•Cancer immunotherapy revolutionize cancer treatment but is associated with unpredictable immune-related adverse events (irAEs).•The tumor microenvironment is complex and changeable and thus it may ...be one potential explanation for varies toxicities.•Toxicities of cancer immunotherapy are highly variable and mostly mild, but life-threatening cases have been reported.•Innocuous symptoms may herald potentially grade 3–4 toxicity; therefore, close attention must be paid to all patients.
Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell therapy are two main promising methods of immunotherapy, which have become increasingly important in cancer treatment. After the wider application of these medicine in clinic, a range of immune related adverse events (irAEs) covering almost any system arouse the concern for being randomness and unpredictability. Even if most adverse events are mild and controllable after thoughtful management, the occurrence of life-threatening toxicities should not be ignored because of the insidious and atypical symptoms, which makes the early diagnosis even more challenging. In this review, a brief introduction of immunotherapy and mechanisms underlying irAEs is involved. We mainly focus on the early diagnostic method and recommended management of toxicities of different systems separately, and consequently maximized effectiveness of immunotherapy can be achieved.
Metal halide perovskites have attracted considerable attention as novel optoelectronic materials for their excellent optical and electrical properties. Inorganic perovskites (CsPbX3, X = Cl, Br, I) ...are now viable alternative candidates for third-generation photovoltaic technology because of their high photoelectric conversion efficiency, high carrier mobility, good defect tolerance, simple preparation method and many other advantages. However, the toxicity of lead is problematic for practical implementation. Thus, the fabrication of lead-free perovskite materials and devices has been actively conducted. In this work, the energy band and photoelectric properties of inorganic perovskites CsBX3 (B = Pb, Sn, Ge, X = Cl, Br, I) have been investigated with the first principles calculation, and the possible defect energy levels and their formation energies in different components, in particular, have been systematically studied. The advantages and disadvantages of Sn and Ge as replacement elements for Pb have been demonstrated from the perspective of defects. This study provides an important basis for the study of the properties and applications of lead-free perovskites.
•A large scale car-following experiment has been performed.•Traffic instability is better characterized by traffic speed than density.•There exists a critical speed between 30km/h and 40km/h for ...Chinese drivers.•Empirical data support the experimental observation.•A new traffic instability mechanism has been proposed.
Traffic instability is an important but undesirable feature of traffic flow. This paper reports our experimental and empirical studies on traffic flow instability. We have carried out a large scale experiment to study the car-following behavior in a 51-car-platoon. The experiment has reproduced the phenomena and confirmed the findings in our previous 25-car-platoon experiment, i.e., standard deviation of vehicle speeds increases in a concave way along the platoon. Based on our experimental results, we argue that traffic speed rather than vehicle spacing (or density) might be a better indicator of traffic instability, because vehicles can have different spacing under the same speed. For these drivers, there exists a critical speed between 30km/h and 40km/h, above which the standard deviation of car velocity is almost saturated (flat) along the 51-car-platoon, indicating that the traffic flow is likely to be stable. In contrast, below this critical speed, traffic flow is unstable and can lead to the formation of traffic jams. Traffic data from the Nanjing Airport Highway support the experimental observation of existence of a critical speed. Based on these findings, we propose an alternative mechanism of traffic instability: the competition between stochastic factors and the so-called speed adaptation effect, which can better explain the concave growth of speed standard deviation in traffic flow.
Generally, the demise of cancer cells in different ways enables the body to clear these harmful cells. However, cancer cells obtain unlimited replication and immortality from successful circumvention ...of cell death
various mechanisms. Some evidence suggests that treatment-induced dying tumor cells even promote cancer progression. Notably, therapeutic interventions to harness the immune system against tumor cells have shown complicated influences in clinics. Herein, there is an urgent need to clarify the underlying mechanisms that influence the outcome and regulation of the immune system during cancer treatment. In this review, we provide an account on the cell death modes and the relationship between dying tumor cells with tumor immune microenvironment during cancer treatment, focusing on immunotherapy, from mechanistic standpoint to emerging limitations and future directions.
The rapid formation and accumulation of inactive lithium (Li) are principally responsible for the limited lifespan of high‐energy‐density Li metal batteries. The construction of composite Li metal ...anode with hosts emerges as a promising strategy to mitigate and accommodate inactive Li. However, the mechanism of inactive Li accumulation in composite Li metal anodes remains unknown, severely plaguing the stability of composite Li metal anodes. Herein, the two‐stage accumulation mechanism of inactive Li in composite Li metal anodes and its correlation with the stability of composite Li metal anodes are comprehensively unveiled in pouch cells by nondestructive 3D X‐ray microscopy. First, inactive Li accumulates in the interior of the host and results in a slowly increased polarization. Second, inactive Li overflows the inside of the host and induces a dramatically increased polarization chiefly responsible for the fast decay of the composite Li metal anodes. The current density and external pressure are identified as key factors to regulate the turning point between the two stages for practical composite Li metal anodes. This work provides original fundamentals for the recognition of inactive Li accumulation in composite Li metal anodes and the design of practical Li metal batteries.
The two‐stage accumulation mechanism of inactive Li in composite Li metal anodes and its correlation with the stability of composite Li metal anodes are comprehensively unveiled in pouch cells, which provides rational design principles of composite Li metal anodes for long‐cycling Li metal pouch cells.
Portable 3D printing biosensing devices have great potential as rapid detection and analytical platforms due to their unique characteristics such as high precision and low cost. In this study, a ...method for rapid determination of lactose in milk was developed based on bioactive paper-3D printing integration technology. The bioactive paper was prepared by combining three enzymes cascade system composed of β -galactosidase, glucose oxidase and Fe-N-C nanozyme (with excellent peroxidase-like activity and superior affinity). In the presence of lactose, the test paper changed from colorless to blue under the condition of TMB, which can be identified by naked eye. With the help of portable chromometer and smart phone, the RGB color index was analyzed and quantified. The entire detection process can be integrated into the 3D printing device that we have designed and completed in 25 min, with the detection limits of qualitative and quantitative were 0.04 g 100 g−1 and 5.61 μg 100 g−1, which could simultaneously satisfy the detection requirements of rapid, sensitive and portable operation. The bioactive paper and 3D printing device are long shelf life (six months) and cost-effective, which means this integration technology has a good application prospect in areas lacking experimental conditions.
•We synthesized Fe-N-C nanozyme to replace peroxidase, which has a wider pH and temperature range.•A 3D printing device based on bioactive paper was designed to integrate from sample processing to output results.•The whole detection process can be completed within 25 min with high sensitivity and specificity.•The biosensor designed by us has a good application prospect in areas lacking experimental conditions.
Four series of novel pyridine derivatives (17 a–i, 18 a–i, 19 a–e, and 20 a–e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target ...compounds showed moderate or high antibacterial activity. The 4‐F substituted compound 17 d (MIC=0.5 μg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 μg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 μg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra‐high concentration (200 μM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.
ABSTRACT
Background: In cross-sectional studies and short-term clinical trials, it has been suggested that there is a positive dose-response relation between alcohol consumption and HDL ...concentrations. However, prospective data have been limited.
Objective: We sought to determine the association between total alcohol intake, the type of alcohol-containing beverage, and the 6-y (2006–2012) longitudinal change in HDL-cholesterol concentrations in a community-based cohort.
Design: A total of 71,379 Chinese adults (mean age: 50 y) who were free of cardiovascular diseases and cancer and did not use cholesterol-lowering agents during follow-up were included in the study. Alcohol intake was assessed via a questionnaire in 2006 (baseline), and participants were classified into the following categories of alcohol consumption: never, past, light (women: 0–0.4 servings/d; men: 0–0.9 servings/d), moderate (women: 0.5–1.0 servings/d; men: 1–2 servings/d), and heavy (women: >1.0 servings/d; men: >2 servings/d). HDL-cholesterol concentrations were measured in 2006, 2008, 2010, and 2012. We used generalized estimating equation models to examine the associations between baseline alcohol intake and the change in HDL-cholesterol concentrations with adjustment for age, sex, smoking, physical activity, obesity, hypertension, diabetes, liver function, and C-reactive protein concentrations.
Results: An umbrella-shaped association was observed between total alcohol consumption and changes in HDL-cholesterol concentrations. Compared with never drinkers, past, light, moderate, and heavy drinkers experienced slower decreases in HDL cholesterol of 0.012 mmol · L−1 · y−1 (95% CI: 0.008, 0.016 mmol · L−1 · y−1), 0.013 mmol · L−1 · y−1 (95% CI: 0.010, 0.016 mmol · L−1 · y−1), 0.017 mmol · L−1 · y−1 (95% CI: 0.009, 0.025 mmol · L−1 · y−1), and 0.008 mmol · L−1 · y−1 (95% CI: 0.005, 0.011 mmol · L−1 · y−1), respectively (P < 0.0001 for all), after adjustment for potential confounders. Moderate alcohol consumption was associated with the slowest increase in total-cholesterol:HDL-cholesterol and triglyceride:HDL-cholesterol ratios. We observed a similar association between hard-liquor consumption and the HDL-cholesterol change. In contrast, greater beer consumption was associated with slower HDL-cholesterol decreases in a dose-response manner.
Conclusion: Moderate alcohol consumption was associated with slower HDL-cholesterol decreases; however, the type of alcoholic beverage had differential effects on the change in the HDL-cholesterol concentration.
During TBM tunnelling, the rock breaking by cutters usually induces vibration. The cutterhead vibration is composed of all cutter vibrations. On the one hand, cutterhead vibration directly affects ...the life of the cutter, cutterhead and main gear. On the other hand, cutterhead vibration reflects the TBM excavation performance. In this paper, a cutterhead vibration monitoring system for TBM tunnelling was developed. The system consisted of the data acquisition module, communication and control module, as well as data processing and display module. Acceleration sensor, gyroscope and clock chip were integrated into a sensor board to acquire triaxial vibration data, cutterhead rotating status and acquisition time. The installation structure with anti-hit and water-proof functions was designed to ensure the stable operation of the system. Three types of data acquisition modes were proposed to meet the different monitoring scenarios. The system was applied in a TBM tunnelling project. Based on the normal monitored data in TBM tunnelling and penetration tests data, the differences in amplitude and frequency of triaxial vibration, as well as the effect of geological conditions and operating parameters on cutterhead vibration characteristics were analyzed. The engineering application showed that this system can reflect the changes of the geological conditions and operating parameters, providing guidance for the TBM tunnelling.
A cutterhead vibration monitoring system for TBM tunnelling was developed.Acceleration sensor, gyroscope and clock chip were integrated into the system.The system was applied in a TBM project and penetration tests were carried out.The influencing factors of cutterhead vibration characteristics were analyzed.
High-mobility group box 1 (HMGB1) is an abundant protein in most eukaryocytes. It can bind to several receptors such as advanced glycation end products (RAGE) and Toll-like receptors (TLRs), in ...direct or indirect way. The biological effects of HMGB1 depend on its expression and subcellular location. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription, telomere maintenance, and genome stability. While outside the nucleus, it possesses more complicated functions, including regulating cell proliferation, autophagy, inflammation and immunity. During tumor development, HMGB1 has been characterized as both a pro- and anti-tumoral protein by either promoting or suppressing tumor growth, proliferation, angiogenesis, invasion and metastasis. However, the current knowledge concerning the positive and negative effects of HMGB1 on tumor development is not explicit. Here, we evaluate the role of HMGB1 in tumor development and attempt to reconcile the dual effects of HMGB1 in carcinogenesis. Furthermore, we would like to present current strategies targeting against HMGB1, its receptor or release, which have shown potentially therapeutic value in cancer intervention.
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