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Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low‐density lipoprotein cholesterol (LDL‐C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL‐C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice. [ABSTRACT FROM AUTHOR]

For the purpose of investigating the coordination behavior of sterically congested alkenes and exploring the possibility of cofacial complexation in the polycyclic aromatic system for the formation of extended polymeric networks, a new tetradentate ligand, 1,1,2,2-tetrakis[4-(1 H-1,2,4-triazol-1-yl)phenyl]ethylene (TTPE), has been designed and synthesized. By using TTPE as a building block with regard to the self-assembly with MnCl2 ⋅4 H2O, a novel two-dimensional coordination framework {[Mn(TTPE)Cl2] ⋅4 CHCl3} n ( 1) can be isolated. Anion-exchange and organic-group-functionalized aromatic guest TTPE-loaded host-guest complex experimental results indicate that coordinated Cl− anions in the 2D framework of 1 can be completely replaced with dissociative ClO4− groups in an irreversible single-crystal-to-single-crystal transformation fashion, as evidenced by the anion-exchange products of {[Mn(TTPE)(H2O)2](ClO4)2 ⋅0.5 TTPE ⋅5.25 H2O} n ( 2). Interestingly, TTPE, acting as an organic template, was encapsulated in the confined space of the 2D grid of 2. To the best of our knowledge, such large organic molecules encapsulated in the reactive organic-group-functionalized aromatic-guest-loaded host-guest complex are unprecedented up to now. Luminescence measurements illustrate that 1 and 2 represent novel examples of sensing materials based on triazole derivatives. Further, 2 has been demonstrated by tuning the fluorescence response of porous metal-organic frameworks as a function of adsorbed small analytes. [ABSTRACT FROM AUTHOR]

Sodium carbonate (Na2CO3) presents a huge challenge to plants by the combined damaging effects of Na+, high pH, and CO32-. Little is known about the cellular responses to Na2CO3 stress. In this study, the transcriptome of maize ( Zea mays L. cv. B73) roots exposed to Na2CO3 stress for 5 h was compared with those of NaCl and NaOH stresses. The expression of 8,319 genes, representing over a quarter of the total number of genes in the maize genome, was altered by Na2CO3 stress, and the downregulated genes (5,232) outnumbered the upregulated genes (3,087). The effects of Na2CO3 differed from those of NaCl and NaOH, primarily by downregulating different categories of genes. Pathways commonly altered by Na2CO3, NaCl, and NaOH were enriched in phenylpropanoid biosynthesis, oxidation of unsaturated fatty acids, ATP-binding cassette (ABC) transporters, as well as the metabolism of secondary metabolites. Genes for brassinosteroid biosynthesis were specifically upregulated by Na2CO3, while genes involved in ascorbate and aldarate metabolism, protein processing in the endoplasmic reticulum and by N-glycosylation, fatty acid biosynthesis, and the circadian rhythm were downregulated. This work provides the first holistic picture of early transcriptomic adaptation to Na2CO3 stress, and highlights potential molecular pathways that could be manipulated to improve tolerance in maize. [ABSTRACT FROM AUTHOR]

For patients with cardiovascular disease, using the antidepressant escitalopram may lead to unexpected adverse events. Here, a rare repeated sinus bradycardia event due to escitalopram is first reported. In an 82-year-old female patient with cardiac dysfunction using digoxin, tachycardia (average heart rate of 93 beats/min) was demonstrated by electrocardiogram (ECG). She began to take escitalopram and lorazepam due to depression, but sinus bradycardia (93.7% heart rate was <60 beats/min) and sinus arrest were first detected after 3 months. Its proportion decreased to 0.1% after discontinuation of digoxin and escitalopram for 1 day, and the rhythm returned to normal 2 weeks later. After 2 months, escitalopram was prescribed again in combination with quetiapine; then, 17.1% heart rate was <60 beats/min. After escitalopram and quetiapine withdrawal, the ECG showed the heart rhythm had normalized again. No other drug changes were made during these periods. Escitalopram was deemed to be a highly possible cause of sinus bradycardia according to its Naranjo's Algorithm score. Furthermore, literature on escitalopram-mediated cardiovascular adverse events was reviewed and analyzed. Empirically, escitalopram should be discontinued immediately if iatrogenic causes cannot be ruled out. Furthermore, ECG monitoring in escitalopram-related cardiovascular adverse events is highlighted, especially in patients receiving certain drug classes simultaneously (i.e., sinoatrial node inhibitors, antipsychotics)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Li, Sun, Lv, Xu, Hu and Shi.)

Research on the distribution of antibiotic resistance genes (ARGs) in urban sewage treatment systems is extensive, but there is still insufficient research on their abundance in industrial wastewater recycling systems. In this study, a printing and dyeing wastewater (PDWW) recycling system was constructed, and 16S rDNA and high-throughput sequencing technology was used to analyze the microbial communities and ARG abundance during the treatment process. A total of 52 ARGs in nine categories were detected, of which the relative abundance of β -lactam resistance genes was the highest. During the treatment cycle, the concentration of aromatic pollutants increased with an increase in the number of cycles, while the abundance of β -lactam resistance genes increased first, decreased, and then increased (reaching 61.85% on the 100th day). At the same time, the abundance of Firmicutes, Actinobacteria, and Cyanobacteria related ARGs decreased significantly (by 84.66%, 64.38%, and 85.15%, respectively). More than 21 kinds of ARGs were significantly affected by the enrichment by the aromatic pollutants. Among them, 6 kinds of ARGs were significantly positively correlated with changes in the concentrations of the aromatic pollutants ( P <0.01), while 6 were significantly negatively correlate ( P <0.01). These results show that the abundance of ARGs was affected by the microbial communities and the aromatic pollutants, which increased at first, decreased, and then increased during the PPDW recycling process. This study reveals the effects of the enrichment of aromatic contaminants and changes in microbial communities on ARGs during PPDW recycling, and provides theoretical guidance for the recycling of PDWW to reduce environmental pollution associated with ARGs.

For the purpose of investigating the coordination behavior of sterically congested alkenes and exploring the possibility of cofacial complexation in the polycyclic aromatic system for the formation of extended polymeric networks, a new tetradentate ligand, 1,1,2,2-tetrakis[4-(1H-1,2,4-triazol-1-yl)phenyl]ethylene (TTPE), has been designed and synthesized. By using TTPE as a building block with regard to the self-assembly with MnCl2 ⋅4 H2 O, a novel two-dimensional coordination framework {[Mn(TTPE)Cl2 ]⋅4 CHCl3 }n (1) can be isolated. Anion-exchange and organic-group-functionalized aromatic guest TTPE-loaded host-guest complex experimental results indicate that coordinated Cl(-) anions in the 2D framework of 1 can be completely replaced with dissociative ClO4 (-) groups in an irreversible single-crystal-to-single-crystal transformation fashion, as evidenced by the anion-exchange products of {[Mn(TTPE)(H2 O)2 ](ClO4 )2 ⋅0.5 TTPE⋅5.25 H2 O}n (2). Interestingly, TTPE, acting as an organic template, was encapsulated in the confined space of the 2D grid of 2. To the best of our knowledge, such large organic molecules encapsulated in the reactive organic-group-functionalized aromatic-guest-loaded host-guest complex are unprecedented up to now. Luminescence measurements illustrate that 1 and 2 represent novel examples of sensing materials based on triazole derivatives. Further, 2 has been demonstrated by tuning the fluorescence response of porous metal-organic frameworks as a function of adsorbed small analytes., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)