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Developing effective electrocatalysts for the nitrate reduction reaction (NO3RR) is a promising alternative to conventional industrial ammonia (NH3) synthesis. Herein, starting from a flexible laser-induced graphene (LIG) film with hierarchical and interconnected macroporous architecture, a binder-free and free-standing Ru-modified LIG electrode (Ru-LIG) is fabricated for electrocatalytic NO3RR via a facile electrodeposition method. The relationship between the laser-scribing parameters and the NO3RR performance of Ru-LIG electrodes is studied in-depth. At -0.59 VRHE, the Ru-LIG electrode exhibited the optimal and stable NO3RR performance (NH3 yield rate of 655.9 µg cm-2 h-1 with NH3 Faradaic efficiency of up to 93.7%) under a laser defocus setting of +2 mm and an applied laser power of 4.8 W, outperforming most of the reported NO3RR electrodes operated under similar conditions. The optimized laser-scribing parameters promoted the surface properties of LIG with increased graphitization degree and decreased charge-transfer resistance, leading to synergistically improved Ru electrodeposition with more exposed NO3RR active sites. This work not only provides a new insight to enhance the electrocatalytic NO3RR performance of LIG-based electrodes via the coordination with metal electrocatalysts as well as identification of the critical laser-scribing parameters but also will inspire the rational design of future advanced laser-induced electrocatalysts for NO3RR.
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Enhancing the flame retardancy of epoxy (EP) resins typically entailed a trade-off with other physical properties. Herein, hyperbranched poly(amidoamine) (HPAA) and phytic acid (PA) were used to functionalize graphene oxide (GO) via electrostatic self-assembly in water to prepare a phosphorus-nitrogen functionalized graphene oxide nanosheet (PN-GOs), which could be utilized as high efficient flame-retardant additive of epoxy resin without sacrificing other properties. The PN-GOs demonstrated improved dispersion and compatibility within the EP matrix, which resulted in significant concurrent enhancements in both the mechanical performance and flame-retardant properties of the PN-GOs/EP nanocomposites over virgin EP. Notably, the incorporation of just 1.0 wt% PN-GOs yielded a 20.4, 6.4 and 42.7 % increases in flexural strength, flexural modulus and impact strength for the PN-GOs/EP nanocomposites, respectively. Furthermore, simultaneous reductions were achieved in the peak heat release rate (pHRR) by 60.0 %, total smoke production (TSP) by 43.0 %, peak CO production rate (pCOP) by 57.9 %, and peak CO2 production rate (pCO2P) by 63.9 %. This study presented a facile method for the design of GO-based nano flame retardants, expanding their application potential in polymer-matrix composites.
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Designing cost-effective electrocatalysts for water decomposition is crucial for achieving environmental-friendly hydrogen production. A transition metal sulfide/hydroxide electrocatalyst (1T-MoS2/Ni3S2/LDH) with double heterogeneous interfaces was developed through a two-step hydrothermal assisted electrodeposition method. The presence of the two built-in electric fields not only accelerated the charge transfer at the interface, but also enhanced the adsorption of the reactants and intermediate groups, and therefore improved the reaction rate and overall catalytic performance. The results suggest that the 1T-MoS2/Ni3S2/LDH catalysts display exceptional electrocatalytic reactivity. Under alkaline conditions, the overpotential of the electrocatalyst was 187 (η50) mV for OER and 104 (η10) mV for HER. Furthermore, the two-electrode system assembled by the electrocatalyst needs only a voltage of 1.55 V to deliver a current density of 10 mA cm-2. Our result provides a simple and effective methodical approach to the design of dual heterogeneous interfacial electrocatalysts.
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Aged nanoplastics (aged-NPs) have unique characteristics endowed by environmental actions, such as rough surface, high oxygen content. Although studies have highlighted the potential hazards of aged-NPs, limited research has provided strategies for aged-NPs pollution remediation. The dietary intervention of quercetin is a novel insight to address the health risks of aged-NPs. This study explored the impact of aged-NPs on intestinal barrier homeostasis at the environmentally relevant dose and investigated the alleviating effects of quercetin on aged-NPs toxicity through transcriptomics and molecular biology analysis. It indicated that aged-NPs induced intestinal barrier dysfunction, which was characterized by higher permeability, increased inflammation, and loss of epithelial integrity, while quercetin restored it. Aged-NPs disrupted redox homeostasis, upregulated inflammatory genes controlled by AP-1, and led to Bax-dependent mitochondrial apoptosis. Quercetin intervention effectively mitigated inflammation and apoptosis by activating the Nrf2. Thus, quercetin decreased intestinal free radical levels, inhibiting the phosphorylation of p38 and JNK. This study unveiled the harmful effects of aged-NPs on intestinal homeostasis and the practicability of dietary intervention against aged-NPs toxicity. These findings broaden the understanding of the NPs toxicity and provide an effective dietary strategy to relieve the health risks of NPs. ENVIRONMENTAL IMPLICATIONS: Growing levels of NPs pollution have represented severe health hazards to the population. This study focuses on the toxic mechanism of aged-NPs on the intestinal barrier and the alleviating effect of quercetin dietary intervention, which considers the environmental action and relevant dose. It revealed the harmful effects of aged-NPs on intestinal inflammation with the key point of free radical generation. Furthermore, a quercetin-rich diet holds significant promise for addressing and reversing intestinal damage caused by aged-NPs by maintaining intracellular redox homeostasis. These findings provide an effective dietary strategy to remediate human health risks caused by NPs.
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Homeostase , Nanopartículas , Quercetina , Quercetina/farmacologia , Homeostase/efeitos dos fármacos , Humanos , Nanopartículas/toxicidade , Nanopartículas/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Apoptose/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Células CACO-2 , Antioxidantes/farmacologiaRESUMO
KEY MESSAGE: Lilium tsingtauense mitogenome comprises 27 independent chromosome molecules, it undergoes frequent genomic recombination, and the rate of recombination and mutation between different repetitive sequences affects the formation of multichromosomal structures. Given the extremely large genome of Lily, which likely harbors additional genetic resources, it serves as an ideal material for studying the phylogenetic evolution of organisms. Although the Lilium chloroplast genome has been documented, the sequence of its mitochondrial genome (mitogenome) remains uncharted. Using BGI short reads and Nanopore long reads, we sequenced, assembled, and annotated the mitogenome of Lilium tsingtauense. This effort culminated in the characterization of Lilium's first complete mitogenome. Comparative analysis with other angiosperms revealed the unique multichromosomal structure of the L. tsingtauense mitogenome, spanning 1,125,108 bp and comprising 27 independent circular chromosomes. It contains 36 protein-coding genes, 12 tRNA genes, and 3 rRNA genes, with a GC content of 44.90%. Notably, three chromosomes in the L. tsingtauense mitogenome lack identifiable genes, hinting at the potential existence of novel genes and noncoding elements. The high degree of observed genome fragmentation implies frequent reorganization, with recombination and mutation rates among diverse repetitive sequences likely driving the formation of multichromosomal structures. Our comprehensive analysis, covering genome size, coding genes, structure, RNA editing, repetitive sequences, and sequence migration, sheds light on the evolutionary and molecular biology of multichromosomal mitochondria in Lilium. This high-quality mitogenome of L. tsingtauense not only enriches our understanding of multichromosomal mitogenomes but also establishes a solid foundation for future genome breeding and germplasm innovation in Lilium.
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Cromossomos de Plantas , Genoma Mitocondrial , Lilium , Filogenia , Genoma Mitocondrial/genética , Lilium/genética , Cromossomos de Plantas/genética , RNA de Transferência/genética , Genoma de Planta/genética , Composição de Bases/genéticaRESUMO
There is growing attention focused toward the problems of ecological sustainability and food safety raised from the abuse of herbicides, which underscores the need for the development of a portable and reliable sensor for simple, rapid, and user-friendly on-site analysis of herbicide residues. Herein, a novel multifunctional hydrogel composite is explored to serve as a portable and flexible sensor for the facile and efficient analysis of atrazine (ATZ) residues. The hydrogel electrode is fabricated by doping graphite-phase carbon nitride (g-C3N4) into the aramid nanofiber reinforced poly(vinyl alcohol) hydrogel via a simple solution-casting procedure. Benefiting from the excellent electroactivity and large specific surface area of the solid nanoscale component, the prepared hydrogel sensor is capable of simple, rapid, and sensitive detection of ATZ with a detection limit down to 0.002 ng/mL and per test time less than 1 min. After combination with a smartphone-controlled portable electrochemical analyzer, the flexible sensor exhibited satisfactory analytical performance for the ATZ assay. We further demonstrated the applications of the sensor in the evaluation of the ATZ residues in real water and soil samples as well as the user-friendly on-site point-of-need detection of ATZ residues on various agricultural products. We envision that this flexible and portable sensor will open a new avenue on the development of next-generation analytical tools for herbicide monitoring in the environment and agricultural products.
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Atrazina , Técnicas Eletroquímicas , Herbicidas , Hidrogéis , Atrazina/análise , Herbicidas/análise , Hidrogéis/química , Técnicas Eletroquímicas/instrumentação , Grafite/química , Eletrodos , Limite de Detecção , Nitrilas/química , Nitrilas/análise , Nanofibras/química , Poluentes Químicos da Água/análiseRESUMO
The slow redox rate of hydrogen peroxide (H2O2) in neutral environments makes the H2O2 sensor inadequate for the detection of low levels of signalling molecules. The aim of this study is to fabricate a flexible sensing electrode by hydrothermally loading micro-nanometer Ni and Co(OH)2 on carbon cloth (CC) and electrochemically depositing poly(3,4-ethylenedioxythiophene) (PEDOT) on the surface of the electrode. The sensor presented high sensitivity (10.43 mA mM-1 cm-2), a wide detection range (0.033-120.848 mM), a low detection limit (0.92 nM), high stability, and excellent anti-interference performance in neutral solutions. Ni-Co(OH)2 provides abundant active sites while CC solves their agglomeration phenomenon and conductivity. The PEDOT film offers heightened conductivity, hydrophilicity, interfacial stability, and an electrochemically active surface area (ECSA). The side area of the chrysanthemum petal like PEDOT is 39 ± 7 times the bottom area, and PEDOT increases the ECSA of the composite to six times that of CC. Electrochemical precise control of PEDOT morphology to improve sensor performance provides a new strategy for the application of PEDOT in sensors.
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The rational design of the dimension and geometry of a plasmonic semiconductor cocatalyst is vitally important for efficient utilization of near-infrared (NIR) light and superior photocatalytic hydrogen generation. Herein, hollow cubic CuSe@CdS composites with different sizes and strong localized surface plasmon resonance (LSPR) were prepared by selenizing size-tunable Cu2O templates and loading CdS nanoparticles. The size of hollow cubic CuSe can affect the surface area and the conduction band potential through the size effect, regulating the carrier behavior of the CuSe@CdS heterojunction. The CuSe@CdS composites show enhanced and wide absorption in the full spectrum due to the LSPR effect of CuSe. Meanwhile, the composites show excellent photocatalytic hydrogen capacity in the full spectrum in a 0.35 M Na2S/0.25 M Na2SO3 sacrificial reagent solution. The best hydrogen production rate of CSCE2 is 1.518 mmol g-1 h-1 (5.54 times higher than that of CdS) under Vis light (780 > λ > 420 nm) irradiation and 0.28 mmol g-1 h-1 under NIR light (λ > 780 nm) illumination. Interestingly, the photocatalytic activity for H2 under Vis-NIR light (λ > 420 nm) is about 3 times (up to 4.45 mmol g-1 h-1) higher than that without NIR light assistance, due to the photothermal effect. Various analyses and DFT calculations demonstrate that the p-n heterojunction formed in the composites consists of p-type CuSe and n-type CdS, which achieves efficient carrier transfer and separation under the synergistic effect of the size effect and the photothermal effect. In addition, the expansion of the photocatalytic performance to the NIR range is mainly due to the "hot-electron" injection mechanism induced by the LSPR effect of CuSe. The reasonable design coupled with the plasmonic materials offers a new path to achieving the highly efficient conversion of solar energy to hydrogen energy.
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Heterotrimeric G-proteins are key modulators of multiple signaling and developmental pathways in plants, in which they act as molecular switches to engage in transmitting various stimuli signals from outside into the cells. Substantial studies have identiï¬ed G proteins as essential components of the organismal response to abiotic stress, leading to adaptation and survival in plants. Meanwhile, sugars are also well acknowledged key players in stress perception, signaling, and gene expression regulation. Connections between the two significant signaling pathways in stress response are of interest to a general audience in plant biology. In this article, advances unraveling a pivotal role of G proteins in the process of sugar signals outside the cells being translated into the operation of autophagy in cells during stress are reviewed. In addition, we have presented recent findings on G proteins regulating the response to drought, salt, alkali, cold, heat and other abiotic stresses. Perspectives on G-protein research are also provided in the end. Since G protein signaling regulates many agronomic traits, elucidation of detailed mechanism of the related pathways would provide useful insights for the breeding of abiotic stress resistant and high-yield crops.
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Proteínas Heterotriméricas de Ligação ao GTP , Proteínas de Plantas , Transdução de Sinais , Estresse Fisiológico , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Açúcares/metabolismo , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Fenômenos Fisiológicos VegetaisRESUMO
Saline-alkali stress is an important abiotic stress factor affecting tomato (Solanum lycopersicum L.) plant growth. Although the involvement of the tomato SlWRKY gene family in responses to saline-alkali stress has been well established, the mechanism underlying resistance to saline-alkali stress remains unclear. In this study, we investigated the role of SlWRKY81 in conferring saline-alkali stress resistance by using overexpression and knockout tomato seedlings obtained via genetic modification. We demonstrated that SlWRKY81 improves the ability of tomato to withstand saline-alkali stress by enhancing antioxidant capacity, root activity, and proline content while reducing malondialdehyde levels. Saline-alkali stress induces an increase in jasmonic acid (JA) content in tomato seedlings, and the SlWRKY81 promoter responds to JA signaling, leading to an increase in SlWRKY81 expression. Furthermore, the interaction between SlJAZ1 and SlWRKY81 represses the expression of SlWRKY81. SlWRKY81 binds to W-box motifs in the promoter regions of SlSPDS2 and SlNHX4, thereby positively regulating their expression. This regulation results in increased spermidine (Spd) content and enhanced potassium (K+) absorption and sodium (Na+) efflux, which contribute to the resistance of tomato to saline-alkali stress. However, JA and SlJAZ1 exhibit antagonistic effects. Elevated JA content reduces the inhibitory effect of SlJAZ1 on SlWRKY81, leading to the release of additional SlWRKY81 protein and further augmenting the resistance of tomato to saline-alkali stress. In summary, the modulation of Spd synthesis and Na+/K+ homeostasis mediated by the interaction between SlWRKY81 and SlJAZ1 represents a novel pathway underlying tomato response to saline-alkali stress.
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Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Potássio , Sódio , Solanum lycopersicum , Espermidina , Álcalis/metabolismo , Ciclopentanos/metabolismo , Homeostase , Oxilipinas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Potássio/metabolismo , Plântula/genética , Plântula/metabolismo , Plântula/fisiologia , Transdução de Sinais , Sódio/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Espermidina/metabolismoRESUMO
Objective: Obesity has become a global health issue and a risk factor for hyperuricemia. However, the associations between obesity and hyperuricemia are sometimes confounding. In the present study, we performed mendelian randomization (MR) analysis to study their relationship and investigate the underlying mechanism by network pharmacology. Method: Body mass index (BMI) and uric acid related to single nucleotide polymorphism were selected as instrumental variables for MR analysis. Three robust analytical methods are used for bidirectional MR analysis such as inverse-variance weighting, weighted median and MR-Egger regression. Then, we further performed sensitivity analysis to evaluate the horizontal pleiotropy, heterogeneities, and stability. The targets related to obesity and hyperuricemia were collected, screened and further conducted for Kyoto Encyclopedia of Genes and Genomes pathway enrichment to explore the mechanism of obesity and hyperuricemia using network pharmacology. Results: The positive causality was indicated between BMI and hyperuricemia based on inverse variance-weighted analysis [odds ratio:1.23, 95% confidence interval: 1.11 to 1.30 for each standard deviation increase in BMI (4.6 kg/m2)]. Conversely, hyperuricemia did not influence BMI. 235 intersected targets from obesity and hyperuricemia were collected. Insulin resistance were the top 1 key target. The mechanism between obesity and hyperuricemia are associated with important pathways including adipocytokine signaling pathway, insulin resistance and cholesterol metabolism et al. Conclusions: Our MR analysis supported the causal association between obesity and hyperuricemia based on availablegenome-wide association analysis summary statistics. Obesity leads to hyperuricemia via insulin resistance, which is a key link in the huge network pathways using network pharmacology.
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Mixed panel count data represent a common complex data structure in longitudinal survey studies. A major challenge in analyzing such data is variable selection and estimation while efficiently incorporating both the panel count and panel binary data components. Analyses in the medical literature have often ignored the panel binary component and treated it as missing with the unknown panel counts, while obviously such a simplification does not effectively utilize the original data information. In this research, we put forward a penalized likelihood variable selection and estimation procedure under the proportional mean model. A computationally efficient EM algorithm is developed that ensures sparse estimation for variable selection, and the resulting estimator is shown to have the desirable oracle property. Simulation studies assessed and confirmed the good finite-sample properties of the proposed method, and the method is applied to analyze a motivating dataset from the Health and Retirement Study.
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Algoritmos , Funções Verossimilhança , Simulação por Computador , Estudos LongitudinaisRESUMO
While performing oxygen-related tumour treatments such as chemotherapy and photodynamic therapy, real-time monitoring hypoxia of tumour is of great value and significance. Here, we design a theranostic combination for light-activated ratiometric hypoxia imaging, hypoxia modulating and prodrug activation. This combination consisted of an oxygen-sensitive near-infrared-emitting ratiometric phosphorescence probe and a hypoxia-activated prodrug-loaded covalent organic framework. In this combination, the probe plays two roles, including quantitative monitoring of oxygen concentration by ratiometric imaging and consuming the oxygen of tumour under light excitation by photodynamic therapy. Meanwhile, the enhanced hypoxia microenvironment of tumour can raise the cytotoxicity of prodrug loaded in covalent organic framework, resulting in boosting antitumour therapeutic effects in vivo. This theranostic combination can precisely provide therapeutic regime and screen hypoxia-activated prodrugs based on real-time tumour hypoxia level, offering a strategy to develop hypoxia mediated tumour theranostics with hypoxia targeted prodrugs.
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Estruturas Metalorgânicas , Neoplasias , Fotoquimioterapia , Pró-Fármacos , Humanos , Medicina de Precisão , Oxigênio , Estruturas Metalorgânicas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Hipóxia/tratamento farmacológico , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Nanomedicina Teranóstica , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente TumoralRESUMO
Objective: Radiation pneumonitis (RP) is the major adverse response of radiation therapy for thoracic malignant tumors, and there is a lack of effective interventions. The aim of this study was to investigate the radioprotective effect of Glycyrrhizin (GL) on RP and its potential mechanism. Method: The body weight and lung weight of mice were monitored. HE staining was used to observe lung injury, and the expression of endoplasmic reticulum (ER) stress biomarkers and the activation of NLRP3 inflammasome were determined by Western blotting and immunohistochemistry. Flow cytometry was performed to check MLE-12 apoptosis. ER stress activator, Tunicamycin (Tuni), was used to verify the potential mechanism of GL. A systemic pharmacology explored the potential targets and pathways of GL. Results: In this study, the lungs of irradiated mice showed significant pneumonic changes. In vivo and in vitro assay, NLRP3 inflammasome was significantly activated, the expression of ER stress biomarkers was elevated, flow cytometry confirms increased apoptosis in irradiated MLE-12 cells. GL inhibits the activation of NLRP3 inflammasome and ER stress pathways. Furthermore, systemic pharmacology revealed that the radioprotective effect of GL may be related to the MAPK signaling pathway. Conclusion: In the present study, the results indicated that GL may regulate NLRP3 inflammasome through ER stress, thus exerting irradiation-protective effects on RP, and the ER stress pathway may be a potential target for RP treatment.
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PURPOSE: This research aimed to develop a prediction model to assess bladder wall dosimetry during radiotherapy for patients with pelvic tumors, thereby facilitating the refinement and evaluation of radiotherapy treatment plans to mitigate bladder toxicity. METHODS: Radiotherapy treatment plans of 49 rectal cancer patients and 45 gynecologic cancer patients were collected, and multiple linear regression analyses were used to generate prediction models for bladder wall dose parameters ( V 10 - 45 G y ( c m 3 ) ${V_{10 - 45Gy\ }}( {{\mathrm{c}}{{\mathrm{m}}^3}} )$ , D m e a n ( Gy ) ${D_{mean}}( {{\mathrm{Gy}}} )$ ). These models were based on the multiscale spatial relationship between the planning target volume (PTV) and the bladder or bladder wall. The proportion of bladder or bladder wall volume overlapped by the different distance expansions of the PTV was used as an indicator of the multiscale spatial relationship. The accuracy of these models was verified in a cohort of 12 new patients, with further refinement of radiotherapy treatment plans using the predicted values as optimization parameters. Model accuracy was assessed using root mean square error (RMSE) and mean percentage error (MPE). RESULTS: Models derived from individual disease data outperformed those derived from combined datasets. Predicted bladder wall dose parameters were accurate, with the majority of initial calculated values for new patients falling within the 95% confidence interval of the model predictions. There was a robust correlation between the predicted and actual dose metrics, with a correlation coefficient of 0.943. Using the predicted values to optimize treatment plans significantly reduced bladder wall dose (p < $\ < \ $ 0.001), with bladder wall D mean ( G y ) ${D_{{\mathrm{mean}}}}( {Gy} )$ and V 10 - 45 G y ( c m 3 ) ${V_{10 - 45Gy\ }}( {{\mathrm{c}}{{\mathrm{m}}^3}} )$ decreasing by 2.27±0.80 Gy (5.8%±1.8%) and 2.96±2.05 cm3 (7.9%±5.4%), respectively. CONCLUSION: The formulated prediction model provides a valuable tool for predicting and minimizing bladder wall dose and for optimizing and evaluating radiotherapy treatment plans for pelvic tumor patients. This approach holds promise for reducing bladder toxicity and potentially improving patient outcomes.
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Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Humanos , Feminino , Bexiga Urinária , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
OBJECTIVE: The present study aimed to elucidate mechanisms of liothyronine on the treatment of ischemic stroke (IS). METHODS: Differential analysis based on R limma package was used to identify differentially expressed genes, which were then mapped into the connectivity map database for identification of liothyronine associated with IS. Tumor necrosis factor (TNF) signaling pathway was verified through pathway enrichment analysis via Enrichr online. Ischemia stroke mouse model was built up for further analysis. Infarct area and regional cerebral blood flow (rCBF) were measured by 2, 3, 5-triphenyltetrazolium chloride and laser Doppler flowmetry, respectively. Light microscope was used for the evaluation of body weight and dark neurons. Serum TXB2 , 6-Keto-PGF1a , TNF-α, and interleukin-6 (IL-6) levels in mice were measured using enzyme-linked immuno sorbent assay. In addition, relative protein expression levels of brain-derived neurotrophic factor, nestin, and Sox2 were detected by Western blot analysis. RESULTS: Liothyronine with a negative connectivity was identified as one promising treatment for IS through TNF signaling pathway. The experimental results showed that liothyronine treatment significantly meliorated infarct area and the number of dark neurons in IS mice. Liothyronine greatly ameliorated the expression levels of TXB2 and 6-Keto-PGF1a . Besides, rCBF and body weight change of IS mice were increased gradually with increase of drug concentration. Based on pathway enrichment analysis, anti-inflammatory response (TNF-α and IL-6) relevant to TNF signaling pathway was identified, which was further validated in vitro. Furthermore, proteins as neural stem cell markers made a difference with liothyronine treatment. CONCLUSION: Liothyronine may be a novel therapeutic component to exploit an effective medicine for the treatment of IS.
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AVC Isquêmico , Camundongos , Animais , Tri-Iodotironina , Fator de Necrose Tumoral alfa/genética , Farmacologia em Rede , Interleucina-6 , Infarto , Peso CorporalRESUMO
BACKGROUND: Metabolic homeostasis is closely related to early impairment of cell fate determination and embryo development. The protein kinase mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism in the body. Inhibition of mTOR signaling in early embryo causes postimplantation development failure, yet the mechanisms are still poorly understood. METHODS: Pregnancy mice and preimplantation mouse embryo were treated with mTOR inhibitor in vivo and in vitro respectively, and subsequently examined the blastocyst formation, implantation, and post-implantation development. We used immunofluorescence staining, RNA-Seq smart2, and genome-wide bisulfite sequencing technologies to investigate the impact of mTOR inhibitors on the quality, cell fate determination, and molecular alterations in developing embryos. RESULTS: We showed mTOR suppression during preimplantation decreases the rate of blastocyst formation and the competency of implantation, impairs the post implantation embryonic development. We discovered that blocking mTOR signaling negatively affected the transformation of 8-cell embryos into blastocysts and caused various deficiencies in blastocyst quality. These included problems with compromised trophectoderm cell differentiation, as well as disruptions in cell fate specification. mTOR suppression significantly affected the transcription and DNA methylation of embryos. Treatment with mTOR inhibitors increase lysosomal activation and disrupts the organization and dynamics of the actin cytoskeleton in blastocysts. CONCLUSIONS: These results demonstrate that mTOR plays a crucial role in 8-cell to blastocyst transition and safeguards embryo quality during early embryo development.
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Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are crucially implicated in the cancer progression. The current study intends to excavate and clarify the mechanisms of the key IGF2BPs in non-small cell lung cancer (NSCLC). The expression of IGF2BPs and kinesin family member 2A (KIF2A) was examined using immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot in NSCLC tissue samples or cell lines. NSCLC cell viability was examined using a cell counting kit-8 assay. Cell apoptotic rate was assessed using flow cytometry analysis. The migration and invasion of H1299 cells were subject to scratch test and Transwell assays, respectively. Starbase 2.0 was used to detect the downstream factors of the IGF2BP1 protein. The binding of IGF2BP with KIF2A was detected using RNA binding protein immunoprecipitation assays. Ki-67 immunohistochemistry assay and TUNEL assays were applied for the evaluation of proliferation and apoptosis in vivo, respectively. IGF2BP1 was upregulated in NSCLC tissue samples and cells. Functionally, IGF2BP1 overexpression promoted the proliferative ability, migration, and invasiveness of H1299 cells, while inhibiting cell apoptosis in vitro. In vivo studies revealed that overexpression of IGF2BP1 promoted tumor growth of NSCLC. Mechanistically, IGF2BP1 was involved in KIF2A mRNA stabilization. KIF2A exerted the same functions as IGF2BP1 via the Wnt/ß-catenin signaling. In conclusion, IGF2BP1 enhances NSCLC malignant progression by stabilizing KIF2A to modulate the Wnt/ß-catenin pathway.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Cinesinas/genética , Cinesinas/metabolismo , Neoplasias Pulmonares/patologia , RNA Mensageiro , Via de Sinalização Wnt/genéticaRESUMO
BACKGROUND: The predictors of success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) through antegrade dissection and re-entry (ADR) using the Stingray system (Stingray ADR) remain elusive, mainly owing to the lack of consecutive angiographic and procedural records of patients. OBJECTIVES: This study aimed to identify indicators that can determine the success of CTO PCI performed using the Stingray ADR technique. METHODS: The clinical data of 115 patients who underwent CTO PCI through Stingray ADR at the same cardiac center were retrospectively and consecutively collected. Multivariate logistic regression analysis was performed to investigate the indicators of the success of ADR attempts. RESULTS: The technical success rate of Stingray ADR in CTO PCI was 72.2%. The overall technical success rate of CTO recanalization was 78.3% in all CTO PCIs having used Stingray Low Profile balloon. Vessel calcification (odds ratio [OR]: 4.03; 95% confidence interval [CI]: 1.49-11.88; p = 0.008), and retrograde puncture indicator (OR: 4.89; 95% CI: 1.51-17.11; p = 0.009) were identified as independent positive predictors. Blunt/no stump proximal to the occlusion segment (OR: 0.22; 95% CI: 0.06-0.64; p = 0.009), decision time before Stingray ADR (per 1 h increase) (OR: 0.54; 95% CI: 0.31-0.92; p = 0.026), operation duration of Stingray ADR (per 10 min increase) (OR: 0.62; 95% CI: 0.40-0.94; p = 0.028), and puncture site at the intraplaque region (OR: 0.24; 95% CI: 0.06-0.84; p = 0.026) were identified as the four negative independent predictors. CONCLUSIONS: This study revealed independent predictors of the success of CTO PCI performed using the Stingray ADR technique. As for CTO characteristics, the presence of calcification in the CTO segment and a tapered stump proximal to the lesion site can facilitate successful Stingray ADR. As for the procedures, the success rate of Stingray ADR can be improved by initiating the technique decisively and promptly, operating the system quickly and accurately and creating a puncture in the distal cap region of CTO under retrograde guidance.
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Oclusão Coronária , Intervenção Coronária Percutânea , Rajidae , Humanos , Animais , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Resultado do Tratamento , Oclusão Coronária/terapia , Oclusão Coronária/cirurgia , Angiografia Coronária , Doença Crônica , Fatores de Risco , Sistema de RegistrosRESUMO
To explore the effect of full-cycle fast track surgical (FTS) nursing in patients with replantation of severed fingers, and observe its effect on functional recovery of replanted fingers and quality of life of patients. From January 2021 to December 2022, 86 patients with replantation of severed fingers were selected from Rizhao People's Hospital, 41 patients were given routine perioperative care, 45 patients were given full-cycle rapid rehabilitation surgical care. Compare the relevant indexes of the 2 groups of patients during hospitalization. Three months after discharge, the finger function recovery of the 2 groups were compared, and the quality of life of the patients was scored with the QL-Index scale, and the satisfaction was evaluated at the same time. The first time of getting out of bed and the time of hospitalization in the full-cycle FTS nursing group were significantly shorter than those in the conventional nursing group, and the incidence of postoperative nausea, vomiting, constipation and venous thromboembolism were significantly lower than those in the conventional nursing group. The anxiety score was significantly lower than that in the conventional nursing group, the difference was statistically significant (Pâ <â .05). There was no significant difference in the incidence of arteriovenous crisis between the 2 groups (Pâ >â .05). Three months after discharge, the scores of finger sensation and movement, quality of life and satisfaction of patients in the FTS nursing group were higher than those in the conventional nursing group, and the difference was statistically significant (Pâ <â .05). Full-cycle fast track surgical nursing model can improve the in-patient experience, reduce the incidence of complications, promote rapid rehabilitation, improve the quality of life of patients, and improve satisfaction.