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Organohalides are vital organic building blocks with applications spanning various fields. However, direct halogenation of certain neutral or unreactive substrates by using solely the regular halogenating reagents has proven challenging. Although various halogenation approaches via activating halogenating reagents or substrates have emerged, a catalytic system enabling broad substrate applicability and diverse halogenation types remains relatively underexplored. Inspired by the halogenation of arenes via thianthrenation of arenes, here we report that thianthrene, in combined use with trifluoromethanesulfonic acid (TfOH), could work as an effective catalytic system to activate regular halogenating reagents (NXS). This new protocol could accomplish multiple types of halogenation of organic compounds including aromatics, olefins, alkynes and ketones. The mechanism study indicated that a highly reactive electrophilic halogen thianthrenium species, formed in situ from the reaction of NXS with thianthrene in the presence of TfOH, was crucial for the efficient halogenation process.
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The existing hypervalent I(III) reagents bearing ONO2 group are limited in types and their applications primarily focused on the nitrooxylation reactions featuring a fully-exo fashion. Herein, a benziodazole-type O2NO-I(III) compound was prepared and its reaction with ß-monosubstituted enamines in the presence of CuI could trigger a radical nitration/cyclization/dehydration cascade to provide a series of less explored but biologically interesting furazan heterocycles. Mechanistically, the benziodazole-type O2NO-I(III) compound acts as a nitrating reagent and incorporates its NO moiety into the final furazan product in a fully-endo model, a process of which was proposed to involve nitration, cyclization and dehydration.
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A series of 4-thio/seleno-cyanated pyrazoles was conveniently synthesized from 4-unsubstituted pyrazoles using NH4SCN/KSeCN as thio/selenocyanogen sources and PhICl2 as the hypervalent iodine oxidant. This metal-free approach was postulated to involve the in situ generation of reactive thio/selenocyanogen chloride (Cl-SCN/SeCN) from the reaction of PhICl2 and NH4SCN/KSeCN, followed by an electrophilic thio/selenocyanation of the pyrazole skeleton.
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Background: The agreement on the identification of sarcopenic obesity remains elusive, and its association with hyperuricemia remains unestablished. This study sought to evaluate the agreement of low lean mass (LLM) with obesity and its correlation with hyperuricemia. Methods: A total of 25,252 study participants, comprising 4,597 individuals with hyperuricemia, were obtained from the National Health and Nutrition Examination Survey spanning the years 1999-2006 and 2011-2018. LLM with obesity was characterized by the coexistence of LLM, determined by the ratio of appendicular lean mass to body mass index (BMI), and three categories of obesity including BMI, body fat percentage (BF%), and waist circumference (WC). We employed Cohen's kappa to evaluate the agreement among the different diagnostic criteria and implemented survey multiple logistic regression and stratified analyses to explicate the connection between LLM with obesity and the risk of hyperuricemia. Results: When defining obesity using BF%, BMI, and WC, the prevalence of LLM with obesity varied from 6.6 to 10.1%, with moderate-to-strong agreement. In the fully adjusted model, individuals with LLM or any of the three types of obesity exhibited notably elevated odds of developing hyperuricemia. Likewise, participants with LLM and obesity had 2.70 (LLM + BMI), 2.44 (LLM + BF%), and 3.12 (LLM + WC) times the risk of hyperuricemia, respectively, compared with healthy individuals. The association between LLM with obesity and hyperuricemia remained stable and significant across different age and sex subgroups. Conclusion: When employing the three definitions of obesity, the incidence of LLM with obesity was not high, and the diagnostic agreement was relatively good. The participants with LLM and obesity exhibited an increased risk of hyperuricemia.
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The combining use of BnSCF2D, mCPBA and Tf2O serves as an efficient multi-component reagents system (MCRS) for the synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines/isocoumarins via intramolecular cyclization/deuteriodifluoromethylthiolation of 2-alkynylbenzamides/2-alkynylbenzoates. The approach features the generation of the crucial reactive electrophilic sulfonium salt through a sequence process involving the oxidation of BnSCF2D by mCPBA followed by Tf2O promoted activation.
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The removal of tetracycline from the sewage plant effluents through advanced treatment methods is key to controlling tetracycline levels in the water environment. In this study, modified quartz sands (QS) were used in a biological sand filter to remove tetracycline. The modified QS, with different surface characteristics, were prepared using glass etching technology combined with subsequent chemical modification methods, including hydroxylation treatment, metal ion modification, and amino modification. The adsorption efficiency of hydroxylated QS was higher than that of metal ion modified and amino modified QS, with adsorption efficiencies of 20.4331 mg/kg, 12.8736 mg/kg, and 10.1737 mg/kg, respectively. Results indicated that QS primarily reduce tetracycline through adsorption. Adsorption on ordinary QS fit the pseudo-first-order kinetic model, while adsorption on other modified QS and biofilm-coated QS fit the pseudo-second-order kinetics model. Biodegradation was identified as another mechanism for tetracycline reduction, which fit the zero-order kinetic model. Pseudomonas alcaligenes and unclassified Pseudomonas accounted for 96.6% of the total tetracycline-degrading bacteria. This study elucidates the effectiveness and mechanisms of five types of QS in treating tetracycline from sewage plant effluents. It provides a novel method for tetracycline reduction in real-world wastewater scenarios.
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Esgotos , Poluentes Químicos da Água , Esgotos/química , Antibacterianos , Tetraciclina , Águas Residuárias , Metais , Poluentes Químicos da Água/química , Adsorção , CinéticaRESUMO
Indole is a prestigious heterocyclic skeleton widely found in both naturally-occurring and biologically-active compounds. Pharmaceutical agents containing an indole skeleton in their framework possess a wide range of pharmacological properties, including antiviral, antitumor, analgesic, and other therapeutic activities, and many indole-containing drugs have been proven to have excellent pharmacokinetic and pharmacological effects. Over the past few decades, the FDA has approved over 40 indole-containing drugs for the treatment of various clinical conditions, and the development of indole-related drugs has attracted significant attention from medicinal chemists. This review aims to provide an overview of all the approved drugs that contain an indole nucleus, focusing on their targets, pharmacological activities, and SAR studies.
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The application of the DMSO/SOCl2 system enabled the intramolecular cyclization/chlorination of N,N-disubstituted 2-alkynylanilines, leading to the synthesis of a series of 3-chloroindoles with moderate to good yields. Differing from the previously reported interrupted Pummerer reaction featuring the introduction of SMe moiety, the current approach adopted an alternative pathway that realized the incorporation of chlorine atom to the indole skeleton via a desulfonylative chlorocyclization process.
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Interleukin 35(IL-35) is a newly discovered inhibitory cytokine of the IL12 family. More recently, IL-35 was found to be increased in the tumor microenvironment (TME) and peripheral blood of many patients with cancer, indicating that it plays an important role in the TME. Tumors secrete cytokines that recruit myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg) into the TME to promote malignant progression, which is a great challenge for cancer treatment. Radiotherapy causes serious adverse effects, and tumor resistance to immune checkpoint inhibitors is still an unsolved challenge. Thus, new cancer therapy approaches are urgently needed. Numerous studies have shown that IL-35 can recruit immunosuppressive cells to enable tumor immune escape by promoting the conversion of immune cells into a tumor growth-promoting phenotype as well as facilitating tumor angiogenesis. IL-35-neutralizing antibodies were found to boost the chemotherapeutic effect of gemcitabine and considerably reduce the microvascular density of pancreatic cancer in mice. Therefore, targeting IL-35 in the TME provides a promising cancer treatment target. In addition, IL-35 may be used as an independent prognostic factor for some tumors in the near future. This review intends to reveal the interplay of IL-35 with immune cells in the TME, which may provide new options for the treatment of cancer.
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Neoplasias , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Microambiente Tumoral , Imunoterapia , Neoplasias/tratamento farmacológico , Citocinas/farmacologia , InterleucinasRESUMO
An array of biologically interesting tri/difluoromethylated chromones and their heteroatom analogues were conveniently synthesized from the reaction of chromones and their heteroatom analogues with CF3SO2Na or HCF2SO2Na in the presence of tert-butyl hydroperoxide under mild conditions. A mechanistic pathway involving the generation of the electrophilic tri/difluoromethyl radical, followed with the radical substitution of chromones and their heteroatom analogues, was postulated.
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In this paper, we work on the discrete modified Leslie type predator-prey model with Holling type II functional response. The existence and local stability of the fixed points of this system are studied. According to bifurcation theory and normal forms, we investigate the codimension 1 and 2 bifurcations of positive fixed points, including the fold, 1:1 strong resonance, fold-flip and 1:2 strong resonance bifurcations. In particular, the discussion of discrete codimension 2 bifurcation is rare and difficult. Our work can be seen as an attempt to complement existing research on this topic. In addition, numerical analysis is used to demonstrate the correctness of the theoretical results. Our analysis of this discrete system revealed quite different dynamical behaviors than the continuous one.
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BACKGROUND: Alternative splicing (AS), a posttranscriptional process, contributes to the complexity of transcripts from a limited number of genes in a genome, and AS is considered a great source of genetic and phenotypic diversity in eukaryotes. In animals, AS is tightly regulated during the processes of cell growth and differentiation, and its dysregulation is involved in many diseases, including cancers. Likewise, in plants, AS occurs in all stages of plant growth and development, and it seems to play important roles in the rapid reprogramming of genes in response to environmental stressors. To date, the prevalence and functional roles of AS have been extensively reviewed in animals and plants. However, AS differences between animals and plants, especially their underlying molecular mechanisms and impact factors, are anecdotal and rarely reviewed. AIM OF REVIEW: This review aims to broaden our understanding of AS roles in a variety of biological processes and provide insights into the underlying mechanisms and impact factors likely leading to AS differences between animals and plants. KEY SCIENTIFIC CONCEPTS OF REVIEW: We briefly summarize the roles of AS regulation in physiological and biochemical activities in animals and plants. Then, we underline the differences in the process of AS between plants and animals and especially analyze the potential impact factors, such as gene exon/intron architecture, 5'/3' untranslated regions (UTRs), spliceosome components, chromatin dynamics and transcription speeds, splicing factors [serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs)], noncoding RNAs, and environmental stimuli, which might lead to the differences. Moreover, we compare the nonsense-mediated mRNA decay (NMD)-mediated turnover of the transcripts with a premature termination codon (PTC) in animals and plants. Finally, we summarize the current AS knowledge published in animals versus plants and discuss the potential development of disease therapies and superior crops in the future.
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C-repeat binding factors (CBFs) are well-known transcription factors (TFs) that regulate plant cold acclimation. RNA sequencing (RNA-seq) data from diverse plant species provide opportunities to identify other TFs involved in the cold response. However, this task is challenging because gene gain and loss has led to an intertwined community of co-orthologs and in-paralogs between and within species. Using orthogroup (closely related homologs) analysis, we identified 10,549 orthogroups in five representative eudicots. A phylotranscriptomic analysis of cold-treated seedlings from eudicots identified 35 high-confidence conserved cold-responsive transcription factor orthogroups (CoCoFos). These 35 CoCoFos included the well-known cold-responsive regulators CBFs, HSFC1, ZAT6/10, and CZF1 among others. We used Arabidopsis BBX29 for experimental validation. Expression and genetic analyses showed that cold-induction of BBX29 is CBF- and abscisic acid-independent, and BBX29 is a negative regulator of cold tolerance. Integrative RNA-seq and Cleavage Under Targets and Tagmentation followed by sequencing analyses revealed that BBX29 represses a set of cold-induced TFs (ZAT12, PRR9, RVE1, MYB96, etc.). Altogether, our analysis yielded a library of eudicot CoCoFos and demonstrated that BBX29 is a negative regulator of cold tolerance in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Aclimatação/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sequência de Bases , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
A metal-free synthesis of a series of fluoroalkyl-containing oxazoles from ß-monosubstituted enamines was developed. This fluoroacyloxylation/cyclization cascade process was mediated by fluoroalkyl-containing hypervalent iodine(III) species formed in situ from the reaction of phenyliodine(III) diacetate (PIDA) and RCF2CO2H (R = H, Cl, Br, F, CF3, CH3, Ph, SAr, OAr).
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Sulfoquinovose (SQ, 6-deoxy-6-sulfo-glucose) constitutes the polar head group of plant sulfolipids and is one of the most abundantly produced organosulfur compounds in nature. Degradation of SQ by bacterial communities contributes to sulfur recycling in many environments. Bacteria have evolved at least four mechanisms for glycolytic degradation of SQ, termed sulfoglycolysis, producing C3 sulfonate (dihydroxypropanesulfonate and sulfolactate) and C2 sulfonate (isethionate) by-products. These sulfonates are further degraded by other bacteria, leading to the mineralization of the sulfonate sulfur. The C2 sulfonate sulfoacetate is widespread in the environment and is also thought to be a product of sulfoglycolysis, although the mechanistic details are yet unknown. Here, we describe a gene cluster in an Acholeplasma sp., from a metagenome derived from deeply circulating subsurface aquifer fluids (GenBank accession no. QZKD01000037), encoding a variant of the recently discovered sulfoglycolytic transketolase (sulfo-TK) pathway that produces sulfoacetate instead of isethionate as a by-product. We report the biochemical characterization of a coenzyme A (CoA)-acylating sulfoacetaldehyde dehydrogenase (SqwD) and an ADP-forming sulfoacetate-CoA ligase (SqwKL), which collectively catalyze the oxidation of the transketolase product sulfoacetaldehyde into sulfoacetate, coupled with ATP formation. A bioinformatics study revealed the presence of this sulfo-TK variant in phylogenetically diverse bacteria, adding to the variety of mechanisms by which bacteria metabolize this ubiquitous sulfo-sugar. IMPORTANCE Many bacteria utilize environmentally widespread C2 sulfonate sulfoacetate as a sulfur source, and the disease-linked human gut sulfate- and sulfite-reducing bacteria can use it as a terminal electron receptor for anaerobic respiration generating toxic H2S. However, the mechanism of sulfoacetate formation is unknown, although it has been proposed that sulfoacetate originates from bacterial degradation of sulfoquinovose (SQ), the polar head group of sulfolipids present in all green plants. Here, we describe a variant of the recently discovered sulfoglycolytic transketolase (sulfo-TK) pathway. Unlike the regular sulfo-TK pathway that produces isethionate, our biochemical assays with recombinant proteins demonstrated that a CoA-acylating sulfoacetaldehyde dehydrogenase (SqwD) and an ADP-forming sulfoacetate-CoA ligase (SqwKL) in this variant pathway collectively catalyze the oxidation of the transketolase product sulfoacetaldehyde into sulfoacetate, coupled with ATP formation. A bioinformatics study revealed the presence of this sulfo-TK variant in phylogenetically diverse bacteria and interpreted the widespread existence of sulfoacetate.
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Bactérias , Transcetolase , Humanos , Bactérias/genética , Bactérias/metabolismo , Alcanossulfonatos/metabolismo , Oxirredutases , Trifosfato de Adenosina , Enxofre/metabolismo , LigasesRESUMO
The obligately anaerobic sulfite-reducing bacterium Bilophila wadsworthia is a common human pathobiont inhabiting the distal intestinal tract. It has a unique ability to utilize a diverse range of food- and host-derived sulfonates to generate sulfite as a terminal electron acceptor (TEA) for anaerobic respiration, converting the sulfonate sulfur to H2S, implicated in inflammatory conditions and colon cancer. The biochemical pathways involved in the metabolism of the C2 sulfonates isethionate and taurine by B. wadsworthia were recently reported. However, its mechanism for metabolizing sulfoacetate, another prevalent C2 sulfonate, remained unknown. Here, we report bioinformatics investigations and in vitro biochemical assays that uncover the molecular basis for the utilization of sulfoacetate as a source of TEA (STEA) for B. wadsworthia, involving conversion to sulfoacetyl-CoA by an ADP-forming sulfoacetate-CoA ligase (SauCD), and stepwise reduction to isethionate by NAD(P)H-dependent enzymes sulfoacetaldehyde dehydrogenase (SauS) and sulfoacetaldehyde reductase (TauF). Isethionate is then cleaved by the O2-sensitive isethionate sulfolyase (IseG), releasing sulfite for dissimilatory reduction to H2S. Sulfoacetate in different environments originates from anthropogenic sources such as detergents, and natural sources such as bacterial metabolism of the highly abundant organosulfonates sulfoquinovose and taurine. Identification of enzymes for anaerobic degradation of this relatively inert and electron-deficient C2 sulfonate provides further insights into sulfur recycling in the anaerobic biosphere, including the human gut microbiome.
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Bilophila , Humanos , Alcanossulfonatos/metabolismo , Bilophila/metabolismo , Sulfitos/metabolismo , Enxofre/metabolismo , Taurina/metabolismo , Microbioma GastrointestinalRESUMO
Angiosperms are one of the most diverse and abundant plant groups that are widely distributed on Earth, from tropical to temperate and polar zones. The wide distribution of angiosperms may be attributed to the evolution of sophisticated mechanisms of environmental adaptability, including cold tolerance. Since the development of high-throughput sequencing, transcriptome has been widely utilized to gain insights into the molecular mechanisms of plants in response to cold stress. However, previous studies generally focused on single or two species, and comparative transcriptome analyses for multispecies responding to cold stress were limited. In this study, we selected 11 representative angiosperm species, performed phylotranscriptome experiments at four time points before and after cold stress, and presented a profile of cold-induced transcriptome changes in angiosperms. Our multispecies cold-responsive RNA-seq datasets provide valuable references for exploring conserved and evolutionary mechanisms of angiosperms in adaptation to cold stress.
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Resposta ao Choque Frio , Magnoliopsida , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Magnoliopsida/genética , Plantas , TranscriptomaRESUMO
As an ambident nucleophile, controlling the reaction selectivities of nitrogen and oxygen atoms in amide moiety is a challenging issue in organic synthesis. Herein, we present a chemodivergent cycloisomerization approach to construct isoquinolinone and iminoisocoumarin skeletons from o-alkenylbenzamide derivatives. The chemo-controllable strategy employed an exclusive 1,2-aryl migration/elimination cascade, enabled by different hypervalent iodine species generated in situ from the reaction of iodosobenzene (PhIO) with MeOH or 2,4,6-tris-isopropylbenzene sulfonic acid. DFT studies revealed that the nitrogen and oxygen atoms of the intermediates in the two reaction systems have different nucleophilicities and thus produce the selectivity of N or O-attack modes.
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The BnSRf (Rf = CF2H or CF3)/mCPBA/Tf2O system was found to be an effective multicomponent reagent system for the one-pot synthesis of di/trifluoromethylthiolated heterocycles from alkynes. The reaction was postulated to proceed via a cascade sequence involving the oxidation of BnSRf by mCPBA, activation of the in situ-generated sulfoxide by Tf2O, and intramolecular cyclization/fluoromethylthiolation of the alkyne substrates enabled by the formed electrophilic sulfonium salt to give di/trifluoromethylthiolated heterocycles.