[Research Advances in the Association Between Alzheimer's Disease and Double-Stranded RNA-Dependent Protein Kinase].

Alzheimer's disease (AD) is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continuously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of ß-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-ß protein (Aß),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aß.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aß accumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treatment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

Electronic transfusion consent and blood delivering pattern improve the management of blood bank in China.

BACKGROUND: The aim of this study was to improve the blood transfusion treatment consent accuracy, simplify the verification process, prolong the temperature control time before the blood transfusion, and save the blood transportation labor cost. METHODS: We designed the blood transfusion consent electronic signing process, which can generate personalized the text content and can automatically check the filling accuracy. The signal can be transmitted to the blood transfusion management system (TMS) to relieving the blood distribution. For blood delivering pattern, we established the blood transport center, recruited full-time nurses and used temperature-controlled blood transfer boxes to deliver blood in batches on a regular basis. RESULTS: A quarterly data analysis of blood transfusion quality showed a 100% blood transfusion consent accuracy after an electronic signing process was implemented. The average confirmation time savings between the electronic content and paper content was 26 min for the Department of Emergency (estimated difference 95% CI = 26 (20 to 36), p < 0.05). The blood delivering pattern reduced the time for each unit by leaving the average temperature control by 7.24 min (estimated difference 95% CI = 7.24 (6.92 to 7.56), p < 0.05). Furthermore, $3.67 was saved for the blood transportation labor cost for each unit as well. CONCLUSION: Blood transfusion consent electronic signing process not only ensures the accuracy, but also saves the verification time. Moreover, the blood delivering pattern prolongs the blood temperature control time and saves blood transportation labor costs. Thus, these two improvements could enhance transfusion management.

Exploring the Influence of Inter- and Intra-crystal Diversity of Surface Barriers in Zeolites on Mass Transport by Using Super-Resolution Microimaging of Time-Resolved Guest Profiles.

The applications of nanoporous crystalline materials are closely related to the mass transfer of guest molecules. However, the fundamental knowledge of mass transfer, and in particular the surface barriers controlled by the permeation of guest molecules through the external surfaces of materials, is still incomplete. The diversity of surface permeability at the single-crystal level, caused by the varying origins of surface transport resistance, hinders the rational materials design and needs better understanding. Herein, we probe the molecular transport in single zeolite crystals with fluorescent 4-(4-diethylaminostyryl-1-methylpyridinium iodide) (DAMPI) using super-resolution structured illumination microscopy (SIM). It showed that both the inter- and intra-crystal diversity of surface barriers could be monitored by detecting the diffusion behaviors on the center and surface planes in single crystals. This adds a new perspective for studying the origins of the surface barriers as well as the molecular transport mechanisms in nanoporous materials.

Electrically controlled 1 × 2 tunable switch using a phase change material embedded silicon microring.

Phase change material Ge2Sb2Te5 (GST) has recently emerged as a highly promising candidate for photonic device applications owing to its high optical contrast, self-holding bi-stability, and fast material response. Here, we propose and analyze a 1×2 tunable switch using a GST embedded silicon microring resonator exploiting high optical contrast during GST phase change and a high thermo-optic coefficient of amorphous phase GST. Our device exhibits high extinction ratios of 25.57 dB and 18.75 dB at through and drop ports, respectively, with just a 1 µm long GST layer. The two states of the switch are realizable by electrically inducing phase change in GST. For post phase change from amorphous to crystalline and vice versa, the fall time down the 80% of phase transition temperature is ∼66ns and ∼45ns, respectively. The resonance wavelength shift per unit active length is 0.661 nm/µm, and the tuning efficiency is 1.16 nm/mW. The large wavelength tunability (4.63 nm) of the proposed switch makes it an attractive option for reconfigurable photonic integrated circuits.

Ultra-dense dual-polarization waveguide superlattices on silicon.

A dual-polarization waveguide superlattice is designed and realized by using 340 nm-thick silicon photonic waveguides. The silicon waveguide superlattices are formed with periodically arranged waveguides. Each period consists of five optical waveguides with core-widths designed optimally for minimizing the crosstalk among the optical waveguides. The optimized core-widths are 390 nm, 320 nm, 260 nm, 360 nm, and 300 nm when the separation between two adjacent waveguides is as small as 0.8 µm. With this design, the silicon waveguide superlattice works with low crosstalk (nearly -18 dB or less) for both polarizations within the range of 1530 nm to 1560 nm, which agrees well with the theoretical analysis.

Design Rule of Mach-Zehnder Interferometer Sensors for Ultra-High Sensitivity.

A design rule for a Mach-Zehnder interferometer (MZI) sensor is presented, allowing tunable sensitivity by appropriately choosing the MZI arm lengths according to the formula given in this paper. The present MZI sensor designed by this method can achieve an ultra-high sensitivity, which is much higher than any other traditional MZI sensors. An example is given with silicon-on-insulator (SOI) nanowires and the device sensitivity is as high as 106 nm/refractive-index -unit (or even higher), by choosing the MZI arms appropriately. This makes it possible for one to realize a low-cost optical sensing system with a detection limit as high as 10-6 refractive-index-unit, even when a cheap optical spectrum analyzer with low-resolution (e.g., 1 nm) is used for the wavelength-shift measurement.

Piezoelectric Sensing Techniques in Structural Health Monitoring: A State-of-the-Art Review.

Recently, there has been a growing interest in deploying smart materials as sensing components of structural health monitoring systems. In this arena, piezoelectric materials offer great promise for researchers to rapidly expand their many potential applications. The main goal of this study is to review the state-of-the-art piezoelectric-based sensing techniques that are currently used in the structural health monitoring area. These techniques range from piezoelectric electromechanical impedance and ultrasonic Lamb wave methods to a class of cutting-edge self-powered sensing systems. We present the principle of the piezoelectric effect and the underlying mechanisms used by the piezoelectric sensing methods to detect the structural response. Furthermore, the pros and cons of the current methodologies are discussed. In the end, we envision a role of the piezoelectric-based techniques in developing the next-generation self-monitoring and self-powering health monitoring systems.

Visualization of Rostral Migratory Stream in the Developing Rat Brain by In Vivo Electroporation.

Interneurons in the olfactory bulb (OB) are generated from neuronal precursor cells migrating from anterior subventricular zone (SVZa) not only in the developing embryo but also throughout the postnatal life of mammals. In the present study, we established an in vivo electroporation assay to label SVZa cells of rat both at embryonic and postnatal ages, and traced SVZa progenitors and followed their migration pathway and differentiation. We found that labeled cells displayed high motility. Interestingly, the postnatal cells migrated faster than the embryonic cells after applying this assay at different ages of brain development. Furthermore, based on brain slice culture and time-lapse imaging, we analyzed the detail migratory properties of these labeled precursor neurons. Finally, tissue transplantation experiments revealed that cells already migrated in subependymal zone of OB were transplanted back into rostral migratory stream (RMS), and these cells could still migrate out tangentially along RMS to OB. Taken together, these findings provide an in vivo labeling assay to follow and trace migrating cells in the RMS, their maturation and integration into OB neuron network, and unrecognized phenomena that postnatal SVZa progenitor cells with higher motility than embryonic cells, and their migration was affected by extrinsic environments.

Photonic integrated circuit implementation of a sub-GHz-selectivity frequency comb filter for optical clock multiplication.

We report a photonic integrated circuit implementation of an optical clock multiplier, or equivalently an optical frequency comb filter. The circuit comprises a novel topology of a ring-resonator-assisted asymmetrical Mach-Zehnder interferometer in a Sagnac loop, providing a reconfigurable comb filter with sub-GHz selectivity and low complexity. A proof-of-concept device is fabricated in a high-index-contrast stoichiometric silicon nitride (Si3N4/SiO2) waveguide, featuring low loss, small size, and large bandwidth. In the experiment, we show a very narrow passband for filters of this kind, i.e. a -3-dB bandwidth of 0.6 GHz and a -20-dB passband of 1.2 GHz at a frequency interval of 12.5 GHz. As an application example, this particular filter shape enables successful demonstrations of five-fold repetition rate multiplication of optical clock signals, i.e. from 2.5 Gpulses/s to 12.5 Gpulses/s and from 10 Gpulses/s to 50 Gpulses/s. This work addresses comb spectrum processing on an integrated platform, pointing towards a device-compact solution for optical clock multipliers (frequency comb filters) which have diverse applications ranging from photonic-based RF spectrum scanners and photonic radars to GHz-granularity WDM switches and LIDARs.

Silicon microring modulator-based RF mixer for millimeter-wave phase-coded signal generation.

Phase-coded radio frequency (RF) pulses are widely adopted for radar systems as an effective signal format to enable high-range resolution. However, generating such signals conventionally requires high-speed electronics and complex RF circuitry that impose burdens on the system cost and power consumption. In particular, modern radar systems desire features such as high frequencies, e.g., in the millimeter-wave region, high compactness, and high system flexibility, which pose great challenges for the conventional all-electronics solutions. In contrast, integrated microwave photonics opens a way to solutions that are able to provide those features simultaneously, together with potential for full integration and low cost fabrication. Here, we present an integrated microwave photonic method of a binary-phase-coded millimeter-wave signal generation. The core device is a silicon microring modulator with a device size of 0.13 mm×0.32 mm and a modulation bandwidth of 23 GHz. Using RF seed frequencies of 17.5 GHz and 20 GHz, respectively, we experimentally demonstrated the generation of binary-phase-coded signals at 35 GHz and 40 GHz using our proposed approach, the performance of which was verified by a pulse compression ratio of 94 and 106, respectively. The result of this work points to the realization of a chip-scale flexible millimeter-wave signal generator.

Nyquist pulse shaping using arrayed waveguide grating routers.

We propose and demonstrate by simulations a novel Nyquist-WDM (N-WDM) superchannel transmitter based on an arrayed waveguide grating router (AWGR). This approach can generate Nyquist pulses at multiple wavelengths using a single AWGR. Results for a 3-channel 960-Gbit/s QPSK superchannel system show that a 10% guard band reduces the inter-channel interference (ICI) sufficiently. The design introduces less than 0.16-dB penalty when the waveguide loss is 2 dB/cm and 0.73-dB penalty when the standard deviation of phase error is 10°. Such Nyquist pulse shapers can be realised on a chip scale using photonic integrated circuits technology, and could be compactly integrated with other functional components to create single-chip N-WDM superchannel transmitters.

Systems performance comparison of three all-optical generation schemes for quasi-Nyquist WDM.

Orthogonal time division multiplexing (OrthTDM) interleaves sinc-shaped pulses to form a high baud-rate signal, with a rectangular spectrum suitable for multiplexing into a Nyquist WDM (N-WDM)-like signal. The problem with generating sinc-shaped pulses is that they theoretically have infinite durations, and even if time bounded for practical implementation, they still require a filter with a long impulse response, hence a large physical size. Previously a method of creating chirped-orthogonal frequency division multiplexing (OFDM) pulses with a chirped arrayed waveguide (AWG) filter, then converting them into interleaved quasi-sinc pulses using dispersive fiber (DF), has been proposed. This produces a signal with a wider spectrum than the equivalent N-WDM signal. We show that a modification to the scheme enables the spectral extent to be reduced for the same data rate. We then analyse the key factors in designing an OrthTDM transmitter, and relate these to the performance of a N-WDM system. We show that the modified transmitter reduces the required guard band between the N-WDM channels. We also simulate a simpler scheme using an unchirped finite-impulse response filter of similar size, which directly creates truncated-sinc pulses without needing a DF. This gives better system performance than either chirped scheme.

Programmable wavelength-tunable second-order optical temporal differentiator based on a linearly chirped fiber Bragg grating and a digital thermal controller.

We proposed and experimentally demonstrated an all-fiber structured wavelength-tunable second-order optical temporal differentiator based on a linearly chirped fiber Bragg grating and a digital-controlled thermal array. The central frequency of the differentiation can be reconfigured from 192.141 to 192.616 THz by a programmable circuit. In the experiment, a second-order differentiator with 3 dB bandwidth of 0.086 THz is achieved with a root mean square error of 4.89%.

Transfusion support for a patient with alloanti-D and the RHD*DV.1 allele.

BACKGROUND: Safe blood transfusion is significantly affected by the complex antigen polymorphism and a high proportion of autoantibodies of the Rh blood group system. THE PATIENT AND METHODS: A male Chinese patient with primary biliary cirrhosis, esophageal and gastric rupture, and bleeding was admitted to our hospital. Blood typing identified that he had serological O and D+ blood groups. Because autoantibody was not detected using routine immediate spin (IS) and indirect antiglobulin test (IAT), he was treated by transfusing D+ red blood cells (RBCs). However, this treatment was ineffective. Thus, manual polybrene test (MPT) and low ionic salt solution indirect antiglobulin test (LISS-IAT) were performed, followed by exon sequencing of the RHD gene. RESULTS: The patient was confirmed as a DV Type 1 individual by gene sequencing, and had 4+ RhD antigen agglutination. The anti-D in serum and elution could only be detected by MPT (2+ agglutination) and LISS-IAT methods (1+/3+ agglutination). It was presumed that attenuated alloantibody contributed to ineffective RBC transfusion, causing a transient increase in hemoglobin (HGB) before falling back to 50 g/L or even lower within four days. CONCLUSION: Genotyping helps to support the specificity of detecting autoantibodies and alloantibodies. Combining more serological methods with molecular technology in blood typing is beneficial to improve the safety and effectiveness of blood transfusion.

The mechanism of viscosity reduction of waxy oils induced by the electric field: A correlation between the viscosity reduction and the charged particle accumulation on wax particles.

Wax molecules crystallize at ambient temperature, causing the crude oil to become a dispersed system, which poses challenges in the flow assurance of pipelines. Improving the cold flowability of crude oil is the fundamental solution to tackle these problems. Applying an electric field to waxy oil may markedly improve its cold flowability. The adhesion of charged particles on wax particles' surface under the electric field has been demonstrated as the essential mechanism of the electrorheological effect. However, the correlation between the accumulated charged particles and the induced viscosity reduction has not been explored quantitatively. In this study, the viscosity and impedance of four crude oils before and after electric treatment were measured. The conductivity changes of the oils' continuous phase were obtained by an equivalent circuit model. And then, the charged particles' concentration before and after electric treatment was calculated by the Stokes equation. The results showed there is a positive correlation between viscosity reduction and charged particle concentration reduction in the continuous phase. Importantly, this correlation is also quantitatively applicable to the results of ten different waxy oils which has been published. This study provides a quantitative basis for the mechanism of electrorheological behavior of waxy oils.

Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei.

Trypanosoma brucei, the pathogen causing African sleeping sickness (trypanosomiasis) in humans, causes debilitating diseases in many regions of the world, but mainly in African countries with tropical and subtropical climates. Enormous efforts have been devoted to controlling trypanosomiasis, including expanding vector control programs, searching for novel anti-trypanosomial agents, and developing vaccines, but with limited success. In this study, we systematically investigated the effect of graphene quantum dots (GQDs) on trypanosomal parasites and their underlying mechanisms. Ultrasmall-sized GQDs can be efficiently endocytosed by T. brucei and with no toxicity to mammalian-derived cells, triggering a cascade of apoptotic reactions, including mitochondrial disorder, intracellular reactive oxygen species (ROS) elevation, Ca2+ accumulation, DNA fragmentation, adenosine triphosphate (ATP) synthesis impairment, and cell cycle arrest. All of these were caused by the direct interaction between GQDs and the proteins associated with cell apoptosis and anti-oxidation responses, such as trypanothione reductase (TryR), a key protein in anti-oxidation. GQDs specifically inhibited the enzymatic activity of TryR, leading to a reduction in the antioxidant capacity and, ultimately, parasite apoptotic death. These data, for the first time, provide a basis for the exploration of GQDs in the development of anti-trypanosomials.

Enhanced Antimalarial Efficacy Obtained by Targeted Delivery of Artemisinin in Heparin-Coated Magnetic Hollow Mesoporous Nanoparticles.

Malaria is one of the deadliest infectious diseases threatening half of the world population. With the deterioration of the parasiticidal effect of the current antimalarials, novel approaches such as screening of more specific inhibitors and targeted delivery of drugs have been under intensive research. Herein, we prepare hollow mesoporous ferrite nanoparticles (HMFNs) of 200 nm with ferromagnetic properties using a one-pot hydrothermal reaction. A magnetically targeted drug-delivery system coloaded with artemisinin in the inner magnetite shell and heparin on the outer mesoporous shell (HMFN@ART@HEP) is developed. Specific targeting of the magnetic nanoparticles to the parasite-infected erythrocytes is achieved by the attraction between the HMFNs and hemozoin (paramagnetic), a vital metabolite of plasmodium in the erythrocytic stage. With the hemozoin production reaching the maximum during the schizont period of the parasite, HMFN@ART@HEPs are adsorbed to the infected red blood cells (iRBCs), which not only interferes with the release of merozoites but also significantly enhances the inhibitory efficacy due to the increased local concentration of artemisinin. Subsequently, the heparin coated on the surface of the nanoparticles can efficiently interfere with the invasion of freshly released merozoites to new RBCs through the specific interaction between the parasite-derived ligands and heparin, which further increases the inhibitory effect on malaria. As a cluster of heparin, heparin-coated nanoparticles provide stronger blocking capability than free heparin, resulting from multivalent interactions with surface receptors on merozoite. Thus, we have developed a HMFN-based delivery system with considerable antimalarial efficacy, which is a promising platform for treatment against malaria.

Structural Instability-Enabled Mechanical Sensors Using Fiber Bragg Grating.

Structural health monitoring (SHM) has been extensively used in civil infrastructures to assess structural condition and situation. Here, we develop a novel type of mechanical sensing technique using the structural instability of cylindrical cells detected by fiber Bragg grating (FBG). The cylinders are fabricated using a 3D printing technique, which are coiled by the FBG wires to detect the transverse deformation. Structural instability under axial compression is obtained in the experiments and the force-displacement relations are validated by the numerical simulations with satisfactory agreements. The wavelength variation of the FBG, caused by the structural instability, is observed and compared with the predefined threshold. Defining the variation larger than the threshold as "1" and smaller as "0", the pattern recognition algorithm is used to convert the FBG results into binary data, which can, therefore, be analyzed to indicate the structural conditions. In the end, we envision the potential applications of the reported sensing technique, such as wireless sensors for structural health monitoring (SHM) in civil infrastructures.

Salt stress increases carotenoid production of Sporidiobolus pararoseus NGR via torulene biosynthetic pathway.

Carotenoids represent a diverse class of aliphatic C40 molecules with a variety of applications in the food and pharmaceutical industries. Sporidiobolus pararoseus NGR produces various carotenoids, including torulene, torularhodin and ß-carotene. Salt stress significantly increases the torulene accumulation of S. pararoseus NGR. However, little is known, about the molecular mechanisms underlying the increased torulene biosynthesis. In this work, we investigated the effects of NaCl treatment on the contents of carotenoids (both qualitatively and quantitatively) and transcriptome. A total of 12.3 Gb of clean bases were generated in six cDNA libraries. These bases were de novo assembled into 9,533 unigenes with an average length of 1,654 nt and N50 of 2,371 nt. Transcriptome analysis revealed that of 3,849 differential expressed genes (DEGs) in response to salt stress, 2,019 were up-regulated, and 1,830 were down-regulated. Among these DEGs, we identified three carotenogenic genes crtE, crtYB, and crtI. In addition, fourteen candidate genes were predicted to participate in the conversion from torulene to torularhodin. Our findings should provide insights into the mechanisms of carotenoid biosynthesis and salt-tolerance of S. pararoseus NGR.

Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells.

Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in intestinal inflammation is controversial and its role in CAC is not elucidated yet. In our present study, we found that IL-27 has protective function in murine model of CAC through suppression of inflammatory cytokines in intestinal epithelial cells (IECs). IL-27Rα (WSX-1) deficiency promotes the CAC development in mice, which is driven by enhanced tumor cell proliferation, more intensive myeloid-derived suppressor cells (MDSC) accumulation in colon lamina propria and higher level of inflammatory cytokines and chemokines in IECs. The levels of IL-6, TNF-α, GM-CSF and CXCL1 triggered in vitro by toll-like receptor ligands are significantly upregulated in IECs from WSX-1 KO mice. Removal of commensal microorganism through antibiotic treatment in mice to eliminate TLR ligands deprives the protective function of IL-27 on CAC tumor growth. Thus, IL-27 suppresses CAC formation through an anti-inflammation mechanism targeting IECs and in turn resists the tumorigenesis. Hence, our study explained how IL-27 exerts its anti-inflammatory function on epithelial cells to fight against chronic-inflammation-associated cancer, which might provide new insights on the potential therapeutic strategies for cancer.