Application of Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696.

LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial production had to be developed for sacubitril. The use of chemocatalysis, biocatalysis, and flow chemistry as state-of-the-art technologies allowed to efficiently build up the structure of sacubitril and achieve the defined performance targets.

[From gene cloning to expressional analysis--practice and experience from educational reform of experimental gene engineering].

Experimental gene engineering is a laboratory course focusing on the molecular structure, expression pattern and biological function of genes. Providing our students with a solid knowledge base and correct ways to conduct research is very important for high-quality education of genetic engineering. Inspired by recent progresses in this field, we improved the experimental gene engineering course by adding more updated knowledge and technologies and emphasizing on the combination of teaching and research, with the aim of offering our students a good start in their scientific careers.

A transcranial magnetic stimulation protocol for decreasing the craving of methamphetamine-dependent patients.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020).

The exploration of optimized protocol for repetitive transcranial magnetic stimulation in the treatment of methamphetamine use disorder: A randomized sham-controlled study.

BACKGROUND: The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations. METHODS: Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317). FINDINGS: The three real TBS groups had more craving decrease effect than the sham group (p<0.01). The changes of craving were positively correlated with the improvement of anxiety and withdrawal symptom. With the highest respondence rate, group C also had shorter respondence time than Group A (p = 0.03). Group C was effective in improve depression symptoms (p = 0.04) and withdrawal symptom (p = 0.02) compared with Group D. Besides, Group C was significant in improve sleep quality (p = 0.04) compared with Group A. Baseline depression scores and spatial working memory were positively predicting the intervention response. INTERPRETATION: The rTMS paradigms involving vmPFC with cTBS are optimized protocols and well-tolerated for methamphetamine-dependent individuals, and they may have better efficacies compared with DLPFC iTBS. Emotion and cognitive function are rTMS treatment response predictors for methamphetamine-dependent patients. FUNDING: This work was supported by the National Key R&D Program of China (2017YFC1310400), National Natural Science Foundation of China (81,771,436, 81,801,319, 81,601,164), Shanghai Municipal Health and Family Planning Commission (2017ZZ02021), Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ013), Qihang Project of Shanghai Mental Health Center (2019-QH-05), Shanghai Sailing Program (19YF1442100), Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500), Program of Shanghai Academic Research Leader (17XD1403300), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), and Shanghai Clinical Research Center for Mental Health (19MC1911100).

Antidiabetic effect of an active fraction extracted from dragon's blood (Dracaena Cochinchinensis).

The active fraction extracted from dragon's blood displayed an inhibitory effect on alpha-glucosidase activity with an IC50 of 0.152 microg/mL, which is nearly half of the crude material. Its inhibition on alpha-glucosidase was noncompetitive. In addition, when this fraction was orally administered to mice dosed with Acarbose (20 mg/kg), the active fraction (100, 300, 500 mg/kg) significantly suppressed increase of blood glucose levels after sucrose loading in a dose-dependent manner. These results suggest that this extract from dragon's blood exerts an anti-diabetic effect by suppressing intestinal carbohydrate absorption and thereby reducing the postprandial increase of blood glucose.