Gel-Based Chemical Cross-Linking Analysis of 20S Proteasome Subunit-Subunit Interactions in Breast Cancer

The ubiquitin-proteasome system plays a pivotal role in breast tumorigenesis by controlling transcription factors, thus promoting cell cycle growth, and degradation of tumor suppressor proteins. However, breast cancer patients have failed to benefit from proteasome inhibitor treatment partially due to proteasome heterogeneity, which is poorly understood in malignant breast neoplasm. Chemical crosslinking is an increasingly important tool for mapping protein three-dimensional structures and proteinprotein interactions. In the present study, two cross-linkers, bis（sulfosuccinimidyl） suberate（BS3） and its water-insoluble analog disuccinimidyl suberate（DSS）, were used to map the subunit-subunit interactions in 20 S proteasome core particle（CP） from MDA-MB-231 cells. Different types of gel electrophoresis technologies were used. In combination with chemical cross-linking and mass spectrometry, we applied these gel electrophoresis technologies to the study of the noncovalent interactions among 20 S proteasome subunits. Firstly, the CP subunit isoforms were profiled. Subsequently, using native/SDSPAGE, it was observed that 0.5 mmol/L BS^3 was a relatively optimal cross-linking concentration for CP subunit-subunit interaction study. 2-DE analysis of the cross-linked CP revealed that α1 might preinteract with α2, and α3 might pre-interact with α4. Moreover, there were different subtypes of α1α2 and α3α4 due to proteasome heterogeneity. There was no significant difference in cross-linking pattern for CP subunits between BS3 and DSS. Taken together, the gel-based characterization in combination with chemical cross-linking could serve as a tool for the study of subunit interactions within a multi-subunit protein complex. The heterogeneity of 20 S proteasome subunit observed in breast cancer cells may provide some key information for proteasome inhibition strategy.

Study on Chemical Cross-linking Modification of Hyaluronan and the Biocompatibility of its Derivatives

Objective: Prepare cross-linked HA gels with higher mechanical stability, lower degradation velocity and desirable biocompatibility,so as to extend the usage of HA.Method:1.Test molecular weight of HA (Mr_ HA ) by viscosimetry;2.prepare cross-linked HA gels by DVS, GTA, DEC;3.discuss the cross-linking and degradation procedure;4.evaluate the biocompatibility of the best HA gels. Results:The mechanical stability and durability to degradation of HA-DVS gels are superior to those of other gels, and when HA:DVS = 40:1(g/g), at 35℃ and in 0.2 M NaOH solution, the HA-DVS gel shows the best mechanical stability, and its cytotoxicity reaches class I, hemolysis ratio is lower than 5%. Conclusion:Our HA-DVS gel can be used to prepare biologic scaffolds.

Chemical cross-linking and mechanically reinforced carbon network constructed by graphene boosts potassium ion storage

Carbon-based electrodes of potassium-ion batteries are of great research interest ascribed to their low cost and environmentally friendly distinctions.However,traditional carbon materials usually exhibit weak mechanical properties and incomplete crosslinking,resulting in poor stability and electrochemical performance.Herein,we report a new strategy for modifying reduced graphene oxide into a uniform few-layer structure through a sol–gel method combined with acid etching treatment.The obtained chemical cross-linking and mechanically reinforced carbon network constructed by graphene(CNCG)demonstrates excellent electrochemical and mechanical properties.Adopted as a free-standing anode(~7 mg·cm^(−2))for potassium ion battery,the asachieved CNCG delivers a high reversible specific capacity of 317.7 mAh·g^(−1) at a current density of 50 mA·g^(−1) and admirable cycle stability(208.4 mAh·g^(−1) at 50 mA·g^(−1) after 500 cycles).The highly reversible structural stability and fully cross-linked properties during potassiation are revealed by ex-situ characterization.This work provides new ideas for the synthesis of new carbon materials and the development of high-performance electrodes.

Fabrication of Covalently Linked PAH/PVS Layer-by-layer Assembled Multilayers via a Post-photochemical Cross-linking Strategy

A post-photochemical cross-linking strategy was successfully demonstrated to enhance the stability of polyelectrolyte poly（allylamine hydrochloride）（PAH）/poly（vinylsulfonic acid sodium salt）（PVS） multilayers. Con- ventional polyelectrolyte multilayers of PAH/PVS are usually fabricated through electrostatic layer-by-layer（LbL） assembly, resulting in poor stability, especially in basic solutions, which leads to the urgent demand for converting weak electrostatic interactions into covalent bonds to enhance the stability of the multilayers. This stability problem has been ultimately addressed by post-infiltrating a photosensitive cross-linking agent, 4,4＇-diazostilbene-2,2＇- disulfonie acid disodium salt（DAS）, into the LbL assembled films to initiate the photochemical reaction to cross-link the multilayers. The obviously improved stability of the photo-cross-linked multilayers was demonstrated through experiments with basic solution treatments. Compared to the complete decomposition of uncross-linked multilayers in basic solution, over 74.4% of the covalently cross-linked multilayers were retained under the same conditions, even after a longer duration of basic solution treatment.

The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

AlkB recognition of a bulky DNA base adduct stabilized by chemical cross-linking

E.coli AlkB is a direct DNA/RNA repair protein that oxidatively reverses N1 alkylated purines and N3 alkylated pyrimidines to regular bases.Previous crystal structures have revealed N1-methyl adenine(1-meA) recognition by AlkB and a unique base flipping mechanism,but how the AlkB active site can accommodate bulky base adducts is largely unknown.Employing a previously developed chemical cross-linking technique,we crystallized AlkB with a duplex DNA containing a caged thymine base(cagedT).The structure revealed a flexible hairpin lid and a reorganized substrate recognition loop used by AlkB to accommodate cagedT.These observations demonstrate,at the molecular level,how bulky DNA adducts may be recognized and processed by AlkB.

Jet formation and penetration performance of a double-layer charge liner with chemically-deposited tungsten as the inner liner

This paper proposes a type of double-layer charge liner fabricated using chemical vapor deposition(CVD)that has tungsten as its inner liner.The feasibility of this design was evaluated through penetration tests.Double-layer charge liners were fabricated by using CVD to deposit tungsten layers on the inner surfaces of pure T2 copper liners.The microstructures of the tungsten layers were analyzed using a scanning electron microscope(SEM).The feasibility analysis was carried out by pulsed X-rays,slug-retrieval test and static penetration tests.The shaped charge jet forming and penetration law of inner tungsten-coated double-layer liner were studied by numerical simulation method.The results showed that the double-layer liners could form well-shaped jets.The errors between the X-ray test results and the numerical results were within 11.07%.A slug-retrieval test was found that the retrieved slug was similar to a numerically simulated slug.Compared with the traditional pure copper shaped charge jet,the penetration depth of the double-layer shaped charge liner increased by 11.4% and>10.8% respectively.In summary,the test results are good,and the numerical simulation is in good agreement with the test,which verified the feasibility of using the CVD method to fabricate double-layer charge liners with a high-density and high-strength refractory metal as the inner liner.

Valorization of Camellia oleifera oil processing byproducts to value-added chemicals and biobased materials: A critical review

The C.oleifera oil processing industry generates large amounts of solid wastes,including C.oleifera shell(COS)and C.oleifera cake(COC).Distinct from generally acknowledged lignocellulosic biomass(corn stover,bamboo,birch,etc.),Camellia wastes contain diverse bioactive substances in addition to the abundant lignocellulosic components,and thus,the biorefinery utilization of C.oleifera processing byproducts involves complicated processing technologies.This reviewfirst summarizes various technologies for extracting and converting the main components in C.oleifera oil processing byproducts into value-added chemicals and biobased materials,as well as their potential applications.Microwave,ultrasound,and Soxhlet extractions are compared for the extraction of functional bioactive components(tannin,flavonoid,saponin,etc.),while solvothermal conversion and pyrolysis are discussed for the conversion of lignocellulosic components into value-added chemicals.The application areas of these chemicals according to their properties are introduced in detail,including utilizing antioxidant and anti-in-flammatory properties of the bioactive substances for the specific application,as well as drop-in chemicals for the substitution of unrenewable fossil fuel-derived products.In addition to chemical production,biochar fabricated from COS and its applications in thefields of adsorption,supercapacitor,soil remediation and wood composites are comprehensively reviewed and discussed.Finally,based on the compositions and structural characteristics of C.oleifera byproducts,the development of full-component valorization strategies and the expansion of the appli-cationfields are proposed.

A novel method for simulating nuclear explosion with chemical explosion to form an approximate plane wave: Field test and numerical simulation

A nuclear explosion in the rock mass medium can produce strong shock waves,seismic shocks,and other destructive effects,which can cause extreme damage to the underground protection infrastructures.With the increase in nuclear explosion power,underground protection engineering enabled by explosion-proof impact theory and technology ushered in a new challenge.This paper proposes to simulate nuclear explosion tests with on-site chemical explosion tests in the form of multi-hole explosions.First,the mechanism of using multi-hole simultaneous blasting to simulate a nuclear explosion to generate approximate plane waves was analyzed.The plane pressure curve at the vault of the underground protective tunnel under the action of the multi-hole simultaneous blasting was then obtained using the impact test in the rock mass at the site.According to the peak pressure at the vault plane,it was divided into three regions:the stress superposition region,the superposition region after surface reflection,and the approximate plane stress wave zone.A numerical simulation approach was developed using PFC and FLAC to study the peak particle velocity in the surrounding rock of the underground protective cave under the action of multi-hole blasting.The time-history curves of pressure and peak pressure partition obtained by the on-site multi-hole simultaneous blasting test and numerical simulation were compared and analyzed,to verify the correctness and rationality of the formation of an approximate plane wave in the simulated nuclear explosion.This comparison and analysis also provided a theoretical foundation and some research ideas for the ensuing study on the impact of a nuclear explosion.

Integrated Effects of Phosphate Rock and Chemical Fertilizers on the Dynamics of Soil Bacterial in Acidic Rice Paddy Soils of Man (Ivory Coast)

In agricultural soils, phosphorus is often limited, leading farmers to employ artificial supplementation through both inorganic and organic fertilization methods due to its restricted availability. Soil fertilization has the potential to augment both the abundance and diversity of bacterial communities. Our study aimed to assess the effects of phosphate amendments, derived from natural phosphate rock, and chemical fertilizers (TSP, NPK), on the density and diversity of bacterial communities within the study plots. We developed and applied eight phosphate amendments during the initial cultivation cycle. Soil samples were collected post 1st and 2nd cultivation cycles, and the quantification of both total and cultivable phosphate-solubilizing bacteria (PSB) was conducted. Additionally, we analyzed bacterial community structure, α-diversity (Shannon Diversity Index, Evenness Index, Chao1 Index). The combination of natural phosphate rock (PR) and chemical fertilizers (TSP, NPK) significantly increased (p 7 bacteria/g dry soil) and phosphate-solubilizing bacteria (0.01 to 6.8 × 107 PSB/g dry soil) in comparison to unamended control soils. The diversity of bacterial phyla (Firmicutes, Actinobacteria, Proteobacteria, Halobacterota, Chloroflexia) observed under each treatment remained consistent regardless of the nature of the phosphate amendment applied. However, changes in the abundance of the bacterial phyla populations were observed as a function of the nature of the phosphate amendment or chemical fertilizer. It appears that the addition of excessive natural phosphate rock does not alter the number and the diversity of soil microorganisms population despite successive cultivation cycles. However, the addition of excessive chemical fertilizer reduces soil microorganisms density and structure after the 2nd cultivation cycle.

Experimental investigation into effects of the natural polymer and nanoclay particles on the EOR performance of chemical flooding in carbonate reservoirs

This paper aims to investigate the tragacanth gum potential as a natural polymer combined with natural clay mineral(montmorillonite,kaolinite,and illite)nanoparticles(NPs)to form NP-polymer suspension for enhanced oil recovery(EOR)in carbonate reservoirs.Thermal gravimetric analysis(TGA)tests were conducted initially in order to evaluate the properties of tragacanth gum.Subsequently,scanning electron microscopy(SEM)and energy-dispersive X-ray(EDX)tests were used to detect the structure of clay particles.In various scenarios,the effects of natural NPs and polymer on the wettability alteration,interfacial tension(IFT)reduction,viscosity improvement,and oil recovery were investigated through contact angle system,ring method,Anton Paar viscometer,and core flooding tests,respectively.The entire experiment was conducted at 25,50,and 75℃,respectively.According to the experimental results,the clay minerals alone did not have a significant effect on viscosity,but the addition of minerals to the polymer solution leads to the viscosity enhancement remarkably,resulting mobility ratio improvement.Among clay NPs,the combination of natural polymer and kaolinite results in increased viscosity at all temperatures.Considerable wettability alteration was also observed in the case of natural polymer and illite NPs.Illite in combination with natural polymer showed an ability in reducing IFT.Finally,the results of displacement experiments revealed that the combination of natural polymer and kaolinite could be the best option for EOR due to its substantial ability to improve the recovery factor.

Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia

AIM:To observe the effects of femtosecond laserassisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking(FS-LASIK Xtra)on corneal densitometry after correcting for high myopia.METHODS:In this prospectively study,130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia.Their right eyes were selected for inclusion in the study,of which 65 cases of 65 eyes in the FS-LASIK group,65 patients with 65 eyes in the FS-LASIK Xtra group.Patients were evaluated for corneal densitometry at 1,3,and 6mo postoperatively using Pentacam Scheimpflug imaging.RESULTS:Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant(P>0.05).Layer-by-layer analysis revealed statistically significant differences in the anterior(120μm),central,and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively(all P<0.05),the FS-LASIK Xtra group is higher than that of the FS-LASIK group.Analysis of different diameter ranges showed statistically significant differences between the FS-LASIK group and the FS-LASIK Xtra group at 1mo postoperatively in the ranges of 0–2,2–6,and 6–10 mm(both P<0.05);At 3mo postoperatively,the FS-LASIK Xtra group is higher than that of the FS-LASIK group in the ranges of 0–2 and 2–6 mm(P<0.05).At 6mo postoperatively,there were no statistically significant differences in corneal densitometry between the FS-LASIK group and the FS-LASIK Xtra group in different diameter ranges(all P>0.05).CONCLUSION:There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia.However,the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery,with the most significant changes observed in the superficial central zone.

Rational design of F,N-rich artificial interphase via chemical prelithiation initiation strategy enabling high coulombic efficiency and stable micro-sized SiO anodes

Silicon monoxide(SiO)is regarded as a potential candidate for anode materials of lithium-ion batteries(LIBs).Unfortunately,the application of SiO is limited by poor initial Coulombic efficiency(ICE)and unsteady solid electrolyte interface(SEI),which induce low energy,short cycling life,and poor rate properties.To address these drawbacks of SiO,we achieve in-situ construction of robust and fast-ion conducting F,N-rich SEI layer on prelithiated micro-sized SiO(P-μSiO)via the simple and continuous treatment ofμSiO in mild lithium 4,4′-dimethylbiphenyl solution and nonflammable hexafluorocyclotriphosphazene solution.Chemical prelithiation eliminates irreversible capacity through pre-forming inactive lithium silicates.Meanwhile,the symbiotic F,N-rich SEI with good mechanical stability and fast Li^(+)permeability is conductive to relieve volume expansion ofμSiO and boost the Li+diffusion kinetics.Consequently,the P-μSiO realizes an impressive electrochemical performance with an elevated ICE of 99.57%and a capacity retention of 90.67%after 350 cycles.Additionally,the full cell with P-μSiO anode and commercial LiFePO_(4) cathode displays an ICE of 92.03%and a high reversible capacity of 144.97 mA h g^(-1).This work offers a general construction strategy of robust and ionically conductive SEI for advanced LIBs.

Mn-doped SrCoO_(3-δ) Perovskite Oxides for Ethylene Production via Chemical Looping Oxidative Dehydrogenation of Ethane

Chemical looping oxidative dehydrogenation (CL-ODH) is an economically promising method for convertingethane into higher value-added ethylene utilizing lattice oxygen in redox catalysts, also known as oxygen carriers. Inthis study, perovskite-type oxide SrCoO_(3-δ) and B-site Mn ion-doped oxygen carriers (SrCo_(1-x)MnxO_(3-δ), x=0.1, 0.2, 0.3)were prepared and tested for the CL-ODH of ethane. The oxygen-deficient perovskite SrCoO_(3-δ) exhibited high ethyleneselectivity of up to 96.7% due to its unique oxygen vacancies and lattice oxygen migration rates. However, its low ethyleneyield limits its application in the CL-ODH of ethane. Mn doping promoted the reducibility of SrCoO_(3-δ) oxygen carriers,thereby improving ethane conversion and ethylene yield, as demonstrated by characterization and evaluation experiments.X-ray diffraction results confirmed the doping of Mn into the lattice of SrCoO_(3-δ), while X-ray photoelectron spectroscopy(XPS) indicated an increase in lattice oxygen ratio upon incorporation of Mn into the SrCoO_(3-δ) lattice. Additionally, H2temperature-programmed reduction (H2-TPR) tests revealed more peaks at lower temperature reduction zones and a declinein peak positions at higher temperatures. Among the four tested oxygen carriers, SrCo0.8Mn0.2O_(3-δ) exhibited satisfactoryperformance with an ethylene yield of 50% at 710 °C and good stability over 20 redox cycles. The synergistic effect of Mnplays a key role in increasing ethylene yields of SrCoO_(3-δ) oxygen carriers. Accordingly, SrCo0.8Mn0.2O_(3-δ) shows promisingpotential for the efficient production of ethylene from ethane via CL-ODH.

Geochemical characteristics and environmental implications of loess sequences in the Loess Plateau

The major,trace,and rare earth elements of the Duanjiapo(DJP)section in the south of the Loess Plateau,the Jiaxian(JX)section in the north,and the Jiuzhoutai(JZT)section in the west are studied.The results show that the main elemental characteristics of loess in three profiles are consistent with the upper continental crust(UCC).In terms of trace elements,Th,Nb,Zr,Hf,Y,Cs,W,Cr,V,Li,and Pb show relative enrichment compared with UCC;Rb,Ba,Sr and Be exhibit relative depletion.The average ofΣREE is 171.91ppm with a negative anomaly forδEu and essentially no anomaly forδCe.The results of K_(2)O/Na_(2)O,Rb/Sr ratios,as well as the leaching co-efficient from three profiles,indicate DJP>JX>JZT,suggesting that DJP experiences the strongest weathering leaching effect.The chemical index of alteration(CIA)reveals that all three profiles of loess are in the primary stage of Ca and Na depletion.DJP is generally in the early to moderate stage of chemical weathering,while JX and JZT are both in the early stage.

Causal temporal graph attention network for fault diagnosis of chemical processes

Fault detection and diagnosis(FDD)plays a significant role in ensuring the safety and stability of chemical processes.With the development of artificial intelligence(AI)and big data technologies,data-driven approaches with excellent performance are widely used for FDD in chemical processes.However,improved predictive accuracy has often been achieved through increased model complexity,which turns models into black-box methods and causes uncertainty regarding their decisions.In this study,a causal temporal graph attention network(CTGAN)is proposed for fault diagnosis of chemical processes.A chemical causal graph is built by causal inference to represent the propagation path of faults.The attention mechanism and chemical causal graph were combined to help us notice the key variables relating to fault fluctuations.Experiments in the Tennessee Eastman(TE)process and the green ammonia(GA)process showed that CTGAN achieved high performance and good explainability.

Extraction,chemical components,bioactive functions and adulteration identification of walnut oils:A review

Walnut oil is a functional wood oil known to researchers that may potentially be a large source of Chinese edible oils.There are various extraction methods for walnut oil,including traditional(pressing,solvent-and enzymeassisted extraction)and novel methods(microwave,ultrasound,supercritical CO_(2),subcritical and other extraction technologies).Walnut oil is rich in nutrients,including phytosterols,tocopherols,polyphenols,squalene and minerals.It provides many health benefits,such as antioxidant,antitumor,anti-inflammatory,antidiabetic and lipid metabolism-related functions.In addition,the authentication of walnut oil has received much research attention.The present review provides detailed research on walnut oil extraction,composition,health benefits and adulteration identification methods.The path toward further walnut oil improvement in the context of the market value of walnut oil is also discussed.

Plant Chemical Defenses against Insect Herbivores—Using theWild Tobacco as a Model

The Nicotiana genus, commonly known as tobacco, holds significant importance as a crucial economic crop. Confrontedwith an abundance of herbivorous insects that pose a substantial threat to yield, tobacco has developed adiverse and sophisticated array of mechanisms, establishing itself as a model of plant ecological defense. Thisreview provides a concise overview of the current understanding of tobacco’s defense strategies against herbivores.Direct defenses, exemplified by its well-known tactic of secreting the alkaloid nicotine, serve as a potent toxinagainst a broad spectrum of herbivorous pests. Moreover, in response to herbivore attacks, tobacco enhancesthe discharge of volatile compounds, harnessing an indirect strategy that attracts the predators of the herbivores.The delicate balance between defense and growth leads to the initiation of most defense strategies only after aherbivore attack. Among plant hormones, notably jasmonic acid (JA), play central roles in coordinating thesedefense processes. JA signaling interacts with other plant hormone signaling pathways to facilitate the extensivetranscriptional and metabolic adjustments in plants following herbivore assault. By shedding light on these ecologicaldefense strategies, this review emphasizes not only tobacco’s remarkable adaptability in its natural habitatbut also offers insights beneficial for enhancing the resilience of current crops.

The chemical environment and structural ordering in liquid Mg-Y-Zn system:An ab-initio molecular dynamics investigation of melt for the formation mechanism of LPSO structure

In an effort to clarify the formation mechanism of LPSO structure in Mg-Y-Zn alloy,the chemical environment and structural ordering in liquid Mg-rich Mg-Y-Zn system are investigated with the aid of ab-initio molecular dynamics simulation.In liquid Mg-rich Mg-Y alloys,the strong Mg-Y interaction is determined,which promotes the formation of fivefold symmetric local structure.For Mg-Zn alloys,the weak Mg-Zn interaction results in the fivefold symmetry weakening in the liquid structure.Due to the coexistence of Y and Zn,the strong attractive interaction is introduced in liquid Mg-Y-Zn ternary alloy,and contributes to the clustering of Mg,Y,Zn launched from Zn.What is more,the distribution of local structures becomes closer to that in pure Mg compared with that in binary Mg-Y and Mg-Zn alloys.These results should relate to the origins of the Y/Zn segregation zone and close-packed stacking mode in LPSO structure,which provides a new insight into the formation mechanism of LPSO structure at atomic level.

Expanding the Boundaries of the Chemical Space of DNA Methyltransferase 1 Modulators

DNA methyltransferase 1 (DNMT1), one of the main epigenetic targets, is involved in the duplication of the DNA methylation pattern during replication, and it is essential for proper mammalian development. Small molecule DNMT1 modulators are attractive for biochemical epigenetic studies and have the potential to become drugs. So far, more than five hundred small molecules have been reported as DNMT1 inhibitors. However, only a limited number of DNMT1 activators have been disclosed because, at least in part, DNMT1 activators are typically regarded as negative data in virtual screening campaigns or optimization projects. This manuscript aims to report the chemical structures and biological activity of small molecules that increase the enzymatic activity of DNMT1. Results of the biochemical experimental assays are discussed. It was found that small molecule activators have a large variety of chemical scaffolds but share pharmacophore features. Visual analysis of the chemical space and multiverse based on molecular fingertips supported that activators are structurally diverse. This is the first report of eight small molecules that increase the enzymatic activity of DNMT1 by more than 400% in an enzymatic-based assay. The outcome warrants further investigation of the epigenetic activity of the compounds in a counter-screen assay, e.g., cell-based and in vivo context.