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Since the advent of formamidinium (FA)-based perovskite photovoltaics (PVs), significant performance enhancements have been achieved. However, a critical challenge persists: the propensity for void formation in the perovskite film at the buried perovskite-interlayer interface has a deleterious effect on device performance. With most emerging perovskite PVs adopting the p-i-n architecture, the specific challenge lies at the perovskite-hole transport layer (HTL) interface, with previous strategies to overcome this limitation being limited to specific perovskite-HTL combinations; thus, the lack of universal approaches represents a bottleneck. Here, we present a novel strategy that overcomes the formation of such voids (microstructural defects) through a film treatment with methylammonium chloride (MACl). Specifically, our work introduces MACl via a sequential deposition method, having a profound impact on the microstructural defect density at the critical buried interface. Our technique is independent of both the HTL and the perovskite film thickness, highlighting the universal nature of this approach. By employing device photoluminescence measurements and conductive atomic force microscopy, we reveal that when present, such voids impede charge extraction, thereby diminishing device short-circuit current. Through comprehensive steady-state and transient photoluminescence spectroscopy analysis, we demonstrate that by implementing our MACl treatment to remedy these voids, devices with reduced defect states, suppressed nonradiative recombination, and extended carrier lifetimes of up to 2.3 µs can be prepared. Furthermore, our novel treatment reduces the stringent constraints around antisolvent choice and dripping time, significantly extending the processing window for the perovskite absorber layer and offering significantly greater flexibility for device fabrication.
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Understanding the maintenance and shift in reproductive strategies is a fundamental question in evolutionary research. Although many efforts have been made to compare different reproductive strategies, the association between reproductive strategies and lineage divergence is largely unknown. To explore the impact of different reproductive strategies on lineage divergence, we investigated the evolution of clonality in Saxifraga sect. Irregulares+Heterisia. By integrating several lines of evidence, we found that the loss of clonality in Irregulares+Heterisia was associated with a progressive increase in diversification rate and intraspecific morphological diversity but with a reduction in species distribution range. Our findings provide insights into the ecological and evolutionary effects of different reproductive strategies, suggesting the necessity of integrating clonality into ecological and evolutional research.
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Total leaf area per plant is an important measure of the photosynthetic capacity of an individual plant that together with plant density drives the canopy leaf area index, that is, the total leaf area per unit ground area. Because the total number of leaves per plant (or per shoot) varies among conspecifics and among mixed species communities, this variation can affect the total leaf area per plant and per canopy but has been little studied. Previous studies have shown a strong linear relationship between the total leaf area per plant (or per shoot) (A T) and the total number of leaves per plant (or per shoot) (N T) on a log-log scale for several growth forms. However, little is known whether such a scaling relationship also holds true for bamboos, which are a group of Poaceae plants with great ecological and economic importance in tropical, subtropical, and warm temperate regions. To test whether the scaling relationship holds true in bamboos, two dwarf bamboo species (Shibataea chinensis Nakai and Sasaella kongosanensis 'Aureostriatus') with a limited but large number of leaves per culm were examined. For the two species, the leaves from 480 and 500 culms, respectively, were sampled and A T was calculated by summing the areas of individual leaves per culm. Linear regression and correlation analyses reconfirmed that there was a significant log-log linear relationship between A T and N T for each species. For S. chinensis, the exponent of the A T versus N T scaling relationship was greater than unity, whereas that of S. kongosanensis 'Aureostriatus' was smaller than unity. The coefficient of variation in individual leaf area increased with increasing N T for each species. The data reconfirm that there is a strong positive power-law relationship between A T and N T for each of the two species, which may reflect adaptations of plants in response to intra- and inter-specific competition for light.
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Periodontitis, characterized by inflammation and loss of periodontal tissue, is a significant health complication for individuals with diabetes mellitus (DM). Buildup of advanced glycation end-products (AGEs) in DM poses an increased risk of periodontitis via inflammaging. Ganoderma immunomodulatory protein (GMI) shows promise in suppressing inflammaging by mitigating oxidative stress and inflammation via Nrf2 modulation. However, its specific protective effects are not fully understood. Thus, this study aimed to investigate GMI's anti-inflammaging properties and its underlying mechanism in diabetic-associated periodontitis (DP). We first simulated DP by culturing human gingival fibroblasts (HGFs) with AGEs and lipopolysaccharides from P. gingivalis (LPS). We then evaluated the impact of GMI on cell proliferation, migration and wound healing. Additionally, we assessed GMI's effects on the components of inflammaging such as reactive oxygen species (ROS) formation, cellular senescence expression, IL-6 and IL-8 secretions, and NF-κB phosphorylation. Next, we explored whether GMI's anti-inflammaging effects are mediated through the Nrf2 pathway by evaluating Nrf2 and HO-1, followed by the assessment of IL-6 and IL-8 post-Nrf2 knockdown. Our findings revealed that GMI treatment suppressed ROS production, cell senescence, IL-6 and IL-8 and NF-κB phosphorylation. Furthermore, GMI upregulated Nrf2/HO-1 expression and its protective effects were reversed when Nrf2 was knocked down. In conclusion, GMI exerts its anti-inflammaging effect via the modulation of the Nrf2/NF-κB signaling axis in DP in vitro, highlighting its potential as an effective adjunct treatment for diabetes-related periodontitis.
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Pure organic phosphorescence resonance energy transfer is a research hotspot. Herein, a single-molecule phosphorescence resonance energy transfer system with a large Stokes shift of 367 nm and near-infrared emission is constructed by guest molecule alkyl-bridged methoxy-tetraphenylethylene-phenylpyridines derivative, cucurbit[n]uril (n = 7, 8) and ß-cyclodextrin modified hyaluronic acid. The high binding affinity of cucurbituril to guest molecules in various stoichiometric ratios not only regulates the topological morphology of supramolecular assembly but also induces different phosphorescence emissions. Varying from the spherical nanoparticles and nanorods for binary assemblies, three-dimensional nanoplate is obtained by the ternary co-assembly of guest with cucurbit[7]uril/cucurbit[8]uril, accompanying enhanced phosphorescence at 540 nm. Uncommonly, the secondary assembly of ß-cyclodextrin modified hyaluronic acid and ternary assembly activates a single intramolecular phosphorescence resonance energy transfer process derived from phenyl pyridines unit to methoxy-tetraphenylethylene function group, enabling a near-infrared delayed fluorescence at 700 nm, which ultimately applied to mitochondrial targeted imaging for cancer cells.
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Transferencia Resonante de Energía de Fluorescencia , Ácido Hialurónico , Imidazoles , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Humanos , Ácido Hialurónico/química , Imidazoles/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Hidrocarburos Aromáticos con Puentes/química , Nanopartículas/química , Estilbenos/química , Piridinas/química , Células HeLa , Nanotubos/química , Mitocondrias/metabolismo , Compuestos Heterocíclicos con 2 Anillos , Compuestos Macrocíclicos , ImidazolidinasRESUMEN
Hazardous Cr(VI) continues to pose critical concerns for environmental and public health, demanding the development of effective remediation methods. In this study, thiol-functionalized black carbon (S-BC) was proposed for Cr(VI) removal by mixing thioglycolic acid (TGA) with black carbon (BC) derived from rice straw residue at 80 °C for 8 h. Using a 1:40 (g mL-1) BC-to-TGA ratio, the resulting S-BC40 sample demonstrated significantly enhanced Cr(VI) sorption capacities of 201.23, 145.78, and 106.60 mg g-1 at pH 3.5, 5.5, and 7.5, surpassing its BC counterpart by 2.0, 2.3, and 2.2 times. Additionally, S-BC40 converted all sorbed Cr into Cr(III) species at pH ≥ 5.5, resulting in an equal distribution of Cr(OH)3 and organic Cr(III) complexes. However, approximately 13% of Cr sorbed on BC remained as Cr(VI) at pH 3.5 and 7.5. Both C-centered and S-centered thiyl radicals might contribute to Cr(VI) reduction; however, sufficient C-S groups replenished via thiol-functionalization was the key for the complete Cr(VI) reduction on S-BC samples as pH ≥ 5.5. Thanks to the exceptional Cr(VI) sorption capacity, affordability, and accessibility, thiol-functionalization stands out as a promising modification method for BC. It presents a distinct opportunity to concurrently achieve the objectives of efficient Cr(VI) remediation and waste recycling.
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Carbono , Cromo , Compuestos de Sulfhidrilo , Adsorción , Cromo/química , Compuestos de Sulfhidrilo/química , Carbono/química , Contaminantes Químicos del Agua/químicaRESUMEN
Halide exchange of (Cp3tms)2ThCl2 (1; Cp3tms = η5-1,2,4-(Me3Si)3C5H2) with Me3SiI furnishes (Cp3tms)2ThI2 (2), which is then reduced with potassium graphite (KC8) in the presence of 2,2'-bipyridine to give the thorium bipyridyl metallocene (Cp3tms)2Th(bipy) (3) in good yield. Complex 3 was fully characterized and readily reacted with various small molecules. For example, 3 may serve as a synthetic equivalent for the (Cp3tms)2Th(II) fragment when exposed to CuI, Ph2S2, organic azides, and CS2. Moreover, upon the addition of thiobenzophenone Ph2CS, p-methylbenzaldehyde (p-MeC6H4)CHO, benzophenone Ph2CO, amidate PhCONH(p-tolyl), seleno-ketone (p,p'-dimethoxy), selenobenzophenone (p-MeOPh)2CSe, di(p-tolyl)methanimine (p-tolyl)2CâNH, 1,2-di(benzylidene)hydrazine (PhCHâN)2, and nitriles PhCN, PhCH2CN, and Ph2CHCN C-C coupling results to give (Cp3tms)2Th[(bipy)(Ph2CS)] (8), (Cp3tms)2Th[(bipy)(p-MePhCHO)] (9), (Cp3tms)2Th[(bipy)(Ph2CO)] (10), (Cp3tms)2Th[(bipy){(p-tolylNH)(Ph)CO}] (11), (Cp3tms)2Th[(bipy){(p-MeOPh)2CSe}] (12), (Cp3tms)2Th[(bipy){(p-tolyl)2CNH}] (13), (Cp3tms)2Th[(bipy)(PhCHNNâCHPh)] (14), (Cp3tms)2Th[(bipy)(PhCN)] (16), (Cp3tms)2Th[(bipy)(PhCH2CN)] (17), and (Cp3tms)2Th[(bipy)(Ph2CHCN)] (18), respectively. However, when thiazole is added to 3, the dimeric sulfido complex [(Cp3tms)2Th]2[µ-(bipy)CH2NCHCHS]2 (15) can be isolated. Moreover, the addition of isonitriles such as Me3CNC and PhCH2NC to 3 results in C-N bond cleavage and C-C coupling processes to form the thorium isocyanido amido complexes (Cp3tms)2Th[4-(Me3C)bipy](NC) (19) and (Cp3tms)2Th[4-(PhCH2)bipy](NC) (20), respectively. Nevertheless, upon exposure of 3 to (trimethylsilyl)diazomethane Me3SiCHN2, the bis-amido complex (Cp3tms)2Th[5,6-(Me3SiCH)bipy] (21), concomitant with N2 release, is isolated.
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Background/purpose: Oral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methods: The cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. Results: Current results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. Conclusion: In a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.
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Background/purpose: Oral submucosal fibrosis (OSF) is a premalignant disorder positively associated with betel nut chewing. Recent studies supported the promising benefits of histone deacetylase (HDAC) inhibitors for fibrosis treatment. Here we aim to clarify the pro-fibrogenic role of HDAC9 in regulating OSF. Materials and methods: Healthy and OSF specimens were collected to investigate the clinical significance of HDAC9. Chronic arecoline treatment process was used to induce arecoline-mediated myofibroblasts-related activation of primary buccal mucosa fibroblasts (BMFs). Functional analysis of collagen gel contraction, transwell migration, and wound-healing assays were performed to assess the change in pro-fibrogenic properties of BMFs and fibrotic BMFs (fBMFs). Lentiviral-mediated HDAC9 knockdown was used to verify the role of HDAC9 in the pro-fibrogenic process. Results: We found that arecoline significantly increased the mRNA and protein expression of HDAC9 of BMFs in a dose-dependent manner. Knockdown of HDAC9 in BMFs reversed the strengthened effects of arecoline on collagen gel contraction, cell migration, and wound-healing ability. We further demonstrated that knockdown of HDAC9 in fBMFs significantly attenuated its inherent pro-fibrogenic properties. Furthermore, we confirmed a significantly increased expression of HDAC9 mRNA in OSF compared to normal tissues, which suggested a positive correlation between the up-regulation of HDAC9 and OSF. Conclusion: We demonstrated that silencing of HDAC9 inhibited arecoline-induced activation and inherent pro-fibrogenic properties, suggesting potential therapeutics by targeting HDAC9 in the OSF treatment.
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PURPOSE: Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes. EXPERIMENTAL DESIGN: Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model. RESULTS: PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden. CONCLUSIONS: The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.
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Neoplasias Óseas , Óxidos N-Cíclicos , Indolizinas , Osteosarcoma , Compuestos de Piridinio , Humanos , Animales , Ratones , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Ensayos Antitumor por Modelo de Xenoinjerto , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Osteosarcoma/metabolismo , Línea Celular Tumoral , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismoRESUMEN
Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P<0.001;r=0.466,P<0.001);ADL was positively correlated with sleep quality(r=0.294,P<0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P<0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.
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Bladder cancer is one of the most prevalent cancers worldwide, with a high rate of recurrence and mortality, which is the ninth most common malignancy globally. Cystoscopy remains the gold standard for clinical bladder cancer diagnosis, but its invasive nature can lead to bacterial infection and inflammation. Urine cytology is a non-invasive and simple diagnostic method, but it has lower sensitivity in detecting low-grade bladder cancer and may yield false negative results. Therefore, identifying ideal diagnostic and prognostic biomarkers is crucial for accurate diagnosis and effective treatment of bladder cancer. Aptamers, characterized as single-stranded DNA or RNA with unique three-dimensional conformations, exhibit the ability to identify various targets, ranging from small molecules to tumor cells. Aptamers, also known as chemical antibodies, are generated by systematic evolution of ligands by exponential enrichment (SELEX) process and can function similarly to traditional antibodies. They hold numerous advantages over antibodies, such as ease of modification, low immunogenicity, and rapid tissue penetration and cell internalization due to their nucleic acid molecule structure. Since their discovery in the 1990s, aptamers have been widely used in biochemical analysis, disease detection, new drug research and other fields. This article provides an overview of aptamer selection and characterization for bladder cancer, discussing the research advancements involving aptamers in diagnosing and treating this disease. It covers aptamers obtained through different SELEX methods, including protein-SELEX, cell-SELEX, tissue-SELEX, and aptamers from other cancer SELEX; the detection in blood samples and urine samples; and application in targeted therapy and immunotherapy for bladder cancer. Currently, several aptamers capable of identifying bladder cancer have been generated, serving as molecular probes that have played a pivotal role in the early detection and treatment of bladder cancer. Bladder cancer perfusion therapy is well-suited for aptamer drug therapy because it does not require internal circulation, making it a suitable clinical indication for aptamer drug development. In addition, bladder cancer can be detected and monitored by collecting urine samples from patients, making it a preferred disease for clinical conversion of aptamers. While aptamers show promise, there is still much room for development compared with antibodies. There are still many clinically applied cancer biomarkers without corresponding aptamers, and more aptamers targeting different biomarkers should be selected and optimized to improve the sensitivity and accuracy for cancer detection and therapy. The field of aptamers urgently needs successful commercial products to promote its development, and home rapid detection/monitoring, imaging and targeted therapy of bladder cancer by infusion may be the breakthrough point for future application of aptamers.
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The structure of and bonding in two base-free terminal actinide imido metallocenes, [η5-1,2,4-(Me3C)3C5H2]2AnâN(p-tolyl) (An = U (1), Th (1')) are compared and connected to their individual reactivity. While structurally rather similar, the U(IV) derivative 1 is slightly more sterically crowded. Furthermore, density functional theory (DFT) studies imply that the 5f orbital contribution to the bonding within the individual actinide imido AnâN(p-tolyl) moieties is significantly larger for 1 than for 1', which makes the bonds between the [η5-1,2,4-(Me3C)3C5H2]2U2+ and [(p-tolyl)N]2- fragments more covalent. Therefore, steric and electronic factors impact the reactivity of these imido complexes. For example, complex 1 is inert toward internal alkynes, but it readily forms Lewis base adducts [η5-1,2,4-(Me3C)3C5H2]2UâN(p-tolyl)(L) (L = OPMe3 (6), dmap (9), PhCN (14), and 2,6-Me2PhNC (17)) with Me3PO, 4-dimethylaminopyridine (dmap), nitrile, PhCN, or isonitrile 2,6-Me2PhNC. It may also react as a nucleophile or undergo a [2 + 2] cycloaddition with CS2, isothiocyanates, thio-ketones, ketones, lactides, and acyl nitriles, forming the four- or five-membered metallaheteroacycles, terminal sulfido, or oxido complexes, and cyanide amidate complexes, respectively. In contrast, after the addition of aldehyde p-tolylCHO, the tetranuclear complex [η5-1,2,4-(Me3C)3C5H2]4[OCH(p-tolyl)CH(p-tolyl)O]2U4O4 (10) is isolated. However, while 1 is unreactive toward dicyclohexylcarbodiimide (DCC), an equilibrium exists in benzene solution between N,N'-diisopropylcarbodiimide (DIC), 1, and the four-membered metallaheterocycle [η5-1,2,4-(Me3C)3C5H2]2U[N(p-tolyl)C(âNiPr)N(iPr)] (12). Furthermore, 1 may also engage in single- and two-electron transfer processes. It is singly oxidized by Ph3CN3, CuI, Ph2S2, and Ph2Se2, yielding the uranium(V) imido complexes [η5-1,2,4-(Me3C)3C5H2]2UâN(p-tolyl)(X) (X = N3 (20), I (22), PhS (23), and PhSe (24)), or is doubly oxidized by organic azides (RN3) and 9-diazofluorene, forming the uranium(VI) bis-imido metallocenes [η5-1,2,4-(Me3C)3C5H2]2UâN(p-tolyl)(=NR) (R = p-tolyl (18), mesityl (19)) and [η5-1,2,4-(Me3C)3C5H2]2U=N(p-tolyl)[=NN=(9-C13H8)] (21), respectively.
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Background: Recent research has demonstrated that machine learning (ML) has the potential to improve several aspects of medical application for critical illness, including sepsis. This scoping review aims to evaluate the feasibility of probabilistic graphical model (PGM) methods in pediatric sepsis application and describe the use of pediatric sepsis definition in these studies. Methods: Literature searches were conducted in PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL+), and Web of Sciences from 2000-2023. Keywords included "pediatric", "neonates", "infants", "machine learning", "probabilistic graphical model", and "sepsis". Results: A total of 3,244 studies were screened, and 72 were included in this scoping review. Sepsis was defined using positive microbiology cultures in 19 studies (26.4%), followed by the 2005's international pediatric sepsis consensus definition in 11 studies (15.3%), and Sepsis-3 definition in seven studies (9.7%). Other sepsis definitions included: bacterial infection, the international classification of diseases, clinicians' assessment, and antibiotic administration time. Among the most common ML approaches used were logistic regression (n=27), random forest (n=24), and Neural Network (n=18). PGMs were used in 13 studies (18.1%), including Bayesian classifiers (n=10), and the Markov Model (n=3). When applied on the same dataset, PGMs show a relatively inferior performance to other ML models in most cases. Other aspects of explainability and transparency were not examined in these studies. Conclusions: Current studies suggest that the performance of probabilistic graphic models is relatively inferior to other ML methods. However, its explainability and transparency advantages make it a potentially viable method for several pediatric sepsis studies and applications.
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The dysregulated expression of cyclin genes can lead to the uncontrolled proliferation of cancer cells. Histone demethylase Jumonji-C domain-containing protein 5 (KDM8, JMJD5) and cyclin A1 (CCNA1) are pivotal in cell cycle progression. A promising candidate for augmenting cancer treatment is Allyl isothiocyanate (AITC), a natural dietary chemotherapeutic and epigenetic modulator. This study aimed to investigate AITC's impact on the KDM8/CCNA1 axis to elucidate its role in oral squamous cell carcinoma (OSCC) tumorigenesis. The expression of KDM8 and CCNA1 was assessed using a tissue microarray (TMA) immunohistochemistry (IHC) assay. In vitro experiments with OSCC cell lines and in vivo experiments with patient-derived tumor xenograft (PDTX) and SAS subcutaneous xenograft tumor models were conducted to explore AITC's effects on their expression and cell proliferation. The results showed elevated KDM8 and CCNA1 levels in the OSCC patient samples. AITC exhibited inhibitory effects on OSCC tumor growth in vitro and in vivo. Additionally, AITC downregulated KDM8 and CCNA1 expression while inducing histone H3K36me2 expression in oral cancer cells. These findings underscore AITC's remarkable anticancer properties against oral cancer, highlighting its potential as a therapeutic option for oral cancer treatment by disrupting the cell cycle by targeting the KDM8/CCNA1 axis.
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Uranium diazomethanediide complexes can be prepared and their synthesis, structure and reactivity were explored. Reaction of the uranium imido compound [η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 U=N(p-tolyl)(dmap) (1) or [η5 -1,3-(Me3 C)2 C5 H3 ]2 U=N(p-tolyl)(dmap) (4) with Me3 SiCHN2 cleanly yields the first isocyanoimido metal complexes [η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 U(=NNC)(µ-CNN=)U(dmap)[η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 (2) and {[η5 -1,3-(Me3 C)2 C5 H3 ]2 U[µ-(=NNC)]}6 (5), respectively. Both compounds exhibit remarkable thermal stability and were fully characterized. According to density functional theory (DFT) studies the bonding between the Cp2 U2+ and [NNC]2- moieties is strongly polarized with a significant 5 f orbital contribution, which is also reflected in the reactivity of these complexes. For example, complex 5 acts as a nucleophile toward alkylsilyl halides and engages in a [2+2] cycloaddition with CS2 , but no reaction occurs in the presence of internal alkynes.
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The Lewis base-supported uranium terminal imido metallocene [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(dmap) (1) readily reacts with various small molecules such as internal alkynes, isothiocyanates, thioketones, amidates, organic nitriles and imines, chlorosilanes, copper iodide, diphenyl disulfide, organic azides and diazoalkane derivatives. For example, treatment of 1 with PhCîCCîCPh and PhNCS forms metallaheterocycles originating from a [2 + 2] cycloaddition to yield [η5-1-(p-tolyl)NC(Ph)îCHCîC(Ph)CH2Si(Me)2-2,4-(Me3Si)2C5H2][η5-1,2,4-(Me3Si)3C5H2]U (2) and [η5-1,2,4-(Me3Si)3C5H2]2U[N(p-tolyl)C(îNPh)S](dmap) (3), respectively. The reaction of 1 with the thioketone Ph2CS forms the known uranium sulfido complex [η5-1,2,4-(Me3Si)3C5H2]2US(dmap) (4), which reacts with a second molecule of Ph2CS to give the disulfido compound [η5-1,2,4-(Me3Si)3C5H2]2U(S2CPh2) (5). The imido moiety also promotes deprotonation reactions as illustrated in the reactions with the amide PhCONH(p-tolyl), the nitrile PhCH2CN and the imine (p-tolyl)2CîNH to form the bis-amidate [η5-1,2,4-(Me3Si)3C5H2]2U[OC(Ph)N(p-tolyl)]2 (7), and the iminato complexes [η5-1,2,4-(Me3Si)3C5H2]2U[N(p-tolyl)C(CH2Ph)îNH](NîCîCHPh) (8) and [η5-1,2,4-(Me3Si)3C5H2]2U[NH(p-tolyl)][NîC(p-tolyl)2] (9), respectively. Addition of PhSiH2Cl to 1 yields [η5-1,2,4-(Me3Si)3C5H2]2U(Cl)[N(p-tolyl)SiH2Ph] (10). In contrast, the uranium(V) imido complexes [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(I) (11) and [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(SPh) (12), may be isolated upon addition of CuI or Ph2S2 to 1, respectively. Uranium(VI) bis-imido metallocenes [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(îNR) (R = p-tolyl (13), mesityl (14)) and [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)[îNNî(9-C13H8)] (15) are accessible from 1 on exposure to RN3 (R = p-tolyl, mesityl) and 9-diazofluorene, respectively. Complexes 2, 3, 5, and 7-15 were characterized by various spectroscopic techniques and, in addition, compounds 2, 3, 5, and 7-13 were structurally authenticated by single-crystal X-ray diffraction analyses.
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Impaired kidney function is associated with increased morbidity and mortality in patients undergoing liver transplantation. Although immunosuppressants are essential in these patients, they impair kidney function. This study aimed to compare adverse kidney outcomes between patients treated with a reduced dose of tacrolimus (calcineurin inhibitor) plus sirolimus or mycophenolate mofetil (MMF) in the liver transplant center at Kaohsiung Chang Gung Memorial Hospital between April 2011 and December 2017. Propensity score matching was used to identify 232 patients. The risk of adverse kidney outcomes was estimated using Cox proportional hazards regression, and changes in kidney function over time were analyzed using linear mixed modeling. Acute kidney disease risks in this study cohort were not significantly different for the two immunosuppressants (aHR 1.04; 95% CI: 0.70-1.55, p = 0.8328). However, sirolimus use was significantly associated with a higher risk of estimated glomerular filtration rate decline > 30% than MMF (aHR, 2.09; 95% CI: 1.33-3.28; p = 0.0014). Our results demonstrate that sirolimus use may have worsened long-term kidney outcomes compared to MMF. Close monitoring of kidney function, dose adjustment, and timely transition to MMF is necessary for LT patients receiving sirolimus.
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Terminal uranium oxido, sulfido, and selenido metallocenes were synthesized, and their reactivity was comprehensively studied. Heating of an equimolar mixture of [η5-1,2,4-(Me3Si)3C5H2]2UMe2 (2) and [η5-1,2,4-(Me3Si)3C5H2]2U(NH-p-tolyl)2 (3) in the presence of 4-dimethylaminopyridine (dmap) in refluxing toluene forms [η5-1,2,4-(Me3Si)3C5H2]2UâN(p-tolyl)(dmap) (4), which is a useful precursor for the preparation of the terminal uranium oxido, sulfido, and selenido metallocenes [η5-1,2,4-(Me3Si)3C5H2]2UâE(dmap) (E = O (5), S (6), Se (7)) employing a cycloaddition-elimination methodology with Ph2CâE (E = O, S) or (p-MeOPh)2CSe, respectively. Metallocenes 5-7 are inert toward alkynes, but they act as nucleophiles in the presence of alkylsilyl halides. The oxido and sulfido metallocenes 5 and 6 undergo [2 + 2] cycloadditions with isothiocyanate PhNCS or CS2, while the selenido derivative 7 does not. The experimental studies are complemented by density functional theory (DFT) computations.
RESUMEN
Background/purpose: Oral submucous fibrosis (OSF) is a premalignant disorder that is associated with betel nut chewing. The purpose of the study was to establish the role of histone deacetylase (HDAC) 8, one of histone deacetylases, in the regulation of fibrotic conditions to provide a therapeutic potential for OSF. Materials and methods: First, we examined the expression of HDAC8 in fibrotic buccal mucosal fibroblasts (fBMFs) and OSF tissues. Markers of myofibroblasts and TGF-ß signaling were conducted in fBMFs with HDAC8 knockdown were examined. Furthermore, epithelial-mesenchymal transition (EMT) markers, collagen gel contraction and migration ability were also examined in fBMFs transfected with sh-HDAC8. HDAC8 inhibitor was used to analyze the collagen gel contraction and wound healing ability in fBMFs. Results: We observed the mRNA expression of HDAC8 was significantly increased in fBMFs. Compared to normal tissues, the protein level of HDAC8 was upregulated in OSF. Next, mRNA and protein expression of HDAC8 was significantly decreased, accompanying downregulation of α-SMA and COL1A1 in fBMFs infected with sh-HDAC8. To determine the critical role of HDAC8 in OSF fibrogenesis, results revealed that TGF-ß secretion and the expression of EMT transcription factor SNAIL and p-Smad were significantly decreased in HDAC8-knockdown fBMFs. We further demonstrated that collagen gel contraction and migration ability were significantly decreased in fBMFs transfected with sh-HDAC8. Last, results revealed that significantly reduced collagen gel contraction and wound healing ability in fBMFs with HDAC8 inhibitor treatment. Conclusion: We concluded that downregulation of HDAC8 alleviated the activities of myofibroblasts and TGF-ß/Smad signaling pathway in OSF.