Protein structure alignment algorithms are often time-consuming, resulting in challenges for large-scale protein structure similarity-based retrieval. There is an urgent need for more efficient ...structure comparison approaches as the number of protein structures increases rapidly. In this paper, we propose an effective graph-based protein structure representation learning method, GraSR, for fast and accurate structure comparison. In GraSR, a graph is constructed based on the intra-residue distance derived from the tertiary structure. Then, deep graph neural networks (GNNs) with a short-cut connection learn graph representations of the tertiary structures under a contrastive learning framework. To further improve GraSR, a novel dynamic training data partition strategy and length-scaling cosine distance are introduced. We objectively evaluate our method GraSR on SCOPe v2.07 and a new released independent test set from PDB database with a designed comprehensive performance metric. Compared with other state-of-the-art methods, GraSR achieves about 7%-10% improvement on two benchmark datasets. GraSR is also much faster than alignment-based methods. We dig into the model and observe that the superiority of GraSR is mainly brought by the learned discriminative residue-level and global descriptors. The web-server and source code of GraSR are freely available at www.csbio.sjtu.edu.cn/bioinf/GraSR/ for academic use.
Sellers are conventionally generous with their return policies for valuation‐uncertain products, such as experience products and new products. However, with the development of online review ...platforms, an increasing number of consumers are engaging in social learning by referring to others' reviews to reduce valuation uncertainty. In this study, we investigate how social learning interacts with sellers' return policies. There are three main conclusions. First, when sellers have a relatively higher expectation of product quality (or simply the product quality is high), social learning makes the sellers offering either no‐refund policies or partial‐refund policies better off in terms of the increased profit. It will cause the no‐refund sellers to choose higher prices and inventory, and the partial‐refund sellers to set lower prices and refund amounts. Second, under social learning, the partial‐refund policy tends to be more beneficial to sellers than both full‐refund and no‐refund policies; although, when the product quality is high, the no‐refund policy tends to bring more benefits to sellers than the full‐refund policy. Hence, sellers may finally switch to the partial‐refund policy. Third, for partial‐refund policies, more often than not, social learning increases social welfare when the product quality is high; specifically, in many cases, it increases not only the profit of the seller but also the welfare of consumers.
The soluble carrier hormone binding protein (HBP) plays an important role in the growth of human and other animals. HBP can also selectively and non-covalently interact with hormone. Therefore, ...accurate identification of HBP is an important prerequisite for understanding its biological functions and molecular mechanisms. Since experimental methods are still labor intensive and cost ineffective to identify HBP, it's necessary to develop computational methods to accurately and efficiently identify HBP. In this paper, a machine learning-based method was proposed to identify HBP, in which the samples were encoded by using the optimal tripeptide composition obtained based on the binomial distribution method. In the 5-fold cross-validation test, the proposed method yielded an overall accuracy of 97.15%. For the convenience of scientific community, a user-friendly webserver called HBPred2.0 was built, which could be freely accessed at http://lin-group.cn/server/HBPred2.0/.
Hypertensive nephropathy is a chronic kidney disease caused by hypertension. Eicosapentaenoic acid (EPA) has been reported to possess an antihypertensive effect, and our previous study suggested that ...EPA-enriched phospholipid (EPA-PL) had more significant bioactivities compared with traditional EPA. However, the effect of dietary EPA-PL on hypertensive nephropathy has not been studied. The current study was designed to examine the protection of EPA-PL against kidney damage in spontaneously hypertensive rats (SHRs). Treatment with EPA-PL for three weeks significantly reduced blood pressure through regulating the renin-angiotensin system in SHRs. Moreover, dietary EPA-PL distinctly alleviated kidney dysfunction in SHRs, evidenced by reduced plasma creatinine, blood urea nitrogen, and 24 h proteinuria. Histology results revealed that treatment of SHRs with EPA-PL alleviated renal injury and reduced tubulointerstitial fibrosis. Further mechanistic studies indicated that dietary EPA-PL remarkably inhibited the activation of TGF-β and Smad 3, elevated the phosphorylation level of PI3K/AKT, suppressed the activation of NF-κB, reduced the expression of pro-inflammatory cytokines, including IL-1β and IL-6, and repressed the oxidative stress and the mitochondria-mediated apoptotic signaling pathway in the kidney. These results indicate that EPA-PL has potential value in the prevention and alleviation of hypertensive nephropathy.
The direct epitaxial growth of graphene on semi‐insulating SiC presents significant potential for a variety of technologically important applications, including next‐generation electronics, ...photonics, and quantum metrology. However, this approach also poses a competitive disadvantage in terms of quality and cost, primarily due to the uncontrollable and time‐consuming nature of the annealing process. Herein, a thermal shock annealing (TSA) method is reported that enables kinetics‐controlled epitaxial growth of graphene on SiC within 10 s, which efficiently fulfills the requirements for producing high‐quality, few‐layer, and low‐cost graphene on SiC. The epitaxial graphene (EG) grown on both β‐SiC nanoparticles (SiC@EG NPs) and centimeter‐scale α‐SiC wafer (EG/SiC) exhibits mono‐ or bi‐layer features with negligible structural defects. Moreover, the findings indicate that the TSA method can efficiently mitigate the persistent issue of step bunching conundrum and improve the flatness of EG/SiC. As an application demonstration, the significant enhancement of surface‐enhanced infrared absorption (SEIRA) by SiC@EG NPs is exhibited. The graphene plasmon arising on SiC@EG NPs enables SEIRA detection sensitivity of up to a monolayer of p‐nitrobenzenethiol (p‐NTP). Consequently, the precise regulation and comprehensive comprehension of TSA afford an exceedingly desirable approach to produce cost‐effective, high‐quality EG growth on SiC for diverse emerging application scenarios.
A thermal shock annealing method that enables kinetics‐controlled epitaxial growth of graphene on SiC within 10 s is reported, which efficiently fulfills the requirements for producing high‐quality, few‐layer, and low‐cost graphene on SiC.
Background
Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of ...autophagy and CDDP resistance of gastric cancer cells is still not clear.
Materials and methods
Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay.
Results
Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo.
Conclusion
METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.
A novel photoredox catalysis for multiple functionalization of two different types of unactivated alkenes in a single operation was reported through a conceptually new mode of annulation–alkynyl ...migration. A wide array of cyclopentane carboxylates were synthesized in a highly selective and functional-group-compatible manner via C-centered radical induced cascade 5-exo-trig/5-exo-dig bicyclization and C–C bond cleavage process. This methodology might open a new entry for designing annulation–functional group migration to create structurally applicable cyclic ring systems.
Artesunate (ART) is an anti-malaria drug that has been shown to exhibit anti-tumor activity, and functional lysosomes are reported to be required for ART-induced cancer cell death, whereas the ...underlying molecular mechanisms remain largely elusive. In this study, we aimed to elucidate the molecular mechanisms underlying ART-induced cell death. We first confirmed that ART induces apoptotic cell death in cancer cells. Interestingly, we found that ART preferably accumulates in the lysosomes and is able to activate lysosomal function via promotion of lysosomal V-ATPase assembly. Furthermore, we found that lysosomes function upstream of mitochondria in reactive oxygen species production. Importantly, we provided evidence showing that lysosomal iron is required for the lysosomal activation and mitochondrial reactive oxygen species production induced by ART. Finally, we showed that ART-induced cell death is mediated by the release of iron in the lysosomes, which results from the lysosomal degradation of ferritin, an iron storage protein. Meanwhile, overexpression of ferritin heavy chain significantly protected cells from ART-induced cell death. In addition, knockdown of nuclear receptor coactivator 4, the adaptor protein for ferritin degradation, was able to block ART-mediated ferritin degradation and rescue the ART-induced cell death. In summary, our study demonstrates that ART treatment activates lysosomal function and then promotes ferritin degradation, subsequently leading to the increase of lysosomal iron that is utilized by ART for its cytotoxic effect on cancer cells. Thus, our data reveal a new mechanistic action underlying ART-induced cell death in cancer cells.
Background: Artesunate is capable of inducing cell death in cancer cells.
Results: Artesunate accumulates in lysosomes and promotes lysosomal function and ferritin degradation, leading to mitochondrial reactive oxygen species production and eventually cell death.
Conclusion: Intracellular iron and ferritin degradation is essential for artesunate-induced lysosomal activation and cell death.
Significance: This work reveals a novel mechanism underlying artesunate-induced cell death.
A general and efficient photocatalytic annulation‐carbohalogenation of 1,7‐enynes with a wide variety of alkyl halides was reported, which led to the atom‐economic synthesis of functionalized ...3,4‐dihydronaphthalen‐1(2H)‐ones with good yields and high stereoselectivity under the mild and oxidant‐free conditions. The reaction demonstrated remarkable compatibility regarding alkyl halides as bifunctional reagents, such as ethyl 2‐bromo‐2,2‐difluoroacetate, ethyl 2,2‐difluoro‐2‐iodoacetate, perfluorobutyl iodide, bromotrichloromethane, and diethyl 2‐bromomalonate, and enabled wide substrate scope, high functional group tolerance, and 100% atom utilization.
Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that ...EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR–/–) mice. Notably, the serum total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced by 33.6 and 38.2%, respectively, by EPA-PlsEtns instead of EPA in the form of ethyl ester (EPA-EE) treatment compared with the model group. EPA-PlsEtn administration also increased total neutral sterol and bile acids in feces by 92 and 39%, respectively, rather than EPA-EE. Mechanistically, EPA-PlsEtns might affect the abundance of gut microbiota contributing to the alteration of bile acid profiles, which might further accelerate bile acid synthesis via increasing cholesterol 7 α-hydroxylase expression induced by the inhibition of farnesoid X receptor activation.
PDF
