Measurement Method for Contact Wire Wear Based on Stereovision.

The contact wire wear is an important parameter to ensure the safety operation of electric railways. The contact wire may break if the wear is serious, which leads to transportation interruptions. This study proposes an optical measurement method of contact wire wear, using stereovision technology. The matching method of stereovision based on line-scan cameras is proposed. A lookup-table method is developed to exactly determine the image resolution caused by the contact wire being in different spatial positions. The wear width of the contact wire is extracted from catenaries' images, and the residual thickness of the contact wire is calculated. The method was verified by field tests. The round-robin tests of the residual thickness at the same location present excellent measurement repetitiveness. The maximum difference value between dynamic test results and ground measurement results is 0.13 mm. This research represents a potential way to implement condition-based maintenance for contact wire wear in the future in order to improve the maintenance efficiency and ensure the safety of catenary infrastructure.

Therapeutic efficacy of omalizumab in children with moderate-to-severe allergic asthma combined with chronic sinusitis.

Background: Omalizumab has been approved for treating moderate-to-severe asthma in children aged over 6 years. Its application to asthmatic children with other allergic diseases has been rarely explored. The present study aims to explore the therapeutic efficacy of omalizumab in children with moderate-to-severe allergic asthma combined with chronic sinusitis. Methods: The clinical data of children diagnosed with moderate-to-severe allergic asthma combined with chronic sinusitis and treated with omalizumab between September 2020 and April 2022 were retrospectively analyzed. Lung function indexes such as Childhood Asthma Control Test (C-ACT) scores, fractional exhaled nitric oxide (FeNO), and forced expiratory volume in the first second (FEV1) percent predicted (FEV1%pred), small airway function indexes, and the clinical symptoms of chronic sinusitis were analyzed. Results: A total of 26 children were observed for 16 weeks. After 16 weeks of omalizumab treatment, the significantly increased C-ACT scores (15.57 ± 3.25 points vs. 24.98 ± 5.21 points, F = 15.7112, P < 0.001) and decreased FeNO (31.55 ± 15.57 ppb vs. 19.86 ± 9.80 ppb, F = 4.4265, P = 0.0022), compared with those at baseline, were suggestive of well-controlled symptoms of asthma and improved lung function. FEV1%pred and FEV1/forced vital capacity (FVC) ratio (the ratio of the forced expiratory volume in the first 1 s to the forced vital capacity) increased after omalizumab treatment, although no significant differences were detected (P = 0.9954 and 0.9382, respectively). Peak expiratory flow (PEF) percent predicted (PEF%pred) and forced expiratory flow at 75% of FVC (FEF75%), 50% of FVC (FEF50%), and 25%-75% of FVC (FEF25%-75%) significantly increased after omalizumab treatment (P = 0.0477, <0.001, <0.001, and <0.001, respectively). Visual analog scale scores significantly decreased after omalizumab treatment (6.40 ± 2.98 points vs. 0.85 ± 0.40 points, t = 27.2419, P < 0.001), suggesting alleviation in the clinical symptoms of chronic sinusitis. Conclusion: In this study, it was found that omalizumab can effectively alleviate clinical symptoms and improve lung function and quality of life in children with moderate-to-severe allergic asthma combined with chronic sinusitis.

Correction: Ensemble model for rail surface defects detection.

[This corrects the article DOI: 10.1371/journal.pone.0268518.].

Ensemble model for rail surface defects detection.

The detection of rail surface defects is vital for high-speed rail maintenance and management. The CNN-based computer vision approach has been proved to be a strong detection tool widely used in various industrial scenarios. However, the CNN-based detection models are diverse from each other in performance, and most of them require sufficient training samples to achieve high detection performance. Selecting an appropriate model and tuning it with insufficient annotated rail defect images is time-consuming and tedious. To overcome this challenge, motivated by ensemble learning that uses multiple learning algorithms to obtain better predictive performance, we develop an ensemble framework for industrialized rail defect detection. We apply multiple backbone networks individually to obtain features, and mix them in a binary format to obtain better and more diverse sub-networks. Image augmentation and feature augmentation operations are randomly applied to further make the model more diverse. A shared feature pyramid network is adopted to reduce model parameters as well as computation cost. Experimental results substantiate that the approach outperforms single detecting architecture in our specified rail defect task. On the collected dataset with 8 defect classes, our algorithm achieves 7.4% higher mAP.5 compared with YOLOv5 and 2.8% higher mAP.5 compared with Faster R-CNN.

Iron Activates cGAS-STING Signaling and Promotes Hepatic Inflammation.

Iron deposition and chronic inflammation are associated with chronic liver diseases, such as alcoholic liver disease, nonalcoholic fatty liver disease, and chronic hepatitis B and C. However, the relationship between iron deposition and chronic inflammation in these diseases is still unclear. In the current study, we aimed to investigate the effect of iron on chronic inflammation in HepG2 cells and mice liver. We demonstrated that iron treatment enhanced the expression of cGAS, STING, and their downstream targets, including TBK1, IRF-3, and NF-κB in HepG2 cells and mice liver. We also found that treatment of HepG2 cells and mice with ferric ammonium citrate increased the expression of inflammatory cytokines, such as IFN-ß. Finally, we found that genes involved in iron metabolism and the STING signaling pathway were up-regulated in liver cancer tissues, and the survival time of patients with high expression of these genes in tumor tissues was significantly shortened. These results suggest that iron overload may promote the progress of the chronic liver disease by activating cGAS-STING-mediated chronic inflammation, which provides a new idea for the development of drugs for the treatment of the chronic liver disease.

Exposure to environmental air pollutants as a risk factor for primary Sjögren's syndrome.

Background: Environmental etiology of primary Sjögren's syndrome (pSS), an autoimmune disease, has been proposed. This study determined whether the exposure to air pollutants was an independent risk factor for pSS. Methods: Participants were enrolled from a population-based cohort registry. Daily average concentrations of air pollutants from 2000 to 2011 were divided into 4 quartiles. Adjusted hazard ratios (aHRs) of pSS for exposure to air pollutants were estimated in a Cox proportional regression model adjusting for age, sex, socioeconomic status, and residential areas. A subgroup analysis stratified by sex was conducted to validate the findings. Windows of susceptibility indicated years of exposure which contributed the most to the observed association. Ingenuity Pathway Analysis was used to identify underlying pathways of air pollutant-associated pSS pathogenesis, using Z-score visualization. Results: Two hundred patients among 177,307 participants developed pSS, with a mean age of 53.1 years at acumulative incidence of 0.11% from 2000 to 2011. Exposure to carbon monoxide (CO), nitric oxide (NO), and methane (CH4) was associated with a higher risk of pSS. Compared to those exposed to the lowest concentration level, the aHRs for pSS were 2.04 (95%CI=1.29-3.25), 1.86 (95%CI=1.22-2.85), and 2.21 (95%CI=1.47-3.31) for those exposed to high levels of CO, NO, and CH4, respectively. The findings persisted in the subgroup analysis, in which females exposed to high levels of CO, NO, and CH4 and males exposed to high levels of CO were associated with significantly great risk of pSS. The cumulative effect of air pollution on pSS was time-dependent. The underlying cellular mechanisms involved chronic inflammatory pathways including the interleukin-6 signaling pathway. Conclusion: Exposure to CO, NO, and CH4 was associated with a high risk of pSS, which was biologically plausible.

Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.

Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model.

Although the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model. Our further mechanism investigation reveals that synergistic therapeutic effect is associated with marked promotion of tumor immune infiltration and recognition in both local and distant tumors as well as spleens. PD-1 blockade has no obvious effect on promotion of tumor immune infiltration and recognition. Localized therapy with ZD55-IL-24, however, can help PD-1 blockade to overcome the limitation of relatively low tumor immune infiltration and recognition. This study provides a rationale for investigation of such combination therapy in the clinic.

The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing.

ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a "nonself" label in tumor cells and then turn the tumor cells from the "self" state into the "nonself" state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.

A Rail Fastener Tightness Detection Approach Using Multi-source Visual Sensor.

At present, the method of two-dimensional image recognition is mainly used to detect the abnormal fastener in the rail-track inspection system. However, the too-tight-or-too-loose fastener condition may cause the clip of the fastener to break or loose due to the high frequency vibration shock, which is difficult to detect from the two-dimensional image. In this practical application background, 3D visual detection technology provides a feasible solution. In this paper, we propose a fundamental multi-source visual data detection method, as well as an accurate and robust fastener location and nut or bolt segmentation algorithm. By combining two-dimensional intensity information and three-dimensional depth information generated by the projection of line structural light, the locating of nut or bolt position and accurate perception of height information can be realized in the dynamic running environment of railway. The experimental results show that the static measurement accuracy in the vertical direction using the structural light vision sensor is 0.1 mm under the laboratory condition, and the dynamic measurement accuracy is 0.5 mm under the dynamic train running environment. We use dynamic template matching algorithm to locate fasteners from 2D intensity map, which achieves 99.4% accuracy, then use the watershed algorithm to segment the nut and bolt from the corresponding depth image of located fastener. Finally, the 3D shape of the nut and bolt is analyzed to determine whether the nut or bolt height meets the local statistical threshold requirements, so as to detect the hidden danger of railway transportation caused by too loose or too tight fasteners.

Novel poly-ß-cyclodextrin derivatives as advanced carriers for 5-fluorouracil for tumor: the impact of charge on antitumor efficiency.

BACKGROUND: With the emergence of more and more cyclodextrin derivatives, cyclodextrin becomes an effective adjuvant for improving the prescription of drugs. Its application in pharmacy, especially in the sustained and controlled release, targeting, transdermal and mucosal drug delivery systems, is also being expanded and deepened. In this study, novel cyclodextrin derivatives were developed to investigate the impact of the charge on antitumor efficiency by introducing different groups (carboxymethyl or quaternary ammonium group) to poly-ß-cyclodextrin (ß-CD). METHODS: These novel ß-CD derivatives were prepared by the nucleophilic substitution reaction and characterized by IR and 1H NMR. Fluorouracil (5-FU) was adopted as a model drug to form inclusion compounds. The content of 5-FU in inclusion compounds was evaluated using fluorine element analysis. Also, the cytotoxicity of poly-ß-CD derivatives was studied. Finally, the effect of negative and positive charges on the antitumor activity of poly-ß-CD derivatives-5-FU inclusion compounds on HepG2 cancer cells was evaluated. Human liver cancer HepG2 cells (CYP3A4G/7R clone 87, RRID: CVCL_1×10) were purchased from Cell Bank, Shanghai Institutes for Biological Sciences (China). RESULTS: The results of IR and 1H NMR indicated consistently that both carboxymethyl poly-ß-CD (poly-CM-ß-CD) and glycidyl trimethyl ammonium chloride (GTMAC) poly-ß-CD (poly-GTAC-ß-CD) were successfully prepared. Fluorouracil was successfully loaded into poly-ß-CD derivatives. The results of fluorine analysis indicated that the content of 5-FU in 1 g poly-ß-CD, poly-GTAC-ß-CD and poly-CM-ß-CD was 1,214, 921 and 1,187 µg, respectively. No cytotoxicity of poly-ß-CD derivatives on HepG2 cells was observed. The killing effect of poly-ß-CD-5-FU on HepG2 cells was similar to that of poly-GTAC-ß-CD-5-FU. Poly-CM-ß-CD-5-FU had the worst killing effect on HepG2 cells. CONCLUSIONS: Charge had impact on antitumor efficiency. These novel poly-ß-CD derivatives have potential applications in tumor sustained-release targeted therapy.

[Genetic diagnosis of a Chinese pedigree affected with neonatal argininosuccinic aciduria].

OBJECTIVE: To explore the genetic basis of a neonate with argininosuccinic aciduria (ASA). METHODS: A neonate with lethargy and food refusal was admitted. The patient had myoclonus, myasthenia, uroschesis, irregular breathing and paroxysmal ventricular tachycardia, and died at 75 hours after birth. Laboratory test showed marked increase in blood ammonia (1249.8 µmol/L). Peripheral blood samples of the patient, her parents and sister were collected and subjected to trio whole-exome sequencing. RESULTS: Whole-exome sequencing revealed that the patient has carried compound heterozygous mutations of the argininosuccinate lyase (ASL) gene, namely c.425(exon5)_c.426(exon5) insAGCTCCCAGCT (p.Thr142Thrfs*37) and c.626(exon8)delT (p.Leu209Argfs*42). The patient was diagnosed as ASA caused by ASL gene mutations. Her parents and her elder sister were heterozygous carriers of the above mutations and had a normal phenotype. CONCLUSION: ASA is a severe congenital genetic metabolic disease and can manifest as onset of hyperammonemia in neonates. The clinical diagnosis is difficult and ASL gene testing may be helpful.

Oxidative stress, apoptosis activation and symbiosis disruption in giant clam Tridacna crocea under high temperature.

Giant clams are one of the most important animals in coral reef ecosystem, and its growth and reproduction are being threatened by heat stress due to global warming. In the present study, the symbiont density, the crucial enzyme activities and the transcriptome were investigated in the outer mantle of giant clam Tridacna crocea after the acute exposure of high temperature. The density of symbiotic zooxanthellae decreased significantly during 12-24 h, with the minimum level (7.75 × 105 cell cm-2, p < 0.05) at 12 h after heat stress. The activities of superoxide dismutase in the heat stress group was significantly lower than that in the control group at 24 h after heat stress, while no significant change in the activities of catalase was observed during the entire stress process. The activation level of caspase3 began to increase significantly at 12 h (1.22-fold, p < 0.05), and reached the highest level at 24 h (1.38-fold, p < 0.05) after heat stress. Six paired-end libraries were sequenced in two groups, including the heat stress and control group at 12 h after heat stress. Through the assembling of 187,116,632 paired-end reads with lengths of 2 × 150 bp, a total of 26,676 genes were obtained which derived from giant clam. Bioinformatics analysis revealed 47 significantly upregulated and 88 significantly downregulated genes at 12 h after the treatment. There were 12 overrepresented GO terms for significantly upregulated genes, mostly related to unfolded protein binding and ATP binding, whereas no GO term was overrepresented for significantly downregulated genes. These results collectively suggest high temperature could induce excessive oxidative stress through the repressed antioxidant ability, the apoptosis activated by the unfolded protein response, and further the collapse of the symbiosis between host and symbiont, which has been threatening the growth and reproduction of the giant clam T. crocea.

Folate-polyethylene glycol conjugated carboxymethyl chitosan for tumor-targeted delivery of 5-fluorouracil.

Targeted drug delivery has been evolving at an increasing rate due to its potential to reduce the minimum effective dose of a drug and its accompanying side effects. It has shown improved therapeutic efficacy at equivalent plasma concentrations; however, the development of effective targeted delivery systems has remained a major task. In this study, a drug carrier was designed and synthesized by conjugation of folate acid (FA) to carboxymethyl chitosan (CMCS) through a polyethylene glycol (PEG) spacer. The resulting conjugates were confirmed by 1H nuclear magnetic resonance and infrared spectroscopy. The cytotoxicity of CMCS and CMCS­5­fluorouracil (5­FU) was determined by a crystal violet stain assay. The potential of CMCS­PEG­FA for use in the targeted delivery of 5­FU was investigated using 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide analysis in two cell lines, HeLa and A549, which contain different numbers of folate receptors on their surfaces. The MTT results revealed that in HeLa cells, the cytotoxicity of (CMCS­5­FU)­PEG­FU cells is greater compared with CMCS­5­FU, suggesting that folate receptor­mediated endocytosis may affect the cellular uptake efficiency of 5­FU­loaded CMCS­PEG­FA. The CMCS­PEG­FA conjugates presented in this study show promise as carriers for chemotherapeutic agents due to their solubility at physiological pH, efficiency in carrying chemotherapeutic agents, low cytotoxicity and targeting ability.

[Effect of ligustrazine on airway remodeling in asthmatic rats].

OBJECTIVE: To observe the effect and mechanism of ligustrazine on the airway remodeling. METHODS: Thirty-two SD rats were randomly divided into 4 groups: the normal group (A), the model group (B), the ligustrazine low-dose group (C, 40 mg/kg) and the ligustrazine high-dose group (D, 80 mg/kg), with 8 rats in each group. The chronic asthmatic model was established by repeated inhalation of ovalbumin. The changes of collagen and transforming growth factor-beta(1) (TGF-beta(1)) contents in the airway wall, the thickness of smooth muscle and basement membrane, inner and outer diameter were measured by the computerized image analysis system. RESULTS: The thickness of smooth muscle and basement membrane were (11.3 +/- 1.3, 11.3 +/- 1.7) microm in D group, (19.7 +/- 1.8, 19.8 +/- 1.6) microm in B group, the difference being significant (P < 0.01), as compared with A group [(10.6 +/- 1.2) microm, (9.8 +/- 1.6) microm] and C group [(11.6 +/- 0.9) microm, (12.3 +/- 1.8) microm], the difference being not significant (all P > 0.05). The difference in the ratio of inner diameter to outer diameter was significant between D group (0.77 +/- 0.06) and B group (0.63 +/- 0.05), P < 0.01. The contents of collagen type III and TGF-beta(1) were (21 +/- 5, 26 +/- 5) in D group, (55 +/- 7, 69 +/- 14) in B group, the difference being significant (P < 0.01). The differences were also significant when C group [32 +/- 8, 38 +/- 10] was compared with D group (P < 0.05) and B group (P < 0.01). The contents of collagen type I showed no difference among the 4 groups (A group: 34 +/- 13, B group: 44 +/- 8, C group: 36 +/- 8, D group: 39 +/- 8; all P > 0.05). A close correlation between TGF-beta(1) and collagen type III was demonstrated (r = 0.844 2, P < 0.01). CONCLUSION: Ligustrazine might suppress airway remodeling by decreasing the expression of TGF-beta(1) and reducing deposition of collagen.