Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

ObjectiveTo analyze the research status and trends in low-level occupational benzene exposure. Methods Articles on low-level occupational benzene exposure from Chinese and English journals from January 1st, 2000, to December 31th, 2022 were retrieved using the Web of Science and the China National Knowledge Infrastructure, and a bibliometric analysis was conducted. Results A total of 327 articles were included in the analysis, comprising 216 English articles and 111 Chinese articles. i) The number of articles published in English fluctuates greatly over the years, without a trend of continuous growth or decline. Authors from 359 research institutions in 45 countries and regions have published relevant English articles in 97 kinds of journals, involving 281 grants from 226 foundations. The top three countries in terms of articles amount were the United States, Italy, and China, with 81, 46, and 43 papers, respectively. The English articles mainly focused on mechanistic research at the genetic level, such as hematotoxicity, oxidative stress, and DNA damage. ii) The number of Chinese articles increased gradually after 2012, with the growth peak in 2017. Authors from 127 research institutions in 26 provinces, autonomous regions, and municipalities published Chinese articles in 51 kinds of journals, involving 154 grants from 78 foundations. Chinese articles tended to focus on benzene-induced hematotoxicity and occupational health damage. Conclusion Most studies on low-level occupational benzene exposure were conducted in China, the United States and Italy, focused on hematotoxicity. Monitoring international research topics and hotspots of the field has certain reference value for related research in China.

Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Objective To investigate whether sodium butyrate(NaB)and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms.Methods CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib,alone or in combination,on proliferation of HepG2 cells,and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe.TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues.The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting.Results NaB(2 mmol/L)significantly reduced the IC50 of sorafenib in HepG2 cells,and combination index analysis confirmed the synergy between sorafenib and NaB.The ferroptosis inhibitor Fer-1 and the YAP activator(XMU)obviously reversed the growth-inhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells.The combined treatment with NaB and sorafenib,as compared with the two agents used alone,significantly inhibited colony formation of HepG2 cells,further enhanced cellular shrinkage and dispersion,and decreased intracellular GSH and lipid ROS levels,and these effects were reversed by Fer-1 and XMU.TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues.NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells.Conclusion NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Abstract: Objective To identify and analyze the phospholipase A (PLA) gene family in Talaromyces marneffei (T. marneffei), providing the basis for further research on the potential pathogenic effect and mechanism of T. marneffei PLA. Methods The members of the PLA gene family in T. marneffei were genome-wide identified by using bioinformatics, and their gene structure, chromosome distribution, protein physicochemical property and structure, conserved motif, as well as phyletic evolution, were analyzed. The expression levels of PLA genes in T. marneffei under macrophage treatment were analyzed using the qRT-PCR method. Results A total of eight PLA genes were identified from the genome of T. marneffei, unevenly located on 5 chromosomes without any tandem duplications or fragment duplications. The amino acid residues of PLA proteins ranged from 577 to 1546, molecular weights from 65 120 to 170 690, and the isoelectric point from 4.47 to 9.28. All PLA proteins were hydrophilic, with all but PLA3 classified as unstable hydrophilic proteins. Phylogenetic analysis revealed that PLA was divided into two subfamilies: PLA2 and patatin-like phospholipase, consisting of 3 and 5 members respectively. Within the same subfamily, gene structures, protein-conserved motifs, and protein structures were relatively similar, whereas significant differences existed between different subfamilies. qRT PCR results showed that the expression levels of PLA3, PLA6, and PLA8 were upregulated in T. marneffei infected with mouse macrophages. Conclusions PLA3, PLA6, and PLA8 may be related to the survival and reproduction of T. marneffei in macrophages.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals ; Autism Spectrum Disorder ; Macaca mulatta ; Disease Models, Animal ; Behavior, Animal ; Macaca fascicularis ; Male ; Humans

OBJECTIVEAccurate segmentation of lung fields in chest radiographs (CXR) is very useful for automatic analysis of CXR. In this work, we propose to use dense matching of local features and label fusion to automatically segment the lung fields in CXR.

METHODSFor an input CXR, the dense Scale Invariant Feature Transform (SIFT) descriptors and raw image patches were extracted as the local features for each pixel. The nearest neighbors of the local features were then quickly searched by dense matching directly from the whole feature dataset of the reference images. The dense matching included three steps: limited random initialization, propagation of nearest neighbor field, and limited random search, with iteration of the last two steps for several times. The label image patches for each pixel were extracted according to the nearest neighbor field and weighted by the matching similarity. Finally, the weighted label patches were rearranged as the label class probability image of the input CXR, from which thresholds were obtained for segmentation of the lung fields.

RESULTSThe Jaccard index of the proposed method reached 95.5% on the public JSRT dataset.

CONCLUSIONA high accuracy and robustness can be obtained by adopting dense matching of local features and label fusion to segment the lung fields in CXR, and the result is better than that of current segmentation method.

AIM:To examine the relationship between the gene defect,change of protein hydrophobicity,spacial structure change and clinical phenotypes of Duchenne muscular dystrophy(DMD),and to explore the molecular pathogenesis of DMD.METHODS:The gene sequences of 59 cases of DMD/BMD patients with deletion from mutation were analyzed.The relationship between the protein hydrophobicity,3D-spacial structure and clinical phenotypes was examined by biological informatic technology.RESULTS:50 cases of frameshift mutation were all DMD.In other 5 cases with codon mutation that involved the 3rd hydrophobic region,4 cases were diagnosed as DMD and the rest one was BMD.The exon 3 deletion leaded to the intortion of dystrophin N-terminal,which in turn affected the combination of dystrophin and troponin resulting in the DMD pathopoiesis.CONCLUSION:The severity of clinical phenotypes of muscular dystrophy diseases is related to whether the deletion destroys the reading frame,involves the 3rd hydrophobic region or changes the protein special structure.The biological informatic technology provides a new potential research methodology for studying the pathogenesis of DMD.