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Life support technology is one of the most critical technologies in manned submersibles, acting for the pilots of the submersible and thus directly affecting its underwater safety. Due to its importance, many countries and international organizations have proposed standards and specifications for life support technology. This paper presents an overview of the life support technology of manned submersibles, comparing the standards proposed for it. Furthermore, it analyzes the specific data of oxygen supply and carbon dioxide absorption, both of which are critical aspects of life support technology in each standard, and identifies the data that is widely acknowledged and recognized as the basis for establishing ISO standard 22252:2020). Finally, ISO standard data such as oxygen and carbon dioxide concentration are further confirmed by the environmental parameters of manned submersibles such as the Fendouzhe.

The resonant magnetoelectric (ME) effect of Fe78Si9B13/Pb(Zr,Ti)O3 (FeSiB/PZT) composites with a surface-modified Fe78Si9B13 amorphous alloy has been studied. The surface-modified FeSiB can improve the ME coefficient at the resonant frequency by optimizing the magnetomechancial power conversion efficiency. The maximum ME coefficient of the surface-modified ribbons combined with soft PZT (PZT5) is two-thirds larger than that of the composites with fully amorphous ribbons. Meanwhile, the maximum value of the ME coefficient with surface-modified FeSiB ribbons and hard PZT (PZT8) is one-third higher compared with the fully amorphous composites. In addition, experimental results of magnetomechanical coupling properties of FeSiB/PZT composites with or without piezoelectric layers indicate that the power efficiency of the composites first decreases and then increases with the increase in the number of FeSiB layers. When the surface crystalline FeSiB ribbons are combined with a commercially available hard piezoelectric ceramic plate, the maximum magnetoelectric coupling coefficient of the ME composite reaches 5522 V/(Oe*cm), of which the electromechanical resonant frequency is 23.89 kHz.

Although extensively studied, it is unknown what is the major cellular energy driving tumor metastasis after anti-cancer radiotherapy. Metabolic reprogramming is one of the fundamental hallmarks in carcinogenesis and tumor progression featured with the increased glycolysis in solid tumors. However, accumulating evidence indicates that in addition to the rudimentary glycolytic pathway, tumor cells are capable of reactivating mitochondrial OXPHOS under genotoxic stress condition to meet the increasing cellular fuel demand for repairing and surviving anti-cancer radiation. Such dynamic metabolic rewiring may play a key role in cancer therapy resistance and metastasis. Interestingly, data from our group and others have demonstrated that cancer cells can re-activate mitochondrial oxidative respiration to boost an annexing energy to meet the increasing cellular fuel demand for tumor cells surviving genotoxic anti-cancer therapy with metastatic potential.

Summary: Delay aging, especially in healthy life extension, brought the most interest to the medical field. Searching for anti-aging drugs with relative safety profiles bring natural products in hotspot. In this study, we find that dioscin promotes the health span extension in wild-type Caenorhabditis elegans. Through the genetic screening in C. elegans, we further reveal that dioscin activates the transcription factor SBP-1/SREBP by the UPRER transcription factor XBP-1 to upregulate transcription of the Δ9 desaturase FAT-5 and FAT-7, resulting in increased monounsaturated fatty acid content which requires for healthy life span extension. Intriguingly, through tissue-specific knockdown, we find that dioscin modulates the health span by activating SBP-1 in the intestine. Unexpectedly, dietary supplementation of POA and OA rescues XBP-1, SBP-1 mutants-induced shortened life span phenotype. Considering the conservation of MUFAs metabolism, dioscin may promote health span in other species, including mammals. Our work suggests that dioscin might be a promising candidate for developing anti-aging agent.

Acquired radioresistance is a challenge for the cure of glioblastoma. Here, the authors show that radioresistant glioblastoma boosts mitochondrial fatty acid oxidation that fuels cell proliferation and induces immunosuppression via CD47 mediated anti-phagocytosis. Inhibition of FAO by etomoxir combined with anti-CD47 antibodies sensitizes glioblastoma to radiotherapy.

Background: EGFR amplification and/or mutation are found in more than half of the cases with glioblastoma. Yet, the role of chromatin interactions and its regulation of gene expression in EGFR-amplified glioblastoma remains unclear. Methods: In this study, we explored alterations in 3D chromatin organization of EGFR-amplified glioblastoma and its subsequent impact by performing a comparative analysis of Hi-C, RNA-seq, and whole-genome sequencing (WGS) on EGFR-amplified glioblastoma-derived A172 and normal astrocytes (HA1800 cell line). Results: A172 cells showed an elevated chromatin relaxation, and unexpected entanglement of chromosome regions. A genome-wide landscape of switched compartments and differentially expressed genes between HA1800 and A172 cell lines demonstrated that compartment activation reshaped chromatin accessibility and activated tumorigenesis-related genes. Topological associating domain (TAD) analysis revealed that altered TAD domains in A172 also contribute to oncogene activation and tumor repressor deactivation. Interestingly, glioblastoma-derived A172 cells showed a different chromatin loop contact propensity. Genes in tumorigenesis-associated signaling pathways were significantly enriched at the anchor loci of altered chromatin loops. Oncogene activation and tumor repressor deactivation were associated with chromatin loop alteration. Structure variations (SVs) had a dramatic impact on the chromatin conformation of EGFR-amplified glioblastoma-derived tumor cells. Moreover, our results revealed that 7p11.2 duplication activated EGFR expression in EGFR-amplified glioblastoma via neo-TAD formation and novel enhancer-promoter interaction emergence between LINC01446 and EGFR. Conclusions: The disordered 3D genomic map and multi-omics data of EGFR-amplified glioblastoma provide a resource for future interrogation of the relationship between chromatin interactions and transcriptome in tumorigenesis.

Summary: The Mammalian/mechanistic target of rapamycin (mTOR) played a central role in cellular survival and aging. Inhibition of mTOR had been proposed as a reasonable strategy to promote lifespan and delay age-related diseases in evolutionarily diverse organisms. The study showed that lifespan extension and age-related diseases improvement could be achieved by targeting evolutionarily conserved mTOR pathways and mechanisms using pharmacological interventions. Using this approach in Caenorhabditis elegans, We found that 2 μM Usnic Acid significantly extended the healthy lifespan in wild-type animals. Furthermore, via genetic screen, we showed that Usnic Acid acted on mTOR, which was followed by the activation of PHA-4/Foxa to extend the healthy lifespan. Intriguingly, Usnic Acid also delayed neurodegeneration diseases such as Alzheimer’s and polyglutamine disease through mTOR-dependent manner. Our work suggested that Usnic Acid might be a viable candidate for the prevention and treatment of aging and age-related diseases.

Metformin, as the first-line oral drug for type 2 diabetes, has proven benefits against aging, cancer and cardiovascular diseases. But the influence of metformin to the immune response and its molecular mechanisms remain obscure. Metformin increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Meanwhile, metformin protects the animals from the infection by enhancing the tolerance to the pathogen infection rather than by reducing the bacterial burden. Through the screening of classical immune pathways in C. elegans, we find metformin enhances innate immunity through p38 MAPK pathway. Furthermore, activated p38/PMK-1 by metformin acts on the intestine for innate immune response. In addition, metformin-treated mice have increased resistance to P. aeruginosa PA14 infection and significantly increased the levels of active PMK-1. Therefore, promoted p38/PMK-1-mediated innate immunity by metformin is conserved from worms to mammals. Our work provides a conserved mechanism by which metformin enhances immune response and boosts its therapeutic application in the treatment of pathogen infection.

Summary: The longevity of an organism is influenced by both genetic and environmental factors. With respect to genetic factors, a significant effort is being made to identify pharmacological agents that extend lifespan by targeting pathways with a defined role in the aging process. Sanguinarine (San) is a benzophenanthridine alkaloid that exerts a broad spectrum of properties. In this study, we utilized Caenorhabditis elegans to examine the mechanisms by which sanguinarine influences aging and innate immunity. We find that 0.2 μM sanguinarine extends healthspan in C. elegans. We further show that sanguinarine generates reactive oxygen species (ROS), which is followed by the activation of PMK-1/SKN-1pathway to extend healthspan. Intriguingly, sanguinarine increases resistance to pathogens by reducing the bacterial burden in the intestine. In addition, we also find that sanguinarine enhances innate immunity through PMK-1/SKN-1 pathway. Our data suggest that sanguinarine may be a viable candidate for the treatment of age-related disorders.

BackgroundIntracranial hemangiopericytoma/solitary fibrous tumor (SFT/HPC) is a rare type of neoplasm containing malignancies of infiltration, peritumoral edema, bleeding, or bone destruction. However, SFT/HPC has similar radiological characteristics as meningioma, which had different clinical managements and outcomes. This study aims to discriminate SFT/HPC and meningioma via deep learning approaches based on routine preoperative MRI.MethodsWe enrolled 236 patients with histopathological diagnosis of SFT/HPC (n = 144) and meningioma (n = 122) from 2010 to 2020 in Xiangya Hospital. Radiological features were extracted manually, and a radiological diagnostic model was applied for classification. And a deep learning pretrained model ResNet-50 was adapted to train T1-contrast images for predicting tumor class. Deep learning model attention mechanism was visualized by class activation maps.ResultsOur study reports that SFT/HPC was found to have more invasion to venous sinus (p = 0.001), more cystic components (p < 0.001), and more heterogeneous enhancement patterns (p < 0.001). Deep learning model achieved a high classification accuracy of 0.889 with receiver-operating characteristic curve area under the curve (AUC) of 0.91 in the validation set. Feature maps showed distinct clustering of SFT/HPC and meningioma in the training and test cohorts, respectively. And the attention of the deep learning model mainly focused on the tumor bulks that represented the solid texture features of both tumors for discrimination.

Abstract Background Glioma, the most frequent primary tumor of the central nervous system, has poor prognosis. The epidermal growth factor receptor (EGFR) pathway and angiogenesis play important roles in glioma growth, invasion, and recurrence. The present study aimed to use proteomic methods to probe into the role of the EGF‐EGFR‐angiogenesis axis in the tumorigenesis of glioma and access the therapeutic efficacy of selumetinib on glioma. Methods Proteomic profiling was used to characterize 200 paired EGFR‐positive and EGFR‐negative glioma tissues of all pathological types. The quantitative mass spectrometry data were used for systematic analysis of the proteomic profiles of 10 EGFR‐positive and 10 EGFR‐negative glioma cases. Consensus‐clustering analysis was used to screen target proteins. Immunofluorescence analysis, cell growth assay, and intracranial xenograft experiments were used to verify and test the therapeutic effect of selumetinib on glioma. Results Advanced proteomic screening demonstrated that the expression of EGF‐like domain multiple 7 (EGFL7) was higher in EGFR‐positive tumor tissues than in EGFR‐negative tumor tissues. In addition, EGFL7 could act as an activator in vitro and in vivo to promote glioma cell proliferation. EGFL7 was associated strongly with EGFR and prognosis. EGFL7 knockdown effectively suppressed glioma cell proliferation. Selumetinib treatment showed tumor reduction effect in EGFR‐positive glioblastoma xenograft mouse model. Conclusions EGFL7 is a potential diagnostic biomarker and therapeutic target of glioma. Selumetinib could target the EGFR pathway and possibly improve the prognosis of EGFR‐positive glioma.

The emergence of tumour adaptive radioresistance can limit the success of radiation therapy and immunotherapy in breast cancer. In this study, the authors demonstrate that CD47 and HER2 are coordinating in tumor response to radiation and that co-blockage of both receptors can eliminate radiorestistant breast cancer cells.

Abstract Background Receptor tyrosine kinase AXL has been found to be highly expressed in osteosarcoma and positively associated with poor prognosis. There are tumor groups with high or low AXL expression, which had different capabilities of invading vessels and forming distal metastases. Exosome‐transmitted lncRNA may be transferred intercellularly to promote tumor cells’ proliferation and invasion. Methods Exosomes were detected by electron microscopy, particle size analysis, and western blotting. High‐throughput sequencing helped to find the highest differentially expressed lncRNA in AXL‐associated exosomes. Clone formation, wound healing, transwell assay, and xenograft model in nude mice were performed to evaluate cells’ proliferation, migration, and invasion in vitro and in vivo. Lentiviral transfection was used to up‐ or down‐regulate the lncRNA levels in cell lines. Luciferase reporter assay and RNA FISH etchelped to indicate the molecular mechanisms. The results in the cell lines were proved in the osteosarcoma tissues with clinical analysis. Results The exosomes derived from donor cells with high AXL expression could promote the proliferation and invasion and upregulate AXL expression of the receiver cells with low AXL. Linc00852 was the highest differentially expressed lncRNA in AXL‐associated exosomes and was also regulated by AXL expression. Although the mechanisms of linc00852 in nucleus were unrevealed, it could upregulate AXL expression partly by competitively binding to miR‐7‐5p. The AXL‐exosome‐linc00852‐AXL positive feedback loop might exist between the donor cells and the receiver cells. Clinically, linc00852 was significantly highly expressed in osteosarcoma tissues and positively associated with tumor volumes and metastases, which was also obviously related with AXL mRNA expression. Conclusion AXL‐associated exosomal linc00852 up‐regulated the proliferation, migration, and invasion of osteosarcoma cells, which would be considered as a new tumor biomarker and a special therapeutic target for osteosarcoma.

Abstract Background Invasive sphenoid sinus aspergillosis is a rare but life-threatening condition usually found in immunocompromised patients. When involving cavernous sinus and surrounding structures, patients are frequently misdiagnosed with a neoplasm or sellar abscess. Timely diagnosis and intervention are crucial to patients’ outcomes. The objective of this study is to review cases of invasive sphenoid sinus aspergillosis to describe disease manifestations, imaging features, treatment, and outcome. Case presentation We describe four patients with invasive sphenoid sinus aspergillosis misdiagnosed as sellar tumors preoperatively. The mass was completely removed in three patients and partially removed in one patient microscopically. Pathological examinations confirmed Aspergillus in all cases. All four patients received anti-fungal agents postoperatively. There was no recurrence at the time of each patient’s follow-up date. One patient with complete resection was lost to follow-up while the other three patients’ neurologic function improved. Additionally, we performed a systematic review regarding invasive sphenoid sinus aspergillosis of existing English literature. Conclusion With regard to clinical symptoms, headache, vision impairment, and ophthalmoplegia were observed in over half of the patients in the literature. A sellar mass with bone destruction on CT and involvement of cavernous sinus is highly suggestive of invasive fungal sphenoid sinusitis. Immediate surgical removal of the lesion is recommended for invasive sphenoid sinus aspergillosis to preserve nerve function and increase the likelihood of survival.

The semiconductor nanowire architecture provides opportunities for non-planar electronics and optoelectronics arising from its unique geometry. This structure gives rise to a large surface area-to-volume ratio and therefore understanding the effect of nanowire surfaces on nanowire optoelectronic properties is necessary for engineering related devices. We present a systematic study of the non-uniform optical properties of Au-catalyzed GaAs/AlGaAs core–shell nanowires introduced by changes in the sidewall faceting. Significant variation in intra-wire photoluminescence (PL) intensity and PL lifetime (τPL) was observed along the nanowire axis, which was strongly correlated with the variation of sidewall facets from {112} to {110} from base to tip. Faster recombination occurred in the vicinity of {112}-oriented GaAs/AlGaAs interfaces. An alternative nanowire heterostructure, the radial quantum well tube consisting of a GaAs layer sandwiched between two AlGaAs barrier layers, is proposed and demonstrates superior uniformity of PL emission along the entire length of nanowires. The results emphasize the significance of nanowire facets and provide important insights for nanowire device design.

Realgar (As4S4) has been used in traditional Chinese medicines for treatment of malignancies. The poor solubility of As4S4 hampered its clinical applications. Realgar quantum dots (RQDs) were developed to overcome these problems. Previous studies revealed that the RQDs were effective against endometrial cancer JEC cells and hepatocarcinoma HepG2 cells via inducing apoptosis.Apoptosis and autophagy are important programmed cell death pathways leading to anticancer effects. This study further examined effects of RQDs on autophagy, focusing on the formation of the autophagosome in JEC cells. CCK8 assay was used to examine cell proliferation. Flow cytometry was used to analyze cell cycle. Transmission electron microscopy (TEM) was used to examine the autophagy, cells were transfected with pEGFP-C3-MAP1LC3B plasmid to examine effects of RQDs on autophagosome via confocal microscope. Autophagy-related proteins were examined by Western blot. RQDs exhibited cytotoxicity in JEC cells in a concentration- and time- dependent manner. RQDs induced G2 and S phase arrest in JEC cells. RQDs significantly induced autophagy, with the double-membrane and autophagosome-like structures by TEM. The diffused distribution of pEGFP-C3-MAP1LC3B green fluorescence were become the punctuate pattern fluorescence after treatment with RQDs in cells transfected with pEGFP-C3-MAP1LC3B plasmid RQDs increased the expression of autophagyregulatory proteins LC3 I/II, Beclin-1, p62 and Atg12 in a concentration-dependent manner, similar to autophagy induced by serum starvation, except for p62, as induction of p62 is a characteristic of arsenic compounds. Taken together, the present study clearly demonstrated that RQDs can induce autophagy in JEC cells as one of mechanisms of anticancer effects, and indicated that RQDs may be developed as an autophagy inducer.

Tumor cells, including cancer stem cells (CSCs) resistant to radio- and chemotherapy, must enhance metabolism to meet the extra energy demands to repair and survive such genotoxic conditions. However, such stress-induced adaptive metabolic alterations, especially in cancer cells that survive radiotherapy, remain unresolved. In this study, we found that CPT1 (Carnitine palmitoyl transferase I) and CPT2 (Carnitine palmitoyl transferase II), a pair of rate-limiting enzymes for mitochondrial fatty acid transportation, play a critical role in increasing fatty acid oxidation (FAO) required for the cellular fuel demands in radioresistant breast cancer cells (RBCs) and radiation-derived breast cancer stem cells (RD-BCSCs). Enhanced CPT1A/CPT2 expression was detected in the recurrent human breast cancers and associated with a worse prognosis in breast cancer patients. Blocking FAO via a FAO inhibitor or by CRISPR-mediated CPT1A/CPT2 gene deficiency inhibited radiation-induced ERK activation and aggressive growth and radioresistance of RBCs and RD-BCSCs. These results revealed that switching to FAO contributes to radiation-induced mitochondrial energy metabolism, and CPT1A/CPT2 is a potential metabolic target in cancer radiotherapy.

Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells. The results reveal that activation of STAT3, a well-defined redox-sensitive transcriptional factor, is causally linked with GBM adaptive radioresistance. Database analysis also agrees with the worse prognosis in GBM patients due to the STAT3 expression-associated low RT responsiveness. However, although the radioresistant GBM cells can be resensitized by inhibition of STAT3, a fraction of radioresistant cells can still survive the RT combined with STAT3 inhibition or CRISPR/Cas9-mediated STAT3 knockout. A complementally enhanced activation of ERK1/2 by STAT3 inhibition is identified responsible for the survival of the remaining resistant tumor cells. Dual inhibition of ERK1/2 and STAT3 remarkably eliminates resistant GBM cells and inhibits tumor regrowth. These findings demonstrate a previously unknown feature ofSTAT3-mediated ERK1/2 regulation and an effective combination of two targets in resensitizing GBM to RT. Keywords: GBM, Radiotherapy, Radioresistance, STAT3, ERK1/2, Tumor regrowth

The development of solar energy is one of the most effective means to deal with the environmental and energy crisis. The floating photovoltaic (PV) system is an attractive type because of its multiple advantages and has been well developed based on fresh water areas on land. This paper focuses on the expansion of this sector towards the ocean, offshore floating PV plants, which is the new growth point with huge potential for the future PV sector. For this new field, the technology readiness level is really low and research to understand the interaction between offshore floating PV plants and marine environment are proceeding. In this paper, we aim to discuss the technological feasibility of offshore floating PV plants as well as analyze potential impacts on the marine environment during the life cycle of PV from manufacturing until disposal. [ABSTRACT FROM AUTHOR]