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UBE2C, a ubiquitin-conjugating enzyme, functions as an oncogene in different types of human cancers. Nonetheless, the exact influence of UBE2C on the development of HCC via regulation of ubiquitination remains uncertain. Here, we found that UBE2C displayed elevated levels of expression in HCC and was associated with an unfavorable prognosis, as evidenced by the analysis of the TCGA database and the examination of clinical specimens. The role of UBE2C in HCC revealed its ability to promote the growth and metastasis of HCC. Mechanistically, UBE2C activated Notch signaling, as evidenced by the upregulation of N1ICD and Hes1, crucial components of the Notch pathway, and activation of the RBP-JK luciferase reporter by UBE2C. Finally, rescue experiments demonstrated that the oncogenic role of UBE2C was eliminated through treatment with the Notch inhibitor DAPT, while overexpression of N1ICD alleviated the anticarcinogenic impact of knockdown of UBE2C. Altogether, the results of our study indicate that UBE2C plays a role in the activation of Notch signaling and could potentially serve as a viable target for therapeutic interventions in HCC., (© 2024. The Author(s).)

Background: Water resources is an essential factor to ensure the sustainable development of the society, but along with the utilization and treatment of water resources, a large amount of carbon emissions will be generated. The study of carbon emissions in social water cycle system is of great significance in promoting the achievement of carbon peaking and carbon neutrality. This study calculated the carbon emissions generated in social water cycle system in nine provinces along the Yellow River, used the Tapio decoupling model to analyze the decoupling relationship between water and carbon emissions, and constructed the STIRPAT expanded model to analyze the main influencing factors of carbon emissions., Results: (1) The total carbon emissions of the nine provinces showed an increasing trend over time, with a growth rate of 25.13%. (2) The carbon emission intensity of water use (1.60kg/m 3 ) and drainage (1.45kg/m 3 ) system is higher, the carbon emission intensity of water supply (0.30kg/m 3 ) and water withdrawal (0.56kg/m 3 ) system is lower. (3) The relationship between water resources utilization and carbon emissions along the Yellow River is generally in a state of negative decoupling and coupling. (4) Energy structure and population growth are the main factors affecting carbon emissions in social water cycle system, while water supply quantity and water use system are secondary factors., Conclusions: Water use system is the main body of carbon emissions in social water cycle system, and as the water consumption increases, the carbon emissions will continue to increase. In order to reduce carbon emissions and mitigate climate change, carbon emission factors should be incorporated into water resources management., (© 2024. The Author(s).)

Objectives: This study utilizes visual analysis methods to retrospectively examine the evolution and trends in exercise interventions for knee osteoarthritis (KOA) research from 2011 to 2022., Design: Bibliometric and visualization analysis review., Setting and Participants: Using the Web of Science database, the literature search range is from January 1, 2011, to December 31, 2022, with the language specified as English and document type set to Article., Methods: Visual analysis was used to analyze literature in the field of exercise interventions for KOA, with KOA and exercise interventions as the key search terms. Visualization maps for countries/regions were created using Tableau and Scimago Graphica software. Institutional, author, and keyword visualization maps were drawn using CiteSpace and VOSviewer software., Results: In total, 3137 articles were included in the visual analysis. The United States emerged as the leading country in terms of publication volume and contribution. Moreover, developed countries such as the United States, Australia, United Kingdom, and Canada have established close and stable cooperative relationships. The University of Melbourne stood out as the institution with both the highest publication volume and centrality. At the forefront of research output in this field was Bennell K.L. from the University of Melbourne. The journal with the highest co-citation frequency was Osteoarthritis and Cartilage. The keyword clustering map highlighted an evolution in the field of exercise interventions for KOA, emphasizing 8 key research themes spanning knee osteoarthritis, serum cartilage, osteoarthritis initiative, patellofemoral pain, total knee arthroplasty, exercise-induced hypoalgesia, isometric exercise, and anterior cruciate ligament reconstruction. Burst analysis revealed that older adult was the earliest and most prominent keyword, with contemporary topics such as patellofemoral pain, safety, musculoskeletal disorder, and neuromuscular exercise considered as research hotspots and future directions in this field., Conclusions and Implications: The global attention on exercise interventions for KOA research is expanding, emphasizing the importance of strengthened connections among developing countries and collaborative author groups. Recent trends have shifted toward topics such as neuromuscular training, treatment safety, and musculoskeletal disorders, whereas research interest in patellofemoral pain remains unabated. Neuromuscular training for KOA represents the current frontier in this field. Future research should delve into the effects of diverse types of exercise interventions for KOA on neuromuscular injury and recovery, exploring feasibility and safety to formulate personalized exercise plans for patients with KOA., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Myasthenia Gravis (MG) is a chronic autoimmune disease that primarily affects the neuromuscular junction, leading to muscle weakness in patients with this condition. Previous studies have identified several dysfunctions in thymus and peripheral blood mononuclear cells (PBMCs), such as the formation of ectopic germinal centers in the thymus and an imbalance of peripheral T helper cells and regulatory T cells, that contribute to the initiation and development of MG. Recent evidences suggest that noncoding RNA, including miRNA, lncRNA and circRNA may play a significant role in MG progression. Additionally, the network between these noncoding RNAs, such as the competing endogenous RNA regulatory network, has been found to be involved in MG progression. In this review, we summarized the roles of miRNA, lncRNA, and circRNA, highlighted their potential application as biomarkers in diagnosing MG, and discussed their potential regulatory networks in the abnormal thymus and PBMCs during MG development., 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 © 2024 Wang, Mei, Yang, Zhang, Li, Zhu, Deng and Wang.)

Background: This study aimed to assess the prevalence of anxiety symptoms among the older adults, explore whether stress mediated the association between social support and anxiety symptoms, and investigate whether media use moderated the direct or indirect effects within the mediation model., Methods: Questionnaires and scales were employed to collect data from 1143 individuals aged 60 years and older across 120 cities in China during the COVID-19 pandemic. The collected information encompassed sociodemographic characteristics, social support, anxiety, stress, and media use. Bivariate correlations were then used to analyze the relationships among the study variables. Finally, the mediation and moderated mediation models were examined using the PROCESS macro for SPSS., Results: During the COVID-19 pandemic, 40.1 % of Chinese elderly experienced anxiety. Social support exhibited a negative correlation with anxiety. And, media use positively influenced both stress and anxiety. Stress partially mediated the relationship between social support and anxiety, with a mediation effect of 50.95 %. Notably, media use moderated the association between social support and anxiety, serving as both an indirect mediator (path a: Social support - Stress: B = 0.071, 95 % CI: 0.022, 0.120) and a direct mediator (path c': Social support - Anxiety: B = -0.066, 95 % CI: -0.111, -0.022)., Limitations: This study used a cross-sectional design, which restricts the ability to infer causal relationships., Conclusion: Social support is proven to be a potent alleviator of anxiety among the elderly. Stress partially mediated this relationship, while the indirect and direct impact of this mediation was influenced by media use., Brief Summary: This study underscores the heightened anxiety prevalence among Chinese elderly during the COVID-19 pandemic, emphasizing the critical role of social support in mitigating these effects. It discovers that while stress acts as a mediator, media use serves as a significant moderator in this dynamic. These findings advocate for the necessity of bolstering social support networks and encouraging prudent media use to effectively manage anxiety and stress among the elderly, particularly in challenging times like a pandemic., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest on this work., (Copyright © 2024. Published by Elsevier B.V.)

Thermochromic hydrogels exhibit a smart capacity for regulating solar spectrum transmission, enabling automatically change their transmissivity in response to the ambient temperature change. This has great importance for energy conservation purposes. Military and civilian emergency thermochromic applications require rapid visible-light stealth (VLS); however, concurrent smart solar transmission and rapid VLS is yet to be realized. Inspired by squid-skin, we propose a micropatterned thermochromic hydrogel (MTH) to realize the concurrent control of smart solar transmittance and rapid VLS at all-working temperatures. The MTH possesses two optical regulation mechanisms: optical property regulation and optical scattering, controlled by temperature and pressure, respectively. The introduced surface micropattern strategy can arbitrarily switch between normal and diffuse transmission, and the VLS response time is within 1 s compared with previous ~180 s. The MTH also has a high solar-transmission regulation range of 61%. Further, the MTH preparation method is scalable and cost-effective. This novel regulation mechanism opens a new pathway towards applications with multifunctional optical requirements., (© 2024. The Author(s).)

Exploring the spatiotemporal variation characteristics of vegetation in the confluent area of water systems in western Jinan and its response mechanism to climatic factors is of great significance for the scientific evaluation of the benefits of the water system connectivity project and eco-environmental protection and can provide a reference for ecotourism development in the Jixi wetland park. Based on the Landsat series of images and meteorological data, this study used ENVI to interpret the normalized difference vegetation index (NDVI) of the confluent area from 2010 to 2021, and the spatiotemporal change characteristics and trends of NDVI were quantitatively analyzed. The response of the growing-season NDVI (GSN) to climate factors and its time-lag effect were explored. The results showed that the overall change in the interannual NDVI in the confluent area from 2010 to 2021 was stable. The GSN in the confluent area was significantly positively correlated with precipitation, average temperature, and relative humidity in 37.64%, 25.52%, and 20.87% of the area respectively, and significantly negatively correlated with sunshine hours in 15.32% of the area. There was a time-lag effect on the response of the GSN to climate factors; the response to precipitation and sunshine hours lagged by 1 month, and the response to average temperature and relative humidity was longer., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Endoscopic submucosal dissection (ESD) of fibrotic colorectal lesions is difficult and has a high complication rate. There are only a few reports on the utility of orthodontic rubber band (ORB) traction in reducing the difficulty of this procedure. This study aimed to investigate the risk factors for perforation when applying ORB traction during ESD of fibrotic colorectal lesions. We continuously collected the clinical data of 119 patients with fibrotic colorectal lesions who underwent ESD with ORB and clip traction between January 2019 and January 2024. Possible risk factors for perforation were analyzed. The median ORB-ESD operative time was 40 (IQR 28-62) min, and the en bloc and R0 resection rates were 94.1% and 84.0%, respectively. Perforation occurred in 16 of 119 patients (13.4%). The lesion size, lesion at the right half of the colon or across an intestinal plica, the degree of fibrosis, operation time, and the surgeon's experience were associated with perforation during ORB-ESD (P < 0.05). Multivariate logistic regression analysis showed that lesions in the right colon (OR 9.027; 95% CI 1.807-45.098; P = 0.007) and those across an intestinal plica (OR 7.771; 95% CI 1.298-46.536; P = 0.025) were independent risk factors for perforation during ORB-ESD. ORB-ESD is an effective and feasible approach to treat fibrotic colorectal lesions. Adequate preoperative evaluation is required for lesions in the right colon and across intestinal plicas to mitigate the risk of perforation., (© 2024. The Author(s).)

The hexadecapole deformation (β&#95;{4}) of the ^{238}U nucleus has not been determined because its effect is overwhelmed by those from the nucleus' large quadrupole deformation (β&#95;{2}) in nuclear electric transition measurements. In this Letter, we identify the nonlinear response of the hexadecapole anisotropy to ellipticity in relativistic U+U collisions that is solely sensitive to β&#95;{4} and insensitive to β&#95;{2}. We demonstrate this by state-of-the-art hydrodynamic calculations and discuss the prospects of discovering the β&#95;{4} of ^{238}U in heavy-ion data at the Relativistic Heavy Ion Collider.

The identification of nitrate sources in reservoir water is important for watershed-scale surface pollution management. Significant fluctuations in river water levels arising from reservoir storage and discharge influence nitrate sources and transport processes. The Sanmenxia Reservoir, in the middle reaches of the Yellow River in China, undergoes significant water level changes (290-316 m), altering the composition of the nitrogen sources. This study employed a δ 15 N and δ 18 O dual-isotope method and MixSIAR modeling to quantify the contributions of nitrate sources. This reveals the impact of reservoir water impoundment and discharge on nitrogen dynamics in the upstream region of the wetland and the model sensitivity for each nitrate source. The results showed that the average concentrations of nitrate‑nitrogen (NO- 3-N) were elevated during the impoundment period compared to the discharge period. Nitrogen sources exhibited varying proportions in surface water, groundwater, and soil water during both the impoundment and discharge periods. The predominant sources include manure and sewage (MS), with a maximum proportion of 57.4 % in surface water. Soil nitrogen (SN) accounted for 25.8 % of groundwater nitrogen and 32.1 % of soil water nitrogen during the impoundment period, whereas, during the discharge period, soil nitrogen made up 41.4 % of surface water nitrogen, manure and sewage contributed 44.8 % of groundwater nitrogen, and manure and sewage dominated with 56.7 % of soil water nitrogen. Sensitivity analysis of the MixSIAR model revealed that the isotopic composition of the manure and sewage primary source most significantly influenced the apportionment results of the riverine nitrate source. Reservoir discharge facilitates the dissimilatory nitrate reduction to ammonium (DNRA). The migration of NO- 3 from surface water to soil water and groundwater occurred from the impoundment period to the discharge period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that might influence the work reported herein., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The perovskite solar cell (PSC) has the benefits of flexibility, inexpensiveness, and high efficiency, and has important prospective applications. However, serious optical losing and low solar energy-utilizing efficiency remain a challenge for the ultra-thin PSCs because of the interface reflection of traditional planar structure. In this study, a hierarchical pore structure with a confined resonant mode is introduced and optimized by electromagnetic theory to improve the solar energy absorbing and utilizing efficiency of ultra-thin PSCs. The large pores in the top layer that support a whispering gallery mode can focus and guide the incident light into the solar cell. The small pores in the bottom layer enable backward scattering of the unabsorbed light and can improve the effective absorption of active layer. The finite-difference time-domain method is employed to optimize the geometric parameters of hierarchical pore structure to improve the light absorption of PSCs. The proposed resonant hierarchical pore structure can greatly improve sunlight absorption of ultra-thin PSCs, and the effective light absorption and photocurrent of PSCs with a hierarchical pore structure is 20.7% higher than that of PSCs with traditional planar structure. This work can offer a beneficial guideline for improving solar energy utilizing efficiency of various thin-film solar cells.

Objective: Develop a method for selecting esophageal cancer patients achieving pathological complete response with pre-neoadjuvant therapy chest-enhanced CT scans., Methods: Two hundred and one patients from center 1 were enrolled, split into training and testing sets (7:3 ratio), with an external validation set of 30 patients from center 2. Radiomics features from intra-tumoral and peritumoral images were extracted and dimensionally reduced using Student's t-test and least absolute shrinkage and selection operator. Four machine learning classifiers were employed to build models, with the best-performing models selected based on accuracy and stability. ROC curves were utilized to determine the top prediction model, and its generalizability was evaluated on the external validation set., Results: Among 16 models, the integrated-XGBoost and integrated-random forest models performed the best, with average ROC AUCs of 0.906 and 0.918, respectively, and RSDs of 6.26 and 6.89 in the training set. In the testing set, AUCs were 0.845 and 0.871, showing no significant difference in ROC curves. External validation set AUCs for integrated-XGBoost and integrated-random forest models were 0.650 and 0.749., Conclusion: Incorporating peritumoral radiomics features into the analysis enhances predictive performance for esophageal cancer patients undergoing neoadjuvant chemoradiotherapy, paving the way for improved treatment outcomes., 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., (© 2024 Published by Elsevier Ltd.)

Oxidative stress (OS) in ruminants is closely associated with disease; thus, improving antioxidant capacity is an important strategy for maintaining host health. Bupleuri Radix (BR) could significantly improve host health and stress levels. However, the clear antioxidant mechanism of the function of BR remains unknown. In the current study, LC-MS metabolomics combined with 16S rRNA gene sequencing was employed to explore the effects of BR on rumen microbiota and metabolites in Shanbei Fine-Wool Sheep (SFWS), and Spearman correlation analyses of rumen microbiota, metabolites, and OS were performed to investigate the mechanism of antioxidant function of BR. Our results indicated that as SFWS grows, levels of OS and antioxidant capacity increase dramatically, but providing BR to SFWS enhances antioxidant capacity while decreasing OS. Rumen microbiota and OS are strongly correlated, with total antioxidant capacity (T-AOC) showing a significant negative correlation with Succiniclasticum and a positive correlation with Ruminococcus . Importantly, the Chao1 index was significantly negatively correlated with malondialdehyde (MDA) and positively correlated with superoxide dismutase (SOD) and T-AOC. Two biomarkers connected to the antioxidant effects of BR, 5,6-DHET and LPA (a-25:0/0:0), were screened according to the results of metabolomics and Spearman analysis of rumen contents, and a significant relationship between the concentration of rumen metabolites and OS was found. Five metabolic pathways, including glycerolipid, glutathione, nucleotide, D-amino acid, and inositol phosphate metabolism, may have a role in OS. The integrated results indicate that rumen microbiota and metabolites are strongly related to OS and that BR is responsible for reducing OS and improving antioxidant capacity in post-weaned SFWS. These findings provide new strategies to reduce OS occurring during SFWS growth.

Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease. Among them, abnormal proliferation, migration and vascularization of fibroblast-like synoviocytes (FLS) are the main pathological basis of persistent synovitis and bone destruction in RA. In the current study, we attempted to find effective molecular mechanisms for the treatment of RA by investigating RA-FLS. Firstly, the study was conducted to identify the potential target gene PTEN and its related signaling pathway through bioinformatics analysis. Subsequently, the target gene PTEN overexpression was regulated by cell transfection. The expression of FOXO signaling factors and autophagy-related proteins were detected by western blotting assay. Cell proliferation was measured by CCK-8 and EdU assays. Inflammation level was detected by ELISA. Cell migration and invasion were detected using wound healing assay and transwell chamber assay, respectively. Cell apoptosis was detected using flow cytometry. The results showed that overexpression of PTEN activated FOXO1 signaling in RA-FLS, and regulated autophagy, proliferation, invasion, migration, and the levels of pro-inflammatory factors in the disease. In conclusion, PTEN might provide an effective therapeutic strategy for rheumatoid arthritis by mediating the FOXO1 signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Liver cancer is a prevalent disease with a dismal prognosis. The aim of the research is to identify subgroups based on malignant cell receptor ligand gene from single-cell RNA, which might lead to customized immunotherapy for patients with liver cancer., Methods: Based on scRNA-seq data, we identified the receptor-ligand genes associated with prognosis and classify patients into molecular subtypes by univariate Cox regression and consensus clustering. LASSO regression was performed to construct a prognostic model, which was validated in TCGA and ICGC datasets. Immune infiltration and prediction of immunotherapy response were analyzed using ssGSEA, ESTIMATE, TIDE, and TRS score calculation. Finally, qPCR and Western blot validation of key genes and protein levels in cell lines., Results: A risk model using 16-gene expression levels predicted liver cancer patients' prognosis. The RiskScore associated significantly with tumor clinical characteristics and immunity, integrated with clinicopathological features for survival prediction. Differential expression of SRXN1 was verified in hepatocellular carcinoma and normal liver cells., Conclusion: Our study utilizes single-cell analysis to investigate the communication between malignant cells and other cell types, identifying molecular subtypes based on malignant cell receptor ligand genes, offering new insights for the development of personalized immunotherapy and prognostic prediction models.

Objectives: Thymic carcinoma and thymic neuroendocrine tumor (NET) are rare and are more likely to develop second malignancies. The purpose of this study was to explore the incidence and lifetime risk of second malignancies in thymic carcinoma and thymic NET., Methods: The standardized incidence ratio (SIR) and the age-adjusted cancer incidence of the thymic carcinoma and thymic NET patients with second malignancies were retrospectively calculated by using the Surveillance, Epidemiology, and End Results (SEER) database. Prognosis results were also determined by Kaplan-Meier analysis and Cox regression., Results: 1130 patients with thymic carcinoma (73 patients had second malignancies) and 263 patients with thymic NET (19 patients had second malignancies) from 2000 to 2018 are included. Patients with thymic carcinoma (SIR: 1.36, 95% CI 1.08-1.69) and with thymic NET (SIR: 1.73, 95% CI 1.13-2.54) demonstrate an increased overall risk of developing second malignancies in various organ systems. The age-adjusted cancer incidence of second malignancies in patients with thymic carcinoma is 3058.48 per 100,000 persons (4178.46 per 100,000 persons in patients with thymic NET). Age at diagnosis is a significant risk factor for the development of second malignancies., Conclusion: The incidence of second malignancies in patients with thymic carcinoma and thymic NET is significantly higher than the patients in the normal population. The occurrence of second malignancies is not related to the use of different treatments. It is important to extend the follow-up period and add other screening methods., (© 2024. The Author(s).)

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and aggressive malignancy, and timely diagnosis of ESCC contributes to an increased cancer survival rate. However, current detection methods for ESCC mainly rely on endoscopic examination, limited by a relatively low participation rate. Herein, ferric-particle-enhanced laser desorption/ionization mass spectrometry (FPELDI MS) is utilized to record the serum metabolic fingerprints (SMFs) from a retrospective cohort (523 non-ESCC participants and 462 ESCC patients) to build diagnostic models toward ESCC. The PFELDI MS achieved high speed (≈30 s per sample), desirable reproducibility (coefficients of variation < 15%), and high throughput (985 samples with ≈124 200 data points for each spectrum). Desirable diagnostic performance with area-under-the-curves (AUCs) of 0.925-0.966 is obtained through machine learning of SMFs. Further, a metabolic biomarker panel is constructed, exhibiting superior diagnostic sensitivity (72.2-79.4%, p < 0.05) as compared with clinical protein biomarker tests (4.3-22.9%). Notably, the biomarker panel afforded an AUC of 0.844 (95% confidence interval [CI]: 0.806-0.880) toward early ESCC diagnosis. This work highlighted the potential of metabolic analysis for accurate screening and early detection of ESCC and offered insights into the metabolic characterization of diseases including but not limited to ESCC., (© 2023 Wiley-VCH GmbH.)

HSPA13, an important member of the heat shock protein family, plays an essential role in the oncogenesis of many organs, but the mechanism and function in hepatocellular carcinoma (HCC) is still unclear. In the present study, we found that HSPA13 was highly expressed in HCC and predicted poor clinical prognosis. Upregulation of HSPA13 was significantly associated with vascular invasion in HCC patients. Functionally, knockdown experiments demonstrated that HSPA13 promoted HCC proliferation, migration, and invasion. Mechanistic investigation showed that HSPA13 could interact with TANK to inhibit its ubiquitination and degradation. In addition, the expression of HSPA13 and TANK were positively correlated in HCC tissues. To conclude, the present study uncovers the oncogenic function of HSPA13 in the progression of HCC by regulating the stability of TANK. These findings suggest that HSPA13 and TANK may serve as promising targets for the diagnosis and treatment of HCC., (© 2023. The Author(s).)

Brain-specific serine/threonine-protein kinase 2 (BRSK2) plays critical roles in insulin secretion and β-cell biology. However, whether BRSK2 is associated with human type 2 diabetes mellitus (T2DM) has not been determined. Here, we report that BRSK2 genetic variants are closely related to worsening glucose metabolism due to hyperinsulinemia and insulin resistance in the Chinese population. BRSK2 protein levels are significantly elevated in β cells from T2DM patients and high-fat diet (HFD)-fed mice due to enhanced protein stability. Mice with inducible β-cell-specific Brsk2 knockout (βKO) exhibit normal metabolism with a high potential for insulin secretion under chow-diet conditions. Moreover, βKO mice are protected from HFD-induced hyperinsulinemia, obesity, insulin resistance, and glucose intolerance. Conversely, gain-of-function BRSK2 in mature β cells reversibly triggers hyperglycemia due to β-cell hypersecretion-coupled insulin resistance. Mechanistically, BRSK2 senses lipid signals and induces basal insulin secretion in a kinase-dependent manner. The enhanced basal insulin secretion drives insulin resistance and β-cell exhaustion and thus the onset of T2DM in mice fed an HFD or with gain-of-function BRSK2 in β cells. These findings reveal that BRSK2 links hyperinsulinemia to systematic insulin resistance via interplay between β cells and insulin-sensitive tissues in the populations carrying human genetic variants or under nutrient-overload conditions., (© The Author(s) (2023). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Background: Fibrous mediastinitis (FM) is a rare mediastinal lesion characterized by proliferation of fibrous tissue within the mediastinum. Previous reports have shown that this lesion can be caused by histoplasmosis and tuberculosis. In extremely rare cases, FM can also be caused by autoimmune diseases such as antineutrophil cytoplasmic antibody-associated vasculitis and large-vessel arteritis., Case Presentation: In our case, we report unexpected fibrous mediastinitis found after robotic thymectomy in a patient with myasthenia gravis (MG). The preoperative imaging indicated no obvious lesion in the mediastinum and the patient denied histories of both histoplasmosis and tuberculosis. After the operation, both proliferation of fibrous tissue and ectopic germinal centres (GCs) could be found in the thymus., Conclusion: This rare case might enrich our knowledge of the relationship between FM and autoimmune diseases., (© 2023. The Author(s).)

The highly reflective solar radiation of passive daytime radiative cooling (PDRC) increases heating energy consumption in the cold winter. Inspired by the temperature-adaptive skin color of chameleon, we efficiently combine temperature-adaptive solar absorption and PDRC technology to achieve "warm in winter and cool in summer". The temperature-adaptive radiative cooling coating (TARCC) with color variability is designed and fabricated, achieving 41% visible light regulation capability. Comprehensive seasonal outdoor tests confirm the reliability of the TARCC: in summer, the TARCC exhibits high solar reflectance (∼93%) and atmospheric transmission window emittance (∼94%), resulting in a 6.5 K subambient temperature. In the winter, the TARCC's dark color strongly absorbs solar radiation, resulting in a 4.3 K temperature rise. Compared with PDRC coatings, the TARCC can save up to 20% of annual energy in midlatitude regions and increase suitable human hours by 55%. With its low cost, easy preparation, and simple construction, the TARCC shows promise for achieving sustainable and comfortable indoor environments.

Background: The aim of this study was to develop a radiomics machine learning model based on computed tomography (CT) that can predict whether thymic epithelial tumors (TETs) can be separated from veins during surgery and to compare the accuracy of the radiomics model to that of radiologists., Methods: Patients who underwent thymectomy at our hospital from 2009 to 2017 were included in the screening process. After the selection of patients according to the inclusion and exclusion criteria, the cohort was randomly divided into training and testing groups, and CT images of these patients were collected. Subsequently, two-dimensional (2D) and three-dimensional (3D) regions of interest were labelled using ITK-SNAP 3.8.0 software, and Radiomics features were extracted using Python software (Python Software Foundation) and selected through the least absolute shrinkage and selection operator (LASSO) regression model. To construct the classifier, a support vector machine (SVM) was employed, and a nomogram was created using logistic regression to predict vascular inseparable TETs based on the radiomics score (radscore) and image features. To assess the accuracy of these models, area under receiver operating characteristic (ROC) curves of these models were calculated, and differences among the models were identified using the Delong test., Results: In this retrospective study, 204 patients with TETs were included, among whom 21 were diagnosed with surgical vascularly inseparable TETs. The area under ROC curve (AUC) of the 2D model, 3D model, 2D + 3D model, and radiologist diagnoses were 0.94, 0.92, 0.95, and 0.87 in the training cohort and 0.95, 0.92, 0.98, and 0.78 in testing cohort, respectively. The Delong test revealed a significant improvement in the performance of the radiomics models compared to radiologists' diagnoses. The logistic regression selected 3 image features, namely maximum diameter of the tumor, degree of abutment of vessel circumference >50%, and absence of the mediastinal fat layer or space between the tumor and surrounding structures. These features, along with the radscore, were included to develop a nomogram. The AUCs of this nomogram were 0.99 in both the training set and testing set, and the Delong test did not find a significant difference between ROC plots of the nomogram and radiomics models., Conclusions: The proposed radiomics model could accurately predict surgical vascularly inseparable TETs preoperatively and was shown to have a higher predictive value than the radiologists., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1050/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The molecular mechanism underlying asymmetric axonemal complexes in sperm flagella is still largely unknown. Here, we showed that the knockout of the coiled-coil domain-containing 176 (CCDC176) in mice led to male infertility due to decreased sperm motility. Ccdc176 knockout specifically destabilized microtubule doublets (MTDs) 1 and 9 during sperm maturation in the corpus epididymis. Single-sperm immunofluorescence showed that most CCDC176 was distributed along the axoneme, and further super-resolution imaging revealed that CCDC176 is asymmetrically localized in the sperm axoneme. CCDC176 could cooperate with microtubule and radial spoke proteins to stabilize MTDs 1 and 9, and its knockout results in the destabilization of some proteins in sperm flagella. Furthermore, as predicted by the sperm multibody dynamics (MBD) model, we found that MTDs 1 and 9 jutted out from the sperm flagellum annulus region in Ccdc176 -/- spermatozoa, and these flagellar defects alter sperm flagellar beat patterns and swimming paths, potentially owing to the reduction and disequilibration of bending torque on the central pair. These results demonstrate that CCDC176 specifically stabilizes MTDs 1 and 9 in the sperm flagellum to ensure proper sperm movement for fertilization., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Helicase-like transcription factor (HLTF) belongs to the family of SWI/SNF proteins, which has been reported to exert oncogenic function in several human cancers. However, to date, its functional role in hepatocellular carcinoma (HCC) has not been revealed. Here, we found that HLTF was highly expressed in HCC tissues compared to nontumor tissues. Additionally, upregulation of HLTF was significantly associated with poor prognosis of patients with HCC. Functional experiments demonstrated that knockdown of HLTF expression significantly inhibited the proliferation, migration, and invasion of HCC cells in vitro, and suppressed tumor growth in vivo. In conclusion, our results suggest that upregulation of HLTF is associated with the development of HCC, and HLTF may be a potential therapeutic target for HCC treatment., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

The ubiquitin-proteasome system governs a wide spectrum of cellular events and offers therapeutic opportunities for pharmacological intervention in cancer treatment. Renal clear cell carcinoma represents the predominant histological subtype and accounts for the majority of cancer death related to kidney malignancies. Through a systematic survey in the association of human ubiquitin-specific proteases with patient prognosis of renal clear cell carcinoma and subsequent phenotypic validation, we uncovered the tumor-promoting role of USP35. Biochemical characterizations confirmed the stabilizing effects of USP35 towards multiple members of the IAP family in an enzymatic activity-dependent manner. USP35 silencing led to reduced expression levels of IAP proteins, which were accompanied with increased cellular apoptosis. Further transcriptomic analysis revealed that USP35 knockdown affected the expression levels of NRF2 downstream transcripts, which were conferred by compromised NRF2 abundance. USP35 functions to maintain NRF2 levels by catalyzing its deubiquitylation and thus antagonizing degradation. NRF2 reduction imposed by USP35 silencing rendered renal clear cell carcinoma cells increased sensitivity to ferroptosis induction. Finally, induced USP35 knockdown markedly attenuated xenograft formation of renal clear cell carcinoma in nude mice. Hence, our findings reveal a number of USP35 substrates and uncover the protecting roles of USP35 against both apoptosis and ferroptosis in renal clear cell carcinoma., (© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Background and Aims: Lenvatinib is a first-line drug commonly used in the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is very limited due to drug resistance. Therefore, there is a great need to explore its combination with other agents to achieve better therapeutic effects. Metformin has been demonstrated to show an anti-cancer effect. This study aimed to investigate the combined effect of lenvatinib with metformin in HCC cells both in vitro and in vivo and elucidate the possible molecular mechanisms., Methods: Flow cytometry, colony formation, CCK-8 and transwell assays were used to study the effect of Lenvatinib-Metformin combination on the malignant behaviour of HCC cells in vitro. Constructing an animal model of tumour-bearing to study the effect of combined drugs on HCC in vivo. Western blot experiments were performed to assess the relationship between AKT and FOXO3 and the cellular translocation of FOXO3., Results: Our results suggested that Lenvatinib and Metformin synergistically inhibited HCC growth and motility. Mechanistically, the combination of Lenvatinib and Metformin synergistically suppressed the activation of the AKT signalling pathway, which in turn reduced the phosphorylation level of downstream effector FOXO3 and induced its nuclear aggregation. In vivo studies further confirmed the synergistic suppression of lenvatinib with metformin in HCC growth., Conclusion: The Lenvatinib-Metformin combination may provide a potential therapeutic strategy to improve the prognosis of HCC patients., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The inherently intermittent feature of solar energy requires reliable energy conversion and storage systems for utilizing the most abundant solar energy. Phase change materials are potential solutions to store a large amount of heat produced by solar light. However, few of the phase change materials have the ability to efficiently convert solar energy into heat; additionally, phase change materials need to be encapsulated in porous substrates for enhancing their leaking resistance and photo-to-thermal performance. In this work, monolithic MXene aerogels, fabricated by Al 3+ cross-linking and freeze-drying, were used as the encapsulation and photothermal materials. The composites phase change materials of MXene/polyethylene glycol can be made with a large polyethylene glycol loading above 90 wt% with the maximum of 97 wt%, owing to the large porosity of MXene aerogels. The low content of MXene has a limited impact on the phase transition temperature and enthalpy of polyethylene glycol, with an enthalpy retention rate ranging from 89.2 to 96.5% for 90-97 wt% polyethylene glycol loadings. MXene aerogels greatly improve the leaking resistance of polyethylene glycol above its melting point of 60 °C, even at 100 °C. The composites phase change materials also show outstanding cycling stability for 500 cycles of heat storage and release, retaining 97.7% of the heat storage capability. The optimized composite phase change material has a solar energy utilization of 93.5%, being superior to most of the reported results. Our strategy produces promising composite phase change materials for solar energy utilization using the MXene aerogels as the encapsulation and photothermal materials.

Surgery remains the preferred treatment option for early-stage gallbladder cancer (GBC). According to the anatomical position of the primary tumor, accurate preoperative stage and strict control of surgical indications, appropriate surgical strategies are selected to achieve the optimal surgical effect. However, most patients have already been at the locally advanced stage or the tumor has metastasized at the initial diagnosis. The postoperative recurrence rate and 5-year survival rate remain unsatisfactory even after radical resection for gallbladder cancer. Hence, there is an urgent need for more treatment options, such as neoadjuvant therapy, postoperative adjuvant therapy and first-line and second-line treatments of local progression and metastasis, in the whole-course treatment management of gallbladder cancer patients. In recent years, the application of molecular targeted drugs and immunotherapy has brought greater hope and broader prospects for the treatment of gallbladder cancer, but their effects in improving the prognosis of patients still lack sufficient evidence-based medicine evidence, so many problems should be addressed by further research. Based on the latest progress in gallbladder cancer research, this review systematically analyzes the treatment trends of gallbladder cancer., 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 Zhou, Yuan, Yang, Ji, Zhou, Ouyang, Wang, Wang, Liu, Li, Zhang, Li, Shan and Zhou.)

Purpose: The purpose of this study was to evaluate the radiotherapy planning feasibility of dose escalation with intensity-modulated proton therapy (IMPT) to hypoxic tumor regions identified on 18F-Fluoromisonidazole (FMISO) positron emission tomography and computed tomography (PET-CT) in NPC., Materials and Methods: Nine patients with stages T3-4N0-3M0 NPC underwent 18F-FMISO PET-CT before and during week 3 of radiotherapy. The hypoxic volume (GTVhypo) is automatically generated by applying a subthresholding algorithm within the gross tumor volume (GTV) with a tumor to muscle standardized uptake value (SUV) ratio of 1.3 on the 18F-FMISO PET-CT scan. Two proton plans were generated for each patient, a standard plan to 70 Gy and dose escalation plan with upfront boost followed by standard 70GyE plan. The stereotactic boost was planned with single-field uniform dose optimization using two fields to deliver 10 GyE in two fractions to GTVhypo. The standard plan was generated with IMPT with robust optimization to deliver 70GyE, 60GyE in 33 fractions using simultaneous integrated boost technique. A plan sum was generated for assessment., Results: Eight of nine patients showed tumor hypoxia on the baseline 18F-FMISO PET-CT scan. The mean hypoxic tumor volume was 3.9 cm 3 (range .9-11.9cm 3 ). The average SUVmax of the hypoxic volume was 2.2 (range 1.44-2.98). All the dose-volume parameters met the planning objectives for target coverage. Dose escalation was not feasible in three of eight patients as the D0.03cc of temporal lobe was greater than 75GyE., Conclusions: The utility of boost to the hypoxic volume before standard course of radiotherapy with IMPT is dosimetrically feasible in selected patients. Clinical trials are warranted to determine the clinical outcomes of this approach., (© 2023 John Wiley & Sons Australia, Ltd.)

The continuous-variable quantum digital signature (CV-QDS) scheme relies on the components of quantum key generation protocol (KGP) to negotiate classical signature, which is more compatible with optical fibers. Nevertheless, the measurement angular error of heterodyne detection or homodyne detection will cause security issues when performing KGP in the distribution stage. For that, we propose to utilize unidimensional modulation in KGP components, which only requires to modulate single quadrature and without the process of basis choice. Numerical simulation results show that the security under collective attack, repudiation attack and forgery attack can be guaranteed. We expect that the unidimensional modulation of KGP components could further simplify the implementation of CV-QDS and circumvent the security issues caused by the measurement angular error.

Glioblastoma (GBM) is a malignant brain tumor. The purpose of this study is to estimate the potential effects and underlying mechanisms of a ubiquitin-specific protease 8 (USP8) small-molecule inhibitor on the phenotypic characteristics of GBM cells. The growth, migration, invasion, and stemness of GBM LN229 and T98G cells were evaluated by conducting cell proliferation, colony formation, wound healing, transwell, Ki-67 staining, spheroid formation, and ionizing radiation assays, and the results collectively showed the suppressive effects of USP8 inhibition on GBM cells. Furthermore, transcriptomic profiling of GBM cells treated with the USP8 inhibitor deubiquitinase (DUB)-IN-1 revealed significantly altered mRNA expression induced by pharmacological USP8 inhibition, from which we confirmed downregulated Aurora kinase A (AURKA) protein levels using immunoblotting assays. Our findings indicated that the proliferation, invasion, and stemness of LN229 and T98G cells were markedly suppressed by USP8 inhibition. Pharmacological USP8 suppression elicits multiple tumor-inhibitory effects, likely through dysregulating various mRNA expression events, including that of the key cell cycle regulator and oncogenic protein AURKA. Therefore, our observations corroborate the GBM-supportive roles of USP8 and suggest pharmacological USP8 inhibition is a viable therapeutic approach to target GBM. The purpose of this study was to investigate the effect and mechanism of action of the USP8 inhibitor DUB-IN-1 on GBM., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

We developed a Cp*Rh(III)-catalyzed C-H arylation of ferrocenethionamides with arylboronic acids for the synthesis of aryl-ferrocenes under mild and base-free conditions, using Ag 2 CO 3 as oxidant. The reaction results in high yields and excellent regioselectivity accommodating a broad scope of substrate range and functional group compatibility, and provides an alternative protocol for the generation of highly functionalized aryl-ferrocene compounds., (© 2022 Wiley-VCH GmbH.)

Background: The purpose of this study was to introduce an "eight-step modularized procedure (M-RET)" for trans-subxiphoid robotic extended thymectomy for patients with myasthenia gravis (MG). Its safety and feasibility were further verified in this study., Materials and Methods: This retrospective study included 87 consecutive MG patients who underwent trans-subxiphoid robotic extended thymectomy at our institution between September 2016 and August 2021. According to different resection models, patients were divided into two groups: traditional trans-subxiphoid robotic extended thymectomy group (T-RET group) and eight-step modularized technique group (M-RET group). Baseline demographic characteristics and operation-related parameters were collected and compared between the two groups., Results: There were 41 (47.1%) patients in the M-RET group and 46 (52.9%) patients in the T-RET group. The M-RET group resected a greater amount of mediastinal adipose tissues and required more dissection time (median and interquartile range: 135.0, 125.0 to 164.0 v. 120.0, 105.0 to 153.8, P = 0.006) compared with the T-RET group. There were no statistically significant differences in terms of the intraoperative blood loss, duration of chest drainage, length of hospital stay, and postoperative complications between the two groups. There was no mortality or conversion in each of the two groups and all patients recovered well upon discharge., Conclusion: The eight-step modularized technique of trans-subxiphoid robotic extended thymectomy was verified to be a safe, effective, radical procedure, which offers unique superiority over ectopic thymic tissue resection., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Quercetin is a widely distributed, bioactive flavonoid compound, which displays potential to inhibit fibrosis in several diseases. The purpose of our study was to determine the effect of quercetin treatment on renal fibrosis and investigate the mechanism. Human proximal tubular epithelial cells (HK-2) stimulated by transforming growth factor-β1 (TGF-β1) and a rat model of unilateral ureter obstruction (UUO) that contributes to fibrosis were used to investigate the role and molecular mechanism of quercetin. PD153035 (N-[3-Bromophenyl]-6,7-dimethoxyquinazolin-4-amine) was used to inactivate EGFR (epidermal growth factor receptor). The level of fibrosis, proliferation, apoptosis, and oxidative stress in HK-2 were measured. All data are presented as means ± standard deviation (SD). p-value < .05 was considered statistically significant. In UUO rats, quercetin reduced the area of fibrosis as well as inflammation, oxidative stress, and cell apoptosis. In cultured HK-2 cells, quercetin significantly ameliorated the EMT induced by TGF-β1, which was accompanied by increased amphiregulin (AREG) expression. Moreover, quercetin inhibited AREG binding to the EGFR receptor, thereby further affecting other downstream pathways. Quercetin may alleviate fibrosis in vitro and in vivo by inhibiting the activation of AREG/EGFR signaling indicating a potential therapeutic effect of quercetin in renal fibrosis., (© 2022 John Wiley & Sons Ltd.)

Tibetan Plateau lakes are sensitive to climate variabilities and affect regional temperature, precipitation and ecosystems. In this study, we investigated the concentrations and carbon isotope ( 14 C and 13 C) compositions of dissolved organic and inorganic carbon (DOC and DIC) along with the concentrations of major lithologic ions (Na + , Mg 2+ , K + , Ca 2+ ) and dissolved silicate (DSi) in a large lake, namely, Qinghai Lake, and its seven inflowing rivers on the northeastern Qinghai-Tibetan Plateau of China. Our results revealed large differences in concentrations and isotopic compositions between DOC and DIC, as well as differences in the concentrations of major ions between the rivers and lake. The chemical weathering of carbonate and silicates in the catchments played important roles in controlling the fates of major ions in the rivers. In Qinghai Lake, evaporation resulted in 40-290 times the accumulation of Na + , Mg 2+ , and K + observed in the rivers, while biological uptake and precipitation reduced the concentrations of Ca 2+ and DSi in the lake by 4-17 times compared with those in the rivers. In addition, the concentrations of DOC and DIC in the lake were 6-7 times those in the rivers. The carbon isotope (δ 13 C and Δ 14 C) signatures of DOC and DIC revealed that the rivers transport millennium-aged DOC (1254 ± 316 years) and DIC (1513 ± 857 years), as influenced largely by the chemical weathering of rocks and preaged soil carbon on the plateau. In contrast, in Qinghai Lake, the ages of DOC are significantly younger (684 ± 378 years) than the ages of riverine DOC, as regulated by newly biologically produced modern DOC. Moreover, the DIC ages in Qinghai Lake are all modern, indicating that exchange with atmospheric CO 2 is the dominant process controlling the lake DIC. The accumulation and removal of riverine-aged DIC in Qinghai Lake, however, are not well understood, and the unbalanced radiocarbon in lake DIC remains a mystery that needs further study., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest relevant to this study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We analyzed total organic carbon (TOC), total nitrogen (TN), and heavy metals in 58 sediment samples from the Laoshan Bay, China. TOC and TN results identified marine primary production as the dominant source for organic matter, and the weak correlations between TOC, TN, and heavy metals indicated the terrestrial origin of heavy metals. Cd showed insignificant correlations with other metals, which suggests that agriculture production is the main anthropogenic activity affecting the distribution of Cd. Pb contamination in past 50 years was likely to have occurred because of fossil fuel combustion. Despite 210 Pb dating, it was still difficult to trace the contamination condition over interannual variations. Nonetheless, these results provide data for monitoring Pb contamination. As Laoshan Bay is an important economic area, it would be beneficial to conduct further studies to determine the sources and degree of contamination for each heavy metal., 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 Ltd. All rights reserved.)

The most common commercial oils in the Chinese market are two petrol types with octane levels of 93 and 97. To determine the source spectrum of air pollutant emissions, we herein investigated the specific emission sizes of the total suspended particles (TSP), total carbon (TC), elemental carbon (EC), organic carbon (OC), and polycyclic aromatic hydrocarbons (PAHs) from a petrol engine fueled with 93# and 97# petrol in 2016 (based on Chinese national IV gasoline standard). We found that while 93# emitted a higher TSP content, 97# emitted greater TC, EC, OC, and PAHs. The highest carbon contents were found in the < 0.25 µm and 0.44-1.0 µm size fractions for the 93# and 97# petrol, respectively. OC content showed a significant positive correlation with EC, and EC2 (at 740 ℃) was the main carbon fragment in both petrol exhausts. The highest PAH content occurred in the 0.25-0.44 µm size-bin, differing from the results for TC, EC, and OC, and medium molecular weight (4 rings) PAHs were the primary component in the emissions. These results indicate that fuel composition and octane sensitivity have a prominent effect on the size distributions of TC (including EC, OC, and PAHs). Thus, more studies on the carbon content at specific emission sizes in petrol exhaust should be conducted to clarify the main factors impacting these variations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rare ectopic mediastinal parathyroid adenoma can result in persistent or recurrent hyperparathyroidism. In this article, we summarized the perioperative outcomes of six patients with mediastinal parathyroid adenoma. All patients underwent minimally invasive surgery (MIS). Abnormal accumulation of sestamibi was observed in four of five patients for preoperative localization of adenoma. Postoperatively, the blood calcium dropped quickly. In addition, we found adenoma function was negatively related to adenoma volume in these patients. In conclusion, although MIS is feasible for parathyroid adenoma, blood calcium should be monitored in a timely manner to avoid hypocalcemia postoperatively. In addition, sestamibi might be a potential pitfall when locating parathyroid adenoma., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: The epidermal growth factor receptor (EGFR) represents a top therapeutic target in the treatment of non-small cell lung cancer. EGFR expression is intricately modulated by receptor endocytosis, during which EGFR ubiquitylation and deubiquitylation play fundamental roles to govern receptor fate. This study aims to uncover novel aspects of the endocytic regulation of EGFR trafficking by deubiquitylases., Methods: The expression and ubiquitylation of EGFR in non-small cell lung cancer cells treated with deubiquitylase inhibitors were assessed by immunoblotting, immunoprecipitation and mass spectrometry analyses. The intracellular EGFR distribution was investigated using immunofluorescence and confocal microscopy assays, and colocalizations with endocytic compartments were examined using GFP-tagged Rab proteins as markers. The influence of the proteasomal deubiquitylase inhibitor b-AP15 on EGF- and HSP90 inhibitor-induced EGFR downregulation was evaluated by immunoblotting. The anticancer effects of b-AP15 were assessed by cell proliferation, colony formation and flow cytometry assays, as well as xenograft animal models., Results: We found that b-AP15 caused a dramatically enhanced ubiquitylation of EGFR in lung cancer cells. Treatment with b-AP15 decreased cell surface EGFR levels and accumulated EGFR on recycling endosomes marked with Rab4A and Rab11A. b-AP15 effectively repressed EGF- and HSP90 inhibitor-induced EGFR degradation. Lung cancer cells exposed to b-AP15 showed markedly reduced cell propagation and significantly increased cell apoptosis. Furthermore, b-AP15 effectively inhibited tumor xenograft growth in nude mice., Conclusion: Proteasomal USP14 and UCHL5 act collectively to promote cell surface recovery of EGFR. Inhibition of proteasomal deubiquitylase activity induces increased EGFR ubiquitylation and retention on recycling endosomes. The USP14 and UCHL5 dual inhibitor b-AP15 elicits potent tumor-suppressive effects to deter cell proliferation and induce apoptotic cell death in lung cancer., (© 2022. Springer Nature Switzerland AG.)

Removal of adipose tissues located behind the left innominate vein and at the aortocaval groove is technically complex for minimally invasive extended thymectomy. The study describes the technical tips of the subxiphoid robotic procedure to remove these adipose tissues. Extended thymectomy by the presented procedure was performed in 39 patients, and 6 patients were diagnosed with ectopic thymic tissues behind the left innominate vein. Satisfactory short-term surgical outcomes demonstrated that dissection of adipose tissues located between mediastinal major vessels is technically feasible and safe by this novel procedure., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Receptor of advanced glycation end products (RAGE) mediates diverse signal transduction following ligand stimulation and plays an important role in diabetes complications and aging associated disease. We have previously verified that advanced glycation end products (AGE) bind to RAGE to cause pancreatic β-cell apoptosis through the mitochondrial pathway. However, the direct interacting protein(s) of RAGE in β cells has never been appreciated. In the present study, we utilized GST pull-down assay combined with mass spectrometry to identify the interacting proteins of the RAGE intracellular domain (C-terminal 43 amino acid of RAGE). Overall four RAGE interacting proteins, including Rab31, were identified with scores over 160. Rab31 was detected in three β-cell lines and confirmed to have interacted with RAGE via co-immunoprecipitation and immunostaining assays. This interaction was further enhanced by glycation-serum (GS) stimulation due to membrane distribution of Rab31 following treatment with GS. We further confirmed that Rab31 promoted RAGE endocytosis and inhibited GS-induced β-cell apoptosis through the pAKT/BCL2 pathway. These findings reveal a new RAGE interaction protein Rab31 that prevents AGE/RAGE-induced pancreatic β-cell apoptosis. Rab31 is therefore a promising therapeutic target for preserving functional β cells under diabetes conditions.

Background: Monochasma savatieri Franch. ex Maxim is a medicinally valuable herb. However, the collection and protection of the wild germplasm resources of M. savatieri are still insufficient, and their genetic diversity and population structure have been poorly studied., Results: We collected and examined 46 M. savatieri individuals from Fujian, Hunan, Jiangxi, and Zhejiang provinces for genetic diversity and population structure, using 33 newly developed expressed sequence tag-simple sequence repeat (EST-SSR) markers. Applying these markers, we detected a total of 208 alleles, with an average of 6.303 alleles per locus. The polymorphic information content varied from 0.138 to 0.884 (average: 0.668), indicating a high level of polymorphism. At the population level, there was a low degree of genetic diversity among populations (I = 0.535, He = 0.342), with Zhejiang individuals showing the highest genetic diversity among the four populations (Fst = 0.497), which indicated little gene flow within the M. savatieri populations (Nm = 0.253). Mantel test analysis revealed a significant positive correlation between geographical and genetic distance among populations (R 2  = 0.3304, p < 0.05), and structure and principal coordinate analyses supported classification of populations into three clusters, which was consistent with the findings of cluster analysis., Conclusions: As a rare medicinal plants, the protection of M. savatieri does not look optimistic, and accordingly, protective efforts should be beefed up on the natural wild populations. This study provided novel tools and insights for designing effective collection and conservation strategies for M. savatieri., (© 2022. The Author(s).)

Background: With the advantage of the robotic suturing capacity, the purse-string suture is technically simple and convenient. This study aimed to present our technical aspects and initial results of robotic Ivor Lewis esophagectomy using two purse-string sutures for circular-stapled anastomosis., Methods: After stomach mobilization, gastric conduit formation, esophagus mobilization and two-field lymphadenectomy, the first robotic hand-sewn purse-string suture was applied to the esophageal muscular layer with an adequate margin above the tumor. A longitudinal incision in the anterior wall of the esophagus was made and the circular stapler anvil was inserted. The esophagus was transected by scissors 1 cm caudal to the first purse-string suture and the purse-string tied to secure the anvil. Then the second robotic hand-sewn purse-string suture was applied to the whole-layer of the proximal end of the esophagus and tied. Finally, the anvil was connected to the body of the stapler and fired., Results: The clinical data of ten patients who underwent robotic Ivor Lewis esophagectomy with an intrathoracic circular-stapled end-to-side anastomosis from February 2022 to April 2022 were collected. There were seven male and three female patients and had a mean age of 63.2 ± 7.6 years. Tissue donuts were complete in all cases and all operations were successfully performed without conversions. The mean overall operative time was 358.2 ± 40.3 min. The mean estimated blood loss was 83.2 ± 15.6 ml. The median length of hospital stay was 11.5 ± 4.1 days. All the patients had an uneventful postoperative period., Conclusion: Two purse-string sutures are necessary to obtain a tight seal of the esophageal tissue around the anvil to avoid potential anastomotic leak and are an essential process for the safety of circular-stapled anastomosis during robotic Ivor Lewis esophagectomy., 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., (© 2022 Zhang, Zuo, Yan, Wang, Yang, Qiu, Chen and Wang.)

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models., (© 2022. The Author(s).)

Background: Myasthenia gravis (MG) is an autoimmune disease that mainly affects neuromuscular junctions and is usually associated with immune disorders in the thymoma. The competitive endogenous RNA (ceRNA) hypothesis has been demonstrated to be an intrinsic mechanism regulating the development of several autoimmune diseases; however, the mechanism where the ceRNA network regulates immune cells in patients with thymoma-associated MG (TAMG) has rarely been explored., Methods: RNA-seq data and clinical information of 124 patients with thymoma were obtained from The Cancer Genome Atlas (TCGA) database. The patients were divided into two groups according to whether they were diagnosed with MG. We applied the propensity score matching method to reduce the incidence of baseline confounders. We then constructed a ceRNA network with differentially expressed RNAs between the groups based on four public databases. The expression of genes of interest was validated by qPCR. Moreover, we predicted the immune cells that infiltrated the thymoma and then analyzed the association between immune cells and RNA in the ceRNA network. To further determine the function of the mRNAs associated with immune cells in patients with TAMG, we performed gene set enrichment analysis in thymoma patients with MG., Results: After matching, 94 patients were included in the following analysis. A total of 847 mRNAs, 409 lncRNAs, and 45 miRNAs were differentially expressed between the groups. The ceRNA network, including 18 lncRNAs, four miRNAs, and 13 mRNAs, was then constructed. We then confirmed that CHST4 and LINC00452, miR-204-3p and miR-204-5p were differentially expressed between patients with TAMG and thymoma patients without MG (NMG) by qPCR. Moreover, we found that the percentage of predicted regulatory T (Treg) cells was significantly decreased in patients with TAMG. Further analysis indicated that the LINC00452/miR-204/CHST4 axis might regulate thymic regulatory T cells (Tregs) in the progression of MG., Conclusions: In this research, we constructed a ceRNA network involved in the progression of TAMG, discovered that thymic Tregs were significantly decreased in patients with TAMG, and assumed that the LINC00452/miR-204/CHST4 axis may regulate thymic Tregs in the development of TAMG. These findings may deepen our understanding of the roles of the ceRNA network in regulating TAMG and highlight the function of CHST4 in recruiting peripheral T cells in the progression of TAMG., 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 © 2022 Wang, Zhang, Qiu, Li and Wang.)

Background: Though robotic Ivor Lewis esophagectomy has been increasingly applied, intrathoracic esophagogastrostomy is still a technical barrier. In this retrospective study, we introduced a double-docking technique for intrathoracic esophagogastrostomy to optimize surgical exposure and facilitate intrathoracic anastomosis. Moreover, we compared the clinical outcomes between the double-docking technique and anastomosis with a single-docking procedure in robotic Ivor Lewis esophagectomy., Methods: From March 2017 to September 2020, the clinical data of 68 patients who underwent robotic Ivor Lewis esophagectomy were reviewed, including 23 patients who underwent the double-docking technique (double-docking group) and 45 patients who underwent single-docking robotic esophagectomy (single-docking group). All patients were diagnosed with esophageal cancer or gastro-esophageal junction by biopsy before surgery. The technical details of the double-docking technique are described in this article., Results: There was no difference in the patient demographics data between the two groups. The median surgical time in the double-docking group was slightly shorter than in the classic group without statistical difference (380 vs. 395 min, p = 0.368). In the double-docking group, the median blood loss was 90 mL, the median number of lymph nodes harvested was 17, and the R0 resection rates were 100% (23/23). There were no differences in the surgical outcomes between the two groups., Conclusions: Based on our experience, the double-docking technique provides good surgical exposure when fashioning anastomosis, and such a technique does not increase the surgical time. Therefore, we believe that the double-docking technique is a safe and effective method for intrathoracic esophagogastrostomy while providing good exposure and ensuring the convenience and reliability of intrathoracic anastomosis., 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 © 2022 Wang, Zhang, Qiu, Wang, Li and Wang.)

Ultrathin, transparent, and free-standing films assembled from low-dimensional nanomaterials (LDMs) are promising for various applications, including transparent heaters and membranes. However, the intact separation of the assembled films, especially those with controlled ultrathin thickness from deposited substrates, is a tremendous challenge, particularly for fast peeling off via self-detaching. Herein, we propose a versatile method to rapidly peel off ultrathin assembled LDM films, including three types of carbon nanotubes, vermiculite, Ag nanowires, and carbon nanotube@graphene, by dissolving the MXene interlayer from the layer-by-layer filtered MXene/LDM Janus films using diluted H 2 O 2 . The MXene sacrificial interlayers play dual roles, including physical isolation of LDM films from filter membranes and the production of bubbles that buoy ultrathin LDM films, making them free-standing. The integrality and self-detaching rate of the LDM films are determined by the loading and reactivity of the MXene interlayers. The intact LDM films can self-detach in 80 s by dissolving the optimized MXene interlayer and producing bubbles. The as-made free-standing ultrathin LDM films can be transferred to arbitrary substrates and exhibit outstanding performance as transparent heaters. This scalable method provides an efficient and versatile method to produce ultrathin, transparent, and free-standing LDM films and finds new applications for the growing MXene family., (© 2021 Wiley-VCH GmbH.)