Mode of action

OBJECTIVE: To assess the feasibility of the robot-assisted retractor. To compare the muscle injury of the two operation modes, intermittent retraction mode and continuous retraction mode in the robot-assisted retractor to find a better robot operation mode. METHODS: A new robot-assisted retractor experimental platform was developed. Three incisions were made on the backs of three beagles. The robot-assisted retractor was used to retract the muscle on both sides of the incisions in intermittent retraction mode and continuous retraction mode, and the operation of the robot system was observed...

PURPOSE: To investigate follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared to oocyte donors and explore its association with ovarian reserve and cumulus cell gene expression. METHODS: 20 Adolescents (16.7 ± 0.6 years old) and 24 oocyte donors (26.2 ± 0.4 years old) undergoing fertility preservation were included in the study. Patient demographics, ovarian stimulation and oocyte retrieval outcomes were analyzed for each group...

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research...

The cereal leaf beetle (CLB, Oulema melanopus) is one of the major cereal pests. The effect of insecticides belonging to different chemical classes, with different mechanisms of action and the active substances' concentrations on the CLB bacterial microbiome, was investigated. Targeted metagenomic analysis of the V3-V4 regions of the 16S ribosomal gene was used to determine the composition of the CLB bacterial microbiome. Each of the insecticides caused a decrease in the abundance of bacteria of the genus Pantoea, and an increase in the abundance of bacteria of the genus Stenotrophomonas, Acinetobacter, compared to untreated insects...

Interaction under amyloidogenic condition between naturally occurring protoberberine alkaloid palmatine and hen egg white lysozyme was executed by adopting spectrofluorometric and theoretical molecular docking and dynamic simulation analysis. In spetrofluorometric method, different types of experiments were performed to explore the overall mode and mechanism of interaction. Intrinsic fluorescence quenching of lysozyme (Trp residues) by palmatine showed effective binding interaction and also yielded different binding parameters like binding constant, quenching constant and number of binding sites...

Signal transducer and activator of transcription (STAT) 3 is extensively involved in the development, homeostasis and function of immune cells, with STAT3 disruption associated with human immune-related disorders. These roles have been assumed to be due to its canonical mode of action as an inducible transcription factor downstream of multiple cytokines, although alternative non-canonical functional modalities have also been described for STAT3. To further understand the roles of STAT3 gained from lineage-specific mouse knockouts, CRISPR/Cas9 was used to generate mutants of the conserved zebrafish Stat3 protein: a loss of function knockout (KO) mutant and a mutant lacking C-terminal sequences including the transactivation domain (ΔTAD)...

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate used for cancer treatment comprising an anti-human epidermal growth factor receptor type 2 (HER2) antibody and the topoisomerase I inhibitor DXd. The present study investigated the intratumor fate of T-DXd. Fluorescence-labeled T-DXd was found to accumulate in tumors of HER2-positive tumor xenograft mice and was observed to be distributed within lysosomes of in vitro tumor cells in accordance with their HER2 expression. DXd was released by cysteine proteases, including cathepsins, in lysosomal fractions in vitro in response to the pH...

This perspective emerged from ongoing dialogue among ecologists initiated by a virtual workshop in 2021. A transdisciplinary group of researchers and practitioners conclude that urban ecology as a science can better contribute to positive futures by focusing on relationships, rather than prioritizing urban structures. Insights from other relational disciplines, such as political ecology, governance, urban design, and conservation also contribute. Relationality is especially powerful given the need to rapidly adapt to the changing social and biophysical drivers of global urban systems...

Foam dressing (FD) and micropower vacuum dressing (MVD) have been applied in the treatment of diabetic foot ulcer (DFU). However, research about the mode of action on the efficacy of the two dressings is extremely rare. This study proposed to explore the mechanism involved in diabetic wound healing under FD or MVD treatment. Macroscopical study was performed to evaluate the effectiveness of FD and MVD on wound healing in a rat model of DFU. Morphological analysis in the wound skin tissue was conducted by hematoxylin and eosin staining...

ETHNOPHARMACOLOGICAL RELEVANCE: Members of Plectranthus genus such as Plectranthus amboinicus (Lour.) Spreng is a well-known folkloric medicine around the globe in treating several human ailments such as cardiovascular, respiratory, digestive, urinary tract, skin and infective diseases. Its therapeutic value is primarily attributed to its essential oil. Although several properties of Plectranthus amboinicus essential oil have been documented, its mechanism of action and safety has not been completely elucidated...

In this issue of Cell Chemical Biology, Gries et al.1 employ an innovative screening approach to identify anti-tuberculosis compounds with dual modes of action: anti-virulence against the type VII secretion system ESX-1 and enhanced ethionamide efficacy. These compounds hold promise for developing multi-target tuberculosis drugs with potential clinical applications.

Methionine (Met) supplementation is common practice in broilers to support nutrition, yet there are gaps in the understanding of its role in systemic physiology. Furthermore, several different Met sources are available that may have different physiological effects. This study evaluated the mode of action of Met deficiency (no Met-supplementation) and supplementation (0.25% DL- or L-Met, 0.41% liquid methionine hydroxy analog-free acid (MHA-FA)), and of Met source (DL-, L- or MHA-FA) in broiler chickens, via host transcriptomics...

The detection of pathogen viability is critically important to evaluate its infectivity. In the study, an integrated microfluidic chip based on dual-mode analytical strategy was developed to rapidly realize detection of bacteria activity (with Salmonella typhimurium, S.T, as a model analyte). Firstly, the composite probes, including deactivated phage modified magnetic beads and nano Pt-antimicrobial peptide (AMP) which can specifically recognize Gram-negative bacteria as nanozyme were prepared. When the composite probes are introduced into the chip together with target bacteria, after enrichment, oscillating and magnetic separation, they will conjugate with S...

Despite accumulating evidence linking defective lysosome function with autoimmune diseases, how the catabolic machinery is regulated to maintain immune homeostasis remains unknown. Late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (Lamtor5) is a subunit of the Ragulator mediating mechanistic target of rapamycin complex 1 (mTORC1) activation in response to amino acids, but its action mode and physiological role are still unclear. Here it is demonstrated that Lamtor5 level is markedly decreased in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE)...

Modified WKB theory for calculating tunneling splittings in symmetric multi-well systems in full dimensionality is re-derived using Cartesian coordinates. It is explicitly shown that the theory rests on the wavefunction that is exact for harmonic potentials. The theory was applied to calculate tunneling splittings in vinyl radical and some of its deuterated isotopologues in their vibrational ground states and the low-lying vibrationally excited states and compared to exact variational results. The exact results are reproduced within a factor of 2 in most states...

A combined computational and experimental approach allowed us to develop the most selective catalysts for the direct hydrogenation of N-methyl and N-alkyl imines described to date. Iridium catalysts with a cyclometallated cyclic imide group provide selectivity of up to 99% enantiomeric excess. Computational studies show that the selectivity results from the combined effect of H-bonding of the imide C=O with the substrate iminium ion and a stabilizing π-π interaction with the cyclometallated ligand...

Breast cancer is still the largest cause of cancer death in women, and around 70% of primary breast cancer patients are estrogen receptor (ER)-positive, which is the most frequent kind of breast cancer. The lemur tyrosine kinase-3 (LMTK3) receptor has been linked to estrogen responsiveness in breast cancer. However, the function of LMTK3 in reaction to cytotoxic chemotherapy has yet to be studied. Breast cancer therapy research remains tricky due to a paucity of structural investigations on LMTK3. We performed structural investigations on LMTK3 using molecular docking and molecular dynamics (MD) simulations of the LMTK3 receptor in complex with the top three inhibitor molecules along with a control inhibitor...

BACKGROUND: IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of IL-15 on tumor cells has not been fully elucidated. Herein, we investigated the effect of IL-15 on lung adenocarcinoma cells. METHODS: Silencing and overexpression techniques were used to modify endogenous IL-15 expression in tumor cells. Transwell assays were used to assess tumor cell migration and invasion; a live-cell analysis system was used to evaluate cell motility; cellular morphological changes were quantified by confocal fluorescence microscopy; the molecular mechanisms underlying the effect of IL-15 on tumor cells were analyzed by western blotting; and RhoA and Cdc42 activities were evaluated by a pulldown assay...

Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress and natural killer cell lysis, thereby promoting their colonization and metastasis to distant organs. Platelets can affect the tumor microenvironment via interactions between platelet-related factors and tumor cells. Metastasis is a key event in cancer-related death and is associated with platelet-related factors in lung, breast, and colorectal cancers...

Organic acids are widely used in foodstuffs to inhibit pathogen and spoiler growth. In this study, six organic acids (acetic, lactic, propionic, phenyllactic, caprylic, and lauric acid) and monolaurin were selected based on their physicochemical properties: their molecular structure (carbon chain length), their lipophilicity (logP), and their ability to dissociate in a liquid environment (pKa). The relation between these physicochemical properties and the inhibitory efficacy against B. weihenstephanensis KBAB4 growth was evaluated...