Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Tinosporae Radix， as a traditional Chinese medicinal herb， is the dried root tuber of Tinospora sagittata or T. capillipes. It was first recorded in the Compendium of Materia Medica Supplement in the Qing Dynasty and included in the previous edition of the Chinese Pharmacopoeia. Tinosporae Radix is excavated in autumn and winter and used after removing fibrous roots， washing， and drying. It is indicated for sore throat， carbuncle boils poison， waist and abdominal pain， and various heat syndromes and is commonly used to treat chronic inflammation. Its efficacy is significantly known as “broad-spectrum antibiotics in Zhuang medicine”. Tinosporae Radix is a traditional Chinese medicinal herb often taken by Zhuang and Yao nationalities in Guangxi province and has a wide range of application and development values and research significance. Modern studies have shown that Tinosporae Radix contains diterpenoids， alkaloids， sterols， anthraquinones， glycosides， fatty acids， volatile oils， and other compounds， which have many pharmacological activities such as anti-inflammatory and analgesic， antibacterial and antibacterial， antioxidant， anti-diabetic， and anti-tumor and anti-cancer effects， and it has achieved good efficacy in inhibiting inflammation and treating sore throat and other diseases. In recent years， there have been many research reports on the status， chemical constituents， pharmacological action， clinical application， and quality evaluation of Tinosporae Radix resources， but there is no systematic review and introduction at present. By consulting the literature and combining it with modern research， this paper systematically summarizes and collates Tinosporae Radix resources to provide guidance for the comprehensive development and utilization of Tinosporae Radix resources and subsequent in-depth study.

Objective: To establish an animal model of hard metal lung disease (HMLD) in rats, and to screen the indications for diagnosis of HMLD. Methods: The rats were randomly divided into 5 groups, each group included 8 rats: saline group, pure cobalt group, pure tungsten carbide group, silica group and hard metal (HM) group. 10 mg subjects were administered in each group by using the pulmonary endotracheal tube. After 8 week, the lung CT scan and lung tissue pathology were observed, the serum and bronchoalveolar lavage fluid (BALF) were collected for KL-6, TGF-beta1 and TGF-beta2. Results: The lung tissue structure of HM group was destroyed, a large number of nuclear giant cells and epithelial like cells appeared in the stroma, and uncommon CT scan images appeared in the lung. KL-6, TGF-beta1, TGF-beta2 expression in each group was not the same, the difference was statistically significant (P<0.05) . The expression of KL-6 and TGF-beta1 in serum was not identical in all the groups, the difference was statistically significant (P<0.05) . The expression of TGF-beta2 had no significant difference between the groups (P>0.05) . Conclusion Rats can be successfully established HMLD model, rats in vivo lung CT scan images appear abnormal, which are provided with assistant diagnostic value for HMLD. The expression of KL-6 and TGF-beta2 in serum and BALF on HMLD rats are not highly specific, and TGF-beta1 has reference value in the rat HMLD auxiliary diagnosis.