Clinical Pharmacology of Asciminib: A Review.

Asciminib is a first-in-class allosteric inhibitor of the kinase activity of BCR::ABL1, specifically targeting the ABL myristoyl pocket (STAMP). This review focuses on the pharmacokinetic (PK) and pharmacodynamic data of asciminib, which is approved at a total daily dose of 80 mg for the treatment of adult patients with chronic myeloid leukemia in chronic phase who are either resistant or intolerant to ≥ 2 tyrosine kinase inhibitors or those harboring the T315I mutation (at a dose of 200 mg twice daily). Asciminib is predicted to be almost completely absorbed from the gut, with an absolute bioavailability (F) of approximately 73%.

Inclusion of dilution quality control samples in quantitative LC-MS bioanalysis.

In LC-MS bioanalysis, sample dilution plays various roles, including bringing analyte concentrations within the validated/qualified dynamic range or alleviating matrix effect for accurate determination of the target analyte(s) in the intended study samples. Adherence to health authority requirements, incorporating good dilution practices, and timely demonstration of dilution integrity whenever samples are diluted in an analytical run are essential to ensure the reliability of bioanalytical results.

Metabolomics analysis of bioactive compositions of Michelia macclurei Dany and its antioxidant and enzyme inhibitory activities.

Background: Michelia macclurei Dandy is a traditional Chinese medicinal plant, but little is understood about the bioactive compositions and biological potential of its different parts, limiting their applications. This study aims to identify the bioactive compositions and analyze differences in accumulation patterns from different parts of Michelia macclurei (heartwood, sapwood, bark, root, leaf, and fruit) using metabolomics. It also seeks to explore their biological potential and analyze the relationship between the bioactive compositions and biological potential.

Study on the Effect of Magnesium Chloride-Modified Straw Waste Biochar on Acidic Soil Properties.

Soil biochar is a kind of organic matter rich in carbon, which is of great significance in soil fertility improvement, fertilizer type innovation and greenhouse gas emission reduction. In this paper, Mg-modified biochar was prepared by thermal cracking using rice straw and corn straw as raw materials. The Mg-modified biochar and unmodified biochar were fully mixed with prepared soil samples at the addition amounts of 0.

[Application of micro-computed tomography (μCT)in quantifying xylem vessels of broadleaved trees].

Quantitative analysis of vessel characteristics at the cellular scale is of great significance for understan-ding plant adaptation strategies to environment. The direct grinding combined with stereo-microscope imaging is one of the main approaches to examine the anatomical structure of xylem (conifer tracheid and hardwood vessel) wood structure, which inevitably damages xylem cells, hindering the accurate understanding of anatomical structures. In this study, we applied X-ray micro-computed tomography (μCT) and stereo-microscope technology to quantitatively measure the diameter and area of vessels of seven Canadian broadleaved tree species (, , , , , , and ).

Optimization of Extraction Process and Analysis of Biological Activity of Flavonoids from Leaves of Cultivated 'Qi-Nan' Agarwood.

Currently, the planting of 'Qi-Nan' is continuously increasing, yet a substantial amount of 'Qi-Nan' leaves have not been properly exploited. To improve the 'Qi-Nan' tree 's utilization value, 'Qi-Nan' leaves were used as a raw material. An ultrasound-assisted method was performed to obtain the flavonoids from the 'Qi-Nan' leaves, followed by optimization of the extraction factors using a one-way and response surface methodology to enhance the extraction of flavonoids.

Meeting Report on the 3rd Chinese American Society for Mass Spectrometry Conference-Advancing Biological and Pharmaceutical Mass Spectrometry.

Following the highly successful Chinese American Society for Mass Spectrometry (CASMS) conferences in the previous 2 years, the 3rd CASMS Conference was held virtually on August 28-31, 2023, using the Gather.Town platform to bring together scientists in the MS field. The conference offered a 4-day agenda with a scientific program consisting of two plenary lectures, and 14 parallel symposia in which a total of 70 speakers presented technological innovations and their applications in proteomics and biological MS and metabo-lipidomics and pharmaceutical MS.

Changes in the physiological activity of parenchyma cells in Dalbergia odorifera xylem and its relationship with heartwood formation.

Background: The formation of a tree's heartwood gives the wood properties such as natural decay resistance and aesthetic color, and often directly determines the value of wood products. Regulating the quantity and quality of heartwood is of great importance to the use of wood. However, the mechanism of heartwood formation has been poorly understood.

The DNA barcode identification of Dalbergia odorifera T. Chen and Dalbergia tonkinensis Prain.

Background: Dalbergia odorifera is a precious tree species with unique economic and medicinal values, which is difficult to distinguish from Dalbergia tonkinensis by traditional identification methods such as morphological characteristics and wood structure characteristics. It has been demonstrated that the identification of tree species can be effectively achieved using DNA barcoding, but there is a lack of study of the combined sequences used as DNA barcodes in the two tree species. In this study, 10 single sequences and 4 combined sequences were selected for analysis, and the identification effect of each sequence was evaluated by the distance-based method, BLAST-based search, character-based method, and tree-based method.

Quality Similarity between Induced Agarwood by Fungus and Wild Agarwood.

To prevent the exploitation of wild agarwood, the development of artificial agarwood through fungal inoculation is a promising method, but finding species that produce efficient high-quality agarwood remains difficult. In this study, a fungal inducer was prepared using wild agarwood containing fungi and high-throughput sequencing was performed to determine its species makeup. Subsequently, it was used to inoculate (Lour.

2022 White Paper on Recent Issues in Bioanalysis: ICH M10 BMV Guideline & Global Harmonization; Hybrid Assays; Oligonucleotides & ADC; Non-Liquid & Rare Matrices; Regulatory Inputs ( - Recommendations on Mass Spectrometry, Chromatography and Sample Preparation, Novel Technologies, Novel Modalities, and Novel Challenges, ICH M10 BMV Guideline & Global Harmonization - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).

The 16 Workshop on Recent Issues in Bioanalysis (16 WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Function of the R2R3-MYB Transcription Factors in and Their Relationship with Heartwood Formation.

R2R3-MYB transcription factors (TFs) form one of the most important TF families involved in regulating various physiological functions in plants. The heartwood of is a kind of high-grade mahogany and valuable herbal medicine with wide application. However, the role of R2R3-MYB genes in the growth and development of , especially their relevance to heartwood formation, has not been revealed.

Effect of Mg-Modified Waste Straw Biochar on the Chemical and Biological Properties of Acidic Soils.

Biochar is important for soil improvement, fertilizer innovation, and greenhouse gas reduction. In this paper, Mg-modified biochar was prepared from rice and corn straw and mixed with soil at a 1% (/) addition in an indoor soil simulation experiment to study the effect of Mg-modified biochar on the chemical properties of acidic soil. The results showed that the addition of Mg-modified biochar reduced soil acidity and improved soil fertility.

LC-MS/MS Bioanalysis of Radioligand Therapeutic Drug Candidate for Preclinical Toxicokinetic Assessment.

Radioligand therapy (RLT) has gained significant momentum in recent years in the diagnosis, treatment, and monitoring of cancers. In preclinical development, the safety profile of RLT drug candidate(s) is investigated at relatively low dose levels using the cold (non-radioactive, e.g.

A Study of the Chemical Composition and Biological Activity of Dandy Heartwood: New Sources of Natural Antioxidants, Enzyme Inhibitors and Bacterial Inhibitors.

The wood of Dandy (MD) is an excellent material that is widely used in the furniture, handicraft, and construction industries. However, less research has been conducted on the chemical composition and biological activity of heartwood, which is the main valuable part of the wood. This study aimed to investigate the chemical composition and biological activities of the heartwood of Dandy (MDHW) and to confirm the active ingredients.

How Closely Does Induced Agarwood's Biological Activity Resemble That of Wild Agarwood?

Continuous innovation in artificially-induced agarwood technology is increasing the amount of agarwood and substantially alleviating shortages. Agarwood is widely utilized in perfumes and fragrances; however, it is unclear whether the overall pharmacological activity of induced agarwood can replace wild agarwood for medicinal use. In this study, the volatile components, total chromone content, and the differences in the overall activities of wild agarwood and induced agarwood, including the antioxidant, anti-acetylcholinesterase, and anti-glucosidase activity were all determined.

Non-regulated LC-MS/MS bioanalysis in support of early drug development: a Novartis perspective.

Scientifically qualified LC-MS/MS methods are essential for the determination of small molecule drug candidates and/or their metabolite(s) in support of various non-regulated safety assessment and absorption, distribution, metabolism and excretion studies in preclinical development. This article outlines an effective method development workflow to fit for this purpose. The workflow features a 'universal' protein precipitation solvent for efficient sample extraction, a mobile phase additive for managing chromatographic resolution and addressing carryover and an internal standard cocktail to select the best analogue internal standard to track the analyte of interest in LC-MS/MS.

Photocatalytic Performance and Kinetic Studies of a Wood Surface Loaded with BiO-Doped Silicon-Titanium Composite Film.

In this paper, a surface self-cleaning wood was obtained by loading BiO-doped silica-titanium composite film on the surface of wood by the sol-gel method. The effects of different Bi doping amounts on the structure and photocatalytic properties of the modified wood were investigated. The doping of BiO inhibited the growth of TiO crystals and the phase transition from anatase to rutile.

Differences in Chemical Constituents between Heartwood and Sapwood and Their Effect on Wood Color.

The purpose of this study was to characterize and quantify the chemical constituents of heartwood and sapwood of extract in order to investigate the chemical components that determine the formation of heartwood's color. In this work, the types of pigments in heartwood and sapwood extract were analyzed using UV-Visible (UV) Spectrophotometer, and the main pigment components of heartwood and sapwood extract were identified and quantified using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). The results showed that the difference in content of the main components between heartwood and sapwood of was slight, and the lignin structure between heartwood and sapwood is basically identical; flavonoid pigments were found to be the primary chromophoric components of heartwood and sapwood extract.

Sensitive LC-MS/MS quantification of unconjugated maytansinoid DM4 and its metabolite S-methyl-DM4 in human plasma.

To report the development and validation of an LC-MS/MS method for the simultaneous determination of unconjugated payload DM4 and its metabolite S-methyl-DM4 in human plasma. A workflow of protein precipitation followed by reduction and solid phase extraction was employed to remove antibody-maytansinoid conjugates from plasma matrix, release DM4 from endogenous conjugates, and generate a clean sample extract for analysis, respectively. Sodium adduct species of both analytes were selected for multiple reaction monitoring to meet the assay sensitivity requirement in liquid chromatography with tandem mass spectrometry.

An integrated outsourcing practice of nonclinical LC-MS bioanalysis and toxicokinetics at Novartis small molecule drug development.

With decommissioning of internal regulated bioanalytical (BA) and toxicokinetic (TK) capabilities, Novartis has relied on external service providers (ESPs) for all nonclinical LC-MS BA and majority of the associated TK work since 2017. This paper outlines an integrated outsourcing practice of the Novartis nonclinical LC-MS BA/TK group, which covers the roles and responsibilities of Novartis nonclinical LC-MS BA/TK expert scientific monitors, selection of ESPs for Novartis nonclinical LC-MS BA/TK studies, qualification of BA/TK ESPs, study conduct and completion, ESP oversight and evaluation, issue mitigation, and future perspectives.