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• Sessile plants constantly experience environmental stresses in nature. They must have evolved effective mechanisms to balance growth with stress response. Here we report the MADS-box transcription factor AGL16 acting as a negative regulator in stress response in Arabidopsis. • Loss-of-AGL16 confers resistance to salt stress in seed germination, root elongation and soil-grown plants, while elevated AGL16 expression confers the opposite phenotypes compared with wild-type. However, the sensitivity to abscisic acid (ABA) in seed germination is inversely correlated with AGL16 expression levels. • Transcriptomic comparison revealed that the improved salt resistance of agl16 mutants was largely attributed to enhanced expression of stress-responsive transcriptional factors and the genes involved in ABA signalling and ion homeostasis. We further demonstrated that AGL16 directly binds to the CArG motifs in the promoter of HKT1;1, HsfA6a and MYB102 and represses their expression. Genetic analyses with double mutants also support that HsfA6a and MYB102 are target genes of AGL16. • Taken together, our results show that AGL16 acts as a negative regulator transcriptionally suppressing key components in the stress response and may play a role in balancing stress response with growth.

Difluoromethylated aromatic compounds are of increasing importance in pharmaceuticals, agrochemicals and materials. Chlorodifluoromethane (ClCF 2 H), an inexpensive, abundant and widely used industrial raw material, represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF 2 H) from ClCF 2 H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF 2 H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate scope, including heteroarylboronic acids, and was used for difluoromethylation of a range of pharmaceuticals and biologically active compounds. Preliminary mechanistic studies revealed that a palladium difluorocarbene intermediate is involved in the reaction. Although numerous metal–difluorocarbene complexes have been prepared, the catalytic synthesis of difluoromethylated or difluoromethylenated compounds involving metal–difluorocarbene complexes has not received much attention. This new reaction therefore also opens the door to understand metal–difluorocarbene complex catalysed reactions. Chlorodifluoromethane (ClCF 2 H), an inexpensive and abundant industrial raw material, represents an ideal and straightforward reagent for introducing the difluoromethyl group. However, efficient approaches for activation of the typically inert ClCF 2 H are limited. Now, ClCF 2 H is employed via a difluorocarbene pathway for palladium-catalysed difluoromethylation of arylboronic acids with broad substrate scope.

As sessile organisms, plants must be highly adaptable to the changing environment by modifying their growth and development. Plants rely on their underground part, the root system, to absorb water and nutrients and to anchor to the ground. The root is a highly dynamic organ of indeterminate growth with new tissues produced by root stem cells. Plants have evolved unique molecular mechanisms to fine-tune root developmental processes, during which phytohormones play vital roles. These hormones often relay environmental signals to auxin signaling that ultimately directs root development programs. Therefore, the crosstalk among hormones is critical in the root development. In this review, we will focus on the recent progresses that jasmonic acid (JA) and ethylene signaling are integrated into auxin in regulating root development of and discuss the key roles of transcription factors (TFs) ethylene response factors (ERFs) and homeobox proteins in the crosstalk.

Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity 1 , 2 . Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies 3 to convert these renewable feedstocks into reagents (glycosyl donors) to make glycans. The direct transformation of native sugars to complex saccharides remains a notable challenge. Here we describe a photoinduced approach to achieve site- and stereoselective chemical glycosylation from widely available native sugar building blocks, which through homolytic (one-electron) chemistry bypasses unnecessary hydroxyl group masking and manipulation. This process is reminiscent of nature in its regiocontrolled generation of a transient glycosyl donor, followed by radical-based cross-coupling with electrophiles on activation with light. Through selective anomeric functionalization of mono- and oligosaccharides, this protecting-group-free ‘cap and glycosylate’ approach offers straightforward access to a wide array of metabolically robust glycosyl compounds. Owing to its biocompatibility, the method was extended to the direct post-translational glycosylation of proteins. A radical-based method for functionalizing native sugars shows a way to remove typical protecting-group manipulations.

Improvement of crop drought resistance and water-use efficiency (WUE) has been a major endeavor in agriculture. Arabidopsis ENHANCED DROUGHT TOLERANCE1/HOMEODOMAIN GLABROUS11 (AtEDT1/HDG11), a homeodomain-START transcription factor we previously identified from the enhanced drought tolerance1 mutant (edt1), has been demonstrated to improve drought tolerance and WUE significantly in multiple plant species when constitutively overexpressed. Here, we report the genetic evidence suggesting a genetic pathway, which consists of EDT1/HDG11, ERECTA, and E2Fa loci, and regulates WUE by modulating stomatal density. AtEDT1/HDG11 transcriptionally activates ERECTA by binding to homeodomain-binding (HD) cis-elements in the ERECTA promoter. ERECTA, in turn, depends on E2Fa to modulate the expression of cell cycle-related genes. This modulation affects the transition from mitosis to endocycle, leading to increased ploidy levels in leaf cells, and therefore increased cell size and decreased stomatal density. Our results suggest a possible EDT1/HDG11-ERECTA-E2Fa genetic pathway that reduces stomatal density by increasing cell size and provide a new avenue to improve WUE of crops.

Difluorocarbene has important applications in pharmaceuticals, agrochemicals and materials, but all these applications proceed using just a few types of reaction by taking advantage of its intrinsic electrophilicity. Here, we report a palladium-catalysed strategy that confers the formed palladium difluorocarbene (Pd=CF 2 ) species with both nucleophilicity and electrophilicity by switching the valence state of the palladium centre (Pd(0) and Pd( ii ), respectively). Controllable catalytic difluorocarbene transfer occurs between readily available arylboronic acids and the difluorocarbene precursor diethyl bromodifluoromethylphosphonate (BrCF 2 PO(OEt) 2 ). From just this simple fluorine source, difluorocarbene transfer enables access to four types of product: difluoromethylated and tetrafluoroethylated arenes and their corresponding fluoroalkylated ketones. The transfer can also be applied to the modification of pharmaceuticals and agrochemicals as well as the one-pot diversified synthesis of fluorinated compounds. Mechanistic and computational studies consistently reveal that competition between nucleophilic and electrophilic palladium difluorocarbene ([Pd]=CF 2 ) is the key factor controlling the catalytic difluorocarbene transfer. Difluorocarbene transfer is mostly limited to reactions that utilize its intrinsic electrophilicity. Now, a controllable palladium-catalysed difluorocarbene transfer reaction is reported that involves nucleophilic and electrophilic palladium difluorocarbene species. The selective reactions between arylboronic acids and the difluorocarbene precursor BrCF 2 PO(OEt) 2 give four different products—difluoromethylated and tetrafluoroethylated arenes and their corresponding fluoroalkylated ketones.

Checkpoint blockade antibodies have been approved as immunotherapy for multiple types of cancer, but the response rate and efficacy are still limited. There are few immunogenic cell death (ICD)-inducing drugs available that can kill cancer cells, enhance tumor immunogenicity, increase the in vivo immune infiltration, and thereby boosting a tumor response to immunotherapy. So far, the ICD markers have been identified as the few immuno-stimulating characteristics of dead cells, but whether the presence of such ICD markers on tumor cells translates into enhanced antitumor immunity in vivo is still investigational. To identify anticancer drugs that could induce tumor cell death and boost T cell response, we performed drug screenings based on both an ICD reporter assay and T cell activation assay. We identified that teniposide, a DNA topoisomerase II inhibitor, could induce high mobility group box 1 (HMGB1) release and type I interferon signaling in tumor cells, and teniposide-treated tumor cells could activate antitumor T cell response both in vitro and in vivo. Mechanistically, teniposide induced tumor cell DNA damage and innate immune signaling including NF-κB activation and STING-dependent type I interferon signaling, both of which contribute to the activation of dendritic cells and subsequent T cells. Furthermore, teniposide potentiated the antitumor efficacy of anti-PD1 on multiple types of mouse tumor models. Our findings showed that teniposide could trigger tumor immunogenicity, and enabled a potential chemo-immunotherapeutic approach to potentiate the therapeutic efficacy of anti-PD1 immunotherapy.

Jasmonic acid (JA) is well known to promote lateral root formation but the mechanisms by which JA signalling is integrated into the pathways responsible for lateral root formation, and how it interacts with auxin in this process remains poorly understood. Here, we report that the highly JA-responsive ethylene response factor 109 (ERF109) mediates cross-talk between JA signalling and auxin biosynthesis to regulate lateral root formation in Arabidopsis . erf109 mutants have fewer lateral roots under MeJA treatments compared with wild type whereas ERF109 overexpression causes a root phenotype that resembles those of auxin overproduction mutants. ERF109 binds directly to GCC-boxes in the promoters of ASA1 and YUC2 , which encode two key enzymes in auxin biosynthesis. Thus, our study reveals a molecular mechanism for JA and auxin cross-talk during JA-induced lateral root formation. Jasmonic acid induces lateral root formation in Arabidopsis by promoting auxin biosynthesis. Here, Cai et al . identify a jasmonate-induced transcription factor that regulates the expression of two auxin biosynthetic enzymes revealing a molecular mechanism for hormonal cross-talk in the root.

Background Systemic inflammation and immune dysfunction has been proved to be significantly associated with cancer progression and metastasis in many cancer types, including colorectal cancer. We examined the prognostic significance of the systemic immune-inflammation index (SII) in patients with metastatic colorectal cancer (mCRC) and the relationship between the lymphocytic response to the tumor and this index. Methods This retrospective study evaluated 240 consecutive patients with newly diagnosed stage IV mCRC who underwent surgical resection. The SII values were calculated based on preoperative laboratory data regarding platelet, neutrophil, and lymphocyte counts. Tumor-infiltrating lymphocytes were evaluated using the surgical specimens. The overall survival and their 95% confidence interval (95% CI) were estimated by regression analyses and the Kaplan–Meier method. Results After a mean follow-up of 26.7 (1.1–92.4) months, 146 patients (60.8%) died. In the univariate analysis, a high SII was significantly associated with poor overall survival ( P  = 0.009). The multivariable analysis also confirmed that a high SII was independently associated with poor overall survival (hazard ratio: 1.462, 95% confidence interval 1.049–2.038, P  = 0.025). The SII value was significantly correlated with the TILs value at the tumor’s center ( P  = 0.04), but not at the invasive margin ( P  = 0.39). When we evaluated overall survival for groupings of the tumor-infiltrating lymphocytes and SII values, we identified three distinct prognostic groups. The group with low tumor-infiltrating lymphocyte values and high SII values had the worst prognosis. Conclusions A high SII value independently predicts poor clinical outcomes among patients with mCRC. In addition, combining the lymphocytic response to the tumor and SII could further enhance prognostication for mCRC.

Silicic magmas are the most viscous of all magmas, however some granitic plutons display remarkably homogeneous compositions, which contradicts the hypothesis that mechanical mixing is the main homogenizing process in the magma chamber. Thus much remains controversial about the mechanisms responsible for the homogeneities of silicic plutons. Here, we present textural observations, elemental mapping, and in situ elemental and Nd‐O isotopic data of apatites from the compositionally homogeneous Late Permian Yuanyang A‐type granitic pluton (SW Yunnan, South China). Apatite grains display oscillatory chemical zonation and resorption‐precipitation texture, suggesting incremental growth dominated by co‐genetic magma batches injection. The intra‐/inter‐grain core to rim elemental and Nd‐O isotopic variations imply crystal transfer and crystallization from different melt domains within the crystal mush. We propose that rejuvenation events associated with hotter cogenetic intermediate magma batch injection has induced crystal mush reactivation and convective stirring in silicic magma chambers, thereby homogenizing the entire reservoir. Plain Language Summary Magma mixing between mafic and viscous felsic magmas is usually incomplete, forming heterogeneous structures and geochemical compositions in felsic magma bodies. However, some silicic magma bodies have homogeneous compositions and structures, such as the Late Permian Yuanyang A‐type granites (YAGs) in southwestern South China, and the actual homogenizing process in silicic magma chamber is still unclear. Accessory apatite is ubiquitous in felsic plutons, whose growth zoning could reflect magma chamber evolution. Apatite grains collected from the YAGs show complex resorption‐precipitation texture. Their core‐rim oscillatory elemental and Nd‐O isotopic variations suggest compositional perturbations of ambient magma, probably caused by the injection/mixing of multiple magma pulses. Accordingly, we propose that hot magma recharge could reactivate the crystal‐mush, causing magma convection and stirring that gradually homogenized the silicic magma chamber. Key Points The apatites from the compositionally homogeneous Yuanyang A‐type granites are texturally and geochemically heterogeneous The identified four apatite zoning domains documented magma replenishment, mixing and crystal mush reactivation Magma convection and stirring induced by magma batches injection are key to homogenizing the silicic magma chamber