Cell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Our current understanding of the detailed organization of cell membranes remains rather elusive, because ...of the challenge to study fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of 10 different membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between the leaflets. The simulations detail how each protein modulates its local lipid environment in a unique way, through enrichment or depletion of specific lipid components, resulting in thickness and curvature gradients. Our results provide a molecular glimpse of the complexity of lipid–protein interactions, with potentially far-reaching implications for our understanding of the overall organization of real cell membranes.
Transmission electron microscope (TEM) is thought as one powerful tool to imaging the atomic-level structure of organic inorganic hybrid perovskite (OIHP) materials, which provides valuable and ...essential guidance toward high performance OIHP-related devices. However, these OIHPs exhibit poor electron beam stability, severely limiting their practical applications in TEM. Here in this article, the application of TEM to obtain atomic-scale image of OIHPs, main obstacles in identifying the degradation product and future prospects of TEM in the characterization of OIHP materials are reviewed and presented. Three potential strategies (sample protection, low temperature technology, and low-dose technologies) are also proposed to overcome the current drawback of TEM technology.
Much progress has been achieved in the commercialization of solar devices, especially perovskite solar cells, which have shown excellent transport properties and low fabrication costs ...
The short lifetime of perovskite solar cell devices limits the application of the technique, which is yet to be resolved, despite many attempts. An important step is made here by the numerical ...modelling method, which reveals the decomposition kinetics under the protection of halogen bonds from excess PbI2. Irregular diffusion behaviour of water molecules is observed when excessive PbI2 is introduced, possibly due to the passivation and hindrance from the halogen bond, resulting in a lifetime enhancement of at least five times. The detailed kinetics are also obtained by analyzing the decomposition rate curve, offering a possible path towards high-stability PCE perovskite solar devices, by increasing the PbI2 concentration to above the threshold, which opens an unprecedented route in perovskite solar cell research, and is, hopefully, of intrinsic interest to the broad materials research community as well.
A photoswitchable 2rotaxane with unique photogated macrocyclic shuttling is constructed by incorporating the photoswitchable azobenzene (AB) and nonphotoactive biphenyl (BP) units into the axle as ...two terminal recognition sites, bridged by a naphthalene (NAP) unit. The UV (λ = 379 nm)/blue (λ = 440–450 nm) lights triggered Z/E photoisomerization of the AB unit can drive the cyclobis(paraquat-p-phenylene) (CBPQT4+) macrocycle to shuttle between the two terminal recognition sites. Such macrocyclic translational movement can be photogated by a steric barrier generating from the green-light (λ = 520–525 nm)-triggered cycloaddition reaction between the NAP unit on the thread and a triazolinedione (TAD) additive. Upon standing in dark, the photocycloadduct undergoes disassociation which restores the phototriggered macrocyclic shuttling ability. The construction of such photogated photoresponsive molecular shuttle can provide new approach to improve the switching controllability of rotaxane, which is beneficial to fabricate rotaxane-based nanosystems and materials with high performance.
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Maternal metabolism dysregulation during pregnancy predisposes offspring to major diseases, including hypertension, in later life, but the mechanism involved remains to be fully elucidated. A ...high-fat-diet (HFD) pregnant rat model was used to investigate whether excessive intrauterine lipid exposure was associated with elevated blood pressure in offspring and increased levels of leptin, an important biomarker and mediator of vascular dysfunction and hypertension. We found that gestational hyperlipidemia predisposed offspring to blood pressure elevation and sustained increases in leptin levels with no difference in body weight in the rat model. Increased leptin expression and leptin promoter hypomethylation were found in adipose tissues of HFD-exposed offspring. The treatment of mesenchymal stem cells with free fatty acids during adipogenic differentiation resulted in increased leptin expression, accompanied by leptin promoter hypomethylation. In addition, we also followed up 121 children to evaluate the association between maternal triglyceride levels and offspring blood pressure. Consistent with the animal study results, we observed elevated serum leptin levels and blood pressure in the offspring born to women with gestational hypertriglyceridemia. Our findings provide new insights that maternal hyperlipidemia is associated with elevated blood pressure in offspring and is associated with increases in leptin levels through epigenetic memory.
Cancer immunotherapies, including immune checkpoint inhibition (ICI) and adoptive immune cells therapy, are promising therapeutic strategies. They reactivate the function of immune cells and induce ...immune responses to attack tumor cells. Although these novel therapies benefited a large amount of cancer patients, many cancer patients have shown fair responses even resistance to cancer immunotherapies, limiting their wide clinical application. Therefore, it is urgent to explore the underlying mechanisms of low response and resistance of cancer immunotherapy to enhance their treatment efficacy. The programmed cell death (PCD) including the ferroptosis, has been demonstrated to play essential roles in antitumor immunity and in regulating the immune response to ICIs. Ferroptosis, a phospholipid peroxidation-mediated, iron-dependent membrane damage, exhibite three critical hallmarks: the oxidation of phospholipids, the lack of lipid peroxide repair capability and the overloading of redox-active iron. Notably, ferroptosis was found to plays important roles in regulating tumor immunity and response to immunotherapy. Therefore, targeting ferroptosis alone or in combination with immunotherapy may provide novel options to promote their antitumor efficacy. However, the effect of ferroptosis on tumor immunity and immunotherapy is affected by the interaction of ferroptosis and cancer cells, immune cells, tumor microenvironment (TME) and others. In this review, we summarized and discussed the critical roles of ferroptosis in regulating antitumor immunity, TME and in the improvement of the therapeutic efficacy of immunotherapy in cancers.
Castor (
L.) seeds produce abundant ricinoleic acid during seed maturation, which is important for plant development and human demands. Ricinoleic acid, as a unique hydroxy fatty acid (HFA), ...possesses a distinct bond structure that could be used as a substitute for fossil fuels. Here, we identified all homologous genes related to glycolysis, hydroxy fatty acid biosynthesis, and triacylglycerol (TAG) accumulation in castor seeds. Furthermore, we investigated their expression patterns globally during five seed development stages. We characterized a total of 66 genes involved in the glycolysis pathway, with the majority exhibiting higher expression levels during the early stage of castor bean seed development. This metabolic process provided abundant acetyl-CoA for fatty acid (FA) biosynthesis. Subsequently, we identified 82 genes involved in the processes of de novo FA biosynthesis and TAG assembly, with the majority exhibiting high expression levels during the middle or late stages. In addition, we examined the expression patterns of the transcription factors involved in carbohydrate and oil metabolism. For instance,
and
exhibited high expression levels during the early stage, whereas
,
, and
showed relatively higher expression levels during the middle and late stages, indicating their crucial roles in seed development and oil accumulation. Our study suggests that the high HFA production in castor seeds is attributed to the interaction of multiple genes from sugar transportation to lipid droplet packaging. Therefore, this research comprehensively characterizes all the genes related to glycolysis, fatty acid biosynthesis, and triacylglycerol (TAG) accumulation in the castor and provides novel insight into exploring the genetic mechanisms underlying seed oil accumulation in the endosperm of castor beans.
Biochemical pregnancy is a type of embryo transfer failure, patients with unexplained repeated implantation failure (RIF) also have higher biochemical pregnancy rate. Our study intends to evaluate ...the effect of granulocyte colony-stimulating factor (G-CSF) in patients with unexplained RIF with low hCG levels in early pregnancy.
Unexplained RIF patients with low hCG levels after embryo transfer were allocated. G-CSF were administrated from the ninth days after embryo transfer. Clinical pregnancy, miscarriage and live birth rates were evaluated.
The clinical pregnancy and live birth rates were 52.5% and 30%.
G-CSF is an effective treatment for potential biochemical pregnancy in unexplained RIF patients.
Scope
GTPs (green tea polyphenols) exert anti‐CRC (colorectal cancer) activity. The intestinal microbiota and intestinal colonization by bacteria of oral origin has been implicated in colorectal ...carcinogenesis. GT modulates the composition of mouse gut microbiota harmonious with anticancer activity. Therefore, the effect of green tea liquid (GTL) consumption on the gut and oral microbiome is investigated in healthy volunteers (n = 12).
Methods and results
16S sequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis of both fecal and saliva samples (collected before intervention, after 2 weeks of GTL (400 mL per day) and after a washout period of one week) in healthy volunteers show changes in microbial diversity and core microbiota and difference in clear classification (partial least squares‐discriminant analysis PLS‐DA). An irreversible, increased FIR:BAC (Firmicutes to Bacteroidetes ratio), elevated SCFA producing genera, and reduction of bacterial LPS synthesis in feces are discovered in response to GTL. GTL alters the salivary microbiota and reduces the functional pathways abundance relevance to carcinogenesis. Similar bacterial networks in fecal and salivary microbiota datasets comprising putative oral bacteria are found and GTL reduces the fecal levels of Fusobacterium. Interestingly, both Lachnospiraceae and B/E (Bifidobacterium to Enterobacteriacea ratio—markers of colonization resistance CR) are negatively associated with the presence of oral‐like bacterial networks in the feces.
Conclusion
These results suggest that GTL consumption causes both oral and gut microbiome alterations.
Green tea (GT) polyphenols exert anticancer activity. The intestinal microbiota and intestinal colonization by bacteria of oral origin has been implicated in colorectal carcinogenesis. GT modulates the composition of mouse gut microbiota harmonious with anticancer activity. Therefore, the effect of GT liquid consumption on the human microbiome is investigated. This study provides evidence that green tea liquid consumption alters the human oral and gut microbiome harmonious with anti‐cancer activity.
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