Interaction of human dendritic cell receptor DEC205/CD205 with keratins.

DEC205 (CD205) is one of the major endocytic receptors on dendritic cells and has been widely used as a receptor target in immune therapies. It has been shown that DEC205 can recognize dead cells through keratins in a pH-dependent manner. However, the mechanism underlying the interaction between DEC205 and keratins remains unclear. Here we determine the crystal structures of an N-terminal fragment of human DEC205 (CysR∼CTLD3). The structural data show that DEC205 shares similar overall features with the other mannose receptor family members such as the mannose receptor and Endo180, but the individual domains of DEC205 in the crystal structure exhibit distinct structural features that may lead to specific ligand binding properties of the molecule. Among them, CTLD3 of DEC205 adopts a unique fold of CTLD, which may correlate with the binding of keratins. Furthermore, we examine the interaction of DEC205 with keratins by mutagenesis and biochemical assays based on the structural information and identify an XGGGX motif on keratins that can be recognized by DEC205, thereby providing insights into the interaction between DEC205 and keratins. Overall, these findings not only improve the understanding of the diverse ligand specificities of the mannose receptor family members at the molecular level but may also give clues for the interactions of keratins with their binding partners in the corresponding pathways.

Piezotronic and Piezo-Phototronic Effects-Enhanced Core-Shell Structure-Based Nanowire Field-Effect Transistors.

Piezotronic and piezo-phototronic effects have been extensively applied to modulate the performance of advanced electronics and optoelectronics. In this study, to systematically investigate the piezotronic and piezo-phototronic effects in field-effect transistors (FETs), a core-shell structure-based Si/ZnO nanowire heterojunction FET (HJFET) model was established using the finite element method. We performed a sweep analysis of several parameters of the model. The results show that the channel current increases with the channel radial thickness and channel doping concentration, while it decreases with the channel length, gate doping concentration, and gate voltage. Under a tensile strain of 0.39‱, the saturation current change rate can reach 38%. Finally, another core-shell structure-based ZnO/Si nanowire HJFET model with the same parameters was established. The simulation results show that at a compressive strain of -0.39‱, the saturation current change rate is about 18%, which is smaller than that of the Si/ZnO case. Piezoelectric potential and photogenerated electromotive force jointly regulate the carrier distribution in the channel, change the width of the channel depletion layer and the channel conductivity, and thus regulate the channel current. The research results provide a certain degree of reference for the subsequent experimental design of Zn-based HJFETs and are applicable to other kinds of FETs.

The Influence of Surface Processing on the Surface Plasmonic Enhancement of an Al-Nanoparticles-Enhanced ZnO UV Photodectector.

Surface Plasmonic Resonance (SPR) induced by metallic nanoparticles can be exploited to enhance the response of photodetectors (PD) to a large degree. Since the interface between metallic nanoparticles and semiconductors plays an important role in SPR, the magnitude of the enhancement is highly dependent on the morphology and roughness of the surface where the nanoparticles are distributed. In this work, we used mechanical polishing to produce different surface roughnesses for the ZnO film. Then, we exploited sputtering to fabricate Al nanoparticles on the ZnO film. The size and spacing of the Al nanoparticles were adjusted by sputtering power and time. Finally, we made a comparison among the PD with surface processing only, the Al-nanoparticles-enhanced PD, and the Al-nanoparticles-enhanced PD with surface processing. The results showed that increasing the surface roughness could enhance the photo response due to the augmentation of light scattering. More interestingly, the SPR induced by the Al nanoparticles could be strengthened by increasing the roughness. The responsivity could be enlarged by three orders of magnitude after we introduced surface roughness to boost the SPR. This work revealed the mechanism behind how surface roughness influences SPR enhancement. This provides new means for improving the photo responses of SPR-enhanced photodetectors.

Pyro-Phototronic Effect for Advanced Photodetectors and Novel Light Energy Harvesting.

Pyroelectricity was discovered long ago and utilized to convert thermal energy that is tiny and usually wasted in daily life into useful electrical energy. The combination of pyroelectricity and optoelectronic yields a novel research field named as Pyro-Phototronic, where light-induced temperature variation of the pyroelectric material produces pyroelectric polarization charges at the interfaces of semiconductor optoelectronic devices, capable of modulating the device performances. In recent years, the pyro-phototronic effect has been vastly adopted and presents huge potential applications in functional optoelectronic devices. Here, we first introduce the basic concept and working mechanism of the pyro-phototronic effect and next summarize the recent progress of the pyro-phototronic effect in advanced photodetectors and light energy harvesting based on diverse materials with different dimensions. The coupling between the pyro-phototronic effect and the piezo-phototronic effect has also been reviewed. This review provides a comprehensive and conceptual summary of the pyro-phototronic effect and perspectives for pyro-phototronic-effect-based potential applications.

On the contact electrification mechanism in semiconductor-semiconductor case by vertical contact-separation triboelectric nanogenerator.

With the speed of industrialization accelerating, the traditional energy is in the predicament of being exhausted. Humans urgently need a clean energy to maintain the peace and development. Triboelectric nanogenerator (TENG) is a tiny device that collects and converts the renewable energy, such as wind, vibration and tidal/blue energy, into electrical energy. As the most significant working principle of TENG, contact electrification (CE) has been broadly studied since it was documented thousands of years ago. A large number of related researches are reported. However, most of them are focused on the polymer materials, device structures and potential applications. There are few literatures about the mechanism of CE, especially in the semiconductor-semiconductor case. Semiconductor-semiconductor CE is a promising method to generate electricity, which has been used in many fields, such as the photodetector and displacement sensor. Therefore, it is necessary to establish a serious and detailed theory in order to deeply explain the underlying mechanisms of semiconductor-semiconductor CE. In this work, a novel Fermi level model based on energy band theory is proposed to illustrate the semiconductor-semiconductor CE mechanism. By assembling a ZnO/Si vertical contact-separation (CS) mode TENG, the charge transfer introduced by CE is systematically measured. According to the energy band theory and TENG governing equation, the experimental data is qualitatively and quantitatively analyzed. Moreover, the effects of different concentrations of growth solutions on the morphology of ZnO nanowires and the Fermi level difference between ZnO and Si are explored as well. Results show that it is the Fermi level difference that dominates the short circuit transfer charge amount and direction of semiconductor-semiconductor CE mechanism. Our work can be applied to understand the CE mechanism in semiconductor-semiconductor case and broaden the application prospects of semiconductor-based TENG.

Pyro-Phototronic Effect Enhanced Pyramid Structured p-Si/n-ZnO Nanowires Heterojunction Photodetector.

The emergence of nanomaterials has brought about the development of miniature photodetectors into a new stage, and ZnO nanomaterials are currently one of the most popular research objects. Here, the performance of a photodetector consisting of micropyramid structured p-Si/n-ZnO NWs heterojunction constructed by an anisotropic chemical etching and hydrothermal method is optimized by using the pyro-phototronic effect, and the photoresponses of the device to 405 and 648 nm lasers are investigated. The results show that, with the introduction of pyro-phototronic effect, the photoresponsivity Rpyro increases to 208 times that of Rphoto when the wavelength is 405 nm and the optical power density is 0.0693 mW/cm2. Moreover, with the increase of the chopper frequency, the photocurrent increases by more than 3 times, and the photoresponsivity is also increased by a factor of 4.5, making it possible to detect ultrafast pulsed light. In addition, in order to increase the current collection efficiency, a thin film Al layer was deposited as the back electrode on the basis of the device, and the photocurrent and photoresponsivity are significantly improved. Finally, the coupling between the pyro-phototronic effect and the piezo-phototronic effect is analyzed by applying compressive strain to the photodetector. When the compressive strain is -1.02%, the photocurrent decreases by 31.4% and the photoresponsivity decreases by 27.9% due to the opposite direction between laser illumination induced pyroelectric polarization charges and compressive strain induced piezoelectric polarization charges. This work not only demonstrates the great potential of pyro-phototronic effect in enhancing the silicon-based heterojunction photodetectors for high-performance photodetection and ultrafast pulsed light detection but also provides assistance for a better understanding of the coupling mechanism between pyro-phototronic and piezo-phototronic effects.

Novel protein kinase inhibitor TT-00420 inhibits gallbladder cancer by inhibiting JNK/JUN-mediated signaling pathway.

PURPOSE: This study aimed to investigate the efficiency of our chemically synthesized TT-00420, a novel spectrum-selective multiple protein kinase inhibitor, in cultured cells and animal models of gallbladder cancer (GBC) and explore its potential mechanism. METHODS: Multiple GBC models were established to assess the anti-tumor efficiency, toxicity, and pharmacokinetics of TT-00420. Integrated transcriptomic, proteomic and phosphoproteomic analysis was conducted to identify potential downstream effectors of TT-00420. Western blotting, qRT-PCR, nuclear-cytoplasm separation, and immunofluorescence were performed to confirm the multi-omic results and explore the molecular mechanism of TT-00420. Immunohistochemistry was used to detect FGFR1 and p-FGFR1 expression levels in GBC samples. Autodock software was utilized to investigate the potential binding mode between the TT-00420 and the human FGFR1. RESULTS: We found that TT-00420 exerted potent growth inhibition of GBC cell lines and multiple xenograft models. Treatment of mice with 15 mg/kg TT-00420 via gavage displayed a half-life of 1.8 h in the blood and rapid distribution to the liver, kidneys, lungs, spleen, and tumors at 0.25 h, but no toxicity to these organs over 2 weeks. Multi-omic analysis revealed c-Jun as a potential downstream effector after TT-00420 treatment. Mechanistically, TT-00420 showed rigorous ability to block FGFR1 and its downstream JNK-JUN (S63/S73) signaling pathway, and induce c-Jun S243-dependent MEK/ERK reactivation, leading to FASLG-dependent tumor cell death. Finally, we found that FGFR1 and p-FGFR1 expression was elevated in GBC patients and these levels correlated with decreased patient survival. CONCLUSIONS: TT-00420 shows potent antitumor efficacy and may serve as a novel agent to improve GBC prognosis.

Measurement of total electron emission yield of insulators based on self-terminating charge neutralization.

For insulators, the accumulated charge on the surface after electron bombardment will interfere with the total electron emission yield (TEEY) measurement. This work develops a novel method to automatically measure the TEEY of insulators based on self-terminating charge neutralization using two neutralization electron guns. We perform theoretical analysis and experimental design for the neutralization of positive and negative charges. Positive charges are neutralized by an electron gun whose cathode is equipotential to the sample. Negative charges are neutralized by another electron gun whose cathode is adjusted to a negative potential with respect to the grounded sample, which is set between EP1/e and EP2/e. We test the control and stability performance of the TEEY measurement system based on the timing design of the electron gun switching and believe that it meets the TEEY measurement requirements. The TEEY measurements of glass, Si, and SiO2 are in good agreement with the data reported in the references, which validates the accuracy of our method in this work. We anticipate that our method provides an essential reference for the rapid TEEY measurements of insulators.

Cancellation method to improve signal to noise ratio of an electrodeless microwave-biased ZnO single crystal x-ray detector.

Semiconductor x-ray detectors are usually fabricated with proper ohmic or Schottky contact electrodes, which make the fabrication process complex and even unable to realize, especially for new materials. In this paper, we demonstrated an electrodeless ZnO single crystal x-ray detector using microwave (MW) bias with a high signal-to-noise ratio obtained by a cancellation method. The MW-biased x-ray detector is fabricated using the split-ring-resonator with the ZnO crystal mounted on the split-ring gap. The analytical response model was built for the detector. The MW cancellation process was realized by a phase and amplitude matching network. By using the cancellation method, the signal-to-noise ratio of the detector is about 59.4 dB, which is 58 dB higher than that of the DC-biased ZnO photodetector. The sensitivity of the detector is 139 µC Gy-1 cm-2 for the x-ray dose rate of 3.54 Gy/s, which is 86 times higher than that of the DC-biased ZnO photodetector. The high sensitivity of the detector is due to the high equivalent stimulated voltage caused by the split-ring resonator. The MW-biased detector can be used for x-ray dose monitoring.

FLT4/VEGFR3 activates AMPK to coordinate glycometabolic reprogramming with autophagy and inflammasome activation for bacterial elimination.

Macrophages rapidly undergo glycolytic reprogramming in response to macroautophagy/autophagy, inflammasome activation and pyroptosis for the clearance of bacteria. Identification the key molecules involved in these three events will provide critical potential therapeutic applications. Upon S. typhimurium infection, FLT4/VEGFR3 and its ligand VEGFC were inducibly expressed in macrophages, and FLT4 signaling inhibited CASP1 (caspase 1)-dependent inflammasome activation and pyroptosis but enhanced MAP1LC3/LC3 activation for elimination of the bacteria. Consistently, FLT4 mutants lacking the extracellular ligand-binding domain increased production of the proinflammatory metabolites such as succinate and lactate, and reduced antimicrobial metabolites including citrate and NAD(P)H in macrophages and liver upon infection. Mechanistically, FLT4 recruited AMP-activated protein kinase (AMPK) and phosphorylated Y247 and Y441/442 in the PRKAA/alpha subunit for AMPK activation. The AMPK agonist AICAR could rescue glycolytic reprogramming and inflammasome activation in macrophages expressing the mutant FLT4, which has potential translational application in patients carrying Flt4 mutations to prevent recurrent infections. Collectively, we have elucidated that the FLT4-AMPK module in macrophages coordinates glycolytic reprogramming, autophagy, inflammasome activation and pyroptosis to eliminate invading bacteria.Abbreviations: 3-MA: 3-methyladenine; AICAR: 5-aminoimidazole-4-carboxamide1-ß-D-ribofuranoside; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATP: adenosine triphosphate; BMDM: bone marrow-derived macrophage; CASP1: caspase 1; CFUs: colony-forming units; FLT4/VEGFR3: FMS-like tyrosine kinase 4; GFP: green fluorescent protein; LDH: lactate dehydrogenase; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PEM: peritoneal exudate macrophage; PRKAA1/AMPKα1: protein kinase, AMP-activated, alpha 1 catalytic subunit; PYCARD/ASC: PYD and CARD domain containing; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TLR4: toll-like receptor 4; ULK1: unc-51 like autophagy activating kinase 1; VEGFC: vascular endothelial growth factor C; WT: wild type.

Assembly and recognition of keratins: A structural perspective.

Keratins are one of the major components of cytoskeletal network and assemble into fibrous structures named intermediate filaments (IFs), which are important for maintaining the mechanical properties of cells and tissues. Over the past decades, evidence has shown that the functions of keratins go beyond providing mechanical support for cells, they interact with multiple cellular components and are widely involved in the pathways of cell proliferation, differentiation, motility and death. However, the structural details of keratins and IFs are largely missing and many questions remain regarding the mechanisms of keratin assembly and recognition. Here we briefly review the current structural models and assembly of keratins as well as the interactions of keratins with the binding partners, which may provide a structural view for understanding the mechanisms of keratins in the biological activities and the related diseases.

Fundamentals and Applications of ZnO-Nanowire-Based Piezotronics and Piezo-Phototronics.

The piezotronic effect is a coupling effect of semiconductor and piezoelectric properties. The piezoelectric potential is used to adjust the p-n junction barrier width and Schottky barrier height to control carrier transportation. At present, it has been applied in the fields of sensors, human-machine interaction, and active flexible electronic devices. The piezo-phototronic effect is a three-field coupling effect of semiconductor, photoexcitation, and piezoelectric properties. The piezoelectric potential generated by the applied strain in the piezoelectric semiconductor controls the generation, transport, separation, and recombination of carriers at the metal-semiconductor contact or p-n junction interface, thereby improving optoelectronic devices performance, such as photodetectors, solar cells, and light-emitting diodes (LED). Since then, the piezotronics and piezo-phototronic effects have attracted vast research interest due to their ability to remarkably enhance the performance of electronic and optoelectronic devices. Meanwhile, ZnO has become an ideal material for studying the piezotronic and piezo-phototronic effects due to its simple preparation process and better biocompatibility. In this review, first, the preparation methods and structural characteristics of ZnO nanowires (NWs) with different doping types were summarized. Then, the theoretical basis of the piezotronic effect and its application in the fields of sensors, biochemistry, energy harvesting, and logic operations (based on piezoelectric transistors) were reviewed. Next, the piezo-phototronic effect in the performance of photodetectors, solar cells, and LEDs was also summarized and analyzed. In addition, modulation of the piezotronic and piezo-phototronic effects was compared and summarized for different materials, structural designs, performance characteristics, and working mechanisms' analysis. This comprehensive review provides fundamental theoretical and applied guidance for future research directions in piezotronics and piezo-phototronics for optoelectronic devices and energy harvesting.

Analytical Transient Responses and Gain-Bandwidth Products of Low-Dimensional High-Gain Photodetectors.

Low-dimensional photodetectors, in particular those in photoconductive mode, often have extraordinarily high photogain. However, high gain always comes along with a slow frequency response. The gain-bandwidth product (GBP) is a figure of merit to evaluate the performance of a photodetector. Whether the high-gain photoconductors can outperform standard PIN photodiodes in terms of GBP remains an open question. In this article, we derived the analytical transient photoresponses of nanowire photoconductors which were validated with the simulations and experiments. Surprisingly, the fall transients do not follow a simple time-dependent exponential function except for some special cases. Given the analytical photogains that were established previously, we derived the theoretical GBP of high-gain nanowire photoconductors. Analysis of the analytical GBP indicates that nanoscale photoconductors, although having extremely high gain, will never outperform typical PIN photodiodes in terms of GBP.

Structure of cell-cell adhesion mediated by the Down syndrome cell adhesion molecule.

The Down syndrome cell adhesion molecule (DSCAM) belongs to the immunoglobulin superfamily (IgSF) and plays important roles in neural development. It has a large ectodomain, including 10 Ig-like domains and 6 fibronectin III (FnIII) domains. Previous data have shown that DSCAM can mediate cell adhesion by forming homophilic dimers between cells and contributes to self-avoidance of neurites or neuronal tiling, which is important for neural network formation. However, the organization and assembly of DSCAM at cell adhesion interfaces has not been fully understood. Here we combine electron microscopy and other biophysical methods to characterize the structure of the DSCAM-mediated cell adhesion and generate three-dimensional views of the adhesion interfaces of DSCAM by electron tomography. The results show that mouse DSCAM forms a regular pattern at the adhesion interfaces. The Ig-like domains contribute to both trans homophilic interactions and cis assembly of the pattern, and the FnIII domains are crucial for the cis pattern formation as well as the interaction with the cell membrane. By contrast, no obvious assembly pattern is observed at the adhesion interfaces mediated by mouse DSCAML1 or Drosophila DSCAMs, suggesting the different structural roles and mechanisms of DSCAMs in mediating cell adhesion and neural network formation.

Recognition of lipoproteins by scavenger receptor class A members.

Scavenger receptor class A (SR-A) proteins are type II transmembrane glycoproteins that form homotrimers on the cell surface. This family has five known members (SCARA1 to 5, or SR-A1 to A5) that recognize a variety of ligands and are involved in multiple biological pathways. Previous reports have shown that some SR-A family members can bind modified low-density lipoproteins (LDLs); however, the mechanisms of the interactions between the SR-A members and these lipoproteins are not fully understood. Here, we systematically characterize the recognition of SR-A receptors with lipoproteins and report that SCARA1 (SR-A1, CD204), MARCO (SCARA2), and SCARA5 recognize acetylated or oxidized LDL and very-low-density lipoprotein in a Ca2+-dependent manner through their C-terminal scavenger receptor cysteine-rich (SRCR) domains. These interactions occur specifically between the SRCR domains and the modified apolipoprotein B component of the lipoproteins, suggesting that they might share a similar mechanism for lipoprotein recognition. Meanwhile, SCARA4, a SR-A member with a carbohydrate recognition domain instead of the SRCR domain at the C terminus, shows low affinity for modified LDL and very-low-density lipoprotein but binds in a Ca2+-independent manner. SCARA3, which does not have a globular domain at the C terminus, was found to have no detectable binding with these lipoproteins. Taken together, these results provide mechanistic insights into the interactions between SR-A family members and lipoproteins that may help us understand the roles of SR-A receptors in lipid transport and related diseases such as atherosclerosis.

Glycometabolism regulates hepatitis C virus release.

HCV cell-culture system uses hepatoma-derived cell lines for efficient virus propagation. Tumor cells cultured in glucose undergo active aerobic glycolysis, but switch to oxidative phosphorylation for energy production when cultured in galactose. Here, we investigated whether modulation of glycolysis in hepatocytes affects HCV infection. We showed HCV release, but not entry, genome replication or virion assembly, is significantly blocked when cells are cultured in galactose, leading to accumulation of intracellular infectious virions within multivesicular body (MVB). Blockade of the MVB-lysosome fusion or treatment with pro-inflammatory cytokines promotes HCV release in galactose. Furthermore, we found this glycometabolic regulation of HCV release is mediated by MAPK-p38 phosphorylation. Finally, we showed HCV cell-to-cell transmission is not affected by glycometabolism, suggesting that HCV cell-to-supernatant release and cell-to-cell transmission are two mechanistically distinct pathways. In summary, we demonstrated glycometabolism regulates the efficiency and route of HCV release. We proposed HCV may exploit the metabolic state in hepatocytes to favor its spread through the cell-to-cell transmission in vivo to evade immune response.

Structural basis for the multi-activity factor Rad5 in replication stress tolerance.

The yeast protein Rad5 and its orthologs in other eukaryotes promote replication stress tolerance and cell survival using their multiple activities, including ubiquitin ligase, replication fork remodeling and DNA lesion targeting activities. Here, we present the crystal structure of a nearly full-length Rad5 protein. The structure shows three distinct, but well-connected, domains required for Rad5's activities. The spatial arrangement of these domains suggest that different domains can have autonomous activities but also undergo intrinsic coordination. Moreover, our structural, biochemical and cellular studies demonstrate that Rad5's HIRAN domain mediates interactions with the DNA metabolism maestro factor PCNA and contributes to its poly-ubiquitination, binds to DNA and contributes to the Rad5-catalyzed replication fork regression, defining a new type of HIRAN domains with multiple activities. Our work provides a framework to understand how Rad5 integrates its various activities in replication stress tolerance.

Conductivity Extraction Using a 180 GHz Quasi-Optical Resonator for Conductive Thin Film Deposited on Conductive Substrate.

Measurement of electrical conductivity of conductive thin film deposited on a conductive substrate is important and challenging. An effective conductivity model was constructed for a bilayer structure to extract thin film conductivity from the measured Q-factor of a quasi-optical resonator. As a demonstration, aluminium films with thickness of 100 nm were evaporated on four silicon wafers whose conductivity ranges from ~101 to ~105 S/m (thus, the proposed method can be verified for a substrate with a wide range of conductivity). Measurement results at ~180 GHz show that average conductivities are 1.66 × 107 S/m (which agrees well with direct current measurements) with 6% standard deviation. The proposed method provides a contactless conductivity evaluation method for conductive thin film deposited on conductive substrate which cannot be achieved by the existing microwave resonant method.

Contactless Measurement of Sheet Resistance of Nanomaterial Using Waveguide Reflection Method.

Conductive nanomaterials are widely studied and used. The four-point probe method has been widely used to measure nanomaterials' sheet resistance, denoted as . However, for materials sensitive to contamination or physical damage, contactless measurement is highly recommended if not required. Feasibility of evaluation using a one-port rectangular waveguide working on the microwave band in a contact-free mode is studied. Compared with existed waveguide methods, the proposed method has three advantages: first, by introducing an air gap between the waveguide flange and the sample surface, it is truly contactless; second, within the specified range of , the substrate's effect may be neglected; third, it does not require a matched load and/or metallization at the sample backside. Both theoretical derivation and simulation showed that the magnitude of the reflection coefficient decreased monotonously with increasing . Through calibration, a quantitative correlation of and was established. Experimental results with various conductive glasses showed that, for in the range of ~10 to 400 Ohm/sq, the estimation error of sheet resistance was below ~20%. The potential effects of air gap size, sample size/location and measurement uncertainty of are discussed. The proposed method is particularly suitable for characterization of conductive glass or related nanomaterials with in the range of tens or hundreds of Ohm/sq.