Simple Substrates Research Articles

Methylacidiphilum caldifontis gen. nov., sp. nov., a thermoacidophilic methane-oxidizing bacterium from an acidic geothermal environment, and descriptions of the family Methylacidiphilaceae fam. nov. and order Methylacidiphilales ord. nov.

Strain IT6T, a thermoacidophilic and facultative methane-oxidizing bacterium, was isolated from a mud-water mixture collected from Pisciarelli hot spring in Pozzuoli, Italy. The novel strain is white when grown in liquid or solid media and forms Gram-negative rod-shaped, non-flagellated, non-motile cells. It conserves energy by aerobically oxidizing methane and hydrogen while deriving carbon from carbon dioxide fixation. Strain IT6T had three complete pmoCAB operons encoding particulate methane monooxygenase and genes encoding group 1d and 3b [NiFe] hydrogenases. Simple carbon-carbon substrates such as ethanol, 2-propanol, acetone, acetol and propane-1,2-diol were used as alternative electron donors and carbon sources. Optimal growth occurred at 50-55°C and between pH 2.0-3.0. The major fatty acids were C18 : 0, C15 : 0 anteiso, C14 : 0 iso, C16 : 0 and C14 : 0, and the main polar lipids were phosphatidylethanolamine, aminophospholipid, phosphatidylglycerol, diphosphatidylglycerol, some unidentified phospholipids and glycolipids, and other unknown polar lipids. Strain IT6T has a genome size of 2.19 Mbp and a G+C content of 40.70 mol%. Relative evolutionary divergence using 120 conserved single-copy marker genes (bac120) and phylogenetic analyses based on bac120 and 16S rRNA gene sequences showed that strain IT6T is affiliated with members of the proposed order 'Methylacidiphilales' of the class Verrucomicrobiia in the phylum Verrucomicrobiota. It shared a 16S rRNA gene sequence identity of >96 % with cultivated isolates in the genus 'Methylacidiphilum' of the family 'Methylacidiphilaceae', which are thermoacidophilic methane-oxidizing bacteria. 'Methylacidiphilum sp.' Phi (100 %), 'Methylacidiphilum infernorum' V4 (99.02 %) and 'Methylacidiphilum sp.' RTK17.1 (99.02 %) were its closest relatives. Its physiological and genomic properties were consistent with those of other isolated 'Methylacidiphilum' species. Based on these results, we propose the name Methylacidiphilum caldifontis gen. nov., sp. nov. to accommodate strain IT6T (=KCTC 92103T=JCM 39288T). We also formally propose that the names Methylacidiphilaceae fam. nov. and Methylacidiphilales ord. nov. to accommodate the genus Methylacidiphilum gen. nov.

A novel tail: One story from the rare taxa of the coal seam microbiome

A substantial portion of global coal seam methane reserves are biogenically produced. To enhance methane production, recent research has focussed on genetic surveying of the microbial life inhabiting these coal seams. These surveys have revealed that the most abundant organisms in these microbial communities are taxa specialised in metabolism of various simple substrates, and are typically methanogens, their (presumably) syntrophic acetate-oxidising bacterial partners, and other bacterial taxa associated with biomass recycling. Although abundant, these microbes are incapable of directly accessing the vast majority of recalcitrant carbon contained within the coal geopolymer. Instead, these more abundant taxa likely rely on the low abundance but diverse taxa, known as the ‘rare taxa’, to transform the carbon within coal into simpler, more labile substrates. Since these rare taxa typically have low taxonomic resolution, their probable activities within the coal seam environment are difficult to infer using the standard 16S rDNA community surveys. Therefore, the present study aimed to develop a method for identifying and characterising these rare taxa using a metagenomic approach. Using this method, a near-complete genome from a Deltaproteobacteria sp. (CSMB_808; designation taken from the Coal Seam Microbiome reference set) was recovered from a metagenome sampling the Surat Basin, Australia, and comprised only 0.5% of the total 16S rDNA sequences recovered from this metagenome. Genetically, CSMB_808 appears to be a motile fatty acid and possibly alkane-degrader within the coal seam environment, and may play an important role in the coal-to-methane degradative pathways. Despite the near-completeness of the recovered genome, the taxonomic resolution of this deltaproteobacterium was unable to be clarified due to insufficient described close relatives. Together, the low taxonomic resolution, relatively low 16S rDNA abundance, and ability to degrade putative upstream metabolites that may facilitate methanogenesis in the coal seam environment, indicates that this method of analysis can assist in understanding other important but uncharacterised rare taxa of the coal seam microbiome. A clearer understanding of the function of these taxa would allow targeted strategies to enhance methane production, as well as contributing valuable knowledge of carbon cycling in the terrestrial subsurface.

Two-Component versus Three-Component Condensations in the Race between Hydrazide, Triketone, and Hydrogen Peroxide-How do All Six Reactive Centers Cooperate to Incorporate the Most Diverse Set of Heteroatomic Bridges in a Tricyclic Frame?

Relief of stereoelectronic frustration drives the acid-catalyzed three-component condensation of β,δ'-triketones with hydrazides and H2O2 to the direction where both nucleophiles and all three electrophilic carbons are involved in the formation of a tricyclic sp3-rich ring system that includes four heteroatoms. The otherwise inaccessible tricyclic N-substituted aminoperoxides are prepared rapidly and selectively from relatively simple substrates in good to high yields.

Advantages of residual phenol in coal chemical wastewater as a co-metabolic substrate for naphthalene degradation by microbial electrolysis cell

The use of co-metabolic substrates is effective for polycyclic aromatic hydrocarbons (PAHs) removal, but the potential of the high phenol concentrations in coal chemical wastewater (CCW) as a co-metabolic substrate in microbial electrolysis cell (MEC) has been neglected. In this study, the efficacy of varying phenol concentrations in comparison to simple substrates for degrading naphthalene in MEC under comparable COD has been explored. Results showed that phenol as a co-metabolic substrate outperformed sodium acetate and glucose in facilitating naphthalene degradation efficiency at 50 mg-COD/L. The naphthalene removal efficiency from RP, RA, and RG was found to be 84.11 ± 0.44 %, 73.80 ± 0.27 % and 72.43 ± 0.34 %, respectively. Similarly, phenol not only enhanced microbial biomass more effectively, but also exhibited optimal COD metabolism capacity. The addition of phenol resulted in a stepwise reduction in the molecular weight of naphthalene, whereas sodium acetate and glucose led to more diverse degradation pathways. Some bacteria with the potential ability to degrade PAHs were detected in phenol-added MEC, including Alicycliphilus, Azospira, Stenotrophomonas, Pseudomonas, and Sedimentibacter. Besides, phenol enhanced the expression of ncrA and nmsA genes, leading to more efficient degradation of naphthalene, with ncrA responsible for mediating the reduction of the benzene ring in naphthalene and nmsA closely associated with the decarboxylation of naphthalene. This study provides guidance for the effective co-degradation of PAHs in CCW with MEC, demonstrating the effectiveness of using phenol as a co-substrate relative to simple substrates in the removal of naphthalene.

Simple and Complex Substrates (Sugar, Acetate and Milk Whey) for In Situ Bioremediation of Groundwater with Nitrate and Actinide Contamination

The complex contamination of groundwater near radioactive waste repositories by nitrates and actinides is a common problem for many nuclear fuel cycle facilities. One of the effective methods to remove nitrates and reduce actinide migration activity is bioremediation through the activation of native microbial communities by soluble electron donors and carbon sources. This work evaluated the effectiveness of using simple and complex electron donors to remove nitrate in the microbial community in an aquifer near the B2 storage of the Siberian Chemical Combine (Seversk, Siberia). The addition of sugar and milk whey led to the maximum efficiency of nitrate-ion removal and a decrease in the redox potential of the system, creating optimal conditions for the immobilization of actinide. Special attention was paid to the behavior of uranium, plutonium, neptunium, and americium under conditions simulating groundwater when sugar, acetate, and milk whey were added and when microbial metabolic products were formed. Neither microbial metabolites nor organic solutions were found to have a significant effect on the leaching of neptunium. At the same time, for plutonium, a decrease in yield was observed when rocks were treated with organic solutions were compared to groundwater treatment without them. Plutonium leaching is significantly affected by rock composition. In rocks with a low clay fraction content, its yield can reach 40%. At the same time, microbial metabolites can increase americium (Am) desorption from rocks with a low clay fraction content. Additionally, particle size analysis was performed using a step-by-step filtration approach, aiming to evaluate the risks that are associated with colloidal phase formation. It was shown that microbiological stimulation resulted in particle enlargement, substantially diminishing the presence of actinides in the form of dissolved or sub-50 nm nanoparticles. This outcome significantly reduced the potential for colloidal and pseudocolloidal transfer, thereby lowering associated risks.

Close-packed small nanocubes assemblies as efficient SERS substrates

Silver-based nanostructures, especially the anisotropic ones such as triangular nanoplates, nanorods, nanocubes or silver nanowires, are used as Surface enhanced Raman scattering substrates for different analytes sensing, with outstanding results, in terms of the limit of detection (LOD), as well as the enhancement factor (EF), being applicable for early clinical diagnosis of cancer, trace level detection of different organic pollutants, or for the pesticides’ detection, and even explosives. Among all these shapes, cubes like nanoparticles (AgNCs) can generate intense hot-spots due to their corners and edges, due to some additional plasmonic modes that occur at different resonance wavelengths in the spectrum, thus, improving SERS sensitivity.In this work we have successfully synthesized silver AgNCs of 60 nm, that were then assembled on a planar silicon substrate, and use it as a simple SERS substrate towards Rh6G dye. We were able to obtain an averaged calculated EF of 1.78 × 108, with a limit of detection of 4. 16 × 10−12 M. Furthermore, the effect of nanocubes’ configurations was investigated through the numerical calculations, being revealed that the edge-to-edge arrangement exhibits the highest EF of about 109, followed by the edge-to-face (8.6 × 108) and face-to-face (9 × 107) arrangements, in good agreement with experimental calculated value, ∼108, considering the frequency of appearance of each configuration.Our studies related to the use of assemblies of smaller AgNCs on planar silicon surface, with no further nanostructuration process, as SERS based substrates towards one of the most known analyte molecules, as well as an organic dye pollutant, are very encouraging, giving the chance to explore the emerging properties of small nanocubes towards low concentration detection of different organic molecules, thus showing great applicability in both scientific research and practical application, like water pollutants or even foodborne pathogen detection.

Synthesis, α‐Glucosidase Inhibitory Activity, and Molecular Docking Studies of Tri(benzo)‐5‐azacrownophanes with a γ‐Piperidone Moiety

AbstractMulticomponent reactions (MCR) are power tools in modern organic synthesis. These reactions have many advantages over single component reactions, including saving time and chemicals. Moreover, compounds with complicated structures can be synthesized based on simple substrates and one‐step reactions, without the tedious work of separating intermediate compounds. Taking full advantage of this tool, over the past 10 years we have synthesized novel crown compounds with the successful introduction of different bioactive moieties into molecules. As part of our ongoing research, this study reports on the synthesis of a new type of crown ether based on a three component reaction of an aldehyde, a ketone, and ammonium acetate in dry solvent, at specific temperature. The structure of the new compounds was identified using physical‐chemical methods of analysis including IR, 1H & 13C NMR, HRMS and single‐X ray diffraction. The effects of the newly synthesized azacrown ethers on the enzyme α‐glucosidase were then explored and they were shown to be potential candidates in the search for new antidiabetic drugs. Among five tested compounds, two compounds are active again the enzyme α‐glucosidase and expressed IC50 values of 407.17±9.01 μM and 345.90±6.75 μM. Molecular docking studies were also performed to investigate the binding mode of the synthetic compounds to α‐glucosidase. Finally, ADMET parameters were assessed to investigate the relationship between structure and biological activities.

Review of Plasma Processing for Polymers and Bio-Materials Using a Commercial Frequency (50/60 Hz)-Generated Discharge

This manuscript introduces the properties and diverse applications of plasma generated using commercial frequencies of 50/60 Hz. Commercial frequency (CF) derived plasma exhibits characteristics similar to DC discharge but with an electrical polarity and a non-continuous discharge. Due to the low-frequency nature, the reactor configurations usually are capacitively coupled plasma type. The advantages of this method include its simple power structure, low-reaction temperature, and low substrate damage. The electrical polarity can prevent charge buildup on the substrates and deposited films, thereby reducing substrate damage. The simple, low-cost, and easy-to-operate power structure makes it suitable for laboratory-scale usage. Additionally, the various applications, including plasma-enhanced vapor deposition, sputtering, dielectric barrier discharge, and surface modification, and their outcomes in the CF-derived plasma processes are summarized. The conclusion drawn is that the CF-derived plasma process is useful for laboratory-scale utilization due to its simplicity, and the results of the plasma process are also outstanding.

Hydrocarbon Oxidation by a Porphyrin-π-Cation Radical Complex.

Heme and chlorin π-cation radical oxidants are widely implicated in biological and synthetic oxidation catalysis. Little insight into the role of π-cation radicals in proton coupled electron transfer (PCET) oxidation is available. We prepared a NiII-porphyrin-π-cation complex ([NiII(P•+)]) and found it to be capable of the oxidation of a variety of simple hydrocarbon substrates. Interestingly, some of the products were hydroxylated, with ([NiII(P•+)]) working in concert with atmospheric O2 to yield hydroxylated hydrocarbons. Kinetic data suggested that the porphyrin-π-cation radical species oxidised substrates via a concerted PCET mechanism, where the nickel porphyrin-π-cation radical accepted the electron, and the proton was transferred to a free anion. Our findings highlight the potential role of π-cation radicals as hydrocarbon activators, demonstrating that porphyrin ligand non-innocence could be a readily manipulated resource for oxidation catalyst development.

Construction of a Bicyclo[2.2.2]octene Skeleton via a Visible-Light-Mediated Radical Cascade Reaction of Amino Acid Derivatives with N-(2-Phenyl)benzoyl Groups.

Bridged polycyclic ring systems constitute the core structures of numerous natural products and biologically active molecules. We found that simple biphenyl substrates derived from amino acids participate in a radical cascade reaction under visible light irradiation in the presence of [Ir{dF(CF3)ppy}2(dtbpy)]PF6 to enable the direct construction of bicyclo[2.2.2]octene structures. Isotopic labeling experiments suggested that intramolecular hydrogen atom transfer is involved in the cascade processes.

Hydrocarbon Oxidation by a Porphyrin‐π‐Cation Radical Complex

AbstractHeme and chlorin π‐cation radical oxidants are widely implicated in biological and synthetic oxidation catalysis. Little insight into the role of π‐cation radicals in proton coupled electron transfer (PCET) oxidation is available. We prepared a NiII‐porphyrin‐π‐cation complex ([NiII(P⋅+)]) and found it to be capable of the oxidation of a variety of simple hydrocarbon substrates. Interestingly, some of the products were hydroxylated, with ([NiII(P⋅+)]) working in concert with atmospheric O2 to yield hydroxylated hydrocarbons. Kinetic data suggested that the porphyrin‐π‐cation radical species oxidised substrates through a concerted PCET mechanism, where the porphyrin‐π‐cation radical accepted the electron, and the proton was transferred to a free anion. Our findings highlight the potential role of π‐cation radicals as hydrocarbon activators, demonstrating that porphyrin ligand non‐innocence could be a readily manipulated resource for oxidation catalyst development.

Coenzyme biosynthesis in response to precursor availability reveals incorporation of β-alanine from pantothenate in prototrophic bacteria

Coenzymes are important for all classes of enzymatic reactions and essential for cellular metabolism. Most coenzymes are synthesized from dedicated precursors, also referred to as vitamins, which prototrophic bacteria can either produce themselves from simpler substrates or take up from the environment. The extent to which prototrophs use supplied vitamins and whether externally available vitamins affect the size of intracellular coenzyme pools and control endogenous vitamin synthesis is currently largely unknown. Here, we studied coenzyme pool sizes and vitamin incorporation into coenzymes during growth on different carbon sources and vitamin supplementation regimes using metabolomics approaches. We found that the model bacterium Escherichia coli incorporated pyridoxal, niacin, and pantothenate into pyridoxal 5'-phosphate, NAD, and coenzyme A (CoA), respectively. In contrast, riboflavin was not taken up and was produced exclusively endogenously. Coenzyme pools were mostly homeostatic and not affected by externally supplied precursors. Remarkably, we found that pantothenate is not incorporated into CoA as such but is first degraded to pantoate and β-alanine and then rebuilt. This pattern was conserved in various bacterial isolates, suggesting a preference for β-alanine over pantothenate utilization in CoA synthesis. Finally, we found that the endogenous synthesis of coenzyme precursors remains active when vitamins are supplied, which is consistent with described expression data of genes for enzymes involved in coenzyme biosynthesis under these conditions. Continued production of endogenous coenzymes may ensure rapid synthesis of the mature coenzyme under changing environmental conditions, protect against coenzyme limitation, and explain vitamin availability in naturally oligotrophic environments.

Predictive model of ice adhesion on non-elastomeric materials

Hypothesis:When ice accumulates on a surface, it can adversely impact functionality and safety of a platform in infrastructure, transportation, and energy sectors. Despite several attempts to model the ice adhesion strength on ice-shedding materials, none have been able to justify variation in the ice adhesion strength measured by various laboratories on a simple bare substrate. This is primarily due to the fact that the effect of underlying substrate of an ice-shedding material has been entirely neglected. Experiments:Here, we establish a comprehensive predictive model for ice adhesion using the shear force method on a multi-layered material. The model considers both shear resistance of the material and shear stress transfer to the underlying substrate. We conducted experiments to validate the model predictions on the effect of coating and substrate properties on the ice adhesion. Findings:The model reveals the importance of the underlying substrate of a coating on ice adhesion. Most importantly, the correlation between the ice adhesion and the coating thickness are entirely different for elastomeric and non-elastomeric materials. This model justifies different measured ice adhesion across various laboratories on the same material and elucidates how one could achieve both low ice adhesion and high mechanical durability. Such predictive model and understanding provides a rich platform to guide the future material innovation with minimal adhesion to the ice.

Spray-On Colorimetric Sensors for Distinguishing the Presence of Lead Ions.

Sprayable stimuli-responsive material coatings represent a new class of detection system which can be quickly implemented to transform a surface into a color-responsive sensor. In this work, we describe a dipicolylamine-terminated diacetylene-containing amphiphile formulation for spray coating on to a simple paper substrate to yield disposable test strips that can be used to detect the presence of lead ions in solution. We find the response to be very selective to only lead ions and that the sensitivity can be modulated by altering the UV curing time after spraying. Sensitive detection to at least 0.1 mM revealed a clear color change from a blue to red phase. This represents the first demonstration of a spray-on sensor system capable of detection of lead ions in solution.

Possibility of exogenous organic carbon input to increase global soil nitrogen supply potential: A meta-analysis

Soil nitrogen (N) mineralization is regulated by the input of exogenous organic carbon (C, ExoC) substrate via changing C availability. Although ExoC input occurs widely among global terrestrial ecosystems, it is still not clear how ExoC input affects soil gross N mineralization (GNM). Here, 265 observations from 63 peer-reviewed publications were collected for a global meta-analysis to investigate the effect and the drivers of ExoC input upon soil GNM. The results showed that ExoC input significantly increased GNM by 40.8%, and the influence depended on the types of ExoC substrate. The input of complex ExoC substrate (straw, animal manure, cellulose, etc.) increased soil GNM by 44.8%, while simple ExoC substrate (glucose, amino acids, oxalic, etc.) had no significant effect on GNM. Only in cropland the ExoC input promote the rate of soil GNM, with no significant effect found in either forest or grassland. Furthermore, the results revealed that the application rate of ExoC was the paramount factor affecting soil GNM, given their significant positive correlations. This study also emphasized that initial soil pH (i.e. soil pH before ExoC input) and pH of ExoC, rather than the change of bulk soil pH, played an important role in regulating soil GNM after the ExoC input, and both were significantly negatively correlated with GNM. In addition, soil GNM was also negatively correlated with mean annual temperature but positively related with soil total N and mean annual precipitation. The findings of this meta-analysis contribute to a comprehensive understanding of how soil N availability and cycling respond to ExoC input on a global scale. That means the factors related to rate of ExoC, soil total N, initial soil pH, the pH of ExoC, and climate factors and the interaction among above factors may affect global soil N supplying potential.

Palladium-Catalyzed Cyanation of Nucleobases: Total Synthesis of Toyocamycin, Sangivamycin, and a Mycalisine A Precursor

AbstractInstallation of cyano group functionality onto nucleosides has always been a challenging task for chemists, and catalytic protocols developed for simple aryl substrates have, in most cases, failed to replicate their success when applied to nucleobase or sugar moieties of nucleosides. Given the importance of the cyano and amide functionalities in nucleoside chemistry, we herein disclose an efficient Pd-catalyzed cyanation protocol specifically applied to iodo nucleobases. Furthermore, the developed cyanation method has been explored for the synthesis of naturally occurring and bioactive nucleosides such as toyocamycin, sangivamycin, and a mycalisine A precursor.

Zero or minimal fluoroscopy catheter ablation: feasibility, efficacy, and safety results

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Fluoroscopy has been used to guide catheter ablation since the beginning of this technique, despite its important secondary effects on both patients and operators. However, three-dimensional electroanatomic mapping systems (3D-EAMP) enable ablation of some substrates using zero or minimal fluoroscopy. The aim of this study is to explore the feasibility, efficacy and safety of a zero or minimal fluoroscopy approach in our center. Methods We performed a retrospective observational study with consecutive patients that underwent catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT), accessory pathways (AP), focal atrial tachycardia and typical atrial flutter in our center, between January 2020 and November 2022. Vascular access was obtained by ultrasound guidance. The objective was zero-fluoroscopy for all patients except those with left AP, in which minimal fluoroscopy was allowed for the transseptal access (ablations with retrograde aortic approach were excluded). Results 319 consecutive patients were included. 56% were male, mean age was 55 ± 16 years. The following substrates were included: AVNRT (43%), typical atrial flutter (41%), AP (12%) and focal atrial tachycardia (5%). We achieved zero-fluoroscopy use in 99.3% of right substrates, using fluoroscopy in just two cases to introduce catheters through femoral access. Mean fluoroscopy time in left AP was 6.1 minutes. Ablation was successful in 97% of cases, and we just experienced three complications (moderate pericardial effusion, femoral hematoma and femoral arteriovenous fistula, all of them solved without requiring intervention). After a mean follow- up of 17 ± 14 months, we noticed three recurrences, performing in all of them a successful second ablation procedure. Baseline characteristics and procedure details are shown in table 1. Conclusions Catheter ablation of simple substrates with zero or minimal fluoroscopy using 3D mapping systems is feasible, effective and safe, with high success rate and low complications rate.

Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3-sp2 Carbon-Carbon Bonds.

Amines and carboxylic acids are abundant synthetic building blocks that are classically united to form an amide bond. To access new pockets of chemical space, we are interested in the development of amine-acid coupling reactions that complement the amide coupling. In particular, the formation of carbon-carbon bonds by formal deamination and decarboxylation would be an impactful addition to the synthesis toolbox. Here, we report a formal cross-coupling of alkyl amines and aryl carboxylic acids to form C(sp3)-C(sp2) bonds following preactivation of the amine-acid building blocks as a pyridinium salt and N-acyl-glutarimide, respectively. Under nickel-catalyzed reductive cross-coupling conditions, a diversity of simple and complex substrates are united in good to excellent yield, and numerous pharmaceuticals are successfully diversified. High-throughput experimentation was leveraged in the development of the reaction and the discovery of performance-enhancing additives such as phthalimide, RuCl3, and GaCl3. Mechanistic investigations suggest phthalimide may play a role in stabilizing productive Ni complexes rather than being involved in oxidative addition of the N-acyl-imide and that RuCl3 supports the decarbonylation event, thereby improving reaction selectivity.

Iron(III)-Catalyzed Carboannulations of Homopropargylic Alcohols: A One-Pot General Synthesis of 4-(2,2-Diarylvinyl)quinolines and 4-(2,2-Diarylvinyl)-2H-chromenes.

A simple and efficient approach for the general synthesis of 4-(2,2-diarylvinyl)quinolines 5 and 4-(2,2-diarylvinyl)-2H-chromenes 6 has been developed using Fe(III)-catalyzed intramolecular annulations of homopropargyl substrates 1 and 2, respectively. The high yields (up to 98%) achieved using simple substrates, an environmentally benign low-cost catalyst, and less hazardous reaction conditions make the methodology inherently attractive.

Ultrasensitive enhanced Raman spectroscopy by hybrid surface-enhanced and interference-enhanced Raman scattering with metal-insulator-metal structures.

High-sensitivity, reproducible, and low-cost substrate has been a major obstacle for practical sensing application of surface-enhancement Raman scattering (SERS). In this work, we report a type of simple SERS substrate which is composed of metal-insulator-metal (MIM) structure of Ag nanoisland (AgNI)-SiO2-Ag film (AgF). The substrates are fabricated by only evaporation and sputtering processes, which are simple, fast and low-cost. By combining the hotspots and interference-enhanced effects in AgNIs and the plasmonic cavity (SiO2) between AgNIs and AgF, the proposed SERS substrate shows an enhancement factor (EF) of 1.83 × 108 with limit of detection (LOD) down to 10-17 mol/L for rhodamine 6 G (R6G) molecules. The EFs are ∼18 times higher than that of conventional AgNIs without MIM structure. In addition, the MIM structure shows excellent reproducibility with relative standard deviation (RSD) less than 9%. The proposed SERS substrate is fabricated only with evaporation and sputtering technique and the conventionally used lithographic methods or chemical synthesis are not required. This work provides a simple way to fabricate ultrasensitive and reproducible SERS substrates which show great promise for developing various biochemical sensors with SERS.