Search

The booming of China's primary aluminum industry (PAI) brought substantial emissions of hazardous air pollutants (HAPs) and greenhouse gases (GHGs). By using life cycle assessment and bottom-up method, a comprehensive emission inventory for multiple typical HAPs and GHGs from China's PAI during 1990-2021 was developed and explored for the first time. Our results show that spatial-temporal emissions trends of HAPs and GHGs from PAI in China diverse significantly. The conventional atmospheric pollutants (including SO 2 , NO x and particulate matter (PM)), fluoride and per fluorinated compound (PFCs) had been effectively suppressed since 2007 due to the implementation of various environmental policies; while, emissions of CO, VOCs, CH 4 , heavy metals and CO 2 had increased at different rates unexpectedly. From the spatial distribution perspective, Henan, Shanxi, Guizhou, Guangxi and Shandong dominated the emissions of PAI in China, but with consumption expansion and environmental constrains, PAI plants start to expand to northwest and southwest areas where are richer in sufficient and cheaper power resources, thus bring significant emission increasing there, particular for conventional atmospheric pollutants in northwest and CO and VOCs in southwest China. By underlying driving forces of PAI emissions, results show that end-of-pipe control measures at various stages have played different roles to reduce emissions of the concerned species at each period, but its reduction effect diminished gradually. Future reduction should seek underlying changes in production technology and energy system. Under constrains of environmental regulation and resource endowment, promoting circular economic development for PAI would be a key strategy to reduce HAPs and GHGs emissions simultaneously in PAI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To preoperatively evaluate the human epidermal growth factor 2 (HER2) status in breast cancer using mammographic radiomics features and clinical characteristics on a multi-vendor and multi-center basis., Methods: This multi-center study included a cohort of 1512 Chinese female with invasive ductal carcinoma of no special type (IDC-NST) from two different hospitals and five devices (1332 from Institution A, used for training and testing the models, and 180 women from Institution B, as the external validation cohort). The Gradient Boosting Machine (GBM) was employed to establish radiomics and multiomics models. Model efficacy was evaluated by the area under the curve (AUC)., Results: The number of HER2-positive patients in the training, testing, and external validation cohort were 245(26.3%), 105 (26.3.8%), and 51(28.3%), respectively, with no statistical differences among the three cohorts (p = 0.842, chi-square test). The radiomics model, based solely on the radiomics features, achieved an AUC of 0.814 (95% CI, 0.784-0.844) in the training cohort, 0.776 (95% CI, 0.727-0.825) in the testing cohort, and 0.702 (95% CI, 0.614-0.790) in the external validation cohort. The multiomics model, incorporated radiomics features with clinical characteristics, consistently outperformed the radiomics model with AUC values of 0.838 (95% CI, 0.810-0.866) in the training cohort, 0.788 (95% CI, 0.741-0.835) in the testing cohort, and 0.722 (95% CI, 0.637-0.811) in the external validation cohort., Conclusions: Our study demonstrates that a model based on radiomics features and clinical characteristics has the potential to accurately predict HER2 status of breast cancer patients across multiple devices and centers., Clinical Relevance Statement: By predicting the HER2 status of breast cancer reliably, the presented model built upon radiomics features and clinical characteristics on a multi-vendor and multi-center basis can help in bolstering the model's applicability and generalizability in real-world clinical scenarios., Key Points: • The mammographic presentation of breast cancer is closely associated with the status of human epidermal growth factor receptor 2 (HER2). • The radiomics model, based solely on radiomics features, exhibits sub-optimal performance in the external validation cohort. • By combining radiomics features and clinical characteristics, the multiomics model can improve the prediction ability in external data., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation has been established as an oncogenic driver in a variety of human cancers, including non-small cell lung cancer (NSCLC). However, despite massive efforts, no specific therapy is currently available to target NRF2 hyperactivation. Here, we identify peptidylprolyl isomerase A (PPIA) is required for NRF2 protein stability. Ablation of PPIA promotes NRF2 protein degradation and blocks NRF2-driven growth in NSCLC cells. Mechanistically, PPIA physically binds to NRF2 and blocks the access of ubiquitin/Kelch Like ECH Associated Protein 1 (KEAP1) to NRF2, thus preventing ubiquitin-mediated degradation. Our X-ray co-crystal structure reveals that PPIA directly interacts with a NRF2 interdomain linker via a trans-proline 174-harboring hydrophobic sequence. We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation. Interestingly, CsA interrupts glutamine metabolism mediated by the NRF2/KLF5/SLC1A5 pathway, consequently suppressing the growth of NRF2-hyperactivated NSCLC cells. CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC., (© 2024. The Author(s).)

Purpose: This study aimed to investigate the effectiveness and practicality of using models like convolutional neural network and transformer in detecting and precise segmenting meningioma from magnetic resonance images., Methods: The retrospective study on T1-weighted and contrast-enhanced images of 523 meningioma patients from 3 centers between 2010 and 2020. A total of 373 cases split 8:2 for training and validation. Three independent test sets were built based on the remaining 150 cases. Six convolutional neural network detection models trained via transfer learning were evaluated using 4 metrics and receiver operating characteristic analysis. Detected images were used for segmentation. Three segmentation models were trained for meningioma segmentation and were evaluated via 4 metrics. In 3 test sets, intraclass consistency values were used to evaluate the consistency of detection and segmentation models with manually annotated results from 3 different levels of radiologists., Results: The average accuracies of the detection model in the 3 test sets were 97.3%, 93.5%, and 96.0%, respectively. The model of segmentation showed mean Dice similarity coefficient values of 0.884, 0.834, and 0.892, respectively. Intraclass consistency values showed that the results of detection and segmentation models were highly consistent with those of intermediate and senior radiologists and lowly consistent with those of junior radiologists., Conclusions: The proposed deep learning system exhibits advanced performance comparable with intermediate and senior radiologists in meningioma detection and segmentation. This system could potentially significantly improve the efficiency of the detection and segmentation of meningiomas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla., Material and Methods: Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool)., Results: Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term ( n = 11, I 2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): -0.01-0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain ( n = 13, I 2 = 89%, weighted mean difference (WMD): -1.24, 95% CI: -1.91- -0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation ( n = 13, I 2 = 0%, RD = 0.03, 95% CI: -0.02-0.09, p = 0.99, RIS = 223) and marginal bone loss ( n = 4, I 2 = 0%, WMD = 0.05, 95% CI: -0.14-0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes., Conclusions: This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

Background: An applicable magnetic resonance imaging (MRI) biomarker for diffuse midline glioma (DMG), H3 K27-altered of the spinal cord is important for non-invasive diagnosis., Purpose: To evaluate the efficacy of conventional MRI (cMRI) in distinguishing between DMGs, H3 K27-altered, gliomas without H3 K27-alteration, and demyelinating lesions in the spinal cord., Material and Methods: Between January 2017 and February 2023, patients with pathology-confirmed spinal cord gliomas (including ependymomas) with definite H3 K27 status and demyelinating diseases diagnosed by recognized criteria were recruited as the training set for this retrospective study. Morphologic parameter assessment was performed by two neuroradiologists on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted imaging. Variables with high inter- and intra-observer agreement were included in univariable correlation analysis and multivariable logistic regression. The performance of the final model was verified by internal and external testing sets., Results: The training cohort included 21 patients with DMGs (13 men; mean age = 34.57 ± 13.489 years), 21 with wild-type gliomas (10 men; mean age = 46.76 ± 17.017 years), and 20 with demyelinating diseases (5 men; mean age = 49.50 ± 18.872 years). A significant difference was observed in MRI features, including cyst(s), hemorrhage, pial thickening with enhancement, and the maximum anteroposterior diameter of the spinal cord. The prediction model, integrating age, age 2 , and morphological characteristics, demonstrated good performance in the internal and external testing cohort (accuracy: 0.810 and 0.800, specificity: 0.810 and 0.720, sensitivity: 0.872 and 0.849, respectively)., Conclusion: Based on cMRI, we developed a model with good performance for differentiating among DMGs, H3 K27-altered, wild-type glioma, and demyelinating lesions in the spinal cord., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, or publication of this article.

Biomaterial scaffolds, including bone substitutes, have evolved from being primarily a biologically passive structural element to one in which material properties such as surface topography and chemistry actively direct bone regeneration by influencing stem cells and the immune microenvironment. Ti-6Al-4V(Ti6Al4V) implants, with a significantly higher elastic modulus than human bone, may lead to stress shielding, necessitating improved stability at the bone-titanium alloy implant interface. Ti-24Nb-4Zr-8Sn (Ti2448), a low elastic modulus β-type titanium alloy devoid of potentially toxic elements, was utilized in this study. We employed 3D printing technology to fabricate a porous scaffold structure to further decrease the structural stiffness of the implant to approximate that of cancellous bone. Microarc oxidation (MAO) surface modification technology is then employed to create a microporous structure and a hydrophilic oxide ceramic layer on the surface and interior of the scaffold. In vitro studies demonstrated that MAO treatment enhances the proliferation, adhesion, and osteogenesis capabilities on the scaffold surface. The chemical composition of the MAO-Ti2448 oxide layer is found to enhance the transcription and expression of osteogenic genes in bone mesenchymal stem cells (BMSCs), potentially related to the enrichment of Nb 2 O 5 and SnO 2 in the oxide layer. The MAO-Ti2448 scaffold, with its synergistic surface activity and low stiffness, significantly activates the anti-inflammatory macrophage phenotype, creating an immune microenvironment that promotes the osteogenic differentiation of BMSCs. In vivo experiments in a rabbit model demonstrated a significant improvement in the quantity and quality of the newly formed bone trabeculae within the scaffold under the contact osteogenesis pattern with a matched elastic modulus. These trabeculae exhibit robust connections to the external structure of the scaffold, accelerating the formation of an interlocking structure between the bone and implant and providing higher implantation stability. These findings suggest that the MAO-Ti2448 scaffold has significant potential as a bone defect repair material by regulating osteoimmunomodulation and osteogenesis to enhance osseointegration. This study demonstrates an optional strategy that combines the mechanism of reducing the elastic modulus with surface modification treatment, thereby extending the application scope of β-type titanium alloy.

Surgical removal together with chemotherapy and radiotherapy has used to be the pillars of cancer treatment. Although these traditional methods are still considered as the first-line or standard treatments, non-operative situation, systemic toxicity or resistance severely weakened the therapeutic effect. More recently, synthetic biological nanocarriers elicited substantial interest and exhibited promising potential for combating cancer. In particular, bacteria and their derivatives are omnipotent to realize intrinsic tumor targeting and inhibit tumor growth with anti-cancer agents secreted and immune response. They are frequently employed in synergistic bacteria-mediated anticancer treatments to strengthen the effectiveness of anti-cancer treatment. In this review, we elaborate on the development, mechanism and advantage of bacterial therapy against cancer and then systematically introduce the bacteria-based nanoprobes against cancer and the recent achievements in synergistic treatment strategies and clinical trials. We also discuss the advantages as well as the limitations of these bacteria-based nanoprobes, especially the questions that hinder their application in human, exhibiting this novel anti-cancer endeavor comprehensively., Competing Interests: The authors declare that they have no competing interests., (© 2024 Lu et al.)

Internal strain and its distribution within the crystal lattice play crucial roles in modulating dislocation activities, thereby affecting mechanical properties of materials. Through the synergistic application of integrated differential phase contrast, in situ transmission electron microscopy characterizations, and computational simulations, a method is unveiled for homogenizing dislocation pinning in NiCoCr multi-principal element alloy (MPEA) through the introduction of a high concentration of oxygen atoms with high diffusion mobility. The doping of massive oxygen atoms creates a high density of strong local pinning points for dislocation motion. Notably, oxygen interstitials exhibit remarkable diffusion and mobility across different octahedral and tetrahedral sites within the distorted crystal lattice of NiCoCrO alloy, even at room temperature. The capability allows for the release of severe stress concentrations arising from dislocation entanglement and the establishment of new strong local pinning points at alternative locations in a uniform way, enabling the material with high strength and outstanding deformability. These findings suggest that interstitial atoms can exhibit significant mobility, even at ambient temperature, in complex MPEAs with spreading lattice distortion, opening new possibilities for dislocation engineering., (© 2023 Wiley-VCH GmbH.)

Purpose: This study aims to combine deep learning features with radiomics features for the computer-assisted preoperative assessment of meningioma consistency., Methods: 202 patients with surgery and pathological diagnosis of meningiomas at our institution between December 2016 and December 2018 were retrospectively included in the study. The T2-fluid attenuated inversion recovery (T2-Flair) images were evaluated to classify meningioma as soft or hard by professional neurosurgeons based on Zada's consistency grading system. All the patients were split randomly into a training cohort (n = 162) and a testing cohort (n = 40). A convolutional neural network (CNN) model was proposed to extract deep learning features. These deep learning features were combined with radiomics features. After multiple feature selections, selected features were used to construct classification models using four classifiers. AUC was used to evaluate the performance of each classifier. A signature was further constructed by using the least absolute shrinkage and selection operator (LASSO). A nomogram based on the signature was created for predicting meningioma consistency., Results: The logistic regression classifier constructed using 17 radiomics features and 9 deep learning features provided the best performance with a precision of 0.855, a recall of 0.854, an F1-score of 0.852 and an AUC of 0.943 (95 % CI, 0.873-1.000) in the testing cohort. The C-index of the nomogram was 0.822 (95 % CI, 0.758-0.885) in the training cohort and 0.943 (95 % CI, 0.873-1.000) in the testing cohort with good calibration. Decision curve analysis further confirmed the clinical usefulness of the nomogram for predicting meningioma consistency., Conclusions: The proposed method for assessing meningioma consistency based on the fusion of deep learning features and radiomics features is potentially clinically valuable. It can be used to assist physicians in the preoperative determination of tumor consistency., 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 © 2023 Elsevier B.V. All rights reserved.)

Objectives: Edema is a complication of gamma knife radiosurgery (GKS) in meningioma patients that leads to a variety of consequences. The aim of this study is to construct radiomics-based machine learning models to predict post-GKS edema development., Methods: In total, 445 meningioma patients who underwent GKS in our institution were enrolled and partitioned into training and internal validation datasets (8:2). A total of 150 cases from multicenter data were included as the external validation dataset. In each case, 1132 radiomics features were extracted from each pre-treatment MRI sequence (contrast-enhanced T1WI, T2WI, and ADC maps). Nine clinical features and eight semantic features were also generated. Nineteen random survival forest (RSF) and nineteen neural network (DeepSurv) models with different combinations of radiomics, clinical, and semantic features were developed with the training dataset, and evaluated with internal and external validation. A nomogram was derived from the model achieving the highest C-index in external validation., Results: All the models were successfully validated on both validation datasets. The RSF model incorporating clinical, semantic, and ADC radiomics features achieved the best performance with a C-index of 0.861 (95% CI: 0.748-0.975) in internal validation, and 0.780 (95% CI: 0.673-0.887) in external validation. It stratifies high-risk and low-risk cases effectively. The nomogram based on the predicted risks provided personalized prediction with a C-index of 0.962 (95%CI: 0.951-0.973) and satisfactory calibration., Conclusion: This RSF model with a nomogram could represent a non-invasive and cost-effective tool to predict post-GKS edema risk, thus facilitating personalized decision-making in meningioma treatment., Clinical Relevance Statement: The RSF model with a nomogram built in this study represents a handy, non-invasive, and cost-effective tool for meningioma patients to assist in better counselling on the risks, appropriate individual treatment decisions, and customized follow-up plans., Key Points: • Machine learning models were built to predict post-GKS edema in meningioma. The random survival forest model with clinical, semantic, and ADC radiomics features achieved excellent performance. • The nomogram based on the predicted risks provides personalized prediction with a C-index of 0.962 (95%CI: 0.951-0.973) and satisfactory calibration and shows the potential to assist in better counselling, appropriate treatment decisions, and customized follow-up plans. • Given the excellent performance and convenient acquisition of the conventional sequence, we envision that this non-invasive and cost-effective tool will facilitate personalized medicine in meningioma treatment., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: Glioblastoma (GB) without peritumoral fluid-attenuated inversion recovery (FLAIR) hyperintensity is atypical and its characteristics are barely known. The aim of this study was to explore the differences in pathological and MRI-based intrinsic features (including morphologic and first-order features) between GBs with peritumoral FLAIR hyperintensity (PFH-bearing GBs) and GBs without peritumoral FLAIR hyperintensity (PFH-free GBs)., Methods: In total, 155 patients with pathologically diagnosed GBs were retrospectively collected, which included 110 PFH-bearing GBs and 45 PFH-free GBs. The pathological and imaging data were collected. The Visually AcceSAble Rembrandt Images (VASARI) features were carefully evaluated. The first-order radiomics features from the tumor region were extracted from FLAIR, apparent diffusion coefficient (ADC), and T1CE (T1-contrast enhanced) images. All parameters were compared between the two groups of GBs., Results: The pathological data showed more alpha thalassemia/mental retardation syndrome X-linked (ATRX)-loss in PFH-free GBs compared to PFH-bearing ones (p < 0.001). Based on VASARI evaluation, PFH-free GBs had larger intra-tumoral enhancing proportion and smaller necrotic proportion (both, p < 0.001), more common non-enhancing tumor (p < 0.001), mild/minimal enhancement (p = 0.003), expansive T1/FLAIR ratio (p < 0.001) and solid enhancement (p = 0.009), and less pial invasion (p = 0.010). Moreover, multiple ADC- and T1CE-based first-order radiomics features demonstrated differences, especially the lower intensity heterogeneity in PFH-free GBs (for all, adjusted p < 0.05)., Conclusions: Compared to PFH-bearing GBs, PFH-free ones demonstrated less immature neovascularization and lower intra-tumoral heterogeneity, which would be helpful in clinical treatment stratification., Clinical Relevance Statement: Glioblastomas without peritumoral FLAIR hyperintensity show less immature neovascularization and lower heterogeneity leading to potential higher treatment benefits due to less drug resistance and treatment failure., Key Points: • The study explored the differences between glioblastomas with and without peritumoral FLAIR hyperintensity. • Glioblastomas without peritumoral FLAIR hyperintensity showed less necrosis and contrast enhancement and lower intensity heterogeneity. • Glioblastomas without peritumoral FLAIR hyperintensity had less immature neovascularization and lower tumor heterogeneity., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Quasi-bilayered actuators composed of Fe 3 O 4 -decorated graphene oxide and polyvinylidene fluoride have been fabricated in a magnetic field. The actuators could stably respond to multiple stimuli including infrared light, acetone vapour and a magnetic field. The actuator is also patternable because of the magnetism-induced spatial distribution of fillers in the matrix.

Neuroblastoma (NB) is the most common extracranial solid tumor that affects developing nerve cells in the fetus, infants, and children. miR-124 is a microRNA (miRNA) enriched in neuronal tissues, and VAMP3 (vesicle-associated membrane protein 3) has been reported to be an miR-124 target, although the relationship between NB and miR-124 or VAMP3 is unknown. Our current work identified that miR-124 levels are high in NB cases and that elevated miR-124 correlates with worse NB outcomes. Conversely, depressed VAMP3 correlates with worse NB outcomes. To investigate the mechanisms by which miR-124 and VAMP3 regulate NB, we altered miR-124 or VAMP3 expression in human NB cells and observed that increased miR-124 and reduced VAMP3 stimulated cell proliferation and suppressed apoptosis, while increased VAMP3 had the opposite effects. Genome-wide mRNA expression analyses identified gene and pathway changes which might explain the NB cell phenotypes. Together, our studies suggest that miR-124 and VAMP3 could be potential new markers of NB and targets of NB treatments.

As a vital organelle in eukaryotic cells, the Golgi apparatus is responsible for processing and transporting proteins in cells. Precisely monitoring the status of the Golgi apparatus with targeted fluorescence imaging technology is of enormous importance but remains a dramatically challenging task. In this study, we demonstrate the construction of the first Golgi apparatus-targeted near-infrared (NIR) fluorescent nanoprobe, termed Golgi-Pdots. As a starting point of our investigation, hydrophobic carbon nanodots (CNDs) with bright NIR fluorescence at 674 nm (fluorescence quantum yield: 12.18%), a narrow emission band of 23 nm, and excellent stability were easily prepared from Magnolia Denudata flowers using an ultrasonic method. Incorporating the CNDs into a polymer matrix modified with Golgi-targeting molecules allowed for the production of the water-soluble Golgi-Pdots, which showed high colloidal stability and similar optical properties compared with pristine CNDs. Further studies revealed that the Golgi-Pdots showed good biocompatibility and Golgi apparatus-targeting capability. Based on these fascinating merits, utilizing Golgi-Pdots for the long-term tracking of the Golgi apparatus inside live cells was immensely successful.

High-entropy alloys (HEAs) have shown promising potential applications in advanced reactors due to the outstanding mechanical properties and irradiation tolerance at elevated temperatures. In this work, the novel low-activation Ti 2 ZrHf x V 0.5 Ta 0.2 HEAs were designed and prepared to explore high-performance HEAs under irradiation. The microstructures and mechanical properties of the Ti 2 ZrHf x V 0.5 Ta 0.2 HEAs before and after irradiation were investigated. The results showed that the unirradiated Ti 2 ZrHf x V 0.5 Ta 0.2 HEAs displayed a single-phase BCC structure. The yield strength of the Ti 2 ZrHf x V 0.5 Ta 0.2 HEAs increased gradually with the increase of Hf content without decreasing the plasticity at room and elevated temperatures. After irradiation, no obvious radiation-induced segregations or precipitations were found in the transmission electron microscope results of the representative Ti 2 ZrHfV 0.5 Ta 0.2 HEA. The size and number density of the He bubbles in the Ti 2 ZrHfV 0.5 Ta 0.2 HEA increased with the improvement of fluence at 1023 K. At the fluences of 1 × 10 16 and 3 × 10 16 ions/cm 2 , the irradiation hardening fractions of the Ti 2 ZrHfV 0.5 Ta 0.2 HEA were 17.7% and 34.1%, respectively, which were lower than those of most reported conventional low-activation materials at similar He ion irradiation fluences. The Ti 2 ZrHfV 0.5 Ta 0.2 HEA showed good comprehensive mechanical properties, structural stability, and irradiation hardening resistance at elevated temperatures, making it a promising structural material candidate for advanced nuclear energy systems.

Objective: Oligodendrocyte transcription factor 2 (OLIG2) is universally expressed in human glioblastoma (GB). Our study explores whether OLIG2 expression impacts GB patients' overall survival and establishes a machine learning model for OLIG2 level prediction in patients with GB based on clinical, semantic, and magnetic resonance imaging radiomic features., Methods: Kaplan-Meier analysis was used to determine the optimal cutoff value of the OLIG2 in 168 GB patients. Three hundred thirteen patients enrolled in the OLIG2 prediction model were randomly divided into training and testing sets in a ratio of 7:3. The radiomic, semantic, and clinical features were collected for each patient. Recursive feature elimination (RFE) was used for feature selection. The random forest (RF) model was built and fine-tuned, and the area under the curve was calculated to evaluate the performance. Finally, a new testing set excluding IDH-mutant patients was built and tested in a predictive model using the fifth edition of the central nervous system tumor classification criteria., Results: One hundred nineteen patients were included in the survival analysis. Oligodendrocyte transcription factor 2 was positively associated with GB survival, with an optimal cutoff of 10% ( P = 0.00093). One hundred thirty-four patients were eligible for the OLIG2 prediction model. An RFE-RF model based on 2 semantic and 21 radiomic signatures achieved areas under the curve of 0.854 in the training set, 0.819 in the testing set, and 0.825 in the new testing set., Conclusions: Glioblastoma patients with ≤10% OLIG2 expression tended to have worse overall survival. An RFE-RF model integrating 23 features can predict the OLIG2 level of GB patients preoperatively, irrespective of the central nervous system classification criteria, further guiding individualized treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Persistent infection with human papillomavirus (HPV) types 31 and 33 is an important causative factor for cervical cancer. The E6/E7 genes are key oncogenes involved in the immortalization and transformation of human epithelial cells. Genetic polymorphism may lead to differences in the virus' carcinogenic potential, the immune reaction of the host, and the potencies of vaccines. Few studies on HPV31/33 E6/E7 genetic polymorphism have been carried out. To study the genetic polymorphism of HPV31 and HPV33 E6/E7 genes in northeast China, these genes (HPV31 E6/E7, n  = 151; HPV33 E6/E7, n  = 136) were sequenced and compared to reference sequences (J04353.1, M12732.1) using BioEdit. Phylogenetic trees were constructed by the neighbor-joining method using MegaX. The diversity of the secondary structure was estimated using the PSIPred server. The positively selected sites were analyzed using PAML4.9. The major histocompatibility complex (MHC) class I and MHCII epitopes were predicted using the ProPred-I server and ProPredserver. B-cell epitopes were predicted using the ABCpred server. In the 151 HPV31E6 sequences, 25 (25/450) single-nucleotide mutations were found, 14 of which were synonymous mutations and 11 were nonsynonymous. In the 151 HPV31E7 sequences, 8 (8/297) nucleotide mutations were found, 3 of which were synonymous mutations and 5 were nonsynonymous. In the 136 HPV33E6 sequences, 17 (17/450) nucleotide mutations were observed, 7 of which were synonymous mutations and 10 were nonsynonymous. C14T/G (T5I/S) was a triallelic mutation. Finally, in the 136 HPV33E7 sequences, 9 (9/294) nucleotide mutations were observed, 3 of which were synonymous mutations and 6 were nonsynonymous. C134T/A (A45V/E) and C278G/A (T93S/N) were triallelic mutations. Lineage A was the most common lineage in both HPV31 and HPV33. In all of the sequences, we only identified one positively selected site, HPV33 E6 (K93N). Most nonsynonymous mutations were localized at sites belonging to MHC and/or B-cell predicted epitopes. Data obtained in this study should contribute to the development and application of detection probes, targeted drugs, and vaccines., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Miao Yu et al.)

The laser remelting technique was applied to the surface modification of the Al 0.65 CoCrFeNi high-entropy alloy (HEA) to further advance its mechanical potential. The microstructure of the remelted layer was refined from coarse dendritic to submicron-scale basket weave compared with the as-cast substrate, resulting in a 1.8-time increase in Vickers microhardness. The nanoindentation tests indicated that the nanohardness of the remelted layer was higher than that of each phase in the substrate. Meanwhile, the remelted layer retained considerable plasticity, as evidenced by its high W p / W t ratio (0.763) and strain hardening exponent (0.302). Additionally, adhesive wear prevailed on the substrate, while only abrasive wear features were observed on the remelted layer. Accordingly, the average friction coefficient and the wear rate of the remelted layer were minimized by 23% and 80%, respectively, compared with the substrate. Our findings explored an industrialized method to enhance the surface properties of the Al 0.65 CoCrFeNi HEA and also provided some helpful references for its laser additive manufacturing.

Background: Colorectal cancer (CRC) is one of the most common tumors globally and a leading cause of cancer-related death. In China, CRC is the third most common cancer type. Sauchinone is known to exhibit anti-tumor and anti-inflammatory activity, but its effects on CRC have not been investigated to-date Objective: To investigate the effects of Sauchinone on CRC development and metastasis and its underlying mechanism( s) of action., Methods: SW480 and HCT116 cells were treated with a range of concentrations of Sauchinone. Cell proliferation was measured using EDU assays and flow cytometry., Results: Treatment with 50 μM Sauchinone decreased the expression of MMP2 and MMP9 and downregulated PD-L1 expression (PD-1/PD-L1) leading to checkpoint inhibition. Sauchinone treatment also enhanced the cytotoxicity of SW840 and HCT116 cells co-cultured with CD8 + T cells. The overexpression of PD-L1 rescued the anti-proliferative and cytotoxic effects of Sauchinone in both types., Conclusions: We show that Sauchinone suppresses CRC cell growth through the downregulation of MMP2 and MM9 expression and PD-1/PD-L1 mediated checkpoint inhibition. Collectively, these data highlight the promise of Sauchinone as a future anti-CRC therapeutic., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Lung squamous cell carcinoma (LUSC) is characterized by poor prognosis and obvious limitations of therapeutic methods. The molecular target and mechanism of quercetin (QR), a natural anticancer product with extensive pharmacological activities, on lung squamous cell carcinoma is still unclear., Method: The effects of QR on LUSC were examined using cell proliferation, migration, and invasion tests. Key target genes were screened using The Cancer Genome Atlas (TCGA) database, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) database, STRING website, topology, and prognosis analysis, molecular docking, and other bioinformatics methods for further analysis. Finally, the effects of QR on the expression of key targets in LUSC cells were detected using a cell cycle assay and western blotting., Results: Our study demonstrates that QR not only inhibits the proliferation of LUSC but also affects the invasion and metastasis of LUSC. After downloading and analyzing the TCGA database, 2150 differentially expressed genes were identified. PLK1, CDC20, and BUB1B were identified using enrichment analysis, topological network analysis, cluster analysis, and molecular docking screening. Subsequent experiments showed that QR could interfere with the cell cycle and downregulate the expression of the target gene PLK1 at the protein level., Conclusions: We found that QR not only inhibits the proliferation, migration, and invasion but also blocks the cell cycle progression of LUSC. QR downregulated the expression of the LUSC target gene PLK1 at the protein level., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yiping Lu et al.)

Background and Objective: Treatment for meningiomas usually includes surgical removal, radiation therapy, and chemotherapy. Accurate segmentation of tumors significantly facilitates complete surgical resection and precise radiotherapy, thereby improving patient survival. In this paper, a deep learning model is constructed for magnetic resonance T1-weighted Contrast Enhancement (T1CE) images to develop an automatic processing scheme for accurate tumor segmentation., Methods: In this paper, a novel Convolutional Neural Network (CNN) model is proposed for the accurate meningioma segmentation in MR images. It can extract fused features in multi-scale receptive fields of the same feature map based on MR image characteristics of meningiomas. The attention mechanism is added as a helpful addition to the model to optimize the feature information transmission., Results and Conclusions: The results were evaluated on two internal testing sets and one external testing set. Mean Dice Similarity Coefficient (DSC) values of 0.886, 0.851, and 0.874 are demonstrated, respectively. In this paper, a deep learning approach is proposed to segment tumors in T1CE images. Multi-center testing sets validated the effectiveness and generalization of the method. The proposed model demonstrates state-of-the-art tumor segmentation performance., 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.)

Few studies have evaluated the influence of meteorological variables on different influenza types in subtropical regions. This study aimed to explore the association between meteorological variables and the onset of influenza A (Flu-A) and B (Flu-B) in Macau. Daily influenza case data in Macau were collected from Kiang Wu Hospital from 1 January, 2014 to 31 December, 2018. Daily meteorological data were obtained from the Macau Meteorological Service. The distributed lag non-linear model (DLNM) was used to estimate the effects of meteorological variables on seasonal influenza outbreaks. Regarding mean air temperature (temp), the peaks of the cumulative relative risks (RRs) of Flu-A and Flu-B were both at 4.0 °C and 28.0 °C. Regarding the diurnal temperature range (DTR), the peaks of the cumulative RR of Flu-A were at 1.0 °C and 5.0 °C, while the cumulative RR of Flu-B increased as the DTR decreased. The association between influenza risks and relative humidity (RH) showed a U-shape curve. The risk of influenza increased when the RH was below 50% or above 90%. The risk of both types of influenza increased significantly when the sunshine duration (SD) was below 3.5 h. Taking the median value as the reference, a significant cold effect was observed over 16-24 days lag for Flu-A. Lag effects were found for both types of influenza in low-DTR, and humid and short SD conditions. This study revealed complex non-linear association between meteorological variables and the different influenza types in Macau., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Background: Cathepsin Z (CTSZ) is a cathepsin family member that plays a dual role in the adhesion and migration of immune and tumor cells., Methods: The expression pattern of CTSZ in clear cell renal cell carcinoma (ccRCC) was observed by immunohistochemistry and validated by using double-labeling immunofluorescence. Publicly available single-cell sequencing data was used to further define the cell type-specific CTSZ expression in ccRCC. Methylation modification, immune infiltration, and tumor-related signaling enrichment analyses involving CTSZ were performed using multi-omics data. Data from two independent cohorts of anti-programmed death-1 (PD-1) therapeutic clinical trials were used to investigate correlations between CTSZ levels and treatment responses., Results: CTSZ was upregulated in ccRCC tissues compared with adjacent normal tissues at the RNA but not in ccRCC cells. Immunohistochemistry indicated that CTSZ was expressed in tumors infiltrated with lymphocytes. Double immunofluorescence demonstrated that CTSZ was co-expressed with CD68 but not CD8. Single-cell transcriptome data showed macrophage-specific expression of CTSZ in ccRCC. High CTSZ expression was significantly correlated with the enrichment of interferon-γ, epithelial-to-mesenchymal transition, cell cycle, apoptosis pathways, and B cell, macrophage, neutrophil, and dendritic cell infiltrations, as well as the expression of immune checkpoints CTLA4, LAG3, HAVCR2, PDCD1LG2, PDCD1, TIGIT, and SIGLEC15. Hypomethylation modification of cg02744249, cg02744249, and cg22145559 were negatively correlated with CTSZ expression, suggesting an epigenetic mechanism for the regulation of CTSZ expression. Clinically, CTSZ levels were associated with the prognosis of patients with ccRCC (hazard ratio=1.5, P=0.007). Notably, patients with higher CTSZ expression had a worse prognosis with anti-PD-1 monotherapy (hazard ratio=1.51, P=0.039)., Conclusion: Macrophage-specific CTSZ was associated with activation of epithelial-to-mesenchymal transition, cell cycle signatures, and a higher infiltration level of B cells, macrophages, neutrophils, and dendritic cells in the tumor microenvironment. High expression of CTSZ could be considered as a prognostic and treatment response biomarker for patients with ccRCC receiving anti-PD-1 immunotherapy., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Zhang et al.)

Background: Cuprotosis is a new form of programmed cell death induced by copper. We explored the correlation of cuprotosis with clear cell renal cell carcinoma (ccRCC) and constructed a cuprotosis-related signature to predict the prognosis of patients with ccRCC. Methods: The clinical and transcriptomic data of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA), cBioPortal, and GEO databases, and cuprotosis-related gene sets were contained in the previous study. A cuprotosis-related signature was developed based on data from TCGA and verified by data from cBioPortal and GEO databases. The immune cell infiltrates and the corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correlation of the signature risk score with immune therapy response. Results: A signature containing six cuprotosis-related genes was identified and can accurately predict the prognosis of ccRCC patients. Patients with downregulated copper-induced programmed death had a worse overall survival (hazard ratio: 1.90, 95% CI: 1.39-2.59, p < 0.001). The higher signature risk score was significantly associated with male gender ( p = 0.026), higher tumor stage ( p < 0.001), and higher histological grade ( p < 0.001). Furthermore, the signature risk score was positively correlated with the infiltration of B cells, CD8 + T cells, NK cells, Tregs, and T cells, whereas it was negatively correlated with eosinophils, mast cells, and neutrophils. However, no correlation between cuprotosis and response to anti-PD-1 therapy was found. Conclusion: We established a cuprotosis signature, which can predict the prognosis of patients with ccRCC. Cuprotosis was significantly correlated with immune cell infiltrates in ccRCC., 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 Zhang, Lin, Feng, Liang, Lu, Liu and Wang.)

Background: The upregulation of amino acid metabolism is an essential form of metabolic reprogramming in cancer. Here, we developed an amino acid metabolism signature to predict prognosis and anti-PD-1 therapy response in clear cell renal cell carcinoma (ccRCC)., Methods: According to the amino acid metabolism-associated gene sets contained in the Molecular Signature Database, consensus clustering was performed to divide patients into two clusters. An amino acid metabolism-associated signature was identified and verified. Immune cell infiltrates and their corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correspondence between the signature risk score and the immune therapy response., Results: Two clusters with different amino acid metabolic levels were identified by consensus clustering. The patients in the two clusters differed in overall survival, progression-free survival, amino acid metabolic status, and tumor microenvironment. We identified a signature containing eight amino acid metabolism-associated genes that could accurately predict the prognosis of patients with ccRCC. The signature risk score was positively correlated with infiltration of M1 macrophages, CD8+ T cells, and regulatory T cells, whereas it was negatively correlated with infiltration of neutrophils, NK cells, and CD4+ T cells. Patients with lower risk scores had better overall survival but worse responses to nivolumab., Conclusion: Amino acid metabolic status is closely correlated with tumor microenvironment, response to checkpoint blockade therapy, and prognosis in patients with ccRCC. The established amino acid metabolism-associated gene signature can predict both survival and anti-PD-1 therapy response in patients with ccRCC., 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 Zhang, Lin, Zhu, Tang, Lu, Liu and Wang.)

Contact infection of bacteria and viruses has been a critical threat to human health. The worldwide outbreak of COVID-19 put forward urgent requirements for the research and development of the self-antibacterial materials, especially the antibacterial alloys. Based on the concept of high-entropy alloys, the present work designed and prepared a novel Co 0.4 FeCr 0.9 Cu 0.3 antibacterial high-entropy alloy with superior antibacterial properties without intricate or rigorous annealing processes, which outperform the antibacterial stainless steels. The antibacterial tests presented a 99.97% antibacterial rate against Escherichia coli and a 99.96% antibacterial rate against Staphylococcus aureus after 24 h. In contrast, the classic antibacterial copper-bearing stainless steel only performed the 71.50% and 80.84% antibacterial rate, respectively. The results of the reactive oxygen species analysis indicated that the copper ion release and the immediate contact with copper-rich phase had a synergistic effect in enhancing antibacterial properties. Moreover, this alloy exhibited excellent corrosion resistance when compared with the classic antibacterial stainless steels, and the compression test indicated the yield strength of the alloy was 1015 MPa. These findings generate fresh insights into guiding the designs of structure-function-integrated antibacterial alloys., Competing Interests: The authors declare no competing financial interests., (38; Technology.)

Accurate evaluation of HIF-1α levels can facilitate the detection of hypoxia niches in glioma and treatment decisions. To investigate the feasibility of intravoxel incoherent motion (IVIM) and R2* Mapping for detecting HIF-1α expression levels, sixteen rats with intracranial C6 gliomas were subjected to IVIM and R2* Mapping using a 7 Tesla MRI scanner. For each model, the brain tissue on the HIF-1α-stained slices was subdivided into multiple square regions of interest (ROIs) with areas of 1 mm 2 , for which HIF-1α expression was assessed by HALO software to form a maps of HIF scores with a 0-300 range. The IVIM and R2* Mapping images were processed to create maps of the D, D*, f and R2* that were then paired with the corresponding HIF score maps. The average D, D*, f, perfusion (f × D*) and R2* values were calculated for the ROIs in the tumor and normal brain regions with different HIF-1α levels and used in further analysis. In this study, the average tumor size of sixteen C6 model rats was 458 ± 46.52 mm 3 , and the 482 included ROIs consisted of 280 tumoral and 202 normal ROIs. The average HIF score for the tumor regions was significantly higher than normal brain tissue (p < 0.001), and higher HIF scores were obtained for the central part of tumors than peripheral parts (p=0.03). Compared with normal brain tissues, elevated perfusion and f values were observed in tumor regions (p = 0.021, 0.004). In tumoral ROIs, the R2* values were higher in the group with high HIF-1α expression than in the group with low HIF-1α expression (p = 0.003). A correlation analysis revealed a positive correlation between the R2* value and HIF scores (r = 0.43, p < 0.001) and a negative correlation between D* and the HIF scores (r = -0.30, p = 0.001). Discrepancies in HIF-1α expression were found among different intratumoral areas, and IVIM and R2* Mapping were found to be promising means of noninvasive detection of the distribution and expression level of HIF-1α., 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, Lu, Li, Mei, Wu, Geng, Wu and Yin.)

Purpose: This study aimed to assess different machine learning models based on radiomic features, Visually Accessible Rembrandt Images features and clinical characteristics in overall survival prediction of glioblastoma and to identify the reproducible features., Materials and Methods: Patients with preoperative magnetic resonance scans were allocated into 3 data sets. The Least Absolute Shrinkage and Selection Operator was used for feature selection. The prediction models were built by random survival forest (RSF) and Cox regression. C-index and integrated Brier scores were calculated to compare model performances., Results: Patients with cortical involvement had shorter survival times in the training set (P = 0.006). Random survival forest showed higher C-index than Cox, and the RSF model based on the radiomic features was the best one (testing set: C-index = 0.935 ± 0.023). Ten reproducible radiomic features were summarized., Conclusions: The RSF model based on radiomic features had promising potential in predicting overall survival of glioblastoma. Ten reproducible features were identified., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To explore the imaging changes of the liver and kidneys in COVID-19 survivors using variable flip angle (VFA) T1 mapping and intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI)., Methods: This prospective study included 37 discharged COVID-19 participants and 24 age-matched non-COVID-19 volunteers who underwent abdominal MRI with VFA T1 mapping and IVIM-DWI sequencing as a COVID-19 group and control group, respectively. Among those discharged COVID-19 participants, 23 patients underwent two follow-up MRI scans, and were enrolled as the 3-month follow-up group and 1-year follow-up group, respectively. The demographics, clinical characteristics, and laboratory tests were collected. Imaging parameters of the liver and kidneys were measured. All collected values were compared among different groups., Results: The 3-month follow-up group had the lowest hepatic T1 value, which was significantly lower than the value in the control group (P < 0.001). Additionally, the 3-month follow-up group had the highest hepatic ADC and D values, cortical ADC and f values, which were significantly higher than those in the control group (for all, P < 0.05). The hepatic D value in the 1-year follow-up group decreased significantly in comparison with that in the 3-month follow-up group (P = 0.001). Compared to non-severe patients, severe cases had significantly higher hepatic D* and f*D* values (P = 0.031, P = 0.015, respectively)., Conclusion: The dynamic alterations of hepatic and renal imaging parameters detected with T1 mapping and IVIM-DWI suggested that COVID-19 survivors might develop mild, non-symptomatic liver and kidney impairments, of which liver impairment could probably relieve over time and kidney impairment might be long-existing., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To identify effective factors and establish a model to distinguish COVID-19 patients from suspected cases., Methods: The clinical characteristics, laboratory results and initial chest CT findings of suspected COVID-19 patients in 3 institutions were retrospectively reviewed. Univariate and multivariate logistic regression were performed to identify significant features. A nomogram was constructed, with calibration validated internally and externally., Results: 239 patients from 2 institutions were enrolled in the primary cohort including 157 COVID-19 and 82 non-COVID-19 patients. 11 features were selected by LASSO selection, and 8 features were found significant using multivariate logistic regression analysis. We found that the COVID-19 group are more likely to have fever (OR 4.22), contact history (OR 284.73), lower WBC count (OR 0.63), left lower lobe involvement (OR 9.42), multifocal lesions (OR 8.98), pleural thickening (OR 5.59), peripheral distribution (OR 0.09), and less mediastinal lymphadenopathy (OR 0.037). The nomogram developed accordingly for clinical practice showed satisfactory internal and external validation., Conclusions: In conclusion, fever, contact history, decreased WBC count, left lower lobe involvement, pleural thickening, multifocal lesions, peripheral distribution, and absence of mediastinal lymphadenopathy are able to distinguish COVID-19 patients from other suspected patients. The corresponding nomogram is a useful tool in clinical practice., (© 2022. The Author(s).)

The facultative intracellular bacterium Listeria monocytogenes ( Lmo ) has great potential for development as a cancer vaccine platform given its properties. However, the clinical application of Lmo has been severely restricted due to its rapid clearance, compromised immune response in tumors, and inevitable side effects such as severe systemic inflammation after intravenous administration. Herein, an immunotherapy system was developed on the basis of natural red blood cell (RBC) membranes encapsulated Lmo with selective deletion of virulence factors ( Lmo @RBC). The biomimetic Lmo @RBC not only generated a low systemic inflammatory response but also enhanced the accumulation in tumors due to the long blood circulation and tumor hypoxic microenvironment favoring anaerobic Lmo colonization. After genome screening of tumors treated with intravenous PBS, Lmo , or Lmo @RBC, it was first found that Lmo @RBC induced extensive pore-forming protein gasdermin C ( GSDMC )-dependent pyroptosis, which reversed immunosuppressive tumor microenvironment and promoted a systemic strong and durable anti-tumor immune response, resulting in an excellent therapeutic effect on solid tumors and tumor metastasis. Overall, Lmo @RBC, as an intravenous living bacterial therapy for the selective initiation of tumor pyrolysis, provided a proof-of-concept of live bacteria vaccine potentiating tumor immune therapy.

Background: Bladder urothelial carcinoma (BLCA) is the most common type of bladder cancer. In this study, the correlation between the metabolic status and the outcome of patients with BLCA was evaluated using data from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Methods: The clinical and transcriptomic data of patients with BLCA were downloaded from the Cancer Genome Atlas and cBioPortal datasets, and energy metabolism-related gene sets were obtained from the Molecular Signature Database. A consensus clustering algorithm was then conducted to classify the patients into two clusters. Tumor prognosis, clinicopathological features, mutations, functional analysis, ferroptosis status analysis, immune infiltration, immune checkpoint-related gene expression level, chemotherapy resistance, and tumor stem cells were analyzed between clusters. An energy metabolism-related signature was further developed and verified using data from cBioPortal datasets. Results: Two clusters (C1 and C2) were identified using a consensus clustering algorithm based on an energy metabolism-related signature. The patients with subtype C1 had more metabolism-related pathways, different ferroptosis status, higher cancer stem cell scores, higher chemotherapy resistance, and better prognosis. Subtype C2 was characterized by an increased number of advanced BLCA cases and immune-related pathways. Higher immune and stromal scores were also observed for the C2 subtype. A signature containing 16 energy metabolism-related genes was then identified, which can accurately predict the prognosis of patients with BLCA. Conclusion: We found that the energy metabolism-associated subtypes of BLCA are closely related to the immune microenvironment, immune checkpoint-related gene expression, ferroptosis status, CSCs, chemotherapy resistance, prognosis, and progression of BLCA patients. The established energy metabolism-related gene signature was able to predict survival in patients with BLCA., 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 Zhang, Liang, Feng, Liu, Wu, Tang, Liu, Lu, Wang and Wei.)

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO 2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8 + and CD4 + T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

The search for natural and efficacious antineoplastic drugs, with minimal toxicity and side effects, is an important part of antitumor drug research and development. Tanshinone IIA is the most evaluated lipophilic active component of Salvia miltiorrhiza . Tanshinone IIA is a path-breaking traditional drug applied in cardiovascular treatment. It has also been found that tanshinone IIA plays an important role in the digestive, respiratory and circulatory systems, as well as in other tumor diseases. Tanshinone IIA significantly inhibits the proliferation of several types of tumors, blocks the cell cycle, induces apoptosis and autophagic death, in addition to inhibiting cell migration and invasion. Among these, the regulation of tumor-cell apoptosis signaling pathways is the key breakthrough point in several modes of antitumor therapy. The PI3K/AKT/MTOR signaling pathway and the JNK pathway are the key pathways for tanshinone IIA to induce tumor cell apoptosis. In addition to glycolysis, reactive oxygen species and signal transduction all play an active role with the participation of tanshinone IIA. Endogenous apoptosis is considered the main mechanism of tumor apoptosis induced by tanshinone IIA. Multiple pathways and targets play a role in the process of endogenous apoptosis. Tanshinone IIA can protect chemotherapy drugs, which is mainly reflected in the protection of the side effects of chemotherapy drugs, such as neurotoxicity and inhibition of the hematopoietic system. Tanshinone IIA also has a certain regulatory effect on tumor angiogenesis, which is mainly manifested in the control of hypoxia. Our findings indicated that tanshinone IIA is an effective treatment agent in the cardiovascular field and plays a significant role in antitumor therapeutics. This paper reviews the pharmacological potential and inhibitory effect of tanshinone IIA on cancer. It is greatly anticipated that tanshinone IIA will be employed as an adjuvant in the treatment of various cancers.

Background: Adrenocortical carcinoma (ACC) is an aggressive cancer with high recurrence rates and poor prognosis, even after radical surgery. The survival benefit of adjuvant radiotherapy (RT) in patients with ACC has not been well explored. The aim of this study was to evaluate the effect of adjuvant RT on the survival outcome of patients with ACC., Patients and Methods: All patients with nonmetastatic ACC who underwent complete resection were identified from the SEER database (2004-2016). Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival., Results: Of 365 patients with nonmetastatic ACC, 55 (15.1%) received adjuvant RT and the remainder underwent surgery alone. Patient characteristics were similar between the 2 groups, but those with a higher disease stage were more likely to receive adjuvant RT. Overall, patients receiving RT seemed to have better survival compared with the non-RT group (3-year OS rate, 63.1% vs 52.8%; P<.062). After adjustment for confounding factors, adjuvant RT was indeed associated with a 48% decreased risk of death (hazard ratio, 0.52; 95% CI, 0.29-0.91; P=.023) for all patients. In addition, adjuvant RT may confer a survival benefit only in patients with a high risk of recurrence (3-year OS rate, 55.1% vs 40.0%; P=.048) rather than in those with low/moderate-risk ACC (P=.559)., Conclusions: Our findings suggest that adjuvant RT may be associated with improved survival in patients with nonmetastatic ACC who underwent radical surgery, especially those with high risk of recurrence.

Phase transformation changes numerous properties of materials. Ti-Pt alloys have received much interest because of high martensitic transformation temperature. However, the intrinsic brittleness of these intermetallic compounds with low crystal symmetry and complicated phase structure limit their applications, especially when composition deviates from stoichiometry ratio. By performing in situ heating high-resolution scanning transmission electron microscopy experiment and micro-mechanical testing on Ti-35 at% Pt that contained majorly Ti 3 Pt and αTiPt phases, it was found that precipitating herringbone twinned αTiPt islands within Ti 3 Pt could occur upon heating, significantly refining mixed-phase structure. The refinement of multi-intermetallic mixed-phase structure endowed brittle material with remarkable capacity for plastic deformation and strain hardening. The plastic deformation mechanisms include phase transformation upon yielding and dislocation slips during hardening, which rarely occurs in intermetallic compounds with low symmetry. The strong interaction between different deformation modes even caused nano-crystallization along slip bands. The results demonstrate that brittle-to-ductile transition in intermetallic compounds can be achieved by tuning mixed-phase structure through phase transformations., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the evolution of radiological findings in the patients with coronavirus disease 2019 (COVID-19) pneumonia with different severities from onset to 1-year follow-up and identify the predictive factors for different pulmonary lesion absorption status in the patients infected with COVID-19. Methods: A retrospective study was performed on the clinical and radiological features of 175 patients with COVID-19 pneumonia hospitalized at three institutions from January 21 to March 20, 2020. All the chest CT scans during hospitalization and follow-ups after discharge were collected. The clinical and radiological features from the chest CT scans both at the peak stage and before discharge from the hospital were used to predict whether the pulmonary lesions would be fully absorbed after discharge by Cox regression. Then, these patients were stratified into two groups with different risks of pulmonary lesion absorption, and an optimal timepoint for the first CT follow-up was selected accordingly. Results: A total of 132 (75.4%) patients were classified into the non-severe group, and 43 (24.6%) patients were classified into the severe group, according to the WHO guidelines. The opacification in both the groups changed from ground-glass opacity (GGO) to consolidation and then from consolidation to GGO. Among the 175 participants, 135 (112 non-severe and 23 severe patients with COVID-19) underwent follow-up CT scans after discharge. Pulmonary residuals could be observed in nearly half of the patients (67/135) with the presentation of opacities and parenchymal bands. The parenchymal bands in nine discharged patients got fully absorbed during the follow-up periods. The age of patient [hazard ratio ( HR ) = 0.95, 95% CI , 0.95-0.99], level of lactate dehydrogenase (LDH) ( HR = 0.99; 95% CI , 0.99-1.00), level of procalcitonin ( HR = 8.72; 95% CI , 1.04-73.03), existence of diffuse lesions ( HR = 0.28; 95% CI , 0.09-0.92), subpleural distribution of lesions ( HR = 2.15; 95% CI, 1.17-3.92), morphology of residuals (linear lesion: HR = 4.58, 95% CI , 1.22-17.11; nodular lesion: HR = 33.07, 95% CI , 3.58-305.74), and pleural traction ( HR = 0.41; 95% CI , 0.22-0.78) from the last scan before discharge were independent factors to predict the absorption status of COVID-19-related pulmonary abnormalities after discharge. According to a Kaplan-Meier analysis, the probability of patients of the low-risk group to have pulmonary lesions fully absorbed within 90 days reached 91.7%. Conclusion: The development of COVID-19 lesions followed the trend from GGO to consolidation and then from consolidation to GGO. The CT manifestations and clinical and laboratory variables before discharge could help predict the absorption status of pulmonary lesions after discharge. The parenchymal bands could be fully absorbed in some COVID-19 cases. In this study, a Cox regression analysis indicated that a timepoint of 3 months since onset was optimal for the radiological follow-up of discharged patients., 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 © 2021 Zhao, Wang, Mei, Yin, Li, Zheng, Xiao, Yu, Qiu, Lu and Liu.)

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. Given the limited treatment options, prognostic assessment of ACC is increasingly crucial. In this study, we aim to assess the correlation between preoperative serum albumin and prognosis in patients with ACC after primary resection., Methods: We retrospectively collected and reviewed medical information about 71 ACC patients who underwent primary resection. Survival analysis was performed by Kaplan-Meier analysis with log-rank test or Breslow test. Receiver operating characteristic (ROC) curve and Jordan index was generated to explore optimal cut-off value of albumin. Univariate and multivariate analysis was conducted using Cox's hazards model. Statistical significance was defined as P < 0.05., Results: Among included patients, 33 patients (46.5%) relapsed at the end of follow-up, while 39 patients (54.9%) died. The median overall survival (OS) of included patients was 17 (range 1-104) months, and median recurrence-free survival (RFS) was 10 (range 0-104) months. In univariate analysis, the albumin was significantly associated with OS (HR:0.491, 95% CI: 0.260-0.930, P = 0.029) and RFS (HR: 0.383, 95% CI: 0.192-0.766, P = 0.007). In multivariate analysis, serum albumin as an independent prognostic factor of OS was confirmed (HR: 0.351, 95% CI: 0.126-0.982, P = 0.046)., Conclusions: Preoperative albumin might be a significant prognostic factor for ACC patients after primary resection. This result may be useful for risk stratification and management of this rare malignancy., (© 2021. The Author(s).)

Background: A long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient's peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD., Methods: 5/6 nephrectomized (5/6Nx) Sprague Dawley rats were intraperitoneally (IP) injected Dianeal (4.25% dextrose, 10 mL/rat/day) and were treated with pMSCs or umbilical cord (UC)-MSCs (approximately 2 × 10 6 /rat/week, IP). Ultrafiltration was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with 1.5-h dewell time, and kidney failure by serum creatinine (SCr) and blood urea nitrogen (BUN). The structure of the PM and kidneys was assessed using histology. Gene expression was examined using quantitative reverse transcription PCR, and protein levels using flow cytometric and Western blot analyses., Results: We showed a slight difference in the morphology between pMSCs and UC-MSCs in plastic dishes, and significantly higher expression levels of stemness-related genes (NANOG, OCT4, SOX2, CCNA2, RAD21, and EXO1) and MSCs surface markers (CD29, CD44, CD90 and CD105) in UC-MSCs than those in pMSCs, but no difference in the differentiation to chondrocytes, osteocytes or adipocytes. pMSC treatment was more effective than UC-MSCs in the protection of the MP and remnant kidneys in 5/6Nx rats from PDS-induced injury, which was associated with higher resistance of pMSCs than UC-MSCs to uremic toxins in culture, and more reduction of peritoneal mesothelial cell death by the secretome from pMSCs than from UC-MSCs in response to PDS exposure. The secretome from both pMSCs and UC-MSCs similarly inactivated NOS2 in activated THP1 cells., Conclusions: As compared to UC-MSCs, pMSCs may more potently prevent PDS-induced PM and remnant kidney injury in this uremic rat model of chronic PD, suggesting that autotransplantation of ex vivo-expanded pMSCs may become a promising therapy for UFF and deterioration of remnant kidney function in PD patients., (© 2021. The Author(s).)

Repeated exposure to fungi-contaminated dust can lead to multiple adverse effects on the lung, such as hypersensitivity pneumonitis, granuloma even irreversible fibrosis. 1,3-β-glucan, a major cell wall component of fungi, is considered as its exposure biomarker. Existing studies showed that a series of Th responses were involved in 1,3-β-glucan induced hypersensitivity pneumonitis, in which macrophages, Treg, and IL-10 producing B cells were reported to participate. The reciprocal interaction among those critical immune cells in 1,3-β-glucan induced inflammation was not investigated yet. To clarify the regulatory mechanism of IL-10 producing B cells on Th and Treg, the current study set up a primary cell co-culture system. The anti-CD22 antibody was injected intraperitoneally to generate IL-10 producing B cells deficiency mouse model. Cells were isolated and purified from C57BL∖6 mice in different groups. Flow cytometry was used to check the phenotype of different cell subtypes. CBA assay and real-time PCR were used to examine the levels of multiple cytokines. Our results indicated that IL-10 producing B cells could modulate the 1,3-β-glucan induced inflammatory response. The modulation of IL-10 producing B cells on Th response after 1,3-β-glucan treatment was cell contact independent. What's more, the modulation pattern of IL-10 producing B cells might be impaired without Treg response. IL-10-producing B cells regulated 1,3-β-glucan induced Th responses in co-ordination with Treg cells., (Copyright © 2021 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Objectives: Based on the current clinical routine, we aimed to develop a novel deep learning model to distinguish coronavirus disease 2019 (COVID-19) pneumonia from other types of pneumonia and validate it with a real-world dataset (RWD)., Methods: A total of 563 chest CT scans of 380 patients (227/380 were diagnosed with COVID-19 pneumonia) from 5 hospitals were collected to train our deep learning (DL) model. Lung regions were extracted by U-net, then transformed and fed to pre-trained ResNet-50-based IDANNet (Identification and Analysis of New covid-19 Net) to produce a diagnostic probability. Fivefold cross-validation was employed to validate the application of our model. Another 318 scans of 316 patients (243/316 were diagnosed with COVID-19 pneumonia) from 2 other hospitals were enrolled prospectively as the RWDs to testify our DL model's performance and compared it with that from 3 experienced radiologists., Results: A three-dimensional DL model was successfully established. The diagnostic threshold to differentiate COVID-19 and non-COVID-19 pneumonia was 0.685 with an AUC of 0.906 (95% CI: 0.886-0.913) in the internal validation group. In the RWD cohort, our model achieved an AUC of 0.868 (95% CI: 0.851-0.876) with the sensitivity of 0.811 and the specificity of 0.822, non-inferior to the performance of 3 experienced radiologists, suggesting promising clinical practical usage., Conclusions: The established DL model was able to achieve accurate identification of COVID-19 pneumonia from other suspected ones in the real-world situation, which could become a reliable tool in clinical routine., Key Points: • In an internal validation set, our DL model achieved the best performance to differentiate COVID-19 from non-COVID-19 pneumonia with a sensitivity of 0.836, a specificity of 0.800, and an AUC of 0.906 (95% CI: 0.886-0.913) when the threshold was set at 0.685. • In the prospective RWD cohort, our DL diagnostic model achieved a sensitivity of 0.811, a specificity of 0.822, and AUC of 0.868 (95% CI: 0.851-0.876), non-inferior to the performance of 3 experienced radiologists. • The attention heatmaps were fully generated by the model without additional manual annotation and the attention regions were highly aligned with the ROIs acquired by human radiologists for diagnosis.

Introduction and Hypothesis: A large variety of agents are available for intravesical instillation treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). The purpose of the study was to compare the efficacy and safety of those agents., Methods: PubMed, the Cochrane Library, and Embase were searched from database inception to February 2020 for randomized controlled trials. The language of publication was limited in English. Population, intervention, comparison, outcome, and study design was used to assess the eligible studies for inclusion and the Cochrane Collaboration's risk of bias tool was used to assess the methodological quality of the studies included. The primary outcome was O'Leary-Sant Interstitial Cystitis Problem Index (ICPI) and O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) improvement., Results: Eleven randomized controlled trials covering 8 agents with 902 patients were enrolled. According to the results of the ICPI and ICSI, 0.1 μM resiniferatoxin was more effective than other therapies. Combination therapy of hyaluronic acid and chondroitin sulphate ranked second in ICSI, third in ICPI, and first in the visual analog scale (VAS). Among regimens included for complication comparison, chondroitin sulphate was safer than other agents, with a probability of 78.5%., Conclusions: Resiniferatoxin (0.1 μM) is more effective at ICPI and ICSI improvement than other agents. More well-designed randomized controlled trials with a large sample size directly comparing the efficacy and safety of those agents are in need in the future to confirm our findings.

Background: Metastatic adrenocortical carcinoma (ACC) is an aggressive cancer with poor prognosis, with limited treatment options. The survival benefit of adrenal surgery in patients with synchronous metastatic disease has not been well explored., Methods: Patients with ACC with synchronous metastases were identified from the Surveillance, Epidemiology, and End Results database (2010-2016). The effect of adrenal surgery on different patterns of distant metastases was assessed. The overall survival was estimated by the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival outcome., Results: A total of 202 patients with synchronous metastatic ACC were identified from the SEER database, 76 (37.6%) patients underwent adrenal surgery. Compared to nonsurgical patients, patients who underwent adrenal surgery had a better survival (median overall survival: 4 vs. 13 months, P < 0.001). In sub-analyses, except for patients with liver metastases (P = 0.670), adrenalectomy could consistently confer a significant survival benefit in patients with lung metastases (P = 0.003), bone metastases (P = 0.020), and multiple metastases (P = 0.002). Cox regression analysis revealed that in addition to adrenalectomy [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.45-0.92; P = 0.017], metastasectomy (HR = 0.48, 95% CI 0.26-0.86; P = 0.013), and chemotherapy (HR = 0.59, 95% CI 0.42-0.82; P = 0.002) were also associated with improved survival., Conclusions: Our findings support the view that adrenal surgery may be associated with improved survival in patients with synchronous metastatic ACC (except for patients with liver metastases), and the metastatic sites have significant prognostic implications on survival outcomes with adrenal surgery.

Introduction: Adrenocortical carcinoma is a rare endocrine malignancy with a high recurrence rate. The aim of this study was to evaluate the role of surgery for patients with local or distant recurrent adrenocortical carcinoma and to attempt to identify prognostic features related to survival benefit in patients undergoing resection of recurrence., Methods: The data of 47 patients with recurrent adrenocortical carcinoma in West China Hospital, Sichuan, China, between 2009 and 2019 were retrospectively collected. These patients were divided into 2 groups according to whether resection of recurrence was performed. The correlation between overall survival after recurrence and reoperation was evaluated. Kaplan-Meier and univariate/multivariate Cox regression methods were used to identify any prognostic factors., Results: Included in our study were 21 patients who underwent reoperation and 26 patients who underwent nonoperative treatments were. The operation group had a better median overall survival after recurrence than the nonoperation group (19 months versus 6.5 months; P = .007). In the operated group, disease-free interval >12 months (P = .002), complete resection of recurrent adrenocortical carcinoma (P = .041), and R0 resection of the primary tumor (P = .005) were associated with prolonged survival after recurrence., Conclusions: Reoperation plays an important role in the management of selected patients with recurrent adrenocortical carcinoma. Disease-free interval, preoperative evaluation for complete resection, and R0 resection of the primary tumor are important prognostic characteristics for the resection of recurrent adrenocortical carcinoma. The overall survival after recurrence was significantly improved for patients who had a disease-free interval >12 months, and initial R0 resection or complete resection of recurrent adrenocortical carcinoma is feasible., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Surgery remains the only potential option for prolonging survival in synchronous metastatic adrenocortical carcinoma (ACC). The purpose of this study is to identify patients who may benefit from adrenalectomy. Using the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), we identified synchronous metastatic ACC patients who underwent adrenalectomy. Cox regression analysis was performed to identify prognostic factors associated with overall survival. A clinical scoring system was created to predict survival after surgery. Sixty-two patients underwent adrenalectomy for synchronous metastatic ACC. Median age was 54.5 years. Median overall survival was 12 months. In univariable analysis revealed that age 65≥years, tumor stage: T3/4, multiple metastases, liver metastases, and no chemotherapy were associated with poor survival. In the multivariable Cox analysis, liver metastases ( P = .017) and no chemotherapy ( P = .039) remained independent predictors of worse prognosis. A clinical scoring system including of 1-point each for the 2 predictors demonstrated good discrimination in predicting survival after adrenalectomy (3-year survival: 45.9% for 0 points and 0% for 1 or 2 points; P < .001, area under the curve = .78). Prolonged survival after adrenalectomy combined with chemotherapy can be potentially achieved in synchronous metastatic ACC patients without liver metastases. Patients with liver metastases should be carefully evaluated for surgery.

Objective: Aberrant expression of the immune checkpoint molecule, CD276, also known as B7-H3, is associated with tumorigenesis. In this review, we aim to comprehensively describe the role of CD276 in malignancies and its potential therapeutic effect., Data Sources: Database including PubMed, EMbase, Cochrane Library, CNKI, and Clinical Trails.gov were searched for eligible studies and reviews. Study selection: Original studies and review articles on the topic of CD276 in tumors were retrieved., Results: CD276 is an immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway. In this review, we evaluated the available evidence on the expression and regulation of CD276. We also assessed the role of CD276 within the immune micro-environment, effect on tumor progression, and the potential therapeutic effect of CD276 targeted therapy for malignancies., Conclusion: CD276 plays an essential role in cell proliferation, invasion, and migration in malignancies. Results from most recent studies indicate CD276 could be a promising therapeutic target for malignant tumors., 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 © 2021 Liu, Liang, Liu, Zhang, Wang, Watson, Zhou, Zhang, Wu, Zhang, Lu and Wang.)