 initiates the Src signal transduction to induce actin remodeling in high fat environment, which in turn promotes LUAD cell metastasis. Our finding provides valuable targets for prevention and treatment of LUAD.

Understanding blastocyst formation and implantation is critical for improving farm animal reproduction but is hampered by a limited supply of embryos. We developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via the assembly of trophoblast stem cells and expanded potential stem cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, and represent an accessible in vitro model for studying bovine embryogenesis.

SUMMARYRecent advances in human blastoids generated from naïve pluripotent stem cells have opened a new avenue for modelling early human development and implantation. Despite the success, however, existing protocols have several limitations, e.g., the use of custom-built microwell arrays impedes wide adoption by the research community, and mass production of human blastoids is hampered by low-output or low-efficiency methods. To address these issues, here we developed an optimized protocol based on commercially available microwell plates, which enabled efficient generation of high-fidelity human blastoids at a large scale. Leveraging on the improved protocol, we identified MAPK. PI3K/AKT and mTOR signaling pathways were activated in both blastoids and blastocyst, and discovered endometrial stromal effects in promoting trophoblast cell survival, proliferation and syncytialization during extended co-culture with blastoids. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, tractable, and ethical model for human blastocysts.

In this work, cathode materials of spent lithium-ion ternary batteries are recovered and used as metal precursor to prepare multi-metal oxides MnOx(SY) and GdMnO3(SY) via combustion method and sol–gel method, respectively. Furthermore, a series of MnOx(SY)-n and GdMnO3(SY)-n (n = 0.05, 0.10, 1.00, 4.00, n represents the dilute HNO3 concentration) catalysts are fabricated by acid treatment of MnOx(SY) and GdMnO3(SY) samples and catalytic activities of oxygenated VOCs oxidation over all the prepared catalysts are investigated. Catalytic evaluation results show that acid-treated MnOx(SY)-0.10 and GdMnO3(SY)-0.05 samples perform the optimum VOCs removal efficiency respectively, which may be attributed to their obvious enhancement of physicochemical properties. In detail, MnOx(SY)-0.10 and GdMnO3(SY)-0.05 samples exhibit the larger specific surface area, bigger amount of surface high-valence metal ions (Mn4+, Co3+, Ni3+), more abundant adsorbed oxygen species and better low-temperature reducibility, which can play a crucial role in the significant improvement of VOCs oxidation. In situ DRIFTS results imply that the possible main intermediates are -OCO, -COO and -C-O species produced during VOCs oxidation. Possible by-products are further determined via TD/GC–MS analysis.

The spent ternary lithium-ion batteries were utilized as the precursors to prepare Sm–Mn and Sm–Co perovskite oxides (SmMnO3-spent ternary lithium-ion battery [STLIB] and SmCoO3-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 SmMnO3-STLIB and SmCoO3-STLIB had been significantly enhanced. The analysis of X-ray photoelectron spectroscopy (XPS) showed that the molar ratios of Mn4+/Mn3+ and Oads/Olatt of SmMnO3-STLIB were higher than that of pure SmMnO3 and the Co3+/Co2+ ratios of SmCoO3-STLIB was much larger than that of pure SmCoO3. The hydrogen temperature-programmed reduction (H2-TPR) and N2 adsorption-desorption tests determined that the reducibilities and specific surface areas of SmMnO3-STLIB and SmCoO3-STLIB were also superior to pure catalysts. Ultimately, the by-products of the catalytic oxidation of propylene glycol methyl ether over SmMnO3-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.

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.

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.

Strong and tough steel Ultrahard materials often do not have similarly impressive fracture toughness. Liu et al. discovered a processing route for medium manganese steel alloy in which ultrahigh strength accompanies high fracture toughness. The steel relies on both transformation-induced plasticity and delamination toughening to boost the fracture properties. The steel is composed of less expensive elements, making it a potentially inexpensive material attractive for structural applications. Science , this issue p. 1347

A cobalt-based oxide catalyst is prepared using recovered metals, such as cobalt, copper, manganese, and nickel, from spent lithium-ion cobaltate batteries, and its catalytic performance in toluene...

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 com...

Highly active samarium manganese perovskite oxides were successfully prepared by employing self-molten-polymerization, coprecipitation, sol–gel, and impregnation methods. The physicochemical proper...

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 str...

In order to recycle and reuse metal resources from spent ternary lithium batteries, manganese-based composite perovskite is synthesized from waste by citrate sol–gel method and is used as catalyst for VOC removal. The characterization results indicate that manganese-based composite perovskite catalyst has a crystal phase of LaMnO 3 , and owns higher specific surface area, better reductivity at low temperature, more abundant Mn 4+ ions and lattice oxygen species than pure manganese perovskite catalyst. The results of catalytic evaluation show that manganese-based composite perovskite catalyst prepared from waste performs better catalytic performance of toluene oxidation in comparison with pure manganese perovskite. The effects of other cations existing in spent ternary lithium batteries are further investigated. The results imply that the catalytic performance can be significantly inhibited with the introduction of lithium ions, while appropriate amounts of copper, nickel and cobalt ions can improve the catalytic performance over pure manganese perovskite catalysts.

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 103 and 105 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.

A series of 3DOM zinc ferrites and silica composites were prepared and applied on the hydrogen sulfide (H2S) removal at 500 °C. With ∼230 nm-sized macropores and 15 nm-sized walls, the morphology analysis showed the as-prepared ZnFe2O4-SiO2 materials were conducted as a typical 3DOM structure. As a solifidation agent, silica significantly influenced not only the composites structure, which induced the homogeneity and stability of 3DOM structure, but also the desulfurization behavior, in which the active phase utilization decreased if the compounded silica amount was too high or too low. Anyway, the 3DOM sorbents exhibited remarkable desulfurization performance due to the unique structure features with high surface area, nano zinc ferrite particles, well arranged macropores with interconnected mesopores, which significantly enhances gaseous reactant diffusion during sulfidation compared with those of bulk sorbent. Sulfates could be formed during both sulfidation and regeneration process, while Fe2(SO4)3 in sulfided sample and ZnSO4 in regenerated sample. 3DOM structure and silica participation enhanced the breakthrough capacity of 50 wt% ZnFe2O4 compounded sorbent and maintained higher desulfurization capacities upon multiple sulfidation/regeneration cycles more ascribed to its special structural feature.

By adopting the variable gauge rolling (VGR) technology and the annealing process, the tailor rolled blanks (TRBs) with both continuously varying thickness and inhomogeneous material properties could be obtained. Through the procedure of subsequent forming and laser welding technology on TRBs, the tailor rolled tubes (TRTs) with axially varying thickness and material properties were successfully produced, and performed by the quasi-static axial crushing afterwards. On the basis of the microstructural transformation at different thickness locations, the relationships between the material properties and thicknesses were analyzed. Moreover, the failure mode and the deformation mechanism of TRTs have been discussed. It is noted that the progressively increased distances between the top and bottom of the plastic hinges is the essential characteristic. Combined with the classical crushing theories and models, a novel predictive mathematical model considering the thickness variation, changing material properties and variety heights of folding elements has been established. Compared with the series conventional computing models, this novel model performed better. On this foundation, the effects of different thickness transition form and distribution of material properties on the crushing performances were investigated. Besides, detailed effects of the tube structure and with or without changing material properties on the crushing capacity were also studied by introducing the concept of equivalent strength and equivalent thickness.

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.

The mechanical properties in tailor rolled blank of dual phase steel (DP-TRB) at different thickness zones present significant differences after annealing. In this paper, the differences in mechanical property of the tailor rolled blank were investigated. The work hardening behavior is analyzed by C-J analysis method. The results indicate that the microstructure of DP-TRB is composed of ferrite and martensite at 800–820 °C. It is interesting that the martensite islands gradually chang to equiaxed morphology from rod-like shape at annealing temperature of 800 °C. In addition, the differences in mechanical properties between different thicknesses zones become less with the increased intercritical temperature from 760 °C to 820 °C. It indicates that the difference in yield strength decreases from 230 MPa to 60 MPa with the intercritical temperature changing from 760 °C to 820 °C. Ferrite recrystallization or not is the main reason for the differential properties. The critical thickness for recrystallization is same ~ 1.6 mm, and the 1.6 mm zones is experimentally proved to possess the largest strength at 760 °C, 800 °C, and 820 °C. The samples in thinner zones are softened because of the recrystallization, while the samples in the larger thickness zone are not strong enough as 1.6 mm with less work-hardening. After the yield point, there is an extra work hardening stage in 1.6 mm and 1.8 mm samples relative to 1.0–1.4 mm samples, which can eliminate nonuniform deformation and prepare for the followed uniform deformation. Consequently, turning of this feature of properties differentiation rationally would play an important role in application of DP-TRB.

A simple and effective self-molten-polymerization strategy utilizing the molten metal salts from heated solid metal salt sources as the solvents to dissolve a self-polymerizable monomer, which acted as a mingling agent, was successfully applied to homogeneously synthesize a series of highly defected manganese/samarium (Mn/Sm-x, where x represents the molar ratio of Mn to Sm) hybrid bimetallic oxides with a mesoporous structure. The values of T50 and T90 over Mn/Sm-2 were 206 °C and 247 °C, respectively, for toluene conversion, as well as 213 °C and 273 °C for CO2 yield under saturated vapor with a weight hourly space velocity of 60 000 ml g−1 h−1, which were far superior to the performances of Mn/Cu-2 (233 °C and 274 °C; 237 °C and 300 °C) and MnOx (242 °C and 294 °C; 255 °C and 315 °C). Meanwhile, the most active catalyst Mn/Sm-4 exhibited complete mineralization of chlorobenzene under saturated vapor and a weight hourly space velocity of 60 000 ml g−1 h−1 at 350 °C. In addition, the Mn/Sm-4 catalyst also showed a high TOFMn value (8.35 × 10−6 s−1) at 140 °C for toluene oxidation and good stability for the catalytic oxidation of toluene and chlorobenzene under a long-term test running for 200 h of uninterrupted reaction. The XRD, Raman, N2 adsorption–desorption, FESEM, XPS, O2-TPD and H2-TPR results confirmed that more surface defects and surface oxygen vacancies were introduced into MnOx using proper doping with Sm. Combined with the in situ DRIFTS and on-line MS measurements, the mechanism for chlorobenzene oxidation over Mn/Sm-4 was also revealed. This work presents an important interpretation for developing improved catalysts to control air pollution.

γ-MnO2, SmMnO3, and γ-MnO2/SmMnO3 catalysts were prepared by facile methods, wherein the SmMnO3 (SMO) perovskite was synthesized through one-step calcination and the γ-MnO2/SmMnO3 was formed by an in situ growth of γ-MnO2 on the surface of SMO. These materials ware characterized by XRD, SEM-mapping, N2-adsorption, XPS and H2-TPR to investigate their textural properties. Compared with that of SMO and γ-MnO2, the γ-MnO2/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 (Olatt/Oads) and better low-temperature reducibility. Besides, for γ-MnO2/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-MnO2/SmMnO3 is also a good catalyst with high stability for aromatic VOCs oxidation, and fulfilled endurability to high humidity (20 vol.%).

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 FceRI+ 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.

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

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells. 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 novel paradigm for tissue patterning by an activator-inhibitor pair.