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Protein glycosylation is a type of protein post-translational modification. One specific example is the modification of proteins with O-linked ß-N-acetylglucosamine (O-GlcNAc) and O-linked α-N-acetylgalactosamine (O-GalNAc). Enhanced levels of both O-GalNAc and O-GlcNAc in bladder cancer (BlCa) have been reported previously. However, the interplay between O-GalNAc and O-GlcNAc has yet to be explored. Herein, we find that the expression level of core1 ß-1,3-galactosyltransferase (C1GalT1), which is responsible for extending and maturing mucin-type O-glycans, is increased in BlCa. This increase is accompanied by O-GlcNAc modification of C1GalT1. This modification stabilizes C1GalT1 expression and strengthens its interaction with its chaperone Cosmc. Mutation at Thr229 or Thr233 attenuates C1GalT1 stability and facilitates its degradation via the proteasome pathway. Furthermore, a decrease in C1GalT1 inhibits the pro-tumorigenic effect on bladder cancer cells by suppressing glycolysis.
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INTRODUCTION: The aberrant up-regulation of meiotic nuclear division 1 (MND1) in somatic cells is considered as one of the driving factors of oncogenesis, whereas its expression and role in breast invasive cancer (BRCA) remain unclear. Hence, this study embarked on a comprehensive evaluation of MND1 across various cancers and identified its roles in BRCA. METHODS: Based on publicly available databases, including but not limited to UCSC Xena, TCGA, GTEx, GEO, STRING, GeneMANIA, and CancerSEA, we evaluated the expression patterns, genomic features, and biological functions of MND1 from a pan-cancer viewpoint and delved into the implications of MND1 in the prognosis and treatment of BRCA. Further molecular biology experiments were undertaken to identify the role of MND1 in proliferation, migration, and apoptosis in BRCA cells. RESULTS: Elevated levels of MND1 were notably observed in a wide array of tumor types, especially in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, STAD, and UCEC. Elevated MND1 expression was markedly associated with shortened OS in several tumors, including BRCA (HR = 1.52 [95%CI, 1.10-2.09], P = 0.011). The up-regulation of MND1 in BRCA was validated in external cohorts and clinical samples. Survival analyses demonstrated that elevated MND1 expression was associated with decreased survival for patients with BRCA. Co-expressed genes of MND1 were identified, and subsequent pathway analyses based on significantly associated genes indicated that MND1 plays key roles in DNA replication, cell cycle regulation, and DNA damage repair. The observed abnormal elevation and activation of MND1 led to increased proliferation and migration, along with decreased apoptosis in BRCA cells. CONCLUSIONS: MND1 emerges as a promising biomarker for diagnostic and therapeutic targeting in various cancers, including BRCA. The abnormal up-regulation and activation of MND1 are linked to carcinogenesis and poor prognosis among BRCA patients, which may be attributed to its involvement in HR-dependent ALT, warranting further scrutiny.
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Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation of substantial amounts of lactate to maintain the energy demand for neurons and other brain cells. Lactate has garnered increasing attention in recent years because of its emerging role in critical biological processes such as inflammation regulation and neuroprotection, particularly through its histone lactylation. Bromodomain-containing protein 4 (BRD4) plays a crucial role in maintaining neural development and promoting memory formation in the central nervous system. Nonetheless, the function and regulatory mechanism of BRD4 and histone lactylation in astrocytes following SAH remain elusive. Our findings indicate that BRD4, a crucial epigenetic regulator, plays a definitive role in histone lactylation. Both in vitro and in vivo, these results demonstrated that targeted silencing of BRD4 in astrocytes can significantly reduce H4K8la lactylation, thereby aggravating the A1 polarization of astrocytes and ultimately affecting the recovery of neural function and prognosis in mice after SAH. In summary, BRD4 plays a pivotal role in modulating astrocyte polarization following SAH via histone lactylation. Targeting this mechanism might offer an efficient therapeutic strategy for SAH.
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Astrocitos , Proteínas que Contienen Bromodominio , Histonas , Hemorragia Subaracnoidea , Factores de Transcripción , Animales , Masculino , Ratones , Astrocitos/metabolismo , Proteínas que Contienen Bromodominio/metabolismo , Polaridad Celular/fisiología , Células Cultivadas , Modelos Animales de Enfermedad , Histonas/metabolismo , Ratones Endogámicos C57BL , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/patología , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
The activation of glial cells is intimately associated with the pathophysiology of neuroinflammation and white matter injury (WMI) during both acute and chronic phases following subarachnoid hemorrhage (SAH). The complement C3a receptor (C3aR) has a dual role in modulating inflammation and contributes to neurodevelopment, neuroplasticity, and neurodegeneration. However, its impact on WMI in the context of SAH remains unclear. In this study, 175 male C57BL/6J mice underwent SAH through endovascular perforation. Oxyhemoglobin (oxy-Hb) was employed to simulate SAH in vitro. A suite of techniques, including immunohistochemistry, transcriptomic sequencing, and a range of molecular biotechnologies, were utilized to evaluate the activation of the C3-C3aR pathway on microglial polarization and WMI. Results revealed that post-SAH abnormal activation of microglia was accompanied by upregulation of complement C3 and C3aR. The inhibition of C3aR decreased abnormal microglial activation, attenuated neuroinflammation, and ameliorated WMI and cognitive deficits following SAH. RNA-Seq indicated that C3aR inhibition downregulated several immune and inflammatory pathways and mitigated cellular injury by reducing p53-induced death domain protein 1 (Pidd1) and Protein kinase RNA-like ER kinase (Perk) expression, two factors mainly function in sensing and responding to cellular stress and endoplasmic reticulum (ER) stress. The deleterious effects of the C3-C3aR axis in the context of SAH may be related to endoplasmic reticulum (ER) stress-dependent cellular injury and inflammasome formation. Agonists of Perk can exacerbate the cellular injury and neuroinflammation, which was attenuated by C3aR inhibition after SAH. Additionally, intranasal administration of C3a during the subacute phase of SAH was found to decrease astrocyte reactivity and alleviate cognitive deficits post-SAH. This research deepens our understanding of the complex pathophysiology of WMI following SAH and underscores the therapeutic potential of C3a treatment in promoting white matter repair and enhancing functional recovery prognosis. These insights pave the way for future clinical application of C3a-based therapies, promising significant benefits in the treatment of SAH and its related complications.
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Complemento C3 , Ratones Endogámicos C57BL , Microglía , Hemorragia Subaracnoidea , Sustancia Blanca , Animales , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/metabolismo , Microglía/metabolismo , Microglía/patología , Masculino , Ratones , Complemento C3/metabolismo , Sustancia Blanca/patología , Sustancia Blanca/metabolismo , Receptores de Complemento/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Subarachnoid hemorrhage (SAH) is recognized as an especially severe stroke variant, notorious for its high mortality and long-term disability rates, in addition to a range of both immediate and enduring neurologic impacts. Over half of the SAH survivors experience varying degrees of neurologic disorders, with many enduring chronic neuropsychiatric conditions. Due to the limitations of traditional imaging techniques in depicting subtle changes within brain tissues posthemorrhage, the accurate detection and diagnosis of white matter (WM) injuries are complicated. Against this backdrop, diffusion tensor imaging (DTI) has emerged as a promising biomarker for structural imaging, renowned for its enhanced sensitivity in identifying axonal damage. This capability positions DTI as an invaluable tool for forming precise and expedient prognoses for SAH survivors. This study synthesizes an assessment of DTI for the diagnosis and prognosis of neurologic dysfunctions in patients with SAH, emphasizing the notable changes observed in DTI metrics and their association with potential pathophysiological processes. Despite challenges associated with scanning technology differences and data processing, DTI demonstrates significant clinical potential for early diagnosis of cognitive impairments following SAH and monitoring therapeutic effects. Future research requires the development of highly standardized imaging paradigms to enhance diagnostic accuracy and devise targeted therapeutic strategies for SAH patients. In sum, DTI technology not only augments our understanding of the impact of SAH but also may offer new avenues for improving patient prognoses.
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Wide-bandgap (WBG) inverted perovskite solar cells (PSCs) are used as the top cell for tandem solar cells, which is an effective way to outperform the Shockley-Queisser limit. However, the low efficiency and poor phase stability still seriously restrict the application of WBG inverted PSCs. Here, the surface of the WBG perovskite film was passivated by the synthesized 1,2,4-tris(3-thienyl)benzene (THB). The THB size well matches with the halogen ion vacancy on the perovskite surface, and the S atom in THB can strongly interact with Pb2+ on the surface of the WBG perovskite film to the greatest extent, which effectively passivates surface defects and suppresses the recombination of carriers caused by these defects. At the same time, the S atom in THB occupied the migration site of the halogen ions, which inhibits the migration of halogen ions. Due to the strong conjugation effect and stability of THB, it can be locked on the surface of perovskite to increase the lattice strength and inhibit the segregation of photoinduced halide, thus improving the performance and operational stability of PSCs. The THB-modified WBG (Eg = 1.71 eV) PSC achieves a maximum power conversion efficiency of 20.75%, and its 99.0% is retained after 1512 h at a relative humidity of 10-25%. Under the irradiation of 1000 lx LED light, the indoor power conversion efficiency of the THB-modified WBG PSC reaches 34.15%.
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An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.
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The electron transport layer (ETL) plays an important role in determining the conversion efficiency and stability of perovskite solar cells (PSCs). Here, TiO2 thin film was prepared by irradiating diisopropoxy diacetylacetone titanium precursor thin film with 172 nm vacuum ultraviolet (VUV) at a low temperature. The prepared TiO2 thin film has higher electron mobility and conductivity. As it is used as an ETL for MAPbI3 PSCs, its band structure is better matched with the perovskite, and at the same time, due to the good interface contact, more uniform perovskite crystals are formed. Most importantly, a large number of hydroxyl radicals were formed during VUV irradiation of the precursor film, which made up for the oxygen defect present on the surface of the TiO2 thin film, and were adsorbed to the film surface. These hydroxyl groups form hydrogen bonds with methylammonium (MA) components on the MAPbI3 buried surface, thus promoting the transfer of photogenerated electrons at the MAPbI3/ETL interface. The power conversion efficiency of PSCs fabricated in air with the ETL prepared by VUV irradiation is 20.46%, which is higher than that of the contrast solar cell based on the sintered ETL (17.96%).
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The thermally stable inorganic cesium-based perovskites promise efficient and stable photovoltaics. Unfortunately, the strong ionic bonds lead to uncontrollable rapid crystallization, making it difficult in fabricating large-area black-phase film for photovoltaics. Herein, we developed a facile hydrogen-bonding assisted strategy for modulating the crystallization of CsPbI2 Br to achieve uniform large-area phase-pure films with much-reduced defects. The simple addition of methylamine acetate in precursors not only promotes the formation of intermediate phase via hydrogen bonding to circumvent the direct crystallization of CsPbI2 Br from ionic precursors but also widens the film processing window, thus enabling to fabricate large-area high-quality phase-pure CsPbI2 Br film under benign conditions. Combining with stable dopant-free poly(3-hexylthiophene), the CsPbI2 Br solar cells achieve the record-high efficiencies of 18.14 % and 16.46 % for 0.1â cm2 and 1â cm2 active area, respectively. The obtained high efficiency of 38.24 % under 1000â lux illumination suggests its potential in indoor photovoltaics for powering the Internet of Things, etc.
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Iodine vacancies and uncoordinated Pb0 defects existing at the perovskite surface have been widely demonstrated to induce deep-level defects, which can greatly limit improvement of the efficiency and stability of perovskite solar cells (PSCs). In this work, a novel strategy is proposed for functionalizing perovskite surface by using trimethylsulfoxonium iodide (TMSI), which can enhance the defect formation energy and inhibit Pb0 defects. Meanwhile, TMSI modification also can fill the iodine vacancies of perovskite surface-terminating ends. Consequently, the optimized device shows the improved charge dynamics and the reduced energy losses, achieving a champion efficiency of up to 24.03% along with excellent air-storage and thermal stabilities. This work offers guidelines for more efficient and stable PSCs based on the management of interface defects.
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Apolipoprotein E (apoE, protein; APOE, gene), divided into three alleles of E2, E3 and E4 in humans, is associated with the progression of white matter lesion load. However, mechanism evidence has not been reported regarding the APOE genotype in early white matter injury (WMI) under subarachnoid hemorrhage (SAH) conditions. In the present study, we investigated the effects of APOE gene polymorphisms, by constructing microglial APOE3 and APOE4-specific overexpression, on WMI and underlying mechanisms of microglia phagocytosis in a mice model of SAH. A total of 167 male C57BL/6J mice (weight 22-26 g) were used. SAH and bleeding environment were induced by endovascular perforation in vivo and oxyHb in vitro, respectively. Multi-technology approaches, including immunohistochemistry, high throughput sequencing, gene editing for adeno-associated viruses, and several molecular biotechnologies were used to validate the effects of APOE polymorphisms on microglial phagocytosis and WMI after SAH. Our results revealed that APOE4 significantly aggravated the WMI and decreased neurobehavioral function by impairing microglial phagocytosis after SAH. Indicators negatively associated with microglial phagocytosis increased like CD16, CD86 and the ratio of CD16/CD206, while the indicators positively associated with microglial phagocytosis decreased like Arg-1 and CD206. The increased ROS and aggravating mitochondrial damage demonstrated that the damaging effects of APOE4 in SAH may be associated with microglial oxidative stress-dependent mitochondrial damage. Inhibiting mitochondrial oxidative stress by Mitoquinone (mitoQ) can enhance the phagocytic function of microglia. In conclusion, anti-oxidative stress and phagocytosis protection may serve as promising treatments in the management of SAH.
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Lesiones Encefálicas , Hemorragia Subaracnoidea , Sustancia Blanca , Ratones , Humanos , Animales , Masculino , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Microglía/metabolismo , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/metabolismo , Sustancia Blanca/patología , Ratones Endogámicos C57BL , Apolipoproteínas E/genética , Lesiones Encefálicas/patología , Apolipoproteína E3/metabolismo , Fagocitosis/genéticaRESUMEN
Wide-bandgap perovskite solar cells (PSCs) are attracting increasing attention because they play an irreplaceable role in tandem solar cells. Nevertheless, wide-bandgap PSCs suffer large open-circuit voltage (VOC ) loss and instability due to photoinduced halide segregation, significantly limiting their application. Herein, a bile salt (sodium glycochenodeoxycholate, GCDC, a natural product), is used to construct an ultrathin self-assembled ionic insulating layer firmly coating the perovskite film, which suppresses halide phase separation, reduces VOC loss, and improves device stability. As a result, 1.68 eV wide-bandgap devices with an inverted structure deliver a VOC of 1.20 V with an efficiency of 20.38%. The unencapsulated GCDC-treated devices are considerably more stable than the control devices, retaining 92% of their initial efficiency after 1392 h storage under ambient conditions and retaining 93% after heating at 65 °C for 1128 h in an N2 atmosphere. This strategy of mitigating ion migration via anchoring a nonconductive layer provides a simple approach to achieving efficient and stable wide-bandgap PSCs.
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Traumatic brain injury (TBI) affects persons of all ages and is recognized as a major cause of death and disability worldwide; it also brings heavy life burden to patients and their families. The treatment of those with secondary injury after TBI is still scarce, however. Alternative splicing (AS) is a crucial post-transcriptional regulatory mechanism associated with various physiological processes, while the contribution of AS in treatment after TBI is poorly illuminated. In this study, we performed and analyzed the transcriptome and proteome datasets of brain tissue at multiple time points in a controlled cortical impact (CCI) mouse model. We found that AS, as an independent change against the transcriptional level, is a novel mechanism linked to cerebral edema after TBI. Bioinformatics analysis further indicated that the transformation of splicing isoforms after TBI was related to cerebral edema. Accordingly, we found that the fourth exon of transient receptor potential channel melastatin 4 (Trpm4) abrogated skipping at 72 h after TBI, resulting in a frameshift of the encoded amino acid and an increase in the proportion of spliced isoforms. Using magnetic resonance imaging (MRI), we have shown the numbers of 3nEx isoforms of Trpm4 may be positively correlated with volume of cerebral edema. Thus alternative splicing of Trpm4 becomes a noteworthy mechanism of potential influence on edema. In summary, alternative splicing of Trpm4 may drive cerebral edema after TBI. Trpm4 is a potential therapeutic targeting cerebral edema in patients with TBI.
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Edema Encefálico , Lesiones Traumáticas del Encéfalo , Canales Catiónicos TRPM , Ratones , Animales , Edema Encefálico/genética , Edema Encefálico/tratamiento farmacológico , Empalme Alternativo/genética , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Encéfalo/patología , Isoformas de Proteínas/genética , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismoRESUMEN
Passivating defects using organic halide salts, especially chlorides, is an effective method to improve power conversion efficiencies (PCEs) of perovskite solar cells (PSCs) arising from the stronger Pb-Cl bonding than Pb-I and Pb-Br bonding. However, Cl- anions with a small radius are prone to incorporation into the perovskite lattice that distorts the lead halide octahedron, degrading the photovoltaic performance. Here, we substitute atomic-Cl-containing organic molecules for widely used ionic-Cl salts, which not only retain the efficient passivation by Cl but also prevent the incorporation of Cl into the bulk lattice, benefiting from the strong covalent bonding between Cl atoms and organic frameworks. We find that only when the distance of Cl atoms in single molecules matches well with the distance of halide ions in perovskites can such a configuration maximize the defect passivation. We thereby optimize the molecular configuration to enable multiple Cl atoms in an optimal spatial position to maximize their binding with surface defects. The resulting PSCs achieve a certified PCE of 25.02%, among the highest PCEs for PSCs, and retain 90% of their initial PCE after 500 h of continuous operation.
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Bone marrow (BM) stroma plays key roles in supporting hematopoietic stem cell (HSC) growth. Glycosylation contributes to the interactions between HSC and surrounding microenvironment. We observed that bisecting N-acetylglucosamine (GlcNAc) structures, in BM stromal cells were significantly lower for MDS/AML patients than for healthy subjects. Malignant clonal cells delivered exosomal miR-188-5p to recipient stromal cells, where it suppressed bisecting GlcNAc by targeting MGAT3 gene. Proteomic analysis revealed reduced GlcNAc structures and enhanced expression of MCAM, a marker of BM niche. We characterized MCAM as a bisecting GlcNAc-bearing target protein, and identified Asn 56 as bisecting GlcNAc modification site on MCAM. MCAM on stromal cell surface with reduced bisecting GlcNAc bound strongly to CD13 on myeloid cells, activated responding ERK signaling, and thereby promoted myeloid cell growth. Our findings, taken together, suggest a novel mechanism whereby MDS/AML clonal cells generate a self-permissive niche by modifying glycosylation level of stromal cells.
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Leucemia Mieloide Aguda , MicroARNs , Humanos , Médula Ósea/patología , Proteómica , Células Madre Hematopoyéticas/metabolismo , Glicosilación , Leucemia Mieloide Aguda/patología , Microambiente Tumoral , Antígeno CD146/metabolismo , MicroARNs/metabolismoRESUMEN
Objective: S100A4 is a pro-inflammatory mediator which has been implicated in airway inflammatory diseases. However, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. The purpose of this study is to determine the expression of S100A4 and evaluate its potential value in distinguishing its endotypes. Methods: Sixty CRSwNP patients, 30 chronic rhinosinusitis without nasal polyps (CRSsNP) patients, and 30 healthy controls (HC) were enrolled in this study, and serum and tissue samples were collected. Serum and tissue S100A4 levels were detected by enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, western blotting and immunofluorescence. Their clinical values in predicting postoperative recurrence of CRSwNP were evaluated by multivariate analysis and ROC curves. Results: Serum levels of S100A4 were notably increased in the CRSwNP group than in the CRSsNP and HC groups (p < 0.05), and positively correlated with tissue and peripheral eosinophil count and percentage (p < 0.05). The serum S100A4 concentrations were significantly elevated in the Eos CRSwNP group in comparison with the non-Eos CRSwNP group (p < 0.05). Multivariate analysis and ROC curve presented that serum S100A4 levels were associated with CRSwNP endotypes. Additionally, tissue S100A4 mRNA and protein levels were significantly enhanced in the CRSwNP group than in the HC group and CRSsNP group, especially in the Eos CRSwNP group. Conclusion: Our results demonstrated that the S100A4 expression was increased in CRSwNP patients and associated with the endotypes. S100A4 could be a serologic biomarker for evaluating tissue eosinophilic inflammation and predicting endotypes in CRSwNP patients.
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A wide plethora of intervention procedures, tissue plasminogen activators, mechanical thrombectomy, and several neuroprotective drugs were reported in stroke research over the last decennium. However, against this vivid background of newly emerging pieces of evidence, there is little to no advancement in the overall functional outcomes. With the advancement of epigenetic tools and technologies associated with intervention medicine, stroke research has entered a new fertile. The stroke involves an overabundance of inflammatory responses arising in part due to the body's immune response to brain injury. Neuroinflammation contributes to significant neuronal cell death and the development of functional impairment and even death in stroke patients. Recent studies have demonstrated that epigenetics plays a key role in post-stroke conditions, leading to inflammatory responses and alteration of the microenvironment within the injured tissue. In this review, we summarize the progress of epigenetics which provides an overview of recent advancements on the emerging key role of secondary brain injury in stroke. We also discuss potential epigenetic therapies related to clinical practice.
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Metal oxides are the most efficient electron transport layers (ETLs) in perovskite solar cells (PSCs). However, issues related to the bulk (i.e., insufficient electron mobility, unfavorable energy level position) and interface of metal oxide/perovskite (detrimental surface hydroxyl groups) limit the transport kinetics of photoinduced electrons and prevent PSCs from unleashing their theoretical efficiency potential. Herein, the inorganic InP colloid quantum dots (CQDs) with outstanding electron mobility (4600 cm2 V-1 s-1) and carboxyl (-COOH) terminal ligands were uniformly distributed into the metal oxide ETL to form consecutive electron transport channels. The hybrid InP CQD-based ETL demonstrates a more N-type characteristic with more than 3-fold improvement in electron mobility. The formation of the Sn-O-In bond facilitates electron extraction due to suitable energy level alignment between the ETL and perovskite. The strong interaction between uncoordinated Pb2+ at the perovskite/ETL interface and the -COO- in the ligand of InP CQDs reduces the density of defects in perovskite. As a result, the hybrid InP CQD-based ETL with an optimized InP ratio (18 wt %) boosts the power conversion efficiency of PSCs from 22.38 to 24.09% (certified efficiency of 23.43%). Meanwhile, the device demonstrates significantly improved photostability and atmospheric storage stability.
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BACKGROUND: Abnormal glycosylation in a variety of cancer types is involved in tumor progression and chemoresistance. Glycosyltransferase C1GALT1, the key enzyme in conversion of Tn antigen to T antigen, is involved in both physiological and pathological conditions. However, the mechanisms of C1GALT1 in enhancing oncogenic phenotypes and its regulatory effects via non-coding RNA are unclear. METHODS: Abnormal expression of C1GALT1 and its products T antigen in human bladder cancer (BLCA) were evaluated with BLCA tissue, plasma samples and cell lines. Effects of C1GALT1 on migratory ability and proliferation were assessed in YTS-1 cells by transwell, CCK8 and colony formation assay in vitro and by mouse subcutaneous xenograft and trans-splenic metastasis models in vivo. Dysregulated circular RNAs (circRNAs) and microRNAs (miRNAs) were profiled in 3 pairs of bladder cancer tissues by RNA-seq. Effects of miR-1-3p and cHP1BP3 (circRNA derived from HP1BP3) on modulating C1GALT1 expression were investigated by target prediction program, correlation analysis and luciferase reporter assay. Functional roles of miR-1-3p and cHP1BP3 on migratory ability and proliferation in BLCA were also investigated by in vitro and in vivo experiments. Additionally, glycoproteomic analysis was employed to identify the target glycoproteins of C1GALT1. RESULTS: In this study, we demonstrated upregulation of C1GALT1 and its product T antigen in BLCA. C1GALT1 silencing suppressed migratory ability and proliferation of BLCA YTS-1 cells in vitro and in vivo. Subsets of circRNAs and miRNAs were dysregulated in BLCA tissues. miR-1-3p, which is reduced in BLCA tissues, inhibited transcription of C1GALT1 by binding directly to its 3'-untranslated region (3'-UTR). miR-1-3p overexpression resulted in decreased migratory ability and proliferation of YTS-1 cells. cHP1BP3 was upregulated in BLCA tissues, and served as an miR-1-3p "sponge". cHP1BP3 was shown to modulate migratory ability, proliferation, and colony formation of YTS-1 cells, and displayed tumor-suppressing activity in BLCA. Target glycoproteins of C1GALT1, including integrins and MUC16, were identified. CONCLUSIONS: This study reveals the pro-metastatic and proliferative function of upregulated glycosyltransferase C1GLAT1, and provides preliminary data on mechanisms underlying dysregulation of C1GALT1 via miR-1-3p / cHP1BP3 axis in BLCA.
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MicroARNs , Neoplasias de la Vejiga Urinaria , Regiones no Traducidas 3' , Animales , Antígenos Virales de Tumores , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular , Galactosiltransferasas/genética , Galactosiltransferasas/metabolismo , Regulación Neoplásica de la Expresión Génica , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Humanos , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Nucleares/metabolismo , ARN Circular , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
A high-conductivity thiocyanate ionic liquid (EMIMSCN) was introduced into perovskite solar cells for the first time. The high conductivity of EMIMSCN ensures an adequate supply of free SCN- anions and EMIM+ cations, so as to multifunctionally passivate the I vacancy and Pb-I antisite defects and realize an optimized interfacial energy level. Consequently, the devices with EMIMSCN treatment achieve a high PCE of 22.55% with substantial enhancement in stability. This simple and efficient strategy provides new insights into the selection of passivation agents for efficient and stable PSCs.