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Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.
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Antibacterianos , Alicerces Teciduais , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Animais , Alicerces Teciduais/química , Camundongos , Cicatrização/efeitos dos fármacos , Raios Infravermelhos , Terapia Fototérmica , Engenharia Tecidual/métodos , Taninos/química , Taninos/farmacologia , Materiais Inteligentes/química , Staphylococcus aureus/efeitos dos fármacos , Masculino , Polietilenoglicóis/químicaRESUMO
In this study, a string of Cr-Mn co-modified activated coke catalysts (XCryMn1-y/AC) were prepared to investigate toluene and Hg0 removal performance. Multifarious characterizations including XRD, TEM, SEM, in situ DRIFTS, BET, XPS and H2-TPR showed that 4%Cr0.5Mn0.5/AC had excellent physicochemical properties and exhibited the best toluene and Hg0 removal efficiency at 200â. By varying the experimental gas components and conditions, it was found that too large weight hourly space velocity would reduce the removal efficiency of toluene and Hg0. Although O2 promoted the abatement of toluene and Hg0, the inhibitory role of H2O and SO2 offset the promoting effect of O2 to some extent. Toluene significantly inhibited Hg0 removal, resulting from that toluene was present at concentrations orders of magnitude greater than mercury's or the catalyst was more prone to adsorb toluene, while Hg0 almost exerted non-existent influence on toluene elimination. The mechanistic analysis showed that the forms of toluene and Hg0 removal included both adsorption and oxidation, where the high-valent metal cations and oxygen vacancy clusters promoted the redox cycle of Cr3+ + Mn3+/Mn4+ â Cr6+ + Mn2+, which facilitated the conversion and replenishment of reactive oxygen species in the oxidation process, and even the CrMn1.5O4 spinel structure could provide a larger catalytic interface, thus enhancing the adsorption/oxidation of toluene and Hg0. Therefore, its excellent physicochemical properties make it a cost-effective potential industrial catalyst with outstanding synergistic toluene and Hg0 removal performance and preeminent resistance to H2O and SO2.
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Poluentes Atmosféricos , Mercúrio , Óxidos , Tolueno , Tolueno/química , Óxidos/química , Poluentes Atmosféricos/química , Mercúrio/química , Coque , Catálise , Cromo/química , Adsorção , Manganês/química , Compostos de Manganês/química , Modelos QuímicosRESUMO
Background: Immunotherapy has revolutionized skin cutaneous melanoma treatment, but response variability due to tumor heterogeneity necessitates robust biomarkers for predicting immunotherapy response. Methods: We used weighted gene co-expression network analysis (WGCNA), consensus clustering, and 10 machine learning algorithms to develop the immunotherapy-related gene model (ITRGM) signature. Multi-omics analyses included bulk and single-cell RNA sequencing of melanoma patients, mouse bulk RNA sequencing, and pathology sections of melanoma patients. Results: We identified 66 consensus immunotherapy prognostic genes (CITPGs) using WGCNA and differentially expressed genes (DEGs) from two melanoma cohorts. The CITPG-high group showed better prognosis and enriched immune activities. DEGs between CITPG-high and CITPG-low groups in the TCGA-SKCM cohort were analyzed in three additional melanoma cohorts using univariate Cox regression, resulting in 44 consensus genes. Using 101 machine learning algorithm combinations, we constructed the ITRGM signature based on seven model genes. The ITRGM outperformed 37 published signatures in predicting immunotherapy prognosis across the training cohort, three testing cohorts, and a meta-cohort. It effectively stratified patients into high-risk or low-risk groups for immunotherapy response. The low-risk group, with high levels of model genes, correlated with increased immune characteristics such as tumor mutation burden and immune cell infiltration, indicating immune-hot tumors with a better prognosis. The ITRGM's relationship with the tumor immune microenvironment was further validated in our experiments using pathology sections with GBP5, an important model gene, and CD8 IHC analysis. The ITRGM also predicted better immunotherapy response in eight cohorts, including urothelial carcinoma and stomach adenocarcinoma, indicating broad applicability. Conclusions: The ITRGM signature is a stable and robust predictor for stratifying melanoma patients into 'immune-hot' and 'immune-cold' tumors, enhancing prognosis and response to immunotherapy.
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Biomarcadores Tumorais , Imunoterapia , Aprendizado de Máquina , Melanoma , Humanos , Melanoma/terapia , Melanoma/imunologia , Melanoma/genética , Imunoterapia/métodos , Biomarcadores Tumorais/genética , Prognóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/genética , Animais , Perfilação da Expressão Gênica , Transcriptoma , Regulação Neoplásica da Expressão Gênica , Camundongos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Resultado do Tratamento , Redes Reguladoras de GenesRESUMO
Background: Colorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development. Methods: We analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant bacterial taxa were identified via MR analysis. Single-cell RNA sequencing and enrichment analyses elucidated underlying pathways, and drug predictions identified potential therapeutics. Results: MR identified 19 bacterial taxa significantly associated with CRC. Protective effects were observed in taxa like RUG343 and Streptococcus_umgs_2425, while HOT-345_umgs_976 and W5053_sp000467935_mgs_712 increased CRC risk. Single-cell RNA sequencing revealed key pathways, including JAK-STAT signaling and tyrosine metabolism. Drug prediction highlighted potential therapeutics like Menadione Sodium Bisulfite and Raloxifene. Conclusion: This study establishes the critical role of the oral microbiome in colorectal cancer development, identifying specific microbial taxa linked to CRC risk. Single-cell RNA sequencing and drug prediction analyses further elucidate key pathways and potential therapeutics, providing novel insights and personalized treatment strategies for CRC.
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Neoplasias Colorretais , Análise da Randomização Mendeliana , Microbiota , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/genética , Humanos , Microbiota/genética , Estudo de Associação Genômica Ampla , Boca/microbiologia , China , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Saliva/microbiologia , Japão , Povo Asiático/genética , Análise de Célula Única , Multiômica , População do Leste AsiáticoRESUMO
INTRODUCTION: Invasive species pose a major threat to global biodiversity and agricultural productivity, yet the genomic mechanisms driving their rapid expansion into new habitats are not fully understood. The fall armyworm, Spodoptera frugiperda, originally from the Americas, has expanded its reach across the Old World, causing substantial reduction in crop yield. Although the hybridization between two genetically distinct strains has been well-documented, the role of such hybridization in enhancing the species' invasive capabilities remains largely unexplored. OBJECTIVES: This study aims to investigate the contributions of hybridization and natural selection to the rapid invasion of the fall armyworm. METHODS: We analyzed the whole-genome resequencing data from 432 individuals spanning its global distribution. We identified the genomic signatures of selection associated with invasion and explored their linkage with the Tpi gene indicating strain differentiation. Furthermore, we detected signatures of balancing selection in native populations for candidate genes that underwent selective sweeps during the invasion process. RESULTS: Our analysis revealed pronounced genomic differentiation between native and invasive populations. Invasive populations displayed a uniform genomic structure distinctly different from that of native populations, indicating hybridization between the strains during invasion. This hybridization likely contributes to maintaining high genetic diversity in invasive regions, which is crucial for survival and adaptation. Additionally, polymorphisms on genes under selection during invasion were possibly preserved through balancing selection in their native environments. CONCLUSION: Our findings reveal the genomic basis of the fall armyworm's successful invasion and rapid adaptation to new environments, highlighting the important role of hybridization in the dynamics of invasive species.
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Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.
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Colite Ulcerativa , Modelos Animais de Doenças , Heme Oxigenase-1 , MicroRNAs , Moxibustão , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Transdução de Sinais , Fatores de Transcrição , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Colite Ulcerativa/terapia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/genética , Camundongos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , DNA Helicases/metabolismo , DNA Helicases/genética , Neoplasias Associadas a Colite/etiologia , Neoplasias Associadas a Colite/patologia , Neoplasias Associadas a Colite/metabolismo , Neoplasias Associadas a Colite/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , HumanosRESUMO
Non-coding RNAs (ncRNAs), which are usually considered not to encode proteins, are widely involved in important activities including signal transduction and cell proliferation. However, recent studies have shown that small peptides encoded by ncRNAs (SPENs) have important roles in the development of malignant tumors. Some SPENs participate in the regulation of skeleton reorganization, intercellular adhesion, signaling and other processes of tumor cells, with effects on the invasive and migratory abilities of the cells. Therefore, SPENs have potential applications as therapeutic targets and biomarkers of malignant tumors. Invasion and migration of malignant tumor cells are the main reasons for poor prognosis of cancer patients and represent the most challenging aspects of treatment of malignant tumors. Currently, the main treatments for tumors include surgery, radiotherapy, targeted drug therapy. Surgery, however, is reserved for early stages of cancer and carries risks and costs. Radiotherapy and targeted therapy have serious side effects. This review describes the mechanisms of SPENs and their roles in tumor invasion and migration, with the aim of providing new targets for tumor diagnosis and treatment.
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Red blood cells (RBCs) naturally trap some bacterial pathogens in the circulation and kill them by oxidative stress. Following neutralization, the bacteria are presented to antigen-presenting cells in the spleen by the RBCs. This ability of RBCs has been harnessed to develop a system where they play a crucial role in enhancing the immune response, offering a novel approach to enhance the body's immunity. In this work, a conjugate, G-OVA, was formed by connecting ß-glucan and OVA through a disulfide bond. Poly (lactic-co-glycolic acid) (PLGA) was then employed to encapsulate G-OVA, yielding G-OVA-PLGA. Finally, the nanoparticles were adsorbed onto RBCs to develop G-OVA-PLGA@RBC. The results demonstrated that the delivery of nanoparticles by RBCs enhanced the antibody response to antigens both in vitro and in vivo. The objective of this study was to investigate the increased immune activity of G-OVA-PLGA nanoparticles facilitated by RBCs transportation and to elucidate some of its underlying mechanisms. These findings are anticipated to contribute valuable insights for the development of efficient and safe immune enhancers.
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Thin-layer MoS2 has attracted much interest because of its potential in diverse technologies, including electronics, optoelectronics and catalysis these few years. In particular, finding a simple and effective solution for large-scale growth of thin-layer semiconductor nanosheets is a prerequisite for achieving their excellent performance. In this paper, we investigated four different substrates under identical conditions for MoS2 film growth and observed a strong correlation between substrate surface conditions and MoS2 growth. To enhance substrate performance, a low-concentration NaCl water solution (25 mg mL-1) was employed for pre-treating the substrate surface, thereby modifying its initial state. In the chemical vapor deposition (CVD) growth environment, the introduced halide ions served as surface dangling bonds. The pre-treated led to a remarkable 90% increase in the growth rate of MoS2 on the substrate surface, facilitating the production of large monolayer MoS2 sheets (â¼200 µm). This growth mechanism further enabled the manufacturing of ultra-large single crystals (â¼1 mm). Consequently, our research presents a straightforward and cost-effective approach for the large-scale production of nanosheets. Field-effect transistors (FETs) based on the pre-treated monolayer MoS2 exhibited high mobility (12 cm2 V-1 s-1) and a large on/off ratio (104). Therefore, our research provides a simple and low-cost approach for large-scale production of nanosheets for use in high-quality electronics over large areas.
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Previous studies confirmed the regenerative capacity of the mammalian neonatal heart. We recently found that adult heart tissue-derived EVs can protect the heart from myocardial ischemia-reperfusion (I/R). However, the role of EVs from neonatal heart tissue in cardiac healing post-ischemia remains unclear. In the present study, we revealed that intramyocardial administration of neonatal cardiac tissue-derived EVs (ncEVs) alleviated cardiac inflammation, mitigated reperfusion injury, and improved cardiac function in murine I/R models. In vitro, ncEVs inhibited M1 polarization of macrophages induced by LPS while up-regulated their phagocytic function via the miR-133a-3p-Ash1l signaling pathway. Moreover, the administration of ncEVs contributed to cardiac angiogenesis and improved cardiac function in murine myocardial infarction models. Collectively, these results suggested that neonatal heart-derived EVs can regulate the function of macrophages and contribute to cardiac regeneration and function recovery in murine cardiac ischemic models. Therefore, the derivatives in neonatal heart tissue-derived EVs might serve as a potential therapeutic strategy in ischemic diseases.
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BACKGROUD: Intussusception is a common acute abdominal disease in children, often leading to acute ileus in infants and young children. OBJECTIVE: This study aimed to develop and validate a nomogram for predicting recurrent intussusception in children within 48 h after pneumatic reduction of primary intussusception. METHODS: Clinical data of children with acute intussusception admitted to multiple hospitals from March 2019 to March 2021 were retrospectively analyzed. The children were divided into a successful reductioncontrol group (control group) and a recurrent intussusception group (RI group) according to the results of pneumatic reduction. RESULTS: A total of 2406 cases were included in this study, including 2198 control group and 208 RI group. In the total sample, 1684 cases were trained and 722 cases were verified. A logistic regression analysis was conducted to establish a predictive model based on age, abdominal pain time, white blood cells count, and hypersensitive C-reactive protein levels as independent predictors of intussusception recurrence. The nomogram successfully predicted recurrent intussusception after pneumatic reduction. CONCLUSION: In this study, a nomogram was developed based on clinical risk factors to predict recurrent intussusception following pneumatic reduction in children. Age, abdominal pain time, white blood cell counts, and hypersensitive C-reactive protein levels were identified as predictors and incorporated into the nomogram. Internal validation demonstrated that this nomogram can offer a clear and convenient tool for identifying risk factors for recurrence of intussusception in children undergoing pneumatic reduction.
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Intussuscepção , Nomogramas , Recidiva , Humanos , Intussuscepção/terapia , Intussuscepção/diagnóstico , Masculino , Feminino , Lactente , Estudos Retrospectivos , Pré-Escolar , Fatores de Risco , CriançaRESUMO
Nitrogen deficiency in low organic matter soils significantly reduces crop yield and plant health. The effects of foliar applications of indole acetic acid (IAA), trehalose (TA), and nanoparticles-coated urea (NPCU) on the growth and physiological attributes of tomatoes in nitrogen-deficient soil are not well documented in the literature. This study aims to explore the influence of IAA, TA, and NPCU on tomato plants in nitrogen-deficient soil. Treatments included control, 2mM IAA, 0.1% TA, and 2mM IAA + 0.1% TA, applied with and without NPCU. Results showed that 2mM IAA + 0.1% TA with NPCU significantly improved shoot length (~ 30%), root length (~ 63%), plant fresh (~ 48%) and dry weight (~ 48%), number of leaves (~ 38%), and leaf area (~ 58%) compared to control (NPCU only). Additionally, significant improvements in chlorophyll content, total protein, and total soluble sugar, along with a decrease in antioxidant activity (POD, SOD, CAT, and APX), validated the effectiveness of 2mM IAA + 0.1% TA with NPCU. The combined application of 2mM IAA + 0.1% TA with NPCU can be recommended as an effective strategy to enhance tomato growth and yield in nitrogen-deficient soils. This approach can be integrated into current agricultural practices to improve crop resilience and productivity, especially in regions with poor soil fertility. To confirm the efficacy of 2mM IAA + 0.1% TA with NPCU in various crops and climatic conditions, additional field studies are required.
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Ácidos Indolacéticos , Nitrogênio , Solo , Solanum lycopersicum , Trealose , Ureia , Óxido de Zinco , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/metabolismo , Ácidos Indolacéticos/farmacologia , Ácidos Indolacéticos/metabolismo , Nitrogênio/metabolismo , Solo/química , Trealose/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Nanopartículas/química , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , FertilizantesRESUMO
OBJECTIVE: Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. METHODS: The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. RESULTS: CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. CONCLUSION: Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.
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Administração Intravenosa , Doenças do Tecido Conjuntivo , Ciclofosfamida , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Masculino , Administração Oral , Estudos Retrospectivos , Pessoa de Meia-Idade , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/complicações , Resultado do Tratamento , Adulto , Fatores de Tempo , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Capacidade Vital , Recuperação de Função Fisiológica , Idoso , Capacidade de Difusão Pulmonar , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Sedimentação Sanguínea , Tolerância ao Exercício/efeitos dos fármacos , Teste de Caminhada , Proteína D Associada a Surfactante Pulmonar/sangue , Mucina-1/sangueRESUMO
The electrochemical splitting of water for hydrogen production faces a major challenge due to its anodic oxygen evolution reaction (OER), necessitating research on the rational design and facile synthesis of OER catalysts to enhance catalytic activity and stability. This study proposes a ligand-induced MOF-on-MOF approach to fabricate various trimetallic MnFeCo-based Prussian blue analog (PBA) nanostructures. The addition of [Fe(CN)6]3- transforms them from cuboids with protruding corners (MnFeCoPBA-I) to core-shell configurations (MnFeCoPBA-II), and finally to hollow structures (MnFeCoPBA-III). After pyrolysis at 800 °C, they are converted into corresponding PBA-derived carbon nanomaterials, featuring uniformly dispersed Mn2Co2C nanoparticles. A comparative analysis demonstrates that the Fe addition enhances catalytic activity, while Mn-doped materials exhibit excellent stability. Specifically, the optimized MnFeCoNC-I-800 demonstrates outstanding OER performance in 1.0 m KOH solution, with an overpotential of 318 mV at 10 mA cm-2, maintaining stability for up to 150 h. Theoretical calculations elucidate synergistic interactions between Fe dopants and the Mn2Co2C matrix, reducing barriers for oxygen intermediates and improving intrinsic OER activity. These findings offer valuable insights into the structure-morphology relationships of MOF precursors, advancing the development of highly active and stable MOF-derived OER catalysts for practical applications.
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The escalating apprehension surrounding the carcinogenic potential of chemicals emphasizes the imperative need for efficient methods of assessing carcinogenicity. Conventional experimental approaches such as in vitro and in vivo assays, albeit effective, suffer from being costly and time-consuming. In response to this challenge, new alternative methodologies, notably machine learning and deep learning techniques, have attracted attention for their potential in developing carcinogenicity prediction models. This article reviews the progress in predicting carcinogenicity using various machine learning and deep learning algorithms. A comparative analysis on these developed models reveals that support vector machine, random forest, and ensemble learning are commonly preferred for their robustness and effectiveness in predicting chemical carcinogenicity. Conversely, models based on deep learning algorithms, such as feedforward neural network, convolutional neural network, graph convolutional neural network, capsule neural network, and hybrid neural networks, exhibit promising capabilities but are limited by the size of available carcinogenicity datasets. This review provides a comprehensive analysis of current machine learning and deep learning models for carcinogenicity prediction, underscoring the importance of high-quality and large datasets. These observations are anticipated to catalyze future advancements in developing effective and generalizable machine learning and deep learning models for predicting chemical carcinogenicity.
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Objective: This study aimed to elucidate the prognostic significance of serum soluble thrombomodulin (sTM), lung ultrasound score (LUS), and lactate levels in patients with extrapulmonary acute respiratory distress syndrome (ARDS), with the goal of refining mortality risk prediction in this cohort. Methods: In a prospective cohort of 95 patients with extrapulmonary ARDS admitted to the intensive care unit, we investigated the primary endpoint of 28-day mortality. Utilizing Lasso-Cox regression analysis, we identified independent prognostic factors for mortality. A predictive nomogram was developed incorporating these factors, and its performance was validated through several statistical measures, including the consistency index, calibration plot, internal validation curve, decision curve analysis, interventions avoided analysis, receiver operating characteristic curve analysis, and Kaplan-Meier survival analysis. We further conducted a subgroup analysis to examine the impact of prone positioning on patient outcomes. Results: The study identified baseline serum sTM, LUS, and lactate levels as independent predictors of 28-day mortality in extrapulmonary ARDS patients. The predictive nomogram demonstrated superior prognostic accuracy compared to the use of sTM, LUS, or lactate levels alone, and outperformed traditional prognostic tools such as the Acute Physiology and Chronic Health Evaluation II score and the partial pressure of arterial oxygen to fractional inspired oxygen ratio. The subgroup analysis did not show a significant impact of prone positioning on the predictive value of the identified biomarkers. Conclusion: Our study results support the development and validation of a novel prognostic nomogram that integrates key clinical biomarkers and ultrasound imaging scores to predict mortality in patients with extrapulmonary ARDS. While our research is preliminary, further studies and validation are required.
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BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with the tumor microenvironment (TME) playing a crucial role in its progression. Aggregated autophagy (AA) has been recognized as a factor that exacerbates CRC progression. This study aims to study the relationship between aggregated autophagy and CRC using single-cell sequencing techniques. Our goal is to explain the heterogeneity of the TME and to explore the potential for targeted personalized therapies. OBJECTIVE: To study the role of AA in CRC, we employed single-cell sequencing to discern distinct subpopulations within the TME. These subpopulations were characterized by their autophagy levels and further analyzed to identify specific biological processes and marker genes. RESULTS: Our study revealed significant correlations between immune factors and both clinical and biological characteristics of the tumor microenvironment (TME), particularly in cells expressing TUBA1B and HSP90AA1. These immune factors were associated with T cell depletion, a reduction in protective factors, diminished efficacy of immune checkpoint blockade (ICB), and enhanced migration of cancer-associated fibroblasts (CAFs), resulting in pronounced inflammation. In vitro experiments showd that silencing TUBA1B and HSP90AA1 using siRNA (Si-TUBA1B and Si-HSP90AA1) significantly reduced the expression of IL-6, IL-7, CXCL1, and CXCL2 and inhibition of tumor cell growth in Caco-2 and Colo-205 cell lines. This reduction led to a substantial alleviation of chronic inflammation and highlighted the heterogeneous nature of the TME. CONCLUSION: This study marks an initial foray into understanding how AA-associated processes may potentiate the TME and weaken immune function. Our findings provide insights into the complex dynamics of the TME and highlight potential targets for therapeutic intervention, suggesting a key role for AA in the advancement of colorectal cancer.
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Four new species of Yunguirius B. Li, Zhao & S.Q. Li, 2023 are described from China, namely: Yunguiriusparvus Wei & Liu, sp. nov. (â), Yunguiriustrigonus Wei & Liu, sp. nov. (â), Yunguiriuswangqiqiae Wei & Liu, sp. nov. (â), and Yunguiriusxiannushanensis Wei & Liu, sp. nov. (â).
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AIMS: Alzheimer's disease (AD) is a neurodegenerative disorder with limited treatment options. This study aimed to investigate the therapeutic effects of Ginkgo biloba leaf extract (GBE) on AD and explore its potential mechanisms of action. METHODS: Key chemical components of GBE, including quercetin, luteolin, and kaempferol, were identified using network pharmacology methods. Bioinformatics analysis revealed their potential roles in AD through modulation of the PI3K/AKT/NF-κB signaling pathway. RESULTS: Mouse experiments demonstrated that GBE improved cognitive function, enhanced neuronal morphology, and reduced serum inflammatory factors. Additionally, GBE modulated the expression of relevant proteins and mRNA. CONCLUSION: GBE shows promise as a potential treatment for AD. Its beneficial effects on cognitive function, neuronal morphology, and inflammation may be attributed to its modulation of the PI3K/AKT/NF-κB signaling pathway. These findings provide experimental evidence for the application of Ginkgo biloba leaf in AD treatment and highlight its potential mechanisms of action.