Research on the Progress of Treating Gastroesophageal Reflux Disease with Modified Classic Traditional Chinese Medicine Prescription

Gastroesophageal reflux disease (GERD) is a high-incidence digestive system disease. Western medicine mainly uses drugs such as proton pump inhibitors to inhibit gastric acid secretion, but some patients are accompanied by symptoms such as non-acid reflux and gas reflux, which cannot effectively treat the disease. It is necessary to actively explore other treatment schemes. Traditional Chinese medicine (TCM) has a long history of research on gastroesophageal reflux disease, which emphasizes the treatment based on syndrome differentiation as a whole. Through the treatment of various and multi-component TCM prescriptions, the patient’s body condition can be adjusted, and the treatment effect on gastroesophageal reflux disease is reliable, which has obvious therapeutic advantages. To further clarify the treatment of gastroesophageal reflux disease, this study reviewed and analyzed the research progress of the treatment of liver disease with modified prescriptions, and the report is as follows.

Controlling antifungal activity with light:Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors

Invasive fungal infections(IFIs)have been associated with high mortality,highlighting the urgent need for developing novel antifungal strategies.Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14a-demethylase(CYP51)inhibitors.The photocaged triazoles completely shielded the CYP51inhibition.The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4%and 83.7%,respectively.Importantly,the shielded antifungal activity(MIC80≥64μg/m L)could be efficiently recovered(MIC80=0.5—8μg/m L)by light irradiation.The new chemical tools enable optical control of fungal growth arrest,morphological conversion and biofilm formation.The ability for highprecision antifungal treatment was validated by in vivo models.The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model.Overall,this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

Discovery of novel triple targeting G–quadruplex and topoisomerase 1/2 ligands from natural products evodiamine and rutaecarpine

Inspired by the indolopyridoquinazoline scaffold of natural products evodiamine and rutaecarpine, novel triple G4 and Top1/2 ligands were rationally designed and synthesized. Systematic structure–activity relationship(SAR) studies led to the discovery of compound 15g, which effectively induced and stabilized G4 and inhibited Top1/2 with potent antitumor activity. Compound 15g represents a valuable chemical tool or lead compound for antitumor drug discovery. This proof-of-concept study also validated the feasibility of using planar natural products scaffold as templates to design new G4 ligands.

中国雪豹的威胁与保护现状

大部分保护机构只有能力在特定种群层面上保护大型食肉动物,而物种的灭绝风险却是在全球尺度进行评估的。因此,要填补这一尺度断层,多机构的工作与意见汇总非常必要。本研究综合了文献和18家中国雪豹(Panthera uncia)研究与保护机构共24位一线工作人员提供的信息,经过两次集体讨论和填写评分表格的方式,识别出21种威胁因素,在全国层面和青海、西藏、新疆、四川和甘肃5个主要雪豹分布省区层面对威胁进行了排序,并汇总了各保护机构实施的17项保护行动,以及各项行动所应对的威胁。全国评分前三的威胁依次是基层保护部门能力不足(9.5分)、气候变化(8.0分)、当地社区保护动力不足(6.8分),不同省区的威胁排序则体现出很大差异性。其中,目前仍没有任何行动措施应对气候变化。虽然已有一些保护行动来应对基层保护能力不足和当地社区保护动力不足的问题,如保护区能力建设、开展社区监测等,但行动的覆盖尺度仍远远不够。

Evodiamine-inspired dual inhibitors of histone deacetylase 1(HDAC1) and topoisomerase 2(TOP2) with potent antitumor activity

A great challenge in multi-targetingdrug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations.Inspired by our previous efforts in designing antitumor evodiamine derivatives,herein selective histone deacetylase 1(HDAC1)and topoisomerase 2(TOP2)dual inhibitors were successfully identified,which showed potent in vitro and in vivo antitumor potency.Particularly,compound 30 a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model(TGI=75.2%,150 mg/kg,p.o.)without significant toxicity,which was more potent than HDAC inhibitor vorinostat,TOP inhibitor evodiamine and their combination.Taken together,this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.

Small molecules for combating multidrug-resistant superbug Candida auris infections

Candida auris is emerging as a major global threat to human health. C. auris infections are associated with high mortality due to intrinsic multi-drug resistance. Currently, therapeutic options for the treatment of C. auris infections are rather limited. We aim to provide a comprehensive review of current strategies, drug candidates, and lead compounds in the discovery and development of novel therapeutic agents against C. auris. The drug resistance profiles and mechanisms are briefly summarized. The structures and activities of clinical candidates, drug combinations, antifungal chemosensitizers, repositioned drugs, new targets, and new types of compounds will be illustrated in detail, and perspectives for guiding future research will be provided. We hope that this review will be helpful to prompting the drug development process to combat this fungal pathogen.