Mass Spectrometry Imaging Reveals the Morphology-Dependent Toxicological Effects of Nanosilvers on Multiple Organs of Adult Zebrafish ().

Nanosilvers with multifarious morphologies have been extensively used in many fields, but their morphology-dependent toxicity toward nontarget aquatic organisms remains largely unclear. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the toxicological effects of silver nanomaterials with various morphologies on spatially resolved lipid profiles within multiple organs in adult zebrafish, especially for the gill, liver, and intestine. Integrated with histopathology, enzyme activity, accumulated Ag contents and amounts, as well as MSI results, we found that nanosilvers exhibit morphology-dependent nanotoxicity by disrupting lipid levels and producing oxidative stress.

Metabolomics and mass spectrometry imaging reveal the chronic toxicity of indoxacarb to adult zebrafish (Danio rerio) livers.

Indoxacarb is a widely used insecticide in the prevention and control of agricultural pests, whereas its negative effects on non-target organisms remain largely unclear. Herein, we demonstrated the integrated metabolomics and mass spectrometry imaging (MSI) methods to investigate the chronic exposure toxicity of indoxacarb at environmentally relevant concentrations in adult zebrafish (Danio rerio) liver. Results showed that movement behaviors of zebrafish can be affected and catalase (CAT), glutamic oxalacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) activities were significantly increased after indoxacarb exposure for 28 days.

Integrated mass spectrometry imaging and metabolomics reveals sublethal effects of indoxacarb on the red fire ant Solenopsis invicta.

Background: Indoxacarb, representing an efficient insecticide, is normally made into a bait to spread the poison among red fire ants so that it can be widely applied in the prevention and control of Solenopsis invicta. However, the potential toxicity mechanism of S. invicta in response to indoxacarb remains to be explored.

Sample preparation optimization of insects and zebrafish for whole-body mass spectrometry imaging.

Appropriate sample preparation is one of the most critical steps in mass spectrometry imaging (MSI), which is closely associated with reproducible and reliable images. Despite that model insects and organisms have been widely used in various research fields, including toxicology, drug discovery, disease models, and neurobiology, a systematic investigation on sample preparation optimization for MSI analysis has been relatively rare. Unlike mammalian tissues with satisfactory homogeneity, freezing sectioning of the whole body of insects is still challenging because some insect tissues are hard on the outside and soft on the inside, especially for some small and fragile insects.

Time-series expression profiles of mRNAs and lncRNAs during mammalian palatogenesis.

Objectives: Mammalian palatogenesis is a highly regulated morphogenetic process to form the intact roof of the oral cavity. Long noncoding RNAs (lncRNAs) and mRNAs participate in numerous biological and pathological processes, but their roles in palatal development and causing orofacial clefts (OFC) remain to be clarified.

Methods: Palatal tissues were separated from ICR mouse embryos at four stages (E10.

Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy.

Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are the first and most successful drugs designed to exploit the concept of synthetic lethality (SL) between PARP-1 and BRCA1/2, which provides a novel strategy for tumor treatment. However, narrowed indications and resistance to PARP-1 inhibitors have hampered their further clinical application. Inducing "BRCAness" by targeting other targets, which will directly or indirectly disturb the homologous recombination (HR) repair pathway of double-strand DNA breaks (DSBs), is a promising strategy for expanding the clinical application of PARP-1 inhibitors and overcoming resistance to these inhibitors.

Small molecule targeting CELF1 RNA-binding activity to control HSC activation and liver fibrosis.

CUGBP Elav-like family member 1 (CELF1), an RNA-binding protein (RBP), plays important roles in the pathogenesis of diseases such as myotonic dystrophy, liver fibrosis and cancers. However, targeting CELF1 is still a challenge, as RBPs are considered largely undruggable. Here, we discovered that compound 27 disrupted CELF1-RNA binding via structure-based virtual screening and biochemical assays.

Stereoselective toxicity mechanism of neonicotinoid dinotefuran in honeybees: New perspective from a spatial metabolomics study.

Development of stereoisomeric neonicotinoid pesticides with lower toxicity is key to preventing global population declines of honeybees, whereas little is known about the in situ metabolic regulation of honeybees in response to stereoisomeric pesticides. Herein, we demonstrate an integrated mass spectrometry imaging (MSI) and untargeted metabolomics method to disclose disturbed metabolic expression levels and spatial differentiation in honeybees (Apis cerana) associated with stereoisomeric dinotefuran. This method affords a metabolic network mapping capability regarding a wide range of metabolites involved in multiple metabolic pathways in honeybees.

Fraxinellone alleviates kidney fibrosis by inhibiting CUG-binding protein 1-mediated fibroblast activation.

Chronic Kidney Disease (CKD) is a serious threat to human health. In addition, kidney fibrosis is a key pathogenic intermediate for the progression of CDK. Moreover, excessive activation of fibroblasts is key to the development of kidney fibrosis and this process is difficult to control.

Landscape of SARS-CoV-2 spike protein-interacting cells in human tissues.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. However, the mechanism of tissue tropism of SARS-CoV-2 remains unclear. Here, recombinant receptor-binding subdomain 1 of spike protein of SARS-CoV-2 (RBD-SD1) was used as a probe to investigate the potential tropism of SARS-CoV-2 in thirty-three types of normal human tissues.

Metal-Free Remote C-H Bond Amidation of 8-Amidoquinolines on the C5 Position under Mild Conditions.

An efficient and facile process was developed for the remote C-H bond amidation of 8-aminoquinoline scaffolds on the C5 position which is geometric. The method only made use of PhI(OAc)2 as a mediator and showed good tolerance toward numerous dibenzenesulfonimides and amides, giving the corresponding products in moderate to excellent yield.