TANDEM ZINC-FINGER/PLUS3 regulates phytochrome B abundance and signaling to fine-tune hypocotyl growth.

TANDEM ZINC-FINGER/PLUS3 (TZP) is a transcriptional regulator that acts at the crossroads of light and photoperiodic signaling. Here, we unveil a role for TZP in fine-tuning hypocotyl elongation under red light and long-day conditions. We provide genetic evidence for a synergistic action between TZP and PHOTOPERIODIC CONTROL OF HYPOCOTYL 1 (PCH1) in regulating the protein abundance of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and downstream gene expression in response to red light and long days (LDs). Furthermore, we show that TZP is a positive regulator of the red/far-red light receptor and thermosensor phytochrome B (phyB) by promoting phyB protein abundance, nuclear body formation, and signaling. Our data therefore assign a function to TZP in regulating two key red light signaling components, phyB and PIF4, but also uncover a new role for PCH1 in regulating hypocotyl elongation in LDs. Our findings provide a framework for the understanding of the mechanisms associated with the TZP signal integration network and their importance for optimizing plant growth and adaptation to a changing environment.

A Fluorescent Probe with Zwitterionic ESIPT Feature for Ratiometric Monitoring of Peroxynitrite In Vitro and In Vivo.

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.

Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.

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.

Theory-Guided Experimental Design of Covalent Triazine Frameworks for Efficient Photocatalytic Hydrogen Production.

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.

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

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.

Histone Deacetylase Complex 1 and histone 1 epigenetically moderate stress responsiveness of Arabidopsis thaliana seedlings.

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.

Cu(II)-Catalyzed [3 + 1 + 1 + 1] Cyclization of 1,3-Diketones and 2-Naphthols Using N,N-Dimethylethanolamine as a Dual Carbon Synthon for the Synthesis of 2H-Chromenes.

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.

Solvent-Controllable C-F Bond Activation for Masked Formylation of α-Trifluoromethyl Alkenes via Organo-Photoredox Catalysis.

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.

Direct α,ß-C-H Difunctionalization of Piperidines for the Construction of the N,O-Acetal Skeleton via 1,5-Hydride Transfer.

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.

Transition-Metal-Free Late-Stage Decarboxylative gem-Difluoroallylation of Primary Alkyl Acids.

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.

Organo-Photoredox Catalyzed gem-Difluoroallylation of Glycine and Glycine Residue in Peptides.

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.

Organo-photoredox catalyzed gem-difluoroallylation of ketone-derived dihydroquinazolinones via C(sp3)-C bond and C(sp3)-F bond cleavage.

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.

Acenaphthoimidazolylidene-Ligated Palladacycle Enabled Suzuki-Miyaura Cross-Coupling Employing Equimolar Organoboron for Tri-Ortho-Substituted Bi(hetero)aryls and Teraryls.

The Pd-catalyzed Suzuki-Miyaura cross-couplings (SMRs) are utilized as the most practical method to construct C-C bond, especial for biaryls. However, a major disadvantage of current protocols is the requirement of excess organoboron coupling partner (1.5-3.0 equiv.). Herein, a novel palladacyclic 1,3-bis(2,6-diisopropylphenyl)acenaphthoimidazol-2-ylidene (AnIPr) precatalyst possessing a chiral oxazoline was designed, which enabled a general protocol towards bulky tri-ortho-substituted biaryls, ternaphthalenes and diarylanthracenes via the Pd-catalyzed SMR employing equimolar organoborons and aryl bromides. A remarkable scope of substrates with various functional groups and heterocycles were well compatible with an adaptability to synthesize useful ligands.

Highly efficient α-arylation of aryl ketones with aryl chlorides by using bulky imidazolylidene-ligated oxazoline palladacycles.

α-Aryl derivatives of carbonyl compounds are important building blocks. Herein, we presented an efficient catalytic system for the α-arylation of aryl ketones with inactive aryl chlorides by firstly using N,N'-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene (IPr)-ligated chiral oxazoline palladacycles, and tolerated a wide range of substrates at low catalyst loadings, leading to the desired products in good to excellent yields.

Photocatalytic C-N cross-coupling mediated by heterogeneous nickel-coordinated carbon nitride.

An easy to prepare nickel-coordinated mesoporous graphitic carbon nitride (Ni-mpg-CN) was introduced as a heterogeneous photocatalyst, which efficiently accelerated the photocatalytic C-N cross-coupling of (hetero)aryl bromides and aliphatic amines, delivering the desired monoaminated products in good yields. In addition, the concise synthesis of the pharmaceutical tetracaine was accomplished in the final stage, further highlighting the practical applicability.

RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy.

BACKGROUND: Red blood cell (RBC) transfusion therapy has greatly reduced mortality and morbidity in multiply transfused patients with oncological malignancies. The aim of this study was to underline the necessity of introducing a policy for extended RBC phenotyping of these patients and for the issuing of antigen-matched blood (at least for E antigen). METHODS: Multivariate logistic regression analysis was used to evaluate the associations of age, gender, transfusion history, and various malignancies with the development of red cell alloimmunization. RESULTS: Given the results of antibody identification, we finally obtained 732 cases to be analyzed, designating them as the p group. The respiratory system (231/732; 31.6%), digestive system (273/732; 37.3%), and female reproductive system (127/732; 17.3%) had the three highest alloimmunization rates in the p group. We screened 81 cases from the p group for which antibody screening in our laboratory had historically yielded negative results. Among the 81 cases with antibody seroconversion, anti-E was the most frequently observed antibody (37%). CONCLUSIONS: The results related to multivariate logistic regression analysis of the Rh group indicate that, in contrast to the other variates, transfusion confers a strongly increased risk of Rh blood system-related red cell alloimmunization. To reduce alloimmunization in tumor patients, it will be essential to introduce a policy for extended RBC phenotyping of high-risk patients and for the issuing of antigen-matched blood (at least for E antigen).

In situ Thermal-Responsive Magnetic Hydrogel for Multidisciplinary Therapy of Hepatocellular Carcinoma.

Current surgical single modality treatments for hepatocellular carcinoma (HCC) were restricted by recurrence, blood loss, significant trauma, and poor prognostic. Although multidisciplinary strategies for HCC treatment have been highly recommended by the clinical guidelines, there was limited choice of materials and treatments. Herein, we reported an in situ formed magnetic hydrogel with promising bioapplicable thermal-responsiveness, strong adhesion in wet conditions, high magnetic hyperthermia, and biocompatibility, leading to efficient HCC multidisciplinary treatment including postoperative treatment and transarterial embolization therapy. In vivo results indicated that this hydrogel could reduce the postoperative recurrence rate. The hemostatic ability of the thermal-responsive hydrogel was further demonstrated in both the liver scratch model and liver tumor resection. Computed tomography imaging suggested that the hydrogel could completely embolize the arterial vessels of rabbit liver tumor by vascular intervention operation, which could serve as multidisciplinary responsive materials to external magnetic field and body temperature for HCC treatment.

CoS2 Nanoparticles Anchored on MoS2 Nanorods As a Superior Bifunctional Electrocatalyst Boosting Li2 O2 Heteroepitaxial Growth for Rechargeable Li-O2 Batteries.

Developing an excellent bifunctional catalyst is essential for the commercial application of Li-O2 batteries. Heterostructures exhibit great application potential in the field of energy catalysis because of the accelerated charge transfer and increased active sites on their surfaces. In this work, CoS2 nanoparticles decorated on MoS2 nanorods are constructed and act as a superior cathode catalyst for Li-O2 batteries. Coupling MoS2 and CoS2 can not only synergistically enhance their electrical conductivity and electrochemical activity, but also promote the heteroepitaxial growth of discharge products on the heterojunction interfaces, thus delivering high discharge capacity, stable cycle performance, and good rate capability.

Application of N,N-Dimethylethanolamine as a One-Carbon Synthon for the Synthesis of Pyrrolo[1,2-a]quinoxalines, Quinazolin-4-ones, and Benzo[4,5]imidazoquinazolines via [5 + 1] Annulation.

The synthesis of N-heterocycles composes a significant part of synthetic chemistry. In this report, a Cu(II)-catalyzed green and efficient synthesis of pyrrolo[1,2-a]quinoxaline, quinazolin-4-one, and benzo[4,5]imidazoquinazoline derivatives was developed, employing N,N-dimethylethanolamine (DMEA) as a C1 synthon. Green oxidant O2 is critical in these transformations, facilitating the formation of a key intermediate─a reactive iminium ion. The method conducted under mild conditions is compatible with a diversity of functional groups, providing an appealing alternative to the previously developed protocols.

Facile construction of C,N-disulfonated 5-amino pyrazoles through an iodine-catalyzed cascade reaction.

A green and facile synthesis of previously unreported C,N-disulfonated 5-amino pyrazoles was established through an iodine-catalyzed cascade reaction of easily accessible sulfonyl hydrazides, ß-ketonitriles, and sodium sulfinates. Diverse C,N-disulfonated 5-amino pyrazoles could be obtained in 38-88% yields. This methodology features green and mild conditions, broad substrate scope, and effortless work-up.