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Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.
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Colitis , Homeostasis , Mitocondrias , Estrés Oxidativo , Animales , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/inmunología , Ratones , Mitocondrias/metabolismo , Inmunoglobulina A/metabolismo , Sulfato de Dextran , Ratones Noqueados , Células Productoras de Anticuerpos/inmunología , Células Productoras de Anticuerpos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL , Glutatión/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Intestinos/inmunología , Apoptosis , Modelos Animales de EnfermedadRESUMEN
The conversion of CO2 into useful chemicals via photocatalysts is a promising strategy for resolving the environmental problems caused by the addition of CO2. Herein, a series of composite photocatalysts MOP@TpPa-CH3 based on MOP-NH2 and TpPa-CH3 through covalent bridging have been prepared via a facile room-temperature evaporation method and employed for photocatalytic CO2 reduction. The photocatalytic performances of MOP@TpPa-CH3 are greater than those of TpPa-CH3 and MOP-NH2, where the CO generation rate of MOP@TpPa-CH3 under 10% CO2 still reaches 119.25 µmol g-1 h-1, which is 2.18 times higher than that under pure CO2 (54.74 µmol g-1 h-1). To investigate the structural factors affecting the photocatalytic activity, MOP@TBPa-CH3 without CâO groups is synthesized, and the photoreduction performance is also evaluated. The controlling experimental results demonstrate that the excellent photoreduction CO2 performance of MOP@TpPa-CH3 in a 10% CO2 atmosphere is due to the presence of CâO groups in TpPa-CH3. This work offers a new design and construction strategy for novel MOP@COF composites.
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Hydrazone-linked covalent organic frameworks (COFs) with structural flexibility, heteroatomic sites, post-modification ability and high hydrolytic stability have attracted great attention from scientific community. Hydrazone-linked COFs, as a subclass of Schiff-base COFs, was firstly reported in 2011 by Yaghi's group and later witnessed prosperous development in various aspects. Their adjustable structures, precise pore channels and plentiful heteroatomic sites of hydrazone-linked structures possess much potential in diverse applications, for example, adsorption/separation, chemical sensing, catalysis and energy storage, etc. Up to date, the systematic reviews about the reported hydrazone-linked COFs are still rare. Therefore, in this review, we will summarize their preparation methods, characteristics and related applications, and discuss the opportunity or challenge of hydrazone-linked COFs. We hope this review could provide new insights about hydrazone-linked COFs for exploring more appealing functions or applications.
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Metal-organic frameworks constructed from Zr usually possess excellent chemical and physical stability. Therefore, they have become attractive platforms in various fields. In this work, two families of hybrid materials based on ZrSQU have been designed and synthesized, named Im@ZrSQU and Cu@ZrSQU, respectively. Im@ZrSQU was prepared through the impregnation method and employed for proton conduction. Im@ZrSQU exhibited terrific proton conduction performance in an anhydrous environment, with the highest proton conduction value of 3.6 × 10-2 S cm-1 at 110 °C. In addition, Cu@ZrSQU was synthesized via the photoinduction method for the photoreduction of CO2, which successfully promoted the conversion of CO2 into CO and achieved the CO generation rate of up to 12.4 µmol g-1 h-1. The photocatalytic performance of Cu@ZrSQU is derived from the synergistic effect of Cu NPs and ZrSQU. Based on an in-depth study and discussion toward ZrSQU, we provide a versatile platform with applications in the field of proton conduction and photocatalysis, which will guide researchers in their further studies.
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The photoreduction deposition method is employed to fabricate a family of silver nanoparticle (Ag NP)-modified polyoxometalate-based metal-organic framework (NENU-5) photocatalysts, named Ag/NENU-5. The title photocatalysts, Ag/NENU-5, can be used for the photocatalytic reduction of CO2 and are observed to efficiently reduce CO2 into CO, in which the highest reduction rate is 22.28 µmol g-1 h-1, 3 times greater than that of NENU-5. Photocatalytic reduction performances of CO2 have been extremely improved after the incorporation of Ag NPs as the cocatalyst. The enhancement of the photocatalytic reduction of CO2 has been attributed to the synergistic effects of Ag NPs and NENU-5, inhibiting the charge recombination during the photocatalytic process and increasing the reaction active sites. Furthermore, the influence of Ag NPs on the photocatalytic activity has also been investigated. The experimental results clearly reveal that the size of Ag NPs could exert a main effect on the photocatalytic activity, and the reasonable size of Ag NPs is able to enhance the photocatalytic reduction activity toward CO2 significantly.
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OBJECTIVE: We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. DESIGN: Dense mapping studies based on GWAS. PATIENTS: A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. MEASUREMENTS: Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. RESULTS: After the first replication stage, four SNPs from three regions with Pfirst < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined = 7.55 × 10-11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined = 5.59 × 10-8 , OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. CONCLUSIONS: Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.
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Enfermedad de Graves/epidemiología , Enfermedad de Graves/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Adulto JovenRESUMEN
Recently, development of a new type of anode material for lithium-ion batteries that possesses multielectron reaction, sufficient charge transfer, and restricted volume suppression has been considered a huge challenge. Herein, we find a simple hot-pressing method to incorporate polyoxometalate (POM)-based metal-organic frameworks (MOFs) onto three-dimensionally structured carbon cloth (CC), denoted as HP-NENU-5/CC, which immobilizes POMs into the MOFs avoiding the leaching of POMs and employs HP-NENU-5/CC as a flexible, conductive, and porous anode material. The HP-NENU-5/CC anode materials show outstanding electrochemical performance, exhibiting high reversible capacity (1723 mAh g-1 at 200 mA g-1), high rate capability (1072 mAh g-1 at 1000 mA g-1), and superior cycling stability (1072 mAh g-1 at 1000 mA g-1 after 400 cycles). Most importantly, the performance of HP-NENU-5/CC is the best among those of all reported POMs and MOF-based materials. In addition, we perform a comparative study for active materials coated on a two-dimensional current collector and CC, and our experimental results and analysis prove that the active material coated on CC does enhance the electrochemical performance.
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Crystalline porous materials are currently a hot research topic in the field of proton-conducting materials. Crystalline porous materials include metal-organic frameworks (MOFs), coordination polymers (CPs), polyoxometalates (POMs) and covalent organic frameworks (COFs). The designable structures and high surface areas of these materials provide great opportunities to orderly accommodate proton carriers and to systemically modify the concentration and mobility of proton carriers in available spaces. Based on the understanding of the relationship between the structure and proton conductivity, controllable synthesis of porous materials with high proton conductivity will gradually be achieved. This review summarizes the emerging studies of these materials and their unique proton conductivities.
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Intratumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) may account for resistance after a period of targeted therapies because drugs destroy only a portion of tumor cells. The recognition of ITH helps identify high-risk patients to make effective treatment decisions. However, ITH studies are confounded by interpatient heterogeneity in NSCLC and a large amount of passenger mutations. To address these issues, we recruited NSCLC patients carrying TP53 mutations and selected driver mutations within recurrently mutated genes in NSCLC. A total of 12-paired normal-tumor tissues were subjected to whole-genome/whole-exome sequencing. From these, 367 non-silent mutations were selected as driver mutations and deeply sequenced in 61 intratumoral microdissections. We identified a universal prevalence of heterogeneity in all 12 tumors, indicating branched evolution. Although TP53 mutations were observed in single biopsy of all 12 tumors, most tumors consist of both TP53 mutated and non-mutated cells in separate regions within the same tumor. This suggests the late molecular timing of the acquisition of TP53 mutations; therefore, the detection of TP53 mutations in a single biopsy may simply not reflect the early malignant potential. In addition, we identified regions of loss of heterozygosity surrounding TP53 and CDKN2A mutations in tumor 711, which also exhibited heterogeneity in different regional samples. Because the ITH of driver mutations likely has clinical consequences, further efforts are needed to limit the impact of ITH and to improve therapeutic efficiency, which will benefit NSCLC patients receiving targeted treatments.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Mutación , Análisis de Secuencia de ADN/métodos , Proteína p53 Supresora de Tumor/genética , Progresión de la Enfermedad , Evolución Molecular , Heterogeneidad Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Pérdida de Heterocigocidad , FilogeniaRESUMEN
Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/l, are associated with significant differences in blood pressure, BMI, dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the variance in TSH levels is thought to be genetically influenced. We conducted a genome-wide association study of TSH levels in 1346 Chinese Han individuals. In the replication study, we genotyped four candidate SNPs with the top association signals in an independent isolated Chinese She cohort (n = 3235). We identified a novel serum TSH susceptibility locus within XKR4 at 8q12.1 (rs2622590, Pcombined = 2.21 × 10(-10)), and we confirmed two previously reported TSH susceptibility loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated with low TSH levels and were found to be nominally associated to patients with papillary thyroid carcinoma (PTC) (OR = 1.41, P= 0.014 for rs2622590_T, and OR = 1.61, P= 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC tissues (P = 2.41 × 10(-4) and P= 0.02). Our findings suggest that the SNPs in XKR4 and near FOXE1 are involved in the regulation of TSH levels.
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Carcinoma/genética , Factores de Transcripción Forkhead/genética , Hipotiroidismo/genética , Proteínas de Transporte de Membrana/genética , Neoplasias de la Tiroides/genética , Tirotropina/sangre , Proteínas Reguladoras de la Apoptosis , Pueblo Asiatico/genética , Proteína CapZ/genética , Carcinoma Papilar , China , Cromosomas Humanos Par 8/genética , Cromosomas Humanos Par 9/genética , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Proteínas de la Membrana , Polimorfismo de Nucleótido Simple , Cáncer Papilar Tiroideo , Tirotropina/genéticaRESUMEN
Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.
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Predisposición Genética a la Enfermedad , Enfermedad de Graves/genética , ARN no Traducido/genética , Factores de Necrosis Tumoral/genética , Sistema del Grupo Sanguíneo ABO/genética , Adulto , Antígenos CD/genética , Secuencia de Bases , Estudios de Casos y Controles , Colágeno , ADN Intergénico , Femenino , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Receptores de Superficie Celular/genética , Receptores Acoplados a Proteínas G/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación LinfocitariaRESUMEN
The BACH2 gene regulates B cell differentiation and function and has been reported to be a shared susceptibility gene for several autoimmune diseases. Our previous genome-wide association study (GWAS) indicated that several single nucleotide polymorphisms (SNPs) in the BACH2 gene are associated with Graves' disease (GD) in the Chinese Han population; however, the association did not achieve genome-wide significance levels. Recently, this association of BACH2 with GD was confirmed in Caucasians in the UK population, but fine mapping in this region has not yet been reported. Here, we provide a refined analysis of a 331-kb region in the BACH2 gene, which harbors 359 SNPs, using GWAS data from 1,442 GD patients and 1,468 controls. The SNPs rs2474619 and rs9344996 were implied as the independent variants associated with GD by forward and two-locus logistic regression analysis. We genotyped eight out of 10 tagSNPs with P < 1 × 10(-3) in 3,508 GD patients and 3,209 controls, the results also showed that rs2474619 was independently associated with GD in the combined population from GWAS and the second stage (P = 1.81 × 10(-5)). The rs2474619 and rs9344996 were further genotyped in the third stage cohorts, and rs2474619 showed evidence of association with GD at genome-wide significance levels in the combined population (P = 3.28 × 10(-8), odds ratio = 1.13). The association of rs9344996 with GD can be explained by its linkage to rs2474619 in the combined population. Our study clearly demonstrated that BACH2 is a susceptibility gene for GD in the Chinese Han population and further supported rs2474619, in intron 2 of BACH2, is the best association signal with GD. However, the mechanism by which BACH2 confers increased risk of GD requires further study.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Etnicidad/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Enfermedad de Graves/genética , Enfermedades Autoinmunes/genética , Secuencia de Bases , China , Cartilla de ADN , Humanos , Modelos Logísticos , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. METHODS: The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. RESULTS: Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %-34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. CONCLUSION: Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients.
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Teorema de Bayes , Comorbilidad , Trastorno Depresivo Mayor , Síndrome Metabólico , Humanos , Trastorno Depresivo Mayor/epidemiología , Síndrome Metabólico/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Factores de Riesgo , China/epidemiología , Modelos Logísticos , Hospitalización/estadística & datos numéricos , Ácido Úrico/sangre , Puntaje de PropensiónRESUMEN
OBJECTIVE: Associations between IL2RA and various autoimmune diseases have been reported in Caucasians. We investigated whether genetic polymorphisms at the IL2RA locus were associated with Graves' disease (GD) in the Chinese Han population. DESIGN: We performed a genome-wide association study (GWAS) in 1 536 GD patients and 1 516 controls. The 1000 Genomes Project data were adopted as references for imputation analysis. After forward and conditional logistic regressions, we found that rs11256313 was the major risk variant in the CD25/IL2RA region. Thus, we further genotyped rs11256313 in a replication cohort with 3 694 GD patients and 3 510 controls using ABI 7900HT TaqMan Real-Time PCR System. RESULTS: Nine single nucleotide polymorphisms (SNPs) in the IL2RA block were nominally associated with GD in our GWAS (0·01 < P < 0·05). After imputation analysis, 13 imputed SNPs in the IL2RA block were weakly associated with GD (P ≤ 0·05). Logistic regression analysis suggested that the imputed rs11256313 could represent the IL2RA block (P = 0·003). However, we failed to replicate the association of rs11256313 in a larger cohort (P = 0·145). A subphenotype analysis of rs11256313 on thyroid hormone receptor antibody (TRAb) and gender showed that there was no association in any of the subphenotype groups (P > 0·05). CONCLUSIONS: The results suggested that common genetic polymorphisms at IL2RA do not exert a significant genetic effect on the development of GD in the Chinese Han population. Previously reported associations between CD25/IL2RA and autoimmune diseases including GD in Caucasians again imply that heterogeneity exists in different ethnic populations.
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Enfermedad de Graves/genética , Subunidad alfa del Receptor de Interleucina-2/genética , Pueblo Asiatico/genética , China/epidemiología , Etnicidad/genética , Estudio de Asociación del Genoma Completo , Genotipo , Enfermedad de Graves/epidemiología , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: To investigate the changes of serum programmed cell death 5 (PDCD5) levels in patients with critical illnesses including systemic inflammatory response syndrome (SIRS, except sepsis), sepsis (except severe sepsis) and severe sepsis. METHODS: A total of 78 patients were enrolled in this study, of whom, 28 were with SIRS, 23 with sepsis and 27 with severe sepsis. Twenty-two healthy individuals were included as controls. The levels of serum PDCD5 were evaluated by enzyme-linked immune sorbent assay. And the correlation analyses were made in the levels of sreum PDCD5 and acute physiology and chronic health evaluation II(APACHE II), high-sensitivity C-reactive protein(hs-CRP), white blood cell count, neutrophil count and age factors. RESULTS: Serum PDCD5 levels in the SIRS, sepsis and severe sepsis groups were (19.07 ± 8.91), (29.03 ± 13.27) and (42.83 ± 17.32) µg/L respectively, which were significantly higher than that in the healthy control group (0.32 ± 0.02) µg/L. Serum PDCD5 levels in SIRS, sepsis and severe sepsis groups were gradually increased with significant difference at any in-between comparison (P<0.05). Moreover, serum PDCD5 levels were positively correlated with the acute physiology and chronic health evaluation II (APACHE II) score (r=0.572, P<0.05). CONCLUSION: The serum PDCD5 levels in the critically ill patients with sepsis were progressively increased with the worsened condition. The up-regulated expression of PDCD5 may play an important role in the development and progression of sepsis.
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Proteínas Reguladoras de la Apoptosis/sangre , Proteínas de Neoplasias/sangre , Sepsis/sangre , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Regulación hacia ArribaRESUMEN
The anhydrous proton conductivity of Im@IEF-11 resulting from the integration of imidazole and porous IEF-11 has been investigated, and the highest proton conductive value can reach up to 7.64 × 10-2 S cm-1. Furthermore, IEF-11 is also developed to reduce CO2 due to its reasonable structure and suitable energy band, and its CO formation rate is 31.86 µmol g-1 h-1.
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Dióxido de Carbono , Estructuras Metalorgánicas , Porosidad , Protones , Titanio , ImidazolesRESUMEN
Metal-organic frameworks (MOFs) provide an ideal platform for loading various guests owing to their available space, and can be developed as a class of multifunctional materials. Herein, we cover the design and synthesis of two kinds of exchanged frameworks with multifunctional applications based on H3ImDC and In(NO3)3·2H2O through guest exchange inside the framework. The guest ammonium ion (NH4+) and [Ru(2,2'-bipyridine)3]2+ (Rubpy) are selected to exchange the dimethylammonium cation (Me2NH2+) encapsulated within In-MOF, giving birth to two kinds of new MOFs, named NH4+@In-MOF and Rubpy@In-MOF respectively. The proton conduction of NH4+@In-MOF and the CO2 photoreduction of Rubpy@In-MOF are investigated. Under different test conditions, the proton conductive behaviors of NH4+@In-MOF are evaluated and the best proton conductive value can reach up to 9.81 × 10-3 S cm-1. Compared to the original In-MOF, Rubpy@In-MOF exhibits a significantly enhanced CO2 photoreduction performance under a pure CO2 atmosphere. Furthermore, its photocatalytic activity is retained even under a 10% CO2 gas atmosphere, displaying a synergistic effect between Rubpy and In-MOF24 within Rubpy@In-MOF.
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Background: The immune landscape, prognostic model, and molecular variations of mantle cell lymphoma (MCL) remain unclear. Hence, an integrated bioinformatics analysis of MCL datasets is required for the development of immunotherapy and the optimization of targeted therapies. Methods: Data were obtained from the Gene Expression Omnibus (GEO) database (GSE32018, GSE45717 and GSE93291). The differentially expressed immune-related genes were selected, and the hub genes were screened by three machine learning algorithms, followed by enrichment and correlation analyses. Next, MCL molecular clusters based on the hub genes were identified by K-Means clustering, the probably approximately correct (PAC) algorithm, and principal component analysis (PCA). The landscape of immune cell infiltration and immune checkpoint molecules in distinct clusters was explored by single-sample gene-set enrichment analysis (ssGSEA) as well as the CIBERSORT and xCell algorithms. The prognostic genes and prognostic risk score model for MCL clusters were identified by least absolute shrinkage and selection operator (LASSO)-Cox analysis and cross-validation for lambda. Correlation analysis was performed to explore the correlation between the screened prognostic genes and immune cells or immune checkpoint molecules. Results: Four immune-related hub genes (CD247, CD3E, CD4, and GATA3) were screened in MCL, mainly enriched in the T-cell receptor signaling pathway. Based on the hub genes, two MCL molecular clusters were recognized. The cluster 2 group had a significantly worse overall survival (OS), with down-regulated hub genes, and a variety of activated immune effector cells declined. The majority of immune checkpoint molecules had also decreased. An efficient prognostic model was established, including six prognostic genes (LGALS2, LAMP3, ICOS, FCAMR, IGFBP4, and C1QA) differentially expressed between two MCL clusters. Patients with a higher risk score in the prognostic model had a poor prognosis. Furthermore, most types of immune cells and a range of immune checkpoint molecules were positively correlated with the prognostic genes. Conclusions: Our study identified distinct molecular clusters based on the immune-related hub genes, and showed that the prognostic model affected the prognosis of MCL patients. These hub genes, modulated immune cells, and immune checkpoint molecules might be involved in oncogenesis and could be potential prognostic biomarkers in MCL.
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AIM: Ghrelin is involved in regulating the differentiation of mesoderm-derived precursor cells. The aim of this study was to investigate whether ghrelin modulated the differentiation of human embryonic stem (hES) cells into cardiomyocytes and, if so, whether the effect was mediated by growth hormone secretagogue receptor 1α (GHS-R1α). METHODS: Cardiomyocyte differentiation from hES cells was performed according to an embryoid body (EB)-based protocol. The cumulative percentage of beating EBs was calculated. The expression of cardiac-specific markers including cardiac troponin I (cTnI) and α-myosin heavy chain (α-MHC) was detected using RT-PCR, real-time PCR and Western blot. The dispersed beating EBs were examined using immunofluorescent staining. RESULTS: The percentage of beating EBs and the expression of cTnI were significantly increased after ghrelin (0.1 and 1 nmol/L) added into the differentiation medium. From 6 to 18 d of differentiation, the increased expression of cTnI and α-MHC by ghrelin (1 nmol/L) was time-dependent, and in line with the alteration of the percentages of beating EBs. Furthermore, the dispersed beating EBs were double-positively immunostained with antibodies against cTnI and α-actinin. However, blockage of GHS-R1α with its specific antagonist D-[lys(3)]-GHRP-6 (1 µmol/L) did not alter the effects of ghrelin on cardiomyocyte differentiation. CONCLUSION: Our data show that ghrelin enhances the generation of cardiomyocytes from hES cells, which is not mediated via GHS-R1α.
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Células Madre Embrionarias/citología , Ghrelina/metabolismo , Miocitos Cardíacos/citología , Receptores de Ghrelina/metabolismo , Diferenciación Celular , Línea Celular , Células Madre Embrionarias/metabolismo , Humanos , Miocitos Cardíacos/metabolismoRESUMEN
Photoreduction of carbon dioxide (CO2) provides an effective perspective for solving the energy crisis and environmental problems. Herein, two types of composite photocatalysts (TiO2/ZIF-8) based on ZIF-8 and TiO2 have been designed and synthesized with the help of the grinding method and the solid-synthesis method. Both composite photocatalysts are employed for the photocatalytic reduction of CO2. In composite photocatalysts prepared by the grinding method, ZIF-8 particles are distributed on the surface of TiO2, and provide extra available spaces for storing CO2, which is beneficial for improving their photoreduction performances. As a result, an enhanced CO formation rate of 21.74 µmol g-1 h-1 with a high selectivity of 99% is obtained for this family of composite photocatalysts via the solid-gas mode without photosensitizers and sacrificial agents. For comparison, the other family of composite photocatalysts synthesized via the solid-synthesis method possesses structures similar to ZIF-8, where TiO2 is encapsulated inside the framework of ZIF-8. This structural feature obstructs the contact between the active sites of TiO2 and CO2, and leads to lower activities. The best CO formation rate of this family is only 10.67 µmol g-1 h-1 with 90% selectivity. Both the structural features of the two families of photocatalysts are described to explain their differences in photoreduction performances. The experimental finding reveals that different synthetic approaches indeed result in diversified structures and varied photocatalytic performances. This work affords a new scalable and efficient approach for the rational design of efficient photocatalysts in the area of artificial photosynthesis.