The Fibulin family is a kind of secreted glycoprotein,belonging to the extracellular matrix protein.A total of 7 family members are widely distributed in basement membrane,elastic fiber and loose connective tissue.The Fibulin family is widely involved in the regulation of cell morphology,growth and adhesion.When Fibulin is disturbed,it can cause a range of diseases,such as skin laxity,tooth hypoplasia and various tumors.The researches show that Fibulin-1 is expressed abnormally in fibrosarcoma,gastric cancer and liver cancer,and the expression of Fibulin-2 is down-regulated in breast cancer and up-regulated in lung cancer.The other members of the family also show abnormal expression in various tumor tissues,which indicates the members of the Fibulin family play important roles in the genesis and development of tumors.

OBJECTIVE： To study the imp rovement effects of Ganoderma lucidum polysaccharides crude extract on estradiol-induced thymus atrophy in mice. METHODS ：Totally 60 female ICR mice were randomly divided into normal control group（normal saline ），model group （normal saline ），G. lucidum polysaccharides crude extract high-dose and low-dose groups （400，100 mg/kg，by crude drug ），with 15 mice in each group. Except for normal control group ，other groups were given estradiol intraperitoneally （0.1 mg/mice，6 times）every other day to establish thymic atrophy model. The next day after modeling finished，they were given relevant medicine intragastrically ，once a day ，for consecutive 14 d. Twenty-four hours after last medication，organ（thymus，spleen）index，MDA content and GST activity in plasma were determined. HE staining was adopted to observe the pathological changes of thymus and spleen tissue in mice. The thymus cell apoptosis was examined by TUNEL assay ， and the T cell subsets in peripheral blood were detected by flow cytometry. RESULTS ：Compared with normal control group ，the thymus index ，proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were decreased significantly in model group （P＜0.01）；spleen index ，MDA content in plasma and thymocyte apoptosis level as well as the proportion of CD 3+CD8+T cell in peripheral blood were all increased significantly （P＜0.05 or P＜0.01）. Thymic cortex and medullary boundary of mice was blurred；the intercellular space was enlarged ；some cells were damaged and apoptotic in cortex ；no pathological changes were found in the spleen. Compared with model group ，thymus index and GST activity in plasma as well as proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were all increased significantly in G. lucidum polysaccharides crude extract high-dose group（P＜0.05 or P＜0.01）；while MDA content in plasma ，the apoptosis level of thymocytes were all decreased significantly （P＜0.01 or P＜0.05）；and the pathological changes of thymus were improved significantly. MDA content in plasma was decreased significantly in G. lucidum polysaccharides crude extract low-dose group （P＜0.01），and other indexes/pathological changes were not obvious. CONCLUSIONS ：High dose （400 mg/kg）of G. lucidum polysaccharides crude extract can improve the thymus atrophy induced by estradiol in mice.

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].