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Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches.
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BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.
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Estenosis Coronaria , Infarto del Miocardio , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Masculino , Estudios Prospectivos , Infarto del Miocardio/genética , Persona de Mediana Edad , Pronóstico , Estenosis Coronaria/genética , Adulto , Apolipoproteína A-I/genética , Intervención Coronaria Percutánea , Serina Endopeptidasas/genética , Genotipo , Apolipoproteína B-100/genética , Predisposición Genética a la EnfermedadRESUMEN
Cytoplasmic male sterility (CMS) is a very important factor to produce hybrid seeds, and the restoration of fertility involves the expression of many fertility-related genes. Our previous study showed that the expression of CaPIPLC5 was significantly up-regulated in pepper restorer accessions and minimally expressed in sterile accessions, speculating that CaPIPLC5 is related to the restoration of fertility. In this study, we further validated the function of CaPIPLC5 in the restoration of fertility. The results showed that CaPIPLC5 was specifically expressed in the anthers of the restorer accessions with the subcellular localization in the cytoplasm. Furthermore, the expression of CaPIPLC5 was significantly higher in restorer lines and restorer combinations than that in CMS lines and their maintainer lines. Silencing CaPIPLC5 led to the number of pollen decreased, pollen grains wrinkled, and the ratio of pollen germination reduced. In addition, the joint analysis of Yeast One-Hybrid (Y1H) and Dual-Luciferase (dual-LUC) assays suggested that transcription factors such as CaARF5, CabZIP24 and CaMYB-like1, interacted with the promoter regions of CaPIPLC5, which regulated the expression of CaPIPLC5. The present results provide new insights into the study of CaPIPLC5 involved in the restoration of fertility in pepper.
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Capsicum , Regulación de la Expresión Génica de las Plantas , Infertilidad Vegetal , Proteínas de Plantas , Polen , Capsicum/genética , Capsicum/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Infertilidad Vegetal/genética , Polen/genética , Polen/fisiología , Fertilidad/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The electrochemical CO2 reduction reaction (CO2RR) is an appealing method for carbon utilization. Alkaline CO2 electrolyzers exhibit high CO2RR activity, low full-cell voltages, and cost-effectiveness. However, the issue of CO2 loss caused by (bi)carbonate formation leads to excessive energy consumption, rendering the process economically impractical. In this study, we propose a trilayer polymer electrolyte (TPE) comprising a perforated anion exchange membrane (PAEM) and a bipolar membrane (BPM) to facilitate alkaline CO2RR. This TPE enables the coexistence of high alkalinity near the catalyst surface and the H+ flux at the interface between the PAEM and the cation exchange layer (CEL) of the BPM, conditions favoring both CO2 reduction to multicarbon products and (bi)carbonate removal in KOH-fed membrane electrode assembly (MEA) reactors. As a result, we achieve a Faradaic efficiency (FE) of approximately 46 % for C2H4, corresponding to a C2+ FE of 64 % at 260â mA cm-2, with a CO2-to-C2H4 single-pass conversion (SPC) of approximately 32 % at 140â mA cm-2-nearly 1.3â times the limiting SPC in conventional AEM-MEA electrolyzers. Furthermore, coupling CO2 reduction with formaldehyde oxidation reaction (FOR) in the TPE-MEA electrolyzer reduces the full-cell voltage to 2.3â V at 100â mA cm-2 without compromising the C2H4 FE.
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The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.
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Enfermedades Inflamatorias del Intestino , Receptores Purinérgicos P2 , Tiofenos , Animales , Tiofenos/farmacología , Tiofenos/síntesis química , Tiofenos/química , Tiofenos/uso terapéutico , Humanos , Ratones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Receptores Purinérgicos P2/metabolismo , Relación Estructura-Actividad , Antagonistas del Receptor Purinérgico P2/farmacología , Antagonistas del Receptor Purinérgico P2/química , Antagonistas del Receptor Purinérgico P2/síntesis química , Antagonistas del Receptor Purinérgico P2/uso terapéutico , Masculino , Descubrimiento de Drogas , Amidas/química , Amidas/farmacología , Amidas/síntesis química , Amidas/uso terapéutico , Microsomas Hepáticos/metabolismo , Simulación de Dinámica Molecular , Colitis/tratamiento farmacológicoRESUMEN
The development of nanoassemblies, activated by the tumor microenvironment, capable of generating photothermal therapy (PTT) and amplifying the "ROS (·OH) storm," is essential for precise and effective synergistic tumor treatment. Herein, an innovative cascade-amplified nanotheranostics based on biodegradable Pd-BSA-GOx nanocomposite for NIR-II photoacoustic imaging (PAI) guides self-enhanced NIR-II PTT/chemodynamic therapy (CDT)/starvation synergistic therapy. The Pd-BSA-GOx demonstrates the ability to selectively convert overexpressed H2O2 into strongly toxic ·OH by a Pd/Pd2+-mediated Fenton-like reaction at a lower pH level. Simultaneously, the GOx generates H2O2 and gluconic acid, effectively disrupting nutrient supply and instigating tumor starvation therapy. More importantly, the heightened levels of H2O2 and increased acidity greatly enhance the Fenton-like reactivity, generating a significant "·OH storm," thereby achieving Pd2+-mediated cascade-amplifying CDT. The specific PTT facilitated by undegraded Pd accelerates the Fenton-like reaction, establishing a positive feedback process for self-enhancing synergetic PTT/CDT/starvation therapy via the NIR-II guided-PAI. Therefore, the multifunctional nanotheranostics presents a simple and versatile strategy for the precision diagnosis and treatment of tumors.
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Perineuronal nets (PNNs) are important functional structures on the surface of nerve cells. Observation of PNNs usually requires dyeing or fluorescent labeling. As a network structure with a micron grid and sub-wavelength thickness but no special optical properties, quantitative phase imaging (QPI) is the only purely optical method for high-resolution imaging of PNNs. We proposed a Scattering Quantitative Interference Imaging (SQII) method which measures the geometric rather than transmission or reflection phase during the scattering process to visualize PNNs. Different from QIP methods, SQII method is sensitive to scattering and not affected by wavelength changes. Via geometric phase shifting method, we simplify the phase shift operation. The SQII method not only focuses on interference phase, but also on the interference contrast. The singularity points and phase lines of the scattering geometric phase depict the edges of the network structure and can be found at the valley area of the interference contrast parameter SINDR under different wavelengths. Our SQII method has its unique imaging properties, is very simple and easy to implement and has more worth for promotion.
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Understanding of nitrous acid (HONO) production is crucial to photochemical studies, especially in polluted environments like eastern China. In-situ measurements of gaseous and particulate compositions were conducted at a rural coastal site during the 2018 spring Ozone Photochemistry and Export from China Experiment (OPECE). This data set was applied to investigate the recycling of reactive nitrogen through daytime heterogeneous HONO production. Although HONO levels increase during agricultural burning, analysis of the observation data does not indicate more efficient HONO production by agricultural burning aerosols than other anthropogenic aerosols. Box and 1-D modeling analyses reveal the intrinsic relationships between nitrogen dioxide (NO2), particulate nitrate (pNO3), and nitric acid (HNO3), resulting in comparable agreement between observed and simulated HONO concentrations with any one of the three heterogeneous HONO production mechanisms, photosensitized NO2 conversion on aerosols, photolysis of pNO3, and conversion from HNO3. This finding underscores the uncertainties in the mechanistic understanding and quantitative parametrizations of daytime heterogeneous HONO production pathways. Furthermore, the implications for reactive nitrogen recycling, ozone (O3) production, and O3 control strategies vary greatly depending on the HONO production mechanism. On a regional scale, the conversion of HONO from pNO3 can drastically enhance O3 production, while the conversion from NO2 can reduce O3 sensitivity to NOx changes in polluted eastern China.
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Ácido Nitroso , Ozono , China , Nitrógeno , Contaminantes Atmosféricos , Aerosoles , Dióxido de NitrógenoRESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease. Targeting NLRP3 inflammasome, specifically its interaction with NEK7 via the LRR domain of NLRP3, is a promising therapeutic strategy. Our research aimed to disrupt this interaction by focusing on the LRR domain. Through virtual screening, we identified five compounds with potent anti-inflammatory effects and ideal LRR binding affinity. Lead compound C878-1943 underwent structural optimization, yielding pyridoimidazole derivatives with different anti-inflammatory activities. Compound I-19 from the initial series effectively inhibited caspase-1 and IL-1ß release in an adjuvant-induced arthritis (AIA) rat model, significantly reducing joint swelling and spleen/thymus indices. To further enhance potency and extend in vivo half-life, a second series including II-8 was developed, demonstrating superior efficacy and longer half-life. Both I-19 and II-8 bind to the LRR domain, inhibiting NLRP3 inflammasome activation. These findings introduce novel small molecule inhibitors targeting the LRR domain of NLRP3 protein and disrupt NLRP3-NEK7 interaction, offering a novel approach for RA treatment.
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Artritis Experimental , Artritis Reumatoide , Quinasas Relacionadas con NIMA , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Quinasas Relacionadas con NIMA/antagonistas & inhibidores , Quinasas Relacionadas con NIMA/metabolismo , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Humanos , Ratas , Artritis Experimental/tratamiento farmacológico , Descubrimiento de Drogas , Relación Estructura-Actividad , Masculino , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Antirreumáticos/farmacología , Antirreumáticos/química , Antirreumáticos/síntesis química , Antirreumáticos/uso terapéuticoRESUMEN
GABBR1 receptors have been implicated in the progression of rheumatoid arthritis (RA), and p38 MAP kinase (MAPK) was shown to be downregulated by GABA and result in unchecked production of pro-inflammatory cytokine. GABBR1 is a member of GABA receptors, and it is known to be upregulated and plays a vital role in RA. Glucocorticoids are efficient therapeutics in rheumatoid arthritis (RA) and are known to regulate GABA actions; therefore, we intended to investigate the potential of glucocorticoids in RA concerning the potential pathway GABBR1/MAPK. Joint specimens were obtained from collagen-induced arthritis mouse model. A double-blind semi-quantitative analysis of vascularity, cell infiltration, as well as lining thickness by help of a 4-point scale setting was used to assess joint inflammation. Expression of GABBR1 and p38 was evaluated immunohistochemically. In vitro peripheral blood (PB), synovial fluid (SF), and mononuclear cells (MCs) were acquired from RA mice. Western blotting was used for detecting expression of GABBR1 and p38 proteins. The presence of high levels of GABBR1 and p38 was prevalent in RA joints relative to healthy joints and related to the inflammation level. Glucocorticoid treatment alters GABBR1 along with p38 protein expression in joints while reducing joint inflammation. Ex vivo and in vitro assays revealed glucocorticoids have a direct impact on p38, such as the decreased GABBR1 expression level after dexamethasone incubation with SFMC. GABBR1 together with p38 expression in RA joints depends on local inflammation and can be targeted by glucocorticoids.
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Artritis Experimental , Artritis Reumatoide , Glucocorticoides , Proteínas Quinasas p38 Activadas por Mitógenos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Animales , Glucocorticoides/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Experimental/patología , Ratones , Masculino , Articulaciones/patología , Articulaciones/efectos de los fármacos , Articulaciones/metabolismo , Ratones Endogámicos DBA , Líquido Sinovial/metabolismo , Líquido Sinovial/efectos de los fármacos , Microambiente Celular/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Despite advancements in breast cancer treatment, bone metastases remain a significant concern for advanced breast cancer patients. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, this work develops an activatable targeted nanomedicine AuMnCO@BSA-N3 (AMCBN) to enable a novel collaborative integration of second near-infrared (NIR-II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employs a chemical coordination between noble metal complex and metal carbonyl (MnCO), with surface modification of azide groups to enhance tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone-binding properties enable the efficient and controlled release of Mn2+ ions and carbon monoxide (CO) in the bone microenvironment, thereby facilitating the expression of osteogenesis-related proteins and establishing a novel synchronous theranostics process for tumor-bone repair.
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BACKGROUND: Artemisia selengensis, classified within the genus Artemisia of the Asteraceae family, is a perennial herb recognized for its dual utility in culinary and medicinal domains. There are few studies on the chloroplast genome of A. selengensis, and the phylogeographic classification is vague, which makes phylogenetic analysis and evolutionary studies very difficult. RESULTS: The chloroplast genomes of 10 A. selengensis in this study were highly conserved in terms of gene content, gene order, and gene intron number. The genome lengths ranged from 151,148 to 151,257 bp and were typical of a quadripartite structure with a total GC content of approximately 37.5%. The chloroplast genomes of all species encode 133 genes, including 88 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Due to the contraction and expansion of the inverted repeats (IR), the overlap of ycf1 and ndhF genes occurred at the inverted repeats B (IRB) and short single copy sequence (SSC) boundaries. According to a codon use study, the frequent base in the chloroplast genome of A. selengensis' third codon position was A/T. The number of SSR repeats was 42-44, most of which were single nucleotide A/T repeats. Sequence alignment analysis of the chloroplast genome showed that variable regions were mainly distributed in single copy regions, nucleotide diversity values of 0 to 0.009 were calculated by sliding window analysis, 8 mutation hotspot regions were detected, and coding regions were more conserved than non-coding regions. Analysis of non-synonymous substitution (Ka) and synonymous substitution (Ks) revealed that accD, rps12, petB, and atpF genes were affected by positive selection and no genes were affected by neutral selection. Based on the findings of the phylogenetic analysis, Artemisia selengensis was sister to the genus Artemisia Chrysanthemum and formed a monophyletic group with other Artemisia genera. CONCLUSIONS: In this research, the present study systematically compared the chloroplast genomic features of A. selengensis and provided important information for the study of the chloroplast genome of A. selengensis and the evolutionary relationships among Asteraceae species.
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Artemisia , Genoma del Cloroplasto , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , Artemisia/genética , Artemisia/clasificación , Composición de Base , Repeticiones de Microsatélite , Evolución Molecular , Uso de CodonesRESUMEN
Atrazine is a widely used herbicide in agriculture, and it has garnered significant attention because of its potential risks to the environment and human health. The extensive utilization of atrazine, alongside its persistence in water and soil, underscores the critical need to develop safe and efficient removal strategies. This comprehensive review aims to spotlight atrazine's potential impact on ecosystems and public health, particularly its enduring presence in soil, water, and plants. As a known toxic endocrine disruptor, atrazine poses environmental and health risks. The review navigates through innovative removal techniques across soil and water environments, elucidating microbial degradation, phytoremediation, and advanced methodologies such as electrokinetic-assisted phytoremediation (EKPR) and photocatalysis. The review notably emphasizes the complex process of atrazine degradation and ongoing scientific efforts to address this, recognizing its potential risks to both the environment and human health.
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Atrazina , Biodegradación Ambiental , Herbicidas , Atrazina/toxicidad , Humanos , Ecosistema , Suelo/química , Contaminantes del SueloRESUMEN
The sand cat swarm optimization algorithm (SCSO) is a novel metaheuristic algorithm that has been proposed in recent years. The algorithm optimizes the search ability of individuals by mimicking the hunting behavior of sand cat groups in nature, thereby achieving robust optimization performance. It is characterized by few control parameters and simple operation. However, due to the lack of population diversity, SCSO is less efficient in solving complex problems and is prone to fall into local optimization. To address these shortcomings and refine the algorithm's efficacy, an improved multi-strategy sand cat optimization algorithm (IMSCSO) is proposed in this paper. In IMSCSO, a roulette fitness-distance balancing strategy is used to select codes to replace random agents in the exploration phase and enhance the convergence performance of the algorithm. To bolster population diversity, a novel population perturbation strategy is introduced, aiming to facilitate the algorithm's escape from local optima. Finally, a best-worst perturbation strategy is developed. The approach not only maintains diversity throughout the optimization process but also enhances the algorithm's exploitation capabilities. To evaluate the performance of the proposed IMSCSO, we conducted experiments in the CEC 2017 test suite and compared IMSCSO with seven other algorithms. The results show that the IMSCSO proposed in this paper has better optimization performance.
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Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the photothermal effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on the surrounding normal tissues. However, the overexpression of heat shock protein 70 (HSP70) and limited effect of single treatment drastically impede the therapeutic efficacy. Herein, the constructed multifunctional core-shell structured Ag-Cu@SiO2-PDA/GOx nanoreactors (APG NRs) that provide a dual inhibition of HSP70 strategy for the second near-infrared photoacoustic (NIR-II PA) imaging-guided combined mild PTT/chemodynamic therapy (CDT). The Ag-Cu cores can convert endogenous H2O2 to hydroxyl radical (â¢OH), which can induce lipid peroxidation (LPO) and further degrade HSP70. The polydopamine (PDA)/glucose oxidase (GOx) shells are utilized as the NIR-II photothermal agent to generate low temperature, and the GOx can reduce the energy supplies and inhibit energy-dependent HSP70 expression. Furthermore, both the generation of â¢OH and GOx-mediated energy shortage can reduce HSP70 expression to sensitize mild PTT under 1064 nm laser, and in turn, GOx and laser self-amplify the catalytic reactions of APG NRs for more production of â¢OH. The multifunctional nanoreactors will provide more potential possibilities for the clinical employment of mild PTT and the advancement of tumor combination therapies.
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In the past decade, perovskite solar cell (PSC) photoelectric conversion efficiency has advanced significantly, and tin dioxide (SnO2) has been extensively used as the electron transport layer (ETL). Due to its high electron mobility, strong chemical stability, energy level matching with perovskite, and easy low-temperature fabrication, SnO2 is one of the most effective ETL materials. However, the SnO2 material as an ETL has its limitations. For example, SnO2 films prepared by low-temperature spin-coating contain a large number of oxygen vacancies, resulting in energy loss and high open-circuit voltage (VOC) loss. In addition, the crystal quality of perovskites is closely related to the substrate, and the disordered crystal orientation will lead to ion migration, resulting in a large number of uncoordinated Pb2+ defects. Therefore, interface optimization is essential to improve the efficiency and stability of the PSC. In this work, 2-(5-chloro-2-benzotriazolyl)-6-tert-butyl-p-cresol (CBTBC) was introduced for ETL modification. On the one hand, the hydroxyl group of CBTBC forms a Lewis mixture with the Sn atom, which reduces the oxygen vacancy defect and prevents nonradiative recombination. On the other hand, the SnO2/CBTBC interface can effectively improve the crystal orientation of perovskite by influencing the crystallization kinetics of perovskite, and the nitrogen element in CBTBC can effectively passivate the uncoordinated Pb2+ defects at the SnO2/perovskite interface. Finally, the prevailing PCE of PSC (1.68 eV) modified by CBTBC was 20.34% (VOC = 1.214 V, JSC = 20.49 mA/cm2, FF = 82.49%).
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Damage of intestinal barrier function (BF) after ischemia/reperfusion (I/R) injury can induce serious complications and high mortality. MicroRNAs (miRNAs) are involved in intestinal mucosal BF and epithelial proliferation after I/R injury have been reported. We aimed to investigate the role and regulatory mechanism of miR-142-3p (miR-142) in intestinal epithelial proliferation and BF after I/R injury. We detected the proliferation, barrier function and miR-142 expression in clinical ischemic intestinal tissues. Furthermore, we induced an in vivo intestinal I/R injury mouse model and in vitro IEC-6 cells hypoxia/reoxygenation (H/R) injury model. After increasing and decreasing expression of miR-142, we detected the proliferation and barrier function of intestinal epithelial cells after I/R or H/R injury. We found that miR-142 expression was significantly increased in clinical ischemic intestinal mucosa and mouse intestinal mucosa exposed to I/R injury, and there was an inverse relationship between miR-142 and proliferation/BF. Inhibition of miR-142 significant promoted intestinal epithelial proliferation and BF after I/R injury. Furthermore, inhibition of miR-142 improved overall survival rate of mice after I/R injury. MiR-142 directly targeted FoxM1 which was identified by bioinformatics analysis and luciferase activity assay in IEC-6 cells. Inhibition of miR-142 promotes intestinal epithelial proliferation and BF after I/R injury in a FoxM1-mediated manner.
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Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near-infrared window (NIR-II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real-time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid-responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti-inflammatory agent, Ti3C2-BSA-CQ4T-H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications.
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OBJECTIVE: Percutaneous vertebroplasty (PVP) is currently the most common surgical procedure for unstable Kummell disease (KD), but cement loosening or displacement often occurs after PVP. We had been using percutaneous pediculoplasty (PPP) or a self-developed bone cement bridging screw system to avoid this severe complication. This study intends to compare these novel surgical procedures through a 2-year follow-up evaluation. METHODS: From May 2017 to May 2021, 77 patients with single-level unstable KD were included in the PPP group, and 42 patients received the PVP-bone cement bridging screw system were included in the screw group. The changes in the vertebral body index (VBI), bisegmental Cobb angle, visual analogue scale (VAS) and Oswestry Disability Index (ODI) and the cement loosening rate and displacement rate at different follow-up time points were used to evaluate the clinical efficacy. RESULTS: There was no significant difference in VBI or bisegmental Cobb angle between the 2 groups (p > 0.05) before operation, immediately after operation and at 6-month followup, while at 1-year and 2-year postoperative evaluations, the screw group had higher VBI and bisegmental Cobb angle than the PPP group (p < 0.05). Before operation, immediately after operation, at 6-month and 1-year follow-up, there was no significant difference in VAS or ODI score between the 2 groups (p > 0.05), while at 2-year follow-up, the screw group still had higher VAS and ODI scores than the PPP group (p < 0.05). No bone cement displacement occurred in both groups, but the rate of bone cement loosening was 14.29% in group PPP, and 0 in screw group (p < 0.05). CONCLUSION: This 2-year follow-up study shows that the PVP-bone cement bridging screw system combined therapy had better midterm treatment efficacy than the PVP-PPP combined therapy in patients with unstable KD, and the bone cement bridging screw system is a preferred therapy with better anti cement loosening ability.
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BACKGROUND: In recent years, infectious diseases like COVID-19 have had profound global socio-economic impacts. mRNA vaccines have gained prominence due to their rapid development, industrial adaptability, simplicity, and responsiveness to new variants. Notably, the 2023 Nobel Prize in Physiology or Medicine recognized significant contributions to mRNA vaccine research. METHODS: Our study employed a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) database, encompassing 5,512 papers on mRNA vaccines from 2003 to 2023. We generated cooperation maps, co-citation analyses, and keyword clustering to evaluate the field's developmental history and achievements. RESULTS: The analysis yielded knowledge maps highlighting countries/institutions, influential authors, frequently published and highly cited journals, and seminal references. Ongoing research hotspots encompass immune responses, stability enhancement, applications in cancer prevention and treatment, and combating infectious diseases using mRNA technology. CONCLUSIONS: mRNA vaccines represent a transformative development in infectious disease prevention. This study provides insights into the field's growth and identifies key research priorities, facilitating advancements in vaccine technology and addressing future challenges.