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Head and neck cancer (HNC) is the seventh most prevalent cancer globally, often characterized by chemo-resistance and immunosuppression, which significantly hampers treatment efficacy. Cold atmospheric plasma (CAP) has recently emerged as a promising adjuvant oncotherapy with substantial potential and advantages. In this study, Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. We aimed to investigate the effects of CAP PZ2 on various types of HNC cells and elucidate the underlying mechanisms. In addition, we endeavored to examine the efficacy of combining CAP PZ2 with chemotherapy drugs (i.e., cisplatin) or immune checkpoint blockade (ICB, i.e., PD1 antibody) in HNC treatment. Firstly, the results demonstrated that CAP PZ2 exerted anti-neoplastic functions through inhibiting cell proliferation, migration and invasion, and promoting apoptosis and autophagy. Secondly, using transcriptomic sequencing, Western blotting, and quantitative real-time PCR, the mechanisms underlying CAP PZ2 treatment in vitro was presumed to be a multitargeted blockade of major cancer survival pathways, such as redox balance, glycolysis, and PI3K/AKT/mTOR/HIF-1α signaling. Lastly, combinatorial thearpy containing CAP PZ2 and cisplatin or PD-1 antibody significantly suppressed tumor growth and prolonged recipient survival in vivo. Collectively, the synergistic effects of CAP PZ2 and cisplatin or PD-1 antibody could serve as a promising solution to enhance head and neck tumor elimination., Competing Interests: Declaration of competing interest The authors declare no competing interests, (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of the current study was to investigate the feasibility of three-dimensional ultrashort echo time quantitative susceptibility mapping (3D UTE-QSM) for the assessment of gadolinium (Gd) deposition in cortical bone. To this end, 40 tibial bovine cortical bone specimens were divided into five groups then soaked in phosphate-buffered saline (PBS) solutions with five different Gd concentrations of 0, 0.4, 0.8, 1.2, and 1.6 mmol/L for 48 h. Additionally, eight rabbits were randomly allocated into three groups, consisting of a normal-dose macrocyclic gadolinium-based contrast agent (GBCA) group (n = 3), a high-dose macrocyclic GBCA group (n = 3), and a control group (n = 2). All bovine and rabbit tibial bone samples underwent magnetic resonance imaging (MRI) on a 3-T clinical MR system. A 3D UTE-Cones sequence was utilized to acquire images with five different echo times (i.e., 0.032, 0.2, 0.4, 0.8, and 1.2 ms). The UTE images were subsequently processed with the morphology-enabled dipole inversion algorithm to yield a susceptibility map. The average susceptibility was calculated in three regions of interest in the middle of each specimen, and the Pearson's correlation between the estimated susceptibility and Gd concentration was calculated. The bone samples soaked in PBS with higher Gd concentrations exhibited elevated susceptibility values. A mean susceptibility value of -2.47 ± 0.23 ppm was observed for bovine bone soaked in regular PBS, while the mean QSM value increased to -1.75 ± 0.24 ppm for bone soaked in PBS with the highest Gd concentration of 1.6 mmol/L. A strong positive correlation was observed between Gd concentrations and QSM values. The mean susceptibility values of rabbit tibial specimens in the control group, normal-dose GBCA group, and high-dose GBCA group were -4.11 ± 1.52, -3.85 ± 1.33, and -3.39 ± 1.35 ppm, respectively. In conclusion, a significant linear correlation between Gd in cortical bone and QSM values was observed. The preliminary results suggest that 3D UTE-QSM may provide sensitive noninvasive assessment of Gd deposition in cortical bone., (© 2023 John Wiley & Sons Ltd.)

Introduction: Diastasis recti abdominis (DRA) is a common condition in postpartum women. Measuring the distance between separated rectus abdominis (RA) in ultrasound images is a reliable method for the diagnosis of this disease. In clinical practice, the RA distance in multiple ultrasound images of a patient is measured by experienced sonographers, which is time-consuming, labor-intensive, and highly dependent on experience of operators. Therefore, an objective and fully automatic technique is highly desired to improve the DRA diagnostic efficiency. This study aimed to demonstrate the deep learning-based methods on the performance of RA segmentation and distance measurement in ultrasound images. Methods: A total of 675 RA ultrasound images were collected from 94 postpartum women, and were split into training (448 images), validation (86 images), and test (141 images) datasets. Three segmentation models including U-Net, UNet++ and Res-UNet were evaluated on their performance of RA segmentation and distance measurement. Results: Res-UNet model outperformed the other two models with the highest Dice score (85.93% ± 0.26%), the highest MIoU score (76.00% ± 0.39%) and the lowest Hausdorff distance (21.80 ± 0.76 mm). The average physical distance between RAs measured from the segmentation masks generated by Res-UNet and that measured by experienced sonographers was only 3.44 ± 0.16 mm. In addition, these two measurements were highly correlated with each other ( r = 0.944), with no systematic difference. Conclusion: Deep learning model Res-UNet has good reliability in RA segmentation and distance measurement in ultrasound images, with great potential in the clinical diagnosis of DRA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Mao, Yan, Ling and Cai.)

With increasingly serious environmental problems caused by the greenhouse effect, it has also become essential to reduce the concentration of CO2 in the atmosphere. In this paper, CaCO3-supported Fe-based catalysts doped with Mn, Al, and K are prepared by a straightforward method and used for CO2 hydrogenation. The fresh and spent catalysts were characterized by SEM-EDS, BET, TG, CO2-TPD, XRD, and XPS. The experimental results show that the highest CO2 conversion rate of Fe10Mn2Al10Ca is 35.99%, the maximum FTY value is 293.98 μmolCO2·g-1 Fe·s-1, the maximum O/P value is 6.61, and the lowest CO selectivity is 32.21%. At the same time, according to the characterization results, the doping of Mn and Al increased the Fe3O4/FeCx ratio. As the Fe3O4/FeCx ratio increases, the proportion of short-chain hydrocarbons (CH4, C2-4) in the products increases, and the proportion of long-chain hydrocarbons (C5+) decrease. Therefore, the co-doping of Mn and Al promotes the conversion of CO and reduces its selectivity, and promotes the formation of light olefins. Finally, it is hoped that this study can provide a reference for further research on CaCO3-supported Fe catalysts., (© 2023 Wiley-VCH GmbH.)

Introduction: Tricuspid regurgitation (TR) is one of the most prevalent types of valvular heart disease linked to poor prognosis in patients with heart failure and is usually ignored. TR has received considerable attention due to the progressive advancements in transcatheter therapies in recent years., Areas Covered: With relatively solid data and rapid technological advancements, tricuspid transcatheter edge-to-edge repair (T-TEER) is the most frequently employed in a series of tricuspid transcatheter interventional treatments for TR. However, the efficacy and technical benefits of T-TEER are limited because of the unique anatomical characteristics and pathological mechanisms of the tricuspid valve. The aim of this review is to summarize reported data on current status of T-TEER and to provide an expert opinion regarding the challenges it is now experiencing and future development direction and approach., Expert Opinion: T-TEER is a significant treatment for TR, but its effectiveness and technical promotion are limited due to the tricuspid valve unique anatomical characteristics and pathological mechanisms. The selection criteria for suitable patients, the choice of when to intervene, device innovation, the advancement of ultrasound technology, and the volume of evidence in evidence-based medicine all indicate that the disorder of TR will eventually be better treated and understood.

Background: Osteosarcoma initially metastasing to bone only shows distinct biological features compared to osteosarcoma that firstly metastasizes to the lung, which suggests us underlying different genomic pathogenetic mechanism., Methods: We analyzed whole-exome sequencing (WES) data for 38 osteosarcoma with paired samples in different relapse patterns. We also sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms., Results: We investigated WES of 12/38 patients with high-grade osteosarcoma (31.6%) with initial bone metastasis (group A) and 26/38 (68.4%) with initial pulmonary metastasis (group B), of whom 15/38 (39.5%) had paired samples of primary lesions and metastatic lesions. We found that osteosarcoma in group A mainly carries single-nucleotide variations displaying higher tumor mutation burden and neoantigen load and more tertiary lymphoid structures, while those in group B mainly exhibits structural variants. High conservation of reported genetic sequencing over time in their evolving cladograms., Conclusions: Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases as well as better immunogenicity in tumor microenvironment., (© 2023 The Authors.)

Purpose: The optimal dose schedule of vincristine, irinotecan, and temozolomide (VIT) in relapsed or refractory patients with Ewing sarcoma requires clarification., Patients and Methods: Patients with relapsed or refractory Ewing sarcoma were randomly assigned (1:1) to either a shorter d × 5 schedule (irinotecan 50 mg/m2/d D1-5, vincristine 1.4 mg/m2 D1) or protracted d × 5×2 schedule (irinotecan 20 mg/m2/d D1-5,8-12, vincristine 1.4 mg/m2 D1,8) together with temozolomide (100 mg/m2/d D1-5). Patients were treated every 3 weeks for up to eight cycles until progression or unacceptable toxic effects occurred. The primary endpoint was objective response rate at 12 weeks (ORR12w). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety., Result: A total of 46 patients presenting with relapsed or refractory Ewing sarcoma were randomly assigned to the d × 5 (n = 24) or d × 5×2 (n = 22) schedules. Median follow-up was 10.7 months in the d × 5 group and 8.3 months in the d × 5×2 group. ORR12w was lower for d × 5 (5/24; 20.8%) patients than for d × 5×2 (12/22; 54.5%; P = 0.019), but no significant difference was found in PFS (median PFS, 2.3 months for d × 5 vs. 4.3 months for d × 5×2) or OS (median OS, 14.8 months for d × 5 and 12.8 months for d × 5×2). Patients receiving the d × 5 schedule reported more grade 3 and 4 adverse events (AE) than those receiving d × 5×2, including diarrhea/abdominal pain and vomiting/nausea., Conclusions: The protracted d × 5×2 VIT schedule showed superior efficacy and favorable tolerability compared with the shorter d × 5 VIT schedule in patients with relapsed or refractory Ewing sarcoma., (©2023 American Association for Cancer Research.)

Background: Kidney renal clear cell carcinoma (KIRC) is a representative histologic subtype of renal cell carcinoma (RCC). RCC exhibits a strong immunogenicity with a prominent dysfunctional immune infiltration. Complement C1q C chain (C1QC) is a polypeptide in serum complement system and is involved in tumorigenesis and the modulation of tumor microenvironment (TME). However, researches have not explored the effect of C1QC expression on prognosis and tumor immunity of KIRC. Methods: The difference in a wide variety of tumor tissues and normal tissues in terms of the C1QC expression was detected using TIMER and TCGA portal databases, and further validation of protein expression of C1QC was conducted via Human Protein Atlas. Then, the associations of C1QC expression with clinicopathological data and other genes were studied with the use of UALCAN database. Subsequently, the association of C1QC expression with prognosis was predicted by searching the Kaplan-Meier plotter database. A protein-protein interaction (PPI) network with the Metascape database was built using STRING software, such that the mechanism underlying the C1QC function can be studied in depth. The TISCH database assisted in the evaluation of C1QC expression in different cell types in KIRC at the single-cell level. Moreover, the association of C1QC and the infiltration level of tumor immune cell was assessed using TIMER platform. The TISIDB website was selected to deeply investigate the Spearman correlation between C1QC and immune-modulator expression. Lastly, how C1QC affected the cell proliferation, migration, and invasion in vitro was assessed using knockdown strategies. Results: KIRC tissues had notably upregulated C1QC level in comparison with adjacent normal tissues, with showed a positive relevance to clinicopathological features including tumor stage, grade, and nodal metastasis, and a negative relevance to clinical prognosis in KIRC. C1QC knockdown inhibited KIRC cell proliferation, migration, and invasion, as indicated by the results of the in vitro experiment. Furthermore, functional and pathway enrichment analysis demonstrated that C1QC was involved in immune system-related biological processes. According to single-cell RNA analysis, C1QC exhibited a specific upregulation in macrophages cluster. Additionally, there was an obvious association of C1QC and a wide variety of tumor-infiltrating immune cells in KIRC. Also, high C1QC expression presented inconsistent prognosis in different enriched immune cells subgroups in KIRC. Immune factors might contribute to C1QC function in KIRC. Conclusion: C1QC is qualified to predict KIRC prognosis and immune infiltration biologically. Targeting C1QC may bring new hope for the treatment of KIRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yao, Liu, Xu, Cai, Hang, Lu, Zhao, Yang and Zong.)

Due to its potential to address low achievement, high dropout rates, and misbehavior among students, school engagement has become an important topic in contemporary developmental psychology and educational research. Although there is a wealth of literature on the causes and effects of student engagement, the current understanding of how student engagement varies in response to different teaching styles is limited. This study examined the engagement and burnout profiles of elementary school pupils (N = 798; 51% females; M age  = 11.54, SD age  = 0.72) and the interactions between those profiles, students' characteristics and their perceptions of instructional behaviors (e.g., supporting criticism, suppressing criticism & independent viewpoints, intruding). Latent profile analysis revealed five types of profiles: moderately burned out, slightly burned out, moderately engaged, highly engaged, and highly burned out. Follow-up logistic regression analysis found that students clustered into engagement groups were likely to report higher autonomy support from teachers, especially when teachers permit criticism and independent thinking from students. In contrast, students clustered into burned out profiles were more likely to rate teacher strategies as autonomy suppressive. This became more obvious when instructors imposed meaningless and uninteresting activities. Taken together, this study indicated that autonomy-supportive teaching behaviors are pivotal in understanding student engagement and school burnout. The significance of the findings was addressed, along with implications and limitations., (© 2023. The Author(s).)

Exploration of highly efficient and cost-effective oxygen evolution reaction (OER) electrocatalysts is of crucial importance for the development of water splitting. In recent years, Cu-based materials have been widely concerned in OER due to their non-toxicity, rich reserves and highest reversibility. Meanwhile, Cu x O nanorods is easy to be prepared in industry. Herein, we report a fast preparation method to construct an integrated Cu x O@CoNi-LDH electrocatalyst with a unique 1D nanowire-2D nanosheet hierarchical core-shell structure by electrodepositing CoNi-LDH nanosheet arrays directly onto Cu x O nanorods (Cu x O were in situ-created on the Cu foam) at a large deposition voltage of -3.0 V vs SCE. The unique heterogeneous core-shell nanostructure, large deposition amount of CoNi-LDH and the synergistic effects between Cu x O core and CoNi-LDH shell can provide abundant active sites, rich open-channels and reduced charge transfer resistance (R ct ) for effective oxygen release and facile electron transport. Consequently, the optimized Cu x O@CoNi-LDH/CF exhibits a low overpotential of 207 mV in 1 M KOH solution at the current density of 10 mV cm -2 and a small Tafel slope of 50.1 mV dec -1 . After 60 h of long-term stability test, the catalytic performance is only slightly weakened. This work demonstrates a new approach to design the high-performance LDH and Cu-related OER catalysts by constructing a unique hierarchical core-shell nanostructure., 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 © 2022 Elsevier Inc. All rights reserved.)

Intelligent Tutoring Systems (ITSs) have a great potential to effectively transform teaching and learning. As more efforts have been put on designing and developing ITSs and integrating them within learning and instruction, mixed types of results about the effectiveness of ITS have been reported. Therefore, it is necessary to investigate how ITSs work in real and natural educational contexts and the associated challenges of ITS application and evaluation. Through a systematic literature review method, this study analyzed 40 qualified studies that applied social experiment methods to examine the effectiveness of ITS during 2011-2022. The obtained results highlighted a complicated landscape regarding the effectiveness of ITS in real educational contexts. Specifically, there was an "intelligent" regional gap regarding the distribution of countries where ITS studies using social experiment methods were conducted. Compared to learning performance, relatively less attention was paid to investigating the impact of ITS on non-cognitive factors, process-oriented factors, and social outcomes, calling for more research in this regard. Considering the complexities and challenges existing in real educational fields, there was a lack of scientific rigor in terms of experimental design and data analysis in some of the studies. Based on these findings, suggestions for future study and implications were proposed., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

With the increasing attention and awareness of the ecological environment, ecotourism is becoming ever more popular, but it still brings problems and challenges to the sustainable development of the environment. To solve such challenges, it is necessary to review literature in the field of ecotourism and determine the key research issues and future research directions. This paper uses scientometrics implemented by CiteSpace to conduct an in-depth systematic review of research and development in the field of ecotourism. Two bibliographic datasets were obtained from the Web of Science, including a core dataset and an expanded dataset, containing articles published between 2003 and 2021. Our research shows that ecotourism has been developing rapidly in recent years. The research field of ecotourism spans many disciplines and is a comprehensive interdisciplinary subject. According to the research results, the evolution of ecotourism can be roughly divided into three phases: human disturbance, ecosystem services and sustainable development. It could be concluded that it has entered the third stage of Shneider's four-stage theory of scientific discipline. The research not only identifies the main clusters and their advance in ecotourism research based on high impact citations and research frontier formed by citations, but also presents readers with new insights through intuitive visual images., Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02190-0., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022.)

Purpose: Pulmonary metastasis was a negative factor of osteosarcoma prognosis. However, there is no universal criteria to confirm pulmonary metastasis at pulmonary micro nodule (PMN, Dmax ≤ 5 mm) stage other than pathology. We aimed to identify prevalence of PMNs, determine prognosis of osteosarcoma with PMNs, and analyze risk factors related to PMN progression., Methods: We retrospectively reviewed 425 consecutive osteosarcoma patients. According to dynamic change in size and number of PMNs, patients were divided into PMN progression and non-progression group. Demographic data, initial laboratory data, radiological features, and oncological evaluations were analyzed. Cox regression was used to identify risk factors for PMN progression. Overall survival rate was measured and analyzed with Kaplan-Meier method. Differences with p < 0.05 were considered significant., Results: PMNs were found in 74% (315/425) osteosarcoma patients, half of whom (157/315) suffering PMN progression. Overall survival rate was 70.2%, while survival rates for PMN progression group and non-progression group were 53.40% and 87.40%, respectively. Clinical risk factors for PMN progression in certain patients included blood vessel invasion, extrapulmonary metastases, low tumour cell necrosis rate, and large tumour size. Radiologic risk factors included greatest diameter, distance to pleura, CT value, solid components, and smooth border., Conclusion: PMN is quite common in osteosarcoma patients. PMN progression is related to both certain clinical and radiological factors, which could assist surgeons to determine its possibility to progress at an early stage., (© 2022. The Author(s) under exclusive licence to SICOT aisbl.)

Necroptosis is a programmed necrosis that is mediated by receptor-interacting protein kinases RIPK1, RIPK3 and the mixed lineage kinase domain-like protein, MLKL. Necroptosis must be strictly regulated to maintain normal tissue homeostasis, and dysregulation of necroptosis leads to the development of various inflammatory, infectious, and degenerative diseases. Ubiquitylation is a widespread post-translational modification that is essential for balancing numerous physiological processes. Over the past decade, considerable progress has been made in the understanding of the role of ubiquitylation in regulating necroptosis. Here, we will discuss the regulatory functions of ubiquitylation in necroptosis signaling pathway. An enhanced understanding of the ubiquitylation enzymes and regulatory proteins in necroptotic signaling pathway will be exploited for the development of new therapeutic strategies for necroptosis-related diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study was to compare the recent Positron emission tomography (PET) Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for evaluating the response of osteosarcoma to neoadjuvant chemotherapy of the extremities., Methods: We retrospectively reviewed patients with osteosarcoma of the extremities who received neoadjuvant chemotherapy and then surgical resection at Peking University People's Hospital. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) and magnetic resonance imaging (MRI) were performed prior to chemotherapy and before surgical resection. Therapeutic response was assessed separately by the PERCIST and RECIST 1.1 criteria. The association between the data acquired by the PERCIST and RECIST 1.1 criteria was then analyzed by Wilcoxon's signed-rank test. The association between the PERCIST criteria and the pathological necrosis rate was analyzed by Fisher's exact test. Finally, the impact of a range of clinicopathological factors on overall survival (OS) and event-free survival (EFS) was analyzed by Cox proportional hazards regression., Results: We recruited 68 patients with a median follow-up of 74 months (range 45-102 months). The evaluations resulting from the RECIST 1.1 and PERCIST criteria were significantly different (p = 0.000). Only two responders were identified according to the RECIST 1.1 criteria. However, 34 responders were identified by the PERCIST criteria. Data arising from the PERCIST criteria were in accordance with the pathological necrosis rate. Survival analysis showed that metastasis at diagnosis, poor pathological response, and disease progression (according to the RECIST 1.1 or PERCIST criteria) were all associated with a poor prognosis (p < 0.05)., Conclusion: Our data indicate that the PERCIST criteria are significantly more sensitive than RECIST 1.1 criteria to identify more responders when evaluating the response of osteosarcoma to neoadjuvant chemotherapy., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: No available meta-analysis has been published that systematically assessed spinal fixation mechanical failure after tumor resection based on largely pooled data. This systematic review and meta-analysis aimed to investigate the spinal fixation failure rate and potential risk factors for hardware failure., Methods: Electronic articles published between January 1, 1979, and January 30, 2021, were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data on the spinal fixation failure rate and potential risk factors., Results: Thirty-eight studies were finally included in the meta-analysis. The pooled spinal fixation mechanical failure rate was 10%. The significant risk factors for hardware failure included tumor level and cage subsidence. Radiotherapy was a potential risk factor., Conclusion: The spinal fixation mechanical failure rate was 10%. Spinal fixation failure is mainly associated with tumor level, cage subsidence and radiotherapy. Durable reconstruction is needed for patients with these risk factors., (© 2022. The Author(s).)

Tumor necrosis happens commonly in advanced solid tumors. We reported that necroptosis plays a major role in tumor necrosis. Although several key necroptosis regulators including receptor interacting protein kinase 1 (RIPK1) have been identified, the regulation of tumor necroptosis during tumor development remains elusive. Here, we report that Z-DNA-binding protein 1 (ZBP1), not RIPK1, mediates tumor necroptosis during tumor development in preclinical cancer models. We found that ZBP1 expression is dramatically elevated in necrotic tumors. Importantly, ZBP1, not RIPK1, deletion blocks tumor necroptosis during tumor development and inhibits metastasis. We showed that glucose deprivation triggers ZBP1-depedent necroptosis in tumor cells. Glucose deprivation causes mitochondrial DNA (mtDNA) release to the cytoplasm and the binding of mtDNA to ZBP1 to activate MLKL in a BCL-2 family protein, NOXA-dependent manner. Therefore, our study reveals ZBP1 as the key regulator of tumor necroptosis and provides a potential drug target for controlling tumor metastasis.

Background: En bloc resection of malignant tumors involving upper thoracic spine is technically difficult. We surgically treated a patient with grade 2 chondrosarcoma involving T1-5, left upper thoracic cavity, and chest wall., Case Presentation: A 37 years old, male patient was referred to our hospital for a huge lump involved left shoulder and chest wall. In order to achieve satisfied surgical margins, anterior approach, posterior approach, and lateral approach were carried out sequentially. After en bloc tumor resection, the upper thoracic spine was reconstructed with a 3D-printed modular vertebral prosthesis, and the huge chest wall defect was repaired by a methyl methacrylate layer between 2 pieces of polypropylene mesh. Postoperatively, the patient suffered from pneumonia and neurological deterioration which fully recovered eventfully. At 24 months after operation, the vertebral prosthesis and internal fixation were intact; there was no tumor local recurrence, and the patient was alive with stable pulmonary metastases., Conclusion: This case report describes resection of a huge chondrosarcoma involving not only multilevel upper thoracic spine, but also entire left upper thoracic cavity and chest wall. Although with complications, en bloc tumor resection with combined surgical approach and effective reconstructions could improve oncologic and functional prognosis in carefully selected spinal tumor patients.

Following the publication of this paper, the authors have contacted the Editorial Office to request that their article be retracted. The reason for this retraction is an inability to be able to replicate certain of their previous results, and also disagreements among the authors as to the interpretation of some of the data. Following further discussion, all authors and the Editor of Molecular Medicine Reports are in agreement that the paper should be retracted; moreover, the authors apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 6506‑6511, 2017; DOI: 10.3892/mmr.2017.7440].

The bromodomain and extra-terminal domain (BET) proteins are promising therapeutic targets to treat refractory solid tumors; however, inherent resistance remains a major challenge in the clinic. Recently, the emerging role of the oncoprotein B cell lymphoma 6 (BCL6) in tumorigenesis and stress response has been unveiled. Here, we demonstrate that BCL6 was upregulated upon BET inhibition in KRAS-mutant cancers, including non-small-cell lung cancer (NSCLC). We further found that BRD3, not BRD2 or BRD4, directly interacted with BCL6 and maintained the negative autoregulatory circuit of BCL6. Disrupting this negative autoregulation by BET inhibitors (BETi) resulted in a striking increase in BCL6 transcription, which further activated the mTOR signaling pathway through repression of the tumor suppressor death-associated protein kinase 2. Importantly, pharmacological inhibition of either BCL6 or mTOR improved the tumor response and enhanced the sensitivity of KRAS-mutant NSCLC to BETi in both in vitro and in vivo settings. Overall, our findings identify a mechanism of BRD3-mediated BCL6 autoregulation and further develop an effective combinatorial strategy to circumvent BETi resistance in KRAS-driven NSCLC.

Coriolus versicolor is an edible medicinal mushroom in China. Two polysaccharides, named as CVPn and CVPa were separated from the dried fruiting bodies of Coriolus versicolor by water extraction and ethanol precipitation. Their chemical structures were well elucidated with overall consideration of monosaccharide composition, methylation analysis and 1D/2D-NMR spectra data. The bioactivities on RAW 264.7 macrophages cells were evaluated, and further structure-bioactivity relationships were concluded. With molecular weight of 29.7 kDa for CVPn and 50.8 kDa for CVPa, the two isolated polysaccharides were both composed of (l → 4)-β-/(1 → 3)-β-d-glucopyranosyl group as backbone with branches attached at O-6 site. Comparing to CVPn, CVPa with relative high molecular weight and less branches showed significant induction of NO production, obvious augmentation of iNOS and TNF-α mRNA expression level, and phagocytosis on RAW 264.7 cells. These results clarified that CVP polysaccharides with less branches and high molecular weight possessed enhanced immunomodulatory ability, and this finding could be a reference for the utilization of Coriolus versicolor., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The osteochondral junction (OCJ) of the knee joint is comprised of multiple tissue components, including a portion of the deep layer cartilage, calcified cartilage, and subchondral bone. The OCJ is of increasing radiological interest as it may be relevant in the early pathogenesis of osteoarthritis (OA). Due to its short transverse relaxation, the OCJ is invisible to clinical MR sequences. The purpose of this study was to develop a fast 3D T 1 -weighted ultrashort echo time cones sequence with fat saturation (FS-UTE-Cones) for high resolution and high contrast imaging of the OCJ on a clinical 3T scanner. First, numerical simulations were performed to investigate how the flip angle affected the signal intensities and contrasts of both short and long T 1 tissues. The results from these simulations demonstrated that higher short T 1 contrast could be achieved with higher flip angle. Next, T 1 relaxation was measured for the different layers of a human patellar cartilage sample, and the results showed that the deepest layer had a significantly shorter T 1 value than other layers. Finally, a healthy knee joint was scanned with different flip angles and the OCJ was highlighted in the T 1 -weighted FS-UTE-Cones sequence using a flip angle greater than 20°. The clinical T 2 -weighted and proton density-weighted FSE sequences were also included for comparison, revealing a dark OCJ region. Representative T 1 -weighted FS-UTE-Cones images of the whole knee of a healthy volunteer showed high signal intensity bands in the OCJ regions of the patella, femur, and tibia. On the other hand, T 1 -weighted FS-UTE-Cones imaging of the knee joints of OA patients revealed regions with reduction or loss of these high signal intensity bands in the OCJ regions, indicating abnormal OCJ tissue composition. The proposed 3D T 1 -weighted FS-UTE-Cones sequence with a 3-min scan time may be very useful for demonstrating the involvement of the OCJ regions in early OA., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Oncogenic KRAS is a major driver in lung adenocarcinoma (LUAD) that has yet to be therapeutically conquered. Here we report that the SLC7A11/glutathione axis displays metabolic synthetic lethality with oncogenic KRAS. Through metabolomics approaches, we found that mutationally activated KRAS strikingly increased intracellular cystine levels and glutathione biosynthesis. SLC7A11, a cystine/glutamate antiporter conferring specificity for cystine uptake, was overexpressed in patients with KRAS-mutant LUAD and showed positive association with tumor progression. Furthermore, SLC7A11 inhibition by either genetic depletion or pharmacological inhibition with sulfasalazine resulted in selective killing across a panel of KRAS-mutant cancer cells in vitro and tumor growth inhibition in vivo, suggesting the functionality and specificity of SLC7A11 as a therapeutic target. Importantly, we further identified a potent SLC7A11 inhibitor, HG106, that markedly decreased cystine uptake and intracellular glutathione biosynthesis. Furthermore, HG106 exhibited selective cytotoxicity toward KRAS-mutant cells by increasing oxidative stress- and ER stress-mediated cell apoptosis. Of note, treatment of KRAS-mutant LUAD with HG106 in several preclinical lung cancer mouse models led to marked tumor suppression and prolonged survival. Overall, our findings reveal that KRAS-mutant LUAD cells are vulnerable to SLC7A11 inhibition, offering potential therapeutic approaches for this currently incurable disease.

Necroptosis, a form of programmed cell death, plays a critical role in various diseases, including inflammatory, infectious, and degenerative diseases. We previously identified N -(7-cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[ d ]thiazol-2-yl)cyclopropanecarboxamide (TAK-632) ( 6 ) as a potent inhibitor of necroptosis by targeting both receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) kinases. Herein, we performed three rounds of structural optimizations of TAK-632 and elucidated structure-activity relationships to generate more potent inhibitors by targeting RIPK3. The analogues with carbamide groups exhibited great antinecroptotic activities, and compound 42 showed >60-fold selectivity for RIPK3 than RIPK1. It blocked necrosome formation by specifically inhibiting the phosphorylation of RIPK3 in necroptotic cells. In a tumor necrosis factor-induced systemic inflammatory response syndrome model, it significantly protected mice from hypothermia and death at a dose of 5 mg/kg, which was much more effective than TAK-632. Moreover, it showed favorable and druglike pharmacokinetic properties in rats with an oral bioavailability of 25.2%. Thus, these RIPK3-targeting small molecules represent promising lead structures for further development.

Three-dimensional (3D) hierarchical CoMn 2 O 4 @Co 3 O 4 core/shell nanoneedle/nanosheet arrays for high-performance supercapacitors were designed and synthesized on Ni foam by a two-step hydrothermal route. The hybrid nanostructure exhibits much more excellent capacitive behavior compared with either the pristine CoMn 2 O 4 nanoneedle arrays alone or Co 3 O 4 nanosheets alone. The formation of an interconnected pore hybrid system is quite beneficial for the facile electrolyte penetration and fast electron transport. The CoMn 2 O 4 @Co 3 O 4 electrode can achieve a high specific capacitance of 1627 F g -1 at 1 A g -1 and 1376 F g -1 at 10 A g -1 . In addition, an asymmetric supercapacitor (ASC) was assembled by using the CoMn 2 O 4 @Co 3 O 4 core/shell hybrid nanostructure arrays on Ni foam as a positive electrode and activated carbon as a negative electrode in an aqueous 3 M KOH electrolyte. A specific capacitance of 125.8 F g -1 at 1 A g -1 (89.2% retention after 5000 charge/discharge cycles at a current density of 2 A g -1 ) and a high energy density of 44.8 W h kg -1 was obtained. The results indicate that the obtained unique integrated CoMn 2 O 4 @Co 3 O 4 nanoarchitecture may show great promise as ASC electrodes for potential applications in energy storage., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Programmed necrosis, also known as necroptosis, is a form of regulated necrotic cell death that is mediated by receptor-interacting protein kinases RIP1 (or RIPK1), RIP3 (or RIPK3), and the mixed lineage kinase domain-like protein, MLKL. Following the induction of programmed necrosis, MLKL is phosphorylated by RIP3 and oligomerizes and then the protein translocates to cell plasma membrane in order to execute programmed necrosis. Here, we describe a detailed protocol to detect MLKL oligomerization in necroptotic cells by Western blotting analysis under nonreducing condition. Therefore, we established the method to detect the activation of programmed necrotic pathway.