Mutations in Cholangiocarcinoma: Prevalence, Prognostic Value, and G12/G13 Detection in Cell-Free DNA.

Background/aim: Cholangiocarcinoma (CCA) is an aggressive hepatobiliary malignancy characterized by genomic heterogeneity. KRAS mutations play a significant role in influencing patient prognosis and guiding therapeutic decision-making. This study aimed to determine the prevalence and prognostic significance of KRAS mutations in CCA, asses the detection of KRAS G12/G13 mutations in plasma cell-free DNA (cfDNA), and evaluate the prognostic value of KRAS G12/G13 mutant allele frequency (MAF) in cfDNA in relation to clinicopathological data and patient survival.

A new coumarin-based "OFF-ON" fluorescent sensor for HS detection in HeLa cells.

A new "OFF-ON" coumarin-based fluorescent probe for HS detection was designed and successfully developed through O-sulfonylation between a dabsyl quencher and 7-hydroxy-4-methylcoumarin as a fluorescent reporter, based on a FRET approach. This HS responsive probe, utilizing HS assisted thiolysis of a sulfonate ester as the sensing strategy, demonstrated excellent performance towards HS with a limit of detection (LoD) of 1.64 µM, along with superb selectivity, good stability and high specificity towards HS without interference from other biomarkers and analytes.

Design, synthesis and Anti-Plasmodial activity of Mortiamide-Lugdunin conjugates.

In this study, two linear and corresponding cyclic heptapeptide versions of mortiamide A-lugdunin hybrids were designed and synthesized by integrating an anti-malarial peptide epitope derived from Mortiamide A, combined with four residues known for their membrane interactions. Using this synthetic strategy, the sequence of mortiamide A was partly re-engineered with an epitope sequence of lugdunin along with an amino acid replacement using all-L and D/L configurations. Importantly, the re-engineered cyclic mortiamides with all-L (3) and D/L (4) configurations exhibited promising anti-malarial activities against the P.

Cryptochrome and quantum biology: unraveling the mysteries of plant magnetoreception.

Magnetoreception, the remarkable ability of organisms to perceive and respond to Earth's magnetic field, has captivated scientists for decades, particularly within the field of quantum biology. In the plant science, the exploration of the complicated interplay between quantum phenomena and classical biology in the context of plant magnetoreception has emerged as an attractive area of research. This comprehensive review investigates into three prominent theoretical models: the Radical Pair Mechanism (RPM), the Level Crossing Mechanism (LCM), and the Magnetite-based MagR theory in plants.

Cocultures of and Induce the Secretion of Bacteriocin-like Substances against .

Lactic acid bacteria (LAB) were screened from (red sea bass), and their antimicrobial activities were evaluated against two species isolated from the , namely, (AV) and (AJ). Three LAB isolates, MU8 (EF_8), MU2 (EFL_2), and MU9 (EFL_9), were found to inhibit both AV and AJ; however, their cell-free supernatant (CFS) did not do so. Interestingly, bacteriocin-like substances (BLS) induced by cocultures of EF_8 with AV exhibited the highest antimicrobial activity against both sp.

A novel γ-lactone isolated from the leaves of (Roxb.) Benth. and its xanthine oxidase activity.

A novel 3-(hydroxymethyl)-4-(methylamino)-dihydrofuran-2(3H)-one was isolated for the first time from the leaves of (Roxb.) Benth., along with kaempferol and kaempferol-3-rhamnoside .

Na 1.6 regulates excitability of mechanosensitive sensory neurons.

Key Points: Voltage-gated sodium channels are critical for peripheral sensory neuron transduction and have been implicated in a number of painful and painless disorders. The β-scorpion toxin, Cn2, is selective for Na 1.6 in dorsal root ganglion neurons.

Expression, purification and biological activity of monomeric insulin precursors from methylotrophic yeasts.

The methylotrophic yeasts Pichia pastoris and Hansenula polymorpha have been used for the production of recombinant monomeric insulin precursor (MIP). Recombinant plasmids with one, two and four cassettes of the MIP gene have been successfully constructed in the pPICZαA expression vector to study the effects of gene copy number on MIP production. The MIP protein can be detected by dot-blot analysis from the culture broth of P.

The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human Na1.6.

We report the chemical synthesis of scorpion toxin Cn2, a potent and highly selective activator of the human voltage-gated sodium channel Na1.6. In an attempt to decouple channel activation from channel binding, we also synthesized the first analogue of this toxin, Cn2[E15R].

Interaction of Synthetic Human SLURP-1 with the Nicotinic Acetylcholine Receptors.

Human SLURP-1 is a secreted protein of the Ly6/uPAR/three-finger neurotoxin family that co-localizes with nicotinic acetylcholine receptors (nAChRs) and modulates their functions. Conflicting biological activities of SLURP-1 at various nAChR subtypes have been based on heterologously produced SLURP-1 containing N- and/or C-terminal extensions. Here, we report the chemical synthesis of the 81 amino acid residue human SLURP-1 protein, characterization of its 3D structure by NMR, and its biological activity at nAChR subtypes.

Interaction of Tarantula Venom Peptide ProTx-II with Lipid Membranes Is a Prerequisite for Its Inhibition of Human Voltage-gated Sodium Channel NaV1.7.

ProTx-II is a disulfide-rich peptide toxin from tarantula venom able to inhibit the human voltage-gated sodium channel 1.7 (hNaV1.7), a channel reported to be involved in nociception, and thus it might have potential as a pain therapeutic.

Potent and specific inhibition of the biological activity of the type-II transmembrane serine protease matriptase by the cyclic microprotein MCoTI-II.

Matriptase is a type-II transmembrane serine protease involved in epithelial homeostasis in both health and disease, and is implicated in the development and progression of a variety of cancers. Matriptase mediates its biological effects both via as yet undefined substrates and pathways, and also by proteolytic cleavage of a variety of well-defined protein substrates, several of which it shares with the closely-related protease hepsin. Development of targeted therapeutic strategies will require discrimination between these proteases.

Loop-mediated isothermal amplification for Rickettsia typhi (the causal agent of murine typhus): problems with diagnosis at the limit of detection.

Murine typhus is a flea-borne disease of worldwide distribution caused by Rickettsia typhi. Although treatment with tetracycline antibiotics is effective, treatment is often misguided or delayed due to diagnostic difficulties. As the gold standard immunofluorescence assay is imperfect, we aimed to develop and evaluate a loop-mediated isothermal amplification (LAMP) assay.

Potent inhibitors of beta-tryptase and human leukocyte elastase based on the MCoTI-II scaffold.

MCoTI-II is a member of a class of microproteins known as cyclotides that possess a macrolactam-cystine knot scaffold imparting exceptional physiological stability and structural rigidity. Modification of residues in the active loop and engineered truncations have resulted in MCoTI-II analogues that possess potent activity against two therapeutically significant serine proteases: beta-tryptase and human leukocyte elastase. These results suggest that MCoTI-II is a versatile scaffold for the development of protease inhibitors against targets in inflammatory disease.

Chemical and biomimetic total syntheses of natural and engineered MCoTI cyclotides.

The naturally-occurring cyclic cystine-knot microprotein trypsin inhibitors MCoTI-I and MCoTI-II have been synthesised using both thia-zip native chemical ligation and a biomimetic strategy featuring chemoenzymatic cyclisation by an immobilised protease. Engineered analogues have been produced containing a range of substitutions at the P1 position that redirect specificity towards alternative protease targets whilst retaining excellent to moderate affinity. Furthermore, we report an MCoTI analogue that is a selective low-microM inhibitor of foot-and-mouth-disease virus (FMDV) 3C protease, the first reported peptide-based inhibitor of this important viral enzyme.

Total synthesis of the macrocyclic cysteine knot microprotein MCoTI-II.

The first total synthesis of MCoTI-II, a cysteine knot microprotein and potent trypsin inhibitor, is described; a synthetic strategy has been developed that combines efficient backbone construction via optimised solid phase peptide synthesis with one-pot 'thia-zip' native chemical ligation and refolding to yield the natural product.

Prediction of mortality by using the standard scoring systems in a medical intensive care unit in Thailand.

In order to evaluate and compare the predictive ability of the APACHE II (Acute Physiology and Chronic Health Evaluation II) and the SAPS (Simplified Acute Physiology Score) scoring systems in relation to outcome in a medical intensive care unit (ICU). The authors reviewed consecutive medical ICU admissions (n = 482) at a tertiary hospital over a 2-year period. For each patient, demographic data, diagnosis, APACHE II score, SAPS score and ICU outcome complied during the first 24 hrs of the ICU stay were obtained.

Stereoselective synthesis of naturally occurring alpha-methylenebis-gamma-butyrolactones: an application of novel oxiranyl "remote" anions.

Stereospecific deprotonation of the epoxy proton at the beta-position of the alpha,beta-epoxy esters 5 and 6 yielded oxiranyl "remote" anions 7 and 8, which could then be used for alkylation. The anions 7 and 8 underwent a consecutive aldol lactonization to give, respectively, epoxy lactones 11 and 13 with high stereoselectivity. Generation of the remote anions as well as their stereoselective reactions served as a new synthetic route to the naturally occurring alpha-methylenebis-gamma-butyrolactones, 1.