Slicing Recognition of Aircraft Integral Panel Generalized Pocket

AbstractTo automatically obtain a machining area in numerical control (NC) programming, a data model of generalized pocket is established by analyzing aircraft integral panel characteristics, and a feature recognition approach is proposed. First, by reference to the practical slice-machining process of an aircraft integral panel, both the part and the blank are sliced in the Z-axis direction; hence a feature profile is created according to the slicing planes and the contours are formed by the intersection of the slicing planes with the part and its blank. Second, the auxiliary features of the generalized pocket are also determined based on the face type and the position, to correct the profile of the pocket. Finally, the generalized pocket feature relationship tree is constructed by matching the vertical relationships among the features. Machining feature information produced by using this method can be directly used to calculate the cutter path. The validity and practicability of the method is verified by NC programming for aircraft panels

A biophoton method for identifying the quality states of fresh Chinese herbs

Introduction: The quality of Chinese herbs is the basis for ensuring their safety and efficacy. However, the quality evaluation system is imperfect. In particular, there is a lack of quality evaluation methods for fresh Chinese herbs during growth. The biophoton is a common phenomenon and provides complete information about the interior of the living system, which is consistent with the holistic concept of traditional Chinese medicine. Therefore, we aim to correlate the biophoton characteristics with the quality states to find the biophoton parameters that can characterize the quality states of fresh Chinese herbs.Methods: The biophoton characteristics of motherwort and safflower were measured and characterized by the counts per second (CPS) in the steady state and the initial intensity (I0) and coherent time (T) of delayed luminescence. The active ingredient content was measured by ultra-high-performance liquid chromatography (UPLC). The pigment content of motherwort leaves was measured by UV spectrophotometry. The t-test and correlation analysis were performed on the experimental results.Results: The CPS and I0 of motherwort and I0 of safflower showed a significant downward trend during the growth process, and their active ingredient content showed a trend that increased and then decreased. The CPS, I0, and the content of active ingredients and pigments in a healthy state were significantly higher than those in a poor state, while T showed the opposite results. The CPS and I0 were all significantly and positively correlated with the content of active ingredients and pigments, while the T of motherwort showed the opposite results.Conclusion: It is feasible to identify the quality states of fresh Chinese herbs by using their biophoton characteristics. Both CPS and I0 have better correlations with the quality states and can be considered characteristic parameters of the quality of fresh Chinese herbs

Efficacy and safety of second-line therapy by S-1 combined with sintilimab and anlotinib in pancreatic cancer patients with liver metastasis: a single-arm, phase II clinical trial

BackgroundPancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second-line treatment strategies. We attempted to evaluate the efficacy and safety of a combination of S-1, sintilimab, and anlotinib as a second-line treatment in pancreatic cancer patients with liver metastasis.MethodsPancreatic cancer patients with liver metastases were recruited. S-1 was administered orally at 25 mg/m2 bid, anlotinib was administered orally at 12 mg qd from day 1 to day 14, and sintilimab was administered intravenously at 200 mg on day 1. This method was repeated every 21 days, and the therapeutic effect was evaluated every 3 cycles. The primary outcome was the objective response rate (ORR).ResultsOverall, 23 patients were enrolled in this study of whom 19 patients had objective efficacy evaluation. The ORR was 10.5% (95% CI 0.4%–25.7%) in the evaluable population. The progression-free survival (PFS) was 3.53 (95% CI 2.50–7.50) months, and the overall survival (mOS) was 8.53 (95% CI 4.97–14.20) months. Grade 3 adverse events were 26.1%, and no grade 4 or above adverse events occurred. High-throughput sequencing was performed on the tumor tissues of 16 patients; patients with HRD-H (n = 10) had shorter PFS than those with HRD-L (n = 6) (2.43 vs. 5.45 months; P = 0.043), but there was no significant difference in OS between the two groups (4.43 vs. 9.35 months; P = 0.11).ConclusionsThis study suggests the advantage of S-1 combined with sintilimab and anlotinib in extending OS as a second-line therapy in pancreatic cancer patients with liver metastasis.Clinical Trial Registration: ChiCTR200003065

Cathepsins and cancer risk: a Mendelian randomization study

BackgroundPrevious observational epidemiological studies reported an association between cathepsins and cancer, however, a causal relationship is uncertain. This study evaluated the causal relationship between cathepsins and cancer using Mendelian randomization (MR) analysis.MethodsWe used publicly available genome-wide association study (GWAS) data for bidirectional MR analysis. Inverse variance weighting (IVW) was used as the primary MR method of MR analysis.ResultsAfter correction for the False Discovery Rate (FDR), two cathepsins were found to be significantly associated with cancer risk: cathepsin H (CTSH) levels increased the risk of lung cancer (OR = 1.070, 95% CI = 1.027–1.114, P = 0.001, PFDR= 0.009), and CTSH levels decreased the risk of basal cell carcinoma (OR = 0.947, 95% CI = 0.919–0.975, P = 0.0002, PFDR= 0.002). In addition, there was no statistically significant effect of the 20 cancers on the nine cathepsins. Some unadjusted low P-value phenotypes are worth mentioning, including a positive correlation between cathepsin O (CTSO) and breast cancer (OR = 1.012, 95% CI = 1.001–1.025, P = 0.041), cathepsin S (CTSS) and pharyngeal cancer (OR = 1.017, 95% CI = 1.001–1.034, P = 0.043), and CTSS and endometrial cancer (OR = 1.055, 95% CI = 1.012–1.101, P = 0.012); and there was a negative correlation between cathepsin Z and ovarian cancer (CTSZ) (OR = 0.970, 95% CI = 0.949–0.991, P = 0.006), CTSS and prostate cancer (OR = 0.947, 95% CI = 0.902–0.944, P = 0.028), and cathepsin E (CTSE) and pancreatic cancer (OR = 0.963, 95% CI = 0.938–0.990, P = 0.006).ConclusionOur MR analyses showed a causal relationship between cathepsins and cancers and may help provide new insights for further mechanistic and clinical studies of cathepsin-mediated cancer

Making “cold” tumors “hot”- radiotherapy remodels the tumor immune microenvironment of pancreatic cancer to benefit from immunotherapy: a case report

Immune checkpoint inhibitors have limited efficacy in metastatic pancreatic cancer due to the complex tumor immune microenvironment (TIME). Studies have shown that radiotherapy can cause cell lesions to release tumor antigens and then take part in the remodeling of the tumor environment and the induction of ectopic effects via regional and systemic immunoregulation. Here, we reported a case of advanced metastatic pancreatic cancer treated with immunotherapy combined with chemotherapy and radiotherapy and a sharp shift of the TIME from T3 to T2 was also observed. One hepatic metastasis within the planning target volume (PTV) was evaluated complete response (CR), the other one was evaluated partial response (PR) and 2 hepatic metastases outside the PTV were surprisingly considered PR. In the study, we found that immunotherapy combined with chemotherapy and radiotherapy achieved significant therapeutic benefits, which may provide a new strategy for the treatment of advanced pancreatic cancer

The Laser Deposited Nickel-Aluminum Bronze Coatings on SUS630 Stainless Steel and Its Corrosion Resistance in 3.5 wt.% NaCl Solution

In this work, three composite structures of nickel-aluminum bronze (NAB) bonded with SUS630 stainless steel with different intermediate layers were fabricated by laser deposition. The microstructure and corrosion behavior of NAB in 3.5 wt.% NaCl solution were studied. The NAB coating directly deposited on steel substrate contains a large number of Fe-rich dendrites due to the dilution by laser energy and the Cu-Fe liquid phase separation characteristics. The microstructures of NAB were independent and isolated well from the steel substrate when the nickel intermediate layer was applied. Immersion corrosion and electrochemical tests indicated that the composite structure with the nickel intermediate layer presented better corrosion resistance than direct deposited the NAB coating, especially with the NiCr alloy intermediate layer, which led to a shallower corrosion depth and formed a denser layer of protective corrosion products

Bifunctional iRGD-anti-CD3 enhances antitumor potency of T cells by facilitating tumor infiltration and T-cell activation

Background Poor infiltration and limited activation of transferred T cells are fundamental factors impeding the development of adoptive cell immunotherapy in solid tumors. A tumor-penetrating peptide iRGD has been widely used to deliver drugs deep into tumor tissues. CD3-targeting bispecific antibodies represent a promising immunotherapy which recruits and activates T cells.Methods T-cell penetration was demonstrated in tumor spheroids using confocal microscope, and in xenografted tumors by histology and in vivo real-time fluorescence imaging. Activation and cytotoxicity of T cells were assessed by flow cytometry and confocal microscope. Bioluminescence imaging was used to evaluate in vivo antitumor effects, and transmission electron microscopy was used for mechanistic studies.Results We generated a novel bifunctional agent iRGD-anti-CD3 which could immobilize iRGD on the surface of T cells through CD3 engaging. We found that iRGD-anti-CD3 modification not only facilitated T-cell infiltration in 3D tumor spheroids and xenografted tumor nodules but also induced T-cell activation and cytotoxicity against target cancer cells. T cells modified with iRGD-anti-CD3 significantly inhibited tumor growth and prolonged survival in several xenograft mouse models, which was further enhanced by the combination of programmed cell death protein 1 (PD-1) blockade. Mechanistic studies revealed that iRGD-anti-CD3 initiated a transport pathway called vesiculovacuolar organelles in the endothelial cytoplasm to promote T-cell extravasation.Conclusion Altogether, we show that iRGD-anti-CD3 modification is an innovative and bifunctional strategy to overcome major bottlenecks in adoptive cell therapy. Moreover, we demonstrate that combination with PD-1 blockade can further improve antitumor efficacy of iRGD-anti-CD3-modified T cells