Metabolic reprogramming by traditional Chinese medicine and its role in effective cancer therapy.

The pharmacology, toxicology and therapeutic potential of anthraquinone derivative emodin.

Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a "gold standard" platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.

NMR as a "Gold Standard" Method in Drug Design and Discovery.

Additive manufacturing of ultra-high strength steels: A review

Emodin is an anthraquinone derivative found in the roots and bark of a variety of plants, molds, and lichens. Emodin has been used as a traditional medication for more than 2000 years and is still common in numerous herbal drugs. Emodin is plentiful in the three plant families, including Polygonaceae (Rheum, Rumex, and Polygonum spp.), Fabaceae (Cassia spp.), and Rhamnaceae (Rhamnus, Frangula, and Ventilago spp.). Emerging experimental evidences indicate that emodin confers a wide range of pharmacological activities; special focus was implemented toward neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, cerebral ischemia, anxiety and depression, schizophrenia, chronic hyperglycemic peripheral neuropathy, etc. Numerous preclinical evidences were established in support of the neuroprotection of emodin. However, this review highlighted the role of emodin as a potent neurotherapeutic agent; therefore, its evidence-based functionality on neurological disorders (NDs). 

Exploring the journey of emodin as a potential neuroprotective agent: Novel therapeutic insights with molecular mechanism of action.

This work investigated the microstructure evolution with aging temperature of laser-powder bed fusion ( L -PBF) 18Ni(300) maraging steel at different scales. Important issues of cell structure changes, precipitation sequence, and austenite reversion were evaluated. The dominant strengthening factor in each state was elucidated based on yield strength modeling. The as built fully martensitic matrix consists of dislocation cell structures, and its yield strength comes from the martensite lath and solid solution strengthening with comparable contributions. Aged at 440 °C, the cell walls kept stable and massive ω particles prominently strengthened matrix by shearing mechanism. At 490 °C, the cell walls were partially destroyed and austenite reversion just began along the lath boundary. Densely distributed η-Ni 3 Ti particles produced the peak strength dominantly by the Orowan mechanism, but the shearing process may also exist meanwhile. At 540 °C, cell walls further degraded and reverted austenite formed along the lath boundaries and around some retained cell walls. Its strength decreased mildly mainly due to the wider inter-particle spacing, but was still maintained quite high by Laves-Fe 2 Mo and η-Ni 3 Ti particles via the Orowan process. The reverted austenite with limited fraction had a minor role in its strength decrease, but improved ductility significantly. • Cell structures change, precipitation sequence and autenite reversion were discussed. • Precipitate types were rigorious identified based on crystallographic information. • Dominant strengthening factors in as built and aged states were elucidated. 

Effect of aging temperature on microstructure evolution and strengthening behavior of L-PBF 18Ni(300) maraging steel

Emodin is a natural anthraquinone derivative that is present in various herbal preparations. The pharmacological effects of emodin include anticancer, hepatoprotective, anti-inflammatory, antioxidant and even antimicrobial activities. However, emodin also has been reported to induce hepatotoxicity, nephrotoxicity, genotoxicity and reproductive toxicity. The mechanism of emodin's adverse effects is complicated and currently not well understood. This study aimed to establish a cell metabonomic method to investigate the toxicity of emodin and explore its potential mechanism and relevant targets. In the present study, metabonomic profiles of cell extracts and cell culture media obtained using the 1H NMR technique were used to assess emodin toxicity in HepG2 cells. Multivariate statistical analyses such as partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to characterize the metabolites that differed between the control and emodin groups. The results indicated that emodin resulted in differences in 33 metabolites, including acetate, arginine, aspartate, creatine, isoleucine, leucine and histidine in the cell extract samples and 23 metabolites, including alanine, formate, glutamate, succinate and isoleucine, in the cell culture media samples. Approximately 8 pathways associated with these metabolites were disrupted in the emodin groups. These results demonstrated the potential for using cell metabonomics approaches to clarify the toxicological effects of emodin, the underlying mechanisms and potential biomarkers. Our findings may help with the development of novel strategies to discover targets for drug toxicity, elucidate the changes in regulatory signal networks and explore its potential mechanism of action.

/pdf/nmr-based-metabolomic-techniques-identify-the-toxicity-of-2cwqmm8ybi.pdf

NMR-based Metabolomic Techniques Identify the Toxicity of Emodin in HepG2 Cells.

Revealing the corrosion product films of ion-implanted biodegradable Zn–Cu alloys

Effect of surface oxidation on wear and tribocorrosion behavior of forged and selective laser melting-based TC4 alloys

In the automobile industry, stamping and paint baking processes are used to strengthen components, and this not only saves costs, but also further reduces the bodyweight of automobiles. In this work, the bake hardening mechanism of the complex phase (CP) steel CP980 was explored by comparing it with that of DP1180, which has a clear bake hardening mechanism and a carbon content similar to that of CP980. By analyzing the bake hardening response and the microstructural changes of the two steels, we found that the bake hardening process of CP980 was divided into three stages. In the first two stages, the carbon atoms diffused into dislocations to form Cottrell atmosphere pinning dislocations, and excess carbon atoms formed carbon clusters or low-temperature carbide pinning dislocations that were similar to DP1180. In the third stage, the dislocation acted as rapid channels for carbon diffusion, and fine cementite gradually formed when the carbon clusters gathered at the dislocations as precursors, resulting in precipitation hardening. This novel bake-hardening (BH) mechanism is crucial for obtaining a comprehensive understanding of the strain-baking behavior of advanced high-strength steals (AHSS). 

Novel bake hardening mechanism for bainite-strengthened complex phase steel

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