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1.
J Org Chem ; 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39377598

ABSTRACT

A transition-metal-free late-stage decarboxylative gem-difluoroallylation of carboxylic acids with α-trifluoromethyl alkenes has been described by the use of organo-photoredox catalysis. Both primary alkyl and heteroaryl acids were readily incorporated. This approach merits feedstock materials, mild reaction conditions, and wide functionality tolerance. The synthetic utility of this approach has been highlighted by the late-stage functionalization of a variety of acid-containing natural products and drug molecules.

2.
J Colloid Interface Sci ; 678(Pt A): 767-775, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39217692

ABSTRACT

Photocatalytic reduction of CO2 in pure H2O media to produce chemicals presents an appealing avenue for simultaneously alleviating energy and environmental crises. However, the rapid recombination of photogenerated charge carriers presents a significant challenge in this promising field. Heterojunction engineering has emerged as an effective approach to address this dilemma. Here, by decorating 2D NiAl-layered double hydroxides (NAL) onto bismuth oxybromide (BOB), we have created a S-scheme heterojunction (N1B1 composite). This catalyst affords CO2-to-CO yields of 102.30 µmol g-1 with a selectivity of 100 %. Ultraviolet photoelectron spectroscopy (UPS) and in-situ irradiated X-ray photoelectron spectroscopy (ISI-XPS) reveal that charge transfer occurs efficiently from BOB to 2D-NAL upon light irradiation. The designed N1B1 heterojunction achieves 7.3-fold and 2.1-fold increase in the internal electric field strength compared to bare 2D-NAL and BOB, respectively, which should be accountable for the improved charge migration. Additionally, pulsed chemisorption and in-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) show the presence of multiple carbonate intermediates with activated OCO bonds upon N1B1 composite, with *CO2- being identified as the most crucial species for CO production.

3.
J Org Chem ; 89(18): 13373-13385, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39236294

ABSTRACT

Herein, we describe an unprecedented Lewis acid-catalyzed annulation of phenols with o-aminobenzaldehydes via a cascade coupling/1,5-hydride transfer/cyclization sequence. The α- and ß-positions of cyclic amines were functionalized utilizing enamines generated in situ. A series of complex N,O-acetal derivatives are synthesized in moderate to good yields in one step. The methodology features high atom and step economy, excellent diastereoselectivity, and water as the sole byproduct.

4.
Chem Commun (Camb) ; 60(77): 10712-10715, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39239740

ABSTRACT

An unprecedented eco-friendly multi-component domino reaction for the synthesis of novel N,O-acetals is reported. The protocol involves sequential coupling, [1,5]-hydride transfer and hetero-Diels-Alder cyclization. This new strategy enables direct α,ß-difunctionalization of cyclic amines utilizing enamines generated in situ. The methodology features high atom and step economy, excellent regioselectivity, a simple work-up procedure and molecular diversity.

5.
BMC Microbiol ; 24(1): 206, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858614

ABSTRACT

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.


Subject(s)
Mutation , Mycobacterium tuberculosis , Polymorphism, Single Nucleotide , Tuberculosis , Whole Genome Sequencing , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/isolation & purification , China/epidemiology , Humans , Tuberculosis/transmission , Tuberculosis/microbiology , Tuberculosis/epidemiology , Genome, Bacterial , Female , Male , Bacterial Proteins/genetics , Adult
6.
Cancer Immunol Immunother ; 73(8): 138, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833177

ABSTRACT

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function. The combination of these three therapies-MWA, IL-21, and anti-PD-1 monoclonal antibodies (mAbs)-has yet to be explored in the context of cancer treatment.In this study, we explored the impact of thermal ablation on IL-21R expression in tumor-infiltrating lymphocytes (TILs). Subsequently, we assessed alterations in the tumor microenvironment (TME) and peripheral lymphoid organs. Additionally, we conducted a thorough examination of tumor-infiltrating CD45+ immune cells across various treatment groups using single-cell RNA sequencing (scRNA-seq). Moreover, we determined the potential anti-tumor effects of the triple combination involving MWA, IL-21, and anti-PD-1 mAbs.Our findings revealed that MWA upregulated the expression of IL-21R on various immune cells in the untreated tumors. The combination of MWA with IL-21 exhibited a robust abscopal anti-tumor effect, enhancing the effector function of CD8+ T cells and facilitating dendritic cells' maturation and antigen presentation in the untreated tumor. Notably, the observed abscopal anti-tumor effect resulting from the combination is contingent upon T-cell recirculation, indicating the reliance of systemic adaptive immunity for this treatment regimen. Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer.


Subject(s)
Immune Checkpoint Inhibitors , Interleukins , Programmed Cell Death 1 Receptor , Tumor Microenvironment , Interleukins/metabolism , Animals , Mice , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Humans , Tumor Microenvironment/immunology , Combined Modality Therapy , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Female , Neoplasms/immunology , Neoplasms/therapy , Mice, Inbred C57BL , Cell Line, Tumor
7.
Org Biomol Chem ; 22(27): 5561-5568, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38916128

ABSTRACT

An organo-photoredox catalyzed gem-difluoroallylation of both acyclic and cyclic ketone derivatives with α-trifluoromethyl alkenes has been demonstrated, thus giving access to a diverse set of gem-difluoroalkenes in moderate to high yields. Pro-aromatic dihydroquinazolinones can be either pre-formed or in situ generated for ketone activation. This reaction is characterized by readily available starting materials, mild reaction conditions, and broad substrate scope. The feasibility of this reaction has been highlighted by the late-stage modification of several natural products and drug-like molecules as well as the in vitro antifungal activity.

8.
Adv Healthc Mater ; 13(22): e2400760, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38703026

ABSTRACT

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.


Subject(s)
Fluorescence Resonance Energy Transfer , Fluorescent Dyes , Polymers , Animals , Fluorescence Resonance Energy Transfer/methods , Fluorescent Dyes/chemistry , Mice , Polymers/chemistry , Nanoparticles/chemistry , Infarction, Middle Cerebral Artery/diagnostic imaging
9.
Infect Drug Resist ; 17: 1477-1490, 2024.
Article in English | MEDLINE | ID: mdl-38634066

ABSTRACT

Purpose: To analyze the time trends in the notification rates of registered tuberculosis (TB) and bacteriologically confirmed TB in Shandong Province. And analyze the changes in TB treatment outcomes during 2005-2021. Patients and Methods: The information of TB patients registered in the Shandong Information Center for Disease Control and Prevention (CDC) was collected during 2005-2021. We calculated the notification rates of registered TB and bacteriologically confirmed TB. Moreover, we calculated the year-to-year change rate of TB in treatment outcomes before and after COVID-19. The time trends were analyzed using the joinpoint regression method and illustrated as the annual percentage change (APC) of notification rates. Results: A total of 236,898 cases of TB were diagnosed during 2005-2021, of which 51.11% were bacteriologically confirmed cases. Since 2008, the notification rates of registered TB have declined. The notification rates of bacteriologically confirmed TB had been declining during 2005-2016, then remained stable after 2016. In subgroup, the notification rates of both registered TB and bacteriologically confirmed TB were higher among men, rural residents, and people aged ≥ 60 years. Compared with clinically confirmed TB, bacteriologically confirmed TB has shown higher rates of poor outcomes since 2008 and higher case fatality rate since 2005. The rate of poor outcomes remained stable during 2008-2019. However, after the COVID-19 outbreak, the rate of poor outcomes and case fatality rate of TB has risen significantly. Conclusion: After unremitting efforts to fight against TB, the notification rates of registered TB and bacteriologically confirmed TB declined in Shandong Province. The rate of poor outcomes remained stable during 2008-2019, then rise significantly after the COVID-19 outbreak. In the context of the long-term existence of COVID-19, further efforts should be made in TB diagnosis and treatment among high-risk population, especially with regard to males, rural residents and older adults.

10.
Front Plant Sci ; 15: 1370362, 2024.
Article in English | MEDLINE | ID: mdl-38576789

ABSTRACT

Introduction: The components of nighttime sap flux (En), which include transpiration (Qn) and stem water recharge (Rn), play important roles in water balance and drought adaptation in plant communities in water-limited regions. However, the quantitative and controlling factors of En components are unclear. Methods: This study used the heat balance method to measure sap flow density in Vitex negundo on the Loess Plateau for a normal precipitation year (2021) and a wetter year (2022). Results: The results showed that the mean values were 1.04 and 2.34 g h-1 cm-2 for Qn, 0.19 and 0.45 g h-1 cm-2 for Rn in 2021 and 2022, respectively, and both variables were greater in the wetter year. The mean contributions of Qn to En were 79.76% and 83.91% in 2021 and 2022, respectively, indicating that the En was mostly used for Qn. Although the vapor pressure deficit (VPD), air temperature (Ta) and soil water content (SWC) were significantly correlated with Qn and Rn on an hourly time scale, they explained a small fraction of the variance in Qn on a daily time scale. The main driving factor was SWC between 40-200 cm on a monthly time scale for the Qn and Rn variations. Rn was little affected by meteorological and SWC factors on a daily scale. During the diurnal course, Qn and Rn initially both declined after sundown because of decreasing VPD and Ta, and Qn was significantly greater than Rn, whereas the two variables increased when VPD was nearly zero and Ta decreased, and Rn was greater than Qn. Discussion: These results provided a new understanding of ecophysiological responses and adaptation of V. negundo plantations to increasing drought severity and duration under climate changes.

11.
Small ; 20(34): e2400541, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38644221

ABSTRACT

The high crystalline covalent triazine framework-1 (CTF-1), composed of alternating triazine and phenylene, has emerged as an efficient photocatalyst for solar-driven hydrogen evolution reaction (HER). However, it is of great challenge to further improve photocatalytic HER performance via increasing crystallinity due to its near-perfect crystallization. Herein, an alternative strategy of scaffold functionalization is employed to optimize the energy band structure of crystalline CTF-1 for boosting hydrogen-evolving activity. Guided by the computational predictions, versatile CTF-based polymer photocatalysts are prepared with different functional groups (OH, NH2, COOH) using binary polymerization for practical hydrogen production. Experiment evidence verifies that the introduction of a limited number of electron-donating groups is sufficient to maintain high crystallinity in CTF, modulate the band structure, broaden visible light absorption, and consequently enhance its photophysical properties. Notably, the functionalization with OH exhibits the most positive effect on CTF-1, delivering a photocatalytic activity with a hydrogen-producing rate exceeding 100 µmol h-1.

12.
J Org Chem ; 89(6): 4056-4066, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38449357

ABSTRACT

An organo-photoredox catalyzed gem-difluoroallylation of glycine with α-trifluoromethyl alkenes via direct C(sp3)-H functionalization of glycine and C-F bond activation of α-trifluoromethyl alkenes has been described. As a consequence, a broad range of gem-difluoroalkene-containing unnatural amino acids are afforded in moderate to excellent yields. This reaction exhibits multiple merits such as readily available starting materials, broad substrate scope, and mild reaction conditions. The feasibility of this reaction has been highlighted by the late-stage modification of several peptides as well as the improved in vitro antifungal activity of compound 3v toward Valsa mali compared to that with commercial azoxystrobin.


Subject(s)
Amino Acids , Glycine , Alkenes , Peptides , Catalysis
13.
Anal Chem ; 96(8): 3600-3608, 2024 02 27.
Article in English | MEDLINE | ID: mdl-38372498

ABSTRACT

Peroxynitrite (ONOO-), as a short-term reactive biological oxidant, could lead to a series of effects in various physiological and pathological processes due to its subtle concentration changes. In vivo monitoring of ONOO- and relevant physiological processes is urgently required. Herein, we describe a novel fluorescent probe termed HBT-Fl-BnB for the ratiometric detection of ONOO- in vitro and in vivo. The probe consists of an HBT core with Fl groups at the ortho and para positions responding to the zwitterionic excited-state intramolecular proton-transfer (zwitterionic ESIPT) process and a boronic acid pinacol ester with dual roles that block the zwitterionic ESIPT and recognize ONOO-. Thanks to the specificity as well as low cytotoxicity, success in imaging of endogenous and exogenous ONOO- in living cells by HBT-Fl-BnB was obtained. Additionally, the applicability of HBT-Fl-BnB to tracking the abnormal expression of ONOO- in vivo induced by inactivated Escherichia coli was also explored. This is the first report of a fluorescent probe for ONOO- sensing via a zwitterionic ESIPT mechanism.


Subject(s)
Fluorescent Dyes , Peroxynitrous Acid , Humans , Fluorescent Dyes/toxicity , Protons , Optical Imaging , HeLa Cells
14.
Discov Oncol ; 15(1): 7, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38191842

ABSTRACT

BACKGROUND: Emerging studies have reported the contribution of cholesterol to hepatocellular carcinoma (HCC) progression. However, the specific role and mechanism of cholesterol metabolism on spontaneous and progressive HCC development from the point of view of ferroptosis are still worth exploring. The present study aimed to reveal a novel mechanism of cholesterol metabolism-related ferroptosis in hepatocellular carcinoma cells. METHODS: Two microarray datasets (GSE25097, GSE22058) related to HCC were downloaded from Gene Expression Omnibus (GEO) datasets. Metabolomics analysis was performed by ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). The cholesterol-related proteins were downloaded from HMBD. Ferroptosis-related genes were extracted from FerrDb database. Data sets were separated into two groups. GSE25097 was used to identify ferroptosis-related genes, and GSE22058 was used to verify results. During these processes, chemical-protein interaction (CPI), protein-protein interaction (PPI), the Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Multivariate logistic regression analysis was used to test the associated pathway. RESULTS: We identified 8 differentially expressed ferroptosis-related genes (HAMP, PTGS2, IL1B, ALOX15B, CDKN2A, RRM2, NQO1 and KIF20A) and 4 differentially expressed cholesterol-related genes (LCAT, CH25H, CEL and CYP7A1). Furthermore, based on the predicted results with STITCH, we identified indomethacin and IL1B as the essential node for cholesterol-mediated ferroptosis in hepatocellular carcinoma cell. Multivariate logistic regression analysis showed the activities of plasma IL1B in liver cancer patients enrolled have been significantly affected by the level of plasma cholesterol (P < 0.001) and the test result of IL1B is a predictor variable causing the changes of serum Fe levels (P < 0.001). CONCLUSIONS: Our findings shed new light on the association between cholesterol metabolism and ferroptosis in HCC, and suggest that IL1B is the necessary node for cholesterol to lead to ferroptosis process in HCC. Also, we identified the potential role of indomethacin in adjuvant therapy of HCC with complications of abnormal cholesterol metabolism.

15.
Int Immunopharmacol ; 126: 111268, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37992442

ABSTRACT

Both preclinical and clinical studies have extensively proven the effectiveness of TIGIT inhibitors in tumor immunotherapy. However, it has been discovered that the presence of CD226 on tumor-infiltrating lymphocytes is crucial for the effectiveness of both anti-TIGIT therapy alone and when combined with anti-PD-1 therapy for tumors. In our investigation, we observed that cordycepin therapy significantly augmented the expression of the Cd226 gene. As a result, it was hypothesized that cordycepin therapy could enhance the effectiveness of anti-TIGIT therapy. By employing single-cell RNA sequencing analysis of immune cells in the MC38 tumor model, we discovered that cordycepin combined with anti-TIGIT therapy led to a significant increase in the proportion of NK cells within the tumor immune microenvironment. This increased NK cell activity and decreased the expression of inhibitory receptors and exhaustion marker genes. In the combination therapy group, CD8+ T cells had lower exhaustion state scores and increased cytotoxicity, indicating a better immune response. The combination therapy group increased DCs in the tumor immune microenvironment and promoted cellular interaction with CD4+ T cell and CD8+ T cell populations while decreasing Treg cell interactions. In conclusion, cordycepin with anti-TIGIT therapy in colon cancer could reshape the tumor immune microenvironment and have notable anticancer effects.


Subject(s)
CD8-Positive T-Lymphocytes , Colonic Neoplasms , Humans , Receptors, Immunologic/metabolism , Sequence Analysis, RNA , Tumor Microenvironment
16.
J Org Chem ; 89(1): 152-162, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38086005

ABSTRACT

Reactions with diverse C1 synthons to realize homologation were well explored. However, homologations occurring twice with one C1 synthon in a reaction were less reported. We disclose herein a Cu(II)-catalyzed novel and efficient synthesis of 2H-chromenes from 2-naphthols, 1,3-diketones, and N,N-dimethylethanolamine (DMEA) as a dual carbon synthon. Various 2H-chromenes with different functional groups are constructed in moderate to good yields. This is the first report that DMEA acts as a dual C1 synthon.

17.
Int J Infect Dis ; 140: 124-131, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37863309

ABSTRACT

OBJECTIVES: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. METHODS: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. RESULTS: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. CONCLUSIONS: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Humans , Phylogeny , Phylogeography , Genotype , Tuberculosis/epidemiology , Tuberculosis/microbiology , China/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology
18.
J Org Chem ; 89(1): 624-632, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38115588

ABSTRACT

A solvent-controllable organo-photoredox-catalyzed C-F bond activation for masked formylation of α-trifluoromethyl alkenes with low-priced 1,3-dioxolane as masked formyl radical equivalent has been described. Consequently, a diversity of masked formylated gem-difluoroalkenes and monofluoroalkenes are constructed in moderate to high yields. This approach merits readily available starting materials, mild reaction conditions, and broad substrate scope. The feasibility of this approach has been highlighted by the one-pot masked formylation/hydrolysis sequence to form γ,γ-difluoroallylic aldehydes and late-stage modification of pharmaceutical and natural product derivatives.

19.
New Phytol ; 241(1): 166-179, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37565540

ABSTRACT

Early responses of plants to environmental stress factors prevent damage but can delay growth and development in fluctuating conditions. Optimising these trade-offs requires tunability of plant responsiveness to environmental signals. We have previously reported that Histone Deacetylase Complex 1 (HDC1), which interacts with multiple proteins in histone deacetylation complexes, regulates the stress responsiveness of Arabidopsis seedlings, but the underlying mechanism remained elusive. Here, we show that HDC1 attenuates transcriptome re-programming in salt-treated seedlings, and we identify two genes (LEA and MAF5) that inhibit seedling establishment under salt stress downstream of HDC1. HDC1 attenuates their transcriptional induction by salt via a dual mechanism involving H3K9/14 deacetylation and H3K27 trimethylation. The latter, but not the former, was also abolished in a triple knockout mutant of the linker histone H1, which partially mimics the hypersensitivity of the hdc1-1 mutant to salt stress. Although stress-induced H3K27me3 accumulation required both H1 and HDC1, it was not fully recovered by complementing hdc1-1 with a truncated, H1-binding competent HDC1 suggesting other players or independent inputs. The combined findings reveal a dual brake function of HDC1 via regulating both active and repressive epigenetic marks on stress-inducible genes. This natural 'anti-panic' device offers a molecular leaver to tune stress responsiveness in plants.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Histones/metabolism , Seedlings , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Gene Expression Regulation, Plant
20.
Org Lett ; 26(1): 22-28, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38127726

ABSTRACT

An efficient catalytic strategy toward the synthesis of N-substituted 3-methylindoles from inactive o-dihaloarenes and N-allylamines was developed by using a 1,3-bis(2,6-diisopropylphenyl)acenaphthoimidazol-2-ylidene (AnIPr)-ligated oxazoline palladacycle. It enabled a very broad substrate scope tolerating different functional groups, electronic properties, and steric bulkiness and afforded desired products in good to excellent yields. Importantly, it showed great potential to synthesize several bioactive compounds and key intermediates of natural products in high yields.

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