The rapid growth of internet usage has led to increased cyberbullying among adolescents, with varying rates reported across countries. This study aimed to investigate the impact of cyber moral literacy on cyberbullying among late adolescents, examining both the mediating role of moral disengagement and the moderating effect of guilt on the relationship between cyber moral literacy and cyberbullying. Data were collected from 7837 late adolescent students (aged 18-21 years) at four universities in Sichuan Province, China.
View Article and Find Full Text PDFModular type I polyketide synthases (PKSs) are remarkable molecular machines that can synthesize structurally complex polyketide natural products with a wide range of biological activities. In these molecular machines, ketosynthase (KS) domains play a central role, typically by catalyzing decarboxylative Claisen condensation for polyketide chain extension. Noncanonical KS domains with catalytic functions rather than Claisen condensation have increasingly been evidenced, further demonstrating the capability of type I PKSs for structural diversity.
View Article and Find Full Text PDFBackground: According to the theory of traditional Chinese medicine (TCM), the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry. After surgery and chemotherapy, patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome, leading to decreased immune function. Buzhong Yiqi decoction, a classic TCM prescription, has the effect of tonifying middle-jiao and invigorating qi, boosting Yang, and suppressing immune-related inflammation.
View Article and Find Full Text PDFPyrroindomycins (PYRs) represent the only spirotetramate natural products discovered in nature, and possess potent activities against methicillin-resistant and vancomycin-resistant . Their unique structure and impressive biological activities make them attractive targets for synthesis and biosynthesis; however, the discovery and generation of new PYRs remains challenging. To date, only the initial components A and B have been reported.
View Article and Find Full Text PDF9,10-Secosteroids are an important group of marine steroids with diverse biological activities. Herein, we report a chemoenzymatic strategy for the concise, modular, and scalable synthesis of ten naturally occurring 9,10-secosteroids from readily available steroids in three to eight steps. The key feature lies in utilizing a Rieske oxygenase-like 3-ketosteroid 9α-hydroxylase (KSH) as the biocatalyst to achieve efficient C9-C10 bond cleavage and A-ring aromatization of tetracyclic steroids through 9α-hydroxylation and fragmentation.
View Article and Find Full Text PDFAberrant N-linked glycosylation is a prominent feature of cancers. Perturbance of oligosaccharide structure on cell surfaces directly affects key processes in tumor development and progression. In spite of the critical role played by N-linked glycans in tumor biology, the discovery of small molecules that specifically disturbs the N-linked glycans is still under investigation.
View Article and Find Full Text PDFModification of organic molecules with fluorine functionalities offers a critical approach to develop new pharmaceuticals. Here, we report a multienzyme strategy for biocatalytic fluoroalkylation using -adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and fluorinated SAM cofactors prepared from ATP and fluorinated l-methionine analogues by an engineered human methionine adenosyltransferase hMAT2A. This work introduces the first example of biocatalytic 3,3-difluoroallylation.
View Article and Find Full Text PDFSanglifehrin A (SFA) is a spirolactam-conjugated, 22-membered macrolide with remarkable immunosuppressive and antiviral activities. This macrolide is a result of a hybrid polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) assembly line that utilizes (2S)-2-ethylmalonamyl as a starter unit. Here, we report that the formation and loading of this starter unit in the SFA assembly line involve two unusual enzymatic reactions that occur on a discrete acyl carrier protein (ACP), SfaO.
View Article and Find Full Text PDFThe decarbonylation reaction has been developed significantly in organic chemistry as an effective approach to various synthetic applications, but enzymatic precedents for this reaction are rare. Based on investigations into the hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line of barbamide, we report an on-line α-ketothioester decarbonylation reaction that leads to one-carbon truncation of the elongating skeleton. This enzymatic editing reaction occurs in the first round of lipopeptide extension and modification involving the multienzymes BarE and BarF, which successively house an NRPS module to initiate the biosynthesis and a PKS module to catalyze the first round of chain extension.
View Article and Find Full Text PDFCycloaddition reactions are among the most widely used reactions in chemical synthesis. Nature achieves these cyclization reactions with a variety of enzymes, including Diels-Alderases that catalyse concerted 4 + 2 cycloadditions, but biosynthetic enzymes with 2 + 2 cyclase activity have yet to be discovered. Here we report that PloI4, a β-barrel-fold protein homologous to the exo-selective 4 + 2 cyclase that functions in the biosynthesis of pyrroindomycins, catalyses competitive 2 + 2 and 4 + 2 cycloaddition reactions.
View Article and Find Full Text PDFThe recruitment of -acting enzymes by nonribosomal peptide synthetase (NRPS) assembly line is rarely reported. ColB1 is a flavin-dependent dehydrogenase that is recruited by an NRPS terminal condensation domain (Ct domain) and catalyzes peptidyl carrier protein (PCP)-tethered cysteine dehydrogenation in collismycin biosynthesis. We here report the crystal structure of ColB1 complexed with FAD and reveal a typical structural fold of acyl-CoA dehydrogenases (ACADs).
View Article and Find Full Text PDFBackground: Heart rate, acidosis, consciousness, oxygenation, and respiratory rate (HACOR) have been used to predict noninvasive ventilation (NIV) failure. However, the HACOR score fails to consider baseline data. Here, we aimed to update the HACOR score to take into account baseline data and test its predictive power for NIV failure primarily after 1-2 h of NIV.
View Article and Find Full Text PDFIntroduction: The patients with community-acquired pneumonia (CAP) and acute exacerbations of COPD (AECOPD) could have a higher risk of acute and severe respiratory illness than those without CAP in AECOPD. Consequently, early identification of pneumonia in AECOPD is quite important. Methods.
View Article and Find Full Text PDFLincomycin fermentation residues (LFR) are the byproducts from the pharmaceutical industry, and contain high concentrations of antibiotics that could pose a threat to the environment. Here, we report that black soldier fly larvae (BSFL) and associated microbiota can effectively degrade LFR and accelerate the degradation of lincomycin in LFR. The degradation rate of lincomycin in LFR can reach 84.
View Article and Find Full Text PDFHere, we report a two-component enzymatic system that efficiently catalyzes the reduction of a carboxylate to an aldehyde in the biosynthesis of 2,2'-bipyridine antibiotics caerulomycins. The associated paradigm involves the activation of carboxylate by ATP-dependent adenylation protein CaeF, followed by its reduction catalyzed by CaeB2, a new class of NADPH-dependent aldehyde dehydrogenase (ALDH) that directly reduces AMP-conjugated carboxylate, which is distinct from the known aldehyde-producing enzymes that reduce ACP- or CoA-conjugated carboxylates.
View Article and Find Full Text PDFChronic obstructive pulmonary disease (COPD) is a global public health issue and is defined as persistent airflow limitation. COPD is a major cause of morbidity and mortality worldwide. Long noncoding RNAs are involved in the course of pulmonary diseases.
View Article and Find Full Text PDFis a pathogenic fungus causing huge economic losses worldwide via crop infection leading to yield reduction and grain contamination. The process through which the fungal invasion occurs remains poorly understood. We recently characterized fusaoctaxin A in , where this octapeptide virulence factor results from an assembly line encoded in , a gene cluster proved to be involved in fungal pathogenicity and host adaptation.
View Article and Find Full Text PDFCorrection for 'Characterization of a carboxyl methyltransferase in Fusarium graminearum provides insights into the biosynthesis of fusarin A' by Qian Yang et al., Org. Biomol.
View Article and Find Full Text PDFThe etiology of acute respiratory distress syndrome (ARDS) may play an important role in the failure of noninvasive ventilation (NIV). To explore the association between ARDS etiology and risk of NIV failure. A multicenter prospective observational study was performed in 17 intensive care units in China from September 2017 to December 2019.
View Article and Find Full Text PDFFusarium graminearum is a major fungal pathogen that causes a series of devastating crop diseases by producing a variety of mycotoxins. Fusarins are a class of polyketide-nonribosomal peptide hybrids. In Fusarium mycotoxins, a variable 2-pyrrolidone ring conjugates with a polyene chain substituted with a methyl ester moiety.
View Article and Find Full Text PDFLinear nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) template the modular biosynthesis of numerous nonribosomal peptides, polyketides and their hybrids through assembly line chemistry. This chemistry can be complex and highly varied, and thus challenges our understanding in NRPS and PKS-programmed, diverse biosynthetic processes using amino acid and carboxylate building blocks. Here, we report that caerulomycin and collismycin peptide-polyketide hybrid antibiotics share an assembly line that involves unusual NRPS activity to engage a trans-acting flavoprotein in C-C bond formation and heterocyclization during 2,2'-bipyridine formation.
View Article and Find Full Text PDFWe studied the mechanisms of activation and stereoselectivity of a monofunctional Diels-Alderase (PyrI4)-catalyzed intramolecular Diels-Alder reaction that leads to formation of the key spiro-tetramate moiety in the biosynthesis of the pyrroindomycin family of natural products. Key activation effects of PyrI4 include acid catalysis and an induced-fit mechanism that cooperate with the unique "lid" feature of PyrI4 to stabilize the Diels-Alder transition state. PyrI4 enhances the intrinsic Diels-Alder stereoselectivity of the substrate and leads to stereospecific formation of the product.
View Article and Find Full Text PDFChronic obstructive pulmonary disease (COPD) is a progressive lung disease that is primarily caused by cigarette smoke (CS)-induced chronic inflammation. In this study, we investigated the function and mechanism of action of the long non-coding RNA (lncRNA) taurine-up-regulated gene 1 (TUG1) in CS-induced COPD. We found that the expression of TUG1 was significantly higher in the sputum cells and lung tissues of patients with COPD as compared to that in non-smokers, and negatively correlated with the percentage of predicted forced expiratory volume in 1 second.
View Article and Find Full Text PDFIn this study, we reported a fluorescent nanoprobe assembled with upconversion core/shell nanoparticles and a chromophore ruthenium complex (N719@UCNPs). Functional groups (NCS) of the ruthenium complex N719 could react with Hg2+, which made N719 lose the efficacy in quenching the fluorescence of upconversion nanoparticles (UCNPs) and resulted in the recovery of the fluorescence intensity of UCNPs eventually. This fluorescent nanoprobe could provide a rapid and efficient detection of Hg2+ ions in vivo based on the fluorescence resonance energy transfer (FRET) between UCNPs and N719, and a detection limit of 0.
View Article and Find Full Text PDFNatural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external.
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