Synergistic Modulation Research Articles

Piezoresistive Pressure Sensors: Synergistic Resistance Modulation toward Ultrahighly Sensitive Piezoresistive Pressure Sensors (Adv. Mater. Technol. 4/2020)

Piezoresistive Pressure Sensors: Synergistic Resistance Modulation toward Ultrahighly Sensitive Piezoresistive Pressure Sensors (Adv. Mater. Technol. 4/2020)

Defect Engineering for Enhancement of Thermoelectric Performance of (Zr, Hf)NiSn-Based n-type Half-Heusler Alloys

Defect engineering in thermoelectric (TE) materials enables the alteration of the crystal lattice by creating an atomic scale disorder, which can facilitate a synergistic modulation of the electric...

Freshwater Cyanobacterium Synechococcus elongatus PCC 7942 Adapts to an Environment with Salt Stress via Ion-Induced Enzymatic Balance of Compatible Solutes.

Salinity is one of the most important abiotic factors in various natural habitats of microbes. Cyanobacteria are the most widely distributed family of photosynthetic microorganisms in environments with fluctuating salinity. In response to salt stress, many cyanobacteria de novo synthesize compatible solutes to maintain osmotic balance in the cell. However, the regulation of intracellular accumulation of these compounds is still not well understood. The freshwater cyanobacterium Synechococcus elongatus PCC 7942 (Syn7942) exclusively accumulates sucrose as a compatible solute upon salt stress and is thus an ideal model microorganism for studying the metabolism of compatible solute dynamics. Here, we focused on elucidating the regulatory mechanisms involved in salt-induced sucrose accumulation in Syn7942. Using a series of physiological and biochemical experiments, we showed that the ionic effect of salt stress plays an important role in inducing sucrose synthesis, whereby elevated ion concentration directly activates the sucrose-synthesizing enzyme sucrose-phosphate synthase and simultaneously inhibits the sucrose-degrading enzyme invertase, resulting in a rapid sucrose accumulation. Thus, we propose a novel mechanism for cyanobacterial adaption to salt stress and fluctuating salinity, i.e., the ion-induced synergistic modulation of the enzymes synthesizing and degrading compatible solutes. These findings greatly enhance our current understanding of microbial adaptation to salt.IMPORTANCE Most microbes de novo synthesize compatible solutes for adaptation to salt stress or fluctuating salinity environments. However, to date, one of the core questions involved in these physiological processes, i.e., the regulation of salt-induced compatible solute biosynthesis, is still not well understood. Here, this issue was systematically investigated by employing the model freshwater cyanobacterium Synechococcus elongatus PCC 7942. A novel mechanism for cyanobacterial adaption to salt stress and fluctuating salinity, i.e., the ion-induced synergistic modulation of key synthesizing and degrading enzymes of compatible solutes, is proposed. Because the ion-induced activation/inhibition of enzymes is a fast and efficient process, it may represent a common strategy of microbes for adaptation to environments with fluctuating salinity.

Efficient CRISPR/Cas9 gene-chemo synergistic cancer therapy via a stimuli-responsive chitosan-based nanocomplex elicits anti-tumorigenic pathway effect

• Nanocomplex for co-delivery of CRISPR/Cas9 and paclitaxel was constructed. • The nanosystem triggered efficient gene-editing with good safety. • The gene therapy of VEGFR2 sensitized the treatment effect of paclitaxel. • The nanosystem exhibited the synergistic modulation for IL-6-IL-8/NF-κB pathway. • The nanosystem achieved significant synergistic gene-chemo HCC treatment. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease system (CRISPR/Cas9) has become a powerful toolbox as a gene fixed-point knock-out method and hold the promising prospect for cancer therapy. However, the biological safety of the viral vectors and the instability of exogenous plasmid in blood circulation limits its application. Herein, we reported a lactobionic acid functionalized and stimuli-responsive chitosan based nanocomplex to co-deliver sgVEGFR2/Cas9 plasmid and paclitaxel for hepatoma carcinoma therapy. The genome editing efficiency of sgVEGFR2/Cas9 in the nanosystem achieved up to 38.6% of HepG2 cells in vitro and 33.4% of tumor tissues in vivo. The nanocomplex suppressed >60% VEGFR2 protein expression of HepG2 cells and inhibited hepatoma carcinoma (HCC) tumor progress by 70% on mice. In vivo study indicated the obvious tumor accumulation and the good biosafety of the nanosystem. Moreover, the gene-drug co-loaded nanoparticles stimulate anti-tumorigenic pathway of HCC by suppressing pro-inflammatory cytokines (IL-6/IL-8) and tumor angiogenesis-related protein (NF-κB p65) expression, which revealed the potential pathway inhibition of PTX when combined with the gene therapy for overexpression VEGFR2 on HCC cells. Overall, this strategy provided a versatile method for high efficiency CRISPR/Cas9 system delivery and showed tremendous application prospect for gene-chemo synergistic therapy.

Synergistic modulation of power factor and thermal conductivity in Cu3SbSe4 towards high thermoelectric performance

Abstract In this study, we develop a synergistic modulation of the thermal conductivity and power factor of Cu3SbSe4-based materials through Sn and Zr or Hf co-doping by using a facile microwave-assisted solvothermal method. A series of Cu3Sb1-xMxSe4 (M = Zr or Hf, x = 0, 0.02, 0.04, 0.06 and 0.08) compounds are firstly synthesized through the microwave-assisted solvothermal method combined with spark plasma sintering (SPS) process. The effect of Zr and Hf doping on the thermoelectric properties of Cu3Sb1-xMxSe4 (M = Zr or Hf) has been investigated. With increasing the content of Hf and Zr, the thermal conductivity of Cu3Sb1-xMxSe4 (M = Zr or Hf) is obviously decreased to 0.518 Wm−1K−1 of Cu3Sb0.92Hf0.08Se4 and 0.433 Wm−1K−1 of Cu3Sb0.92Zr0.08Se4 at 623 K, respectively. In addition, Sn doping further improves the low electrical conductivity and boosts the power factor, yielding a peak zT value of ~0.82 of Cu3Sb0.91Sn0.03Hf0.06Se4 at 623 K, which is ~228% higher than that of the pristine Cu3SbSe4. Our work provides a new methodology for the decoupling of thermal and electrical properties of the Cu3SbSe4-based thermoelectric materials.

Synergistic Modulation of Active Sites and Charge Transport: N/S Co-doped C Encapsulated NiCo2O4/NiO Hollow Microrods for Boosting Oxygen Evolution Catalysis.

Developing high-efficiency and cost-effective electrocatalysts for the oxygen evolution reaction (OER) is crucial for various energy conversion systems. Herein, N/S co-doped C encapsulated hollow NiCo2O4/NiO hexagonal rods (HNHR@N/S-C) as the electrocatalysts for OER have been successfully prepared with rational control of structure and composition. Experimental and theoretical results have highlighted that the NiCo2O4/NiO heterojunction in the obtained electrocatalyst can provide abundant active Ni and Co sites for the OER, leading to the highly enhanced OER performance. Moreover, attributed to the hierarchical hollow structure, which can provide a large surface area, and the improved electric conductivity with a coating of the N/S co-doped carbon layer, which can facilitate charge transport during the catalytic processes, a remarkable OER activity over HNHR@N/S-C with a low overpotential (η) of 285 mV (at j = 10 mA cm-2) and a Tafel slope of 53.0 mV decade-1 has been achieved, which is comparable to that of the noble metal catalyst IrO2. Because of the protection of the N/S doped C layer coating, HNHR@N/S-C can also maintain the current density of 10 mA cm-2 for at least 12 h in alkaline media without obvious losses of activity.

Synergistic Resistance Modulation toward Ultrahighly Sensitive Piezoresistive Pressure Sensors

AbstractImprovement of sensitivity of electrical piezoresistive sensors is critical for high‐precision and ultrasensitive detection, which mainly depends on the modulation ability of total resistance of sensor under applied pressure. However, in most of the reported sensor devices, the contact resistance and body resistance (the key parts of total resistance of sensor) generally cannot be modulated simultaneously, which results in the limited sensitivity. In this work, an ultrahighly sensitive piezoresistive pressure sensor with an exquisitely designed structure is demonstrated, providing an uncomparable advantage of synergistic modulation of contact resistance and body resistance under applied pressure. As a result, the sensor shows excellent sensing performance, with the highest sensitivity up to 11 668.6 kPa−1, the detection limit as low as 0.425 Pa, and the great stability over 20 000 cycle measurements. In respect of practical application, the high sensitivity endows the sensor with high‐precision recognition ability for detecting the weak pressure signals such as sound wave of ringtone and fluctuation of breath or pulse. These results suggest the synergistic resistance modulation to be an effective method toward piezoresistive pressure sensors with ultrahigh sensitivity and offer a new strategy for the achievement of high‐performance pressure sensors.

Tuning the crystal and electronic structure of Li4Ti5O12 via Mg/La Co-doping for fast and stable lithium storage

“Zero-strain” Li4Ti5O12 has become one of the most promising anode materials for lithium-ion battery but its low electronic and ionic conductivity lead to the poor rate capability. Herein, the high-rate performance and the cycling stability of Li4Ti5O12 have been largely enhanced by replacing Li and Ti with a little amount of Mg and La, respectively. The synergistic modulation mechanism of Mg and La co-doping on the crystal/electronic structure and electrochemical performances has been unveiled. Firstly, Mg and La co-doping enlarges the lattice parameters, unit cell volume and Li1–O bond. These facilitate the lithium-ion migration and enhance the rate capability. Secondly, Ti–O bond is shortened which enhances the structure stability and cyclic performance. Thirdly, the first-principles calculations further confirm that Mg/La co-doping modulates the electronic density of states and decreases the Li+ migration barrier. The polarization and charge transfer impedance are effectively alleviated. Moreover, the diffusion coefficient of lithium ions is further improved because of the reduction of much more Ti3+. At 10C, it delivers a discharge capacity of 107.8mAh/g after 500cyles which reserves 92.2% of the initial capacity. This study provides some insights into optimizing the electrochemical performances of Li4Ti5O12 by tuning the crystal and electronic structure with lattice doping.

Direct Growth of Continuous and Uniform MoS2 Film on SiO2/Si Substrate Catalyzed by Sodium Sulfate.

Because of its unique electronic band structure, molybdenum disulfide (MoS2) has been regarded as a star semiconducting material. However, direct growth of continuous and high-quality MoS2 films on SiO2/Si substrates is still very challenging. Here, we report a facile chemical vapor deposition (CVD) method based on synergistic modulation of precursor and Na2SO4 catalysis, realizing the centimeter scale growth of a continuous MoS2 film on SiO2/Si substrates. The as-grown MoS2 film had an excellent spatial homogeneity and crystal quality, with an edge length of the composite domain as large as 632 μm. Both experimental and theoretical results proved that Na tended to bond with SiO2 substrates rather than to interfere with as-grown MoS2. Thus, they showed decent and uniform electrical performance, with electron mobilities as high as 5.9 cm2 V-1 s-1. We believe our method will pave a new way for MoS2 toward real application in modern electronics.

NiCo2S4 quantum dots with high redox reactivity for hybrid supercapacitors

Despite advances in the synthetic methodology and multi-dimensional morphology engineering of ternary nickel cobalt sulfides for supercapacitors electrode materials, the intrinsic incentive mechanism of nickel cobalt sulfides in elevating charge storage property still remains cryptic. Here, we successfully synthesized high quality NiCo2S4 quantum dots (QDs) with good monodispersity and size distribution. Combining DFT theoretical calculation with ex-situ XPS characterization results, we elucidate that the synergistic modulation between reactive Ni and Co donates more active electrons near the Fermi level, as well as advantageous reaction surface and decreased energy barrier. This synergistically enhanced reactivity boosts larger proportion of Ni and Co from the NiCo2S4 QDs involved in the redox reaction, contributing to more than three times augment in specific capacity over the NiS2 or CoS2 QDs. Meanwhile, electrochemical studies indicate that the structural superiorities of NiCo2S4 QDs accelerate ions diffusion and reaction kinetics. Benefiting from these aspects, a hybrid supercapacitor constructed by the NiCo2S4 QDs as cathode and nitrogen-doped reduced graphene oxide nanosheets as anode delivers an ultrahigh energy density of 67.5Wh·kg−1 at power density of 850 W·kg−1, as well as excellent rate performance and robust cyclic stability.

Vanadium-doping in interlayer-expanded MoS2 nanosheets for the efficient electrocatalytic hydrogen evolution reaction

Synergistic modulations of vanadium doping, interlayer expansion and hybrid 1T&2H phases of few-layered MoS2 nanosheets are realized to gain structural and electronic benefits for enhanced hydrogen evolution reaction performance.

Continuous phase regulation of MoSe2 from 2H to 1T for the optimization of peroxidase-like catalysis.

Nanozymes are a new generation of artificial enzymes that address the limitations of natural enzymes, with numerous reports on the development of high performance nanozymes for various applications. Herein, the phase regulation of network-like MoSe2 from the metal 1T phase to semiconductor 2H phase was achieved under different reaction conditions by a facile but efficient microwave-assisted solvothermal method. The coexisting 1T/2H-MoSe2 with edge enriched and defective nanostructures showed great enhancement of the peroxidase-like properties. This high enzymatic activity may arise from optimized active sites of 1T/2H-MoSe2, effectively leading to a rapid charge transfer within the substrate. In addition, chitosan functionalization not only greatly improves the dispersion stability of MoSe2, but also significantly increases its peroxidase-like activity, probably due to its enhanced affinity to hydrogen peroxide (H2O2). Based on these results we have established a highly sensitive colorimetric assay for the detection of H2O2 and glucose in human serum.

Multi-channel V-doped CoP hollow nanofibers as high-performance hydrogen evolution reaction electrocatalysts.

Rational design and construction of high-efficiency and low-cost non-noble metal-based electrocatalysts for the hydrogen evolution reaction (HER) is critical for future renewable energy systems. Herein, a multi-channel V-doped CoP (MC-V-CoP) hollow nanofiber is fabricated via electrospinning and a subsequent oxidation/phosphorization process. The formation of a multi-channel hollow structure and V doping can enlarge the exposure of active sites, facilitate the electron transfer and tune the electronic structure of the active sites, resulting in the enhancement of the HER performance. As a result, the MC-V-CoP hollow nanofiber exhibits excellent HER activity with a low overpotential of 65 and 189 mV at 10 and 300 mA cm-2 in alkaline medium, respectively. This is superior to the commercial 20 wt% Pt/C catalyst at a high current density (212 mV at 300 mA cm-2), manifesting its outstanding performance toward the HER at a high current density. In addition, the MC-V-CoP hollow nanofiber also exhibits outstanding HER activity in neutral medium. The proposed strategy for fabricating multi-channel hollow nanofibers can also be used to prepare other transition metal phosphides for advanced electrochemical applications.

The Potential Synergistic Modulation of AMPK by Lippia citriodora Compounds as a Target in Metabolic Disorders.

Lippia citriodora (LC) represents a complex plant-derived source of polyphenols and iridoids that has shown beneficial properties against obesity-related metabolic disorders. The complete extract and its major compound, verbascoside, have shown AMPK-activating capacity in cell and animal models. In this work, we aimed to elucidate the contribution of the different compounds present in the LC extract on the AMPK activation capacity of the whole extract. Semipreparative reversed-phase high-performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (RP-HPLC-ESI-TOF-MS) was used to identify the major compounds with bioassay-guided fractionation in an adipocyte cell model for the measurement of AMPK activity. Twenty-two compounds were identified and purified almost to homogeneity in 16 fractions, and three compounds, namely verbascoside, luteolin-7-diglucuronide and loganic acid, showed the highest AMPK-activating capacity. The synergy study using the checkerboard and fractional inhibitory concentration index (FICI) methods exhibited synergistic behavior between loganic acid and luteolin-7-diglucuronide. Molecular docking experiments revealed that these three compounds might act as direct agonists of AMPK, binding to the AMP binding sites of the gamma subunit and/or the different sites of the interaction zones between the gamma and beta subunits. Although our findings conclude that the bioactivity of the extract is mainly due to verbascoside, the synergy found between loganic acid and luteolin-7-diglucuronide deserves further research aimed to develop optimized combinations of polyphenols as a new nutritional strategy against obesity-related metabolic disorders.

Synergistic modulation of signaling pathways to expand and maintain the bipotency of human hepatoblasts

BackgroundThe limited proliferative ability of hepatocytes is a major limitation to meet their demand for cell-based therapy, bio-artificial liver device, and drug tests. One strategy is to amplify cells at the hepatoblast (HB) stage. However, expansion of HBs with their bipotency preserved is challenging. Most HB expansion methods hardly maintain the bipotency and also lack functional confirmation.MethodsOn the basis of analyzing and manipulating related signaling pathways during HB (derived from human induced pluripotent stem cells, iPSCs) differentiation and proliferation, we established a specific chemically defined cocktails to synergistically regulate the related signaling pathways that optimize the balance of HB proliferation ability and stemness maintenance, to expand the HBs and investigate their capacity for injured liver repopulation in immune-deficient mice.ResultsWe found that the proliferative ability progressively declines during HB differentiation process. Small molecule activation of Wnt or inhibition of TGF-β pathways promoted HB proliferation but diminished their bipotency, whereas activation of hedgehog (HH) signaling stimulated proliferation and sustained HB phenotypes. A cocktail synergistically regulating the BMP/WNT/TGF-β/HH pathways created a fine balance for expansion and maintenance of the bipotency of HBs. After purification, colony formation, and expansion for 20 passages, HBs retained their RNA profile integrity, normal karyotype, and ability to differentiate into mature hepatocytes and cholangiocytes. Moreover, upon transplantation into liver injured mice, the expanded HBs could engraft and differentiate into mature human hepatocytes and repopulate liver tissue with restoring hepatocyte mass.ConclusionOur data contribute to the understanding of some signaling pathways for human HB proliferation in vitro. Simultaneous BMP/HGF induction, activation of Wnt and HH, and inhibition of TGF-β pathways created a reliable method for long-term stable large-scale expansion of HBs to obtain mature hepatocytes that may have substantial clinical applications.Graphical abstract

Identifying miRNA synergism using multiple-intervention causal inference

BackgroundStudying multiple microRNAs (miRNAs) synergism in gene regulation could help to understand the regulatory mechanisms of complicated human diseases caused by miRNAs. Several existing methods have been presented to infer miRNA synergism. Most of the current methods assume that miRNAs with shared targets at the sequence level are working synergistically. However, it is unclear if miRNAs with shared targets are working in concert to regulate the targets or they individually regulate the targets at different time points or different biological processes. A standard method to test the synergistic activities is to knock-down multiple miRNAs at the same time and measure the changes in the target genes. However, this approach may not be practical as we would have too many sets of miRNAs to test.Resultsn this paper, we present a novel framework called miRsyn for inferring miRNA synergism by using a causal inference method that mimics the multiple-intervention experiments, e.g. knocking-down multiple miRNAs, with observational data. Our results show that several miRNA-miRNA pairs that have shared targets at the sequence level are not working synergistically at the expression level. Moreover, the identified miRNA synergistic network is small-world and biologically meaningful, and a number of miRNA synergistic modules are significantly enriched in breast cancer. Our further analyses also reveal that most of synergistic miRNA-miRNA pairs show the same expression patterns. The comparison results indicate that the proposed multiple-intervention causal inference method performs better than the single-intervention causal inference method in identifying miRNA synergistic network.ConclusionsTaken together, the results imply that miRsyn is a promising framework for identifying miRNA synergism, and it could enhance the understanding of miRNA synergism in breast cancer.

An evaluation of lumateperone tosylate for the treatment of schizophrenia

ABSTRACTIntroduction: Schizophrenia, a devastating disorder with onset in adolescence or young adulthood, afflicts 1% of the population leading to severe social, educational, and occupational impairments. Lumateperone is a first-in-class investigational drug under development for the treatment of multiple neuropsychiatric and neurodegenerative disorders including schizophrenia. Its unique receptor affinity profile together with synergistic modulation of serotonergic, glutamatergic, and dopaminergic pathways imparts efficacy over a broad-spectrum of symptoms associated with schizophrenia.Areas covered: This narrative drug evaluation includes a review of lumateperone tosylate (lumateperone, ITI-007, ITI-722, Intra-Cellular Therapies, Inc.) for patients with schizophrenia. This review describes the receptor affinity profile, pharmacodynamics, pharmacokinetics, distribution, metabolism, and clinical trials that address how lumateperone could potentially emerge as an important therapeutic option for schizophrenia patients.Expert opinion: The unique pharmacological properties of lumateperone may provide the key to dramatically ameliorate the symptoms of schizophrenia as indicated by some clinical trials. Future clinical trials may be enhanced by the administration of more comprehensive long-term behavioral measures and utilization of molecular imaging to confirm the target engagement of the many possible sites of action. The results of ongoing and future studies will provide the evidence to determine if lumateperone will revolutionize the therapy of schizophrenia.

Enhancement of Thermoelectric Performance of Layered SnSe2 by Synergistic Modulation of Carrier Concentration and Suppression of Lattice Thermal Conductivity

Eco-friendly and low-cost layered SnSe2-based materials have been attracting great attention in the thermoelectric field for their intrinsically low thermal conductivity. In this work, we applied A...

Rapid and sustained homeostatic control of presynaptic exocytosis at a central synapse

Animal behavior is remarkably robust despite constant changes in neural activity. Homeostatic plasticity stabilizes central nervous system (CNS) function on time scales of hours to days. If and how CNS function is stabilized on more rapid time scales remains unknown. Here, we discovered that mossy fiber synapses in the mouse cerebellum homeostatically control synaptic efficacy within minutes after pharmacological glutamate receptor impairment. This rapid form of homeostatic plasticity is expressed presynaptically. We show that modulations of readily releasable vesicle pool size and release probability normalize synaptic strength in a hierarchical fashion upon acute pharmacological and prolonged genetic receptor perturbation. Presynaptic membrane capacitance measurements directly demonstrate regulation of vesicle pool size upon receptor impairment. Moreover, presynaptic voltage-clamp analysis revealed increased Ca2+-current density under specific experimental conditions. Thus, homeostatic modulation of presynaptic exocytosis through specific mechanisms stabilizes synaptic transmission in a CNS circuit on time scales ranging from minutes to months. Rapid presynaptic homeostatic plasticity may ensure stable neural circuit function in light of rapid activity-dependent plasticity.

Facile Dual-Ligand Modulation Tactic toward Nickel-Cobalt Sulfides/Phosphides/Selenides as Supercapacitor Electrodes with Long-Term Durability and Electrochemical Activity.

The use of high electrochemical active binary nickel-cobalt sulfides/phosphides/selenides (Ni-Co-X, X = S, P, Se) as electrochemical energy storage materials still has a space for improvement because they become electrochemically unstable during long-term use. Herein, a facile and cost-effective dual-ligand synergistic modulation tactic is described to substantially improve the durability of Ni-Co-X (X = S, P, Se) at the atomic level by partially substituting S, P, and Se ligands into the nickel-cobalt hydroxide precursor, respectively. Remarkably, the dual-ligand electrodes on Ni-foam achieve superior durability and high electrochemical activity when used as positive electrodes in supercapacitors. Impressively, the density functional theory calculations demonstrate that the OH ligand in NiCo2(MOH)x (M = S, P, Se) could attract electrons from metal-S/metal-P/metal-Se bonds to the metal-O bond, enhancing the binding energy of metal-S/metal-P/metal-Se bonds and improving the long-term durability of Ni-Co-X (X = S, P, Se) in alkaline electrolytes. Moreover, OH and S/P/Se ligands could effectively alter the electron structure and result in favorable electrochemical activity. Overall, this tactic could offer an exciting avenue to achieve long-term durability and electrochemical activity of supercapacitor electrodes simultaneously.