Launching a Drop via Interplay of Buoyancy and Stick-Jump Dissolution.

According to Archimedes' principle, a submerged object with a density lower than that of aqueous acid solution is more buoyant than a smaller one. In this work, a remarkable phenomenon is reported wherein a dissolving drop on a substrate rises in the water only after it has diminished to a much smaller size, though the buoyancy is smaller. The drop consisting of a polymer solution reacts with the acid in the surrounding, yielding a water-soluble product. During drop dissolution, water-rich microdroplets form within the drop, merging with the external aqueous phase along the drop-substrate boundary. Two key elements determine the drop rise dynamics. The first is the stick-jump behavior during drop dissolution. The second is that buoyancy exerts a strong enough force on the drop at an Archimedean number greater than 1, while the stick-jump behavior is ongoing. The time of the drop rise is controlled by the initial size and the reaction rate of the drop. This novel mechanism for programmable drop rise may be beneficial for many future applications, such as microfluidics, microrobotics, and device engineering where the spontaneous drop detachment may be utilized to trigger a cascade of events in a dense medium.

Spontaneous Rise of Hydrogen Microbubbles in Interfacial Gas Evolution Reaction.

Liquid organic hydrogen carrier is a promising option for the transport and storage of hydrogen as a clean energy source. This study examines the stability and behavior of organic drops immobilized on a substrate during an interfacial hydrogen-evolution reaction (HER) at the drop surface and its surrounding aqueous solution. Hydrogen microbubbles form within the drop and rise to the drop apex. The growth rate of the hydrogen in-drop bubble increases with the concentration of the reactant in the surrounding medium. The drop remains stable till the buoyancy acting on the in-drop bubble is large enough to overcome the capillary force and the external viscous drag. The bubble spontaneously rises and carries a portion drop liquid to the solution surface. These spontaneous rising in-drop bubbles are detected in measurements using a high-precision sensor placed on the upper surface of the aqueous solution, reversing the settling phase from phase separation in the reactive emulsion. The finding from this work provides new insights into the behaviors of drops and bubbles in many interfacial gas evolution reactions in clean technologies.

IGFBP3 induces PD-L1 expression to promote glioblastoma immune evasion.

BACKGROUND: Glioblastoma (GBM) characterized by immune escape is the most malignant primary brain tumors, which has strong immunosuppressive effect. Programmed death ligand-1 (PD-L1) is a recognized immunosuppressive member on the surface of tumor cells, and plays a crucial role in immune evasion of tumors. Actually, little is known about the regulation of PD-L1 expression in GBM. Insulin-like growth factor binding protein 3 (IGFBP3) is upregulated in GBM and is related to poor patient prognosis. However, it remains unclear whether IGFBP3 plays a role in the regulation of PD-L1 expression in GBM. METHODS: The role of IGFBP3 in the glioma immune microenvironment was investigated using the CIBERSORT algorithm. The correlation between IGFBP3 and PD-L1 expression was analyzed using TCGA and CGGA databases. QRT-PCR, immunoblotting and RNA-seq were used to examine the regulatory effect of IGFBP3 on PD-L1 expression. Co-culture assay, cell counting kit (CCK-8), qRT-PCR, ELISA and flow cytometry were performed to explore the function of IGFBP3 in inducing immunosuppression. The biological role of IGFBP3 was verified using immunohistochemical, immunofluorescence and mice orthotopic tumor model. RESULTS: In this study, we analyzed immune cells infiltration in gliomas and found that IGFBP3 may be associated with an immunosuppressive microenvironment. Then, by analyzing TCGA and CGGA databases, our results showed that IGFBP3 and PD-L1 expression were positively correlated in GBM patients, but not in LGG patients. In vitro experiments conducted on different GBM cell lines revealed that the overexpression of IGFBP3 led to an increase in PD-L1 expression, which was reversible upon knockdown IGFBP3. Mechanistically, IGFBP3 activated the JAK2/STAT3 signaling pathway, leading to an increase in PD-L1 expression. Additionally, co-culture experiments results showed IGFBP3 overexpression induced upregulation of PD-L1 expression promoted apoptosis in Jurkat cells, and this effect was blocked by IGFBP3 antibody and PDL-1 inhibitors. Importantly, in vivo experiments targeting IGFBP3 suppressed tumor growth and significantly prolonged the survival of mice. CONCLUSIONS: This research demonstrated IGFBP3 is a novel regulator for PD-L1 expression in GBM, and identified a new mechanism by which IGFBP3 regulates immune evasion through PD-L1, suggesting that IGFBP3 may be a potential novel target for GBM therapy.

Flexible Surface-Enhanced Raman Scattering Tape Based on Ag Nanostructured Substrate for On-Site Analyte Detection.

Surface-enhanced Raman scattering (SERS) has emerged as a powerful surface analytical technique that amplifies Raman scattering signals of molecules adsorbed onto metal nanostructured surfaces. The droplet reaction method has recently been employed to fabricate large-scale microring patterns of silver (Ag) nanostructures on rigid substrates, which enables sensitive detection within the ring area. However, these rigid substrates present limitations for direct on-site detection of analyte residues on irregular sample surfaces. There is a need to develop soft and flexible SERS substrates that can intimately conform to arbitrary surfaces. In this study, we presented a SERS substrate using flexible and adhesive tape as the supporting material. This SERS tape was fabricated by repeatedly transferring presynthesized Ag nanostructures from a rigid substrate to the tape. For a model compound adenine, our SERS tape exhibited a good linear response from 5 × 10-4 M to 5 × 10-5 M with a low limit of detection (LOD) of 5 × 10-7 M and displayed a SERS enhancement factor (EF) of 3.2 × 105. The relative standard deviation (RSD) of SERS intensity achieved was as low as 1.93%, indicating its outstanding uniformity. The as-prepared SERS tape was used for in situ detection of pesticide residue on an apple surface and dye residue on human hair. Leveraging the large surface area of Ag nanostructure patterns from the droplet reaction, the developed SERS tape demonstrates excellent performance in terms of sensitivity and uniformity. The successful detection of analyte residues on arbitrary surfaces of apple and human hair highlights the potential of this flexible SERS tape for real-world applications across various industries for enhanced diagnostic accuracy.

A Tandem Regiospecific [3 + 2] Annulation/Ring Cleavage Reaction for the Synthesis of ß-Ketoenamides.

A series of ß-ketoenamines was synthesized from various phenacyl sulfoxides bearing 1-methyl-1H-tetrazole and oximes in moderate to excellent yields. The proposed mechanism involved the generation of α-sulfines from sulfoxides through thermolytic elimination, regiospecific formal [3 + 2] annulations, and elimination of SO2. This protocol provides convenient access to a variety of synthetically valuable N-unprotected ß-enaminones with absolute Z selectivity.

Determination of Trace Organic Contaminant Concentration via Machine Classification of Surface-Enhanced Raman Spectra.

Surface-enhanced Raman spectroscopy (SERS) has been well explored as a highly effective characterization technique that is capable of chemical pollutant detection and identification at very low concentrations. Machine learning has been previously used to identify compounds based on SERS spectral data. However, utilization of SERS to quantify concentrations, with or without machine learning, has been difficult due to the spectral intensity being sensitive to confounding factors such as the substrate parameters, orientation of the analyte, and sample preparation technique. Here, we demonstrate an approach for predicting the concentration of sample pollutants from SERS spectra using machine learning. Frequency domain transform methods, including the Fourier and Walsh-Hadamard transforms, are applied to spectral data sets of three analytes (rhodamine 6G, chlorpyrifos, and triclosan), which are then used to train machine learning algorithms. Using standard machine learning models, the concentration of the sample pollutants is predicted with >80% cross-validation accuracy from raw SERS data. A cross-validation accuracy of 85% was achieved using deep learning for a moderately sized data set (∼100 spectra), and 70-80% was achieved for small data sets (∼50 spectra). Performance can be maintained within this range even when combining various sample preparation techniques and environmental media interference. Additionally, as a spectral pretreatment, the Fourier and Hadamard transforms are shown to consistently improve prediction accuracy across multiple data sets. Finally, standard models were shown to accurately identify characteristic peaks of compounds via analysis of their importance scores, further verifying their predictive value.

Effects of Ultrasonic Power on the Structure and Rheological Properties of Skin Collagen from Albacore (Thunnus alalunga).

The effects of ultrasonic power (0, 150, 300, 450, and 600 W) on the extraction yield and the structure and rheological properties of pepsin-soluble collagen (PSC) from albacore skin were investigated. Compared with the conventional pepsin extraction method, ultrasonic treatment (UPSC) significantly increased the extraction yield of collagen from albacore skin, with a maximum increase of 8.56%. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that peptides of low molecular weight were produced when the ultrasonic power exceeded 300 W. Meanwhile, secondary structure, tertiary structure, and X-ray diffraction analyses showed that the original triple helix structure of collagen was intact after the ultrasonic treatment. The collagen solutions extracted under different ultrasonic powers had significant effects on the dynamic frequency sweep, but a steady shear test suggested that the collagen extracted at 150 W had the best viscosity. These results indicate that an ultrasonic power between 150 and 300 W can improve not only the extraction yield of natural collagen, but also the rheological properties of the collagen solution without compromising the triple helix structure.

Effect of Potentilla anserina L. powder on gel properties and volatile flavor characteristics of silver carp surimi.

BACKGROUND: Potentilla anserina L. is rich in various nutrients, active ingredients and unique flavor, comprising a natural nutrition and health food. However, its application in aquatic food has been rarely reported. Therefore, the effects of Potentilla anserina L. powder (PAP) on gel properties and volatile flavor profile of silver carp surimi were investigated. RESULTS: The gel strength and water-holding capacity of the surimi gels were significantly improved (P < 0.05), and the whiteness and cooking loss of all the samples decreased slightly with the increase in PAP content. The addition of PAP shortened the relaxation time (T2) of the surimi gels and converted some of the free water into immobile or bound water, which resulted in a better immobilization of water in the surimi. Scanning electron microscopy images demonstrated that the network of surimi gels with PAP added was denser and had a smoother surface compared to the control. Volatile components (VCs) analysis showed that 33 VCs were identified in the surimi gel samples with different additions of PAP, among which aldehydes, alcohols and esters were the major VCs, accounting for more than 50% of the VCs in the surimi gels. PAP addition reduced the fishy and rancid flavor compounds in surimi gels, such as 1-propanol, 1-octen-3-ol, etc., and promoted the production of aldehydes, alcohols, esters and other flavor substances. CONCLUSION: These results of the present study provide theoretical support for the investigation and development of new nutrient-health-flavored surimi products. © 2024 Society of Chemical Industry.

Jahn-Teller Distortions Induced by in situ Li Migration in λ-MnO2 for Boosting Electrocatalytic Nitrogen Fixation.

Lithium-mediated electrochemical nitrogen reduction reaction (Li-NRR) completely eschews the competitive hydrogen evolution reaction (HER) occurred in aqueous system, whereas the continuous deposition of lithium readily blocks the active sites and further reduces the reaction kinetics. Herein, we propose an innovative in situ Li migration strategy to realize that Li substitutes Mn sites in λ-MnO2 instead of evolving into the dead Li. Comprehensive characterizations corroborate that the intercalation of Li+ at high voltage breaks the structural integrity of MnO6 octahedron and further triggers unique Jahn-Teller distortions, which promotes the spin state regulation of Mn sites to generate the ameliorative eg orbital configuration and accelerates N≡N bond cleavage via eg -σ and eg -π* interaction. To this end, the resulted cationic disordered LiMnO4 delivers the recorded highest NH3 yield rate of 220 µg h-1 cm-2 and a Faradaic efficiency (FE) 83.80 % in organic electrolyte.

A Simple and Effective Physical Ball-Milling Strategy to Prepare Super-Tough and Stretchable PVA@MXene@PPy Hydrogel for Flexible Capacitive Electronics.

Biomimetic flexible electronics for E-skin have received increasing attention, due to their ability to sense various movements. However, the development of smart skin-mimic material remains a challenge. Here, a simple and effective approach is reported to fabricate super-tough, stretchable, and self-healing conductive hydrogel consisting of polyvinyl alcohol (PVA), Ti3 C2 Tx MXene nanosheets, and polypyrrole (PPy) (PMP hydrogel). The MXene nanosheets and Fe3+ serve as multifunctional cross-linkers and effective stress transfer centers, to facilitate a considerable high conductivity, super toughness, and ultra-high stretchability (elongation up to 4300%) for the PMP hydrogel with. The hydrogels also exhibit rapid self-healing and repeatable self-adhesive capacity because of the presence of dynamic borate ester bond. The flexible capacitive strain sensor made by PMP hydrogel shows a relatively broad range of strain sensing (up to 400%), with a self-healing feature. The sensor can precisely monitor various human physiological signals, including joint movements, facial expressions, and pulse waves. The PMP hydrogel-based supercapacitor is demonstrated with a high capacitance retention of ≈92.83% and a coulombic efficiency of ≈100%.

Long-term outcomes of single-incision plus one-port laparoscopic surgery versus conventional laparoscopic surgery for rectosigmoid cancer: a randomized controlled trial.

BACKGROUND: Though our previous study has demonstrated that the single-incision plus one-port laparoscopic surgery (SILS + 1) is safe and feasible for sigmoid colon and upper rectal cancer and has better short-term outcomes compared with conventional laparoscopic surgery (CLS), the long-term outcomes of SILS + 1 remains uncertain and are needed to evaluated by an RCT. METHODS: Patients with clinical stage T1-4aN0-2M0 rectosigmoid cancer were enrolled. The participants were randomly assigned to either SILS + 1 (n = 99) or CLS (n = 99). The 3-year DFS, 5-year OS, and recurrence patterns were analyzed. RESULTS: Between April 2014 and July 2016, 198 patients were randomly assigned to either the SILS + 1 group (n = 99) or CLS group (n = 99). The median follow-up in the SILS + 1 group was 64.0 months and in CLS group was 65.0 months. The 3-year DFS was 87.8% (95% CI, 81.6-94.8%) in SILS + 1 group and 86.9% (95% CI, 81.3-94.5%) in CLS group (hazard ratio: 1.09 (95% CI, 0.48-2.47; P = 0.84)). The 5-year OS was 86.7% (95% CI,79.6-93.8%) in the SILS + 1 group and 80.5% (95% CI,72.5-88.5%) in the CLS group (hazard ratio: 1.53 (95% CI, 0.74-3.18; P = 0.25)). There were no significant differences in the recurrence patterns between the two groups. CONCLUSIONS: We found no significant difference in 3-year DFS and 5-year OS of patients with sigmoid colon and upper rectal cancer treated with SILS + 1 vs. CLS. SILS + 1 is noninferior to CLS when performed by expert surgeons. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02117557 (registered on 21/04/2014).

Evolution of Morphology and Distribution of Salt Crystals on a Photothermal Layer during Solar Interfacial Evaporation.

Solar interfacial evaporation (SIE) by leveraging photothermal conversion could be a clean and sustainable solution to the scarcity of fresh water, decontamination of wastewater, and steam sterilization. However, the process of salt crystallization on photothermal materials used in SIE, especially from saltwater evaporation, has not been completely understood. We report the temporal and spatial evolution of salt crystals on the photothermal layer during SIE. By using a typical oil lamp evaporator, we found that salt crystallization always initiates from the edge of the evaporation surface of the photothermal layer due to the local fast flux of the vapor to the surroundings. Interestingly, the salt crystals exhibit either compact or loose morphology, depending on the location and evaporation duration. By employing a suite of complementary analytical techniques of Raman and infrared spectroscopy and temperature mapping, we followed the evolution and spatial distribution of salt crystals, interfacial water, and surface temperature during evaporation. Our results suggested that the compact crystal structure may emerge from the recrystallization of salt in an initially porous structure, driven by continuous water evaporation from the porous and loose crystals. The holistic view provided in this study may lay the foundation for effective strategies for mitigation of the negative impact of salt crystallization in solar evaporation.

Dissolution dynamics of a binary switchable hydrophilicity solvent-polymer drop into an acidic aqueous phase.

Switchable hydrophilicity solvents (SHSs) are solvents defined by their ability to switch from their hydrophobic form to a hydrophilic form when brought into contact with an acidic trigger such as CO2. As a consequence, SHSs qualify as promising alternatives to volatile organic compounds during industrial solvent extraction processes, as greener and inexpensive methods can be applied to separate and recover SHSs. Furthermore, because of their less volatile nature, SHSs are less flammable and so increase the safety of a larger scale extraction process. In this work, we study the dynamics and in-drop phase separation during the dissolution process of a drop composed of a SHS and a polymer, triggered by an acid in the surrounding aqueous environment. From 70 different experimental conditions, we found a scaling relationship between the drop dissolution time and the initial volume with an overall scaling coefficient of ∼0.53. We quantitatively assessed and found a shorter dissolution time related to a decrease in the pH of the aqueous phase or an increase in the initial polymer concentration in the drop. Examining the internal state of the drop during the dissolution revealed an in-drop phase separation behavior, resulting in a porous morphology of the final polymer particle. Our experimental results provide a microscopic view of the SHS dissolution process from droplets, and findings may help design SHS extraction processes for particle formation from emulsions.

Shvo-Catalyzed Hydrogenation of CO2 in the Presence or Absence of Ionic Liquids for Tandem Reactions.

Ionic liquids (ILs) have been widely used in transition metal-catalyzed processes, but the precise behavior of ILs and catalysts in these reactions is unknown. Herein, the role of ILs and the interaction pattern between Shvo's catalyst and ILs have been revealed with characterization by 1H NMR and crystallography based on the catalytic hydrogenation of CO2. ILs promote the dissociation of Shvo's catalyst and enhance the rate of production of CO. The CO that is produced is subsequently used in the tandem hydroformylation-reduction of alkenes to produce valuable alcohols. In the absence of ILs, formamides can be obtained by N-formylation of most primary or secondary amines.

Short-term and long-term outcomes of single-incision plus one-port laparoscopic surgery for colorectal cancer: a propensity-matched cohort study with conventional laparoscopic surgery.

BACKGROUND: Single-incision plus one-port laparoscopic surgery (SILS + 1) has been demonstrated to be minimally invasive while possessing better cosmesis and less pain compared with conventional laparoscopic surgery (CLS). However, SILS + 1 as an alternative to CLS for colorectal cancer is still controversial. METHODS: A total of 1071 patients who underwent curative laparoscopic surgery for colon cancer between 2015 and 2018 were included. Of these patients, 258 SILS + 1 cases and 516 CLS cases were analyzed using propensity score matching. The baseline characteristics, surgical outcomes, pathologic findings and recovery course, morbidity and mortality within postoperative 30 days and 3-year disease-free and overall survival were compared. RESULTS: Baseline characteristics were balanced between the groups. The mean operating time was significantly shorter in SILS + 1 group, with less estimated blood loss. Tumor size, tumor differentiation, number of harvested lymph nodes, resection margin and pathologic T, N, TNM stage was similar between the groups. There was no significant difference in overall perioperative complications. Uni- and multivariate analyses revealed that SILS + 1 was not a risk factor for complications. Postoperatively, SILS + 1 group showed faster recovery than CLS group in terms of ambulation, bowel function, oral intake and discharge. The 3-year disease-free survival rates of SILS + 1 and CLS groups were 90.1% and 87.3%(p = 0.59), respectively and the 3-year overall survival rates were 93.3% vs. 89.8%(p = 0.172). DISCUSSION: Our study revealed that SILS + 1 is safe, feasible, oncologically efficient, and may be considered as a surgical option for selected patients with colorectal cancer.

Growth Rates of Hydrogen Microbubbles in Reacting Femtoliter Droplets.

Chemical reactions in small droplets are extensively explored to accelerate the discovery of new materials and increase the efficiency and specificity in catalytic biphasic conversion and high-throughput analytics. In this work, we investigate the local rate of the gas-evolution reaction within femtoliter droplets immobilized on a solid surface. The growth rate of hydrogen microbubbles (≥500 nm in radius) produced from the reaction was measured online with high-resolution confocal microscopic images. The growth rate of bubbles was faster in smaller droplets and near the droplet rim in the same droplet. The results were consistent for both pure and binary reacting droplets and on substrates of different wettability. Our theoretical analysis based on diffusion, chemical reaction, and bubble growth predicted that the concentration of the reactant depended on the droplet size and the bubble location inside the droplet, in good agreement with experimental results. Our results reveal that the reaction rate may be spatially nonuniform in the reacting microdroplets. The findings may have implications for formulating the chemical properties and uses of these droplets.

Surface Nanodroplet-Based Extraction Combined with Offline Analytic Techniques for Chemical Detection and Quantification.

Liquid-liquid extraction based on surface nanodroplets can be a green and sustainable technique to extract and concentrate analytes from a sample flow. However, because of the extremely small volume of each droplet (<10 fL, tens of micrometers in base radius and a few or less than 1 µm in height), only a few in situ analytical techniques, such as surface-enhanced Raman spectroscopy, were applicable for the online detection and analysis based on nanodroplet extraction. To demonstrate the versatility of surface nanodroplet-based extraction, in this work, the formation of octanol surface nanodroplets and extraction were performed inside a 3 m Teflon capillary tube. After extraction, surface nanodroplets were collected by injecting air into the tube, by which the contact line of surface droplets was collected by the capillary force. As the capillary allows for the formation of ∼1012 surface nanodroplets on the capillary wall, ≥2 mL of octanol can be collected after extraction. The volume of the collected octanol was enough for the analysis of offline analytical techniques such as UV-vis, GC-MS, and others. Coupled with UV-vis, reliable extraction and detection of two common water pollutants, triclosan and chlorpyrifos, was shown by a linear relationship between the analyte concentration in the sample solution and UV-vis absorbance. Moreover, the limit of detection (LOD) as low as 2 × 10-9 M for triclosan (∼0.58 µg/L) and 3 × 10-9 M for chlorpyrifos (∼1.05 µg/L) could be achieved. The collected surface droplets were also analyzed via gas chromatography (GC) and fluorescence microscopy. Our work shows that surface nanodroplet extraction may potentially streamline the process in sample pretreatment for sensitive chemical detection and quantification by using common analytic tools.

Evaporation of a Sessile Colloidal Water-Glycerol Droplet: Marangoni Ring Formation.

The transport and aggregation of particles in suspensions is an important process in many physicochemical and industrial processes. In this work, we study the transport of particles in an evaporating binary droplet. Surprisingly, the accumulation of particles occurs not only at the contact line (due to the coffee-stain effect) or at the solid substrate (due to sedimentation) but also at a particular radial position near the liquid-air interface, forming a "ring", which we term as the Marangoni ring. The formation of this ring is primarily attributed to the solutal Marangoni flow triggered by the evaporation dynamics of the water-glycerol droplet. Experiments and simulations show fair agreement in the volume evolution and the general structure of the solutal Marangoni flow, that is, the Marangoni vortex. Experiments show that the location of the Marangoni ring is strongly correlated with the Marangoni vortex. However, finite element numerical simulations fail to describe the particle distribution seen in the experiments. Interestingly, the particles not only accumulate to form the Marangoni ring but also assemble as colloidal crystals close to the liquid-air interface, yielding iridescence. The formation of the colloidal crystals in the experiments is strong evidence that non-hydrodynamic interactions, which are not represented in the simulations, also play a significant role in our system.

Identification of ruptured intracranial aneurysms using the aneurysm-specific prediction score in patients with multiple aneurysms with subarachnoid hemorrhages- a Chinese population based external validation study.

BACKGROUND: For patients with aneurysmal subarachnoid hemorrhages (SAHs) and multiple intracranial aneurysms (MIAs), a simple and fast imaging method that can identify ruptured intracranial aneurysms (RIAs) may have great clinical value. We sought to use the aneurysm-specific prediction score to identify RIAs in patients with MIAs and evaluate the aneurysm-specific prediction score. METHODS: Between May 2018 and May 2021, 134 patients with 290 MIAs were retrospectively analyzed. All patients had an SAH due to IA rupture. CT angiography (CTA) was used to assess the maximum diameter, shape, and location of IAs to calculate the aneurysm-specific prediction score. Then, the aneurysm-specific prediction score was applied to RIAs in patients with MIAs. RESULTS: The IAs with the highest aneurysm-specific prediction scores had not ruptured in 17 (12.7%) of the 134 patients with 290 MIAs. The sensitivity, specificity, false omission rate, diagnostic error rate, and diagnostic accuracy of the aneurysm-specific prediction score were higher than those of the maximum diameter, shape, and location of IAs. CONCLUSIONS: The present study suggests that the aneurysm-specific prediction score has high diagnostic accuracy in identifying RIAs in patients with MIAs and SAH, but that it needs further evaluation.

Switching-behavior improvement in HfO2/ZnO bilayer memory devices by tailoring of interfacial and microstructural characteristics.

We investigated the effect of top contact interface and microstructural characteristics of the insulating layers on resistive switching behaviors by fabricating and characterizing the HfO2/ZnO bilayer heterostructures. Different thickness of ZnO underlying layer and different deposition temperatures of the upper HfO2layer were designed to analyze the intrinsic contribution of the crystalline microstructure of the insulating bilayer. Pt and Ti top electrodes were used to demonstrate the extrinsic contribution of the interface configuration. It was observed that all devices show bipolar RS characteristics. Unlike the device composed of Pt/HfO2/ZnO/Pt that exhibit an abrupt switching, a gradually continuous switching in the reset process was identified in the device composed of Ti/HfO2/ZnO/Pt. Interfacial charge migration process/characteristic plays a key role in the RS process as well as its conduction mechanism. The RS performance of the former is significantly better than that of the latter, including much lower reset voltage, two orders of magnitude larger OFF/ON ratio and HRS resistance. In addition, as compared to the intrinsic contribution arising from the microstructure of the HfO2/ZnO bilayer to the RS performances and current transport mechanism, the extrinsic effect contributed from the electrode characteristics (and its interface) is dominant.