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The successful treatment of oncological malignancies which results in long-term disease control or the complete eradication of cancerous cells necessitates the onset of adaptive immune responses targeting tumor-specific antigens. Such desirable anticancer immunity can be triggered via the induction of immunogenic cell death (ICD) of cancer cells, thus converting malignant cells into an in situ vaccine that elicits T cell mediated adaptive immune responses and establishes durable immunological memory. The exploration of ICD for cancer treatment has been subject to extensive research. However, functional heterogeneity among ICD activating therapies in many cases requires specific co-medications to achieve full-blown efficacy. Here, we described the hallmarks of ICD and classify ICD activators into three distinct functional categories namely, according to their mode of action: (i) ICD inducers, which increase the immunogenicity of malignant cells, (ii) ICD sensitizers, which prime cellular circuitries for ICD induction by conventional cytotoxic agents, and (iii) ICD enhancers, which improve the perception of ICD signals by antigen presenting dendritic cells. Altogether, ICD induction, sensitization and enhancement offer the possibility to convert well-established conventional anticancer therapies into immunotherapeutic approaches that activate T cell-mediated anticancer immunity.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/patología , Antineoplásicos/farmacología , Muerte Celular , Antígenos de Neoplasias , Linfocitos TRESUMEN
Increased expression of angiotensin II AT1A receptor (encoded by Agtr1a) and Na+-K+-Cl- cotransporter-1 (NKCC1, encoded by Slc12a2) in the hypothalamic paraventricular nucleus (PVN) contributes to hypertension development. However, little is known about their transcriptional control in the PVN in hypertension. DNA methylation is a critical epigenetic mechanism that regulates gene expression. Here, we determined whether transcriptional activation of Agtr1a and Slc12a2 results from altered DNA methylation in spontaneously hypertensive rats (SHR). Methylated DNA immunoprecipitation and bisulfite sequencing-PCR showed that CpG methylation at Agtr1a and Slc12a2 promoters in the PVN was progressively diminished in SHR compared with normotensive Wistar-Kyoto rats (WKY). Chromatin immunoprecipitation-quantitative PCR revealed that enrichment of DNA methyltransferases (DNMT1 and DNMT3A) and methyl-CpG binding protein 2, a DNA methylation reader protein, at Agtr1a and Slc12a2 promoters in the PVN was profoundly reduced in SHR compared with WKY. By contrast, the abundance of ten-eleven translocation enzymes (TET1-3) at Agtr1a and Slc12a2 promoters in the PVN was much greater in SHR than in WKY. Furthermore, microinjecting of RG108, a selective DNMT inhibitor, into the PVN of WKY increased arterial blood pressure and correspondingly potentiated Agtr1a and Slc12a2 mRNA levels in the PVN. Conversely, microinjection of C35, a specific TET inhibitor, into the PVN of SHR markedly reduced arterial blood pressure, accompanied by a decrease in Agtr1a and Slc12a2 mRNA levels in the PVN. Collectively, our findings suggest that DNA hypomethylation resulting from the DNMT/TET switch at gene promoters in the PVN promotes transcription of Agtr1a and Slc12a2 and hypertension development.
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Desmetilación del ADN , Hipotálamo , Receptor de Angiotensina Tipo 1 , Miembro 2 de la Familia de Transportadores de Soluto 12 , Animales , Ratas , Presión Sanguínea , ADN/metabolismo , Hipertensión/metabolismo , Hipotálamo/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/metabolismo , ARN Mensajero/genética , Sistema Nervioso Simpático/metabolismo , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismoRESUMEN
Hypertension is a major adverse effect of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, used clinically as immunosuppressants. Calcineurin inhibitor-induced hypertension (CIH) is linked to augmented sympathetic output from the hypothalamic paraventricular nucleus (PVN). GluA2-lacking, Ca2+-permeable AMPA receptors (CP-AMPARs) are a key feature of glutamatergic synaptic plasticity, yet their role in CIH remains elusive. Here, we found that systemic administration of FK506 in rats significantly increased serine phosphorylation of GluA1 and GluA2 in PVN synaptosomes. Strikingly, FK506 treatment reduced GluA1/GluA2 heteromers in both synaptosomes and endoplasmic reticulum-enriched fractions from the PVN. Blocking CP-AMPARs with IEM-1460 induced a larger reduction of AMPAR-mediated excitatory postsynaptic current (AMPAR-EPSC) amplitudes in retrogradely labelled, spinally projecting PVN neurons in FK506-treated rats than in vehicle-treated rats. Furthermore, FK506 treatment shifted the current-voltage relationship of AMPAR-EPSCs from linear to inward rectification in labelled PVN neurons. FK506 treatment profoundly enhanced physical interactions of α2δ-1 with GluA1 and GluA2 in the PVN. Inhibiting α2δ-1 with gabapentin, α2δ-1 genetic knockout, or disrupting α2δ-1-AMPAR interactions with an α2δ-1 C terminus peptide restored GluA1/GluA2 heteromers in the PVN and diminished inward rectification of AMPAR-EPSCs in labelled PVN neurons induced by FK506 treatment. Additionally, microinjection of IEM-1460 or α2δ-1 C terminus peptide into the PVN reduced renal sympathetic nerve discharges and arterial blood pressure elevated in FK506-treated rats but not in vehicle-treated rats. Thus, calcineurin in the hypothalamus constitutively regulates AMPAR subunit composition and phenotypes by controlling GluA1/GluA2 interactions with α2δ-1. Synaptic CP-AMPARs in PVN presympathetic neurons contribute to augmented sympathetic outflow in CIH. KEY POINTS: Systemic treatment with the calcineurin inhibitor increases serine phosphorylation of synaptic GluA1 and GluA2 in the PVN. Calcineurin inhibition enhances the prevalence of postsynaptic Ca2+-permeable AMPARs in PVN presympathetic neurons. Calcineurin inhibition potentiates α2δ-1 interactions with GluA1 and GluA2, disrupting intracellular assembly of GluA1/GluA2 heterotetramers in the PVN. Blocking Ca2+-permeable AMPARs or α2δ-1-AMPAR interactions in the PVN attenuates sympathetic outflow augmented by the calcineurin inhibitor.
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Calcineurina , Neuronas , Núcleo Hipotalámico Paraventricular , Ratas Sprague-Dawley , Receptores AMPA , Tacrolimus , Animales , Receptores AMPA/metabolismo , Receptores AMPA/fisiología , Calcineurina/metabolismo , Masculino , Tacrolimus/farmacología , Ratas , Neuronas/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/fisiología , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Calcio/metabolismo , Potenciales Postsinápticos Excitadores/fisiología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Inhibidores de la Calcineurina/farmacología , Sinapsis/fisiología , Sinapsis/efectos de los fármacos , Sinapsis/metabolismoRESUMEN
Before the COVID-19 pandemic, Mycoplasma pneumoniae infections emerged during spring to summer yearly in Taiwan, but infections were few during the pandemic. M. pneumoniae macrolide resistance soared to 85.7% in 2020 but declined to 0% during 2022-2023. Continued molecular surveillance is necessary to monitor trends in macrolide-resistant M. pneumoniae.
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Antibacterianos , COVID-19 , Farmacorresistencia Bacteriana , Macrólidos , Mycoplasma pneumoniae , Neumonía por Mycoplasma , SARS-CoV-2 , Humanos , Taiwán/epidemiología , Macrólidos/farmacología , Macrólidos/uso terapéutico , Mycoplasma pneumoniae/efectos de los fármacos , Mycoplasma pneumoniae/genética , Neumonía por Mycoplasma/epidemiología , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/microbiología , COVID-19/epidemiología , Niño , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Preescolar , Pandemias , Masculino , Femenino , Lactante , Adolescente , Pruebas de Sensibilidad MicrobianaRESUMEN
Immune checkpoint inhibitor (ICI) therapies for tumors of different systems have attained significant achievements and have changed the current situation of tumor treatment due to their therapeutic characteristics of high specificity and low side effects. The immune checkpoint Programmed death 1/Programmed cell death-Ligand 1 (PD-1/PD-L1) axis exerts a vital role in the immune escape of tumor cells. As a result, it has become a key target for tumor immunotherapy. Therefore, to perfect research into potential regulatory factors for the PD-1/PD-L1 axis, in order to understand and illustrate tumor ICI therapy mechanisms, is a significant goal. Moreover, ncRNA has been verified to regulate the PD-1/PD-L1 axis in the tumor immune microenvironment to regulate tumor genesis and development. ncRNAs can improve or decrease the efficacy of ICI therapy by modulating PD-L1 expression. This review aimed to investigate the mechanisms of action of ncRNA in regulating the PD-1/PD-L1 axis in ICI therapy, to provide more efficient immunotherapy for tumors of different systems.
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Damage of reactive oxygen species to various molecules such as DNA has been related to many chronic and degenerative human diseases, aging, and even cancer. 8-Oxo-7,8-dihydroguanine (OG), the most significant oxidation product of guanine (G), has become a biomarker of oxidative stress as well as gene regulation. The positive effect of OG in activating transcription and the negative effect in inducing mutation are a double-edged sword; thus, site-specific quantification is helpful to quickly reveal the functional mechanism of OG at hotspots. Due to the possible biological effects of OG at extremely low abundance in the genome, the monitoring of OG is vulnerable to signal interference from a large amount of G. Herein, based on rolling circle amplification-induced G-triplex formation and Thioflavin T fluorescence enhancement, an ultrasensitive strategy for locus-specific OG quantification was constructed. Owing to the difference in the hydrogen-bonding pattern between OG and G, the nonspecific background signal of G sites was completely suppressed through enzymatic ligation of DNA probes and the triggered specificity of rolling circle amplification. After the signal amplification strategy was optimized, the high detection sensitivity of OG sites with an ultralow detection limit of 0.18 amol was achieved. Under the interference of G sites, as little as 0.05% of OG-containing DNA was first distinguished. This method was further used for qualitative and quantitative monitoring of locus-specific OG in genomic DNA under oxidative stress and identification of key OG sites with biological function.
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ADN , Guanina , Humanos , ADN/genética , Estrés Oxidativo , Especies Reactivas de Oxígeno , Técnicas de Amplificación de Ácido NucleicoRESUMEN
Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.
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Técnicas Biosensibles , Antígeno Carcinoembrionario , Técnicas Electroquímicas , alfa-Fetoproteínas , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/inmunología , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/inmunología , Técnicas Biosensibles/métodos , Humanos , Inmunoensayo/métodos , Oro/química , Límite de DetecciónRESUMEN
G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.
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Benzotiazoles , ADN , Colorantes Fluorescentes , Uracil-ADN Glicosidasa , Benzotiazoles/química , Benzotiazoles/metabolismo , Colorantes Fluorescentes/química , ADN/química , ADN/metabolismo , Uracil-ADN Glicosidasa/metabolismo , Uracil-ADN Glicosidasa/química , Espectrometría de Fluorescencia , Fluorescencia , Técnicas Biosensibles/métodos , Dicroismo Circular , HumanosRESUMEN
INTRODUCTION: Postendoscopic submucosal dissection (ESD) coagulation syndrome (PECS) prevention is one of the common postoperative complications of colorectal ESD. Considering the increasing incidence of PECS, it is critical to investigate various prevention methods. The objective of this study was to evaluate the efficacy of transrectal drainage tubes (TDTs) in PECS prevention in patients following colorectal ESD. METHODS: From July 2022 to July 2023, a multicenter, randomized controlled clinical trial was conducted in 3 hospitals in China. Patients with superficial colorectal lesions ≥20 mm who had undergone ESD for a single lesion were enrolled. Initially, 229 patients were included in the study and 5 were excluded. Two hundred twenty-four were randomly assigned to the TDT and non-TDT group in the end. This open-label study utilized a parallel design with a 1:1 allocation ratio, and endoscopists and patients were not blind to the randomization, and a 24 Fr drainage tube was inserted approximately 10-15 cm above the anus after the ESD under the endoscopy and tightly attached to a drainage bag. The TDTs were removed in 1-3 days following the ESD. RESULTS: A total of 229 eligible patients were enrolled in this study, and 5 patients were excluded. Ultimately, 224 patients were assigned to the TDT group (n = 112) and non-TDT group (n = 112). The median age for the patients was 63.45 years (IQR 57-71; 59 men [52.68%]) in the TDT group and 60.95 years (IQR 54-68; 60 men [53.57%]) in the non-TDT group. Intention-to-treat analysis showed patients in the TDT group had a lower incidence of PECS than patients in the non-TDT group (7 [6.25%] vs 20 [17.86%]; relative risk, 0.350; 95% confidence interval [CI], 0.154-0.795; P = 0.008). In the subgroup analysis, TDTs were found to prevent PECS in patients of the female gender (odd ratio, 0.097; 95% CI, 0.021-0.449; P = 0.001), tumor size <4 cm (odd ratio, 0.203; 95% CI, 0.056-0.728; P = 0.011), tumor located in the left-sided colorectum (odd ratio, 0. 339 95% CI, 0.120-0.957; P = 0.035), and shorter procedure time (<45 minutes) (odd ratio, 0.316; 95% CI, 0.113-0.879; P = 0.023). The tube fell off in 1 case (0.89%) accidentally ahead of time. No TDT-related complication was observed. DISCUSSION: The results from this randomized clinical study indicate that the application of TDTs effectively reduced the incidence of PECS in patients after colorectal ESD ( chictr.org.cn Identifier: ChiCTR2200062164).
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Alkaline anion-exchange-membrane water electrolyzers (AEMWEs) using earth-abundant catalysts is a promising approach for the generation of green H2. However, the AEMWEs with alkaline electrolytes suffer from poor performance at high current density compared to proton exchange membrane electrolyzers. Here, atomically dispersed Pt-Ru dual sites co-embedded in nanoporous nickel selenides (np/Pt1Ru1-Ni0.85Se) are developed by a rapid melt-quenching approach to achieve highly-efficient alkaline hydrogen evolution reaction. The np/Pt1Ru1-Ni0.85Se catalyst shows ampere-level current density with a low overpotential (46 mV at 10 mA cm-2 and 225 mV at 1000 mA cm-2), low Tafel slope (32.4 mV dec-1), and excellent long-term durability, significantly outperforming the benchmark Pt/C catalyst and other advanced large-current catalysts. The remarkable HER performance of nanoporous Pt1Ru1-Ni0.85Se is attributed to the strong intracrystal electronic metal-support interaction (IEMSI) between Pt-Se-Ru sites and Ni0.85Se support which can greatly enlarge the charge redistribution density, reduce the energy barrier of water dissociation, and optimize the potential determining step. Furthermore, the assembled alkaline AEMWE with an ultralow Pt and Ru loading realizes an industrial-level current density of 1 A cm-2 at 1.84 volts with high durability.
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Converting hierarchical biomass structure into cutting-edge architecture of electrocatalysts can effectively relieve the extreme dependency of nonrenewable fossil-fuel-resources typically suffering from low cost-effectiveness, scarce supplies, and adverse environmental impacts. A cost-effective cobalt-coordinated nanocellulose (CNF) strategy is reported for realizing a high-performance 2e-ORR electrocatalysts through molecular engineering of hybrid ZIFs-CNF architecture. By a coordination and pyrolysis process, it generates substantial oxygen-capturing active sites within the typically oxygen-insulating cellulose, promoting O2 mass and electron transfer efficiency along the nanostructured Co3O4 anchored with CNF-based biochar. The Co-CNF electrocatalyst exhibits an exceptional H2O2 electrosynthesis efficiency of ≈510.58 mg L-1 cm-2 h-1 with an exceptional superiority over the existing biochar-, or fossil-fuel-derived electrocatalysts. The combination of the electrocatalysts with stainless steel mesh serving as a dual cathode can strongly decompose regular organic pollutants (up to 99.43% removal efficiency by 30 min), showing to be a desirable approach for clean environmental remediation with sustainability, ecological safety, and high-performance.
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The kinetically retarded sulfur evolution reactions and notorious lithium dendrites as the major obstacles hamper the practical implementation of lithium-sulfur batteries (LSBs). Dual metal atom catalysts as a new model are expected to show higher activity by their rational coupling. Herein, the dual-atom catalyst with coupled NiâCo atom pairs (Ni/Co-DAC) is designed successfully by programmed approaches. The NiâCo atom pairs alter the local electron structure and optimize the coordination configuration of Ni/Co-DAC, leading to the coupling effect for promoting the interconversion of sulfur and guiding lithium plating/striping. The LSB delivers a remarkable capacity of 818 mA h g-1 at 3.0 C and a low degeneration rate of 0.053% per cycle over 500 cycles. Moreover, the LSB with a high sulfur mass loading of 6.1 mg cm-2 and lean electrolyte dosage of 6.0 µL mgS -1 shows a remarkable areal capacity of 5.7 mA h cm-2.
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OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.
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Braquiterapia , Craneofaringioma , Neoplasias Hipofisarias , Humanos , Braquiterapia/métodos , Braquiterapia/efectos adversos , Craneofaringioma/radioterapia , Estudios de Seguimiento , Neoplasias Hipofisarias/radioterapia , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
This study attempted to build a prostate cancer (PC) prognostic risk model with mitochondrial feature genes. PC-related MTGs were screened for Cox regression analyses, followed by establishing a prognostic model. Model validity was analyzed via survival analysis and receiver operating characteristic (ROC) curves, and model accuracy was validated in the GEO dataset. Combining risk score with clinical factors, the independence of the risk score was verified by using Cox analysis, followed by generating a nomogram. The Gleason score, microsatellite instability (MSI), immune microenvironment, and tumor mutation burden were analyzed in two risk groups. Finally, the prognostic feature genes were verified through a q-PCR test. Ten PC-associated MTGs were screened, and a prognostic model was built. Survival analysis and ROC curves illustrated that the model was a good predictor for the risk of PC. Cox regression analysis revealed that risk score acted as an independent prognostic factor. The Gleason score and MSI in the high-risk group were substantially higher than in the low-risk group. Levels of ESTIMATE Score, Immune Score, Stromal Score, immune cells, immune function, immune checkpoint, and immunopheno score of partial immune checkpoints in the high-risk group were significantly lower than in the low-risk group. Genes with the highest mutation frequencies in the two groups were SPOP, TTN, and TP53. The q-PCR results of the feature genes were consistent with the gene expression results in the database. The 10-gene model based on MTGs could accurately predict the prognosis of PC patients and their responses to immunotherapy.
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A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.
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Ácido Ascórbico , Estructuras Metalorgánicas , Termodinámica , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ácido Ascórbico/química , Cinética , Humanos , Teoría Funcional de la Densidad , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Estructura Molecular , Liberación de FármacosRESUMEN
The polymer solar cells (PSCs) have garnered substantial interest owing to their lightweight, cost-effectiveness, and flexibility, making them ideal for large-scale roll-to-roll manufacturing. In this study, two wide-bandgap (WBG) donor polymers, PFBiTPD and PClBiTPD, utilizing bithieno[3,4-c]pyrrole-4,6-dione (BiTPD) as the electron-accepting unit and fluorinated/chlorinated benzo[1,2-b:4,5-b']dithiophene (BDT) as the electron-donating moiety are designed and synthesized. The polymers demonstrated large optical bandgaps (exceeding 1.80 eV) and are blended with ITIC-4F to form the active layers in PSCs. The PFBiTPD-based devices showed a well-dispersed fibrillar network, facilitating efficient charge generation and transport. Thus, these devices attained a power conversion efficiency (PCE) of 8.60%, featuring a fill factor (FF) of 62.89%, an open-circuit voltage (Voc) of 0.88 V and a short-circuit current density (Jsc) of 15.54 mA cm-2. In contrast, PClBiTPD-based devices displayed lower performance due to less favorable morphology. The study underscores the importance of polymer design and morphology control in optimizing the photovoltaic performance of PSCs.
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Solar-driven H2 production from water splitting with efficient photocatalysts is a sustainable strategy to meet the clean energy demand and alleviate the approaching environmental issues caused by fossil fuel consumption. Among various semiconductor-based photocatalysts, graphitic carbon nitride (g-C3N4) has attracted much attention due to its advantages of long term-stability, visible light response, low cost, and easy preparation. However, the intrinsic Coulombic attraction between charge carriers and the interlayer electrostatic barrier of bulk g-C3N4 result in severe charge recombination and low charge separation efficiency. This perspective summarizes the recent progress in the development of g-C3N4 photocatalytic systems, and focuses on three main modification strategies for promoting charge transfer and minimizing charge recombination, including structural modulation, heterojunction construction, and cocatalyst loading. Based on this progress, we provide conclusions regarding the current challenges of further improving photocatalytic efficiency to fulfill commercial requirements, and propose some recommendations for the design of novel and satisfactory g-C3N4 photocatalysts, which is expected to progress the solar-to-hydrogen conversion.
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The trend toward further miniaturization of micronano antiferromagnetic (AFM) spintronic devices has led to a strong demand for low-dimensional materials. The assembly of AFM clusters to produce such materials is a potential pathway that promotes studies on such clusters. In this work, we report on the discovery of the AFM Cr2Snx (x = 3-20) clusters with a stepwise growth at the density functional theory (DFT) level. In comparison, the two Cr atoms tend to stay together and be buried by Sn atoms, forming endohedral structures with one Cr atom encapsulated at size 9 and finally forming a full-encapsulated structure at size 17. Each successive cluster size is composed of its predecessor with an extra Sn atom adsorbed onto the face, giving evidence of stepwise growth. All these Cr2Snx (x = 3-20) clusters are antiferromagnets, except for the triplet-state ferrimagnetic Cr2Sn11, and all their singly negatively and positively charged ions are ferromagnets. The found stable Cr2Sn17 cluster can dimerize, yielding dimers and trimers without noticeably distorting the geometrical structure and magnetic properties of each of its constituent cluster monomers, making it possible as a building block for AFM materials.
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OBJECTIVE: Summarize and analyze the characteristics of patients with Multiple Endocrine Neoplasia type 1 (MEN-1) who were diagnosed with malignant tumors that do not belong to MEN-1 components. METHODS: Clinical data from patients with MEN-1 who visited Peking Union Medical College Hospital between April 2012 and April 2022 were collected. We compared the clinical characteristics of patients with malignant tumors outside of their MEN-1 components to those without additional tumors. MEN-1 gene testing was performed on most of these patients using Sanger sequencing, whole-exome sequencing, or MLPA. RESULTS: A total of 221 MEN-1 patients were diagnosed, of which 23 (10.40%) were found to have malignant tumors that did not belong to MEN-1 components, including papillary thyroid carcinoma (PTC) (4.52%), breast cancer (1.81%), urologic neoplasms (1.35%), primary hepatic carcinoma (PCC) (0.09%), meningeal sarcoma (0.05%), glioblastoma (0.05%), cervical cancer (0.05%), and lung carcinoma (0.05%). MEN-1 gene mutations were identified in 11 patients, including missense mutations, frameshift mutations, and splice mutations. The prevalence of each endocrine neoplasm, particularly gastroenteropancreatic neuroendocrine tumor, was higher in MEN-1 patients with other malignant tumors compared to MEN-1 patients without malignant tumors. CONCLUSION: Our retrospective study revealed a higher incidence of non-MEN-1 component malignant tumors in MEN-1 patients, especially breast cancer, PTC, and urologic neoplasms. These patients also exhibit more severe clinical phenotypes of MEN-1.
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Neoplasia Endocrina Múltiple Tipo 1 , Humanos , Femenino , Masculino , Neoplasia Endocrina Múltiple Tipo 1/genética , Neoplasia Endocrina Múltiple Tipo 1/epidemiología , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Adulto , Persona de Mediana Edad , Mutación , Adulto Joven , Anciano , Adolescente , Estudios Retrospectivos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/epidemiología , Factores de Riesgo , Proteínas Proto-OncogénicasRESUMEN
BACKGROUND: The vestibular aqueduct (VA) serves an essential role in homeostasis of the inner ear and pathogenesis of Ménière's disease (MD). The bony VA can be clearly depicted by high-resolution computed tomography (HRCT), whereas the optimal sequences and parameters for magnetic resonance imaging (MRI) are not yet established. We investigated VA characteristics and potential factors influencing MRI-VA visibility in unilateral MD patients. METHODS: One hundred patients with unilateral MD underwent MRI with three-dimensional sampling perfection with application optimized contrasts using different flip angle evolutions (3D-SPACE) sequence and HRCT evaluation. The imaging variables included MRI-VA and CT-VA visibility, CT-VA morphology and CT-peri-VA pneumatization. RESULTS: The most frequent type of MRI-VA and CT-VA visualization was invisible VA and continuous VA, respectively. The MRI-VA visibility was significantly lower than CT-VA visibility. MRI-VA visibility had a weak positive correlation with ipsilateral CT-VA visualization. For the affected side, the MRI-VA visualization was negatively correlated with the incidence of obliterated-shaped CT-VA and positively with that of tubular-shaped CT-VA. MRI-VA visualization was not affected by CT-peri-VA pneumatization. CONCLUSION: In patients with MD, the VA visualization on 3D-SPACE MRI is poorer than that observed on CT and may be affected by its osseous configuration. These findings may provide a basis for further characterization of VA demonstrated by MRI and its clinical significance.