Nickel/Photoredox-Catalyzed Carbonylative Cross-Electrophile Coupling of Organohalides and Carboxylic Acid Esters with Phenyl Formate.

A photoinduced nickel-catalyzed reductive carbonylative coupling from organohalides and N-(acyloxy)phthalimide esters with phenyl formate as the carbonyl source has been developed. This reaction could perform smoothly under mild conditions, and a series of aryl-alkyl and alkyl-alkyl unsymmetrical ketones were produced without the need of stoichiometric metal reductants. Mechanistic studies indicate that this reaction was initiated from radical capture by Ni(I)-carbonyl species and subsequent rapid carbonyl insertion.

One-Pot Two-Stage Biocatalytic Cascade to Produce l-Phosphinothricin by Two Enantioselective Complementary Aminotransferases at High Substrate Loading via a Deracemization Process.

The bioderacemization of racemic phosphinothricin (D, L-PPT) is a promising route for the synthesis of l-phosphinothricin (L-PPT). However, the low activity and tolerance of wild-type enzymes restrict their industrial applications. Two stereocomplementary aminotransferases with high activity and substrate tolerance were identified in a metagenomic library, and a one-pot, two-stage artificial cascade biocatalytic system was developed to produce L-PPT through kinetic resolution and asymmetric amination. We observed that 500 mM D, L-PPT (100 g/L) could be converted into L-PPT with 94% final conversion and >99.9% enantiomeric excess (e.e.) within 24 h, with only 0.02 eq amino acceptor pyruvate and 1.2 eq amino donor l-aspartate required. The process could be scaled up to 10 L under sufficient oxygen and stirring. The superior catalytic performance of this system provides an eco-friendly and sustainable approach to the industrial deracemization of D, L-PPT to L-PPT.

MIR396-GRF/GIF enhances in planta shoot regeneration of Dendrobium catenatum.

Recent studies on co-transformation of the growth regulator, TaGRF4-GIF1 chimera (Growth Regulating Factor 4-GRF Interacting Factor 1), in cultivated wheat varieties (Triticum aestivum), showed improved regeneration efficiency, marking a significant breakthrough. Here, a simple and reproducible protocol using the GRF4-GIF1 chimera was established and tested in the medicinal orchid Dendrobium catenatum, a monocot orchid species. TaGRF4-GIF1 from T. aestivum and DcGRF4-GIF1 from D. catenatum were reconstructed, with the chimeras significantly enhancing the regeneration efficiency of D. catenatum through in planta transformation. Further, mutating the microRNA396 (miR396) target sites in TaGRF4 and DcGRF4 improved regeneration efficiency. The target mimicry version of miR396 (MIM396) not only boosted shoot regeneration but also enhanced plant growth. Our methods revealed a powerful tool for the enhanced regeneration and genetic transformation of D. catenatum.

Construction of Macromolecules of Depolymerized Lignite.

Preparing ash-less coal and further converting it into chemicals is an efficient and promising means for lignite utilization. This work performed depolymerization of lignite to prepare ash-less coal (SDP) and separated it into the hexane-soluble fraction (HS), toluene-soluble fraction (TS), and tetrahydrofuran-soluble fraction (THFS). The structure of SDP and those of subfractions were characterized by elemental analysis, gel permeation chromatography, Fourier transform infrared spectroscopy, and synchronous fluorescence spectroscopy. The results show that SDP is a mixture of aromatic derivatives containing alkyl substituents and oxygen-containing functional groups. The number of condensed aromatic rings, the amount of oxygen-containing functional groups, and the molecular weight gradually increase as HS < TS < THFS. SDP was further analyzed by 1H-NMR and 13C-NMR to calculate its structural parameters. The macromolecule of THFS contains 15.8 total ring systems with 9.2 aromatic rings and 6.6 naphthenic rings. On average, each THFS molecule contains 6.1 alcohol hydroxyl groups, 3.9 phenol hydroxyl groups, 1.4 carboxyl groups, and 1.0 inactive oxygen-containing functional groups. The dominant reactions occurred during depolymerization are the breakage of ether linkages. The average THFS molecule consists of 3.3 structural units with aromatic nuclei (2.8 rings on average) linked with methylene, naphthene, and so forth.

Color doppler ultrasound analysis of pathological myopia induced changes in retrobulbar blood flow and its relationship with characteristic changes in myopia.

Objective: To analyze changes in retrobulbar blood flow in patients with pathological myopia using color doppler ultrasound (CDU), and to explore the relationship of these changes with the characteristic changes resulting from myopia. Methods: One hundred and twenty patients who met the selection criteria in the ophthalmology department of He Eye Specialist Hospital from May 2020 to May 2022 were included in this study. Patients with normal vision (n=40) were considered Group-A, patients with low and moderate myopia (n=40) were considered Group-B, and patients with pathological myopia (n=40) were considered Group-C. All three groups underwent ultrasonography. The peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV), and resistance index (RI) of the ophthalmic artery, central retinal artery, and posterior ciliary artery were recorded and compared, and the characteristics of these parameters and myopia severity were analyzed. Results: Pathological myopia resulted in significantly lower PSV and EDV of the ophthalmic artery, central retinal artery and posterior ciliary artery and higher RI values than patients with normal vision and low/moderate myopia (P<0.05). Pearson correlation analysis showed that retrobulbar blood flow changes were significantly correlated with age, eye axis, best corrected visual acuity, and retinal choroidal atrophy. Conclusion: CDU can objectively evaluate the retrobulbar blood flow changes in pathological myopia, and such blood flow changes are significantly correlated with the characteristic changes of myopia.

Metabolic Pathway Engineering Improves Dendrobine Production in Dendrobium catenatum.

The sesquiterpene alkaloid dendrobine, widely recognized as the main active compound and a quality control standard of medicinal orchids in the Chinese Pharmacopoeia, demonstrates diverse biological functions. In this study, we engineered Dendrobium catenatum as a chassis plant for the production of dendrobine through the screening and pyramiding of key biosynthesis genes. Initially, previously predicted upstream key genes in the methyl-D-erythritol 4-phosphate (MEP) pathway for dendrobine synthesis, including 4-(Cytidine 5'-Diphospho)-2-C-Methyl-d-Erythritol Kinase (CMK), 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase (DXR), 2-C-Methyl-d-Erythritol 4-Phosphate Cytidylyltransferase (MCT), and Strictosidine Synthase 1 (STR1), and a few downstream post-modification genes, including Cytochrome P450 94C1 (CYP94C1), Branched-Chain-Amino-Acid Aminotransferase 2 (BCAT2), and Methyltransferase-like Protein 23 (METTL23), were chosen due to their deduced roles in enhancing dendrobine production. The seven genes (SG) were then stacked and transiently expressed in the leaves of D. catenatum, resulting in a dendrobine yield that was two-fold higher compared to that of the empty vector control (EV). Further, RNA-seq analysis identified Copper Methylamine Oxidase (CMEAO) as a strong candidate with predicted functions in the post-modification processes of alkaloid biosynthesis. Overexpression of CMEAO increased dendrobine content by two-fold. Additionally, co-expression analysis of the differentially expressed genes (DEGs) by weighted gene co-expression network analysis (WGCNA) retrieved one regulatory transcription factor gene MYB61. Overexpression of MYB61 increased dendrobine levels by more than two-fold in D. catenatum. In short, this work provides an efficient strategy and prospective candidates for the genetic engineering of D. catenatum to produce dendrobine, thereby improving its medicinal value.

Genome-wide identification and characterization of active ingredients related ß-Glucosidases in Dendrobium catenatum.

BACKGROUND: Dendrobium catenatum/D. officinale (here after D. catenatum), a well-known economically important traditional medicinal herb, produces a variety of bioactive metabolites including polysaccharides, alkaloids, and flavonoids with excellent pharmacological and clinical values. Although many genes associated with the biosynthesis of medicinal components have been cloned and characterized, the biosynthetic pathway, especially the downstream and regulatory pathway of major medicinal components in the herb, is far from clear. ß-glucosidases (BGLUs) comprise a diverse group of enzymes that widely exist in plants and play essential functions in cell wall modification, defense response, phytohormone signaling, secondary metabolism, herbivore resistance, and scent release by hydrolyzing ß-D-glycosidic bond from a carbohydrate moiety. The recent release of the chromosome-level reference genome of D. catenatum enables the characterization of gene families. Although the genome-wide analysis of the BGLU gene family has been successfully conducted in various plants, no systematic analysis is available for the D. catenatum. We previously isolated DcBGLU2 in the BGLU family as a key regulator for polysaccharide biosynthesis in D. catenatum. Yet, the exact number of DcBGLUs in the D. catenatum genome and their possible roles in bioactive compound production deserve more attention. RESULTS: To investigate the role of BGLUs in active metabolites production, 22 BGLUs (DcBGLU1-22) of the glycoside hydrolase family 1 (GH1) were identified from D. catenatum genome. Protein prediction showed that most of the DcBGLUs were acidic and phylogenetic analysis classified the family into four distinct clusters. The sequence alignments revealed several conserved motifs among the DcBGLU proteins and analyses of the putative signal peptides and N-glycosylation site revealed that the majority of DcBGLU members dually targeted to the vacuole and/or chloroplast. Organ-specific expression profiles and specific responses to MeJA and MF23 were also determined. Furthermore, four DcBGLUs were selected to test their involvement in metabolism regulation. Overexpression of DcBGLU2, 6, 8, and 13 significantly increased contents of flavonoid, reducing-polysaccharide, alkaloid and soluble-polysaccharide, respectively. CONCLUSION: The genome-wide systematic analysis identified candidate DcBGLU genes with possible roles in medicinal metabolites production and laid a theoretical foundation for further functional characterization and molecular breeding of D. catenatum.

Development and validation of an RNA sequencing panel for gene fusions in soft tissue sarcoma.

Gene fusions are one of the most common genomic alterations in soft tissue sarcomas (STS), which contain more than 70 subtypes. In this study, a custom-designed RNA sequencing panel including 67 genes was developed and validated to identify gene fusions in STS. In total, 92 STS samples were analyzed using the RNA panel and 95.7% (88/92) successfully passed all the quality control parameters. Fusion transcripts were detected in 60.2% (53/88) of samples, including three novel fusions (MEG3-PLAG1, SH3BP1-NTRK1, and RPSAP52-HMGA2). The panel demonstrated excellent analytic accuracy, with 93.9% sensitivity and 100% specificity. The intra-assay, inter-assay, and personnel consistencies were all 100.0% in four samples and three replicates. In addition, different variants of ESWR1-FLI, COL1A1-PDGFB, NAB2-STAT6, and SS18-SSX were also identified in the corresponding subtypes of STS. In combination with histological and molecular diagnosis, 14.8% (13/88) patients finally changed preliminary histology-based classification. Collectively, this RNA panel developed in our study shows excellent performance on RNA from formalin-fixed, paraffin-embedded samples and can complement DNA-based assay, thereby facilitating precise diagnosis and novel fusion detection.

Deep Learning Analysis of Polaritonic Wave Images.

Deep learning (DL) is an emerging analysis tool across the sciences and engineering. Encouraged by the successes of DL in revealing quantitative trends in massive imaging data, we applied this approach to nanoscale deeply subdiffractional images of propagating polaritonic waves in complex materials. Utilizing the convolutional neural network (CNN), we developed a practical protocol for the rapid regression of images that quantifies the wavelength and the quality factor of polaritonic waves. Using simulated near-field images as training data, the CNN can be made to simultaneously extract polaritonic characteristics and material parameters in a time scale that is at least 3 orders of magnitude faster than common fitting/processing procedures. The CNN-based analysis was validated by examining the experimental near-field images of charge-transfer plasmon polaritons at graphene/α-RuCl3 interfaces. Our work provides a general framework for extracting quantitative information from images generated with a variety of scanning probe methods.

Characteristics and Implications of Nanocoatings on Gouges in a Seismically Active Fault Zone.

Using a ZEISS Axio Scope A1 ordinary polarizing microscope, a ZEISS Sigma 300 scanning electron microscope and a HITACHI S4800 scanning electron microscope, we observe micro/nanocharacteristics of slip planes in gouges sampled from the Tanlu fault zone, the Haiyuan fault zone and several other Late Pleistocene active faults, such as the Haiyang fault, the Shuangshan-Lijiazhuang fault and the Xintai-Mengyin fault, in Shandong Province. Based on microscopic observation of gouges, a straight slip zone is a sign of seismic stick slipping. According to scanning electron microscopy results, the surface of gouges is commonly covered by nanocoatings. Such coatings feature nanoparticles, aggregations, scratches, grooves, cracks and "silver lines." According to the characteristics of nanomaterials, we believe that nanocoatings on gouges could help rapidly unload tectonic stress in the process of energy accumulation and weaken the strength of the active fault, which is beneficial to creep slipping and has a weakening effect on seismogenesis.

Experimental Evidence and Characteristic Recognition of the Nanoweakening of Slip Deformation Zones.

A central issue in the study of fault evolution is to identify shear weakening and its mechanism; currently, studies of fault weakening in narrow slip deformation zones, including those of various slipping planes such as schistosity, foliation, cleavage, joints and faults in rocks, are ongoing. To verify the nanoweakening in shear slipping, we carried out experiments: triaxial compression experiments on sandstones and uniaxial compression experiments on granites. Furthermore, on the basis of scanning electron microscopy (SEM) observations and experimental data analyses, we suggested three kinds of nanoweakening in terms of the corresponding strain stages: (1) The slip nanoweakening caused by the strain hardening deformation stage of the shear slip, which creates nanograins with dense coatings that may be due to the nanocoating on the shear planes, can result in rolling friction rather than with sliding friction, and the former is a principal mechanism of sliding nanoweakening. (2) The rheological nanoweakening caused by the strain softening deformation stage; in view of developing weakened deformation due to grain boundary migration (GBM), the flow of synkinematic minerals and melt coating phenomena lead to rheological nanoweakening. (3) The dynamic nanoweakening caused by thermal pressurization and fluid pressurization during the strain softening stage and strain degenerating stage. Thus, when these aspects are considered in defining the relationship between the nanoweakening at the slipping planes and the strain stages, the representative mechanism and its behavior rules can be obtained.

Gigantol Attenuates the Metastasis of Human Bladder Cancer Cells, Possibly Through Wnt/EMT Signaling.

BACKGROUND: Bladder cancer has long been recognized as one of the most common and aggressive human malignant carcinomas due to the increased invasiveness and metastasis. The discovery and development of natural compounds from Dendrobium species for cancer therapy have garnered increasing attention in recent years. Among those natural elements, the bibenzyl compound gigantol has promising therapeutic potential against several cancer cell lines; however, its roles on bladder tumor metastasis have not been investigated. MATERIALS AND METHODS: Here in this in vitro study, we utilized viability tests, cell migration, cell invasion and apoptosis assays to evaluate the anti-tumor activity of gigantol on three human bladder cancer cell lines (SW780, 5637, and T24) and a normal human bladder cell line (SVHUC-1). Cells were treated with different concentrations of gigantol (0, 40, 80, and 160 µM) for 24, 48 and 72 h. RESULTS: Here in this study, we showed that gigantol suppressed cancer cell proliferation but not normal SVHUC-1 cells. The inhibitory effect of the compound on cell migration and invasion was also exhibited in the cancer cell lines. Cell apoptosis assay by flow cytometry revealed enhanced apoptotic effects of gigantol on cancer cells. Gene expression analysis revealed that Wnt/EMT signaling might involve in the response of bladder cancer cells to gigantol. CONCLUSION: Therefore, the present data demonstrate gigantol as a strong anticancer reagent against bladder cancer possibly through Wnt/EMT signaling.

Transcriptomic Landscape of Medicinal Dendrobium Reveals Genes Associated With the Biosynthesis of Bioactive Components.

Many plants of Dendrobium genus are precious traditional herbs with high commercial value and excellent medicinal effects. They are perennial aerophytes or epiphytes of terrestrial orchids growing on cliffs and tree trunks covered with mosses in forests throughout the tropical and subtropical Asia and eastern Australia. The stem contains a variety of bioactive components, including polysaccharides and alkaloids, with strong antioxidant, neuroprotective, and immunomodulatory effects. Great attention has been drawn to the Dendrobium genus regarding its medicinal effectiveness, and the related researches have been accumulating rapidly in recent years. The bioactive components are mainly the intermediates or final products produced in specialized metabolite biosynthesis. Thus far, the activity, molecular structure, and composition of major medicinal ingredients have been partially elucidated, and the sequencing of several transcriptomes has been starting to shed new light on the biosynthesis regulation mechanism. This paper reviewed the advances of researches concerning the biosynthetic pathways of medicinal specialized metabolites from Dendrobium, especially the large number of related genes, with the hope of further promoting the development and utilization of those components and correspondingly protecting the Dendrobium resources in more effective ways.

A long way to the battlefront: CAR T cell therapy against solid cancers.

Chimeric antigen receptors (CARs) are engineered synthetic receptors that redirect and reprogram T cells to tumor surface antigens for subsequent eradication. The unprecedented efficacy of CD19-CAR T cells against B-cell malignancies has inspired oncologists to extend these efforts for the treatment of solid tumors. However, limited success has been achieved so far, partially due to some of the formidable challenges, e.g. suppression of full activation, inhibition of T cell localization, lacking of ideal targets, inefficient trafficking and infiltration, immunosuppression of microenvironment, and the probability of off targets and associated side effects. Significant progresses have being made recently. Thus, an updated summary is urgently needed. Here in this review, we discuss the advantages and some of the key hurdles encountered by CAR T cell therapy in solid tumors as well as the strategies adopted to improve therapeutic outcomes of this approach. Continuing efforts to increase therapeutic potential and decrease the adverse effects of adaptive cell transfer are suggested as well.

Extracellular matrix protein 1 (ECM1) is associated with carcinogenesis potential of human bladder cancer.

BACKGROUND: Bladder cancer (BCa) is a common urological malignant tumor worldwide, and recurrence and death still remain high. New therapeutic targets are needed to treat patients who are not sensitive to current therapy. Extracellular matrix protein 1 (ECM1) is a key player in multiple epithelial malignancies. However, the knowledge regarding the expression of ECM1 in BCa and the mechanisms by which ECM1 affects BCa tumor progression is unclear. MATERIALS AND METHODS: ECM1 expression levels in BCa tissues and cells were detected by quantitative real-time PCR (qRT-PCR), immunohistochemistry and Western blot. ECM1 expression was suppressed by shRNAs. Cell Counting Kit-8 (CCK-8), luminescent cell viability assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect cell proliferation. Flow cytometry and transwell assay were used to evaluate cell apoptosis and invasion, respectively. All statistical analyses were performed by using the GraphPad Prism 7 software package. RESULTS: In this study, the expression of ECM1 in BCa specimens and cell lines was examined and displayed a significant increase compared with noncancerous counterparts, while ECM1-knockdown affected not only cell proliferation and migration, but also cell invasion ability and apoptosis potential, corresponding to the finding that ECM1 overexpression in BCa patients was associated with a poor prognosis. Additionally, after suppression of ECM1, the expression of glucose transporter 1 (GLUT1), lactate dehydrogenase (LDHA) and hypoxia-inducible factor 1α (HIF-1α), genes involved in Warburg effect regulation, were significantly decreased, and the lactate production was also obviously reduced in ECM1-silenced cells. CONCLUSION: Our investigations revealed that the expression of ECM1 was closely associated with tumor cell growth, migration and apoptosis at least in part through regulation of Warburg effect, defining ECM1 as an effective predictor in the carcinogenesis and postoperative recurrence of human BCa.

TCP transcription factors interact with ZED1-related kinases as components of the temperature-regulated immunity.

The elevation of ambient temperature generally inhibits plant immunity, but the molecular regulations of immunity by ambient temperature in plants are largely elusive. We previously reported that the Arabidopsis HOPZ-ETI-DEFICIENT 1 (ZED1)-related kinases (ZRKs) mediate the temperature-sensitive immunity by inhibiting the transcription of SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1). Here, we further demonstrate that the nucleus-localized ZED1 and ZRKs facilitate such inhibitory role in associating with the TEOSINTE BRANCHED1, CYCLOIDEA AND PROLIFERATING CELL FACTOR (TCP) transcription factors. We show that some of TCP members could physically interact with ZRKs and are induced by elevated temperature. Disruption of TCPs leads to a mild autoimmune phenotype, whereas overexpression of the TCP15 could suppress the autoimmunity activated by the overexpressed SNC1 in the snc1-2. These findings demonstrate that the TCP transcription factors associate with nuclear ZRK as components of the temperature-regulated immunity, which discloses a possible molecular mechanism underlying the regulation of immunity by ambient temperature in plants.

Semi-synthesis of Twelve Known 20Z/E Pseudo-Ginsenosides and Their Comparative Study of Antioxidative Activity in Free Radical Induced Hemolysis of Rabbit Erythrocytes.

Twelve pseudo-ginsenosides were synthesized under a mild condition, via a simple three-step called acetylation, elimination-addition and saponification. The inhibitory effects of these twelve pseudo-ginsenosides were screened on the hemolysis of rabbit erythrocytes caused by 2,2'-azobis (2-amidinopropane hydrochloride) (AAPH). It was found that the IC50 values followed the sequence of (20Z) pseudo-protopanaxatriol (pseudo-PPT)<(20Z) pseudo-protopanaxadiol (pseudo-PPD)<(20Z) pseudo-Rh2<(20E) pseudo-PPT<(20E) pseudo-PPD<(20E) pseudo-Rh2<(20Z) pseudo-Rg2<(20E) pseudo-Rg2

Enhanced catalytic efficiency and enantioselectivity of epoxide hydrolase from Agrobacterium radiobacter AD1 by iterative saturation mutagenesis for (R)-epichlorohydrin synthesis.

Enantioselective hydrolysis of epoxides by epoxide hydrolase (EH) is one of the most attractive approaches for the synthesis of chiral epoxides. So far, attempts to develop an efficient epoxide hydrolase -mediated biotransformation have been limited by either the low activity or insufficient enantioselectivity of epoxide hydrolase. In this study, iterative saturation mutagenesis (ISM) of epoxide hydrolase from Agrobacterium radiobacter AD1 (ArEH) was performed for efficient production of (R)-epichlorohydrin. Six amino acid residues, I108, A110, D131, I133, T247, and G245, were selected for site saturation mutagenesis, and a sequential combination of positive mutants using ISM was constructed. Targeted mutagenesis generated five mutants (T247K, I108L, D131S, T247K/I108L, and T247K/I108L/D131S) with improved activity and enantioselectivity. Kinetics analysis showed that the best mutant, T247K/I108L/D131S, exhibited a 4.5-fold higher catalytic efficiency (k cat/K m) value and a 2.1-fold higher enantioselectivity (E value) towards epichlorohydrin than the wild-type (WT) enzyme. Molecular docking computations support the source of notably improved enantioselectivity. In addition, the triple mutant also displayed a significantly enhanced thermostability, with > 8-fold longer half-life at 50 °C than WT. A gram-scale kinetic resolution of (R,S)-epichlorohydrin was performed using T247K/I108L/D131S mutant as biocatalyst, affording a (R)-epichlorohydrin yield of 40.2% (> 99.9% enantiomeric excess) and an average productivity of 1410 g L-1 d-1. The engineered T247K/I108L/D131S variant is a promising biocatalyst for the enzymatic synthesis of (R)-epichlorohydrin.

Expansion of the Tibetan Plateau during the Neogene.

The appearance of detritus shed from mountain ranges along the northern margin of the Tibetan Plateau heralds the Cenozoic development of high topography. Current estimates of the age of the basal conglomerate in the Qaidam basin place this event in Paleocene-Eocene. Here we present new magnetostratigraphy and mammalian biostratigraphy that refine the onset of basin fill to ∼25.5 Myr and reveal that sediment accumulated continuously until ∼4.8 Myr. Sediment provenance implies a sustained source in the East Kunlun Shan throughout this time period. However, the appearance of detritus from the Qilian Shan at ∼12 Myr suggests emergence of topography north of the Qaidam occurred during the late Miocene. Our results imply that deformation and mountain building significantly post-date Indo-Asian collision and challenge the suggestion that the extent of the plateau has remained constant through time. Rather, our results require expansion of high topography during the past 25 Myr.

Arabidopsis ZED1-related kinases mediate the temperature-sensitive intersection of immune response and growth homeostasis.

Activation of the immune response in plants antagonizes growth and development in the absence of pathogens, and such an autoimmune phenotype is often suppressed by the elevation of ambient temperature. However, molecular regulation of the ambient temperature-sensitive intersection of immune response and growth is largely elusive. A genetic screen identified an Arabidopsis mutant, zed1-D, by its high temperature-dependent growth retardation. A combination of molecular, cytological and genetic approaches was used to investigate the molecular basis behind the temperature-sensitive growth and immune response in zed1-D. A dominant mutation in HOPZ-ETI-DEFICIENT 1 (ZED1) is responsible for a high temperature-dependent autoimmunity and growth retardation in zed1-D. The autoimmune phenotype in zed1-D is dependent on the HOPZ-ACTIVATED RESISTANCE 1 (ZAR1). ZED1 and some ZED1-related kinases (ZRKs) are induced by elevated temperature and function cooperatively to suppress the immune response by modulating the transcription of SUPPRESSOR OF NPR1-1 CONSTITUTIVE 1 (SNC1) in the absence of pathogens. Our data reveal a previously unidentified role of ZRKs in the ambient temperature-sensitive immune response in the absence of pathogens, and thus reveals a possible molecular mechanism underlying the temperature-mediated intersection of immune response and growth in plants.