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The development of luminescent materials via mechanochemistry embodies a compelling yet intricate frontier within materials science. Herein, we delineate a methodology for the synthesis of brightly luminescent polymers, achieved by the mechanochemical coupling of aggregation-induced emission (AIE) prefluorophores with generic polymers. An array of AIE moieties tethered to the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical are synthesized as prefluorophores, which initially exhibit weak fluorescence due to intramolecular quenching. Remarkably, the mechanical coupling of these prefluorophores with macromolecular radicals, engendered through ball milling of generic polymers, leads to substantial augmentation of fluorescence within the resultant polymers. We meticulously evaluate the tunable emission of the AIE-modified polymers, encompassing an extensive spectrum from the visible to the near-infrared region. This study elucidates the potential of such materials in stimuli-responsive systems with a focus on information storage and encryption displays. By circumventing the complexity inherent to the conventional synthesis of luminescent polymers, this approach contributes a paradigm to the field of AIE-based polymers with implications for advanced technological applications.
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Quantum information, a field in which great advances have been made in the past decades, now presents opportunities for advanced chemistry. One roadblock to progress, especially for experimental chemical science, is that new concepts and technical definitions need to be learned. In this paper, we review some basic, but sometimes misunderstood, concepts of quantum information based on the mathematical formulation of quantum mechanics that will be useful for chemists interested in discovering ways that chemistry can contribute to the quantum information field. We cover topics including qubits and their density matrix formalism, quantum measurement as a quantum operation, information theory, and entanglement. We focus on the difference between the concepts in the quantum context and the classic context. We also discuss the relation and distinction among entanglement, correlation, and coherence. We aim to clarify the rigorous definition of these concepts and then indicate some examples in physical chemistry.
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Objective: This study aimed to investigate whether analgesia nociception index (ANI) could be an indicator of perioperative pain during laparoscopic trocar insertion. Methods: A total of 280 participants of anesthesia receiving laparoscopic surgery were enrolled. Anesthesia induction and maintenance were performed using the Marsh model for target propofol and the Minto model for remifentanil. Systolic blood pressure (SBP), heart rate (HR), and ANI were recorded at skin incision, the first-, second, the last-trocar insertion, and 5 min after the last trocar insertion. Results: ANI was significantly different among the five groups in the last four time points (all P < 0.05). Pearson's correlation showed that ANI was negatively correlated with SBP (r = -0.114, P = 0.077) and HR (r = -0.247, P < 0.001). The area under the curve of ANI was positively correlated with those of SBP (r = 0.493, P < 0.001) and HR (r = -0.420, P < 0.001). Multivariate logistic regression showed that the ANI was an independent factor associated with intraoperative hemodynamic adverse events only at 5 min after the last trocar insertion. Conclusions: Under general anesthesia, the change in ANI was consistent with changes in the balance between analgesia and nociceptive stimuli. The ANI can reflect the extent of transient pain but had a poor predictive performance for hemodynamic adverse events.
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Nitric oxide (NO) is a crucial signal molecule closely linked to the biological immune response, especially in macrophage polarization. When activated, macrophages enter a pro-inflammatory state and produce NO, a marker for the M1 phenotype. In contrast, the anti-inflammatory M2 phenotype does not produce NO. We developed a mitochondria-targeted two-photon iridium-based complex (Ir-ImNO) probe that can detect endogenous NO and monitor macrophages' different immune response states using various imaging techniques, such as one- and two-photon phosphorescence imaging and phosphorescence lifetime imaging. Ir-ImNO was used to monitor the immune activation of macrophages in mice. This technology aims to provide a clear and comprehensive visualization of macrophage immune responses.
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Macrófagos , Mitocôndrias , Óxido Nítrico , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Animais , Macrófagos/imunologia , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/química , Camundongos , Células RAW 264.7 , Irídio/química , Imagem Multimodal , Corantes Fluorescentes/química , Camundongos Endogâmicos C57BL , Imagem ÓpticaRESUMO
Base excision repair (BER) is a critical genome defense pathway that copes with a broad range of DNA lesions induced by endogenous or exogenous genotoxic agents. AP endonucleases in the BER pathway are responsible for removing the damaged bases and nicking the abasic sites. In plants, the BER pathway plays a critical role in the active demethylation of 5-methylcytosine (5mC) DNA modification. Here, we have determined the crystal structures of Arabidopsis AP endonuclease AtARP in complex with the double-stranded DNA containing tetrahydrofuran (THF) that mimics the abasic site. We identified the critical residues in AtARP for binding and removing the abasic site and the unique residues for interacting with the orphan base. Additionally, we investigated the differences among the three plant AP endonucleases and evaluated the general DNA repair capacity of AtARP in a mammalian cell line. Our studies provide further mechanistic insights into the BER pathway in plants.
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Proteínas de Arabidopsis , Arabidopsis , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Modelos Moleculares , Humanos , Arabidopsis/metabolismo , Arabidopsis/enzimologia , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , DNA/metabolismo , DNA/química , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/química , Furanos/metabolismo , Furanos/química , Ligação ProteicaRESUMO
Poly(ADP-ribosyl)ation (PARylation) is a critical posttranslational modification that plays a vital role in maintaining genomic stability via a variety of molecular mechanisms, including activation of replication stress and the DNA damage response. The nudix hydrolase NUDT16 was recently identified as a phosphodiesterase that is responsible for removing ADP-ribose units and that plays an important role in DNA repair. However, the roles of NUDT16 in coordinating replication stress and cell cycle progression remain elusive. Here, we report that SETD3, which is a member of the SET-domain containing protein (SETD) family, is a novel substrate for NUDT16, that its protein levels fluctuate during cell cycle progression, and that its stability is strictly regulated by NUDT16-mediated dePARylation. Moreover, our data indicated that the E3 ligase CHFR is responsible for the recognition and degradation of endogenous SETD3 in a PARP1-mediated PARylation-dependent manner. Mechanistically, we revealed that SETD3 associates with BRCA2 and promotes its recruitment to stalled replication fork and DNA damage sites upon replication stress or DNA double-strand breaks, respectively. Importantly, depletion of SETD3 in NUDT16-deficient cells did not further exacerbate DNA breaks or enhance the sensitivity of cancer cells to IR exposure, suggesting that the NUDT16-SETD3 pathway may play critical roles in the induction of tolerance to radiotherapy. Collectively, these data showed that NUDT16 functions as a key upstream regulator of SETD3 protein stability by reversing the ADP-ribosylation of SETD3, and NUDT16 participates in the resolution of replication stress and facilitates HR repair.
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ADP-Ribosilação , Neoplasias , Quebras de DNA de Cadeia Dupla , Dano ao DNA , Reparo do DNA , Neoplasias/genética , Neoplasias/radioterapia , Poli(ADP-Ribose) Polimerase-1/genética , Processamento de Proteína Pós-Traducional , Humanos , Linhagem Celular , Pirofosfatases/genética , Pirofosfatases/metabolismo , Histona Metiltransferases/genética , Histona Metiltransferases/metabolismoRESUMO
3D printing technology has revolutionized the field of wound dressings, offering tailored solutions with mechanical support to facilitate wound closure. In addition to personalization, the intricate nature of the wound healing process requires wound dressing materials with diverse properties, such as moisturization, flexibility, adhesion, anti-oxidation and degradability. Unfortunately, current materials used in digital light processing (DLP) 3D printing have been inadequate in meeting these crucial criteria. This study introduces a novel DLP resin that is biocompatible and consists of only three commonly employed non-toxic compounds in biomaterials, that is, dopamine, poly(ethylene glycol) diacrylate, and N-vinylpyrrolidone. Simple as it is, this material system fulfills all essential functions for effective wound healing. Unlike most DLP resins that are non-degradable and rigid, this material exhibits tunable and rapid degradation kinetics, allowing for complete hydrolysis within a few hours. Furthermore, the high flexibility enables conformal application of complex dressings in challenging areas such as finger joints. Using a difficult-to-heal wound model, the manifold positive effects on wound healing in vivo, including granulation tissue formation, inflammation regulation, and vascularization are substantiated. The simplicity and versatility of this material make it a promising option for personalized wound care, holding significant potential for future translation.
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Adesivos , Polietilenoglicóis , Cicatrização , Bandagens , Impressão TridimensionalRESUMO
BACKGROUND: One reason patients with cancer cannot benefit from immunotherapy is the lack of immune cell infiltration in tumor tissues. Cancer-associated fibroblasts (CAFs) are emerging as central players in immune regulation that shapes tumor microenvironment (TME). Earlier we reported that integrin α5 was enriched in CAFs in colorectal cancer (CRC), however, its role in TME and cancer immunotherapy remains unclear. Here, we aimed to investigate the role for integrin α5 in fibroblasts in modulating antitumor immunity and therapeutic efficacy combined with checkpoint blockade in CRC. METHODS: We analyzed the CRC single-cell RNA sequencing (scRNA-seq) database to define the expression of ITGA5 in CRC tumor stroma. Experimentally, we carried out in vivo mouse tumor xenograft models to confirm the targeting efficacy of combined α5ß1 inhibition and anti-Programmed death ligand 1 (PD-L1) blockade and in vitro cell-co-culture assay to investigate the role of α5 in fibroblasts in affecting T-cell activity. Clinically, we analyzed the association between α5 expression and infiltrating T cells and evaluated their correlation with patient survival and immunotherapy prognosis in CRC. RESULTS: We revealed that ITGA5 was enriched in FAP-CAFs. Both ITGA5 knockout fibroblasts and therapeutic targeting of α5 improved response to anti-PD-L1 treatment in mouse subcutaneous tumor models. Mechanistically, these treatments led to increased tumor-infiltrating CD8+ T cells. Furthermore, we found that α5 in fibroblasts correlated with extracellular matrix (ECM)-related genes and affected ECM deposition in CRC tumor stroma. Both in vivo analysis and in vitro culture and cell killing experiment showed that ECM proteins and α5 expression in fibroblasts influence T-cell infiltration and activity. Clinically, we confirmed that high α5 expression was associated with fewer CD3+ T and CD8+ T cells, and tissues with low α5 and high CD3+ T levels correlated with better patient survival and immunotherapy response in a CRC cohort with 29 patients. CONCLUSIONS: Our study identified a role for integrin α5 in fibroblasts in modulating antitumor immunity by affecting ECM deposition and showed therapeutic efficacy for combined α5ß1 inhibition and PD-L1 blockade in CRC.
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Antígeno B7-H1 , Neoplasias Colorretais , Humanos , Animais , Camundongos , Linfócitos T CD8-Positivos , Integrina alfa5 , Fibroblastos , Neoplasias Colorretais/genética , Matriz Extracelular/metabolismo , Microambiente TumoralRESUMO
Non-uniform environmental conditioning has established substantial energy-saving and conditioning effects in residential buildings, however, few studies on the technology applied in greenhouses have been conducted. Semi-enclosed greenhouse development is hindered by energy consumption. To better apply non-uniform environmental conditioning technology in greenhouses, it is necessary to investigate the non-uniform characteristics of field environment parameters. Therefore, spatial and temporal measurements of indoor temperature and relative humidity in a Venlo-type greenhouse in Yangling, China, were conducted on June 5-11, 2022. Temperature and humidity sensors were arranged in the greenhouse at 4.5 m intervals, in the canopy, cultivation, center, and root areas. Temperature and humidity measurement points on the greenhouse walls were selected. The measurement results showed large fluctuations in the indoor temperature and relative humidity over time. The difference between indoor and outdoor average temperatures ranged from -5-10 °C and temperatures unsuitable for tomato growth were identified, although some passive conditioning methods such as ventilation and water spraying were employed, which indicates the necessity of active heating and cooling. Based on the measured data, the nonuniformity coefficients of temperature and relative humidity in different directions in the greenhouse were calculated. A larger non-uniformity in the vertical direction was found compared to that in the horizontal direction. These results suggest the possibility of non-uniform environmental conditioning. A rough estimation of the energy consumption by the two different condition modes, namely zone-specific and overall conditioning, was made. A huge energy saving of 69.6 % by the zone-specific conditioning mode was revealed compared to the overall conditioning. This implies a huge advantage in energy efficiency by non-unform environmental conditioning technologies applied in greenhouses. The study provides useful data for understanding non-uniform environments in greenhouses and the application of non-uniform environmental conditioning technologies.
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Background: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC. Methods: Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed. Results: We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC. Conclusion: Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation.
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Nitric oxide (NO) serves as a ubiquitous and fundamental signaling molecule involved in intricate effects on both physiological and pathological processes. NO, biosynthesized by nitric oxide synthase (NOS) or generated from nitrite, can form nitrosation reagent N2O3 (4NO + O2 = 2N2O3) through its oxidation or quickly produce peroxynitrite anion ONOO- (NO + â¢O2- = ONOO-) by reacting with superoxide anion (â¢O2-). However, most of the existing luminescent probes for NO just focus on specificity and utilize only a single signal to distinguish products N2O3 or ONOO-. In most of the present work, they differentiate one product from another simply by fluorescence signal or fluorescence intensity, which is not enough to distinguish accurately the behavior of NO in living cells. Herein, a new mitochondria-targeted and two-photon near-infrared (NIR) phosphorescent iridium(III) complex, known as Ir-NBD, has been designed for accurate detection and simultaneous imaging of two downstream products of endogenous NO, i.e., N2O3 and ONOO-. Ir-NBD exhibits a rapid response to N2O3 and ONOO- in enhanced phosphorescence intensity, increased phosphorescence lifetime, and an exceptionally high two-photon cross-section, reaching values of 78 and 85 GM, respectively, after the reaction. Furthermore, we employed multiple imaging methods, phosphorescence intensity imaging, and phosphorescence lifetime imaging together to image even distinguish N2O3 and ONOO- by probe Ir-NBD. Thus, coupled with its excellent photometrics, Ir-NBD enabled the detection of the basal level of intracellular NO accurately by responding to N2O3 and ONOO- in the lipopolysaccharide-stimulated macrophage model in virtue of fluorescence signal and phosphorescence lifetime imaging, revealing precisely the endogenous mitochondrial NO distribution during inflammation in a cell environment.
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Irídio , Óxido Nítrico , Óxido Nítrico/metabolismo , Oxirredução , Mitocôndrias/metabolismo , Fótons , Ácido Peroxinitroso/metabolismo , Corantes Fluorescentes/metabolismoRESUMO
Cytoskeleton-associated protein 4 (CKAP4) acts as a key transmembrane protein that connects the endoplasmic reticulum (ER) to microtubule dynamics. Researchers have not examined the roles of CKAP4 in nasopharyngeal carcinoma (NPC). The study aimed at evaluating the prognostic value and metastasis-regulating effect of CKAP4 in NPC. CKAP4 protein could be observed in 86.36% of 557 NPC specimens but not in normal nasopharyngeal epithelial tissue. According to immunoblot assays, NPC cell lines presented high CKAP4 expression relative to NP69 immortalized nasopharyngeal epithelial cells. Moreover, CKAP4 was highly expressed at the NPC tumor front and in matched liver, lung, and lymph node metastasis samples. Furthermore, high CKAP4 expression reported poor overall survival (OS) and presented a positive relevance to tumor (T) classification, recurrence, and metastasis. According to multivariate analysis, CKAP4 could independently and negatively predict patients' prognosis. Stable knockdown of CKAP4 expression in NPC cells inhibited cell migration, invasion and metastasis in vitro and in vivo. Moreover, CKAP4 promoted epithelial-mesenchymal transition (EMT) in NPC cells. CKAP4 knockdown was followed by the downregulation of the interstitial marker vimentin, and upregulation of the epithelial marker E-cadherin. In NPC tissues, high CKAP4 expression exhibited a positive relevance to vimentin expression and a negative relevance to E-cadherin expression. In conclusion, CKAP4 is an independent predictor of NPC, and CKAP4 might contribute NPC progression and metastasis, which may be involved in EMT with vimentin and E-cadherin.
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Neoplasias Nasofaríngeas , Humanos , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Citoesqueleto/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/genética , VimentinaRESUMO
This paper compared the effects of air and nitrogen on the freezing characteristics, color, and cell structures of chestnut kernels at different rates of heat transfer and adopted liquid nitrogen spray quick-freezing (NF-40 °C/-60 °C/-80 °C/-100 °C) and still air freezing (AF-20 °C/-40 °C) as the freezing methods. The ratio of heat transfer coefficients in N2 groups was two times as high as those in air groups, and NF-100 °C and NF-80 °C showed better freezing characteristics, good protection for cytoskeletons, and the color was similar to those of the fresh group. Taking both Multivariate Analysis of Variance (Principal Components Analysis and Cluster Analysis) and economic factors, NF-80 °C can be used as a suitable method for chestnut kernel freezing. When the ambient freezing temperature was lower than Tg, both NF and AF treatment groups presented poor quality. The rate and medium of heat transfer jointly influenced the freezing characteristics and quality. The former had a greater effect than the latter, however.
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Aberrant SUMOylation contributes to the progression of hepatocellular carcinoma (HCC), yet the molecular mechanisms have not been well elucidated. RING-type E3 ubiquitin ligase RNF146 is a key regulator of the Wnt/ß-catenin signaling pathway, which is frequently hyperactivated in HCC. Here, it is identified that RNF146 can be modified by SUMO3. By mutating all lysines in RNF146, we found that K19, K61, K174 and K175 are the major sites for SUMOylation. UBC9/PIAS3/MMS21 and SENP1/2/6 mediated the conjugation and deconjugation of SUMO3, respectively. Furthermore, SUMOylation of RNF146 promoted its nuclear localization, while deSUMOylation induced its cytoplasmic localization. Importantly, SUMOylation promotes the association of RNF146 with Axin to accelerate the ubiquitination and degradation of Axin. Intriguingly, only UBC9/PIAS3 and SENP1 can act at K19/K175 in RNF146 and affect its role in regulating the stability of Axin. In addition, inhibiting RNF146 SUMOylation suppressed the progression of HCC both in vitro and in vivo. And, patients with higher expression of RNF146 and UBC9 have the worst prognosis. Taken together, we conclude that RNF146 SUMOylation at K19/K175 promotes its association with Axin and accelerates Axin degradation, thereby enhancing ß-catenin signaling and contributing to cancer progression. Our findings reveal that RNF146 SUMOylation is a potential therapeutic target in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteína Axina/genética , Proteína Axina/metabolismo , beta Catenina/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Chaperonas Moleculares/metabolismo , Proteínas Inibidoras de STAT Ativados , Sumoilação , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Via de Sinalização WntRESUMO
Multifunctional nanoaggregates are widely used in cancer phototheranostics. However, it is challenging to construct their multifunctionality with a single component, and deliver them rapidly and efficiently without complex modifications. Herein, a NIR-absorbing small molecule named TBT-2(TP-DPA) is designed and certify its theranostic potentials. Then, their nanoaggregates, which are simply encapsulated by DSPE-PEG, demonstrate a photothermal efficiency of 51% while keeping a high photoluminescence quantum yield in the NIR region. Moreover, the nanoaggregates can be excited and delivered by an 808 nm pulse laser to solid tumors within only 40 min. The delivery efficiency and theranostic efficacy are better than that of the traditional enhanced permeability and retention (EPR) effect (generally longer than 24 hours). This platform is first termed as the photoinduced thermoacoustic (PTA) process, and confirm its application requires both NIR-responsive materials and pulse laser irradiation. This study not only inspires the design of multifunctional nanoaggregates, but also offers a feasible approach to their fast delivery. The platform reported here provides a promising prospect to boost the development of multifunctional theranostic drugs and maximize the efficacy of used medicines for their clinical applications.
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Neoplasias , Medicina de Precisão , Humanos , Nanomedicina Teranóstica/métodosRESUMO
The common aldehyde dehydrogenase 2 (ALDH2) alcohol flushing variant known as ALDH2*2 affects â¼8% of the world's population. Even in heterozygous carriers, this missense variant leads to a severe loss of ALDH2 enzymatic activity and has been linked to an increased risk of coronary artery disease (CAD). Endothelial cell (EC) dysfunction plays a determining role in all stages of CAD pathogenesis, including early-onset CAD. However, the contribution of ALDH2*2 to EC dysfunction and its relation to CAD are not fully understood. In a large genome-wide association study (GWAS) from Biobank Japan, ALDH2*2 was found to be one of the strongest single-nucleotide polymorphisms associated with CAD. Clinical assessment of endothelial function showed that human participants carrying ALDH2*2 exhibited impaired vasodilation after light alcohol drinking. Using human induced pluripotent stem cell-derived ECs (iPSC-ECs) and CRISPR-Cas9-corrected ALDH2*2 iPSC-ECs, we modeled ALDH2*2-induced EC dysfunction in vitro, demonstrating an increase in oxidative stress and inflammatory markers and a decrease in nitric oxide (NO) production and tube formation capacity, which was further exacerbated by ethanol exposure. We subsequently found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin mitigated ALDH2*2-associated EC dysfunction. Studies in ALDH2*2 knock-in mice further demonstrated that empagliflozin attenuated ALDH2*2-mediated vascular dysfunction in vivo. Mechanistically, empagliflozin inhibited Na+/H+-exchanger 1 (NHE-1) and activated AKT kinase and endothelial NO synthase (eNOS) pathways to ameliorate ALDH2*2-induced EC dysfunction. Together, our results suggest that ALDH2*2 induces EC dysfunction and that SGLT2i may potentially be used as a preventative measure against CAD for ALDH2*2 carriers.
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Doença da Artéria Coronariana , Células-Tronco Pluripotentes Induzidas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Camundongos , Animais , Aldeído-Desidrogenase Mitocondrial/genética , Estudo de Associação Genômica Ampla , Células-Tronco Pluripotentes Induzidas/metabolismo , Aldeído DesidrogenaseRESUMO
Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in regulating plant immunity. MAPKs usually transduce signals and regulate plant immunity by phosphorylating the downstream defence-related components. Our previous study indicates that StMPK7 positively regulates plant defence to Phytophthora pathogens via SA signalling pathway. However, the downstream component of StMPK7 remains unknown. In this study, we employed GFP-StMPK7 transgenic potato and performed immunoprecipitation-mass spectrometry (IP-MS) to identify the downstream component of StMPK7. We found that an RNA binding protein StUBA2a/b interacted with StMPK7, as revealed by luciferase complementation imaging (LCI) and coimmunoprecipitation (co-IP) assays. Transient expression of StUBA2a/b in Nicociana benthamiana enhanced plant resistance to Phytophthora pathogens, while silencing of UBA2a/b decreased the resistance, suggesting a positive regulator role of UBA2a/b in plant immunity. Similar to StMPK7, StUBA2a/b was also involved in SA signalling pathway and induced SGT1-dependent cell death as constitutively activated (CA)-StMPK7 did. Immune blotting indicated that StMPK7 phosphorylates StUBA2a/b at thr248 and thr408 (T248/408) sites and stabilizes StUBA2a/b. Silencing of MPK7 in N. benthamiana suppressed StUBA2a/b-induced cell death, while co-expression with StMPK7 enhanced the cell death. Besides, StUBA2a/bT248/408A mutant showed decreased ability to trigger cell death and elevate the expression of PR genes, indicating the phosphorylation by StMPK7 enhances the functions of StUBA2a/b. Moreover, CA-StMPK7-induced cell death was largely suppressed by silencing of NbUBA2a/b, genetically implying UBA2a/b acts as the downstream component of StMPK7. Collectively, our results reveal that StMPK7 phosphorylates and stabilizes its downstream substrate StUBA2a/b to enhance plant immunity via the SA signalling pathway.
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Cavity quantum electrodynamics has been studied as a potential approach to modify free charge carrier generation in donor-acceptor heterojunctions because of the delocalization and controllable energy level properties of hybridized light-matter states known as polaritons. However, in many experimental systems, cavity coupling decreases charge separation. Here, we theoretically study the quantum dynamics of a coherent and dissipative donor-acceptor cavity system, to investigate the dynamical mechanism and further discover the conditions under which polaritons may enhance free charge carrier generation. We use open quantum system methods based on single-pulse pumping to find that polaritons have the potential to connect excitonic states and charge separated states, further enhancing free charge generation on an ultrafast timescale of several hundred femtoseconds. The mechanism involves polaritons with optimal energy levels that allow the exciton to overcome the high Coulomb barrier induced by electron-hole attraction. Moreover, we propose that a second-hybridization between a polariton state and dark states with similar energy enables the formation of the hybrid charge separated states that are optically active. These two mechanisms lead to a maximum of 50% enhancement of free charge carrier generation on a short timescale. However, our simulation reveals that on the longer timescale of picoseconds, internal conversion and cavity loss dominate and suppress free charge carrier generation, reproducing the experimental results. Thus, our work shows that polaritons can affect the charge separation mechanism and promote free charge carrier generation efficiency, but predominantly on a short timescale after photoexcitation.
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A filtering slot antenna with a simple structure combination using characteristic mode analysis (CMA) is proposed. To realize filtering characteristics, characteristic magnetic currents of line and ring slots are analyzed and designed. Then, the folding-line slot and double-ring slot are selected to realize radiation null separately and combined to construct the basic slot antenna. By properly exciting the selected characteristic modes, a wide filtering bandwidth and a stable gain are obtained. To validate the design process, a prototype antenna with a finite ground plane of about 1.1 λ × 1.1 λ is designed and fabricated. Simulated and measured results agree well, which both show a sharping roll rate in the lower and higher frequency and a flat gain realization in the pass band. The filtering bandwidth is 32.7%, the out-of-band suppression level at the higher frequency is over 20 dB, and the gain in the working frequency varies from 3.9 to 5.2 dB.
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This review aims to provide insight into the role of N6-methyladenosine (m6A) modification in neoplastic immunity and subsequent tumorigenesis. m6A modification, which is catalyzed by methyltransferases, demethylases and reader proteins, has emerged as a widespread regulatory mechanism that controls immune-related gene expression and immune reactions during tumorigenesis. Aberrant m6A modification changes the neoplastic immune response in multiple cancers by regulating immune cell infiltration, tumor-promoting inflammation, immunosuppression, immune surveillance, and antitumor immune responses. m6A modification affects immune cell recruitment and cancer-promoting inflammation in hepatocellular carcinoma (HCC) to alter the progression of HCC. m6A modification has been implicated in the infiltration of immune cells and the activation of immune pathways, changing the proliferation and metastasis of gastric cancer. Immune surveillance and the antitumor immune response in breast cancer were enhanced via m6A modification, which inhibited tumor proliferation. m6A modification participates in neoplastic immunoregulation to influence tumor progression.