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1.
Environ Pollut ; 351: 124084, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697245

RESUMO

Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 µm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O2.-) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L-1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate.

2.
Toxicol Lett ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734219

RESUMO

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5minutes after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20minutes. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

3.
J Mater Chem B ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690797

RESUMO

Hypoxic microenvironment and glutathione (GSH) accumulation in tumours limit the efficacy of cytotoxic reactive oxygen species (ROS) anti-tumour therapy. To address this challenge, we increased the consumption of GSH and the production of ROS through a novel nanoplatform with the action of inorganic nanoenzymes. In this study, we prepared mesoporous FeS2 using a simple template method, efficiently loaded AIPH, and assembled Ti3C2/FeS2-AIPH@BSA (TFAB) nanocomposites through self-assembly with BSA and 2D Ti3C2. The constructed TFAB nanotherapeutic platform enhanced chemodynamic therapy (CDT) by generating toxic hydroxyl radicals (˙OH) via FeS2, while consuming GSH to reduce the loss of generated ˙OH via glutathione oxidase-like (GSH-OXD). In addition, TFAB is able to stimulate the decomposition of AIPH under 808 nm laser irradiation to produce oxygen-independent biotoxic alkyl radicals (˙R) for thermodynamic therapy (TDT). In conclusion, TFAB represents an innovative nanoplatform that effectively addresses the limitations of free radical-based treatment strategies. Through the synergistic therapeutic strategy of photothermal therapy (PTT), CDT, and TDT within the tumor microenvironment, TFAB nanoplatforms achieve controlled AIPH release, ROS generation, intracellular GSH consumption, and precise temperature elevation, resulting in enhanced intracellular oxidative stress, significant apoptotic cell death, and notable tumor growth inhibition. This comprehensive treatment strategy shows great promise in the field of tumor therapy.

4.
Nano Lett ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747343

RESUMO

Ion transport through nanoporous two-dimensional (2D) membranes is predicted to be tunable by controlling the charging status of the membranes' planar surfaces, the behavior of which though remains to be assessed experimentally. Here we investigate ion transport through intrinsically porous membranes made of 2D metal-organic-framework layers. In the presence of certain cations, we observe a linear-to-nonlinear transition of the ionic current in response to the applied electric field, the behavior of which is analogous to the cation gating effect in the biological ion channels. Specifically, the ionic currents saturate at transmembrane voltages exceeding a few hundreds of millivolts, depending on the concentration of the gating cations. This is attributed to the binding of cations at the membranes' surfaces, tuning the charging states there and affecting the entry/exit process of translocating ions. Our work also provides 2D membranes as candidates for building nanofluidic devices with tunable transport properties.

5.
mSystems ; : e0121023, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747603

RESUMO

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery. IMPORTANCE: Serving as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.

7.
Invest Ophthalmol Vis Sci ; 65(5): 16, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717425

RESUMO

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.


Assuntos
Envelhecimento , Cognição , Degeneração Macular , Retina , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Idoso , Feminino , Estudos Transversais , Envelhecimento/fisiologia , Idoso de 80 Anos ou mais , Degeneração Macular/fisiopatologia , Cognição/fisiologia , Retina/diagnóstico por imagem , Retina/patologia , Retina/fisiopatologia , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia
8.
PLoS One ; 19(5): e0301095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38739604

RESUMO

BACKGROUND: Myofascial pelvic pain (MFPP), which is identified by tender points in the pelvic floor musculature, is a prevalent source of chronic pelvic pain in women. It may lead to physical and mental exhaustion, reproductive concerns, and coping difficulties in daily life and work than the disease itself. Pain-related cognitive processes can affect pain relief and quality of life. Kinesiophobia, self-efficacy and pain catastrophizing are frequently treated as mediators between pain and its related consequences. Greater kinesiophobia and pain catastrophizing have been shown to be associated with adverse functional outcomes, while higher self-efficacy has been related with improved quality of life. Regarding MFPP in females of childbearing age, it remains unclear whether the effects of kinesiophobia, self-efficacy and pain catastrophizing on daily interference are direct or indirect; the influence on each variable is, therefore, not entirely evident. AIM: The present study aimed to evaluate the relationship between pain and daily interference in reproductive-age women with MFPP through kinesiophobia, self-efficacy and pain catastrophizing, as well as to identify areas for future investigation and intervention based on the data collected from this population. METHODS: This is a multi-center cross-sectional study. The study was conducted from November 15, 2022 to November 10, 2023, 202 reproductive-age women with MFPP were recruited from 14 hospitals in ten provinces of China. The demographic variables, Brief Pain Inventory, Tampa Scale of Kinesiophobia, Pain Self-Efficacy Questionnaire, and Pain Catastrophizing Scale were used to measure the participants' related information. The data was described and analyzed using Descriptive analyses, Pearson correlation analysis, and Serial mediation modeling. RESULTS: Pain not only had a direct positive impact (B = 0.575; SE = 0.081; 95%CI: LL = 0.415, UL = 0.735) on daily interference, but also had an indirect impact on daily interference through the independent mediating role of pain catastrophizing (B = 0.088; SE = 0.028; 95%CI: LL = 0.038, UL = 0.148), the chain mediating of kinesiophobia and catastrophizing (B = 0.057; SE = 0.019; 95%CI: LL = 0.024, UL = 0.098), and the four-stage serial mediating of kinesiophobia, self-efficacy and catastrophizing (B = 0.013; SE = 0.006; 95%CI: LL = 0.003, UL = 0.027). The proposed serial mediation model showed a good fit with the collected data. CONCLUSION: The findings illustrate the significance of addressing pain catastrophizing and kinesiophobia (especially catastrophizing), and increasing self-efficacy in pain therapy, and suggest that functional recovery be integrated into pain therapy for reproductive-age women suffering from MFPP.


Assuntos
Catastrofização , Dor Pélvica , Autoeficácia , Humanos , Feminino , Catastrofização/psicologia , Adulto , Dor Pélvica/psicologia , Adulto Jovem , Qualidade de Vida/psicologia , Medição da Dor , Síndromes da Dor Miofascial/psicologia , Estudos Transversais , Pessoa de Meia-Idade , Medo/psicologia , Transtornos Fóbicos/psicologia , Inquéritos e Questionários , Adolescente , Cinesiofobia
9.
Sci Rep ; 14(1): 10945, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740919

RESUMO

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.


Assuntos
Artéria Carótida Interna , Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Masculino , Feminino , Idoso , Placa Aterosclerótica/cirurgia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/complicações , Artéria Carótida Interna/cirurgia , Artéria Carótida Interna/patologia , Pessoa de Meia-Idade , Estenose das Carótidas/cirurgia , Estenose das Carótidas/patologia , Estenose das Carótidas/complicações , Endarterectomia das Carótidas/métodos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Idoso de 80 Anos ou mais , Fatores de Risco
10.
Am J Dermatopathol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38718164

RESUMO

ABSTRACT: In 4%-11% of cases, melanoma recurrences present as in-transit (IT) metastases, and their prognosis is quite poor. Consequently, an early diagnosis and treatment of IT metastasis assume paramount significance. Despite this, the diagnosis of cutaneous IT metastases persistently presents a formidable challenge due to the diversity in clinical and dermoscopic characteristics. We provide a novel melanoma IT metastases pattern with interesting dermoscopic features and magnetic resonance imaging via presenting an unusual case characterized by diffuse subcutaneous intravascular lesions to supplement the understanding of cutaneous melanoma IT metastases.

11.
COPD ; 21(1): 2342797, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38712759

RESUMO

Objective: To investigate the effects of cigarette smoke (CS) on Serine/Threonine Kinase 11 (STK11) and to determine STK11's role in CS-induced airway epithelial cell cytotoxicity.Methods: STK11 expression levels in the lung tissues of smokers with or without COPD and mice exposed to CS or room air (RA) were determined by immunoblotting and RT-PCR. BEAS-2Bs-human bronchial airway epithelial cells were exposed to CS extract (CSE), and the changes in STK11 expression levels were determined by immunoblotting and RT-PCR. BEAS-2B cells were transfected with STK11-specific siRNA or STK11 expression plasmid, and the effects of CSE on airway epithelial cell cytotoxicity were measured. To determine the specific STK11 degradation-proteolytic pathway, BEAS-2Bs were treated with cycloheximide alone or combined with MG132 or leupeptin. Finally, to identify the F-box protein mediating the STK11 degradation, a screening assay was performed using transfection with a panel of FBXL E3 ligase subunits.Results: STK11 protein levels were significantly decreased in the lung tissues of smokers with COPD relative to smokers without COPD. STK11 protein levels were also significantly decreased in mouse lung tissues exposed to CS compared to RA. Exposure to CSE shortened the STK11 mRNA and protein half-life to 4 h in BEAS-2B cells. STK11 protein overexpression attenuated the CSE-induced cytotoxicity; in contrast, its knockdown augmented CSE-induced cytotoxicity. FBXL19 mediates CSE-induced STK11 protein degradation via the ubiquitin-proteasome pathway in cultured BEAS-2B cells. FBXL19 overexpression led to accelerated STK11 ubiquitination and degradation in a dose-dependent manner.Conclusions: Our results suggest that CSE enhances the degradation of STK11 protein in airway epithelial cells via the FBXL19-mediated ubiquitin-proteasomal pathway, leading to augmented cell death.HIGHLIGHTSLung tissues of COPD-smokers exhibited a decreased STK11 RNA and protein expression.STK11 overexpression attenuates CS-induced airway epithelial cell cytotoxicity.STK11 depletion augments CS-induced airway epithelial cell cytotoxicity.CS diminishes STK11 via FBXL19-mediated ubiquitin-proteasome degradation.


Assuntos
Proteínas Quinases Ativadas por AMP , Células Epiteliais , Proteínas F-Box , Proteínas Serina-Treonina Quinases , Doença Pulmonar Obstrutiva Crônica , Fumaça , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Animais , Humanos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Camundongos , Fumaça/efeitos adversos , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Quinases Proteína-Quinases Ativadas por AMP , Linhagem Celular , Proteólise/efeitos dos fármacos , Leupeptinas/farmacologia , Masculino , Cicloeximida/farmacologia , RNA Interferente Pequeno , Camundongos Endogâmicos C57BL , Mucosa Respiratória/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Fumar Cigarros/efeitos adversos
12.
Cell Signal ; 120: 111197, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697447

RESUMO

OBJECTIVES: The clinical T1 stage solid lung cancer with metastasis is a serious threat to human life and health. In this study, we performed RNA sequencing on T1 advanced-stage lung cancer and adjacent tissues to identify a novel biomarker and explore its roles in lung cancer. METHODS: Quantitative reversed-transcription PCR, reverse transcription PCR and Western blot, MSP and Methtarget were utilized to evaluate FIBIN expression levels at both the transcriptional and protein levels as well as its methylation status. Differential target protein was evaluated for relative and absolute quantitation by isobaric tags. Co-IP was performed to detect the interactions between target protein. Precise location and expression levels of target proteins were revealed by immunofluorescence staining and component protein extraction using specific kits, respectively. RESULTS: We reported that FIBIN was frequently silenced due to promoter hypermethylation in lung cancer. Additionally, both in vitro and in vivo experiments confirmed the significant anti-proliferation and anti-metastasis capabilities of FIBIN. Mechanistically, FIBIN decreased the nuclear accumulation of ß-catenin by reducing the binding activity of GSK3ß with ANXA2 while promoting interaction between GSK3ß and ß-catenin. CONCLUSION: Our findings firstly identify FIBIN is a tumor suppressor, frequently silenced due to promoter hypermethylation. FIBIN may serve as a predictive biomarker for progression or metastasis among early-stage lung cancer patients.

13.
Heliyon ; 10(9): e30345, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38711669

RESUMO

In this study, the sodium dodecyl sulfate intercalated modified magnesium-aluminum hydrotalcite/sodium alginate/sodium carboxymethylcellulose (modified LDHs/SA/CMC) composite gel spheres were synthesized and their efficacies in adsorbing the cationic dye rhodamine B (RhB) from aqueous solutions were evaluated. The effects of adsorption time, pH and temperature on the adsorption of RhB by spheres were investigated. Remarkably, the modified LDHs/SA/CMC gel spheres achieved adsorption equilibrium after 600 min at 25 °C, and the removal rate of RhB at 60 mg/L reached 91.49 % with the maximum adsorption capacity of 59.64 mg/g. The gel spheres maintained over 80 % efficacy across four adsorption cycles. Kinetic and isotherm analyses revealed that the adsorption of RhB conformed to the secondary kinetic model and the Langmuir isotherm, indicating a spontaneous and exothermic nature of the adsorption process. The adsorption mechanisms of modified LDHs/SA/CMC gel spheres on RhB dyes include electrostatic adsorption, hydrogen bonding and hydrophobic interactions. In conclusion, modified LDHs/SA/CMC gel sphere is a green, simple, recyclable and efficient adsorbent, which is expected to be widely used for the treatment of cationic dye wastewater.

14.
J Oleo Sci ; 73(5): 729-742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692895

RESUMO

Astaxanthin is a keto-based carotenoid mainly obtained from marine organisms, like Haematococcus pluvialis (H. pluvialis). Previous studies indicated the protective effects of Astaxanthin and H. pluvialis on aging related oxidative injury in liver, while the potential mechanisms are largely unknown. In addition, H. pluvialis residue is a by-product after astaxanthin extraction, which is rarely studied and utilized. The present study aimed to compare the effects of astaxanthin, H. pluvialis and H. pluvialis residue on the oxidant injury of liver in D-galactose-induced aging mice and explore the potential mechanisms through gut-liver axis. The results showed that all the three supplements prevented D-galactose-induced tissue injury, oxidative stress and chronic inflammation in liver and improved liver function. Gut microbiota analysis indicated that astaxanthin notably increased fecal levels of Bacteroidetes, unclassified_f__ Lachnospiraceae, norank_f__Lachnospiraceae, norank_f__norank_o__Clostridia_UCG-014, Prevotellaceae_ UCG-001, unclassified_f__Prevotellaceae in D-galactose-fed mice (p < 0.05). Compared to aging mice, H. pluvialis group had higher fecal levels of norank_f__Lachnospiraceae and Lachnospiraceae_UCG-006 (p < 0.05). H. pluvialis residue group displayed higher relative levels of Bacteroidetes, Streptococcus, and Rikenellaceae_RC9_gut_group (p < 0.05). Moreover, the production of fecal microbial metabolites, like SCFAs and LPS was also differently restored by the three supplements. Overall, our results suggest astaxanthin, H. pluvialis and H. pluvialis residue could prevent aging related hepatic injury through gutliver axis and provide evidence for exploiting of H. pluvialis residue as a functional ingredient for the treatment of liver diseases. Future studies are needed to further clarify the effect and mechanism of dominant components of H. pluvialis residue on liver injury, which is expected to provide a reference for the high-value utilization of H. pluvialis resources.


Assuntos
Envelhecimento , Galactose , Microbioma Gastrointestinal , Fígado , Estresse Oxidativo , Xantofilas , Animais , Masculino , Camundongos , Envelhecimento/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Suplementos Nutricionais , Galactose/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/isolamento & purificação
15.
Comput Biol Chem ; 110: 108077, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38691895

RESUMO

A wealth of experimental evidence has suggested that open chromatin regions (OCRs) are involved in many critical biological activities, such as DNA replication, enhancer activity, and gene transcription. Accurately identifying OCRs in livestock species can provide critical insights into the distribution and characteristics of OCRs for disease treatment in livestock, thereby improving animal welfare. However, most current machine-learning methods for OCR prediction were originally designed for a limited number of model organisms, such as humans and some model organisms, and thus their performance on non-model organisms, specifically livestock, is often unsatisfactory. To bridge this gap, we propose DeepOCR, a lightweight depth-separable residual network model for predicting OCRs in livestock, including chicken, cattle, and sheep. DeepOCR integrates a single convolution layer and two improved residue structure blocks to extract and learn important features from the input DNA sequences. A fully connected layer was also employed to further process the extracted features and improve the robustness of the entire network. Our benchmarking experiments demonstrated superior prediction performance of DeepOCR compared to state-of-the-art approaches on testing datasets of the three species. The source code of DeepOCR is freely available for academic purposes at https://github.com/jasonzhao371/DeepOCR/. We anticipate DeepOCR servers as a practical and reliable computational tool for OCR-related studies in livestock species.

16.
Transl Cancer Res ; 13(4): 1954-1968, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38737677

RESUMO

Background: Cancer has the highest mortality rate among gynecological cancers and poses a serious threat to women's lives. However, the treatment options for ovarian cancer are still limited, and exploring effective targeted biomarkers is particularly important for predicting and treating ovarian cancer. Therefore, it is necessary to explore the molecular mechanisms of the occurrence and development of ovarian cancer. Methods: This investigation encompassed the analysis of gene expression profiles, measurement of transcription levels of potential target genes in peripheral blood samples from ovarian cancer patients and characterization of the ovarian cancer-related secretory protein sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Through bioinformatics analysis, potential target genes were identified, and their association with overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients was assessed utilizing relevant databases. Subsequently, differences in target gene expression in ovarian cancer tissue samples were validated through protein blotting and quantitative real-time PCR (qRT-qPCR). Cell proliferation assays using the cell count kit-8 (CCK-8) method, as well as transwell chamber assay and pre coated matrix gel chamber assay were employed to elucidate the role of SMPDL3B in ovarian cancer cell migration and invasion. Results: This study revealed a substantial upregulation of SMPDL3B in the serum of ovarian cancer patients, correlating with an unfavorable prognosis. High SMPDL3B expression was linked not only to increased proliferation of ovarian cancer cells, but also enhanced migration and invasion. Remarkably, the knockdown the human alkaline ceramidase 2 (ACER2) gene in cancer cells with heightened SMPDL3B expression significantly inhibited cell proliferation, migration, and invasion induced by SMPDL3B activation (P<0.05), highlighting the functional interplay between ACER2 and SMPDL3B in ovarian cancer. Conclusions: In summary, this study proposes SMPDL3B as a prognostic marker for ovarian cancer, with implications for potential therapeutic intervention targeting the ACER2-SMPDL3B axis.

17.
Molecules ; 29(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731488

RESUMO

This study synthesized a novel oat ß-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.


Assuntos
Cromo , Hipoglicemiantes , alfa-Glucosidases , beta-Glucanas , Humanos , Cromo/química , Cromo/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , beta-Glucanas/química , beta-Glucanas/farmacologia , Células Hep G2 , alfa-Glucosidases/metabolismo , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , Resistência à Insulina , Glucose/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Avena/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química
18.
Sci Total Environ ; 929: 172572, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38641113

RESUMO

Carbonate bound arsenic act as an important reservoir for arsenic (As) in nature aquifers. Sulfate-reducing bacteria (SRB), one of the dominant bacterial species in reductive groundwater, profoundly affects the biogeochemical cycling of As. However, whether and how SRB act on the migration and transformation of carbonate bound arsenic remains to be elucidated. Batch culture experiment was employed using filed collected arsenic bearing calcite to investigate the release and species transformation of As by SRB. We found that arsenic in the carbonate samples mostly exist as inorganic As(V) (93.92 %) and As(III). The present of SRB significantly facilitated arsenic release from carbonates with a maximum of 22.3 µg/L. The main release mechanisms of As by SRB include 1) calcite dissolution and the liberate of arsenic in calcite lattices, and 2) the break of H-bonds frees arsenic absorbed on carbonate surface. A redistribution of arsenic during culture incubation took place which may due to the precipitation of As2Sx or secondary FeAl minerals. To our best knowledge, it is the first experimental study focusing on the release of carbonate bound arsenic by SRB. This study provides new insights into the fate and transport of arsenic mediated by microorganism within high arsenic groundwater-sediment system.


Assuntos
Arsênio , Carbonatos , Água Subterrânea , Sulfatos , Poluentes Químicos da Água , Arsênio/metabolismo , Água Subterrânea/química , Água Subterrânea/microbiologia , Poluentes Químicos da Água/metabolismo , Carbonatos/metabolismo , Sulfatos/metabolismo , Bactérias/metabolismo , Carbonato de Cálcio/metabolismo , Carbonato de Cálcio/química
19.
Heliyon ; 10(8): e29453, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628729

RESUMO

Objective: Structural support for depressed tibial plateau fractures is receiving increasing attention. Currently, there has been little biomechanical evaluation of structural support. This work aimed to investigate the effect of structural support size and position on fracture fixation stability. Methods: A split-depressed tibial plateau fracture model was created according to the fracture map. Cortical screws combined with structural filler were used for fracture fixation. The filler diameter was set to small, medium and large, and the filler position was set to the center and offset by 1, 2 and 3 mm to study the effect of position and size on stability. Results: The maximum stress on the implant in all scenarios occurs at the lower contact surface between the anterior screw and the filler. Increased support size resulted in increased mean maximum screw stress, depressed fragment axial displacement and separated fragment transverse displacement (screw stress: 266.6 ± 37.7 MPa vs. 266.7 ± 51.0 MPa vs. 273.8 ± 41.5 MPa; depressed displacement: 0.123 ± 0.036 mm vs. 0.133 ± 0.049 mm vs. 0.158 ± 0.050 mm; separated displacement: 0.402 ± 0.031 mm VS 0.412 ± 0.047 mm VS 0.437 ± 0.049 mm). The larger the offset of the support position was, the larger the peak screw stress and the larger the reduction loss of depressed and separated fragment reduction, regardless of the support size. The medium support combined with the central position presented the minimum of peak stress and reduction loss. Cortical bone was below 2 % and trabecular strain was below 10 % for all scenarios. Conclusion: Central placement of structural support provides superior stability for the treatment of depressed tibial plateau fractures compared to the eccentric placement. When a support is placed centrally, optimal stability is achieved when the diameter matches the diameter of the depressed region. Thus, the utilization of equal-diameter fillers to provide central support appears to be an ideal selection for depressed tibial plateau fractures.

20.
J Biomater Sci Polym Ed ; : 1-22, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652755

RESUMO

Titanium (Ti) implants are widely used in orthopedic and dental applications due to their excellent biocompatibility and mechanical properties. However, bacterial adhesion and subsequent biofilm formation on implant surfaces pose a significant risk of postoperative infections and complications. Conventional surface modifications often lack long-lasting antibacterial efficacy, necessitating the development of novel coatings with enhanced antimicrobial properties. This study aims to develop a novel Ag-TiO2-OTS (Silver-Titanium dioxide-Octadecyltrichlorosilane, ATO) nanocomposite coating, through a chemical plating method. By employing a 'resist-killing-disintegrate' approach, the coating is designed to inhibit bacterial adhesion effectively, and facilitate pollutant removal with lasting effects. Characterization of the coatings was performed using spectroscopy, electron microscopy, and contact angle analysis. Antibacterial efficacy, quantitatively evaluated against E. coli and S. aureus over 168 h, showed a significant reduction in bacterial adhesion by 76.6% and 66.5% respectively, and bacterial removal rates were up to 83.8% and 73.3% in comparison to uncoated Ti-base material. Additionally, antibacterial assays indicated that the ratio of the Lifshitz-van der Waals apolar component to electron donor surface energy components significantly influences bacterial adhesion and removal, underscoring a tunable parameter for optimizing antibacterial surfaces. Biocompatibility assessments with the L929 cell line revealed that the ATO coatings exhibited excellent biocompatibility, with minimal cytotoxicity and no significant impact on cell proliferation or apoptosis. The ATO coatings provided a multi-functionality surface that not only resists bacterial colonization but also possesses self-cleaning capabilities, thereby marking a substantial advancement in the development of antibacterial coatings for medical implants.

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