The root-knot nematode effector MiEFF12 targets the host ER quality control system to suppress immune responses and allow parasitism.

Root-knot nematodes (RKNs) are microscopic parasitic worms able to infest the roots of thousands of plant species, causing massive crop yield losses worldwide. They evade the plant's immune system and manipulate plant cell physiology and metabolism to transform a few root cells into giant cells, which serve as feeding sites for the nematode. RKN parasitism is facilitated by the secretion in planta of effector molecules, mostly proteins that hijack host cellular processes. We describe here a conserved RKN-specific effector, effector 12 (EFF12), that is synthesized exclusively in the oesophageal glands of the nematode, and we demonstrate its function in parasitism. In the plant, MiEFF12 localizes to the endoplasmic reticulum (ER). A combination of RNA-sequencing analysis and immunity-suppression bioassays revealed the contribution of MiEFF12 to the modulation of host immunity. Yeast two-hybrid, split luciferase and co-immunoprecipitation approaches identified an essential component of the ER quality control system, the Solanum lycopersicum plant bap-like (PBL), and basic leucine zipper 60 (BZIP60) proteins as host targets of MiEFF12. Finally, silencing the PBL genes in Nicotiana benthamiana decreased susceptibility to Meloidogyne incognita infection. Our results suggest that EFF12 manipulates PBL function to modify plant immune responses to allow parasitism.

Nonreciprocal magnon blockade via the Barnett effect.

We propose a scheme to achieve nonreciprocal magnon blockade via the Barnett effect in a magnon-based hybrid system. Due to the rotating yttrium iron garnet (YIG) sphere, the Barnett shift induced by the Barnett effect can be tuned from positive to negative via controlling magnetic field direction, leading to nonreciprocity. We show that a nonreciprocal unconventional magnon blockade (UMB) can emerge only from one magnetic field direction but not from the other side. Particularly, by further tuning system parameters, we simultaneously observe a nonreciprocal conventional magnon blockade (CMB) and a nonreciprocal UMB. This result achieves a switch between efficiency (UMB) and purity (CMB) of a single-magnon blockade. Interestingly, stronger UMB can be reached under stronger qubit-magnon coupling, even the strong coupling regime. Moreover, the nonreciprocity of the magnon blockade is sensitive to temperature. This work opens up a way for achieving quantum nonreciprocal magnetic devices and chiral magnon communications.

The root-knot nematode effector Mi2G02 hijacks a host plant trihelix transcription factor to promote nematode parasitism.

Root-knot nematodes (RKNs) cause huge agricultural losses every year. They secrete a repertoire of effectors to facilitate parasitism through the induction of plant-derived giant feeding cells, which serve as their sole source of nutrients. However, the mode of action of these effectors and their targeted host proteins remain largely unknown. In this study, we investigated the role of the effector Mi2G02 in Meloidogyne incognita parasitism. Host-derived Mi2G02 RNA interference in Arabidopsis thaliana affected giant cell development, whereas ectopic expression of Mi2G02 promoted root growth and increased plant susceptibility to M. incognita. We used various combinations of approaches to study the specific interactions between Mi2G02 and A. thaliana GT-3a, a trihelix transcription factor. GT-3a knockout in A. thaliana affected feeding-site development, resulting in production of fewer egg masses, whereas GT-3a overexpression in A. thaliana increased susceptibility to M. incognita and also root growth. Moreover, we demonstrated that Mi2G02 plays a role in maintaining GT-3a protein stabilization by inhibiting the 26S proteasome-dependent pathway, leading to suppression of TOZ and RAD23C expression and thus promoting nematode parasitism. This work enhances our understanding of how a pathogen effector manipulates the role and regulation of a transcription factor by interfering with a proteolysis pathway to reprogram gene expression for development of nematode feeding cells.

A root-knot nematode effector manipulates the rhizosphere microbiome for establishing parasitism relationship with hosts.

Introduction: Root-knot nematode (RKN; Meloidogyne spp.) is one of the most infamous soilborne plant diseases, causing severe crop losses every year. Effector proteins secreted by RKNs play crucial roles during plant-nematode interaction. However, less is known about whether RKN effector proteins can impact the rhizosphere microbial environment. Methods: In this study, we investigated the rhizosphere microbiome community of MiMIF-2 (a plant immunity-modulating effector) transgenic Arabidopsis thaliana with or without nematode infection using the Illumina high-throughput sequencing analysis. Results and discussion: The results showed that the bacterial species richness index increased, while the fungi species richness index decreased in M. incognita-infected MiMIF-2 transgenic A. thaliana plants. The relative abundance of genera such as Clitopilus, Komagataeibacter, Lactobacillus, Prevotella, Moritella, Vibrio, Escherichia-Shigella, and Pseudomonas was reduced in MiMIF-2 transgenic A. thaliana plants compared to wild type, but was significantly increased after inoculation with M. incognita. The Cluster of Orthologous Genes (COG) function classification analysis revealed a decrease in the relative abundance of defense mechanisms, secondary metabolite biosynthesis, transport, and nematode infection catabolism-related functions in MiMIF-2 lines compared to the wild type. These differences may be the reason for the increased susceptibility of MiMIF-2 transgenic A. thaliana to nematode infection. Our results provide a new insight into RKN effector proteins and their association with the microbial community, host, and plant pathogens, which will lead to the exploration of new innovative ideas for future biological control of RKNs.

Impact of the teach-back method on caregiver outcomes using the "Timing it Right" framework for hemodialysis patients.

Background: The caregivers play vital roles in the health care of hemodialysis patients. Ineffective education strategy for the caregivers negatively affects the care ability of caregivers. This study aimed to evaluate the effectiveness of the teach-back method based on the "Timing it Right" framework on the caregivers' care ability, emotions and health-related quality of life for hemodialysis patients. Methods: The study involved 78 caregivers of 78 hemodialysis patients. Participants in the control group received routine nursing care and traditional oral health education, while those in the intervention group received health education through the teach-back method based on the "Timing it Right" framework. All participants were followed for 6 months. The degree of anxiety and depression of caregivers was evaluated through the Self-rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), respectively. The care ability of caregivers was assessed by the Family Caregiver Task Inventory (FCTI). The health-related quality of life of hemodialysis patients was evaluated using the 36-item Short Form Health Survey (SF-36). Results: Compared to baseline (T0), the SAS, SDS and FCTI scores of the intervention group were significantly reduced at the time of discharge (T1), three (T2) and 6 months (T3) (all p < 0.001). Besides, at T1, T2, and T3, the FCTI scores of the intervention group were significantly lower than that in control group (all p < 0.001). The SAS and SDS scores were also significantly lower in the intervention group at T1, T2, and T3 compared to the control group (all p < 0.001). For SF-36 scores, all domains of the intervention group were significantly higher than those of the control group at T1, T2 and T3, including physical functioning (p < 0.001), role physical (p = 0.007), bodily pain (p < 0.001), general health (p = 0.002), vitality (p = 0.043), social functioning (p = 0.016), role emotional (p = 0.002), and mental health(p = 0.025). Conclusion: The application of teach-back method based on the "Timing it Right" framework could obviously alleviate the anxiety and depression of caregivers for hemodialysis patients. Furthermore, it could significantly improve the care ability of caregivers and the quality of life of patients.

Nonreciprocal sideband responses in a spinning microwave magnomechanical system.

Nonreciprocal sideband responses in a spinning microwave magnomechanical system consists of a spinning resonator coupled with a yttrium iron garnet sphere are proposed. We show that the efficiency of sideband generation can be enhanced in one driving direction but restrained in the opposite. This nonreciprocity results from Sagnac effect induced by the spinning resonator, leading to asymmetric magnonic responses in two different driving directions. Beyond the conventional linearized description, the properties of nonreciprocal two-color second-order sideband are demonstrated. By adjusting Sagnac-Fizeau shift and the power of control field, the degree of asymmetric magnonic responses can be strengthened, therefore causing stronger nonreciprocity of sideband. Especially, for the case of strong Sagnac-Fizeau shift and the control field, high level of efficiency and isolation ratio of sideband are achieved simultaneously and the operational bandwidth of strong nonreciprocity can be expanded. Our proposal provides an effective avenue for the manipulation of the nonreciprocity of sideband and has potentially practical applications in on-chip microwave isolation devices and magnon-based precision measurement.

Parametric-amplification-induced nonreciprocal magnon laser.

We theoretically propose a scheme to achieve all-optical nonreciprocal magnon lasing action in a composite cavity optomagnonical system considering of a yttrium iron garnet sphere coupled to a parametric resonator. The magnon lasing behavior can be engendered via the magnon-induced Brillouin scattering process in the cavity optomagnonical system. By unidirectionally driving the χ(2)-nonlinear resonator with a classical coherent field, the squeezed effect occurs only in the selected direction due to the phase-matching condition, resulting in asymmetric detuning between the two resonators, which is the physical mechanism to generate a nonreciprocal magnon laser. We further examine the gain factor and power threshold of the magnon laser. Moreover, the isolation rate can reach 21 dB by adjusting the amplitude of the parametric amplification. Our work shows a path to obtain an all-optical nonreciprocal magnon laser, which provides a means for the preparation of a coherent magnon laser and laser protection.

Tunable microstructures of ultralong organic phosphorescence materials.

Three kinds of microstructures were prepared for one organic phosphor based on a solution-concentration-controlled self-assembly strategy. These microstructures show different phosphorescence efficiencies, which holds considerable promise for the miniaturized optical device applications of ultralong organic phosphorescence materials.

Hydrophilic Ultralong Organic Nanophosphors.

Ultralong organic phosphorescence (UOP), enabling of persistent luminescence after removal of external excitation light, shows great promise in biological applications such as bioimaging in virtue of antibackground fluorescence interference. Despite of good biocompatibility and outstanding phosphorescent properties, most current organic phosphors are hydrophobic with poor water solubility in the form of bulk crystal with large size, limiting their potential in the biological field. Here, a facile and versatile approach is provided to obtain nanoscale hydrophilic phosphorescent phosphors (HPPs) by physically loading ultralong organic phosphors into hollow mesoporous silica nanoparticles. The as-prepared HPPs can be well suspended in aqueous solution and effectively internalized by HeLa cells with very low cytotoxicity. Such HPPs are successfully applied for afterglow bioimaging in living nude mice with a very high signal-to-noise ratio up to 31. The current study not only provides a universal strategy to realize UOP in aqueous media but also demonstrates their great potential for biomedical purposes as an advanced imaging indicator with long-lived emission lifetime.

Polymorphism-Dependent Dynamic Ultralong Organic Phosphorescence.

Developing ultralong organic phosphorescence (UOP) materials with smart response to external stimuli is of great interest in photonics applications, whereas the manipulation of molecular stacking on tuning such dynamic UOP is still a formidable challenge. Herein, we have reported two polymorphs with distinct photoactivated dynamic UOP behavior based on a pyridine derivative for the first time. Our experiment revealed that the dynamic UOP behavior including photoactivation and deactivation feature is highly dependent on irradiation intensity and environmental atmosphere. Additionally, given the unique dynamic UOP feature, these phosphors have been successfully applied to phosphorescence-dependent molecular logic gate and timing data storage. This result not only paves a way to design smart functional materials but also expands the scope of the applications on organic phosphorescence materials.

Amorphous Ionic Polymers with Color-Tunable Ultralong Organic Phosphorescence.

Amorphous purely organic phosphorescence materials with long-lived and color-tunable emission are rare. Herein, we report a concise chemical ionization strategy to endow conventional poly(4-vinylpyridine) (PVP) derivatives with ultralong organic phosphorescence (UOP) under ambient conditions. After the ionization of 1,4-butanesultone, the resulting PVP-S phosphor showed a UOP lifetime of 578.36 ms, which is 525 times longer than that of PVP polymer itself. Remarkably, multicolor UOP emission ranging from blue to red was observed with variation of the excitation wavelength, which has rarely been reported for organic luminescent materials. This finding not only provides a guideline for developing amorphous polymers with UOP properties, but also extends the scope of room-temperature phosphorescence (RTP) materials for practical applications in photoelectric fields.

Enabling long-lived organic room temperature phosphorescence in polymers by subunit interlocking.

Long-lived room temperature phosphorescence (LRTP) is an attractive optical phenomenon in organic electronics and photonics. Despite the rapid advance, it is still a formidable challenge to explore a universal approach to obtain LRTP in amorphous polymers. Based on the traditional polyethylene derivatives, we herein present a facile and concise chemical strategy to achieve ultralong phosphorescence in polymers by ionic bonding cross-linking. Impressively, a record LRTP lifetime of up to 2.1 s in amorphous polymers under ambient conditions is set up. Moreover, multicolor long-lived phosphorescent emission can be procured by tuning the excitation wavelength in single-component polymer materials. These results outline a fundamental principle for the construction of polymer materials with LRTP, endowing traditional polymers with fresh features for potential applications.

Elevated TNIP3 mRNA Expression in TNF-α-Secreting Cells from Patients with Major Depressive Disorder.

OBJECTIVE: Elevated levels of pro-inflammatory cytokines, in particular tumor necrotic factor alpha (TNF-α), and abnormalities in negative regulation in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Previous research by our group disclosed lower expression of TNF-α-induced protein 3 (TNFAIP3), one of the negative regulators of the TLR4 signaling pathway, in depressive patients than in healthy controls. METHODS: In this study, we assessed the mRNA levels of TNFAIP3, TNFAIP3-interacting proteins (TNIP), including TNIP1, TNIP2, and TNIP3, and TNFAIP3-like proteins, such as cezanne1, cezanne2, trabid, and VCIP135, in TNF-α-secreting cells and examined their association with severity of depression using the 17-item Hamilton Depression Rating Scale (HAMD-17) scores from 30 MDD patients and 30 healthy controls. Twenty-six patients received a second assessment after treatment with antidepressants for 4 weeks. RESULTS: TNF-α-secreting cells displayed higher TNIP3 mRNA expression in MDD patients than in healthy controls before treatment, which was marginally decreased after antidepressant treatment. In addition, the TNIP2 level could be effectively applied to predict changes in HAMD scores after linear regression analysis. CONCLUSION: Our collective findings suggest that molecules associated with negative regulation of innate immunity are aberrantly expressed in patients with MDD and present potential therapeutic targets.

A Highly Efficient Red Metal-free Organic Phosphor for Time-Resolved Luminescence Imaging and Photodynamic Therapy.

Developing highly efficient red metal-free organic phosphors for biological applications is a formidable challenge. Here, we report a novel molecular design principle to obtain red metal-free organic phosphors with long emission lifetime (504.6 µs) and high phosphorescence efficiency (14.6%) from the isolated molecules in the crystal. Furthermore, the well-dispersed phosphorescent nanodots (PNDs) with the particle size around 5 nm are prepared through polymer-encapsulation in an aqueous solution, which show good biocompatibility and low cytotoxicity. The metal-free PNDs are successfully applied to time-resolved luminescence imaging to eliminate background fluorescence interference both in vitro and vivo as well as effective photodynamic anticancer therapy for the first time. This work will not only pave a pathway to develop highly efficient metal-free RTP materials but also expand the scope of their applications to biomedical fields.

Highly Efficient Ultralong Organic Phosphorescence through Intramolecular-Space Heavy-Atom Effect.

Metal-free organic phosphorescent materials have attracted considerable attention in the fields of organic electronics and bioelectronics. However, it remains a great challenge to achieve organic phosphors with high quantum efficiency in a single-component system. We designed and synthesized two organic phosphors (PDCz and PDBCz) with an ultralong organic phosphorescence (UOP) feature. Both molecules showed ultralong emission lifetime of >200 ms. For PDBCz crystal, it was found that the absolute phosphorescence quantum efficiency reaches up to 38.1%. Combining the experimental and theoretical studies, the highly efficient UOP was mainly attributed to the intramolecular space heavy-metal effect, which facilitates the spin-orbit coupling between singlet and triplet excited states to effectively promote the intersystem crossing. This study will provide a new platform to rationally design highly efficient UOP materials and show its potential in the field of flexible electronics.

TNFAIP3 mRNA Level Is Associated with Psychological Anxiety in Major Depressive Disorder.

BACKGROUND: Major depressive disorder has been shown to be associated with inflammation and the dysregulation of innate immune responses. Previously, we showed an inverse correlation between the severity of depression and level of TNFAIP3 mRNA expression. The present study further evaluated the association between TNFAIP3 mRNA expression level and symptoms of major depressive disorder (MDD) in 91 patients (20 men and 71 women). METHODS: The relationships between subscores on the 17-item Hamilton Depression Rating Scale (HAMD-17) and TNFAIP3 mRNA levels were assessed by multiple linear regression. RESULTS: Only psychological anxiety on the HAMD-17 correlated significantly with TNFAIP3 mRNA expression. Other symptoms, such as depressed mood, insomnia, work and activities, and suicide, were not associated with TNFAIP3 mRNA expression. CONCLUSION: These findings suggest a significant association between anxiety and TNFAIP3 mRNA levels in patients with MDD.

Purification, Characterization and Biological Activity of Polysaccharides from Dendrobium officinale.

Polysaccharide (DOPA) from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2) of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of DOPA-1 and DOPA-2 were 394 kDa and 362 kDa, respectively. They were mainly composed of d-mannose, d-glucose, and had a backbone consisting of 1,4-linked ß-d-Manp and 1,4-linked ß-d-Glcp with O-acetyl groups. Bioactivity studies indicated that both DOPA and its purified fractions (DOPA-1 and DOPA-2) could activate splenocytes and macrophages. The D. officinale polysaccharides had stimulatory effects on splenocytes, T-lymphocytes and B-lymphocytes, promoting the cell viability and NO production of RAW 264.7 macrophages. Furthermore, DOPA, DOPA-1 and DOPA-2 were found to protect RAW 264.7 macrophages against hydrogen peroxide (H2O2)-induced oxidative injury by promoting cell viability, suppressing apoptosis and ameliorating oxidative lesions. These results suggested that D. officinale polysaccharides possessed antioxidant activity and mild immunostimulatory activity.

Antidepressants normalize elevated Toll-like receptor profile in major depressive disorder.

RATIONALE: Abnormalities in Toll-like receptor (TLR) expression in depression have been inferred in part from observed increases in TLR4 levels in peripheral blood mononuclear cells (PBMCs) and postmortem brains of depressed and suicidal patients. Our previous study found differences in the TLR expression in PBMCs between healthy controls and patients with major depressive disorder. Normalization of increased TLR4 in PBMCs by cognitive behavior psychotherapy has been reported. However, the effects of antidepressants remain unknown. OBJECTIVES: Changes in TLR1-9 expression levels of PBMCs were examined in 56 patients with MDD. The 17-item Hamilton Depression Rating Scale (HAMD-17) and mRNA expression levels of TLRs were assessed in parallel with a housekeeping gene using qRT-PCR before and after treatment with antidepressants. RESULTS: TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 were expressed at elevated levels in patients with MDD and were significantly decreased by treatment with antidepressants for 4 weeks. Antidepressant treatment completely normalized TLR3, TLR5, TLR7, TLR8, and TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 were decreased to below normal levels. A subgroup analysis found that only TLR3 was significantly higher at baseline in the nonremission group. In addition, a multiple linear regression analysis revealed that only low TLR3 before treatment predicted improvement in HAMD-17 scores. CONCLUSIONS: These findings suggest that antidepressant treatment exerts anti-inflammatory effects in patients with MDD and identify TLR profiles as a predictor of response to antidepressant therapy. Further studies investigating the effects of manipulating individual TLRs on depression are needed to fully elucidate the underlying mechanism.

Association between toll-like receptor 4 expression and symptoms of major depressive disorder.

BACKGROUND: In our previous study, toll-like receptor 4 (TLR4) mRNA expression level was associated with severity of major depressive disorder (MDD) evaluated with the 17-item Hamilton Depression Rating Scale (HAMD-17). However, there are few studies that have investigated the relationship between symptoms of MDD and changes in TLR4 expression. Therefore, the aim of the present study was to further analyze the association between subscales of HAMD-17 and TLR4. METHODS: Fifty-one patients with MDD (15 male and 36 female) participated in this study. HAMD-17 was used to assess the symptoms of major depression. The mRNA expression levels of TLR4 were examined in parallel with a housekeeping gene, using real-time polymerase chain reaction. A stepwise linear regression forward model was used to evaluate the relationships between items of HAMD-17 and TLR4 expression. RESULTS: Some sickness behavior-associated symptoms, including suicide, somatic symptoms of anxiety, or performance of work and activities, were not associated with TLR4 expression. However, psychological signs of anxiety and loss of weight in HAMD-17 can predict the expression level of TLR4. CONCLUSION: Our results suggest a significant association between anxiety, body weight loss, and TLR4 mRNA levels in patients with MDD. Larger longitudinal studies combining both subjective and objective measures of depression are needed to clarify the link between TLR4 and symptoms of depression.

Association between toll-like receptors expression and major depressive disorder.

Accumulating evidences suggest that Toll-like receptors (TLRs) were involved in the pathophysiology of major depressive disorder. TLR4 was thought to be associated with major depressive disorder in animal model, but the others were still unknown. In order to examine TLR1-9 mRNA expression levels in peripheral blood and their relationships with the psychopathology of major depressive disorder, 30 patients with major depressive disorder were compared with 29 healthy controls. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess the severity of major depression. The mRNA expression levels of TLRs were examined in parallel with a housekeeping gene using real-time polymerase chain reaction (RT-PCR). Analysis of covariance with age and body mass index adjustment revealed a significantly higher expression of TLR3, 4, 5 and 7 mRNA but lower expression of TLR1 and 6 in patients with major depressive disorder as compared with healthy controls. Multiple linear regression analysis revealed that TLR4 was an independent risk factor relating to severity of major depression. These findings suggest that TLRs, especially TLR4, may be involved in the psychopathology of major depression.