Associations of arterial oxygen partial pressure with all­cause mortality in critically ill ischemic stroke patients: a retrospective cohort study from MIMIC IV 2.2.

BACKGROUND: As a supportive treatment, the effectiveness of oxygen therapy in ischemic stroke (IS) patients remains unclear. This study aimed to evaluate the relationships between arterial partial pressure of oxygen (PaO2) and both consciousness at discharge and all-cause mortality risk in ICU IS patients. METHODS: Blood gas measurements for all patients diagnosed with IS were extracted from the MIMIC-IV database. Patients were classified into four groups based on their average PaO2 during the first ICU day: hypoxemia (PaO2 < 80 mmHg), normoxemia (PaO2 80-120 mmHg), mild hyperoxemia (PaO2 121-199 mmHg), and moderate/severe hyperoxemia (PaO2 ≥ 200 mmHg). The primary endpoint was 90-day all-cause mortality. Secondary outcomes included the level of consciousness at discharge, assessed by the Glasgow Coma Scale (GCS), and 30-day all-cause mortality. Multivariate Cox regression and Restricted cubic spline (RCS) analysis were used to investigate the relationship between mean PaO2 and mortality, and to assess the nonlinear association between exposure and outcomes. RESULTS: This study included a total of 946 IS patients. The cumulative incidence of 30-day and 90-day all-cause mortality increased with decreasing PaO2 levels. RCS analysis revealed a nonlinear relationship between PaO2 and the risk of 30-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001), as well as a nonlinear association between PaO2 and 90-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001). The results remained consistent after excluding the small subset of patients who received reperfusion therapy. Sensitivity analysis indicated that the favorable impact on survival tends to increase with the extended duration of elevated PaO2. CONCLUSIONS: For IS patients who do not receive reperfusion therapy or whose recanalization status is unknown, a lower PaO2 early during ICU admission is considered an independent risk factor for short-term and recent mortality. Adjusting respiratory parameters to maintain supraphysiological levels of PaO2 appears to be beneficial for survival, although this finding requires further validation through additional studies. TRIAL REGISTRATION: Not applicable.

Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.

Pyruvate dehydrogenase complex (PDC) is a crucial enzyme that connects glycolysis and the tricarboxylic acid (TCA) cycle pathway. It plays an essential role in regulating glucose metabolism for energy production by catalyzing the oxidative decarboxylation of pyruvate to acetyl coenzyme A. Importantly, the activity of PDC is regulated through post-translational modifications (PTMs), phosphorylation, acetylation, and O-GlcNAcylation. These PTMs have significant effects on PDC activity under both physiological and pathophysiological conditions, making them potential targets for metabolism-related diseases. This review specifically focuses on the PTMs of PDC in cardiovascular diseases (CVDs) such as myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, obesity-related cardiomyopathy, heart failure (HF), and vascular diseases. The findings from this review offer theoretical references for the diagnosis, treatment, and prognosis of CVD.

Enhanced light extraction efficiency for the inclined-sidewall-shaped AlGaN-based DUV LED by using an omni-directional reflector with a thin hybrid dielectric layer.

In this Letter, an omni-directional reflector (ODR) with a thin hybrid dielectric layer (hybrid-ODR) is proposed to enhance the light extraction efficiency (LEE) for inclined-sidewall-shaped AlGaN-based deep ultraviolet light-emitting diode (DUV LED) by inserting a thin diamond with high refraction index into a conventional Al/Al2O3-based ODR. The three-dimensional finite-difference time-domain (3D FDTD) simulation results show that the LEE of TM-polarized light for the DUV LED with hybrid-ODR is enhanced by 18.5% compared with Al/Al2O3-based ODR. It is because the diamond can transform the evanescent wave in Al2O3 into the propagating light wave in diamond, thereby preventing effective excitation of the surface plasmon polariton (SPP) on the surface of the metal Al. Moreover, the Brewster's angle effect causes the TM-polarized light in diamond to propagate effectively into AlGaN. Furthermore, decreasing the total thickness of the dielectric layer also improves the scattering effect of the inclined sidewall. However, the utilization of hybrid-ODR results in a slight reduction in the LEE for transverse electric (TE) polarized light because the light is confined to the diamond layer and eventually absorbed by the metal Al.

MG53 inhibits ferroptosis by targeting the p53/SLC7A11/GPX4 pathway to alleviate doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is an anthracycline medication that is commonly used to treat solid tumors. However, DOX has limited clinical efficacy due to known cardiotoxicity. Ferroptosis is involved in DOX-induced cardiotoxicity (DIC). Although mitsugumin-53 (MG53) has cardioprotective effects and is expected to attenuate myocardial ischemic injury, its ability to inhibit DOX-induced ferroptosis has not been extensively studied. This research aims to investigate the pathophysiological impact of MG53 on DOX induced ferroptosis. Here, MG53 levels were evaluated in relation to the extent of ferroptosis by establishing in vivo and in vitro DIC mouse models. Additionally, myocardial specific MG53 overexpressing mice were used to study the effect of MG53 on cardiac function in DIC mice. The study found that the MG53 expression decreased in DOX treated mouse hearts or cardiomyocytes. However, MG53-overexpressing improved cardiac function in the DIC model and effectively reduced myocardial ferroptosis by increasing solute carrier family 7 member 11 (SLC7A11) and Glutathione peroxidase 4 (GPX4) levels, which were decreased by DOX. Mechanistically, MG53 binds to tumor suppressor 53 (p53) to regulate its ubiquitination and degradation. Ferroptosis induced by DOX was prevented by either MG53 overexpression or p53 knockdown in cardiomyocytes. The modulation of the p53/SLC7A11/GPX4 pathway by overexpression of MG53 can alleviate DOX induced ferroptosis. The study indicates that MG53 can provide protection against DIC by increasing p53 ubiquitination. These results highlight the previously unidentified role of MG53 in inhibiting ferroptosis to prevent DIC.

A Real-Time Intelligent Valve Monitoring Approach through Cameras Based on Computer Vision Methods.

Abnormal valve positions can lead to fluctuations in the process industry, potentially triggering serious accidents. For processes that frequently require operational switching, such as green chemical processes based on renewable energy or biotechnological fermentation processes, this issue becomes even more severe. Despite this risk, many plants still rely on manual inspections to check valve status. The widespread use of cameras in large plants now makes it feasible to monitor valve positions through computer vision technology. This paper proposes a novel real-time valve monitoring approach based on computer vision to detect abnormalities in valve positions. Utilizing an improved network architecture based on YOLO V8, the method performs valve detection and feature recognition. To address the challenge of small, relatively fixed-position valves in the images, a coord attention module is introduced, embedding position information into the feature channels and enhancing the accuracy of valve rotation feature extraction. The valve position is then calculated using a rotation algorithm with the valve's center point and bounding box coordinates, triggering an alarm for valves that exceed a pre-set threshold. The accuracy and generalization ability of the proposed approach are evaluated through experiments on three different types of valves in two industrial scenarios. The results demonstrate that the method meets the accuracy and robustness standards required for real-time valve monitoring in industrial applications.

Transparent and high-porosity aluminum alkoxide network-forming glasses.

Metal-organic network-forming glasses are an emerging type of material capable of combining the modular design and high porosity of metal-organic frameworks and the high processability and optical transparency of glasses. However, a generalizable strategy for achieving both high porosity and high glass-forming ability in modularly designed metal-organic networks has yet to be developed. Herein, we develop a series of aluminum alkoxide glasses and monoliths by linking aluminum-oxo clusters with alcohol linkers. A bulky monodentate alcohol modulator is introduced during synthesis and act as both network plasticizer and pore template, which can be removed by the subsequent solvent exchange to give gas accessible pores. Glasses synthesized with the modulator template exhibit well-defined glass transitions in their as-synthesized form and high surface areas up to 500 m2/g after activation, making them among the most porous glassy materials. The aluminum alkoxide glasses also have optical transparency and fluorescent properties, and their structures are elucidated by pair-distribution functions, spectroscopic and compositional analysis. These findings could significantly expand the library of microporous metal-organic network-forming glasses and enable their future applications.

FveDREB1B improves cold tolerance of woodland strawberry by positively regulating FveSCL23 and FveCHS.

Cold stress has seriously inhibited the growth and development of strawberry during production. CBF/DREB1 is a key central transcription factor regulating plant cold tolerance, but its regulatory mechanisms are varied in different plants. Especially in strawberry, the molecular mechanism of CBF/DREB1 regulating cold tolerance is still unclear. In this study, we found that FveDREB1B was most significantly induced by cold stress in CBF/DREB1 family of diploid woodland strawberry. FveDREB1B was localized to the nucleus, and DREB1B sequences were highly conserved in diploid and octoploid strawberry, and even similar in Rosaceae. And FveDREB1B overexpressed strawberry plants showed delayed flowering and increased cold tolerance, while FveDREB1B silenced plants showed early flowering and decreased cold tolerance. Under cold stress, FveDREB1B activated FveSCL23 expression by directly binding to its promoter. Meanwhile, FveDREB1B and FveSCL23 interacted with FveDELLA, respectively. In addition, we also found that FveDREB1B promoted anthocyanin accumulation in strawberry leaves by directly activating FveCHS expression after cold treatment and recovery to 25°C. DREB1B genes were also detected to be highly expressed in cold-tolerant strawberry resources 'Fragaria mandschurica' and 'Fragaria nipponica'. In conclusion, our study reveals the molecular mechanism of FveDREB1B-FveSCL23-FveDELLA module and FveDREB1B-FveCHS module to enhance the cold tolerance of woodland strawberry. It provides a new idea for improving the cold tolerance of cultivated strawberry and evaluating the cold tolerance of strawberry germplasm resources.

A putative Na+/H+ antiporter BpSOS1 contributes to salt tolerance in birch.

White birch (Betula platyphylla Suk.) is an important pioneer tree which plays a critical role in maintaining ecosystem stability and forest regeneration. The growth of birch is dramatically inhibited by salt stress, especially the root inhibition. Salt Overly Sensitive 1 (SOS1) is the only extensively characterized Na+ efflux transporter in multiple plant species. The salt-hypersensitive mutant, sos1, display significant inhibition of root growth by NaCl. However, the role of SOS1 in birch responses to salt stress remains unclear. Here, we characterized a putative Na+/H+ antiporter BpSOS1 in birch and generated the loss-of-function mutants of the birch BpSOS1 by CRISPR/Cas9 approach. The bpsos1 mutant exhibit exceptional increased salt sensitivity which links to excessive Na+ accumulation in root, stem and old leaves. We observed a dramatic reduction of K+ contents in leaves of the bpsos1 mutant plants under salt stress. Furthermore, the Na+/K+ ratio of roots and leaves is significant higher in the bpsos1 mutants than the wild-type plants under salt stress. The ability of Na+ efflux in the root meristem zone is found to be impaired which might result the imbalance of Na+ and K+ in the bpsos1 mutants. Our findings indicate that the Na+/H+ exchanger BpSOS1 plays a critical role in birch salt tolerance by maintaining Na+ homeostasis and provide evidence for molecular breeding to improve salt tolerance in birch and other trees.

Trimerized S expressed by modified vaccinia virus Ankara (MVA) confers superior protection against lethal SARS-CoV-2 challenge in mice.

The reoccurrence of successive waves of SARS-CoV-2 variants suggests the exploration of more vaccine alternatives is imperative. Modified vaccinia virus Ankara (MVA) is a virus vector exhibiting excellent safety as well as efficacy for vaccine development. Here, a series of recombinant MVAs (rMVAs) expressing monomerized or trimerized S proteins from different SARS-CoV-2 variants are engineered. Trimerized S expressed from rMVAs is found predominantly as trimers on the surface of infected cells. Remarkably, immunization of mice with rMVAs demonstrates that S expressed in trimer elicits higher levels of binding IgG and IgA, as well as neutralizing antibodies for matched and mismatched S proteins than S in the monomer. In addition, trimerized S expressed by rMVA induces enhanced cytotoxic T-cell responses than S in the monomer. Importantly, the rMVA vaccines expressing trimerized S exhibit superior protection against a lethal SARS-CoV-2 challenge as the immunized animals all survive without displaying any pathological conditions. This study suggests that opting for trimerized S may represent a more effective approach and highlights that the MVA platform serves as an ideal foundation to continuously advance SARS-CoV-2 vaccine development. IMPORTANCE: MVA is a promising vaccine vector and has been approved as a vaccine for smallpox and mpox. Our analyses suggested that recombinant MVA expressing S in trimer (rMVA-ST) elicited robust cellular and humoral immunity and was more effective than MVA-S-monomer. Importantly, the rMVA-ST vaccine was able to stimulate decent cross-reactive neutralization against pseudoviruses packaged using S from different sublineages, including Wuhan, Delta, and Omicron. Remarkably, mice immunized with rMVA-ST were completely protected from a lethal challenge of SARS-CoV-2 without displaying any pathological conditions. Our results demonstrated that an MVA vectored vaccine expressing trimerized S is a promising vaccine candidate for SARS-CoV-2 and the strategy might be adapted for future vaccine development for coronaviruses.

Radish residue carbon dots-based novel starch/chitosan film with high antioxidant, biocompatibility, and antibacterial activities for salmon fillets' active packaging.

The corruption of refrigerated marine fish results in global economic losses exceeding 25 billion euros annually. However, conventional preservatives present challenges, including singular functionality, potential toxicity, and high cost. In response, we developed multifunctional, safe, cost-effective, and environmentally friendly carbon dots derived from radish residues (R-CDs) by using the one-pot hydrothermal method. The surface of R-CDs is enriched with hydroxyl groups, conferring broad-spectrum antioxidant and antibacterial characteristics. R-CDs exhibited a notable 72.92 % inhibition rate on lipid peroxidation, surpassing the effectiveness of vitamin C (46 %). Additionally, R-CDs demonstrated impressive scavenging rates of 93.8 % for 2,2-diphenyl-1-picrylhydrazyl free radicals and 99.36 % for 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid-free radicals. In combating spoilage bacteria such as Aeromonas sobria and Hafnia alvei, R-CDs disrupted cell structures and influenced intracellular substance content. Importantly, co-cultivation with R-CDs showed no significant cytotoxicity. Further incorporating R-CDs into films using starch and chitosan (S/CS/R-CDs films) for efficient and convenient use in salmon fillets preservation. S/CS/R-CDs films effectively inhibited the growth of spoilage bacteria, lipid oxidation, and protein decomposition in salmon fillets, thereby extending shelf life by 4 days. This combination of antioxidant and antibacterial properties in R-CDs, along with the functional films, presents a promising approach for enhancing salmon fillet preservation.

Enhancing light extraction efficiency of the inclined-sidewall-shaped DUV micro-LED array by hybridizing a nanopatterned sapphire substrate and an air-cavity reflector.

In this work, we hybridize an air cavity reflector and a nanopatterned sapphire substrate (NPSS) for making an inclined-sidewall-shaped deep ultraviolet micro light-emitting diode (DUV micro-LED) array to enhance the light extraction efficiency (LEE). A cost-effective hybrid photolithography process involving positive and negative photoresist (PR) is explored to fabricate air-cavity reflectors. The experimental results demonstrate a 9.88% increase in the optical power for the DUV micro-LED array with a bottom air-cavity reflector when compared with the conventional DUV micro-LED array with only a sidewall metal reflector. The bottom air-cavity reflector significantly contributes to the reduction of the light absorption and provides more escape paths for light, which in turn increases the LEE. Our investigations also report that such a designed air-cavity reflector exhibits a more pronounced impact on small-size micro-LED arrays, because more photons can propagate into escape cones by experiencing fewer scattering events from the air-cavity structure. Furthermore, the NPSS can enlarge the escape cone and serve as scattering centers to eliminate the waveguiding effect, which further enables the improved LEE for the DUV micro-LED array with an air-cavity reflector.

On the origin of the enhanced light extraction efficiency of DUV LED by using inclined sidewalls.

It is known that light extraction efficiency (LEE) for AlGaN-based deep ultraviolet (DUV) light-emitting diodes (LEDs) can be enhanced by using an inclined sidewall of mesa. However, the reported optimal inclined angles are different. In this work, to explore the origin for enhancing the LEE of DUV LED by using inclined sidewalls, we investigate the effect of an inclined sidewall angle on the LEE for AlGaN-based DUV LEDs with different mesa diameters by using ray tracing. It is found that when compared to large-size DUV LEDs with inclined sidewall, the LEE of small-size DUV LEDs with inclined sidewall is enhanced from both the bottom and side surfaces due to the reduced scattering length and material absorption. Additionally, the optimal inclined sidewall angle is recommended within the range of 25°-65°, and the optimal angle for DUV LEDs decreases as the chip size increases. It can be attributed to the fact that there are two scattering mechanisms for the inclined sidewall. For smaller chip sizes, most of the light is directly scattered into escape cones by the inclined sidewall, resulting in a larger optimal angle. For larger chip sizes, the light firstly experiences total internal reflections by the out-light plane and then is scattered into escape cones by the inclined sidewalls, leading to a smaller optimal angle.

Heterojunction polarization enhancement and shielding for AlGaN-based solar-blind ultraviolet avalanche detectors.

AlGaN-based solar-blind ultraviolet avalanche detectors have huge potentials in the fields of corona discharge monitoring, biological imaging, etc. Here, we study the impact of the heterojunction polarization-related effects on the AlGaN-based solar-blind ultraviolet avalanche detectors. Our work confirms that the polarization heterojunction is beneficial to reducing avalanche bias and lifting avalanche gain by improving the electric field in the depletion region, while the polarization-induced fixed charges will lead to a redistribution of the electrons, in turn shielding the charges and weakening the electric field enhancement effect. This shielding effect will need external bias to eliminate, and that is why the polarization heterojunction cannot work at relatively low bias but has an enhancement effect at high bias. Controlling the doping level between the hetero-interface can affect the shielding effect. An unintentionally doped polarization heterojunction can effectively reduce the shielding effect, thus reducing the avalanche bias. The conclusions also hold true for the negative polarization regime. We believe our findings can provide some useful insights for the design of the AlGaN-based solar-blind ultraviolet detectors.

[Correlation study of NCF2 in chronic rhinosinusitis with nasal polyps].

Objective:After selecting NCF2 based on bioinformatics, clinical experiments were conducted to verify the expression of NCF2 in chronic rhinosinusitis with nasal polyps to study its correlation. Methods:The differentially expressed genes（DEGs） between CRSwNP and non-CRS patients were explored using the CRS-related dataset from the gene expression omnibus GEO database. The weighted gene co-expression network（WGCNA） was used for cluster analysis. The expression and cell distribution of NCF2 in the tissues were determined by single gene enrichment analysis（GSEA）, immune inflammatory infiltration analysis, and principal component（PCA） analysis. The expression degree of NCF2 in the tissues of the subjects was determined by immunohistochemistry, and the percentage of EOS in the peripheral blood of the subjects was detected and the correlation was analyzed. EOS in the tissues of the subjects were counted under a microscope and compared. Results:①The Venn diagram was obtained by crossing the module with the highest correlation between DEGs and WGCNA to determine the core gene NCF2. ②GSEA analysis showed that NCF2 was significantly related to the immunological processes such as allogeneic rejection and asthma. ③The area under the ROC curve was 1, indicating that NCF2 had diagnostic value for CRSwNP. ④NCF2 was highly expressed in nasal polyps, mainly distributed in monocytes and eosinophils. ⑤HE staining showed that the number of EOS in ECRSwNP tissues and the percentage of eosinophils in peripheral blood were higher than those in nonECRSwNP and control groups. ⑥The immunohistochemistry results showed that NCF2 was significantly expressed in the nasal polyps of ECRSwNP patients, which was higher than that in the nasal mucosa of nonECRSwNP group and control group. ⑦The expression of NCF2 in tissues was positively correlated with EOS count in ECRSwNP group and EOS expression in peripheral blood. Conclusion:The expression of NCF2 is increased in eosinophilic chronic rhinosinusitis with nasal polyps, and it is significantly correlated with the expression of eosinophils in peripheral blood and tissues, suggesting that NCF2 may be used as a basis for the intrinsic classification of ECRSwNP and a reference index for clinical diagnosis and treatment.

Intensive Versus Standard Blood Pressure Management after Endovascular Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-analysis.

Prospective clinical studies on blood pressure (BP) management targets after endovascular therapy (EVT) for acute ischemic stroke (AIS) have recently been published. Our objective was to assess the impact on clinical outcomes of BP management guided by established systolic BP (SBP) targets within the first 24 hours after successful EVT. Four randomized controlled trials (RCTs) including 1556 participants across 5 SBP target settings identified from 5 databases up to September 6, 2023 were included in this systematic review and meta-analysis. All the intensive SBP target groups in these RCTs were combined to facilitate head-to-head comparisons. Patients receiving intensive SBP management had lower risk of 90-day functional independence as assessed by the modified Rankin scale score (relative risk [RR], 0.81; 95% confidence interval [CI], 0.72 to 0.91; I2, 12%), excellent outcomes (RR,0.86; 95% CI, 0.75 to 0.99; I2, 7%), favorable outcomes (RR, 0.85; 95% CI, 0.78 to 0.92; I2, 0%), and quality of life (standardized mean difference, -0.22; 95% CI, -0.35 to -0.10; I2,0%). There were no differences in the probability of any intracerebral hemorrhage (RR, 1.04; 95% CI, 0.92 to 1.19; I2,0%), symptomatic intracerebral hemorrhage (RR, 1.10; 95% CI, 0.76 to 1.60; I2, 0%), stroke-related death (RR, 1.16; 95% CI, 0.80 to 1.68; I2, 0%), or parenchymal hematoma (RR, 1.71; 95% CI, 0.74 to 3.98; I2, 47%) between SBP targets. This meta-analysis provides evidence from RCTs suggesting that intensive SBP control (target<160 mm Hg) may be detrimental to clinical outcomes in AIS patients with successful reperfusion after EVT.

Climate-related naturally occurring epimutation and their roles in plant adaptation in A. thaliana.

DNA methylation has been proposed to be an important mechanism that allows plants to respond to their environments sometimes entirely uncoupled from genetic variation. To understand the genetic basis, biological functions and climatic relationships of DNA methylation at a population scale in Arabidopsis thaliana, we performed a genome-wide association analysis with high-quality single nucleotide polymorphisms (SNPs), and found that ~56% on average, especially in the CHH sequence context (71%), of the differentially methylated regions (DMRs) are not tagged by SNPs. Among them, a total of 3235 DMRs are significantly associated with gene expressions and potentially heritable. 655 of the 3235 DMRs are associated with climatic variables, and we experimentally verified one of them, HEI10 (HUMAN ENHANCER OF CELL INVASION NO.10). Such epigenetic loci could be subjected to natural selection thereby affecting plant adaptation, and would be expected to be an indicator of accessions at risk. We therefore incorporated these climate-related DMRs into a gradient forest model, and found that the natural A. thaliana accessions in Southern Europe that may be most at risk under future climate change. Our findings highlight the importance of integrating DNA methylation that is independent of genetic variations, and climatic data to predict plants' vulnerability to future climate change.

A comparative study on grasping-related muscles in five Accipitriformes species.

Accipitriformes are diverse in their prey preferences and use their grasping feet for hunting. Little is known about the architectural design of muscles related to grasping among species of different sizes, diets, and foraging behaviors. In the present study, we report quantitative data and analysis of the pelvic musculature of the Japanese sparrowhawk (Accipiter gularis), Eurasian sparrowhawk (Accipiter nisus), common buzzard (Buteo buteo), northern goshawk (Accipiter gentilis), and cinereous vulture (Aegypius monachus). As expected, mass and architecture of the considered muscles were very different between the cinereous vulture and the four other species. The cinereous vulture allocates more mass and physiological cross-sectional area (PCSA) to the proximally inserted flexor muscles, which indicates the rudimentary grasping ability of the foot and is a myological reflection of its carrion preference. Furthermore, in the cinereous vulture, muscles were built with the lowest architectural index (AI) compared with the other species, and the intrinsic foot muscles were short-fibered, which is disadvantageous for rapid manipulation and foot dexterity. The other four species, as a whole, featured large flexor hallucis longus (FHL) muscles and better development of distally inserted flexors, reflecting their predatory lifestyle. Some differences were also found between the species that consumed birds and those that consumed mammals. The two avivorous species were superior in AI and fiber length of the intrinsic foot muscles which are suitable for good hunting speed and digit flexibility, the prerequisition for hunting agile prey.

ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner.

Background: N6-methyladenosine (m6A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development. However, the role of m6A methylation in skin cutaneous melanoma (SKCM) is not yet clear. This study analyzed the expression of m6A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m6A modification and its potential mechanism in human SKCM. Methods: Based on public databases, the m6A-related gene expression landscape in SKCM was portrayed. MeRIP-Seq and RNA-Seq were used to recognize the downstream target of ALKBH5. In vivo and in vitro functional phenotype and rescue functional experiments were performed to explore the mechanism of the ALKBH5-m6A-ABCA1 axis in SKCM. Results: We found ALKBH5 upregulated in SKCM, associated with poor prognosis. ALKBH5 can promote melanoma cell proliferation, colony formation, migration, and invasion and inhibit autophagy in vitro, facilitating tumor growth and metastasis in vivo. We identified ABCA1, a membrane protein that assists cholesterol efflux, as a downstream target of ALKBH5-mediated m6A demethylation. Finally, our data demonstrated that ALKBH5 promoted SKCM via mediating ABCA1 downregulation by reducing ABCA1 mRNA stability in an m6A-dependent manner. Conclusion: Our findings exhibited the functional value of the key demethylase ALKBH5 mediated m6A modification in the progression of SKCM, suggesting the ALKBH5-m6A-ABCA1 axis as a potential therapeutic target in SKCM.

Novel LncRNA LINC02936 Suppresses Ferroptosis and Promotes Tumor Progression by Interacting with SIX1/CP Axis in Endometrial Cancer.

Endometrial cancer (EC) is a prevalent gynecological malignancy, and metabolic disorders are among its most significant risk factors. Abnormal iron metabolism is associated with the progression of cancer malignancy. Nevertheless, the involvement of iron metabolism in the EC remains uncertain. Ceruloplasmin (CP) functions as a multicopper oxidase and ferroxidase, playing a crucial role in maintaining the metabolic balance between copper and iron. Prior research has demonstrated that the dysregulated expression of CP has important clinical implications in EC. However, ​the specific underlying molecular mechanisms remains uncertain. This research examined the impact of CP on the malignant advancement of EC by suppressing ferroptosis. Next, we explored the possibility that Long non-coding RNA (lncRNA) LINC02936/SIX1/CP axis may be a key pathway for inhibiting ferroptosis and promoting cancer progression in EC. Mechanistically, SIX1 modulates the expression of CP, whereas LINC02936 interacts with SIX1 and recruits SIX1 to the CP promoter, leading to upregulation of CP, inhibition of ferroptosis, and promotion of EC progression. Administration of a small peptide cloud block the LINC02936-SIX1 interaction, thereby inhibits EC progression by promoting ferroptosis. Altogether, this is the first report on the lncRNA regulation of ferroptosis in EC. Our research enhances the knowledge of the lncRNA-mediated regulation of ferroptosis in EC progression and indicates the potential therapeutic significance of the LINC02936/SIX1/CP axis in treating EC.

CENPA promotes glutamine metabolism and tumor progression by up-regulating SLC38A1 in endometrial cancer.

Glutamine addiction is a significant hallmark of metabolic reprogramming in tumors and is crucial to the progression of cancer. Nevertheless, the regulatory mechanisms of glutamine metabolism in endometrial cancer (EC) remains elusive. In this research, we found that elevated expression of CENPA and solute carrier family 38 member 1 (SLC38A1) were firmly associated with worse clinical stage and unfavorable outcomes in EC patients. In addition, ectopic overexpression or silencing of CENPA could either enhance or diminish glutamine metabolism and tumor progression in EC. Mechanistically, CENPA directly regulated the transcriptional activity of the target gene, SLC38A1, leading to enhanced glutamine uptake and metabolism, thereby promoting EC progression. Notably, a prognostic model utilizing the expression levels of CENPA and SLC38A1 genes independently emerged as a prognostic factor for EC. More importantly, CENPA and SLC38A1 were significantly elevated and positively correlated, as well as indicative of poor prognosis in multiple cancers. In brief, our study confirmed that CENPA is a critical transcription factor involved in glutamine metabolism and tumor progression through modulating SLC38A1. This revelation suggests that targeting CENPA could be an appealing therapeutic approach to address pan-cancer glutamine addiction.