Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

Significantly increasing crop yield is a major and worldwide challenge for food supply and security. It is well-known that rice cultivated at Taoyuan in Yunnan of China can produce the highest yield worldwide. Yet, the gene regulatory mechanism underpinning this ultrahigh yield has been a mystery. Here, we systematically collected the transcriptome data for seven key tissues at different developmental stages using rice cultivated both at Taoyuan as the case group and at another regular rice planting place Jinghong as the control group. We identified the top 24 candi-date high-yield genes with their network modules from these well-designed datasets by developing a novel computational systems biology method, i.e., dynamic cross-tissue (DCT) network analysis. We used one of the candidate genes, OsSPL4, whose function was previously unknown, for gene editing experimental validation of the high yield, and confirmed that OsSPL4 significantly affects panicle branching and increases the rice yield. This study, which included extensive field phenotyping, cross-tissue systems biology analyses, and functional validation, uncovered the key genes and gene regulatory networks underpinning the ultrahigh yield of rice. The DCT method could be applied to other plant or animal systems if different phenotypes under various environments with the common genome sequences of the examined sample. DCT can be downloaded from https://github.com/zt-pub/DCT.

BACKGROUND:Bone marrow mesenchymal stem cel transplantation has not been thoroughly reported on its effects on apoptosis in hepatoma carcinoma cel s and inflammatory factor level.
OBJECTIVE:To investigate the effect of rat bone marrow mesenchymal stem cel s on dynamic change of inflammatory factors and cel apoptosis during hepatocarcinogenesis.
METHODS:Sixty healthy Sprague-Dawley rats were divided randomly into healthy group (n=30), control group (n=30) and transplantation group (n=30). Healthy group was given ordinary feed and normal water, while other groups were given diethylnitrosamine solution in drinking water to induce liver cancer models. Then, rats in the transplantation group were subjected to bone marrow mesenchymal stem cel transplantation via the tail vein. Two weeks after cel transplantation, CXCL5, interleukin-8 and interleukin-6 levels were tested by ELISA, mRNA level of hepatocyte nuclear factor 1αdetected by RT-PCR, expression of Bcl-2 and Bax in liver tissue measured by immunohistochemical method, and liver cancer cel apoptosis index detected by TUNEL technique.
RESULTS AND CONCLUSION:After modeling, the expressions of CXCL5, interleukin-8 and interleukin-6 in the control group were significantly higher than those in the healthy group (P<0.05), while these indexes were reduced significantly after bone marrow mesenchymal stem cel transplantation (P<0.05) and close to the normal levels (P>0.05). Bone marrow mesenchymal stem cel transplantation significantly up-regulated the mRNA level of hepatocyte nuclear factor 1αin the liver tissue that was decreased obviously after modeling (P<0.05). In addition, the expression of Bcl-2 was reduced, while the expression of Bax and the apoptosis index increased significantly in the transplantation group compared with the control group (P<0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation contributes to hepatocyte differentiation and regeneration in liver cancer rats by reducing serum inflammatory factor levels and promoting apoptosis in hepatoma carcinoma cel s.

ObjectiveTo evaluate the effect and safety of recombinant human erythropoietin (rhEPO) in treatment of lung cancer chemotherapy-related anemia.MethodsNinety-eight lung cancer chemotherapy-related anemia patients were divided into treatment group and control group with 49 cases each by random digits table method.The patients in treatment group were given rhEPO and chalybeate.The patients in control group were merely given chalybeate.The hemoglobin (Hb),hematocrit,allogeneic blood transfusion rate and quality of life between two groups were observed and compared.ResultsThree cases were rejected in treatment group,and 3 cases with anergy and dizzy and 2 cases with local injection site pain and sclerosis recovered spontaneously.Hb and hematocrit showed downward trend after treatment in control group,but there was no significant differences (P ＞ 0.05).Hb and hematocfit had upgrade trend after treatment in treatment group,and there were significant differences between after 4 - 8 months treatment and before treatment (P ＜ 0.05 ).The allogeneic blood transfusion rate was 24.5％ (12/49) in control group and 6.5％ (3/46) in treatment group,and there was significant difference between two groups (P ＜ 0.05 ).The quality of life in treatment group was increased compared with that in control group.There were significant differences in the effective rate after 4 or 8 weeks treatment between two groups [52.2％(24/46) vs.6.1％(3/49) and 95.7％ (44/46) vs.20.4％ ( 10/49 )].ConclusionsrhEPO is effective and safe in treatment of lung cancer chemotherapy-related anemia.rhEPO has little adverse reaction and can improve the quality of life.