ABSTRACT
Metal organic frameworks (MOFs) constructed with bismuth metal have not been widely reported, especially multifunctional Bi-MOFs. Therefore, developing multifunctional MOFs is of great significance due to the increasing requirements of materials. In this work, a 3D Bi-MOF (Bi-TCPE) with multifunctionality was successfully constructed, demonstrating high thermal stability, water stability, a porous structure, and strong blue fluorescence emission. We evaluated the properties of Bi-TCPE in detecting anions (S2-, Cr2O72-, and CrO42-) in aqueous solution, along with the rapid visual detection of H2S gas and proton conduction. In terms of anion detection, Bi-TCPE achieved the rapid detection of trace S2- in aqueous solutions, while the Ksv value was 1.224 × 104 M-1 with a limit of detection (LOD) value of 1.93 µM through titration experiments. Furthermore, Bi-TCPE could sensitively detect Cr2O72- and CrO42-, with Ksv values of 1.144 × 104 and 1.066 × 104 M-1, respectively, while LOD reached 2.07 and 2.18 µM. Subsequently, we conducted H2S gas detection experiments, and the results indicated that Bi-TCPE could selectively detect H2S gas at extremely low concentrations (2.08 ppm) and with a fast response time (<10 s). We also observed significant color changes under both UV light and sunlight. Therefore, we developed a H2S detection test paper for the rapid visual detection of H2S gas. Finally, we evaluated the proton conductivity of Bi-TCPE, and the experimental results showed that the proton conductivity of Bi-TCPE reached 4.77 × 10-2 S·cm-1 at 98% RH and 90 °C, achieving an excellent value for unmodified and encapsulated MOFs. In addition, Bi-TCPE showed high stability in proton conduction experiments (it remained stable after 21 consecutive days of testing and 12 cycles of testing), demonstrating relatively high application value. These results indicate that Bi-TCPE is a multifunctional MOF material with great application potential.
ABSTRACT
BACKGROUND: This study aims to explore machine learning(ML) methods for non-invasive assessment of WHO/ISUP nuclear grading in clear cell renal cell carcinoma(ccRCC) using contrast-enhanced ultrasound(CEUS) radiomics. METHODS: This retrospective study included 122 patients diagnosed as ccRCC after surgical resection. They were divided into a training set (n = 86) and a testing set(n = 36). CEUS radiographic features were extracted from CEUS images, and XGBoost ML models (US, CP, and MP model) with independent features at different phases were established. Multivariate regression analysis was performed on the characteristics of different radiomics phases to determine the indicators used for developing the prediction model of the combined CEUS model and establishing the XGBoost model. The training set was used to train the above four kinds of radiomics models, which were then tested in the testing set. Radiologists evaluated tumor characteristics, established a CEUS reading model, and compared the diagnostic efficacy of CEUS reading model with independent characteristics and combined CEUS model prediction models. RESULTS: The combined CEUS radiomics model demonstrated the best performance in the training set, with an area under the curve (AUC) of 0.84, accuracy of 0.779, sensitivity of 0.717, specificity of 0.879, positive predictive value (PPV) of 0.905, and negative predictive value (NPV) of0.659. In the testing set, the AUC was 0.811, with an accuracy of 0.784, sensitivity of 0.783, specificity of 0.786, PPV of 0.857, and NPV of 0.688. CONCLUSIONS: The radiomics model based on CEUS exhibits high accuracy in non-invasive prediction of ccRCC. This model can be utilized for non-invasive detection of WHO/ISUP nuclear grading of ccRCC and can serve as an effective tool to assist clinical decision-making processes.
Subject(s)
Carcinoma, Renal Cell , Contrast Media , Kidney Neoplasms , Machine Learning , Neoplasm Grading , Ultrasonography , Humans , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Female , Retrospective Studies , Male , Middle Aged , Ultrasonography/methods , Aged , Adult , RadiomicsABSTRACT
Atherigona orientalis Schiner (1868) is an acknowledged agricultural pest owing to its feeding habits and breeding locations. This insect is a tropical and subtropical pest in fruits and vegetables, in which >50 varieties of fruits and vegetables in 26 families, such as Capsicum annuum, Lycopersicon esculentum, and Cucumis melo have been attacked. Moreover, A. orientalis may also develop in rotten crops and feces or insect carcasses, which are also considered one kind of sanitary pest and medical insect. At present, the invasion ranges of A. orientalis are still increasing and more preventive and management measures are to be processed. To gain a better understanding of the molecular mechanisms involved in olfactory reception in A. orientalis, the transcriptome of male and female antennae and legs was systematically analyzed. In total, 131 chemosensory-related genes, including 63 odorant receptors (ORs), 20 gustatory receptors (GRs), 18 ionotropic receptors (IRs), 27 odorant binding proteins (OBPs), 1 chemosensory protein (CSP), and 2 sensory neuron membrane proteins (SNMPs), were identified. The analysis focused on obtaining expression information of candidate olfactory genes at the transcriptomic level by examining the differentially expressed genes (DEGs) in all samples. Totally, 41 DEGs were identified between male antennae (MA) and female antennae (FA), including 32 ORs, 5 OBPs, 1 IR, 2 GRs and 1 SNMP. In MA versus male legs (ML), 78 DEGs were identified (45 ORs, 18 OBPs, 6 GRs, 6 IRs, 1 CSP and 2 SNMPs). In FA and female legs (FL), 96 DEGs were identified (51 ORs, 21 OBPs, 9 GRs, 12 IRs, 1 CSP and 2 SNMPs). For ML and FL, 3 DEGs were identified, including 2 ORs and 1 SNMP. Our results supplement valuable insights for future research on the chemoreception mechanisms in A. orientalis.
Subject(s)
Arthropod Antennae , Gene Expression Profiling , Insect Proteins , Receptors, Odorant , Transcriptome , Male , Female , Animals , Arthropod Antennae/metabolism , Insect Proteins/genetics , Receptors, Odorant/genetics , Extremities , Genes, InsectABSTRACT
Survival of olfactory mucosal mesenchymal stem cells (OM-MSCs) remains the low level in the cerebral microenvironment during intracerebral hemorrhage (ICH). This article aims to reveal the differential expression profile of ICH-stimulated OM-MSCs based on whole transcriptome sequence analysis. OM-MSCs were isolated from 6-week C57BL/6 mice. Morphology and surface markers of OM-MSCs were investigated by light microscope and flow cytometry, respectively. OM-MSCs were incubated with 20 U/mL thrombin for 24 h to mimic ICH-induced injury in vitro. Total RNA was extracted for whole transcriptome sequencing and qPCR. OM-MSCs were characterized by negative for CD45 and CD34, and positive for CD44, CD90 and CD29. Thrombin led to decrease in cell viability and increase in senescence and apoptosis in OM-MSCs. In total, 736 lncRNAs (upregulated: 393; downregulated: 343), 21 miRNAs (upregulated: 7; downregulated: 14) and 807 mRNAs (upregulated: 422; downregulated: 385) were identified. GO and KEGG pathways were enriched in protein heterodimerization activity, trans-synaptic signaling, membrane pathway, alcohol metabolic process, organic hydroxy compound biosynthesis process, secondary alcohol metabolic process, alcoholism, neutrophil extracellular trap formation, systemic lupus erythematosus, metabolic process, steroid biosynthesis and drug metabolism-cytochrome P450. 200 lncRNA-miRNA-mRNA were predicted in thrombin-induced OM-MSCs. Based on qPCR, we validated COMMD1B, MOAP1, lncRNA CAPN15, lncRNA ALDH1L2, miR-3473b and miR-1964-3p were upregulated in thrombin-stimulated OM-MSCs, and GM20431, lncRNA GAPDH and miR-122b-3p were downregulated. Our findings provide novel understanding for thrombin-induced injury in OM-MSCs. Differently-expressed RNAs can be the targets of improving therapeutic application of OM-MSCs.
ABSTRACT
A rapid induction of antiviral genes is critical for eliminating viruses, which requires activated transcription factors and opened chromatins to initiate transcription. However, it remains elusive how the accessibility of specific chromatin is regulated during infection. Here, we found that XAF1 functioned as an epigenetic regulator that liberated repressed chromatin after infection. Upon RNA virus infection, MAVS recruited XAF1 and TBK1. TBK1 phosphorylated XAF1 at serine-252 and promoted its nuclear translocation. XAF1 then interacted with TRIM28 with the guidance of IRF1 to the specific locus of antiviral genes. XAF1 de-SUMOylated TRIM28 through its PHD domain, which led to increased accessibility of the chromatin and robust induction of antiviral genes. XAF1-deficient mice were susceptible to RNA virus due to impaired induction of antiviral genes. Together, XAF1 acts as an epigenetic regulator that promotes the opening of chromatin and activation of antiviral immunity by targeting TRIM28 during infection.
Subject(s)
Chromatin , RNA Virus Infections , Animals , Mice , Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins , Chromatin/genetics , Epigenomics , Immunity , RNA , RNA Virus Infections/immunologyABSTRACT
OTUD6A is a deubiquitinase that plays crucial roles in various human diseases. However, the precise regulatory mechanism of OTUD6A remains unclear. In this study, we found that OTUD6A significantly inhibited the production of type I interferon. Consistently, peritoneal macrophages and bone marrow-derived macrophages from Otud6a-/- mice produced more type I interferon after virus infection compared to cells from WT mice. Otud6a-/-- mice also exhibited increased resistance to lethal HSV-1 and VSV infections, as well as LPS attacks due to decreased inflammatory responses. Mechanistically, mass spectrometry results revealed that UBC13 was an OTUD6A-interacting protein, and the interaction was significantly enhanced after HSV-1 stimulation. Taken together, our findings suggest that OTUD6A plays a crucial role in the innate immune response and may serve as a potential therapeutic target for infectious disease.
Subject(s)
Herpesvirus 1, Human , Interferon Type I , Humans , Animals , Mice , Immunity, Innate , Macrophages , Deubiquitinating EnzymesABSTRACT
OBJECTIVE: Osteoarthritis is a condition characterized by articular cartilage degradation. The increased expression of ß1,4-Galactosyltransferase-I (ß1,4-GalT-I) in the articular cartilage of osteoarthritis patients was related to an inflammatory response. The aim of this study was to elucidate the role of ß1,4-GalT-I in osteoarthritis. This study aimed to determine the function of 1,4-GalT-I in osteoarthritis. METHODS: The osteoarthritis mouse model with the destabilization of the medial meniscus was established by microsurgical technique. Pathological changes in articular cartilage were observed by hematoxylin and eosin staining and safranin O-fast green staining. Quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays were used to observe mRNA and protein expression, respectively. RNA interactions were verified by a luciferase reporter assay. SA-ß-Gal staining was used to assess chondrocyte senescence. Immunofluorescence staining was conducted to observe the localization of Nuclear Factor-kappaB (NF-κB). RESULTS: ß1,4-GalT-I and microRNA-15a (miR-15a) show high and low expression in the articular cartilage of osteoarthritis, respectively. MiR-15a inhibits the mRNA translation of ß1,4-GalT-I. ß1,4-GalT-I promotes extracellular matrix degradation, senescence, and NF-κB activation in IL-1ß-stimulated chondrocytes, which can be reversed by overexpression of miR-15a. Intra-articular injection of microRNA-15a ameliorates cartilage degeneration by inhibiting ß1,4-GalT-I and phosphorylation of NF-κB in vivo. CONCLUSION: The authors clarified that the miR-15a/ß1,4-GalT-I axis inhibits the phosphorylation of NF-κB thereby inhibiting extracellular matrix degradation and senescence in chondrocytes to alleviate cartilage degeneration in osteoarthritis. MiR-15a and ß1,4-GalT-I may serve as potentially effective targets for the future treatment of osteoarthritis.
Subject(s)
Cartilage, Articular , MicroRNAs , Osteoarthritis , Animals , Mice , Cartilage, Articular/pathology , Chondrocytes/pathology , Interleukin-1beta , MicroRNAs/genetics , NF-kappa B/metabolism , Osteoarthritis/genetics , Signal TransductionABSTRACT
Introduction: Identifying the HER2 status of breast cancer patients is important for treatment options. Previous studies have shown that ultrasound features are closely related to the subtype of breast cancer. Methods: In this study, we used features of conventional ultrasound and ultrasound elastography to predict HER2 status. Results and Discussion: The performance of model (AUROC) with features of conventional ultrasound and ultrasound elastography is higher than that of the model with features of conventional ultrasound (0.82 vs. 0.53). The SHAP method was used to explore the interpretability of the models. Compared with HER2- tumors, HER2+ tumors usually have greater elastic modulus parameters and microcalcifications. Therefore, we concluded that the features of conventional ultrasound combined with ultrasound elastography could improve the accuracy for predicting HER2 status.
ABSTRACT
Perovskite solar cells (PSCs) have demonstrated over 25% power conversion efficiency (PCE) via efficient surface passivation. Unfortunately, state-of-the-art perovskite post-treatment strategies can solely heal the top interface defects. Herein, an ion-diffusion management strategy is proposed to concurrently modulate the top interfaces, buried interfaces, and bulk interfaces (i.e., grain boundaries) of perovskite film, enabling all-interface defect passivation. Specifically, this method is enabled by applying double interactive salts of octylammonium iodide (OAI) and guanidinium chloride (GACl) onto the 3D perovskite surface. It is revealed that the hydrogen-bonding interaction between OA+ and GA+ decelerates the OA+ diffusion and therefore forms a dimensionally broadened 2D capping layer. Additionally, the diffusion of GA+ and Cl- determines the composition of the bulk and buried interface of PSCs. As a result, n-inter-i-inter-p, i.e., five-layer structured PSCs can be obtained with a champion PCE of 25.43% (certified 24.4%). This approach also enables the substantially improved operational stability of perovskite solar cells.
ABSTRACT
Constructing 2D/3D perovskite heterojunctions is effective for the surface passivation of perovskite solar cells (PSCs). However, previous reports that studying perovskite post-treatment only physically deposits 2D perovskite on the 3D perovskite, and the bulk 3D perovskite remains defective. Herein, we propose Cl2-dissolved chloroform as a multifunctional solvent for concurrently constructing 2D/3D perovskite heterojunction and inducing the secondary growth of the bulk grains. The mechanism of how Cl2 affects the performance of PSCs is clarified. Specifically, the dissolved Cl2 reacts with the 3D perovskite, leading to Cl/I ionic exchange and Ostwald ripening of the bulk grains. The generated Cl- further diffuses to passivate the bulk crystal and buried interface of PSCs. Hexylammonium bromide dissolved in the solvent reacts with the residual PbI2 to form 2D/3D heterojunctions on the surface. As a result, we achieved high-performance PSCs with a champion efficiency of 24.21% and substantially improved thermal, ambient, and operational stability.
Subject(s)
Calcium Compounds , Oxides , Oxidation-Reduction , SolventsABSTRACT
Background and Objective: Astrocytes play an important role in healthy brain function, including the development and maintenance of blood-brain barrier (BBB), structural support, brain homeostasis, neurovascular coupling and secretion of neuroprotective factors. Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH) including neuroinflammation, glutamate toxicity, brain edema, vasospasm, BBB disruption, cortical spreading depolarization (SD). Methods: We searched PubMed up to 31 May, 2022 and evaluated the articles for screening and inclusion for subsequent systemic review. We found 198 articles with the searched terms. After exclusion based on the selection criteria, we selected 30 articles to start the systemic review. Key Content and Findings: We summarized the response of astrocytes induced by SAH. Astrocytes are critical for brain edema formation, BBB reconstruction and neuroprotection in the acute stage of SAH. Astrocytes clear extracellular glutamate by increasing the uptake of glutamate and Na+/K+ ATPase activity after SAH. Neurotrophic factors released by astrocytes contribute to neurological recovery after SAH. Meanwhile, Astrocytes also form glial scars which hinder axon regeneration, produce proinflammatory cytokines, free radicals, and neurotoxic molecules. Conclusions: Preclinical studies showed that therapeutic targeting the astrocytes response could have a beneficial effect in ameliorating neuronal injury and cognitive impairment after SAH. Clinical trials and preclinical animal studies are still urgently needed in order to determine where astrocytes stand in various pathway of brain damage and repair after SAH and, above all, to develop therapeutic approaches which benefit patient outcomes.
ABSTRACT
BACKGROUD: The frequencies of morbidity and impairment associated with spontaneous intracerebral haemorrhage (ICH) are comparatively high. Blood-brain barrier (BBB) integrity was compromised due to subsequent brain injury induced by ICH, which is crucial for a poor prognosis. Polymorphonuclear leukocyte (PMN) strongly modulate the disruption of BBB in the central nervous system (CNS). The lysophosphatidic acid receptor 1 (LPA1) mediated thrombospondin-1 (TSP1) regulation in astrocytes, which induce macrophage inflammatory protein 2(MIP2) secretion. MIP2 enhance PMN recruitment through CXC chemokine type 2 (CXCR2) activation. The purpose of this study was to investigate whether the LPA1-mediated inhibition of PMN recruitment and BBB protection after ICH is regulated by TSP1 and CXCR2 networks. METHODS: ICH induction was performed in CD1 mice using collagenase administration. AM966, a targeted LPA1 antagonist, was orally administered 1 and 12 h following ICH. further identify possible LPA1-mediated BBB protection mechanisms, we intracerebroventricularly (ICV) administered a CXCR2 ligand MIP2, as well as TSP1 CRISPR activation (ACT) with AM966. Consequently, we performed neurobehavioral, brain water content (BWC), Evans blue staining (EBS), immunofluorescence (IF), and western blot (WB) analyses. RESULTS: After ICH, astrocytes showed signs of LPA1, which peaked after 24 h, while PMN\ displayed evidence of CXCR2. The AM966-mediated LPA1 suppression relieved PMN recruitment, diminished brain oedema, demonstrated extravasation (as evidenced by EBS), protected BBB integrity, and enhanced neurologic activity following ICH. AM966 treatment strongly reduced TSP1, CXCR2, Occludin, and Claudin-5 expressions and PMN recruitment following ICH, and their expressions were restored by MIP2 and TSP1 CRISPR (ACT). CONCLUSIONS: This study shows that LAP1 suppression reduced PMN recruitment after ICH in mice via TSP1/CXCR2 signalling, which minimized BBB disruption and improved the CNS's neurobehavioral functioning. Hence, LPA1 is a strong candidate for therapy to reduce PMN recruitment and offer protection of BBB integrity after ICH.
Subject(s)
Blood-Brain Barrier , Brain Edema , Mice , Animals , Blood-Brain Barrier/metabolism , Receptors, Lysophosphatidic Acid/metabolism , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/metabolism , Brain/metabolism , Brain Edema/metabolismABSTRACT
Wide-bandgap (WBG) perovskite solar cells suffer from severe non-radiative recombination and exhibit relatively large open-circuit voltage (VOC) deficits, limiting their photovoltaic performance. Here, we address these issues by in-situ forming a well-defined 2D perovskite (PMA)2PbCl4 (phenmethylammonium is referred to as PMA) passivation layer on top of the WBG active layer. The 2D layer with highly pure dimensionality and halide components is realized by intentionally tailoring the side-chain substituent at the aryl ring of the post-treatment reagent. First-principle calculation and single-crystal X-ray diffraction results reveal that weak intermolecular interactions between bulky PMA cations and relatively low cation-halide hydrogen bonding strength are crucial in forming the well-defined 2D phase. The (PMA)2PbCl4 forms improved type-I energy level alignment with the WBG perovskite, reducing the electron recombination at the perovskite/hole-transport-layer interface. Applying this strategy in fabricating semi-transparent WBG perovskite solar cells (indium tin oxide as the back electrode), the VOC deficits can be reduced to 0.49 V, comparable with the reported state-of-the-art WBG perovskite solar cells using metal electrodes. Consequently, we obtain hysteresis-free 18.60%-efficient WBG perovskite solar cells with a high VOC of 1.23 V.
ABSTRACT
BACKGROUND: The CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. RESULTS: Here, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects. Mechanistically, we show that RfxCas13d exhibits collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene pathway. CONCLUSIONS: These findings provide new mechanistic insights into the collateral activity of RfxCas13d in mammalian cells and warn that the biosafety of the CRISPR-Cas13 system needs further evaluation before application to clinical treatments.
Subject(s)
CRISPR-Cas Systems , RNA , Animals , Mice , MAP Kinase Signaling System , RNA/genetics , TranscriptomeABSTRACT
Current approved therapies for acute ischemic stroke have a restricted therapeutic time window. Delayed recanalization, which has been utilized clinically in patients who have missed the time window for administration, may be a promising alternative for stroke patients. However, the underlying molecular mechanisms remain undiscovered. Herein, we hypothesized that delayed recanalization would increase M2 microglial polarization through the IL-4R (interleukin-4 receptor)/STAT6 (signal transducer and activators of transcription 6)/PPARγ (peroxisome proliferator-activated receptor γ) pathway, subsequently promoting stroke recovery in rats. The permanent middle cerebral artery occlusion (pMCAO) model was induced via intravascular filament insertion. Recanalization was induced by withdrawing the filament at 3 days after MCAO (rMCAO). Interleukin (IL)-4 was administered intranasally at 3 days after pMCAO. AS1517499, a specific STAT6 inhibitor, was administered intranasally at 3 days after MCAO induction. Immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, volumetric measurements of brain infarct, and neurological behavior tests were conducted. Delayed recanalization at 3 days after MCAO increased the polarization of M2 microglia, decreased inflammation, and improved neurological behavior. IL-4 treatment administered on the 3rd day after pMCAO increased M2 microglial polarization, improved neurological behavior, and reduced infarction volume of pMCAO rats. The inhibition of STAT6 decreased the level of p-STAT6 and PPARγ in rats treated with delayed recanalization. Delayed recanalization improved neurological function by increasing microglial M2 polarization, possibly involved with the IL-4R/STAT6/PPARγ pathway after MCAO in rats.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Rats , Animals , Infarction, Middle Cerebral Artery/metabolism , Microglia/metabolism , PPAR gamma , Ischemic Stroke/metabolism , Stroke/drug therapy , Brain Ischemia/drug therapyABSTRACT
NLRP3 inflammasomes have been reported to be an essential mediator in the inflammatory response during early brain injury (EBI) following subarachnoid hemorrhage (SAH). Recent studies have indicated that NLRP3 inflammasome-mediated pyroptosis and long non-coding RNA (lncRNA) H19 can participate in the inflammatory response. However, the roles and functions of lncRNA H19 in NLRP3 inflammasome-mediated pyroptosis during EBI after SAH are unknown and need to be further elucidated. NLRP3 inflammasome proteins were significantly elevated in CSF of human with SAH induced EBI and presented a positive correlation with severity. In ipsilateral hemisphere cortex of rats, these NLRP3 inflammasome proteins were also increased and accompanied with upregulation of H19, and both of NLRP3 and H19 were peaked at 24 h after SAH. However, knockdown of H19 markedly decreased the expression of NLRP3 inflammasome proteins at 24 h after SAH in rats and also ameliorated EBI, showing improved neurobehavioral deficits, cerebral edema, and neuronal injury. Moreover, knocking down of H19 downregulated the expression of Gasdermin D (GSDMD) in microglia in SAH rats. Similarly, knockdown of H19 also alleviated OxyHb-induced pyroptosis and NLRP3-mediated inflammasomes activation in primary microglia. Lastly, H19 competitively sponged with rno-miR-138-5p and then upregulated NLRP3 expression in the post-SAH inflammatory response. lncRNA H19 promotes NLRP3-mediated pyroptosis by functioning as rno-miR-138-5p sponge in rats during EBI after SAH, which might provide a potential therapeutic target for post-SAH inflammation regulation.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Subarachnoid Hemorrhage , Rats , Humans , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , RNA, Long Noncoding/genetics , Rats, Sprague-Dawley , Subarachnoid Hemorrhage/complications , MicroRNAs/genetics , MicroRNAs/therapeutic useABSTRACT
Abstract Objective Osteoarthritis is a condition characterized by articular cartilage degradation. The increased expression of β1,4-Galactosyltransferase-I (β1,4-GalT-I) in the articular cartilage of osteoarthritis patients was related to an inflammatory response. The aim of this study was to elucidate the role of β1,4-GalT-I in osteoarthritis. This study aimed to determine the function of 1,4-GalT-I in osteoarthritis. Methods The osteoarthritis mouse model with the destabilization of the medial meniscus was established by microsurgical technique. Pathological changes in articular cartilage were observed by hematoxylin and eosin staining and safranin O-fast green staining. Quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays were used to observe mRNA and protein expression, respectively. RNA interactions were verified by a luciferase reporter assay. SA-β-Gal staining was used to assess chondrocyte senescence. Immunofluorescence staining was conducted to observe the localization of Nuclear Factor-kappaB (NF-κB). Results β1,4-GalT-I and microRNA-15a (miR-15a) show high and low expression in the articular cartilage of osteoarthritis, respectively. MiR-15a inhibits the mRNA translation of β1,4-GalT-I. β1,4-GalT-I promotes extracellular matrix degradation, senescence, and NF-κB activation in IL-1β-stimulated chondrocytes, which can be reversed by overexpression of miR-15a. Intra-articular injection of microRNA-15a ameliorates cartilage degeneration by inhibiting β1,4-GalT-I and phosphorylation of NF-κB in vivo. Conclusion The authors clarified that the miR-15a/β1,4-GalT-I axis inhibits the phosphorylation of NF-κB thereby inhibiting extracellular matrix degradation and senescence in chondrocytes to alleviate cartilage degeneration in osteoarthritis. MiR-15a and β1,4-GalT-I may serve as potentially effective targets for the future treatment of osteoarthritis.
ABSTRACT
The relativistic charge carriers in monolayer graphene can be manipulated in manners akin to conventional optics. Klein tunneling and Veselago lensing have been previously demonstrated in ballistic graphene pn-junction devices, but collimation and focusing efficiency remains relatively low, preventing realization of advanced quantum devices and controlled quantum interference. Here, we present a graphene microcavity defined by carefully-engineered local strain and electrostatic fields. Electrons are manipulated to form an interference path inside the cavity at zero magnetic field via consecutive Veselago refractions. The observation of unique Veselago interference peaks via transport measurement and their magnetic field dependence agrees with the theoretical expectation. We further utilize Veselago interference to demonstrate localization of uncollimated electrons and thus improvement in collimation efficiency. Our work sheds new light on relativistic single-particle physics and provide a new device concept toward next-generation quantum devices based on manipulation of ballistic electron trajectory.
ABSTRACT
Waves impart momentum and exert force on obstacles in their path. The transfer of wave momentum is a fundamental mechanism for contactless manipulation, yet the rules of conventional scattering intrinsically limit the radiation force based on the shape and the size of the manipulated object. Here, we show that this intrinsic limit can be broken for acoustic waves with subwavelength-structured surfaces (metasurfaces), where the force becomes controllable by the arrangement of surface features, independent of the object's overall shape and size. Harnessing such anomalous metasurface scattering, we demonstrate complex actuation phenomena: self-guidance, where a metasurface object is autonomously guided by an acoustic wave, and tractor beaming, where a metasurface object is pulled by the wave. Our results show that bringing the metasurface physics of acoustic waves, and its full arsenal of tools, to the domain of mechanical manipulation opens new frontiers in contactless actuation and enables diverse actuation mechanisms that are beyond the limits of traditional wave-matter interactions.
ABSTRACT
A dual-loaded multi-targeted drug delivery nanosystem was constructed to simultaneously load paclitaxel (PTX) and 5-fluorouracil (5-FU) for targeted delivery and sustained release at tumor sites. Hollow mesoporous silica nanoparticles (HMSNs) were prepared by the inverse microemulsion method, then modified with folic acid and pH- and temperature-responsive materials, co-loaded with PTX and 5-FU, and finally encapsulated into lipid membranes. The obtained nanosystem was selectively internalized by human breast cancer MCF-7 cells that overexpress folate receptors through an energy-dependent process, and it released both drugs in vitro in a simulated tumor microenvironment. Moreover, the inhibitory effect of the dual-loaded nanoparticles was significantly better than that of the free drugs, suggesting that the composite nanosystem has the potential to selectively target tumor sites and perform the synergistic effect of PTX and 5-FU, while reducing their toxic effects on normal tissues.