Mesenchymal stem cell-derived exosomes: a potential cell-free therapy for orthodontic tooth stability management.

Orthodontic relapse (OR) occurs at a rate of over 70%. Retention is the current attempt at prevention, but it requires a considerable amount of time and cannot fully block OR. It's imperative to find a safe and effective method for managing post-orthodontic tooth stability. Periodontal bone remodeling is one crucial biological foundation of OR. Mesenchymal stem cell-derived exosomes (MSC-Exo) show promise in relapse management by regulating periodontal bone remodeling. MSC-Exo can prevent relapse by regulating periodontal ligament function, osteoclast activity, osteoblast differentiation, macrophage polarization, and periodontal microcirculation. In recent years, exosome-loaded hydrogels, which achieve controlled exosome release, have demonstrated efficacy in promoting bone regeneration and remodeling, offering promising prospects for OR management. This review aims to highlight the use of MSC-Exo-based therapy for preventing OR, offering new insights for future research focused on improving tooth stability and enhancing orthodontic anchorage.

Alcohol promotes hepatocyte injury via ER stress sensor XBP1s mediated regulation of autophagy and lysosomal activity.

OBJECTIVE: Endoplasmic reticulum stress (ERS) plays an important role in the development of Alcoholic liver injury (ALI), but the exact mechanism needs further exploration. This study aims to investigate the role of ERS-XBP1s in ALI, and providing new target for the treatment of liver injury. METHOD: The ALI model was constructed using the NIAAA method and was validated by several methods. ERS was detected using western-blot, RT-PCR and immunohistochemistry. Apoptosis was measured by TUNEL staining, Hoechst staining, western-blot and Annexin V-FITC. Lysosomal function and autophagy were measured by Lyso-Tracker Green probe, western-blot and immunofluorescence, respectively. RESULTS: The ALI model was successfully constructed as demonstrated by increased liver steatosis, inflammation and oxidative stress, and higher levels of serum ALT, AST and TG. Alcohol significantly increased the expression of ERS-related molecules, such as PERK, IRE1α, GRP78 and XBP1s, and promoted the nuclear translocation of XBP1s. Moreover, alcohol significantly increased apoptosis and inhibition of XBP1s could reverse this effect in vivo and in vitro. Interestingly, we found that alcohol significantly elevated hepatocyte LC3-II/I levels and concomitantly accumulation of P62, and this phenomenon was reversed by inhibiting XBP1s both in vivo and in vitro. Mechanistically, we found that alcohol activation of ER stress sensor XBP1s which promoted liver injury via inhibiting lysosomal function and autophagy activity in hepatocytes, whereas inhibition of XBP1s reduces hepatocyte apoptosis by restoring lysosomal activity and activating of autophagy. CONCLUSION: Alcohol promotes hepatocytes injury via ER stress sensor XBP1s mediated inhibition of autophagy. Therefore, inhibition of XBP1 may protect the liver from alcohol-induced damage.

Activating Metal-Organic Cages by Incorporating Functional M(ImPhen)3 Metalloligands: From Structural Design to Applications.

ConspectusThe emulation of ingenious biofunctions has been a research focus for several decades. Metal-organic cages (MOCs), as a type of discrete supramolecular assembly with well-defined shapes and cavities, have aroused great interest in chemists to imitate natural protein cages or enzymes. However, to genuinely achieve tailored functionalities or reactivities of enzymes, the design of cage structures combining both the confined microenvironment and the active site is a prerequisite. Therefore, the integration of functionalized motifs into MOCs is expected to provide a feasible approach to construct biofunctional confined nanospaces, which not only allows the modulation of cage properties for applications such as molecular recognition, transport, and catalysis but also creates unique microenvironments that promote enzymatic effects for special reactivities and selectivities, thereby providing a versatile platform to achieve exceptional biomimetic functions and beyond.In this Account, we specifically focus on our research toward engineering active confined-nanospaces in MOCs via incorporation of M(ImPhen)3 metalloligands, a typical tris-chelate coordination moiety comprising imidazophenanthroline ligands and variable metal ions, as the principle functional units for stepwise assembly of active-MOCs. Starting from their structure design and merits, we describe the versatility of M(ImPhen)3 centers for multifunctionalization of the confined cage-nanospaces. By integrating different metal ions like Ru, Os, Fe, Co, Ni, Zn, the metal ion inherent properties, e.g., redox activity of Fe/Co-centers, chirality, and photoactivity of Ru-centers, and dynamics of Co/Zn-centers, could be integrated and tailored on the cages as isostructural nanosized containers or reactors. Changing the Pd or Pt cage vertices to organic clips could remarkably enhance acid-base stability and endow cages with flexibility and allostery. Utilization of ImPhen organic ligands containing imidazole groups introduces proton transfer capability, which can couple with the high-positive charges on the cage to create amphoteric microenvironments in the porous open-cage solution. Moreover, the nonplanar stereoconfiguration of M(ImPhen)3 confers multiple peripheral pockets on the cage, which render multisite, high-order, and dynamics guest binding for the benefit of applications such as drug delivery, molecular separation, and catalytic turnover.The construction of active-MOCs from tailorable M(ImPhen)3 metalloligands provides us with a new perspective on their structural design and functionalities. Merging the cage confinement with distinct physicochemical properties on a supramolecular level makes it practical to realize synergistic and cooperative effects for functionality enhancement beyond molecular components or the reactivity different from the bulky solution, which could largely expand the potential of MOCs as a multirole platform to wide application scenarios such as artificial photosynthesis, unconventional catalysis, and theranostic nanomedicine.

Promoting WLED-Excited High Temperature Long Afterglow by Orthogonally Anchoring Chromophores into 0D Metal-Organic Cages.

Afterglow materials have garnered significant interest due to distinct photophysical characteristics. However, it is still difficult to achieve long afterglow phosphorescence from organic molecules due to aggregation-caused quenching (ACQ) and energy dissipation. In addition, most materials reported so far have long afterglow emission only at room or even low temperatures, and mainly use UV light as an excitation source. In this work, we report a strategy to achieve high temperature long afterglow emission through the assembly of isolated 0D metal-organic cages (MOCs). In which, both ACQ and phosphorescence quenching effects are effectively mitigated by altering the stacking mode of organic chromophores through orthogonally anchoring into the edges of cubic MOCs. Furthermore, improvement in molecular rigidity, promotion of spin-orbit coupling and broadening of the absorption range are achieved through the MOC- engineering strategy. As a result, we successfully synthesized MOCs that can produce afterglow emission even after excitation by WLEDs at high temperatures (380 K). Moreover, the MOCs are capable of generating afterglow emissions when excited by mobile phone flashlight at room temperature. Given these features, the potential applications of MOCs in the visual identification of explosives, information encryption and multicolor display are explored.

Assessment of Five-Year Relative Survival of Patients With Endometrial Cancer: A Period Analysis.

Background: Endometrial cancer is one of the most common female cancers globally and in China. Although timely assessment of 5-year relative survival is crucial for guiding secondary prevention and early screening programs for endometrial cancer patients, those kinds of data are scarce in China. We aimed to provide a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from eastern China. Methods: Overall, 945 patients diagnosed with endometrial cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, eastern China were included. Period analysis was used to calculate 5-year relative survival for overall and the stratification by age at diagnosis and region. Model-based period analysis was used to predict the 5-year relative survival for the upcoming period of 2019 - 2023. Results: We found that 5-year relative survival during 2014 - 2018 reached 86.4% for overall, while urban areas had higher survival compared to rural areas (91.3% vs. 85.3%). Furthermore, there was a clear age gradient, decreasing from 89.3% for age < 55 years to 80.5% for age > 74 years. Predicted 5-year relative survival for the upcoming period 2019 - 2023 could reach 88.4%. Conclusions: We provide, a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from Taizhou, eastern China, reaching 86.4% for overall. Our finding has important implications for the overall evaluation of early detection and screening programs for patients with endometrial cancer in eastern China.

A Stand-Off Laser-Induced Breakdown Spectroscopy (LIBS) System for Remote Bacteria Identification.

Bacteria are the primary cause of infectious diseases, making rapid and accurate identification crucial for timely pathogen diagnosis and disease control. However, traditional identification techniques such as polymerase chain reaction and loop-mediated isothermal amplification are complex, time-consuming, and pose infection risks. This study explores remote (~3 m) bacterial identification using laser-induced breakdown spectroscopy (LIBS) with a Cassegrain reflective telescope. Principal component analysis (PCA) was employed to reduce the dimensionality of the LIBS spectral data, and the accuracy of support vector machine (SVM) and Random Forest (RF) algorithms was compared. Multiple repeated experiments showed that the RF model achieved a classification accuracy, recall, precision, and F1-score of 99.81%, 99.80%, 99.79%, and 0.9979, respectively, outperforming the SVM model and providing more accurate remote bacterial identification. The method based on laser-induced plasma spectroscopy and machine learning has broad application prospects, supporting noncontact disease diagnosis, improving public health, and advancing medical research and technological development.

Characterization of Exosomes Released from Mycobacterium abscessus-Infected Macrophages.

Extracellular vesicles (EVs), such as exosomes, play a critical role in cell-to-cell communication and regulating cellular processes in recipient cells. Non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus, are a group of environmental bacteria that can cause severe lung infections in populations with pre-existing lung conditions, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). There is limited knowledge of the engagement of EVs in the host-pathogen interactions in the context of NTM infections. In this study, we found that M. abscessus infection increased the release of a subpopulation of exosomes (CD9, CD63, and/or CD81 positive) by mouse macrophages in cell culture. Proteomic analysis of these vesicles demonstrated that M. abscessus infection affects the enrichment of host proteins in exosomes released by macrophages. When compared to exosomes from uninfected macrophages, exosomes released by M. abscessus-infected macrophages significantly improved M. abscessus growth and downregulated the intracellular level of glutamine in recipient macrophages in cell culture. Increasing glutamine concentration in the medium rescued intracellular glutamine levels and M. abscessus killing in recipient macrophages that were treated with exosomes from M. abscessus-infected macrophages. Taken together, our results indicate that exosomes may serve as extracellular glutamine eliminators that interfere with glutamine-dependent M. abscessus killing in recipient macrophages.

Host long noncoding RNAs in bacterial infections.

Bacterial infections remain a significant global health concern, necessitating a comprehensive understanding of the intricate host-pathogen interactions that play a critical role in the outcome of infectious diseases. Recent investigations have revealed that noncoding RNAs (ncRNAs) are key regulators of these complex interactions. Among them, long noncoding RNAs (lncRNAs) have gained significant attention because of their diverse regulatory roles in gene expression, cellular processes and the production of cytokines and chemokines in response to bacterial infections. The host utilizes lncRNAs as a defense mechanism to limit microbial pathogen invasion and replication. On the other hand, some host lncRNAs contribute to the establishment and maintenance of bacterial pathogen reservoirs within the host by promoting bacterial pathogen survival, replication, and dissemination. However, our understanding of host lncRNAs in the context of bacterial infections remains limited. This review focuses on the impact of host lncRNAs in shaping host-pathogen interactions, shedding light on their multifaceted functions in both host defense and bacterial survival, and paving the way for future research aimed at harnessing their regulatory potential for clinical applications.

Electrolyte Engineering with TFA- Anion-Rich Solvation Structure to Construct Highly Stable Zn2+/Na+ Dual-Salt Batteries.

Electrolyte engineering is recognized as an effective technique for high-performance aqueous zinc-ion rechargeable batteries, addressing difficulties such as free water decomposition, zinc anode corrosion, and zinc dendrite growth. Different from traditional strategies in aqueous electrolyte systems, this work focuses on organic electrolytes involving zinc trifluoroacetate hydrate (Zn(TFA)2·xH2O), sodium trifluoroacetate (NaTFA) dual-salt and acetonitrile (AN) solvent, in which trifluoroacetate anions (TFA- anions) have strong affinity toward zinc ions to form anion-rich solvates, thus inducing an inorganic-rich solid electrolyte interphase (SEI) to protect Zn from dendrite growth and side reactions. The Zn anode manifests long-term cycling over 2400 h at a current density of 0.5 mA cm-2 with a high Coulombic efficiency (CE) of 99.75%, showing an areal capacity as high as 5 mAh cm-2. Owing to the high reversibility of the sodium ions intercalation/deintercalation process in Na2MnFe(CN)6, the Zn//Na2MnFe(CN)6 full cells with the dual-salt electrolyte perform much better in terms of capacity retention than a device with Zn(TFA)2/AN electrolyte. This approach may open a new avenue for efficient zinc-ion rechargeable batteries via developing organic electrolytes.

Dysregulation of Serum Exosomal Lipid Metabolism in Schizophrenia: A Biomarker Perspective.

Exosomes, crucial extracellular vesicles, have emerged as potential biomarkers for neurological conditions, including schizophrenia (SCZ). However, the exploration of exosomal lipids in the context of SCZ remains scarce, necessitating in-depth investigation. Leveraging ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), this study aimed to characterize the lipidomic profile of serum exosomes from SCZ patients, assessing their potential as novel biomarkers for SCZ diagnosis through absolute quantitative lipidomics. Our comprehensive lipidomic analysis unveiled 39 serum exosomal lipids that were differentially expressed between SCZ patients (n = 20) and healthy controls (HC, n = 20). These findings revealed a profound dysregulation in lipid metabolism pathways, notably in sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. Among these, seven exosomal lipids stood out for their diagnostic potential, exhibiting remarkable ability to differentiate SCZ patients from HCs with an unparalleled classification performance, evidenced by an area under the curve (AUC) of 0.94 (95% CI, 0.82-1.00). These lipids included specific ceramides and phosphoethanolamines, pointing to a distinct lipid metabolic fingerprint associated with SCZ. Furthermore, bioinformatic analyses reinforced the pivotal involvement of these lipids in SCZ-related lipid metabolic processes, suggesting their integral role in the disorder's pathophysiology. This study significantly advances our understanding of SCZ by pinpointing dysregulated exosomal lipid metabolism as a key factor in its pathology. The identified serum exosome-derived lipids emerge as compelling biomarkers for SCZ diagnosis, offering a promising avenue towards the development of objective and reliable diagnostic tools.

Metformin Attenuates Partial Epithelial-Mesenchymal Transition in Salivary Gland Inflammation via PI3K/Akt/GSK3ß/Snail Signaling Axis.

Chronic inflammation in the salivary glands (SG) often triggers epithelial-mesenchymal transition (EMT), leading to the loss of acinar function and promoting fibrosis. This study explores the role of Metformin in mitigating partial EMT in SG inflammation. In vitro, human salivary gland epithelial cells (hSGECs) were treated with lipopolysaccharide (LPS) and Metformin. EMT markers and the PI3K/Akt/GSK3ß/Snail signaling axis were assessed using RNA-seq and Western blot analysis. In vivo, a Wharton's duct ligation rat model was employed to mimic chronic sialadenitis (CS). Nine Wistar rats were randomly divided into three groups: Control, Ligation and Ligation + Metformin groups, with three rats per group. After ductal ligation, the Ligation + Metformin group received 100 mg/kg of Metformin via intragastric administration, while the Control and Ligation groups received an equivalent saline every 24 h. Histological analysis, immunohistochemical and immunofluorescence staining were conducted to evaluate acinar morphology, EMT, and the PI3K/Akt/GSK3ß/Snail signaling axis. The results showed that in CS tissues, atrophied acinar cells underwent partial EMT. In vitro, Metformin reversed LPS-induced EMT in hSGECs. RNA-seq and Western blot revealed that Metformin achieved this effect by targeting the PI3K/Akt/GSK3ß/Snail signaling axis (P < 0.01). In ductal ligation models, Metformin treatment restored ligation-induced acinar damage and functional loss (P < 0.01). Further histological evidence supported that Metformin mitigated EMT by inhibiting inflammatory activation of PI3K/Akt/GSK3ß/Snail signaling axis (P < 0.01). In conclusion, Metformin alleviates partial EMT in SG inflammation by targeting the PI3K/Akt/GSK3ß/Snail signaling axis, highlighting its potential as a therapeutic strategy for SG inflammation.

Improved encapsulation efficiency and storage stability of lutein by soy protein isolate nanocarriers with thermal and trypsin treatments.

BACKGROUND: Encapsulation of bioactive compounds within protein-based nanoparticles has garnered considerable attention in the food and pharmaceutical industries because of its potential to enhance stability and delivery. Soy protein isolate (SPI) has emerged as a promising candidate, prompting the present study aiming to modify its properties through controlled thermal and trypsin treatments for improved encapsulation efficiency (EE) of lutein and its storage stability. RESULTS: The EE of lutein nanoparticles encapsulated using SPI trypsin hydrolysates (SPIT) with three varying degrees of hydrolysis (4.11%, 6.91% and 10.61% for SPIT1, SPIT2 and SPIT3, respectively) increased by 12.00%, 15.78% and 18.59%, respectively, compared to SPI. Additionally, the photostability of SPIT2 showed a remarkable increase of 38.21% compared to SPI. The superior encapsulation efficiency and photostability of SPIT2 was attributed to increased exposure of hydrophobic groups, excellent antioxidant activity and uniform particle stability, despite exhibiting lower binding affinity to lutein compared to SPI. Furthermore, in SPIT2, the protein structure unfolded, with minimal impact on overall secondary structure upon lutein addition. CONCLUSION: The precise application of controlled thermal and trypsin treatments to SPI has been shown to effectively produce protein nanoparticles with substantially improved encapsulation efficiency for lutein and enhanced storage stability of the encapsulated lutein. These findings underscore the potential of controlled thermal and trypsin treatments to modify protein properties effectively and offer significant opportunities for expanding the applications of protein-based formulations across diverse fields. © 2024 Society of Chemical Industry.

MicroRNAs: pioneering regulators in Alzheimer's disease pathogenesis, diagnosis, and therapy.

This article delves into Alzheimer's disease (AD), a prevalent neurodegenerative condition primarily affecting the elderly. It is characterized by progressive memory and cognitive impairments, severely disrupting daily life. Recent research highlights the potential involvement of microRNAs in the pathogenesis of AD. MicroRNAs (MiRNAs), short non-coding RNAs comprising 20-24 nucleotides, significantly influence gene regulation by hindering translation or promoting degradation of target genes. This review explores the role of specific miRNAs in AD progression, focusing on their impact on ß-amyloid (Aß) peptide accumulation, intracellular aggregation of hyperphosphorylated tau proteins, mitochondrial dysfunction, neuroinflammation, oxidative stress, and the expression of the APOE4 gene. Our insights contribute to understanding AD's pathology, offering new avenues for identifying diagnostic markers and developing novel therapeutic targets.

Methods of Manipulation of Acoustic Radiation Using Metamaterials with a Focus on Polymers: Design and Mechanism Insights.

The manipulation of acoustic waves is becoming increasingly crucial in research and practical applications. The coordinate transformation methods and acoustic metamaterials represent two significant areas of study that offer innovative strategies for precise acoustic wave control. This review highlights the applications of these methods in acoustic wave manipulation and examines their synergistic effects. We present the fundamental concepts of the coordinate transformation methods and their primary techniques for modulating electromagnetic and acoustic waves. Following this, we deeply study the principle of acoustic metamaterials, with particular emphasis on the superior acoustic properties of polymers. Moreover, the polymers have the characteristics of design flexibility and a light weight, which shows significant advantages in the preparation of acoustic metamaterials. The current research on the manipulation of various acoustic characteristics is reviewed. Furthermore, the paper discusses the combined use of the coordinate transformation methods and polymer acoustic metamaterials, emphasizing their complementary nature. Finally, this article envisions future research directions and challenges in acoustic wave manipulation, considering further technological progress and polymers' application potential. These efforts aim to unlock new possibilities and foster innovative ideas in the field.

LRRC45 promotes lung cancer proliferation and progression by enhancing c-MYC, slug, MMP2, and MMP9 expression.

BACKGROUND: The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung cancer remains unexplored. This study investigated the impact and underlying mechanisms of LRRC45 on the proliferative, migratory, and invasive capacities of lung adenocarcinoma (LUAD) cells, potentially identifying new targets for therapeutic intervention. MATERIAL AND METHODS: The importance of LRRC45 in lung cancer was analyzed using the online databases of UCSC Xena, TCGA, TISIDB, and UALCAN, whereas to detect target gene expression, we used the qRT-PCR, Western blot, and immunofluorescence confocal. The cell growth was monitored by colony formation assay and migration was examined by cell migration assay. Finally, a xenograft mouse tumor model using A549 â€‹cells was used to explore the in vivo effect of LRRC45 in lung cancer. RESULTS: Inhibition of LRRC45 expression led to a notable decrease in proliferation, migration, and invasion of A549 and H1299 â€‹cells. LRRC45 silencing significantly reduced the tumor volume and improved the mice's survival. Additionally, inhibition of LRRC45 expression dramatically suppressed c-MYC, Slug, MMP2, and MMP9 expression. Overexpression of c-MYC and/or Slug in the LRRC45-deficient cells can partially or totally restore the LRRC45 deficiency-suppressed growth. Moreover, the overexpression of MMP2 and/or MMP9 could partially or totally restore LRRC45 deficiency-reduced cell metastasis. CONCLUSIONS: LRRC45 could promote the proliferative, migrative, and invasive capacities of lung cancer cells by increasing c-MYC, Slug, MMP2, and MMP9 expression, indicating the therapeutic implications and potential significance of these pathways in lung cancer.

Quantitative Electroencephalography for Predication of Neurological Dysfunction in Type A Aortic Dissection: A Prospective Observational Study.

BACKGROUND: Type A aortic dissection presents challenges with postoperative cerebral complications, and this study evaluates the predictive value of quantitative electroencephalography for perioperative brain function prognosis. METHODS AND RESULTS: Amplitude-integrated electroencephalography (aEEG) processes raw signals through filtering, amplitude integration, and time compression, displaying the data in a semilogarithmic format. Using this method, postoperative relative band power (post-RBP) α% and dynamic aEEG (ΔaEEG) grade were significantly associated with neurological dysfunction in univariate and multivariable analyses, with area under the receiver operating characteristic curve of 0.876 (95% CI, 0.825-0.926) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with adverse outcomes, with area under the receiver operating characteristic curve of 0.903 (95% CI, 0.835-0.971) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with transient neurological dysfunction and stroke, with areas under the receiver operating characteristic curve of 0.818 (95% CI, 0.760-0.876) and 0.868 (95% CI, 0.810-0.926) for transient neurological dysfunction, and 0.815 (95% CI, 0.743-0.886) and 0.831 (95% CI, 0.746-0.916) for stroke. Among 56 patients, the Alberta Stroke Program Early Computed Tomography score was superior to ΔaEEG in predicting neurological outcomes (area under the receiver operating characteristic curve of 0.872 versus 0.708 [95% CI, 0.633-0.783]; P<0.05). CONCLUSIONS: Perioperative quantitative electroencephalography monitoring offers valuable insights into brain function changes in patients with type A aortic dissection. ∆aEEG grades can aid in early detection of adverse outcomes, while postoperative relative band power and ∆aEEG grades predict transient neurological dysfunction. Quantitative electroencephalography can assist cardiac surgeons in assessing brain function and improving outcomes in patients with type A aortic dissection. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2200055980.

Ultra-Microporous Fe-MOF with Prolonged NO Delivery in Biological Media for Therapeutic Application.

Nitric oxide (NO), a key element in the regulation of essential biological mechanisms, presents huge potential as therapeutic agent in the treatment and prevention of chronic diseases. Metal-organic frameworks (MOFs) with open metal sites are promising carriers for NO therapies but delivering it over an extended period in biological media remains a great challenge due to i) a fast degradation of the material in body fluids and/or ii) a rapid replacement of NO by water molecules onto the Lewis acid sites. Here, a new ultra-narrow pores Fe bisphosphonate MOF, denoted MIP-210(Fe) or Fe(H2O)(Hmbpa) (H4mbpa = p-xylenediphosphonic acid) is described that adsorbs NO due to an unprecedented sorption mechanism: coordination of NO through the Fe(III) sites is unusually preferred, replacing bound water, and creating a stable interaction with the free H2O and P-OH groups delimiting the ultra-narrow pores. This, associated with the high chemical stability of the MOF in body fluids, enables an unprecedented slow replacement of NO by water molecules in biological media, achieving an extraordinarily extended NO delivery time over at least 70 h, exceeding by far the NO kinetics release reported with others porous materials, paving the way for the development of safe and successful gas therapies.

The RNA N6-methyladenosine demethylase FTO regulates ATG5 to inhibit malignant progression of uveal melanoma.

PURPOSE: This research aimed to identify the function of fat mass- and obesity-associated protein (FTO), an eraser of N6-methyladenosine (m6A), and explore its possible mechanisms in uveal melanoma (UVM). METHODS: We performed quantitative real-time PCR (qPCR), Western blotting and gene correlation analysis with GEPIA2 to assess FTO expression and identify its potential targets in UVM. CCK-8, colony formation, cell cycle, cell apoptosis, wound healing and Transwell invasion assays were utilized to assess cell viability, cell cycle distribution, apoptosis, migration and invasion. Western blotting, qPCR and methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were carried out to explore the underlying mechanism of FTO in 2 UVM cell lines. RESULTS: FTO, a key m6A demethylase, was found to be upregulated in human UVM tissues compared with normal choroid tissues. Knockdown of FTO in Mel270 and OMM2.3 cells significantly promoted proliferation and migration and suppressed apoptosis. Mechanistically, knockdown of FTO decreased the expression of ATG5, an autophagy-related gene, leading to attenuation of autophagosome formation, thereby inhibiting autophagy. Upon FTO knockdown, increased levels of methylated ATG5 and decreased ATG5 stability were detected. Furthermore, ATG5 dramatically alleviated FTO downregulation-induced tumor growth and metastasis. CONCLUSIONS: Our research highlights the importance of the m6A demethylase FTO in UVM by demonstrating that it direct regulates ATG5-induced autophagy in an m6A-dependent manner. These findings suggest that FTO may serve as a potential therapeutic target for UVM.