Pathogen protein modularity enables elaborate mimicry of a host phosphatase.

Pathogens produce diverse effector proteins to manipulate host cellular processes. However, how functional diversity is generated in an effector repertoire is poorly understood. Many effectors in the devastating plant pathogen Phytophthora contain tandem repeats of the "(L)WY" motif, which are structurally conserved but variable in sequences. Here, we discovered a functional module formed by a specific (L)WY-LWY combination in multiple Phytophthora effectors, which efficiently recruits the serine/threonine protein phosphatase 2A (PP2A) core enzyme in plant hosts. Crystal structure of an effector-PP2A complex shows that the (L)WY-LWY module enables hijacking of the host PP2A core enzyme to form functional holoenzymes. While sharing the PP2A-interacting module at the amino terminus, these effectors possess divergent C-terminal LWY units and regulate distinct sets of phosphoproteins in the host. Our results highlight the appropriation of an essential host phosphatase through molecular mimicry by pathogens and diversification promoted by protein modularity in an effector repertoire.

PABP/purine-rich motif as an initiation module for cap-independent translation in pattern-triggered immunity.

Upon stress, eukaryotes typically reprogram their translatome through GCN2-mediated phosphorylation of the eukaryotic translation initiation factor, eIF2α, to inhibit general translation initiation while selectively translating essential stress regulators. Unexpectedly, in plants, pattern-triggered immunity (PTI) and response to other environmental stresses occur independently of the GCN2/eIF2α pathway. Here, we show that while PTI induces mRNA decapping to inhibit general translation, defense mRNAs with a purine-rich element ("R-motif") are selectively translated using R-motif as an internal ribosome entry site (IRES). R-motif-dependent translation is executed by poly(A)-binding proteins (PABPs) through preferential association with the PTI-activating eIFiso4G over the repressive eIF4G. Phosphorylation by PTI regulators mitogen-activated protein kinase 3 and 6 (MPK3/6) inhibits eIF4G's activity while enhancing PABP binding to the R-motif and promoting eIFiso4G-mediated defense mRNA translation, establishing a link between PTI signaling and protein synthesis. Given its prevalence in both plants and animals, the PABP/R-motif translation initiation module may have a broader role in reprogramming the stress translatome.

A Regulatory Module Controlling Homeostasis of a Plant Immune Kinase.

Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identified the calcium-dependent protein kinase CPK28 and heterotrimeric G proteins as negative and positive regulators of BIK1 accumulation, respectively. However, mechanisms underlying this regulation remain unknown. Here we show that the plant U-box proteins PUB25 and PUB26 are homologous E3 ligases that mark BIK1 for degradation to negatively regulate immunity. We demonstrate that the heterotrimeric G proteins inhibit PUB25/26 activity to stabilize BIK1, whereas CPK28 specifically phosphorylates conserved residues in PUB25/26 to enhance their activity and promote BIK1 degradation. Interestingly, PUB25/26 specifically target non-activated BIK1, suggesting that activated BIK1 is maintained for immune signaling. Our findings reveal a multi-protein regulatory module that enables robust yet tightly regulated immune responses.

AcrIIC4 inhibits type II-C Cas9 by preventing R-loop formation.

Anti-CRISPR (Acr) proteins are encoded by phages and other mobile genetic elements and inhibit host CRISPR-Cas immunity using versatile strategies. AcrIIC4 is a broad-spectrum Acr that inhibits the type II-C CRISPR-Cas9 system in several species by an unknown mechanism. Here, we determined a series of structures of Haemophilus parainfluenzae Cas9 (HpaCas9)-sgRNA in complex with AcrIIC4 and/or target DNA, as well as the crystal structure of AcrIIC4 alone. We found that AcrIIC4 resides in the crevice between the REC1 and REC2 domains of HpaCas9, where its extensive interactions restrict the mobility of the REC2 domain and prevent the unwinding of target double-stranded (ds) DNA at the PAM-distal end. Therefore, the full-length guide RNA:target DNA heteroduplex fails to form in the presence of AcrIIC4, preventing Cas9 nuclease activation. Altogether, our structural and biochemical studies illuminate a unique Acr mechanism that allows DNA binding to the Cas9 effector complex but blocks its cleavage by preventing R-loop formation, a key step supporting DNA cleavage by Cas9.

Low PDE4A expression promoted the progression of ovarian cancer by inducing Snail nuclear translocation.

Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis.

Anti-CRISPR AcrIIC5 is a dsDNA mimic that inhibits type II-C Cas9 effectors by blocking PAM recognition.

Anti-CRISPR proteins are encoded by phages to inhibit the CRISPR-Cas systems of the hosts. AcrIIC5 inhibits several naturally high-fidelity type II-C Cas9 enzymes, including orthologs from Neisseria meningitidis (Nme1Cas9) and Simonsiella muelleri (SmuCas9). Here, we solve the structure of AcrIIC5 in complex with Nme1Cas9 and sgRNA. We show that AcrIIC5 adopts a novel fold to mimic the size and charge distribution of double-stranded DNA, and uses its negatively charged grooves to bind and occlude the protospacer adjacent motif (PAM) binding site in the target DNA cleft of Cas9. AcrIIC5 is positioned into the crevice between the WED and PI domains of Cas9, and one end of the anti-CRISPR interacts with the phosphate lock loop and a linker between the RuvC and BH domains. We employ biochemical and mutational analyses to build a model for AcrIIC5's mechanism of action, and identify residues on both the anti-CRISPR and Cas9 that are important for their interaction and inhibition. Together, the structure and mechanism of AcrIIC5 reveal convergent evolution among disparate anti-CRISPR proteins that use a DNA-mimic strategy to inhibit diverse CRISPR-Cas surveillance complexes, and provide new insights into a tool for potent inhibition of type II-C Cas9 orthologs.

High Strength and Toughness Polymeric Triboelectric Materials Enabled by Dense Crystal-Domain Cross-Linking.

Lightweight, easily processed, and durable polymeric materials play a crucial role in wearable sensor devices. However, achieving simultaneously high strength and toughness remains a challenge. This study addresses this by utilizing an ion-specific effect to control crystalline domains, enabling the fabrication of a polymeric triboelectric material with tunable mechanical properties. The dense crystal-domain cross-linking enhances energy dissipation, resulting in a material boasting both high tensile strength (58.0 MPa) and toughness (198.8 MJ m-3), alongside a remarkable 416.7% fracture elongation and 545.0 MPa modulus. Leveraging these properties, the material is successfully integrated into wearable self-powered devices, enabling real-time feedback on human joint movement. This work presents a valuable strategy for overcoming the strength-toughness trade-off in polymeric materials, paving the way for their enhanced applicability and broader use in diverse sensing applications.

Directional Moisture-Wicking Triboelectric Materials Enabled by Laplace Pressure Differences.

Wearable sensors are experiencing vibrant growth in the fields of health monitoring systems and human motion detection, with comfort becoming a significant research direction for wearable sensing devices. However, the weak moisture-wicking capability of sensor materials leads to liquid retention, severely restricting the comfort of the wearable sensors. This study employs a pattern-guided alignment strategy to construct microhill arrays, endowing triboelectric materials with directional moisture-wicking capability. Within 2.25 s, triboelectric materials can quickly and directionally remove the droplets, driven by the Laplace pressure differences and the wettability gradient. The directional moisture-wicking triboelectric materials exhibit excellent pressure sensing performance, enabling rapid response/recovery (29.1/37.0 ms), thereby achieving real-time online monitoring of human respiration and movement states. This work addresses the long-standing challenge of insufficient moisture-wicking driving force in flexible electronic sensing materials, holding significant implications for enhancing the comfort and application potential of electronic skin and wearable electronic devices.

Phase-Directed Assembly of Triboelectric Nanopaper for Self-Powered Noncontact Sensing.

Noncontact sensing technology serves as a pivotal medium for seamless data acquisition and intelligent perception in the era of the Internet of Things (IoT), bringing innovative interactive experiences to wearable human-machine interaction perception networks. However, the pervasive limitations of current noncontact sensing devices posed by harsh environmental conditions hinder the precision and stability of signals. In this study, the triboelectric nanopaper prepared by a phase-directed assembly strategy is presented, which possesses low charge transfer mobility (1618 cm2 V-1 s-1) and exceptional high-temperature stability. Wearable self-powered noncontact sensors constructed from triboelectric nanopaper operate stably under high temperatures (200 °C). Furthermore, a temperature warning system for workers in hazardous environments is demonstrated, capable of nonintrusively identifying harmful thermal stimuli and detecting motion status. This research not only establishes a technological foundation for accurate and stable noncontact sensing under high temperatures but also promotes the sustainable intelligent development of wearable IoT devices under extreme environments.

Lightweight and Strong Cellulosic Triboelectric Materials Enabled by Cell Wall Nanoengineering.

As intelligent technology surges forward, wearable electronics have emerged as versatile tools for monitoring health and sensing our surroundings. Among these advancements, porous triboelectric materials have garnered significant attention for their lightness. However, these materials face the challenge of improving structural stability to further enhance the sensing accuracy of triboelectric sensors. In this study, a lightweight and strong porous cellulosic triboelectric material is designed by cell wall nanoengineering. By tailoring of the cell wall structure, the material shows a high mechanical strength of 51.8 MPa. The self-powered sensor constructed by this material has a high sensitivity of 33.61 kPa-1, a fast response time of 36 ms, and excellent pressure detection durability. Notably, the sensor still enables a high sensing performance after the porous cellulosic triboelectric material exposure to 200 °C and achieves real-time feedback of human motion, thereby demonstrating great potential in the field of wearable electronic devices.

Graded Nanotexturing Architectural Wearable Triboelectric Sensor for Programmable Haptic Exploration.

Emulating biological perception mechanisms to construct intelligent sensing devices and systems represents a paradigm for promoting human-computer interaction in the Internet of Everything era. Nonetheless, developing highly sensitive, real-time sensing and rapidly integrated intelligent interaction units remains a challenging and time-consuming endeavor. This study employs a low-temperature glow discharge technique to rapidly fabricate graded nanotexturing architectural triboelectric nanopaper, upon which wearable triboelectric sensors for real-time tactile detection are designed. The structure enhances the contact area under an external force. Additionally, the Z-stacking structure design enables the sensor to achieve a remarkable sensitivity of 10.3 kPa-1 and a rapid response time of 52 ms. Furthermore, a tactile sensor array was designed to demonstrate the triboelectric sensor's ability to recognize characteristic pressures. With programmable machine learning techniques, the object recognition rate reached 97%. This study supports material structural design across disciplines, laying a solid foundation for the rapid fabrication and integration of transient wearable electronics.

Triboelectrically Empowered Biomimetic Heterogeneous Wettability Surface for Efficient Fog Collection.

Biomimetic engineering surfaces featuring heterogeneous wettability are vital for atmospheric water harvesting applications. Existing research predominantly focuses on the coordinated regulation of surface wettability through structural and chemical modifications, often overlooking the prevalent triboelectric charge effect at the liquid-solid interface. In this work, we designed a heterogeneous wettability surface by strategic masking and activated its latent triboelectric charge using triboelectric brushes, thereby enhancing the removal and renewal of surface droplets. By examining the dynamic evolution of droplets, the mechanism of triboelectric enhancement in the water collection efficiency is elucidated. Leveraging this inherent triboelectric charge interaction, fog collection capacity can be augmented by 29% by activating the system for 5 s every 60 s. Consequently, the advancement of triboelectric charge-enhanced fog collection technology holds both theoretical and practical significance for overcoming the limitations of traditional surface wettability regulation.

Interfacial-Assembly-Induced In Situ Transformation from Aligned 1D Nanowires to Quasi-2D Nanofilms.

As the dimensionality of materials generally affects their characteristics, thin films composed of low-dimensional nanomaterials, such as nanowires (NWs) or nanoplates, are of great importance in modern engineering. Among various bottom-up film fabrication strategies, interfacial assembly of nanoscale building blocks holds great promise in constructing large-scale aligned thin films, leading to emergent or enhanced collective properties compared to individual building blocks. As for 1D nanostructures, the interfacial self-assembly causes the morphology orientation, effectively achieving anisotropic electrical, thermal, and optical conduction. However, issues such as defects between each nanoscale building block, crystal orientation, and homogeneity constrain the application of ordered films. The precise control of transdimensional synthesis and the formation mechanism from 1D to 2D are rarely reported. To meet this gap, we introduce an interfacial-assembly-induced interfacial synthesis strategy and successfully synthesize quasi-2D nanofilms via the oriented attachment of 1D NWs on the liquid interface. Theoretical sampling and simulation show that NWs on the liquid interface maintain their lowest interaction energy for the ordered crystal plane (110) orientation and then rearrange and attach to the quasi-2D nanofilm. This quasi-2D nanofilm shows enhanced electric conductivity and unique optical properties compared with its corresponding 1D geometry materials. Uncovering these growth pathways of the 1D-to-2D transition provides opportunities for future material design and synthesis at the interface.

Dynamic Thermostable Cellulosic Triboelectric Materials from Multilevel-Non-Covalent Interactions.

Triboelectric materials present great potential for harvesting huge amounts of dispersed energy, and converting them directly into useful electricity, a process that generates power more sustainably. Triboelectric nanogenerators (TENGs) have emerged as a technology to power electronics and sensors, and it is expected to solve the problem of energy harvesting and self-powered sensing from extreme environments. In this paper, a high-temperature-resistant triboelectric material is designed based on multilevel non-covalent bonding interactions, which achieves an ultra-high surface charge density of 192 µC m-2 at high temperatures. TENGs based on the triboelectric material exhibit more than an order of magnitude higher power output (2750 mW m-2 at 200 °C) than the existing devices at high temperatures. These remarkable properties are achieved based on enthalpy-driven molecular assembly in highly unbonded states. Thus, the material maintains bond strength and ultra-high surface charge density in entropy-dominated high-temperature environments. This molecular design concept points out a promising direction for the preparation of polymers with excellent triboelectric properties.

Rational Design of Triboelectric Materials and Devices for Self-Powered Food Sensing.

Against the backdrop of rapid advancements in 5G and Internet of Things (IoT) technologies, there is an urgent need to upgrade food sensing systems to achieve automation, digitalization, and intelligence. However, this transformation process faces numerous challenges. Triboelectric nanogenerators (TENGs), as an emerging energy conversion and sensing technology, play a crucial role in this context. They not only provide power to functional devices but also serve as sensors in multifunctional self-powered food sensing systems, capable of detecting various physical and chemical information. This review explores the development of TENGs in the field of food sensing, focusing on the working principles of their self-powered sensing. The review also systematically organizes and classifies the material and device designs used for TENGs in various food applications. Based on the performance of TENGs, a detailed introduction is provided on the specific applications of self-powered food sterilization, self-powered food quality monitoring, and self-powered taste sensing in the field of food safety. Finally, this paper discusses the challenges and corresponding strategies of TENGs in the food sensing field. The aim is to further promote unmanned and smart services and management in the food sector and to provide new research perspectives.

A DFT Investigation of B-Doped C3 N as Single Atom Electrocatalysts for N2 -to-NH3 Conversion.

The NH3 synthesis from N2 plays an important role in the ecological cycle and industrial production. Different from industrial NH3 synthesis with high pollution and energy consumption, electrocatalytic NH3 synthesis is favored because of its environmental protection, energy saving, ambient reaction conditions and other characteristics. However, due to the low efficiency and poor reaction selectivity of the existing electrocatalysts, which can not be used actually, the development of new electrocatalysts for nitrogen reduction reaction (NRR) is particularly urgent. Herein, we designed a series of transition metal atoms anchored B-doped defective C3 N surface (TM@B2 C3 N) as single-atom catalysts. Through the screening process of N2 adsorption activation, N2 H formation and NH3 desorption, finally the excellent electrocatalysts with strong stability and high activity (Cr@B2 C3 N and Mn@B2 C3 N) were obtained. After simulating the entire pathway, it was found that the NRR process on Cr@B2 C3 N and Mn@B2 C3 N via consecutive and distal pathways with the lowest limiting potential of -0.42 and -0.52 V, which have the good ability to inhibit hydrogen evolution reaction. Finally, the electronic properties were analyzed, and the reason for their high catalytic activity was summarized. This work provides a new idea for the rational design of NRR electrocatalysts and promotes the practical application of electrocatalysts.

B-N Co-Doped Graphene: Stability and Catalytic Activity in Oxygen Reduction Reaction - A Theoretical Insight.

We systematically investigated the stable configurations and catalytic activity in the Oxygen Reduction Reaction (ORR) of graphene co-doped with boron and nitrogen (B-N) using first-principles methods. Compared to single B/N doping, co-doping with BN is energetically favored. We found that intermediate species of ORR process adsorb on boron atoms, which act as catalytic sites. The presence of neighboring nitrogen atoms around boron plays a crucial role in modulating the catalytic activity of boron. For the same adsorption configuration, the adsorption energy of the adsorbate increases with the number of neighboring nitrogen atoms around boron and generally correlates positively with the number of electrons gained by the adsorbate. Regarding the catalytic activity of ORR, excessively strong adsorption of adsorbates impedes their hydrogenation. The best substrates for ORR catalytic activity are B-N-graphene and N-B2-graphene, with the rate-determining step being the hydrogenation of *OO and overpotentials of 0.49 V and 0.54 V, respectively.

Cloning and characterization of a novel nitric oxide synthase gene from Exiguobacterium profundum and its expression in Escherichia coli.

The recognition and characterization of gene-encoded nitric oxide synthase (NOS) from Exiguobacterium profundum are reported in this study. A new gene was sequenced and cloned from E. profundum and heterologously expressed in E. coli for functional identification, followed by protein purification using the His-tag. The stability and activity characteristics of the recombinant NOS were evaluated using different concentrations of IPTG at various time points. A band of approximately 42 kDa was observed by SDS-PAGE. The Km value of NOS, calculated based on the Michaelis-Menten equation was 0.59 µmol/L. Additionally, homologous sequence alignment analysis indicated that the new NOS shared 80.48 % similarity with the same protein from Bacillus subtilis and Umezawaea. The construction of the NOS expression vector and the purification of the recombinant protein provide a foundation for further functional research and inhibitor development.

MolLoG: A Molecular Level Interpretability Model Bridging Local to Global for Predicting Drug Target Interactions.

Developing new pharmaceuticals is a costly and time-consuming endeavor fraught with significant safety risks. A critical aspect of drug research and disease therapy is discerning the existence of interactions between drugs and proteins. The evolution of deep learning (DL) in computer science has been remarkably aided in this regard in recent years. Yet, two challenges remain: (i) balancing the extraction of profound, local cohesive characteristics while warding off gradient disappearance and (ii) globally representing and understanding the interactions between the drug and target local attributes, which is vital for delivering molecular level insights indispensable to drug development. In response to these challenges, we propose a DL network structure, MolLoG, primarily comprising two modules: local feature encoders (LFE) and global interactive learning (GIL). Within the LFE module, graph convolution networks and leap blocks capture the local features of drug and protein molecules, respectively. The GIL module enables the efficient amalgamation of feature information, facilitating the global learning of feature structural semantics and procuring multihead attention weights for abstract features stemming from two modalities, providing biologically pertinent explanations for black-box results. Finally, predictive outcomes are achieved by decoding the unified representation via a multilayer perceptron. Our experimental analysis reveals that MolLoG outperforms several cutting-edge baselines across four data sets, delivering superior overall performance and providing satisfactory results when elucidating various facets of drug-target interaction predictions.

Atomic layer deposition of Al-doped ZnO nanomembrane within situmonitoring.

Due to shortcomings such as poor homogeneity of Al doping, precisely controlling the thickness, inability to conformally deposit on high aspect ratio devices and high pinhole rate, the applications of Al-doped ZnO (AZO) nanomembrane in integrated optoelectronic devices are remarkably influenced. Here, we reportin situmonitoring during the atomic layer deposition (ALD) of AZO nanomembrane by using an integrated spectroscopic ellipsometer. AZO nanomembranes with different compositions were deposited with real-time and precise atomic level monitoring of the deposition process. We specifically investigate the half-reaction and thickness evolution during the ALD processes and the influence of the chamber temperature is also disclosed. Structural characterizations demonstrate that the obtained AZO nanomembranes without any post-treatment are uniform, dense and pinhole-free. The transmittances of the nanomembranes in visible range are >94%, and the optimal conductivity can reach up to 1210 S cm-1. The output of current research may pave the way for AZO nanomembrane to become promising in integrated optoelectronic devices.