Targeting SRSF3 restores immune mRNA translation in microglia/macrophages following cerebral ischemia.

We recently described a novel ribosome-based regulatory mechanism/checkpoint that controls innate immune gene translation and microglial activation in non-sterile inflammation orchestrated by RNA binding protein SRSF3. Here we describe a role of SRSF3 in the regulation of microglia/macrophage activation phenotypes after experimental stroke. Using a model-system for analysis of the dynamic translational state of microglial ribosomes we show that 24 h after stroke highly upregulated immune mRNAs are not translated resulting in a marked dissociation of mRNA and protein networks in activated microglia/macrophages. Next, microglial activation after stroke was characterized by a robust increase in pSRSF3/SRSF3 expression levels. Targeted knockdown of SRSF3 using intranasal delivery of siRNA 24 h after stroke caused a marked knockdown of endogenous protein. Further analyses revealed that treatment with SRSF3-siRNA alleviated translational arrest of selected genes and induced a transient but significant increase in innate immune signaling and IBA1+ immunoreactivity peaking 5 days after initial injury. Importantly, delayed SRSF3-mediated increase in immune signaling markedly reduced the size of ischemic lesion measured 7 days after stroke. Together, our findings suggest that targeting SRSF3 and immune mRNA translation may open new avenues for molecular/therapeutic reprogramming of innate immune response after ischemic injury.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Quantum Control of a Single Magnon in a Macroscopic Spin System.

Nonclassical quantum states are the pivotal features of a quantum system that differs from its classical counterpart. However, the generation and coherent control of quantum states in a macroscopic spin system remain an outstanding challenge. Here we experimentally demonstrate the quantum control of a single magnon in a macroscopic spin system (i.e., 1 mm-diameter yttrium-iron-garnet sphere) coupled to a superconducting qubit via a microwave cavity. By tuning the qubit frequency in situ via the Autler-Townes effect, we manipulate this single magnon to generate its nonclassical quantum states, including the single-magnon state and the superposition of single-magnon state and vacuum (zero magnon) state. Moreover, we confirm the deterministic generation of these nonclassical states by Wigner tomography. Our experiment offers the first reported deterministic generation of the nonclassical quantum states in a macroscopic spin system and paves a way to explore its promising applications in quantum engineering.

YEATS2 regulates the activation of TAK1/NF-κB pathway and is critical for pancreatic ductal adenocarcinoma cell survival.

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is poor despite diagnostic progress and new chemotherapeutic regimens. Constitutive activation of NF-κB is frequently observed in PDAC. In this study, we found that YEATS2, a scaffolding protein of ATAC complex, was highly expressed in human PDAC. Depletion of YEATS2 reduced the growth, survival, and tumorigenesis of PDAC cells. The binding of YEATS2 is crucial for maintaining TAK1 activation and NF-κB transcriptional activity. Of importance, our results reveal that YEATS2 promotes NF-κB transcriptional activity through modulating TAK1 abundance and directly interacting with NF-κB as a co-transcriptional factor.

circSNX6 (hsa_circ_0031608) enhances drug resistance of non-small cell lung cancer (NSCLC) via miR-137.

circRNAs have been suggested to modulate NSCLC tumorigenesis and drug resistance. Whether circSNX6 affects NSCLC remains unclear. In this study, we aim to investigate the role of circSNX6 in drug resistance of NSCLC exposed to cisplatin. RT-qPCR method was used to investigate expression levels of circSNX6, miR-137 and CXCL12. MTT, cell colony formation and TUNEL assays were utilized to assess cell viability, proliferation, apoptosis, respectively. Xenograft assay was conducted to examinein vivotumor growth. circSNX6 overexpression caused enhanced cell viability and proliferation of H1299 and Calu-1, while it inhibited apoptosis under cisplatin treatment. miR-137 inhibitor greatly rescued cell viability, proliferation and apoptosis of circSNX6 knockdown H1299 cells. miR-137 mimic increased ROS generation, as well as reduced GSH and SOD levels, whereas miR-137 inhibitor exerted opposing effect. circSNX6 knockdown also enhanced ROS generation, as well as decreased GSH and SOD levels. CXCL12 partially restored miR-137 mimic-modulated cell viability, proliferation and apoptosis. Herein, our group proposes circSNX6 as key regulator for drug resistance of NSCLC. The findings provide solid groundings for understanding of NSCLC pathogenesis and development of therapeutics.

Cinobufacini Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting M1 Macrophage Polarization.

Cinobufacini is a traditional Chinese medicine used clinically that has antitumor and anti-inflammatory effects. It improves colitis outcomes in the clinical setting, but the mechanism underlying its function yet to be uncovered. We investigated the protective effects and mechanisms of cinobufacini on colitis using a dextran sulfate sodium (DSS)-induced colitis mouse model, mainly focusing on the impact of macrophage polarization. Our results showed that cinobufacini dramatically ameliorated DSS-induced colitis in mice. Cinobufacini treatment reduced the infiltration of activated F4/80+ and/or CD68+ macrophages into the colon in DSS-induced colitis mice. More importantly, cinobufacini significantly decreased the quantity of M1 macrophages and the expression of proinflammatory cytokines such as interleukin-6, tumor necrosis factor α, and inducible nitric oxide synthase. Cinobufacini also increased the population of M2 macrophages and the expression of anti-inflammatory factors such as interleukin-10 and arginase-1 in DSS-induced colitis mice. Furthermore, our study demonstrated that cinobufacini inhibited M1 macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells. Mechanistically, our in vivo and in vitro results showed that cinobufacini inhibition of M1 macrophage polarization may be associated with the suppression of nuclear factor κB activation. Our study suggests that cinobufacini could ameliorate DSS-induced colitis in mice by inhibiting M1 macrophage polarization.

Age-related deregulation of TDP-43 after stroke enhances NF-κB-mediated inflammation and neuronal damage.

BACKGROUND: TDP-43 has been identified as a disease-associated protein in several chronic neurodegenerative disorders and increasing evidence suggests its potentially pathogenic role following brain injuries. Normally expressed in nucleus, under pathological conditions TDP-43 forms cytoplasmic ubiquitinated inclusions in which it is abnormally phosphorylated and cleaved to generate a 35 and a 25 kDa C-terminal fragments. In the present study, we investigated age-related expression patterns of TDP-43 in neurons and glia and its role as modulator of inflammation following ischemic injury. METHODS: Wild-type and TDP-43 transgenic mice of different age groups were subjected to transient middle cerebral artery occlusion. The role of TDP-43 in modulation of inflammation was assessed using immunofluorescence, Western blot analysis, and in vivo bioluminescence imaging. Finally, post-mortem stroke human brain sections were analyzed for TDP-43 protein by immunohistochemistry. RESULTS: We report here an age-related increase and formation of ubiquitinated TDP-43 cytoplasmic inclusions after stroke. The observed deregulation in TDP-43 expression patterns was associated with an increase in microglial activation and innate immune signaling as revealed by in vivo bioluminescence imaging and immunofluorescence analysis. The presence of ubiquitinated TDP-43 aggregates and its cleaved TDP-35 and TDP-25 fragments was markedly increased in older, 12-month-old mice leading to larger infarctions and a significant increase in in neuronal death. Importantly, unlike the hallmark neuropathological features associated with chronic neurodegenerative disorders, the TDP-43-positive cytoplasmic inclusions detected after stroke were not phosphorylated. Next, we showed that an increase and/or overexpression of the cytoplasmic TDP-43 drives the pathogenic NF-κB response and further increases levels of pro-inflammatory markers and ischemic injury after stroke in age-dependent manner. Finally, analyses of the post-mortem stroke brain tissues revealed the presence of the cytoplasmic TDP-43 immunoreactive structures after human stroke. CONCLUSION: Together, our findings suggest that the level of cytoplasmic TDP-43 increases with aging and may act as an age-related mediator of inflammation and neuronal injury after stroke. Thus, targeting cytoplasmic TDP-43 may have a therapeutic potential after stroke.

Anti-influenza activity of berberine improves prognosis by reducing viral replication in mice.

Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti-inflammatory, antibacterial, antifungal, and antihelminthic effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro. The results showed that berberine strongly suppressed viral replication in A549 cells and in mouse lungs. Meanwhile, berberine relieved pulmonary inflammation and reduced necrosis, inflammatory cell infiltration, and pulmonary edema induced by viral infection in mice when compared with vehicle-treated mice. Berberine suppressed the viral infection-induced up-regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the mRNA and protein levels. Furthermore, berberine significantly inhibited the viral infection-induced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. Our data provide new insight into the potential of berberine as a therapeutic agent for viral infection via its antiviral activity.

Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia.

BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury. METHODS: To visualize effects of neuroinflammation on neurogenesis/gliogenesis, we created a transgenic model bearing the dual reporter system luciferase and GFP under transcriptional control of the murine nestin promoter. In this model, transcriptional activation of nestin was visualized from the brains of living animals using biophotonic/bioluminescence molecular imaging and a high resolution charged coupled device camera. Nestin induction profiles in vivo and in tissue sections were analyzed in two different experimental paradigms: middle cerebral artery occlusion and lipopolysaccharide-induced innate immune stimuli. RESULTS: We report here a context- and injury-dependent induction and cellular expression profile of nestin. While in the baseline conditions the nestin signal and/or GFP expression was restricted to neuronal progenitors, the cellular expression patterns of nestin following innate immune challenge and after stroke markedly differed shifting the cellular expression patterns towards activated microglia/macrophages and astrocytes. CONCLUSIONS: Our results suggest that nestin may serve as a context-dependent biomarker of inflammatory response in glial cells including activated microglia/macrophages.

Adam17, a Target of Mir-326, Promotes Emt-Induced Cells Invasion in Lung Adenocarcinoma.

BACKGROUND/AIMS: A disintegrin and metalloprotease (ADAM) 17 has been reported to be implicated in cancer cells invasion. Nevertheless, its potential role in lung adenocarcinoma has not been addressed clearly. METHODS: RT-PCR and Western blot were used to detect the expression of miR-326 and ADAM17 in lung adenocarcinoma samples (n=73). miR-326 mimics and inhibitor were tansfected in human A549 and SPCA1 cell lines. The transwell assay was used to detect the cell invasive ability. The regulation mechanism was evaluated by luciferase reporter assay. The markers of (epithelial-to-mesenchymal transition) EMT were detected by using Western blot assay. RESULTS: We found increased expression of ADAM17 in lung adenocarcinoma and cell lines. In vitro, up-regulation of ADAM17 promoted cells invasion, while silencing of ADAM17 inhibited cells invasion. Meanwhile, ADAM17 could affect the markers of EMT. Furthermore, we confirmed that ADAM17 is a target of miR-326, which is involved in EMT and cells invasion. CONCLUSIONS: These findings revealed that ADAM17, a target of miR-326, promoted EMT-induced cells invasion in lung adenocarcinoma.

Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A2 receptors.

The adenosine subfamily G protein-coupled receptors A2AR and A2BR have been identified as promising cancer immunotherapy candidates. One of the A2AR/A2BR dual antagonists, AB928, has progressed to a phase II clinical trial to treat rectal cancer. However, the precise mechanism underlying its dual-antagonistic properties remains elusive. Herein, we report crystal structures of the A2AR complexed with AB928 and a selective A2AR antagonist 2-118. The structures revealed a common binding mode on A2AR, wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets. In contrast, the cAMP assay and A2AR and A2BR molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A2BR. Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A2BR pocket, while 2-118 did not due to intrinsic differences. This disparity potentially accounted for the difference in inhibitory efficacy between A2BR and A2AR. This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A2AR/A2BR for cancer therapy.

Subtle Structural Changes across the Boundary between A2AR/A2BR Dual Antagonism and A2BR Antagonism: A Novel Class of 2-Aminopyrimidine-Based Derivatives.

Aberrantly elevated adenosine in the tumor microenvironment exerts its immunosuppressive functions through adenosine receptors A2AR and A2BR. Antagonism of A2AR and A2BR has the potential to suppress tumor growth. Herein, we report a systemic assessment of the effects of an indole modification at position 4, 5, 6, or 7 on both A2AR/A2BR activity and selectivity of novel 2-aminopyrimidine compounds. Substituting indole at the 4-/5-position produced potent A2AR/A2BR dual antagonism, whereas the 6-position of indole substitution gave highly selective A2BR antagonism. Molecular dynamics simulation showed that the 5-cyano compound 7ai had a lower binding free energy than the 6-cyano compound 7aj due to water-bridged hydrogen bond interactions with E169 or F168 in A2AR. Of note, dual A2AR/A2BR antagonism by compound 7ai can profoundly promote the activation and cytotoxic function of T cells. This work provided a strategy for obtaining novel dual A2AR/A2BR or A2BR antagonists by fine-tuning structural modification.

A Deep-Learning Model for Diagnosing Fresh Vertebral Fractures on Magnetic Resonance Images.

BACKGROUND: The accurate diagnosis of fresh vertebral fractures (VFs) was critical to optimizing treatment outcomes. Existing studies, however, demonstrated insufficient accuracy, sensitivity, and specificity in detecting fresh fractures using magnetic resonance imaging (MRI), and fall short in localizing the fracture sites. METHODS: This prospective study comprised 716 patients with fresh VFs. We obtained 849 Short TI Inversion Recovery (STIR) image slices for training and validation of the AI model. The AI models employed were yolov7 and resnet50, to detect fresh VFs. RESULTS: The AI model demonstrated a diagnostic accuracy of 97.6% for fresh VFs, with a sensitivity of 98% and a specificity of 97%. The performance of the model displayed a high degree of consistency when compared to the evaluations by spine surgeons. In the external testing dataset, the model exhibited a classification accuracy of 92.4%, a sensitivity of 93%, and a specificity of 92%. CONCLUSIONS: Our findings highlighted the potential of AI in diagnosing fresh VFs, offering an accurate and efficient way to aid physicians with diagnosis and treatment decisions.

Galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury.

Growing evidence suggests that galectin-3 is involved in fine tuning of the inflammatory responses at the periphery, however, its role in injured brain is far less clear. Our previous work demonstrated upregulation and coexpression of galectin-3 and IGF-1 in a subset of activated/proliferating microglial cells after stroke. Here, we tested the hypothesis that galectin-3 plays a pivotal role in mediating injury-induced microglial activation and proliferation. By using a galectin-3 knock-out mouse (Gal-3KO), we demonstrated that targeted disruption of the galectin-3 gene significantly alters microglia activation and induces ∼4-fold decrease in microglia proliferation. Defective microglia activation/proliferation was further associated with significant increase in the size of ischemic lesion, ∼2-fold increase in the number of apoptotic neurons, and a marked deregulation of the IGF-1 levels. Next, our results revealed that contrary to WT cells, the Gal3-KO microglia failed to proliferate in response to IGF-1. Moreover, the IGF-1-mediated mitogenic microglia response was reduced by N-glycosylation inhibitor tunicamycine while coimmunoprecipitation experiments revealed galectin-3 binding to IGF-receptor 1 (R1), thus suggesting that interaction of galectin-3 with the N-linked glycans of receptors for growth factors is involved in IGF-R1 signaling. While the canonical IGF-1 signaling pathways were not affected, we observed an overexpression of IL-6 and SOCS3, suggesting an overactivation of JAK/STAT3, a shared signaling pathway for IGF-1/IL-6. Together, our findings suggest that galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury.

Inhibition of gastric cancer cell growth in vivo by overexpression of adeno-associated virus-mediated survivin mutant C84A.

Survivin is overexpressed in most of human cancer cells and tissues. Its overexpression is associated with apoptosis inhibition, drug resistance, and poor prognosis. In this study, we investigated the effect of adeno-associated virus (AAV)-mediated survivin mutant Cys84Ala [rAAV-Sur-Mut(C84A)] on gastric cancer growth. Sur-Mut(C84A) was subcloned into the AAV expression vector pAM/CAG to generate recombinant (r)AAV-Sur-Mut(C84A) virus. Cell survival was determined by the MTT method. Apoptosis was measured by FACS analysis and TUNEL. Tumor growth was assessed using a xenograft mouse model. Results showed that treatment of rAAV-Sur-Mut(C84A) virus significantly reduced cell survival, induced apoptosis, and sensitized gastric cancer cells to 5-fluorouracil in vitro. Furthermore, treatment of rAAV-Sur-Mut(C84A) virus markedly induced apoptosis and inhibited gastric cancer growth in vivo. Moreover, rAAV-Sur-Mut(C84A) treatment strongly enhanced the antitumor activity of 5-fluorouracil. Our results suggest that the combination of rAAV-Sur-Mut(C84A) with chemotherapy may be a promising strategy for gastric cancer therapy.

Matrix metalloproteinase activity in early-stage lung cancer.

BACKGROUND: The matrix metalloproteinases (MMPs)-2, -9 and -7 are thought to be associated with tumor invasion, metastasis, and angiogenesis. However, their possible roles in early-stage lung cancer are not clear. We measured the activity of MMP-2, -7 and -9 in early-stage lung cancer tissues. MATERIAL AND METHODS: Normal lung tissues and cancer tissues were collected from 60 consecutive stage-I non-small cell lung cancer (NSCLC) patients. The activities of MMP-2 and MMP-9 were determined by gelatin zymography, and the activity of MMP-7 was determined by casein zymography. Furthermore, the ratio of the active form of MMP-2 in tumor tissue (T) compared with normal tissue (N) was determined, and the survival in the groups with different MMP-2 T:N ratio was compared. RESULTS: The activity of both MMP-2 and MMP-9 was detected in all cancer and normal tissues. Interestingly, MMP-9 activity was significantly reduced, whereas MMP-2 activity was significantly increased, in cancer tissues compared to normal tissues. The survival rate of the MMP-2 T:N ratio > 2.5 group was 57.45%, which was significantly reduced compared with that of the T:N ratio ≤ 2.5 group (86.78%). CONCLUSION: Our findings suggest that MMP-2, but not MMP-9 and MMP-7, may be implicated in early-stage tumor invasion, metastasis, and angiogenesis in NSCLC.

Hydroxycamptothecin induces apoptosis and inhibits tumor growth in colon cancer by the downregulation of survivin and XIAP expression.

BACKGROUND: 10-Hydroxycamptothecin (10-HCPT), isolated from a Chinese tree Camptotheca acuminate, inhibits the activity of topoisomerase I and has a broad spectrum of anticancer activity in vitro and in vivo. It has been shown that HCPT is more active and less toxic than conventional camptothecins and can induce cancer cell apoptosis. However, the mechanisms of HCPT-induced apoptosis in colon cancer cells remain unclear. In this study, we investigated the effects of HCPT on apoptosis of colon cancer and underlying mechanism. METHODS: Cell proliferation was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, and apoptosis was measured using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Expression of genes was detected using real-time reverse transcription-polymerase chain reaction (real time-PCR) and Western blot. Tumor growth in vivo was evaluated using a nude mouse xenograft model. RESULTS: HCPT could significantly inhibit cell proliferation and induce apoptosis in colon cancer SW1116 and Colo 205 cells in dose- and time-dependent manners. HCPT treatment activated the activities of caspase 3, 7, 8 and 9, downregulated the expression of survivin, survivinΔEx3, survivin-3B and XIAP, and upregulated expression of surviving 2B. Moreover, the combination of HCPT and 5-fluorouracial (5-FU) synergistically induced apoptosis and downregulated the expression of survivin and XIAP. Knockdown of survivin and XIAP by siRNA sensitized colon cancer to HCTP-induced apoptosis. Furthermore, HCPT treatment significantly inhibited SW1116 xenograft tumor growth. CONCLUSIONS: Our results elucidate new mechanisms of HCPT antitumor by the downregulation of survivin and XIAP expression. The combination of HCPT with 5-FU or IAP inhibitors may be a potential strategy for colon cancer treatment.

Hsa_circ_0070440 promotes lung adenocarcinoma progression by SLC7A11-mediated-ferroptosis.

BACKGROUND: Circular RNA (circRNA) has recently emerged as having a key role in cancer initiation and progression. A prior study exhibited that hsa_circ_0070440 (circ_0070440) was significantly up-regulated in lung cancer cells, but the role and molecular mechanism of circ_0070440 during lung adenocarcinoma (LUAD) development remain unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR), Reverse transcription-PCR (RT-PCR), RNase R digestion, and Nuclear/cytoplasmic fractionation assay were employed to validate circ_0070440. Proliferation, apoptosis, viability, and ferrous iron level were measured by colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), Annexin V-FITC/PI double staining, Cell Counting Kit-8 (CCK-8), and iron assay in LUAD cells. A xenograft mouse model was used for tumor growth in vivo. Western blot (WB) and immunohistochemistry (IHC) assays were utilized to determine the expression of solute carrier family 7 member 11 (SLC7A11), c-myc, and bcl-xL. The interactions between the circ_0070440/SLC7A11 axis and miR-485-5p were verified by RNA pull-down assay and dual-luciferase reporter assay. RESULTS: Circ_0070440 was significantly up-regulated in LUAD cells. Knockdown of circ_0070440 inhibited growth and promoted both apoptosis and ferroptosis of LUAD cells. Moreover, our results showed that circ_0070440 contributed to malignant progression and suppressed ferroptosis of LUAD by sponging miR-485-5p and upregulating SLC7A11 expression. Furthermore, circ_0070440 and SLC7A11 levels were up-regulated, and the miR-485-5p level was more down-regulated in the tumor tissues than in normal tissues of LUAD patients. CONCLUSION: Circ_0070440 modulated LUAD malignant progression and ferroptosis via targeting SLC7A11, implying a significant role of the circ_0070440/miR-485-5p/SLC7A11 axis in the diagnosis and treatment of LUAD.

The influence of cognitive activity on subsequent daytime nap: A deep neural network model based on sleep spindles.

OBJECTIVES: Understanding the influence of cognitive activity on subsequent sleep has both theoretical and applied implications. This study aims to investigate the effect of pre-sleep cognitive activity, in the context of avoiding emotional interference, on macro-sleep and sleep spindles. METHODS: In a within-subjects design, participants' sleep electroencephalography was collected in both the with and without pre-sleep cognitive activity conditions. Subsequent macro-sleep (i.e., sleep stage distribution and sleep parameters) and spindle characteristics (i.e., density, amplitude, duration, and frequency) were analyzed. In addition, a novel machine learning framework (i.e., deep neural network, DNN) was used to discriminate between cognitive activity and control conditions. RESULTS: There were no significant differences in macro-sleep and sleep spindles between the cognitive activity and control conditions. Spindles-based DNN models achieved over 96% accuracy in differentiating between the two conditions, with fast spindles performing better than full-range and slow spindles. CONCLUSIONS: These results suggest a weak but positive effect of pre-sleep cognitive activity on subsequent sleep. It sheds light on a possible low-cost and easily accessible sleep intervention strategy for clinical and educational purposes.