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Understanding the association of pyroptosis with tumor progression, prognosis and effect on immunotherapeutic response in breast cancer (BC) is limited. This study analysed forty pyroptosis-related genes to construct the pyroptosis score. Association of the pyroptosis score with the overall survival, clinical features, tumor mutation load, immune cell infiltration, and treatment sensitivity of patients with BC was analysed. Out of 983 BC samples, 304 (30.93%) had genetic alterations with the highest TP53 frequency. We identified three separate subtypes associated with pyroptosis action. These subtypes correlate with the clinicopathological characteristics, TME immune cell infiltration, and disease prognosis. Based on the expression levels of the pyroptosis genes, we divided the pyroptosis score into a high group and a low group. The immune-activated pyroptosis subtype had a higher score with a better prognosis. We also observed that the pyroptosis score correlates with the tumor mutation burden. The pyroptosis score and disease prognosis were directly proportional. A higher pyroptosis score indicated a better prognosis. Results suggest that the pyroptosis-related gene prognosis model is closely related to the immune cell infiltration of BC. The three pyroptosis subtypes associated with BC assist in accurately identifying the tumor subtype, the prognosis of immunotherapy drugs and the patient's therapeutic response. [ABSTRACT FROM AUTHOR]

Approximately 20% of aged captive giant pandas (Ailuropoda melanoleuca) have cataracts that impair their quality of life. To identify potential biomarkers of cataract formation, we carried out a quantitative proteomics analysis of 10 giant pandas to find proteins differing in abundance between healthy and cataract-bearing animals. We identified almost 150 proteins exceeding our threshold for differential abundance, most of which were associated with GO categories related to extracellular localization. The most significant differential abundance was associated with components of the proteasome and other proteins with a role in proteolysis or its regulation, most of which were depleted in pandas with cataracts. Other modulated proteins included components of the extracellular matrix or cytoskeleton, as well as associated signaling proteins and regulators, but we did not find any differentially expressed transcription factors. These results indicate that the formation of cataracts involves a complex post-transcriptional network of signaling inside and outside lens cells to drive stress responses as a means to address the accumulation of protein aggregates triggered by oxidative damage. The modulated proteins also indicate that it should be possible to predict the onset of cataracts in captive pandas by taking blood samples and testing them for the presence or absence of specific protein markers. [ABSTRACT FROM AUTHOR]

Microsecond pulsed electric fields (PEF) have previously been used for various tumour therapies, such as gene therapy, electrochemotherapy and irreversible electroporation (IRE), due to its demonstrated ability. However, recently nanosecond pulsed electric fields (nsPEF) have also been used as a potential tumor therapy via inducing cell apoptosis or immunogenic cell death to prevent recurrence and metastasis by interacting with intracellular organelles. A large proportion of the existing in-vitro studies of nsPEF on cells also suggests cell necrosis and swelling/blebbing can be induced, but the replicability and potential for other effects on cells suggesting a complicated process which requires further investigation. Therefore, this study investigated the effects of pulse width and intensity of nsPEF on the murine melanoma cells (B16) and normal murine fibroblast cells (L929) through electromagnetic simulation and in-vitro experiments. Through examining the evolution patterns of potential difference and electric fields on the intracellular compartments, the simulation has shown a differential effect of nsPEF on normal and cancerous skin cells, which explains well the results observed in the reported experiments. In addition, the modelling has provided a clear evidence that a few hundreds of ns PEF may have caused a mixed mode of effects, i.e. a 'cocktail effect', including cell electroporation and IRE due to an over their threshold voltage induced on the plasma membrane, as well as cell apoptosis and other biological effects caused by its interaction with the intracellular compartments. The in-vitro experiments in the pulse range of the hundreds of nanoseconds showed a possible differential cytotoxicity threshold of electric field intensity between B16 cells and L929 cells. [ABSTRACT FROM AUTHOR]

Circular saw blades are widely used in stone processing. The circular saw blade cutting hard rock numerical simulation model based on ANSYS/LS-DYNA was established to investigate the complex dynamic problem in rock cutting. The failure mechanism of the rock and the influence of cutting parameters on the cutting force and rock fragments were studied by numerical simulation. The results demonstrated that the failure modes of the rock were mainly tensile failure with some shear failure and compressive failure. The cutting force and the number of fragments increased with the feed speed. With the increasing circular saw blade rotational speed, the cutting force and the number of fragments decreased and tended to stabilize. With the distance between the circular saw blades increasing, the cutting force and rock fragments number increase and then maintain basic stability, and when the distance between double circular saw blades reaches 25 mm, it will form a completed rock plate and the interaction of circular saw blades will decrease. The numerical simulation can accurately simulate rock breakage and force when a circular saw blade cuts rock. [ABSTRACT FROM AUTHOR]

To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS. [ABSTRACT FROM AUTHOR]

Nitrate is an important precursor of tobacco-specific nitrosamines (TSNAs) and a remarkable difference in nitrate accumulation between lamina and midrib of flue-cured tobacco has long been observed. However, the physiological and molecular mechanisms underpinning this difference remain poorly understood. In this study, physiological and genetic factors impacting nitrate accumulation were identified in pot experiments using flue-cured tobacco K326 with contrasting nitrate content between lamina and midrib. The results showed that three times higher NO3-N content was observed in midrib than that in the lamina, along with lower pigment, NH4-N content, nitrate reductase activity (NRA), sucrose synthetase activity (SSA), and glutamine synthetase activity (GSA) in midrib. Transcriptome analysis revealed that expression of genes involved in porphyrin and chlorophyll metabolism, carotenoid biosynthesis, photosynthesis-antenna proteins, photosynthesis, carbon fixation in photosynthetic organisms, starch and sucrose metabolism, nitrogen metabolism, and biosynthesis of amino acids were significantly lower in midrib than in lamina. qRT-PCR results showed that the expression level of nitrate transporter genes LOC107782967, LOC107806749, LOC107775674, LOC107829632, LOC107799198, LOC107768465 decreased by 2.74, 1.81, 49.5, 3.5, 2.64 and 2.96-folds while LOC107789301 increased by 8.23-folds in midrib but not in lamina. Reduced chlorophyll content might result in low carbohydrate formation which is the source of energy and carbon skeleton supply, then the low capacity of nitrogen reduction, assimilation and transportation, and the poor ability of nitrate reallocation but the high capacity of accumulation might lead to nitrate accumulation in midrib. The results laid the foundation for reducing nitrate content and TSNA formation in tobacco midribs and their products. [ABSTRACT FROM AUTHOR]

Giant magnetostrictive injector using giant magnetostrictive material acting an electronic controlled injector may be one new promising injector to acquire adjustable injection rates while maintaining large injection quantity. An electronic controlled injector driven by a giant magnetostrictive actuator was designed through combining the driving requirement and output characteristics of the material. To promote responding speed of the coil current, the driving voltage with open-hold-fall type waveform was employed just like using in an electromagnetic injector. Simulation model for the injection characteristic of the injector was established using AMEsim software and verified using experimental results collected by the single injection meter. From simulation and experimental results, designed giant magnetostrictive injector showed good performances as maximum spray rate of 4.5 L/min and minimum spray pulse width of 0.21 ms, and realized the boot shape injection when generated by the designed voltage wave. Furthermore, duration time and amplitude of the pilot spray part in a boot shape injection were respectively adjusted through changing the dwell time and opening time. The boot shape injection reached by the giant magnetostrictive injector can reach quite accurate control of fuel injection and then promote fuel efficiency effectively. [ABSTRACT FROM AUTHOR]