The clade III subfamily of OsSWEETs directly suppresses rice immunity by interacting with OsHMGB1 and OsHsp20L.

The clade III subfamily of OsSWEETs includes transmembrane proteins necessary for susceptibility to bacterial blight (BB). These genes are targeted by the specific transcription activator-like effector (TALE) of Xanthomonas oryzae pv. oryzae and mediate sucrose efflux for bacterial proliferation. However, the mechanism through which OsSWEETs regulate rice immunity has not been fully elucidated. Here, we demonstrated that the cytosolic carboxyl terminus of OsSWEET11a/Xa13 is required for complementing susceptibility to PXO99 in IRBB13 (xa13/xa13). Interestingly, the C-terminus of ZmXa13, the maize homologue of OsSWEET11a/Xa13, could perfectly substitute for the C-terminus of OsSWEET11a/Xa13. Furthermore, OsSWEET11a/Xa13 interacted with the high-mobility group B1 (OsHMGB1) protein and the small heat shock-like protein OsHsp20L through the same regions in the C-terminus. Consistent with the physical interactions, knockdown or knockout of either OsHMGB1 or OsHsp20L caused an enhanced PXO99-resistant phenotype similar to that of OsSWEET11a/OsXa13. Surprisingly, the plants in which OsHMGB1 or OsHsp20L was repressed developed increased resistance to PXO86, PXO61 and YN24, which carry TALEs targeting OsSWEET14/Xa41 or OsSWEET11a/Xa13. Additionally, OsHsp20L can interact with all six members of clade III OsSWEETs, whereas OsHMGB1 can interact with five other members in addition to OsSWEET12. Overall, we revealed that OsHMGB1 and OsHsp20L mediate conserved BB susceptibility by interacting with clade III OsSWEETs, which are candidates for breeding broad-spectrum disease-resistant rice.

The MYB transcription factor OsMYBxoc1 regulates resistance to Xoc by directly repressing transcription of the iron transport gene OsNRAMP5 in rice.

Bacterial leaf streak caused by Xanthomonas oryzae pv. oryzicola (Xoc) is a continuous threat to rice cultivation, leading to substantial yield losses with socioeconomic implications. Iron ions are essential mineral nutrients for plant growth, but little information is available on how they influence mechanisms of rice immunity against Xoc. Here, we investigated the role of the myeloblastosis-related (MYB) transcriptional repressor OsMYBxoc1 in modulation of rice resistance through control of iron ion transport. Overexpression of OsMYBxoc1 significantly increased rice resistance, whereas OsMYBxoc1 RNA-interference lines and knockout mutants showed the opposite result. Suppression of OsMYBxoc1 expression dampened the immune response induced by pathogen-associated molecular patterns. We demonstrated that OsMYBxoc1 binds specifically to the OsNRAMP5 promoter and represses transcription of OsNRAMP5. OsNRAMP5, a negative regulator of rice resistance to bacterial leaf streak, possesses metal ion transport activity, and inhibition of OsMYBxoc1 expression increased the iron ion content in rice. Activity of the ion-dependent H2O2 scavenging enzyme catalase was increased in plants with suppressed expression of OsMYBxoc1 or overexpression of OsNRAMP5. We found that iron ions promoted Xoc infection and interfered with the production of reactive oxygen species induced by Xoc. The type III effector XopAK directly inhibited OsMYBxoc1 transcription, indicating that the pathogen may promote its own proliferation by relieving restriction of iron ion transport in plants. In addition, iron complemented the pathogenicity defects of the RS105_ΔXopAK mutant strain, further confirming that iron utilization by Xoc may be dependent upon XopAK. In conclusion, our study reveals a novel mechanism by which OsMYBxoc1 modulates rice resistance by regulating iron accumulation and demonstrates that Xoc can accumulate iron ions by secreting the effector XopAK to promote its own infection.

NIT24 and NIT29-mediated IAA synthesis of Xanthomonas oryzae pv. oryzicola suppresses immunity and boosts growth in rice.

Auxin plays a pivotal role in the co-evolution of plants and microorganisms. Xanthomonas oryzae pv. oryzicola (Xoc) stands as a significant factor that affects rice yield and quality. However, the current understanding of Xoc's capability for indole 3-acetic acid (IAA) synthesis and its mechanistic implications remains elusive. In this study, we performed a comprehensive genomic analysis of Xoc strain RS105, leading to the identification of two nitrilase enzyme family (NIT) genes, designated as AKO15524.1 and AKO15829.1, subsequently named NIT24 and NIT29, respectively. Our investigation unveiled that the deletion of NIT24 and NIT29 resulted in a notable reduction in IAA synthesis capacity within RS105, thereby impacting extracellular polysaccharide production. This deficiency was partially ameliorated through exogenous IAA supplementation. The study further substantiated that NIT24 and NIT29 have nitrilase activity and the ability to catalyse IAA production in vitro. The lesion length and bacterial population statistics experiments confirmed that NIT24 and NIT29 positively regulated the pathogenicity of RS105, suggesting that NIT24 and NIT29 may regulate Xoc invasion by affecting IAA synthesis. Furthermore, our analysis corroborated mutant strains, RS105_ΔNIT24 and RS105_ΔNIT29, which elicited the outbreak of reactive oxygen species, the deposition of callose and the upregulation of defence-related gene expression in rice. IAA exerted a significant dampening effect on the immune responses incited by these mutant strains in rice. In addition, the absence of NIT24 and NIT29 affected the growth-promoting effect of Xoc on rice. This implies that Xoc may promote rice growth by secreting IAA, thus providing a more suitable microenvironment for its own colonization. In summary, our study provides compelling evidence for the existence of a nitrilase-dependent IAA biosynthesis pathway in Xoc. IAA synthesis-related genes promote Xoc colonization by inhibiting rice immune defence response and affecting rice growth by increasing IAA content in Xoc.

Microbial volatile organic compounds 2-heptanol and acetoin control Fusarium crown and root rot of tomato.

Some microbial volatile organic compounds (mVOCs) can act as antagonistic weapons against plant pathogens, but little information is available on the contribution of individual mVOC to biocontrol and how they interact with plant pathogens. In this study, the Bacillus subtilis strain N-18 isolated from the rhizosphere of healthy plants grown in areas where Fusarium crown and root rot (FCRR) of tomato occurs could reduce the 30% of the incidence of FCRR. Moreover, the volatile organic compounds (VOCs) produced by N-18 had inhibitory effects on Fusarium oxysporum f. sp. radicis-lycopersici (FORL). The identification of VOCs of N-18 was analyzed by the solid-phase microextraction coupled to gas chromatography-mass spectrometry. Meanwhile, we conducted sensitivity tests with these potential active ingredients and found that the volatile substances acetoin and 2-heptanol can reduce the 41.33% and 35% of the incidence of FCRR in tomato plants. In addition, the potential target protein of acetoin, found in the cheminformatics and bioinformatics database, was F. oxysporum of hypothetical protein AU210_012600 (FUSOX). Molecular docking results further predicted that acetoin interacts with FUSOX protein. These results reveal the VOCs of N-18 and their active ingredients in response to FORL and provide a basis for further research on regulating and controlling FCRR.

Tal2b targets and activates the expression of OsF3H03g to hijack OsUGT74H4 and synergistically interfere with rice immunity.

Transcription activator-like (TAL) effectors are major virulence factors secreted by the type III secretion systems of Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo), causing bacterial leaf streak and bacterial blight, respectively, in rice. However, the knowledge of Xoc TAL effector function in promoting bacterial virulence remains limited. Here, we isolated the highly virulent Xoc strain HGA4 from the outbreak region of Huanggang (Hubei, China), which contains four TAL effectors not found in the Chinese model strain RS105. Among these, Tal2b was selected for introduction into RS105, which resulted in a longer lesion length than that in the control. Tal2b directly binds to the promoter region of the gene and activates the expression of OsF3H03g , which encodes 2-oxoglutarate-dependent dioxygenase in rice. OsF3H03g negatively regulates salicylic acid (SA)-related defense by directly reducing SA, and it plays a positive role in susceptibility to both Xoc and Xoo in rice. OsF3H03g interacts with a uridine diphosphate-glycosyltransferase protein (OsUGT74H4), which positively regulates bacterial leaf streak susceptibility and may inactivate SA via glycosylation modification.

Reversing the cytotoxicity of uric acid by supramolecular encapsulation with acyclic cucurbit[n]uril.

Supramolecular encapsulation, which removes harmful substances from organisms, has evolved into a new strategy. In this paper, three supramolecular complexes of acyclic cucurbit[n]urils (ACBs) with uric acid (UA) were prepared, and the inclusion behavior of ACBs and UA was studied by fluorescence spectroscopy, UV-vis spectroscopy and nuclear magnetic resonance. Furthermore, the effect of the complexes of UA with ACBs on the expression of inflammatory biomarkers in human hepatoma HepG2 cell lines was characterized through C-reactive protein (CRP) western blot. The results showed UA molecules can be recognized by three ACBs with different binding constants, and ACBs successfully blocked the inflammatory stimulation of UA on HepG2 cell lines and inhibited the expression of the major inflammatory factor CRP by the formation of complexes between UA and ACBs. This article proves that ACBs can efficiently reverse the cytotoxicity of UA, which provides a new method for treating hyperuricemia disease.

Neural mechanisms underlying visual and auditory processing impairments in schizophrenia: insight into the etiology and implications for tailoring preventive and therapeutic interventions.

Schizophrenia is a complex and devastating neuropsychiatric disorder with an unknown etiology. Patients with schizophrenia have a high prevalence of visual disturbances, commonly accompanied by auditory impairments. In recent review articles, the perceptual deficits of visual and auditory sensory processing have been downplayed. However, visual and auditory impairments are associated with hallucinations, which is characteristic of schizophrenia across all cultures. Despite decades of research, the common neural mechanisms underlying hallucinations remain largely unknown. In recent years, neuroimaging technologies have empowered researchers to investigate the underlying neural mechanisms. In this review article, we performed a literature search of studies that assessed visual and auditory processing impairments, along with their relationship to visual disturbances and auditory hallucinations, in schizophrenia. We proposed that the pulvinar may play a critical role. In addition, disrupted visual and auditory projections from the pulvinar to the visual and auditory cortices could be shared pathways in relation to visual disturbances and auditory hallucinations in schizophrenia. Our findings suggest that early visual and auditory processing deficits may occur before the onset of the initial psychotic episode, including hallucinations, and the full manifestation of schizophrenia. Furthermore, we discussed the directions for future studies. Our findings from this review offer unique insights into the distinct underlying neural mechanisms of schizophrenia, which may help develop tailored preventive and therapeutic interventions in the future.

OsPGIP1-Mediated Resistance to Bacterial Leaf Streak in Rice is Beyond Responsive to the Polygalacturonase of Xanthomonas oryzae pv. oryzicola.

Polygalacturonase-inhibiting proteins (PGIPs) have been shown to recognize fungal polygalacturonases (PGs), which initiate innate immunity in various plant species. Notably, the connection between rice OsPGIPs and PGs in Xanthomonas oryzae pv. oryzicola (Xoc), which causes bacterial leaf streak (BLS), remains unclear. Here, we show that OsPGIP1 was strongly induced after inoculating rice with the Xoc strain RS105. Furthermore, OsPGIP1-overexpressing (OV) and RNA interference (RNAi) rice lines increased and decreased, respectively, the resistance of rice to RS105, indicating that OsPGIP1 contributes to BLS resistance. Subsequently, we generated the unique PG mutant RS105Δpg, the virulence of which is attenuated compared to that of RS105. Surprisingly, the lesion lengths caused by RS105Δpg were similar to those caused by RS105 in the OV lines compared with wild-type ZH11 with reduced Xoc susceptibility. However, the lesion lengths caused by RS105Δpg were still significantly shorter in the OV lines than in ZH11, implying that OsPGIP1-mediated BLS resistance could respond to other virulence factors in addition to PGs. To explore the OsPGIP1-mediated resistance, RNA-seq analysis were performed and showed that many plant cell wall-associated genes and several MYB transcription factor genes were specifically expressed or more highly induced in the OV lines compared to ZH11 postinoculation with RS105. Consistent with the expression of the differentially expressed genes, the OV plants accumulated a higher content of jasmonic acid (JA) than ZH11 postinoculation with RS105, suggesting that the OsPGIP1-mediated resistance to BLS is mainly dependent on the plant cell wall-associated immunity and the JA signaling pathway.

OsASR2 regulates the expression of a defence-related gene, Os2H16, by targeting the GT-1 cis-element.

The GT-1 cis-element widely exists in many plant gene promoters. However, the molecular mechanism that underlies the response of the GT-1 cis-element to abiotic and biotic stresses remains elusive in rice. We previously isolated a rice short-chain peptide-encoding gene, Os2H16, and demonstrated that it plays important roles in both disease resistance and drought tolerance. Here, we conducted a promoter assay of Os2H16 and identified GT-1 as an important cis-element that mediates Os2H16 expression in response to pathogen attack and osmotic stress. Using the repeated GT-1 as bait, we characterized an abscisic acid, stress and ripening 2 (ASR2) protein from yeast-one hybridization screening. Sequence alignments showed that the carboxy-terminal domain of OsASR2 containing residues 80-138 was the DNA-binding domain. Furthermore, we identified that OsASR2 was specifically bound to GT-1 and activated the expression of the target gene Os2H16, as well as GFP driven by the chimeric promoter of 2 × GT-1-35S mini construct. Additionally, the expression of OsASR2 was elevated by pathogens and osmotic stress challenges. Overexpression of OsASR2 enhanced the resistance against Xanthomonas oryzae pv. oryzae and Rhizoctonia solani, and tolerance to drought in rice. These results suggest that the interaction between OsASR2 and GT-1 plays an important role in the crosstalk of the response of rice to biotic and abiotic stresses.

Functional analysis of the GRMZM2G174449 promoter to identify Rhizoctonia solani-inducible cis-elements in maize.

BACKGROUND: Banded leaf and sheath blight (BLSB), caused by the necrotrophic fungus Rhizoctonia solani, is a highly devastating disease in most maize and rice growing areas of the world. However, the molecular mechanisms of perceiving pathogen signals are poorly understood in hosts. RESULTS: Here, we identified a Rhizoctonia solani-inducible promoter pGRMZM2G174449 in maize. Deletion analysis showed that the -574 to -455 fragment was necessary for pGRMZM2G174449 in responding to R. solani and this fragment contained the unknown pathogen-inducible cis-elements according to the bioinformatics analysis. Furthermore, detailed quantitative assays showed that two cis-elements, GCTGA in the -567 to -563 region and TATAT in the -485 to -481 region, were specifically responsible for the R. solani-inducible activity. A series of point mutation analysis indicated that the two cis-elements have the conserved motifs of NHWGN and DWYWT, respectively. CONCLUSION: Our results indicated that pGRMZM2G174449 is a good R. solani-inducible promoter suitable for genetic engineering of BLSB resistance. And NHWGN and DWYWT are two R. solani-inducible cis-elements that play important roles in pGRMZM2G174449 responding to R. solani.

Lower risk of liver cancer in patients with schizophrenia: a systematic review and meta-analysis of cohort studies.

Previous studies regarding the association between schizophrenia and the subsequent risk of liver cancer have shown inconsistent results. We aimed to perform a systematic review and meta-analysis to evaluate the association between schizophrenia and liver cancer incidence. We systematically searched the PubMed and Embase electronic databases for cohort studies reporting the standardized incidence ratio (SIR) for the risk of liver cancer in patents with schizophrenia as compared with the general population. A random-effects model was used to analyze the data. Stratified analyses were performed according to the gender of the patients. Seven studies comprising 312,834 patients with schizophrenia were included. During follow-up, 581 liver cancer cases were confirmed. The meta-analysis results showed that schizophrenia was associated with a trend of a lower liver cancer incidence (SIR: 0.83, 95% confidence interval [CI]: 0.66-1.04, p = 0.10) with significant heterogeneity (I2 = 81%). Sensitivity analysis of five cohorts of patients with cancer events before the diagnosis of schizophrenia indicated that schizophrenia was associated with a significantly lower incidence of liver cancer (SIR: 0.76, 95% CI: 0.61-0.96, p = 0.02; I2 = 84%). The reduction of a subsequent incidence of liver cancer was significant in male patients with schizophrenia (SIR: 0.71, p = 0.005), and a trend of a reduced risk of liver cancer was also detected in female patients (SIR: 0.83, p = 0.12). Significant publication bias was detected. However, "trim and fill" analyses by including the imputed unpublished studies showed similar results. In summary, schizophrenia may be protective against the incidence of liver cancer.

Identification of two novel Rhizoctonia solani-inducible cis-acting elements in the promoter of the maize gene, GRMZM2G315431.

Plants are continuously exposed to myriad pathogen stresses. However, the molecular mechanisms by which these stress signals are perceived and transduced are poorly understood. In this study, the maize gene GRMZM2G315431 was identified to be highly inducible by Rhizoctonia solani infection, suggesting that the promoter of GRMZM2G315431 (pGRMZM2G315431) might contain a specific cis-acting element responsive to R. solani attack. To identify the R. solani-responsive element in pGRMZM2G315431, a series of binary plant transformation vectors were constructed by fusing pGRMZM2G315431 or its deletion-derivatives with the reporter genes. In the transient gene expression system of Nicotiana benthamiana leaves inoculated with R. solani, GUS quantification suggested that the DNA fragment contains the unknown pathogen-inducible cis-elements in the -1323 to -1212 region. Furthermore, detailed quantitative assays showed that two novel cis-elements, GTTGA in the -1243 to -1239 region and TATTT in the -1232 to -1228 region, were responsible for the R. solani-inducible activity. These two cis-elements were also identified to have R. solani-specific-inducible activity in stable transgenic rice plants, suggesting the existence of a novel regulation mechanism involved in the interaction between R. solani and Zea mays.