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Chlorantraniliprole (CAP), a diamide insecticide, is extensively used in agricultural production. With the increasing adoption of the rice-crayfish integrated farming model, pesticide application has become more frequent. However, the potential risk of CAP to crayfish (Procambarus clarkii) remains unclear. In this study, crayfish were exposed to 30, 60, 90 mg/L CAP for 96 h. As CAP exposure time and concentration increased, crayfish survival rates and total hemocyte counts (THC) decreased. Biochemical indicators revealed that CAP exposure induced oxidative stress and immunosuppression in crayfish, leading to metabolic disorders and reduced ATP content. Additionally, pathological analysis and 16S rDNA sequencing demonstrated that CAP exposure compromised the intestinal barrier of crayfish, altered the intestinal microbial community structure, and caused apoptosis. Differential gene expression analysis showed that CAP exposure significantly suppressed the expression of genes related to immune and energy metabolism pathways, resulting in immune dysfunction and insufficient energy supply, while activating the PI3K/AKT/mTOR signaling pathway. PI3K knockdown reduced antioxidant and digestive activities, increased the expression of proinflammatory and apoptosis genes, and exacerbated CAP-induced intestinal toxicity. This study is the first to explore the characterization and function of PI3K in crustaceans, providing new insights for further research on crustacean antioxidants and defense mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Zinc is a significant source of heavy metal pollution that poses risks to both human health and biodiversity. Excessive concentrations of zinc can hinder the growth and development of insects and trigger cell death through oxidative damage. The midgut is the main organ affected by exposure to heavy metals. The silkworm, a prominent insect species belonging to the Lepidoptera class and widely used in China, serves as a model for studying the genetic response to heavy metal stress. In this study, high-throughput sequencing technology was employed to investigate detoxification-related genes in the midgut that are induced by zinc exposure. A total of 11,320 unigenes and 14,723 transcripts were identified, with 553 differentially expressed genes (DEGs) detected, among which 394 were up-regulated and 159 were down-regulated. The Gene Ontology (GO) analysis revealed that 452 DEGs were involved in 18 biological process subclasses, 14 cellular component subclasses and 8 molecular functional subclasses. Furthermore, the KEGG analysis demonstrated enrichment in pathways such as Protein digestion, absorption and Lysosome. Validation of the expression levels of 9 detoxification-related DEGs through qRT-PCR confirmed the accuracy of the RNA-seq results. This study not only contributes new insights into the detoxification mechanisms mechanism of silkworms against zinc contamination, but also serves as a foundation basis for understanding the molecular detoxification processes in lepidopteran insects., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as no potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: With the rapid advancement of medical imaging technology, the demand for accurate segmentation of medical images is increasing. However, most existing methods are unable to capture locality and long-range dependency information in integrated ways for medical images., Method: In this paper, we propose an elegant segmentation framework for medical images named TC-Net, which can utilize both the locality-aware and long-range dependencies in the medical images. As for the locality-aware perspective, we employ a CNN-based encoder and decoder structure. The CNN branch uses the locality of convolution operations to dig out local information in medical images. As for the long-range dependencies, we construct a Transformer branch to focus on the global context. Additionally, we proposed a locality-aware and long-range dependency concatenation strategy (LLCS) to aggregate the feature maps obtained from the two subbranches. Finally, we present a dynamic cyclical focal loss (DCFL) to address the class imbalance problem in multi-lesion segmentation., Results: Comprehensive experiments were conducted on lesion segmentation tasks using two fundus image databases and a skin image database. The TC-Net achieves scores of 0.6985 and 0.5171 in the metric of mean pixel accuracy on the IDRiD and DDR databases, respectively. Moreover, on the skin image database, the TC-Net reached mean pixel accuracy of 0.8886. The experiment results demonstrate that the proposed method achieves better performance than other deep learning segmentation schemes. Furthermore, the proposed DCFL achieves higher performance than other loss functions in multi-lesion segmentation., Significance: The proposed TC-Net is a promising new framework for multi-lesion medical image segmentation and many other challenging image segmentation tasks. © 2001 Elsevier Science. All rights reserved., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu Li reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Although intensity-modulated radiation therapy (IMPT) is dosimetrically superior to passive scattering proton therapy (PSPT) for locally advanced NSCLC (LA-NSCLC), direct comparisons of clinical outcomes are lacking. Here, we compare toxicity profiles and clinical outcomes after IMPT versus PSPT for LA-NSCLC., Methods: This is a nonrandomized, comparative study of two independent cohorts with LA-NSCLC (stage II-IIIB, stage IV with solitary brain metastasis) treated with concurrent chemotherapy and proton beam therapy. Toxicity (Common Terminology Criteria for Adverse Events version 4.0) and outcomes were prospectively collected as part of a clinical trial (ClinicalTrials.gov identifier NCT00915005) or prospective registry (ClinicalTrials.gov identifier NCT00991094)., Results: Of 139 patients, 86 (62%) received PSPT and 53 (38%) IMPT; median follow-up times were 23.9 and 29.0 months, respectively. IMPT delivered lower mean radiation doses to the lungs (PSPT 16.0 Gy versus IMPT 13.0 Gy, p < 0.001), heart (10.7 Gy versus 6.6 Gy, p = 0.004), and esophagus (27.4 Gy versus 21.8 Gy, p = 0.005). Consequently, the IMPT cohort had lower rates of grade 3 or higher pulmonary (17% versus 2%, p = 0.005) and cardiac (11% versus 0%, p = 0.01) toxicities. Six patients (7%) with PSPT and zero patients (0%) with IMPT experienced grade 4 or 5 toxicity. Lower rates of pulmonary (28% versus 3%, p = 0.006) and cardiac (14% versus 0%, p = 0.05) toxicities were observed in the IMPT cohort even after propensity score matching for baseline imbalances. There was also a trend toward longer median overall survival in the IMPT group (23.9 mo versus 36.2 mo, p = 0.09). No difference was found in the 3-year rates of local (25% versus 20%, p = 0.44), local-regional (29% versus 36%, p = 0.56) and distant (52% versus 51%, p = 0.71) recurrences., Conclusions: IMPT is associated with lower radiation doses to the lung, heart, and esophagus, and lower rates of grade 3 or higher cardiopulmonary toxicity; additional clinical studies will be needed to assess the potential differences in survival between the two techniques., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Reliable prediction of progression patterns and failure sites for patients with stage IV lung adenocarcinoma is valuable for physicians to deliver personalized tyrosine kinase inhibitor (TKI) treatment., Patients and Methods: We retrospectively enrolled 266 patients who had stage IV lung adenocarcinoma and received first-line TKI treatment from 2013 to 2017 in Shanghai Chest Hospital. The clinical characteristics at initial diagnosis, progression patterns, and failure sites were analyzed with the attempt to identify some predictive factors for progression patterns and failure sites., Results: Among all patients, 62.4% developed systemic progression, and 37.6% developed oligoprogression. Both cohorts had a median progression-free survival (PFS) of 9 months. The percentage of patients who developed original and distant failure was 39.1% and 60.9%, respectively. Patients with oligometastasis at initial diagnosis were more prone to develop oligoprogression (odds ratio [OR], 4.370; 95% confidence interval [CI], 1.881-10.151; P = .001), whereas pulmonary metastasis was negatively correlated with oligoprogression (OR, 0.567; 95% CI, 0.330-0.974; P = .04). Both oligometastasis diagnosis (OR, 2.959; 95% CI, 1.347-6.500; P = .007) and the maximum diameter of the primary lung lesion (threshold 3.25 cm: OR, 3.646; 95% CI, 2.041-6.515; P = .0001) were strong predictive factors for original failures. Osseous metastasis at initial diagnosis might be an indication for distant failure (OR, 0.536; 95% CI, 0.316-0.909; P = .021)., Conclusion: Over one-half of patients with stage IV lung adenocarcinoma receiving first-line TKI treatment developed systemic progression and distant failure. Metastasis patterns at initial diagnosis was the most important predictive factor for progression patterns and failure sites. The maximum diameter of the primary lung lesion and evidence of osseous metastasis were also found to be significant indicative factors for failure sites., (Copyright © 2020. Published by Elsevier Inc.)

Regulatory Factor X-box binding transcriptional factor 6 (Rfx6) plays an important role in the differentiation and development of pancreas in mammals. However, the direct target genes of Rfx6 to regulate this process were largely unknown. The present study aimed to investigate the function of Rfx6 on regulating pancreatic differentiation and development in a physiologically-relevant context. We performed the chromatin immunoprecipitation followed by the next generation sequencing analysis (ChIP-seq) using whole pancreatic tissue harvested from C57/BL6 adult mice to find target genes of Rfx6. We captured 4146 unique peaks in the genome region of the adult murine pancreas. Among all these binding peaks, a majority were located in intron or intergenic regions. We further annotated all peaks to their nearest gene, and over 1000 genes were captured as Rfx6-binding genes in the pancreas. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis found that Rfx6-binding genes to be associated with the pancreas developmental process. A portion of selected ChIP-seq targets related with pancreas differentiation including Pdx1, Neurod1, Hnf1a, Nkx6-1, St18 and Shox2 were selected and validated as true targets by independent qPCR experiments. In addition, Rfx6 can directly bind to upstream of MiR-145, MiR-195, and possibly other non-protein-coding functional RNAs to control adult mouse pancreatic differentiation. Interestingly, our study revealed that Rfx6 played an important role in insulin translation by binding to the Eif2ak1, Upf1, and Eif5. Our data provide direct target genes of Rfx6 during pancreas development and point to Rfx6 as a potential therapeutic target for improving insulin protein content., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Reirradiation of thoracic malignancies is a treatment challenge, with concerns for toxicity and the inability to deliver definitive doses. Intensity modulated proton therapy (IMPT) may allow safe delivery of a higher dose of radiation to the tumor while minimizing toxicities., Methods and Materials: Between 2011 and 2016, 27 patients who received IMPT for reirradiation of thoracic malignancies with definitive intent were retrospectively analyzed. Patients were included if they received a prior thoracic radiation course. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). Patients received IMPT to a median dose of 66 EQD2 Gy (range, 43.2-84 Gy) for recurrence of thoracic cancer (93%) or sequentially after a course of thoracic stereotactic ablative radiation therapy (7%)., Results: Twenty-two patients (81%) were treated for non-small cell lung cancer. The median time to reirradiation was 29.5 months. At a median follow-up for all patients of 11.2 months (25.9 surviving patients), the median overall survival was 18.0 months, with a 1-year overall survival of 54%. Four patients (15%) experienced an in-field local failure (LF), with a 1-year freedom from LF rate of 78%. The 1-year freedom from locoregional failure and 1-year progression-free survival rates were 61% and 51%, respectively. Patients who received 66 EQD2 Gy or higher had improved 1-year freedom from LF (100% vs 49%; P = .013), 1-year freedom from locoregional failure (84% vs 23%; P = .035), and 1-year progression-free survival (76% vs 14%; P = .050). Reirradiation was well tolerated, with only 2 patients (7%) experiencing late grade 3 pulmonary toxicity, and none with grade 3 or higher esophagitis. There were no grade 4-5 toxicities., Conclusions: These data represent the largest series of patients treated with IMPT for definitive reirradiation of thoracic cancers. They demonstrate that IMPT provided durable local control with minimal toxicity and suggest that higher doses may improve outcomes., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to describe our experience implementing intensity modulated proton therapy (IMPT) for lung-intact malignant pleural mesothelioma (MPM), including patient selection, treatment planning, dose verification, and process optimization., Methods and Materials: Seven patients with epithelioid MPM were reviewed; 6 underwent pleurectomy, whereas 1 had biopsy alone. Four patients received IMPT and 3 received intensity modulated radiation therapy. Treatment plans for the other modality were created for dosimetric comparisons. Quality assurance processes included dose verification and robustness analysis. Image-guided setup was performed with the first isocenter, and couch shifts were applied to reposition to the second isocenter., Results: Treatment with IMPT was well tolerated and completed without breaks. IMPT plans were designed with 2 isocenters, 4 beams, and ≤64 energy layers per beam. Dose verification processes were completed in 3 hours. Total daily treatment time was approximately 45 minutes (20 minutes for setup and 25 minutes for delivery). IMPT produced lower mean doses to the contralateral lung, heart, esophagus, liver, and ipsilateral kidney, with increased contralateral lung sparing when mediastinal boost was required for nodal disease., Conclusions: Our initial experience showed that IMPT was feasible for routine care of patients with lung-intact MPM., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: We compared conventionally optimized intensity modulated proton therapy (IMPT) treatment plans against worst-case scenario optimized treatment plans for lung cancer. The comparison of the 2 IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient setup, inherent proton range uncertainty, and dose perturbation caused by respiratory motion., Methods and Materials: For each of the 9 lung cancer cases, 2 treatment plans were created that accounted for treatment uncertainties in 2 different ways. The first used the conventional method: delivery of prescribed dose to the planning target volume that is geometrically expanded from the internal target volume (ITV). The second used a worst-case scenario optimization scheme that addressed setup and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of changes in patient anatomy attributable to respiratory motion were investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the 2 groups were compared with 2-sided paired Student t tests., Results: Without respiratory motion considered, we affirmed that worst-case scenario optimization is superior to planning target volume-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, worst-case scenario optimization still achieved more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality (D95% ITV, 96.6% vs 96.1% [P = .26]; D5%- D95% ITV, 10.0% vs 12.3% [P = .082]; D1% spinal cord, 31.8% vs 36.5% [P = .035])., Conclusions: Worst-case scenario optimization led to superior solutions for lung IMPT. Despite the fact that worst-case scenario optimization did not explicitly account for respiratory motion, it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The clinical advantage of intensity modulated proton therapy (IMPT) may be diminished by range and patient setup uncertainties. We evaluated the effectiveness of robust optimization that incorporates uncertainties into the treatment planning optimization algorithm for treatment of base of skull cancers., Methods and Materials: We compared 2 IMPT planning methods for 10 patients with base of skull chordomas and chondrosarcomas: (1) conventional optimization, in which uncertainties are dealt with by creating a planning target volume (PTV); and (2) robust optimization, in which uncertainties are dealt with by optimizing individual spot weights without a PTV. We calculated root-mean-square deviation doses (RMSDs) for every voxel to generate RMSD volume histograms (RVHs). The area under the RVH curve was used for relative comparison of the 2 methods' plan robustness. Potential benefits of robust planning, in terms of target dose coverage and homogeneity and sparing of organs at risk (OARs) were evaluated using established clinical metrics. Then the plan evaluation metrics were averaged and compared with 2-sided paired t tests. The impact of tumor volume on the effectiveness of robust optimization was also analyzed., Results: Relative to conventionally optimized plans, robustly optimized plans were less sensitive for both targets and OARs. In the nominal scenario, robust and conventional optimization resulted in similar D95% doses (D95% clinical target volume [CTV]: 63.3 and 64.8 Gy relative biologic effectiveness [RBE]), P <.01]) and D5%-D95% (D5%-D95% CTV: 8.0 and 7.1 Gy[RBE], [P <.01); irradiation of OARs was less with robust optimization (brainstem V60: 0.076 vs 0.26 cm(3) [P <.01], left temporal lobe V70: 0.22 vs 0.41 cm(3), [P = .068], right temporal lobe V70: 0.016 vs 0.11 cm(3), [P = .096], left cochlea Dmean: 28.1 vs 30.1 Gy[RBE], [P = .023], right cochlea Dmean: 23.7 vs 25.2 Gy[RBE], [P = .059]). Results in the worst-case scenario were analogous., Conclusions: Robust optimization is effective for creating clinically feasible IMPT plans for tumors of the base of skull.

Hypodermin A (HA), a serine protease secreted by first-instar larvae of Hypoderma lineatum (Diptera: Oestridae) is associated with inflammatory and the specific immune responses in cattle hosts. In the present study, the cDNA sequence of HA was synthesized, and found to have fifteen amino acids which differed from the sequence available in GenBank. We then examined the association between recombinant HA and guinea-pig complement component 3 (C3) through a co-immunoprecipitation assay. Cos7 cells stably expressing HA were generated, and were found to be more resistant to lysis by guinea-pig C3 than the controls. HA was also able to degrade the C6 and C5b-9 of guinea-pig C3. The presumed DNA binding site of HA with guinea-pig C3 was detected by an electrophoretic mobility shift assay (EMSA). In contrast, after stable transfection, mHA was unable to reduce the amount of C3 or to inhibit its cytotoxicity, while HA could degrade guinea-pig C3 and inhibit the complement pathway. The findings suggest that recombinant HA could serve as an immunosuppressive agent against organ rejection after xenotransplantation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This paper reports on the first use of supercritical fluid extraction (SFE) of polychlorinated biphenyls (PCBs) from pine needles. Supercritical carbon dioxide was used as extraction fluid, and exhibited good extraction efficiencies and recoveries (>90%). GC-MS (selected ion monitoring mode) achieved both accurate identification and quantification of the PCBs. Compared with traditional time consuming multi-step sample preparation methods, SFE with carbon dioxide is easier to perform, and is a feasible alternative extraction procedure for the monitoring of PCBs in pine needle samples.