Characterization and Roles of Cherry Valley Duck NLRP3 in Innate Immunity During Avian Pathogenic Escherichia coli Infection

The nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain containing 3 (NLRP3) is a pattern recognition receptor that is involved in host innate immunity and located in the cytoplasm. In the present study, the full-length cDNA of Cherry Valley duck NLRP3 (duNLRP3) (2,805 bp encode 935 amino acids) was firstly cloned from the spleen of healthy Cherry Valley ducks, and the phylogenetic tree indicated that the duNLRP3 has the closest relationship with Anas platyrhynchos in the bird branch. According to quantitative real-time PCR analysis, the duNLRP3 mRNA has a broad expression spectrum in healthy Cherry Valley duck tissues, and the highest expression is in the pancreas. There was significant up-regulation of duNLRP3 mRNA expression in the liver and down-regulation in the spleen after infection with avian pathogenic Escherichia coli (APEC) O1K1, especially at 3 days after the infection. Ducks hatched from NLRP3-lentiviral vector-injected eggs had significantly higher duNLRP3 mRNA expression in the liver, spleen, brain, and cecum, which are tissues usually with lower background expression. The mRNA expression levels of inflammatory cytokines IL-1β, IL-18, and TNF-α significantly increased after the APEC infection in those tissues. The bacterial content in the liver and spleen decreased significantly compared with the NC-lentiviral vector-injected ducks. In addition, in the duck embryo fibroblasts, both of the overexpression and knockdown of duNLRP3 can trigger the innate immune response during the E. coli infection. Specifically, overexpression induced antibacterial activation, and knockdown reduced the antibacterial activity of the host cells. The IL-1β, IL-18, and TNF-α mRNA expressions showed up-regulation or down-regulation. The results demonstrate that duNLRP3 has a certain antibacterial activity during E. coli infection. These findings also contribute to better understanding the importance of duNLRP3 in regulating the inflammatory response and the innate immune system of ducks

Analysis of the sources of uncertainty for EDR2 film-based IMRT quality assurance

In our institution, patient-specific quality assurance (QA) for intensity-modulated radiation therapy (IMRT) is usually performed by measuring the dose to a point using an ion chamber and by measuring the dose to a plane using film. In order to perform absolute dose comparison measurements using film, an accurate calibration curve should be used. In this paper, we investigate the film response curve uncertainty factors, including film batch differences, film processor temperature effect, film digitization, and treatment unit. In addition, we reviewed 50 patientspecific IMRT QA procedures performed in our institution in order to quantify the sources of error in film-based dosimetry. Our study showed that the EDR2 film dosimetry can be done with less than 3 % uncertainty. The EDR2 film response was not affected by the choice of treatment unit provided the nominal energy was the same. This investigation of the different sources of uncertainties in the film calibration procedure can provide a better understanding of the film-based dosimetry and can improve quality control for IMRT QA

A Blockchain-Based Secure Inter-Hospital EMR Sharing System

In recent years, blockchain-related technologies and applications have gradually emerged. Blockchain technology is essentially a decentralized database maintained by the collective, and it is now widely applied in various fields. At the same time, with the growth of medical technology, medical information is becoming increasingly important in terms of patient identity background, medical payment records, and medical history. Medical information can be the most private information about a person, but due to issues such as operation errors within the network or a hacking attack by a malicious person, there have been major leaks of sensitive personal information in the past. In any case, this has become an issue worth studying to ensure the privacy of patients and protect these medical materials. On the other hand, under the current medical system, the patient’s EMR (electronic medical record) cannot be searched across the hospital. When the patient attends the hospital for treatment, repeated examinations will occur, resulting in a waste of medical resources. Therefore, we propose a blockchain-based secure inter-hospital EMR sharing system in this article. Through the programmatic authorization mechanism by smart contracts, the security of EMR is guaranteed. In addition to the essential mutual authentication, the proposed scheme also provides and guarantees data integrity, nonrepudiation, user untraceability, forward and backward secrecy, and resistance to replay attack

Cost-effectiveness analysis of sorafenib, lenvatinib, atezolizumab plus bevacizumab and sintilimab plus bevacizumab for the treatment of advanced hepatocellular carcinoma in China

Key points With the approval of new first-and second-line drugs and the establishment of treatment based on immune checkpoint inhibitors as standard treatment, treatment options for advanced hepatocellular carcinoma are more diverse than ever before. Therefore, clinical decision-making requires a multidisciplinary team to develop individualized treatment strategies according to the patients' disease and financial ability to pay. Here, we point out that lenvatinib, sintilimab plus bevacizumab and atezolizumab plus bevacizumab are more effective in the treatment of advanced hepatocellular carcinoma, but the cost of treatment is beyond the affordability of the patient. We outlined better drug purchase prices and health insurance reimbursement policies to enable patients to get the optimal treatment

Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1β on the Risk of Silicosis: A Case-Control Study.

To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL)-1β genes and occupational dust exposure on the risk of silicosis.We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE) for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1β genes. We estimated odds ratios(ORs), 95% confidence intervals(95%CIs), and p-values using logistic regression models adjusted for selected confounders.After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12-5.12] and 3.62 [1.63-8.02], respectively). Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C in Nalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24[0.06-0.88]). Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04-6.12] and 5.19[1.88-14.35], respectively). Among subjects with CDE greater than 120 mg/m3×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35-207.39] and 3.47[1.40-8.64], respectively).Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status

Investigation on the mechanism of carbon structural evolution of Huolinhe lignite during different pretreatment processes

The depth understanding of the organic structure characteristics of coal and its evolution is beneficial to the clean and efficient coal directional conversion. This research probes the evolution path and mechanism of carbon structure of lignite during the hydrothermal transitions dewatering (HTD) and tetralin solvent thermal transitions dewatering (TTD). The structural evolution with these two transitions was explored using 13C NMR and XRD in an autoclave at different temperatures. The moisture content in lignite is effectively decreased during HTD and TTD processes, and this is mainly due to the removal of O-containing functional groups and the decrease of water holding capacity. The TTD process is achieved a higher dehydration and deoxidation for lignite compared with HTD process. This is possibly due to that the dehydrating energy of TTD process not only comes from the thermal energy, but also the tetralin is more likely to form hydrogen bonds with water. The aromaticity is increased during HTD and TTD processes, and this increase is possibly contributed by aromatization while the contribution of aromatic rings condensation was limited because the molar ratio of aromatic bridgehead carbon has changed little. Also, from the XRD data, the stacking of aromatic structural units are significantly promoted and are not obvious for the lateral extended size for crystal structural evolution during HTD and TTD processes. when the pretreatment temperature was at 310 °C, the aromaticity increase from 60.94% to 69.50% and 69.68% during HTD and TTD processes, respectively. The stacking height increase from 8.94 Å to 12.06 Å and 13.27 Å, and the stacking number increase from 2.49 to 3.51 and 3.86, the lateral sizes have changed little. The increase of aromaticity is finally manifested in aromatic units vertical stacking height and stacking layer number. These results indicate that the graphitization and ordering are promoted to some degree during HTD and TTD processes. Compared with the HTD, the TTD had the greater impact on the conversion of lignite carbon structure to high-rank coal. Those results are potentially useful to the clean and efficient utilization of lignite