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Checkpoint blockade antibodies have been approved as immunotherapy for multiple types of cancer, but the response rate and efficacy are still limited. There are few immunogenic cell death-inducing (ICD-inducing) drugs available that can kill cancer cells, enhance tumor immunogenicity, increase in vivo immune infiltration, and thereby boost a tumor response to immunotherapy. So far, the ICD markers have been identified as the few immunostimulating characteristics of dead cells, but whether the presence of such ICD markers on tumor cells translates into enhanced antitumor immunity in vivo is still being investigated. To identify anticancer drugs that could induce tumor cell death and boost T cell response, we performed drug screenings based on both an ICD reporter assay and a T cell activation assay. We showed that teniposide, a DNA topoisomerase II inhibitor, could induce high-mobility group box 1 (HMGB1) release and type I IFN signaling in tumor cells and that teniposide-treated tumor cells could activate antitumor T cell response both in vitro and in vivo. Mechanistically, teniposide induced tumor cell DNA damage and innate immune signaling, including NF-[kappa]B activation and stimulator of IFN genes-dependent (STING-dependent) type I IFN signaling, both of which contribute to the activation of dendritic cells and subsequent T cells. Furthermore, teniposide potentiated the antitumor efficacy of anti-PD1 in multiple types of mouse tumor models. Our findings showed that teniposide could trigger tumor immunogenicity and enabled a potential chemoimmunotherapeutic approach to potentiating the therapeutic efficacy of anti-PD1 immunotherapy., Introduction Cancer immunotherapy has become the major theme of cancer treatment regimens in the last few years, testifying to the genuine capability of the immune control of cancer (1, 2). [...]

Postmortem computed tomography (PMCT) has a limited value in investigating coronary artery disease, despite several obvious advantages over the conventional autopsy. To address this issue, postmortem computed tomography angiography (PMCTA) has been introduced into various studies, where it has been used to investigate natural and unnatural deaths involving vascular damage, occlusion, or other pathologies of the vascular system. To investigate the application value of PMCTA in the diagnosis of coronary artery stenosis in ex situ hearts, the water-based contrast media were injected into isolated hearts, scaned, and finally compared with gold standards (autopsy and histology findings of the coronary artery). This study involved 16 subjects from the Academy of Forensic Science who were suspected to have died of sudden death without traumatic injuries. Unenhanced PMCT was performed first, followed by PMCTA using a water-based contrast agent, injected into the coronary arteries of isolated hearts using a self-designed angiography device. The image data were reconstructed into three-dimensional (3D) angiography images using software in the angiography facility. The 3D images were recorded and evaluated by two radiologists and then statistically analysed. The results of PMCTA were consistent with the gold standards for the diagnosis of coronary artery stenosis (P  > 0.05). However, water-based contrast media can only be used to examine the pathological changes of blood vessels, which may have limitations in the diagnosis of causes of death such as myocardial oedema. PMCTA can be used as a new method to evaluate the degree of coronary atherosclerosis in addition to traditional autopsy. The 3D reconstruction technique reveals the coronary artery lesions more objectively and vividly and provides the opportunity to re-read the data at any time. Key points The methods and parameters for coronary angiography in isolated human hearts were standardized based on the previous researcher. PMCTA in isolated human hearts is including the 3D reconstruction technique that reveals the coronary artery lesions more objectively and vividly, and provides the opportunity to re-read the data at anytime. PMCTA could only be used to examine the pathological changes of blood vessels, which might have limitations for the diagnosis of causes of death. PMCTA in isolated human hearts can be viewed as an auxiliary method for establishing the cause of death, which can provide an assessment of degree and extent of arterial stenosis and accurately help determine the abnormal location. [ABSTRACT FROM AUTHOR]

The characteristics of the earthquake activity in the Eurasian earthquake zone, which is the second largest earthquake zone in the world, was investigated by researchers. The earthquake activity of the Eurasian earthquake zone was analysed in various disciplines, such as earth dynamics, rock mechanics, geology and tectonics. The emergence of fractal theory provided a new direction in exploring the characteristics of the earthquake activity in the Eurasian earthquake zone. This study processed the data on the earthquake activity in the Eurasian earthquake zone by self-similarity method and scaled invariant feature test and used the rescaled range analysis method to analyse the nonlinear time series fractal characteristics of the earthquake activity in the Eurasian earthquake zone. Results show that the time series of earthquake activity in the study area is not an independent Poisson process, which exhibits the characteristics of scale invariance and long-range correlation. Approximately 80% of the H values of the earthquake activity iteratively increase and decrease for moderate earthquakes, which is mainly concentrated during the increasing stage. The time difference of the H value between the two-neighbouring earthquake shows that the H value fluctuates in the active earthquake region and is stationary in the relatively stable region. Strong earthquakes will likely occur in the next few years because the H value fluctuates.

A complete scientific system of earthquake prediction has yet to be developed, and most studies on the time–space sequence of seismic activity analysis are based on existing seismic models. By applying fractal theory with the two aspects of magnitude and intensity, a new dimension is added. In this study, we applied multifractal theory to analyse data of the Circum-Pacific seismic belt, which contains multifractal spectrums such as the relation, relation, and relation. The results suggest that earthquakes in the area which we studied contain multifractal features. The study also shows that the time–space propagation characteristics of the earthquakes are affected by the internal geological structures of the region and the adjacent area.

Mycobacteriophages have played an important role in the development of genetic tools and diagnostics for pathogenic mycobacteria, including Mycobacterium tuberculosis. However, despite the isolation of numerous phages that infect mycobacteria, the mechanisms of mycobacteriophage infection remain poorly understood, and knowledge about phage receptors is minimal. In an effort to identify the receptor for phage I3, we screened a library of Mycobacterium smegmatis transposon mutants for phage-resistant strains. All four phage I3-resistant mutants isolated were found to have transposon insertions in genes located in a cluster involved in the biosynthesis of the cell-wall-associated glycopeptidolipid (GPL), and consequently the mutants did not synthesize GPLs. The loss of GPLs correlated specifically with phage 13 resistance, as all mutants retained sensitivity to two other mycobacteriophages: D29 and Bxz1. In order to define the minimal receptor for phage I3, we then tested the phage sensitivity of previously described GPL-deficient mutants of M. smegmatis that accumulate biosynthesis intermediates of GPLs. The results indicated that, while the removal of most sugar residues from the fatty acyl tetrapeptide (FATP) core of GPL did not affect sensitivity to phage I3, a single methylated rhamnose, transferred by the rharnnosyltransferase Gtf2 to the FATP core, was critical for phage binding. DOI 10.1099/mic.0.033209-0