Combating bacterial infections with host defense peptides: Shifting focus from bacteria to host immunity.

The increasing prevalence of multidrug-resistant bacterial infections necessitates the exploration of novel paradigms for anti-infective therapy. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), have garnered extensive recognition as immunomodulatory molecules that leverage natural host mechanisms to enhance therapeutic benefits. The unique immune mechanism exhibited by certain HDPs that involves self-assembly into supramolecular nanonets capable of inducing bacterial agglutination and entrapping is significantly important. This process effectively prevents microbial invasion and subsequent dissemination and significantly mitigates selective pressure for the evolution of microbial resistance, highlighting the potential of HDP-based antimicrobial therapy. Recent advancements in this field have focused on developing bio-responsive materials in the form of supramolecular nanonets. A comprehensive overview of the immunomodulatory and bacteria-agglutinating activities of HDPs, along with a discussion on optimization strategies for synthetic derivatives, is presented in this article. These optimized derivatives exhibit improved biological properties and therapeutic potential, making them suitable for future clinical applications as effective anti-infective therapeutics.

A fungal effector and a rice NLR protein have antagonistic effects on a Bowman-Birk trypsin inhibitor.

Bowman-Birk trypsin inhibitors (BBIs) play important roles in animal and plant immunity, but how these protease inhibitors are involved in the immune system remains unclear. Here, we show that the rice (Oryza sativa) BBI protein APIP4 is a common target of a fungal effector and an NLR receptor for innate immunity. APIP4 exhibited trypsin inhibitor activity in vitro and in vivo. Knockout of APIP4 in rice enhanced susceptibility, and overexpression of APIP4 increased resistance to the fungal pathogen Magnaporthe oryzae. The M. oryzae effector AvrPiz-t interacted with APIP4 and suppressed APIP4 trypsin inhibitor activity. By contrast, the rice NLR protein Piz-t interacted with APIP4, enhancing APIP4 transcript and protein levels, and protease inhibitor activity. Our findings reveal a novel host defence mechanism in which a host protease inhibitor targeted by a fungal pathogen is protected by an NLR receptor.

Interlayer Biatomic Pair Bridging the van der Waals Gap for 100% Activation of 2D Layered Material.

2D layered materials are regarded as prospective catalyst candidates due to their advantageous atomic exposure ratio. Nevertheless, the predominant population of atoms residing on the basal plane with saturated coordination, exhibit inert behavior, while a mere fraction of atoms located at the periphery display reactivity. Here, a novel approach is reported to attain complete atom activation in 2D layered materials through the construction of an interlayer biatomic pair bridge. The atoms in question have been strategically optimized to achieve a highly favorable state for the adsorption of intermediates. This optimization results from the introduction of new gap states around the Fermi level. Moreover, the presence of the interlayer bridge facilitates the electron transfer across the van der Waals gap, thereby enhancing the reaction kinetics. The hydrogen evolution reaction exhibits an impressive ultrahigh current density of 2000 mA cm-2 at 397 mV, surpassing the pristine MoS2 by approximately two orders of magnitude (26 mA cm-2 at 397 mV). This study provides new insights for enhancing the efficacy of 2D layered catalysts.

Wheat hypersensitive-induced reaction genes TaHIR1 and TaHIR3 are involved in response to stripe rust fungus infection and abiotic stresses.

KEY MESSAGE : TaHIR1 and TaHIR3 play positive roles in resistance to the stripe rust fungus via inducing HR and regulating defense-related genes, but are negatively regulated by various abiotic stimuli. Plant hypersensitive-induced reaction (HIR) genes are known to be associated with the hypersensitive response and disease defense. In wheat, two HIR genes, TaHIR1 and TaHIR3, have been identified and found to be up-regulated after infection with the stripe rust fungus. Here, we further determined their roles in defense against abiotic stresses and the stripe rust pathogen, Puccinia striiformis f. sp. tritici. TaHIR1 and TaHIR3 proteins were localized in the plasma membrane of tobacco cells. The expression of TaHIR1 and TaHIR3 was reduced by the environmental stimuli, including low temperature, drought, and high salinity stresses. In addition, the expression of TaHIR1 and TaHIR3 was down-regulated by exogenously applied ethrel and abscisic acid, whereas expression was not affected by treatments with salicylic acid and methyl jasmonate. Furthermore, barley stripe mosaic virus-induced gene silencing of TaHIR1 and TaHIR3 reduced resistance in wheat cultivar Suwon11 against an avirulent stripe rust pathotype CYR23 and area of necrotic cells neighboring the infection sites, and altered the expression levels of defense-related genes. These results suggest that TaHIR1 and TaHIR3 function positively in the incompatible interaction of wheat-stripe rust fungus, but exhibit negative transcriptional response to abiotic stresses.

Vanadate ion promoting the transformation of α-phase molybdenum trioxide (α-MoO3) to h-phase MoO3 (h-MoO3) for boosted Zn-ion storage.

Molybdenum trioxide (MoO3) has been widely studied in the energy storage field due to its various phase states and unique structural advantages. Among them, lamellar α-phase MoO3 (α-MoO3) and tunnel-like h-phase MoO3 (h-MoO3) have attracted much attention. In this study, we demonstrate that vanadate ion (VO3-) can transform α-MoO3 (a thermodynamically stable phase) to h-MoO3 (a metastable phase) by altering the connection of [MoO6] octahedra configurations. h-MoO3 with VO3- inserted (referred to as h-MoO3-V) as the cathode material for aqueous zinc ion batteries (AZIBs) exhibits excellent Zn2+ storage performances. The improvement in electrochemical properties is attributed to the open tunneling structure of the h-MoO3-V, which offers more active sites for Zn2+ (de)intercalation and diffusion. As expected, the Zn//h-MoO3-V battery delivers specific capacity of 250 mAh·g-1 at 0.1 A·g-1 and rate capability (73% retention from 0.1 to 1 A·g-1, 80 cycles), well exceeding those of Zn//h-MoO3 and Zn//α-MoO3 batteries. This study demonstrates that the tunneling structure of h-MoO3 can be modulated by VO3- to enhance the electrochemical properties for AZIBs. Furthermore, it provides valuable insights for the synthesis, development and future applications of h-MoO3.

Design of Multi-DC Overdriving Waveform of Electrowetting Displays for Gray Scale Consistency.

Gray scale consistency in pixels was extremely important for electrowetting displays (EWDs). However, traditional electrowetting display driving waveforms could not obtain a pixel aperture ratio consistency, which led to the occurrence of gray inconsistency even if it was the same driving waveform. In addition, the oil backflow caused by charge trapping could not be sustained. Therefore, a multi-direct current (DC) overdriving waveform for gray scale consistency was proposed in this paper, which could effectively improve the performance of EWDs. The driving waveform was divided into a start-up driving phase and a stable driving phase. The stable driving phase was composed of a square wave with a duty cycle of 79% and a frequency of 43 Hz. Subsequently, an overdriving pulse was also introduced in the stable driving phase. The multi-DC driving waveform for gray scale consistency was applied to a thin film transistor-electrowetting display (TFT-EWD). The average difference between increasing driving voltage and decreasing driving voltage was only 2.79%. The proposed driving waveform has an aperture ratio of 3.7 times at low voltages compared to DC driving.

TaMCA4, a novel wheat metacaspase gene functions in programmed cell death induced by the fungal pathogen Puccinia striiformis f. sp. tritici.

Programmed cell death (PCD) is a physiological process to remove redundant or harmful cells, for the development of multicellular organisms, or for restricting the spread of pathogens (hypersensitive response). Metacaspases are cysteine-dependent proteases which play an essential role in PCD. Triticum aestivum metacaspase 4 (TaMCA4) is a type II metacaspase gene cloned from 'Suwon11' wheat, with typical structural features such as peptidase C14 caspase domain and a long linker sequence between the two subunits. Transient expression of TaMCA4 in tobacco leaves failed to induce PCD directly but enhanced cell death triggered by a mouse Bax gene or a candidate effector gene from Puccinia striiformis f. sp. tritici. Enhancement of PCD was also observed in wheat leaves co-bombarded with TaMCA4. When challenged with the avirulent race of P. striiformis f. sp. tritici, the expression level of TaMCA4 in wheat leaves was sharply upregulated, whereas the transcript level was not significantly induced by the virulent race. Moreover, knocking down TaMCA4 expression by virus-induced gene silencing enhanced the susceptibility of Suwon11 to the avirulent race of P. striiformis f. sp. tritici and reduced the necrotic area at infection sites.

Red Display for Three-Color Electrophoretic Displays with High Saturation via a Separation Stage between Black and Red Particles.

A three-color electrophoretic display (EPD) can solve the defect of an insufficient color display of black/white EPDs, but it is difficult to achieve a high red saturation due to the same driving polarity between black and red electrophoretic particles. In this work, a separation stage was proposed in the driving process to increase the red saturation in three-color EPDs. Firstly, red particles' motion was analyzed by the electrophoretic theory and Stokes' theorem to optimize driving parameters. Secondly, the activity of black particles was analyzed by testing different driving process parameters, and an optimal activation parameter for red particles was obtained. Next, the separation stage parameters were analyzed to reduce the mixing degree of black and red electrophoretic particles. Experimental results showed that the red and black electrophoretic particles could be effectively separated. Compared with an existing driving method, the red saturation was increased by 23.4%.

Dynamic Adaptive Display System for Electrowetting Displays Based on Alternating Current and Direct Current.

As a representative of the new reflective display technology, electrowetting display (EWD) technology can be used as a video playback display device due to its fast response characteristics. Direct current (DC) driving brings excellent reflectivity, but static images cannot be displayed continually due to charge trapping, and it can cause afterimages when playing a dynamic video due to contact angle hysteresis. Alternating current (AC) driving brings a good dynamic video refresh ability to EWDs, but that can cause flickers. In this paper, a dynamic adaptive display model based on thin film transistor-electrowetting display (TFT-EWD) was proposed. According to the displayed image content, the TFT-EWD display driver was dynamically adjusted by AC and DC driving models. A DC hybrid driving model was suitable for static image display, which could effectively suppress oil backflow and achieve static image display while ensuring high reflectivity. A source data non-polarized model (SNPM) is an AC driving model which was suitable for dynamic video display and was proposed at the same time. Compared with DC driving, it could obtain smooth display performance with a loss of about 10 absorbance units (A.U.) of reflective luminance, which could solve the flicker problem. With the DC hybrid driving model, the ability to continuously display static images could be obtained with a loss of 2 (A.U.) of luminance. Under the AC driving in SNPM, the reflected luminance was as high as 67 A.U., which was 8 A.U. higher than the source data polarized model (SPM), and it was closer to the reflected luminance under DC driving.

A Separated Reset Waveform Design for Suppressing Oil Backflow in Active Matrix Electrowetting Displays.

The electrowetting display (EWD) is a kind of reflective paper-like display. Flicker and grayscale distortion are caused by oil backflow, which is one of the important factors restricting the wide application of EWDs. The charge embedding caused by the electric field force in the dielectric layer is the cause of oil backflow. To suppress oil backflow, a separated reset waveform based on the study of oil movement is proposed in this paper. The driving waveform is divided into two parts: a reset waveform and a grayscale waveform. The reset waveform generated by a reset circuit can be used to output various voltages. The grayscale waveform is set as a traditional PWM waveform. The reset waveform is composed of a charge-releasing stage and oil-moving back stage. Two phases are contained in the charge releasing stage. The overdriving voltage is used during the first phase to reverse the voltage of all pixels. The trapped charges can then be released from the dielectric layer during the second phase. A higher voltage is used during the oil-moving back stage to drive the oil faster in the pixel. By comparing the experimental data, the oil backflow time is extended 761 times by the reset waveform. The four grayscales can be maintained by the reset waveform after driving for 300 s.

Detecting cerebral microbleeds via deep learning with features enhancement by reusing ground truth.

BACKGROUND AND OBJECTIVES: Cerebral microbleeds (CMBs) are cerebral small vascular diseases and are often used to diagnose symptoms such as stroke and dementia. Manual detection of cerebral microbleeds is a time-consuming and error-prone task, so the application of microbleed detection algorithms based on deep learning is of great significance. This study presents the feature enhancement technology applying to improve the performances of detecting CMBs. The primary purpose of the feature enhancement is emphasizing the meaningful features, leading deep learning network easier and correctly to optimize. METHOD: In this study, we applied feature enhancement in detecting CMBs from brain MRI images. Feature enhancement enhanced specific intervals and suppressed the useless intervals of the feature map. This method was applied in SSD-512 and SSD-300 algorithm, using VGG architecture pre-trained in the ImageNet dataset. RESULTS: The proposed method was applied in SSD-512. Moreover, the model was trained and tested on the sequence of SWAN images of brain MRI images. The results of the experiment demonstrate that our method effectively improves the detection performance of the SSD network in detecting CMBs. We train SSD-512 120000 iterations and test results on the test datasets, by applying the feature enhancement layer, improving the precision with 3.3% and the mAP of 2.3%. In the same way, we trained SSD-300, improving the mAP of 2.0%. 2.8% and 7.4% precision are improved by applying feature enhancement layer In ResNet-34 and MobileNet. CONCLUSIONS: The proposed method achieved more effective performance, demonstrated that feature enhancement can be a helpful algorithm to enhance the deep learning model.

The manifold actions of signaling peptides on subcellular dynamics of a receptor specify stomatal cell fate.

Receptor endocytosis is important for signal activation, transduction, and deactivation. However, how a receptor interprets conflicting signals to adjust cellular output is not clearly understood. Using genetic, cell biological, and pharmacological approaches, we report here that ERECTA-LIKE1 (ERL1), the major receptor restricting plant stomatal differentiation, undergoes dynamic subcellular behaviors in response to different EPIDERMAL PATTERNING FACTOR (EPF) peptides. Activation of ERL1 by EPF1 induces rapid ERL1 internalization via multivesicular bodies/late endosomes to vacuolar degradation, whereas ERL1 constitutively internalizes in the absence of EPF1. The co-receptor, TOO MANY MOUTHS is essential for ERL1 internalization induced by EPF1 but not by EPFL6. The peptide antagonist, Stomagen, triggers retention of ERL1 in the endoplasmic reticulum, likely coupled with reduced endocytosis. In contrast, the dominant-negative ERL1 remained dysfunctional in ligand-induced subcellular trafficking. Our study elucidates that multiple related yet unique peptides specify cell fate by deploying the differential subcellular dynamics of a single receptor.

Modeling of Oil/Water Interfacial Dynamics in Three-Dimensional Bistable Electrowetting Display Pixels.

Electrowetting has drawn significant interest because of the potential applications of displays, lab-on-a-chip microfluidic devices, electro-optical switches, and so forth. However, electrowetting display (EWD) is monostable, which needs extra continuous voltage supply to keep contracting the oil. This paper is concerned with the simulation of two-phase liquid flow in three-dimensional EWD pixels with two electrodes (E1 and E2) demonstrating bistability, where power is only needed to move the oil droplet between two stable states. The effects of E1 geometry, E2 geometry, and E2 pulse characteristics on the dynamics of the oil droplet motion have been analyzed. Also, predictions of the transient states in four stages of the reversible bistable operation process have been carried out by employing the finite element method, in qualitative agreement with our experimental results of the monostable EWD and the existing literature. We seek to shed more light on the fundamental two-phase liquid flow in three-dimensional pixels exhibiting bistability for low power EWD and guide optimizing the electrodes to the perfect patterns with the aid of rigorous modeling.

Role of lysine residues of the Magnaporthe oryzae effector AvrPiz-t in effector- and PAMP-triggered immunity.

Magnaporthe oryzae is an important fungal pathogen of both rice and wheat. However, how M. oryzae effectors modulate plant immunity is not fully understood. Previous studies have shown that the M. oryzae effector AvrPiz-t targets the host ubiquitin-proteasome system to manipulate plant defence. In return, two rice ubiquitin E3 ligases, APIP6 and APIP10, ubiquitinate AvrPiz-t for degradation. To determine how lysine residues contribute to the stability and function of AvrPiz-t, we generated double (K1,2R-AvrPiz-t), triple (K1,2,3R-AvrPiz-t) and lysine-free (LF-AvrPiz-t) mutants by mutating lysines into arginines in AvrPiz-t. LF-AvrPiz-t showed the highest protein accumulation when transiently expressed in rice protoplasts. When co-expressed with APIP10 in Nicotiana benthamiana, LF-AvrPiz-t was more stable than AvrPiz-t and was less able to degrade APIP10. The avirulence of LF-AvrPiz-t on Piz-t:HA plants was less than that of AvrPiz-t, which led to resistance reduction and lower accumulation of the Piz-t:HA protein after inoculation with the LF-AvrPiz-t-carrying isolate. Chitin- and flg22-induced production of reactive oxygen species (ROS) was higher in LF-AvrPiz-t than in AvrPiz-t transgenic plants. In addition, LF-AvrPiz-t transgenic plants were less susceptible than AvrPiz-t transgenic plants to a virulent isolate. Furthermore, both AvrPiz-t and LF-AvrPiz-t interacted with OsRac1, but the suppression of OsRac1-mediated ROS generation by LF-AvrPiz-t was significantly lower than that by AvrPiz-t. Together, these results suggest that the lysine residues of AvrPiz-t are required for its avirulence and virulence functions in rice.

Microstructure, mechanical properties and springback behaviour of Ti­6Al­4V alloy connection rod for spinal fixation device.

The effect of annealing condition on microstructure, mechanical properties and springback behaviour was examined in the connection rod of Ti-6Al-4V alloy for spinal fixation devices. Compared with the deformed microstructure in the sample before annealing, relatively few equiaxed grains were present after annealing at 1003 K after 1.8 ks, and a considerable amount appeared at 7.2 ks. When annealing time was extended to 36 ks, the recrystallised grains further grew. Vickers hardness, tensile strength and bending strength decreased with increasing annealing time, whereas the elastic and bending moduli showed no significant change with annealing time of up to 7.2 ks and then slightly decreased at 36 ks. The springback ratio was closely associated with strength and modulus and applied bending deflection. The springback ratio reached the highest and lowest values in the sample before and after annealing for 7.2 ks, respectively. A good combination of strength, modulus and springback ratio was obtained in the sample after annealing for 7.2 ks.

[Development of dynamic EMG scanning signal generator].

Development of a dynamic EMG scanning signal general based on microcontroller is introduced to be used in such fields as research of dynamic magnetic resonance scanning and moving muscle surface EMG. Optical fiber and photoelectrical switch are applied to work in strong electromagnetic environments to produce trigger signal which is similar to ECG. The occurrence of signals and the activity of the scanned bodies can be delayed at will. The results show that it not only has complete functions, simple operation, but also has superior capability of stabilization and credibility than the same product.

The Monocot-Specific Receptor-like Kinase SDS2 Controls Cell Death and Immunity in Rice.

Programmed cell death (PCD) plays critical roles in plant immunity but must be regulated to prevent excessive damage. The E3 ubiquitin ligase SPL11 negatively regulates PCD and immunity in plants. We show that SPL11 cell-death suppressor 2 (SDS2), an S-domain receptor-like kinase, positively regulates PCD and immunity in rice by engaging and regulating SPL11 and related kinases controlling defense responses. An sds2 mutant shows reduced immune responses and enhanced susceptibility to the blast fungus Magnaporthe oryzae. Conversely, SDS2 over-expression induces constitutive PCD accompanied by elevated immune responses and enhanced resistance to M. oryzae. SDS2 interacts with and phosphorylates SPL11, which in turn ubiquitinates SDS2, leading to its degradation. In addition, SDS2 interacts with related receptor-like cytoplasmic kinases, OsRLCK118/176, that positively regulate immunity by phosphorylating the NADPH oxidase OsRbohB to stimulate ROS production. Thus, a plasma membrane-resident protein complex consisting of SDS2, SPL11, and OsRLCK118/176 controls PCD and immunity in rice.

The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammatory disease in the lower gastrointestinal tract. Mounting evidence suggests that the predominance of the classically activated (M1) macrophages versus the alternatively activated (M2) macrophages plays a role in the progression of IBD. Thus, agents able to shift pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages may be beneficial to IBD. The pentacyclic triterpene Lup-20(29)-en-3ß-ol (Lupeol), a potent anti-inflammatory natural product, has been shown to inhibit pro-inflammatory cytokine production, suggesting it is potentially able to modulate macrophage polarization, thereby beneficial to IBD. METHODS: CD4(+) monocytes were differentiated to M1 or M2 macrophages, which were cocultured with epithelial cell lines, T84 and Caco-2, in the absence or presence of Lupeol (10µM). Experimental colitis was induced with dextran sodium sulfate (DSS), with or without oral administration of Lupeol (50mg/kg, q.d.). Cytokines were measured with Luminex kits. M1/M2 genes were measured with real-time polymerase chain reaction. Macrophage phenotypes were defined by measuring M1 and M2 markers with confocal microscopy. Proteins were measured with Western blotting, while cell surface markers were measured with confocal microscopy or flow cytometry. Histology was evaluated with H&E staining. RESULTS: Treatment of M1 macrophages with Lupeol resulted in a marked decrease in the production of pro-inflammatory cytokines, including IL-12, IL6, IL-1ß and TNFα, and a marked increase in the production of IL-10, an anti-inflammatory cytokine. This was associated with a down-regulation of CD86, a typical marker of M1 macrophages, and an up-regulation of CD206, a typical M2 macrophage marker. IRF5, a transcription factor that is critically involved in M1 polarization, was down-regulated in M1 macrophages after being incubated with Lupeol, associated with a marked decrease in the phosphorylation of p38 mitogen activated protein kinase. Coculture of epithelial cells with M1 macrophages resulted in down-regulation of the tight junction protein ZO-1 and disruption of epithelial integrity, which were blocked by Lupeol treatment of the M1 macrophages. Moreover, oral administration of Lupeol to dextran sulfate sodium (DSS)-induced colitis mice resulted in mitigated intestinal inflammation and increased survival from lethal colitis, associated with decreased expression of M1-related genes and increased expression of M2-related genes. CONCLUSION: Lupeol ameliorates experimental inflammatory bowel disease through, at least in part, inhibiting M1 and promoting M2 macrophages.

Microfluidics for electronic paper-like displays.

Displays are ubiquitous in modern life, and there is a growing need to develop active, full color, video-rate reflective displays that perform well in high-light conditions. The core of display technology is to generate or manipulate light in the visible wavelength. Colored fluids or fluids with particles can be used to tune the light intensity (greyscale) or wavelength (colors) of reflective displays by different actuation methods. Microfluidic technology plays an increasing role in fluidic manipulation in microscale devices used in display areas. In this article, we will review microfluidic technologies based on different actuation methods used for display applications: pressure-driven flow, electrophoresis, electroosmosis, electrowetting, magnetic-driven flow, and cell-actuation principles.

Wheat zinc finger protein TaLSD1, a negative regulator of programmed cell death, is involved in wheat resistance against stripe rust fungus.

Genetic characterization of the Arabidopsis lesion simulating disease 1 (lsd1) mutant, a lesion mimic mutant (LMM), has revealed the essential role of AtLSD1 in the negative regulation of cell death and disease resistance. The three zinc-finger motifs found in AtLSD1 revealed a novel plant-specific gene family, whose members are significantly related to programmed cell death (PCD). In this study, we characterized a functional homologue to AtLSD1, TaLSD1, in the wheat-stripe rust fungus pathosystem. The expression of TaLSD1 was differentially induced during incompatible and compatible interactions between wheat and Puccinia striiformis f. sp. tritici (Pst) and was up-regulated by oxidative stress generated by methyl viologen (MV). TaLSD1 was found to be predominately localized in the nucleus of onion epidermal cell. Transient overexpression assays in Nicotiana benthamiana demonstrated that TaLSD1 partially inhibited programmed cell death triggered by a mouse Bax protein, whereas expression of TaLSD1 alone had no influence on the phenotype of tobacco. Knocking down the expression of TaLSD1 through virus-induced gene silencing (VIGS) increased wheat resistance against Pst accompanied by an enhanced hypersensitive response (HR), an increase in PR1 gene expression and a reduction in Pst hyphal growth. Our results suggest that TaLSD1 functions negatively in regulating the plant hypersensitive cell death and is involved in disease resistance of wheat against the stripe rust pathogen.