Understanding and manipulating the recognition of necrosis-inducing secreted protein 1 (NIS1) by BRI1-associated receptor kinase 1 (BAK1).

Necrosis-inducing secreted protein 1 (NIS1) is a core effector of Ascomycota and Basidiomycota fungi. They inhibit the immune responses of host plants mainly through interaction with the multi-functional coreceptor BRI1-associated receptor kinase 1 (BAK1). However, the structural mechanism of the NIS1 family and how they are recognized by BAK1 are unknown. Herein, we report the first crystal structure of the NIS1 family protein, the Magnaporthe oryzae NIS1 (MoNIS1), analyze the recognition mechanism of NIS1s by BAK1, and explore regulation of the NIS1-BAK1 interaction by a chemical compound. MoNIS1 exists as a ß barrel formed by eight ß strands, a folding mode that has not been reported. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) assay suggested that ß4-ß5 loop and ß5 strand of MoNIS1 participate in OsBAK1 interaction, which was supported by further single-point mutational assays. For OsBAK1, HDX-MS assay suggested four regions involved in MoNIS1 interaction. Additionally, we identified a compound that blocks MoNIS1-OsBAK1 interaction in vitro and inhibits the virulence of M. oryzae on rice. Collectively, we determined the first structure of NIS1 family effectors, presented the recognition mechanism of NIS1 by BAK1, and showed that blocking NIS1-BAK1 interaction could be a new target for fungicide development.

Mode-Symmetry-Assisted Optical Pulling by Bound States in the Continuum.

Aside from optical pushing and trapping that have been implemented successfully, the transportation of objects backward to the source by the optical pulling forces (OPFs) has attracted tremendous attention, which was usually achieved by increasing the forward momentum of light. However, the limited momentum transfer between light and object greatly constrains the amplitudes of OPFs. Here, we present a mechanism to generate strong interactions between object and background through the bound states in the continuums, which can generate large OPFs without increasing the forward momentum of light. The underlying physics is the extraction of momentum from the designed background lattice units assisted by mode symmetry. This work paves the way for extraordinary optical manipulations and shows great potential for exploring the momenta of light in media.

Transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex reduced attentional bias toward natural emotional sounds.

Previous research has indicated that the left dorsolateral prefrontal cortex (DLPFC) exerts an influence on attentional bias toward visual emotional information. However, it remains unclear whether the left DLPFC also play an important role in attentional bias toward natural emotional sounds. The current research employed the emotional spatial cueing paradigm, incorporating natural emotional sounds of considerable ecological validity as auditory cues. Additionally, high-definition transcranial direct current stimulation (HD-tDCS) was utilized to examine the impact of left dorsolateral prefrontal cortex (DLPFC) on attentional bias and its subcomponents, namely attentional engagement and attentional disengagement. The results showed that (1) compared to sham condition, anodal HD-tDCS over the left DLPFC reduced the attentional bias toward positive and negative sounds; (2) anodal HD-tDCS over the left DLPFC reduced the attentional engagement toward positive and negative sounds, whereas it did not affect attentional disengagement away from natural emotional sounds. Taken together, the present study has shown that left DLPFC, which was closely related with the top-down attention regulatory function, plays an important role in auditory emotional attentional bias.

Association mechanism between Arabidopsis immune coreceptor BAK1 and Pseudomonas syringae effector HopF2.

Brassinosteroid activated kinase 1 (BAK1) is a cell-surface coreceptor which plays multiple roles in innate immunity of plants. HopF2 is an effector secreted by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 into Arabidopsis and suppresses host immune system through interaction with BAK1 as well as its downstream kinase MKK5. The association mechanism of HopF2 to BAK1 remains unclear, which prohibits our understanding and subsequent interfering of their interaction for pathogen management. Herein, we found the kinase domain of BAK1 (BAK1-KD) is sufficient for HopF2 association. With a combination of hydrogen/deuterium exchange mass spectrometry and mutational assays, we found a region of BAK1-KD N-lobe and a region of HopF2 head subdomain are critical for intermolecular interaction, which is also supported by unbiased protein-protein docking with ClusPro and kinase activity assay. Collectively, this research presents the interaction mechanism between Arabidopsis BAK1 and P. syringae HopF2, which could pave the way for bactericide development that blocking the functioning of HopF2 toward BAK1.

Sub-surface Imaging of Porous GaN Distributed Bragg Reflectors via Backscattered Electrons.

In this article, porous GaN distributed Bragg reflectors (DBRs) were fabricated by epitaxy of undoped/doped multilayers followed by electrochemical etching. We present backscattered electron scanning electron microscopy (BSE-SEM) for sub-surface plan-view imaging, enabling efficient, non-destructive pore morphology characterization. In mesoporous GaN DBRs, BSE-SEM images the same branching pores and Voronoi-like domains as scanning transmission electron microscopy. In microporous GaN DBRs, micrographs were dominated by first porous layer features (45 nm to 108 nm sub-surface) with diffuse second layer (153 nm to 216 nm sub-surface) contributions. The optimum primary electron landing energy (LE) for image contrast and spatial resolution in a Zeiss GeminiSEM 300 was approximately 20 keV. BSE-SEM detects porosity ca. 295 nm sub-surface in an overgrown porous GaN DBR, yielding low contrast that is still first porous layer dominated. Imaging through a ca. 190 nm GaN cap improves contrast. We derived image contrast, spatial resolution, and information depth expectations from semi-empirical expressions. These theoretical studies echo our experiments as image contrast and spatial resolution can improve with higher LE, plateauing towards 30 keV. BSE-SEM is predicted to be dominated by the uppermost porous layer's uppermost region, congruent with experimental analysis. Most pertinently, information depth increases with LE, as observed.

Can Perceivers Differentiate Intense Facial Expressions? Eye Movement Patterns.

Recent research on intense real-life faces has shown that although there was an objective difference in facial activities between intense winning faces and losing faces, viewers failed to differentiate the valence of such expressions. In the present study, we explored whether participants could perceive the difference between intense positive facial expressions and intense negative facial expressions in a forced-choice response task using eye-tracking techniques. Behavioral results showed that the recognition accuracy rate for intense facial expressions was significantly above the chance level. For eye-movement patterns, the results indicated that participants gazed more and longer toward the upper facial region (eyes) than the lower region (mouth) for intense losing faces. However, the gaze patterns were reversed for intense winning faces. The eye movement pattern for successful differentiation trials did not differ from failed differentiation trials. These findings provided preliminary evidence that viewers can utilize intense facial expression information and perceive the difference between intense winning faces and intense losing faces produced by tennis players in a forced-choice response task.

The synthetic NLR RGA5HMA5 requires multiple interfaces within and outside the integrated domain for effector recognition.

Some plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). Rice RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here, we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.

Nitrogen atom insertion into arenols to access benzazepines.

Advances in site-selective molecular editing have enabled structural modification on complex molecules. However, thus far, their applications have been restricted to C-H functionalization chemistry. The modification of the underlying molecular skeleton remains limited. Here, we describe a skeletal editing approach that provides access to benzazepine structures through direct nitrogen atom insertion into arenols. Using widely available arenols as benzazepine precursors, this alternative approach allowed the streamlined assembly of benzazepines with broad functional group tolerance. Experimental mechanistic studies support a reaction pathway involving dearomatizative azidation and then aryl migration. This study further highlights the potential for carbon-nitrogen transmutation sequences through combinations with oxidative carbon atom deletion, providing an alternative for the development of N-heteroarenes and demonstrating significant potential in materials chemistry.

Toll-like Receptor 4 Signaling Mediates Gastritis and Gastric Cancer.

The stomach is a crucial digestive organ in the human body, highly susceptible to inflammation or pathogen invasion, which can lead to various gastric diseases, including gastric cancer. Toll-like receptors (TLRs) are the first line of defense against pathogen invasion. TLR4, a member of the TLRs family, recognizes pathogen and danger-related molecular patterns to induce inflammatory responses. Helicobacter pylori (H. pylori) is a significant factor in gastric health, and TLR4 recognizes H. pylori -LPS to trigger an inflammatory response. Downstream TLR4 signaling generates proinflammatory cytokines that initiate inflammation in the gastric mucosa. In addition, TLR4 gene polymorphisms can increase health risks. This study aims to investigate the contribution of TLR4 to the inflammatory response in gastric diseases and the relation between TLR4 and H. pylori, TLR4 gene polymorphisms, and how TLR4 affects gastric diseases' possible pathways to provide further insight for future prevention and clinical treatment strategies.

Smartphone-assisted nanozyme sensor array constructed based on reaction kinetics for the discrimination and identification of phenolic compounds.

Although the research on nanozymes has attracted widespread attention in recent years, the development of highly active and multifunctional nanozymes remains a challenge. Here, a bifunctional AMP-Cu nanozyme with laccase- and catecholase-like activities was successfully prepared at room temperature with Cu2+ as the metal ion and adenosine-5'-monophosphate (AMP) as the ligand molecule. Based on the excellent catalytic performance of AMP-Cu, a three-channel colorimetric sensor array was constructed using reaction kinetics as the sensing unit to achieve high-throughput detection and identification of six common phenolic compounds at low concentrations. This strategy simplifies the construction of sensor array and demonstrates the capacity to obtain multidimensional data from a single material. Finally, with the assistance of smartphones and homemade dark boxes, a portable on-site detection method for phenolic compounds was developed. This work would contribute to the development of portable sensors and the highly efficient identification of phenolic compounds in complex samples.

Emotion contagion and physiological synchrony: The more intimate relationships, the more contagion of positive emotions.

The study aimed to explore how interpersonal closeness (friends vs. strangers) and emotion type (positive vs. negative) influenced emotion contagion and physiological synchrony between interacting partners. Twenty-eight friend dyads (n = 56) and 29 stranger dyads (n = 58) participated in an emotion contagion laboratory task. In each dyad, one participant, the 'sender', was randomly asked to watch a film clip (neutral, positive, or negative), while their partner, the 'observer' passively observed the sender's facial expressions. Participants' electrocardiograms (ECG) and facial electromyography (EMG) signals were recorded using the BIOPAC system. Results revealed that observing the sender's facial expressions led to the observer's spontaneous mimicry and emotional contagion, accompanied by enhanced physiological synchrony between interacting partners. In the positive emotion condition, the observers reported more positive emotions and displayed stronger zygomaticus major activity in friend dyads than in stranger dyads. Greater physiological synchrony (heart rate and heart rate variability) between interacting partners was also observed in friend dyads than in stranger dyads in the positive emotion condition. These results indicate that positive emotion contagion is more likely to occur between close partners than negative emotion contagion.

Video telehealth emotional awareness and expression therapy for older U.S. military veterans with chronic pain: A pilot study.

OBJECTIVES: Emotional Awareness and Expression Therapy (EAET) targets trauma and emotional conflict to reduce or eliminate chronic pain, but video telehealth administration is untested. This uncontrolled pilot assessed acceptability, feasibility, and preliminary efficacy of group-based video telehealth EAET (vEAET) for older veterans with chronic musculoskeletal pain. METHODS: Twenty veterans were screened, and 16 initiated vEAET, delivered as one 60-minute individual session and eight 90-minute group sessions. Veterans completed posttreatment satisfaction ratings and pain severity (primary outcome), pain interference, anxiety, depression, functioning, social connectedness, shame, and anger questionnaires at baseline, posttreatment, and 2-month follow-up. RESULTS: Satisfaction was high, and veterans attended 7.4 (SD = 0.6) of 8 group sessions; none discontinued treatment. Veterans attained significant, large reductions in pain severity from baseline to posttreatment (p < .001, Hedges' g = -1.54) and follow-up (p < .001, g = -1.20); 14 of 16 achieved clinically significant (≥ 30%) pain reduction, and 3 achieved 90-100% pain reduction. Secondary outcomes demonstrated significant, medium-to-large improvements. CONCLUSIONS: In this small sample, vEAET produced better attendance, similar benefits, and fewer dropouts than in-person EAET in prior studies. Larger, controlled trials are needed. CLINICAL IMPLICATIONS: Group vEAET appears feasible and highly effective for older veterans with chronic pain.

Carotenoids synthesis affects the salt tolerance mechanism of Rhodopseudomonas palustris.

Rhodopseudomonas palustris CGA009 is a Gram-negative, purple non-sulfur, metabolically diverse bacterium with wide-ranging habitats. The extraordinary ability of R. palustris to decompose a variety of raw materials and convert them into high-value products makes it an attractive host for biotechnology and industrial applications. However, being a freshwater bacterium R. palustris has limited application in highly-saline environments. Therefore, it is of great significance to obtain the salt-tolerant strain of R. palustris and understand its tolerance mechanism. In this study, R. palustris CGA009 was successfully evolved into eight salt-tolerant strains using an adaptive laboratory evolution technique. RPAS-11 (R. palustris anti-salt strain 11) was selected as the best salt-tolerant strain and was used in further studies to explore the salt-tolerance mechanism. The expression of most genes associated with the carotenoid synthesis in RPAS-11 increased significantly under high concentration of salt stress, suggesting that carotenoid synthesis is one of the reasons for the salt tolerance of RPAS-11. Gene overexpression and knockout experiments were performed to get clear about the role of carotenoids in salt stress tolerance. RPAS-11-IDI, the mutant with overexpression of IDI (Isopentenyl diphosphate isomerase) exhibited enhanced salt tolerance, whereas the knockout mutant CGA009-∆crtI showed a decline in salt tolerance. In addition, the results indicated that rhodopin, a carotenoid compound, was the key pigment responsible for the salt tolerance in R. palustris. Furthermore, the production of lycopene, a widely-used carotenoid, was also increased. Taken together, our research helps to deepen the understanding of the salt tolerance mechanism of R. palustris and also widens the application of R. palustris in highly-saline environments.

A circRNA therapy based on Rnf103 to inhibit Vibrio anguillarum infection.

The losses caused by Vibrio infections in the aquaculture industry are challenging to quantify. In the face of antibiotic resistance, a natural and environmentally friendly alternative is urgently needed. In this study, we identify E3 ubiquitin-protein ligase RNF103 (rnf103) as a crucial target involved in immune evasion by Vibrio anguillarum. Our research demonstrates that Rnf103 promotes immune escape by inhibiting Traf6. Interestingly, we discover a circular RNA (circRNA), circRnf103, formed by reverse splicing of the Rnf103 gene. Predictive analysis and experimentation reveal that circRnf103 encodes Rnf103-177aa, a protein that competes with Rnf103 and binds to Traf6, preventing its degradation. Notably, circRnf103 therapy induces Rnf103-177aa protein production in zebrafish. In zebrafish models, circRnf103 exhibits significant effectiveness in treating V. anguillarum infections, reducing organ burden. These findings highlight the potential of circRNA therapy as a natural and innovative approach to combat infectious diseases sustainably, particularly in aquaculture and environmental management.

Preparation and application of high-brightness red carbon quantum dots for pH and oxidized L-glutathione dual response.

Carbon dots (CDs) with red fluorescence emission are highly desirable for use in bioimaging and trace- substance detection, with potential applications in biotherapy, photothermal therapy, and tumor visualization. Most CDs emit green or blue fluorescence, thus limiting their applicability. We report a novel fluorescent detection platform based on high-brightness red fluorescence emission carbon dots (R-CDs) co-doped with nitrogen and bromine, which exhibit pH and oxidized L-glutathione (GSSG) dual-responsive characteristics. The absolute quantum yield of the R-CDs was as high as 11.93%. We discovered that the R-CDs were able to detect acidic pH in live cells and zebrafish owing to protonation and deprotonation. In addition, GSSG was detected in vitro over a broad linear range (8-200 µM) using the R-CDs with excitation-independent emission. Furthermore, cell imaging and bioimaging experiments demonstrated that the R-CDs were highly cytocompatible and could be used as fluorescent probes to target lysosomes and nucleolus. These studies highlight the promising prospects of R-CDs as biosensing tools for bioimaging and trace-substance detection applications.

Nitrogen-doped orange emitting carbon dots for ß-carotene detection and lysosomal imaging.

ß-Carotene is a natural antioxidant that has an indispensable effect on the growth and immunity of the human body. For intracellular and in vitro detection of ß-carotene, N-doped carbon quantum dots (O-CDs) were prepared by co-heating carbonization of 1,5-naphthalenediamine and nitric acid in ethanol solvent for 2 h at 200 °C. O-CDs have longer wavelength orange light emission, with an optimal excitation peak of 470 nm and an optimal emission peak of 590 nm. According to the principle of the internal filtering effect on which the detection system is based, O-CDs present a good linear relationship with ß-carotene within a wide range of 0-2000 µM, and the R2 coefficient of the linear regression equation is 0.999. In addition, O-CDs showed targeting of lysosomes in cell imaging and could be used to detect intracellular lysosomal movement. These experiments show that O-CDs can be used for in vivo and in vitro detection of ß-carotene and can serve as a potential substitute to commercial lysosome targeting probes.

Three-Photon Excitation of InGaN Quantum Dots.

We demonstrate that semiconductor quantum dots can be excited efficiently in a resonant three-photon process, while resonant two-photon excitation is highly suppressed. Time-dependent Floquet theory is used to quantify the strength of the multiphoton processes and model the experimental results. The efficiency of these transitions can be drawn directly from parity considerations in the electron and hole wave functions in semiconductor quantum dots. Finally, we exploit this technique to probe intrinsic properties of InGaN quantum dots. In contrast to nonresonant excitation, slow relaxation of charge carriers is avoided, which allows us to measure directly the radiative lifetime of the lowest energy exciton states. Since the emission energy is detuned far from the resonant driving laser field, polarization filtering is not required and emission with a greater degree of linear polarization is observed compared to nonresonant excitation.

Host-mediated RNA editing in viruses.

Viruses rely on hosts for life and reproduction, cause a variety of symptoms from common cold to AIDS to COVID-19 and provoke public health threats claiming millions of lives around the globe. RNA editing, as a crucial co-/post-transcriptional modification inducing nucleotide alterations on both endogenous and exogenous RNA sequences, exerts significant influences on virus replication, protein synthesis, infectivity and toxicity. Hitherto, a number of host-mediated RNA editing sites have been identified in diverse viruses, yet lacking a full picture of RNA editing-associated mechanisms and effects in different classes of viruses. Here we synthesize the current knowledge of host-mediated RNA editing in a variety of viruses by considering two enzyme families, viz., ADARs and APOBECs, thereby presenting a landscape of diverse editing mechanisms and effects between viruses and hosts. In the ongoing pandemic, our study promises to provide potentially valuable insights for better understanding host-mediated RNA editing on ever-reported and newly-emerging viruses.

Critical influence of cytokines and immune cells in autoimmune gastritis.

Gastric cancer (GC) is a type of the most common cancers. Autoimmune gastritis (AIG) and infection with Helicobacter pylori (HP) are the risk factors of triggering GC. With the emphasis on the treatment of HP, the incidence and prevalence of HP infection in population is decreasing. However, AIG lacks accurate diagnosis and treatment methods, which occupies high cancer risk factors. AIG is controlled by the immune environment of the stomach, including immune cells, inflammatory cells, and infiltrating intercellular material. Various immune cells or cytokines play a central role in the process of regulating gastric parietal cells. Abnormal expression levels of cytokines involved in immunity are bound to face the risk of tumorigenesis. Therefore, it is particularly important for preventing or treating AIG and avoiding the risk of gastric cancer to clarify the confirmed action mode of immune cells and cytokines in the gastric system. Herein, we briefly reviewed the role of the immune environment under AIG, focussing on describing these double-edged effects between immune cells and cytokines, and pointing out potential research challenges.

Flourishing Antibacterial Strategies for Osteomyelitis Therapy.

Osteomyelitis is a destructive disease of bone tissue caused by infection with pathogenic microorganisms. Because of the complex and long-term abnormal conditions, osteomyelitis is one of the refractory diseases in orthopedics. Currently, anti-infective therapy is the primary modality for osteomyelitis therapy in addition to thorough surgical debridement. However, bacterial resistance has gradually reduced the benefits of traditional antibiotics, and the development of advanced antibacterial agents has received growing attention. This review introduces the main targets of antibacterial agents for treating osteomyelitis, including bacterial cell wall, cell membrane, intracellular macromolecules, and bacterial energy metabolism, focuses on their mechanisms, and predicts prospects for clinical applications.