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The healing of epoxy coatings in damaged areas significantly influences their service life and protection quality. Intrinsic self-healing coatings, which enable multiple healing cycles without the need for additional functional carriers, have emerged as a promising coating technology. Nevertheless, the cross-linked structure of thermoset epoxy coating system restricts the large-scale migration of molecular chains, posing a significant challenge to achieve intrinsic healing of resin without compromising its mechanical properties. In this study, we report a design scheme for epoxy coating with intrinsic self-healing properties based on active multiple hydrogen bonds. Grafting aminobenzothiazole at the end of polyetheramine D230 chain, the grafted polyetheramine (GD230) was synthesized and served as the auxiliary curing agent, whose accurate molecular structure has been confirmed by different characterizations. The self-healing coating with reversible dynamics network based on hydrogen bonds was prepared by crosslinking through epoxy resin and mixed curing agent of polyetheramine D230 and GD230. Various measurements have been adopted to evaluate the self healing and anticorrosion performance. Results showed that the functional coating with a ratio of 8:2 for D230 to GD230 has satisfied both performances on the steel substrate. After immersion in 3 wt% NaCl solution for 120 days, the impedance value of functional coating still remains about 1010 Ω cm2. After the coating was scratched and immersion for 96 h, the impedance value of functional coating increased by about two orders of magnitude compared to that in blank coating. Mechanical testing and theoretical calculations were used to support dynamic crosslinking model to reveal the self-healing mechanism.

Background: Stage III and IVA–B hypopharyngeal carcinoma presents a substantial risk of recurrence and metastasis. The treatment strategy remains uncertain. The objective of this observational study was to compare the outcomes of induction chemotherapy followed by radiotherapy (ICRT) and induction chemotherapy followed by chemoradiotherapy (ICCRT) in the treatment of locally advanced hypopharyngeal squamous cell carcinoma. Methods: 58 patients with stage III and IVA–B hypopharyngeal squamous cell carcinoma treated with ICRT (n = 26) or ICCRT (n = 32) were enrolled in the study. Baseline variables and toxicity rates were compared by Chi-squared test. Survival curves were constructed by the Kaplan-Meier method and compared by log-rank test. Multivariate Cox proportional hazard analysis was performed to evaluate the potential survival effects. Results: There were no significant differences in gender, age, smoking, drinking, T category, N category, overall stage, induction chemotherapy schemes and cycles between the two groups. The median follow-up time was 36.3 months (range, 2.3–97.5 months). The 2-year recurrence-free survival (RFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and the 1-year, 2-year overall survival (OS) expressed no significant differences between the two groups. Furthermore, induction chemotherapy regimen of TPF achieved better OS than TP or PF (hazard ratio [HR] 0.395, 95 % confidence interval [CI] 0.178–0.879; P = 0.023), OS of patients in N2-3 category was worse than N0-1 (HR 2.594, 95 % CI 1.230–5.471; P = 0.012). In addition, the grade 3–4 therapy-associated toxicities during radiotherapy were higher in the chemoradiotherapy group than in radiotherapy alone group (P = 0.020). Conclusion: Following induction chemotherapy in patients with stage III/IVA-B hypopharyngeal squamous cell carcinoma, the concurrent chemoradiotherapy regimen provided similar survival rates with radiotherapy alone. Meanwhile, the incidence of treatment-related side effects during radiotherapy after induction chemotherapy were lower than that during chemoradiotherapy.

The healing mechanism of traditional self-healing coatings can be divided into “extrinsic” and “intrinsic” types according to the reactants, among which intrinsic restorations can be recycled multiple times and have great potential for applications. But epoxy resin is difficult to achieve intrinsic healing process through secondary bonding and reaction between polymers owing to the high chain rigidity and cross-linking density. In this study, a composite coating combining both “extrinsic” and “intrinsic” healing methods has been fabricated by adding a novel polymer filler (MBT-PGMS), which was synthesized via grafting copolymerization of glycidyl-methacrylate, styrene, methyl-methacrylate and 2-mercaptobenzothiazole (MBT). Multiple analytical techniques have been used to characterize the structure and properties of fillers, and the effect on the anti-corrosion performance and self-healing efficiency of epoxy coatings in 3 wt.% NaCl solution has been studied by electrochemistry measurements and mechanical analysis. Results indicated that the intact coating containing MBT-PGMS (MBT-PGMS/EP) showed prominent corrosion resistance during the immersion of 90 days. Once the coating was scratched, the impedance of MBT-PGMS/EP increased gradually with increasing the immersion time, and reached the optimal performance as the filler amount at 5 wt.%, while the impedance modulus was about 2.8 × 108 Ω cm2 after immersion for 144 h. A dynamic crosslinking model in MBT-PGMS/EP has been proposed to explain the self-healing mechanism.

Introduction: Widespread intra-peritoneal metastases is a main feature of high grade serous ovarian carcinoma (HGSOC). Recently, the extent of tumour heterogeneity was used to evaluate the cancer genomes among multi-regions in HGSOC. However, there is no consensus on the effect of tumour heterogeneity on the evolution of the tumour metastasis process in HGSOC. Objectives: We performed whole-exome sequencing in multiple regions of matched primary and metastatic HGSOC specimens to reveal the genetic mechanisms of ovarian tumourigenesis and malignant progression. Methods: 63 samples (including ovarian carcinoma, omentum metastasis, and normal tissues) were used. We analyzed the genomic heterogeneity, traced the subclone dissemination and establishment history and compared the different genetic characters of cancer evolutionary models in HGSOC. Results: We found that HGSOC had substantial intra-tumour heterogeneity (median 54.2, range 0 ∼ 106.7), high inter-patient heterogeneity (P

Objective: To conduct a bibliometric analysis of literature on hemorrhagic shock published between 2000 and 2021 with the help of Citespace to explore the current status, hotspots and research trends in this regard, with the results presented in a visualized manner. Methods: The data over the past 22 years were retrieved from the Web of Science (WOS) Core Collection database and downloaded as the “Full Record and Cited References”. Cooperative analysis, cluster analysis, co-citation analysis, and burst analysis were performed based on the data on countries/regions, institutions, journals, authors, and keywords through Citespace. Results: A total of 2027 articles were retrieved. The number of annual publications fluctuated but was generally on an upward trend. The United States stands out as the most productive country (989 articles), the University of Pittsburgh the most productive publishing institution (109 articles), SHOCK the most cited journal (1486 articles), TAO LI the most productive author (40 articles), DEITCH EA the most cited author (261 times of citation), hemorrhagic shock the most frequent keyword (725 times of occurrence), and “traumatic brain injury” the most covered article in keyword clustering (29 articles). The burst analysis revealed Harvard University as the institution with the highest strength value and the Journal of Trauma and Acute Care Surgery the most important journal. It was also concluded that HASAN B ALAM, AARON M WILLIAMS, and LIMIN ZHANG may continue to publish high-quality articles in the future. In the meanwhile, both “protect” and “transfusion” were considered the hotspots and trends in current research. Conclusions: The United States has been a major contributor to the publication of the articles over the past 22 years, with the most productive publishing institution, the most cited journal, and the most cited author all coming from the US. Hemorrhagic shock, injury, resuscitation, trauma, models, activation, expression, fluid resuscitation, rats, and nitric oxide are hot topics in relevant research. According to the keyword burst analysis, the areas related to “protect” and “transfusion” may rise as the research directions in the future. However, since the hotspots in the research of hemorrhagic shock are short-lived and fast-changing, the researchers should pay more attention to the development trend in this field.

The use of radiotherapy for hypopharyngeal cancer (HC) treatment is increasing, and it is currently the primary treatment option for this cancer. However, radioresistance occurs in a proportion of patients. Here, we found that radiation increased proteasomal gene expression and that proteasome assembly was dependent on the induction of transcription factor NRF1 in HC. Through screening assays, we identified a mechanism by which proteasome-mediated degradation of DEP domain-containing mTOR-interacting protein (DEPTOR) contributes to the elevation of mTORC1 signaling after radiation. Therefore, after treatment with proteasome inhibitors (PIs), stabilization of DEPTOR inhibited mTORC1 signaling elevated by radiation and ultimately sensitized HC to radiotherapy. Mechanically, PIs not only interrupted the deubiquitination and degradation of DEPTOR but also suppressed the ubiquitination of DEPTOR mediated by β-TrCP. Clinically, the high levels of DEPTOR in HC cells were associated with sensitivity to radiotherapy and favorable prognosis. Stabilizing DEPTOR through targeting proteasome-mediated degradation is a potential strategy for sensitizing HC to radiotherapy.

Summary: Background: Induction chemotherapy regimens of docetaxel and cisplatin plus fluorouracil (TPF) are currently clinically used for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but have well-known side effects, such as myelosuppression and diarrhea. A docetaxel plus cisplatin (TP) regimen was developed to decrease the toxic effects induced by fluorouracil. In this trial, we assessed whether the TP induction chemotherapy regimen was noninferior to the TPF regimen. Methods: We performed an open-label, noninferiority, phase 3, multicentre, randomised, controlled trial at six centres in China. Eligible patients with NPC (stage III-IVA (excluding T3-4N0), Karnofsky's Performance Scoring ≥70) were randomly assigned (1:1) to receive either TP (docetaxel (75 mg per square meter, d1, intravenous infusion) and cisplatin (75 mg per square meter of body-surface area, d1, intravenous infusion)) or TPF (docetaxel (60 mg per square meter, d1, intravenous infusion) plus cisplatin (60 mg per square meter, d1, intravenous infusion) and 5-fluorouracil (600 mg per square meter, d1-d5, intravenous 120-hour infusion)) administered every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy. The primary endpoint was failure-free survival at 2 years. Secondary endpoints included overall survival, safety, and treatment compliance. The trial was stopped early because of strong evidence for noninferiority (margin was -10%) of TP in failure-free survival. Efficacy analyses were performed in both the intention-to-treat and per-protocol trial populations and we included the patients who started treatment in each group for the safety analysis. The study was registered with chictr.org.cn, ChiCTR1800016337. Findings: Between June 1, 2018 and October 31, 2021, we randomly assigned 361 patients to the TP (n = 181) or TPF (n = 180) induction chemotherapy group. The 2-year failure-free survival was 91·3% (95% CI 86·2-96·4) in the TP group and 82·4% (84·8-88·9) in the TPF group (P = 0·029). Patients in the TPF group had a higher frequency of grade 1 or 2 neutropenia (53 (30·0%) vs. 28 (15·7%); P = 0·0010), grade 1 or 2 diarrhea (20 (11·3%) vs. 9 (5·1%); P = 0·032), and grade 3 or 4 neutropenia (43 (24·3%) vs. 25 (14·0%); P = 0·014) in the induction chemotherapy period. There was no treatment-related death. Interpretation: The preliminary results revealed that TP induction chemotherapy regimen was found to be clearly non-inferior compared to the TPF regimen in failure-free survival, with a lower frequency of neutropenia, anaemia and diarrhoea. The more convenient and beneficial survival regimen of the TP regimen should be recommended in patients with LA-NPC. Funding: This study was supported by grants from the Natural Science Foundation of Guangdong Province, China [grant number 2021A1515011182], Natural Science Foundation of Guangdong Province, China [grant number 2022A1515012272], National Natural Science Foundation of China [grant number 82072029] and National Natural Science Foundation of China [grant number 81903037].