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Tracking the immune microenvironment of tumours is essential for understanding the mechanisms behind the effectiveness of cancer immunotherapies. Molecular imaging of tumour-infiltrating leukocytes (TILs) can be used to non-invasively monitor the tumour immune microenvironment, but current imaging agents do not distinguish TILs from leukocytes resident in other tissues. Here we report a library of activatable molecular probes for the imaging, via near-infrared fluorescence, of specific TILs (including M1 macrophages, cytotoxic T lymphocytes and neutrophils) in vivo in real time and also via excreted urine, owing to the probes' renal clearance. The fluorescence of the probes is activated only in the presence of both tumour and leukocyte biomarkers, which allows for the imaging of populations of specific TILs in mouse models of cancers with sensitivities and specificities similar to those achieved via flow-cytometric analyses of biopsied tumour tissues. We also show that the probes enable the non-invasive evaluation of the immunogenicity of different tumours, the dynamic monitoring of responses to immunotherapies and the accurate prediction of tumour growth under various treatments. Ministry of Education (MOE) National Research Foundation (NRF) K.P. thanks the Singapore Ministry of Education, Academic Research Fund Tier 1 (RG125/19; RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042; MOE-T2EP30220-0010) and the Singapore National Research Foundation (NRF-NRFI07-2021-0005) for financial support.

Ovarian cancer has the highest mortality rate among gynecologic tumors, with a 5-year survival rate of less than 25%. There is an urgent need for early diagnosis and new drugs to reduce the disease burden of ovarian cancer. The aim of this study was to investigate the effectiveness of SLC11A2 as a therapeutic target and marker for ovarian cancer. Expression data of SLC11A2 were obtained from public databases. Then, the biological functions of SLC11A2 were validated in four ovarian cancer cell lines. Finally, we collected ovarian cancer clinical tissues, serum, and plasma exosomes and used immunohistochemistry, Elisa, and liquid chromatography-mass spectrometry (LC–MS) to validate the test efficacy of SLC11A2. The results showed that ovarian cancers with high SLC11A2 mRNA expression had shorter 5-year PFS and MST. Knockdown of SLC11A2 reduced ovarian cancer migration and increased cisplatin-induced apoptosis. Serum SLC11A2 may help improve the detection rate of ovarian cancer.

CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment. However, development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges. Herein, a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system (NPCSPt/pEZH2) and synergistic treatment of prostate cancer. The pEZH2/Pt(II) could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells. The EZH2 gene disruption efficiency could be achieved up to 32.2% of PC-3 cells in vitro and 21.3% of tumor tissues in vivo, leading to effective suppression of EZH2 protein expression. Moreover, significant H3K27me3 downregulation could occur after EZH2 suppression, resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II) to nuclear DNA for enhanced apoptosis. Taken together, substantial proliferation inhibition of prostate cancer cells and further 85.4% growth repression against subcutaneous xenograft tumor could be achieved. This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery, but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.

Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice; however, to improve anticancer efficacy, combination chemotherapy still remains challenge. Dichloroacetate (DCA) could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism. Radiation therapy with fast neutrons (FNT) has high relative biolgical effectiveness compared to other radiotherapeutics. Herein, we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives. We first synthesized a biodegradable polylysine to condense DCA with negative charge, or to conjugate DCA by condensing synthesis, to obtain Ion-DCA and Co-DCA, respectively. DCA, Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats. Upon adhesion on the surface of subcutaneous and orthotopic liver tumors, the multilayer drug-loaded mats realized a controllable release of DCA, which reversed the Warburg effect and inhibited cancer cell proliferation. Meantime, irradiation of fast neutrons could seriously damage DNA structure. Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro, and the tumor inhibition in vivo. This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.

Topographical relief is a key factor that limits population distribution and economic development in mountainous areas. The limitation is especially apparent in the mountain- plain transition zone. Taking the transition zone between the Qinling Mountains and the North China Plain (i.e. the mountainous area in western Henan Province) as an example and based on the 200-m resolution DEM data, we used the mean change-point analysis to determine the optimal statistical unit for topographical relief, and thereafter extracted the relief degree. Taking the 1:100,000 land use data, township population and county-level industrial data, population and economic spatial models were constructed, and 200-m resolution grid population and economic density maps were generated. Afterwards, statistical analysis was carried out to quantitatively reveal the impact of topographical relief on population and economy. In addition, the impacts of other topographical factors were discussed. The results showed the following. (1) The relief degree in western Henan is generally low, where 58.6% of the regional topography does not exceed half the height of a reference mountain (relative elevation ⩽250 m). Spatially, the relief degree is high in the west while low in the east, and high in the middle while low in the north and south. There is a positive correlation between relief degree and elevation, and a much stronger correlation between relief degree and slope. (2) The linear fitting degree between the population and economic validation data and the corresponding simulation data are 0.943 and 0.909, respectively, indicating that the spatialized results can reflect the actual population and economic distribution. (3) The impact of topographical relief on population and economy was stronger than that of other topographical factors. The relief degree showed a good logarithmic fit relationship with population density (0.911) and economic density (0.874). Specifically, 88.65% of the population lives in areas where the topographical relief is ⩽0.5 and 88.03% of the gross regional product was from areas where the relief is ⩽0.3. Compared with the population distribution, the economic development showed an obvious agglomeration trend towards low relief areas.

Background The Rab27 family of small GTPases promotes the progression of breast cancer, melanoma, and other human cancers. In this review, we discuss the role of Rab27 GTPases in cancer progression and the potential applications of these targets in cancer treatment. Main body Elevated expression of Rab27 GTPases is associated with poor prognosis and cancer metastasis. Moreover, these GTPases govern a variety of oncogenic functions, including cell proliferation, cell motility, and chemosensitivity. In addition, small GTPases promote tumor growth and metastasis by enhancing exosome secretion, which alters intracellular microRNA levels, signaling molecule expression, and the tumor microenvironment. Conclusion Rab27 GTPases may have applications as prognostic markers and therapeutic targets in cancer treatment.

The present study aimed to elucidate the mechanism of myocardial damage induced by simulated transport stress. Sprague-Dawley rats were subjected to 35 °C and 60 rpm (0.1×g rcf) on a constant temperature shaker. The blood samples were prepared for detection of epinephrine (E), norepinephrine (NE), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and serum cardiac troponin T (cTNT); myocardium samples were prepared for morphological examination and signaling protein quantitative. The result showed that plasma norepinephrine (NE) and epinephrine (E) concentrations increased in all stressed groups (P < 0.01). Levels of serum cardiac troponin T (cTNT) were elevated in both the S2d (P < 0.05) and S3d groups (P < 0.01). The concentration of plasma BNP was increased significantly in S3d group (P < 0.05); the difference in ANP was not remarkable. Morphological observation demonstrated obvious microstructure and ultrastructure damage after simulated transport stress. There was also a significant increase in the number of TUNEL-positive cardiomyocytes in stressed hearts. Western blot analysis found that the mitogen-activated protein kinase (MAPK) pathways were activated by strengthening phosphorylation of ASK-1, JNK, P38 and ERK in rat myocardial tissue after simulated transport stress (P < 0.05, P < 0.01). In addition, the ratio of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins was increased in stressed rats (P < 0.01), and the amount of cleaved-caspase3 increased in all stressed rats (P < 0.01). The expression of cleaved-caspase9 protein was also elevated in S2d and S3d groups (P < 0.01). Consequently simulated transport stress induced obvious myocardial damage, which may be attributed to the activation of caspase 9-mediated mitochondrial apoptotic pathway and MAPK pathways.

Background As the world warms up, heat stress is becoming a major cause of economic loss in the livestock industry. Long-time exposure of animals to hyperthermia causes extensive cell apoptosis, which is harmful to them. AKT and AKT-related serine–threonine kinases are known to be involved in signaling cascades that regulate cell survival, but the mechanism remains elusive. In the present study, we demonstrate that phosphoinositide 3-kinase (PI3K) /AKT signal pathway provides protection against apoptosis induced by heat stress to ascertain the key point for treatment. Results Under heat stress, rats showed increased shedding of intestinal epithelial cells. These rats also had elevated levels of serum cortisol and improved expression of heat shock proteins (Hsp27, Hsp70 and Hsp90) in response to heat stress. Apoptosis analysis by TUNEL assay revealed a higher number of villi epithelial cells that were undergoing apoptosis in heat-treated rats than in the normal control. This is supported by gene expression analysis, which showed an increased ratio of Bax/Bcl-2 (p