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

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

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

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

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

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

Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk.

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.

Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis.

Smoking carcinogen nicotine-derived nitrosamine ketone (NNK) is the most potent contributor to lung adenocarcinoma (LUAD) development, but the mechanism has not been fully elucidated. Here, we reported that fatty acid translocase CD36 was significantly overexpressed in both human LUAD tissues and NNK-induced A/J mice LUAD tumors. The overexpressed CD36 was positively correlated with Src kinase activation, smoking status, metastasis, and worse overall survival of patients with smoking history. Upon NNK binding with α7 nicotinic acetylcholine receptor (α7nAChR), sarcolemmal CD36 was increased and it interacted with surface α7nAChR and cytosol Src simultaneously, which in turn activated Src and downstream pro-carcinogenic kinase ERK1/2 and Akt, and finally caused LUAD cells to form subcutaneous and pulmonary metastatic tumors. This process could be blocked by CD36 knockdown and CD36 irreversible inhibitor SSO. Furthermore, the effect of NNK was inhibited obviously in CD36-/- A/J mice. Thus, targeting CD36 may provide a breakthrough therapy of LUAD.

The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment.

Obesity/overweight and lipid metabolism disorders have become increased risk factors for lung cancer. Fatty acid translocase CD36 promotes cellular uptake of fatty acids. Whether and how CD36 facilitates lung adenocarcinoma (LUAD) growth in high-fat environment is unknown. Here, we demonstrated that palmitic acid (PA) or high-fat diet (HFD) promoted LUAD cell proliferation and metastasis in a CD36-dependent manner. Mechanistically, CD36 translocated from cytoplasm to cell membrane and interacted with Src kinase upon PA stimulation in human LUAD cells. Akt and ERK, downstream of Src, were then activated to mediate LUAD cell proliferation and metastasis. Furthermore, 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. Compared with normal-chew diet (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, which were accompanied by obvious sarcolemmal actin remodeling and were blocked by simultaneous CD36 knockdown in LUAD cells. 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. CD36 inhibitor SSO significantly inhibited LUAD cell metastasis to the lung. Collectively, CD36 initiates Src signaling to promote LUAD cell proliferation and actin remodeling-involved metastasis under high-fat environment. Our study provides the new insights that CD36 is a valid target for LUAD therapy.

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

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

Bovine blastocyst-like structures derived from stem cell cultures.

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.

Ex utero monkey embryogenesis from blastocyst to early organogenesis.

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

Downregulation of mTORC1 and Mcl-1 by lipid-oversupply contributes to islet ß-cell apoptosis and dysfunction.

Pancreatic ß-cell apoptosis is a key feature of diabetes and can be induced by chronic exposure to saturated fatty acids (FAs). However, the underlying mechanisms remain poorly understood. We presently evaluated the role of Mcl-1 and mTOR in mice fed with high-fat-diet (HFD) and ß-cells exposed to the overloaded palmitic acid (PA). Compared with normal-chow-diet (NCD)-fed mice, HFD group showed impaired glucose tolerance after two months. Along with the diabetes progression, pancreatic islets first became hypertrophic and then atrophic, the ratio of ß-cell:α-cell increased in the islets of four months HFD-fed mice while decreased after six months. This process was accompanied by significantly increased ß-cell apoptosis and AMPK activity, and decreased Mcl-1 expression and mTOR activity. Consistently, glucose-induced insulin secretion dropped. In terms of mechanism, PA with lipotoxic dose could activate AMPK, which in turn inhibited ERK-stimulated Mcl-1Thr163 phosphorylation. Meanwhile, AMPK blocked Akt activity to release Akt inhibition on GSK3ß, followed by GSK3ß-initiated Mcl-1Ser159 phosphorylation. The context of Mcl-1 phosphorylation finally led to its degradation by ubiquitination. Also, AMPK inhibited the activity of mTORC1, resulting in a lower level of Mcl-1. Suppression of mTORC1 activity and Mcl-1 expression positively related to ß-cell failure. Alteration of Mcl-1 or mTOR expression rendered different tolerance of ß-cell to different dose of PA. In conclusion, lipid oversupply-induced dual modulation of mTORC1 and Mcl-1 finally led to ß-cell apoptosis and impaired insulin secretion. The study may help further understand the pathogenesis of ß-cell dysfunction in case of dyslipidemia, and provide promising therapeutic targets for diabetes.

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

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

RNA Sensing and Innate Immunity Constitutes a Barrier for Interspecies Chimerism.

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 of Ddx58/Ifih1-Mavs-Irf7 axis compromised the "winner" status of mouse PSCs and their ability to outcompete PSCs from evolutionarily distant species during co-culture. Furthermore, by using Mavs-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.

Tunable Interfacial Charge Transfer in a 2D-2D Composite for Efficient Visible-Light-Driven CO2 Conversion.

Photocatalytic CO2 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 CO2 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 CO2 reduction performance of the optimized Bi/BMOVs (CO and CH4 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 CH4 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.

Negative Life Events and Procrastination among Adolescents: The Roles of Negative Emotions and Rumination, as Well as the Potential Gender Differences.

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 (Mage = 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.

Positive Self-Disclosure on Social Network Sites and Adolescents' Friendship Quality: The Mediating Role of Positive Feedback and the Moderating Role of Social Anxiety.

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.

Primate gastrulation and early organogenesis at single-cell resolution.

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

[Chemical Reaction Activity and Source Apportionment of Atmospheric VOCs in Summer in Dalian].

To investigate the characteristics and source apportionment of atmospheric volatile organic compounds (VOCs) in Dalian, the concentration level, composition characteristics, reaction activity, and source apportionment of atmospheric VOCs in Dalian were analyzed based on high-resolution online observation VOCs data from June to August 2020. The results showed that the average φ(VOCs) was (10.21±5.71)×10-9, in which alkanes accounted for 66.35%, alkenes for 11.89%, alkynes for 7.75%, and aromatics for 14.01%. VOCs and NOx were high at night and low during the day, whereas the change trend of O3 was opposite. Considering the species activity, it was determined that toluene, ethylene, m/p-xylene, 1-hexene, n-butane, isopentane, n-pentane, and isoprene were the key species affecting atmospheric VOCs in Dalian. Priority control of olefin and aromatic hydrocarbon emissions is the key to improve O3 pollution in summer in Dalian. By applying the positive matrix factorization (PMF) model, six major VOCs sources were extracted, namely traffic sources (26.38%), combustion sources (22.75%), industrial emission sources (17.09%), solvent usage sources (14.59%), natural sources (11.72%), and others (7.47%). The emissions of traffic sources and combustion sources are the key pollution sources for O3 prevention and control in Dalian in summer.

Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids.

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.

In-situ regulation of acid sites on Mn-based perovskite@mullite composite for promoting catalytic oxidation of chlorobenzene.

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.

Terminal Cyclohexane-Type Meroterpenoids from the Fruiting Bodies of Ganoderma cochlear.

Eleven new cyclohexane-type meroterpenoids (1, 3-5, 7, 8, 11-15) and four known similar meroterpenoids (2, 6, 9, and 10) were isolated from Ganoderma cochlear. Their structures and absolute configurations at stereogenic centers were elucidated by using HRESIMS, NMR spectroscopy and computational methods. In addition, the structure of the known meroterpenoid, cochlearol G (2), was revised, and the absolute configurations at the stereogenic centers of known meroterpenoids 9 and 10 were determined. All the isolated meroterpenoids were evaluated for their activities against renal fibrosis and triple negative breast cancer, and their insulin resistance. The results of the renal fibrosis study showed that meroterpenoid 11 inhibits over-expression of fibronectin, collagen I and α-SMA. Results of the wound healing study revealed that 4, 6 and 8 significantly inhibit migration of BT549 cells. Observations made in Western blotting experiments showed that 6 decreases the levels of TWIST1 and ZEB1, and increases the level of E-cadherin. Finally, meroterpenoids 7, 9, 11, and 15 significantly up-regulate p-AMPK protein expression in normal L6 myotubes cells.