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2.
Med Oncol ; 41(6): 153, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743323

RESUMO

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.


Assuntos
Antraquinonas , Ciclo Celular , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases , DNA Metiltransferase 3B , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Antraquinonas/farmacologia , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Rheum/química , Biologia Computacional
3.
Front Med (Lausanne) ; 11: 1344107, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576708

RESUMO

Background: As the most common acute optic neuropathy in older patients, nonarteritic anterior ischemic optic neuropathy (NAION) presents with varying degrees of visual acuity loss and visual field defect. However, there is no generally accepted treatment for NAION. Objectives: To evaluate the efficacy and safety of platelet-rich plasma (PRP) for patients with acute NAION within 2 months. Design: A prospective, nonrandomized controlled trial. Methods: Twenty-five eyes of 25 patients were enrolled. Of them, 13 received anisodine hydrobromide and butylphthalide-sodium chloride injection continuously for 10 days as basic treatment in the control group, and 12 received two tenon capsule injections of PRP on a 10 days interval as an additional treatment in the PRP group. We compared the best-corrected visual acuity (BCVA) and capillary perfusion density (CPD) of radial peripapillary capillaries and the moth-eaten eara of the peripapillary superficial capillary plexus and deep capillary plexus at 1 day (D1) before the first PRP treatment and 7 days (D7), 14 days (D14), and 30 days (D30) after the first PRP injection. Ocular and systemic adverse effects were assessed. Results: In the PRP group, a better BCVA occurred at D30 (adjusted p = 0.005, compared with D1, recovered from 0.67 ± 0.59 to 0.43 ± 0.59), and a significant improvement in CPD was observed at D30 (adjusted p < 0.001, p = 0.027, p = 0.027, compared with D1, D7, D14, in sequence, the value was 35.97 ± 4.65, 38.73 ± 4.61, 39.05 ± 5.26, 42.71 ± 4.72, respectively). CPD at D7 in the PRP group was better than that in the control group (p = 0.043). However, neither BCVA nor the moth-eaten area index were significantly different (all p > 0.5) between the two groups. The main adverse effect was local discomfort resolved within 1 week, and no other systemic adverse events occurred. Conclusion: Tenon capsule injection of PRP was a safe treatment for AION and could improve capillary perfusion of the optic nerve head and might be helpful in increasing short-term vision in patients with acute NAION.

4.
Sci Rep ; 14(1): 7683, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561502

RESUMO

Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1ß, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1ß, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.


Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Helicobacter , Neoplasias Gástricas , Humanos , Citocinas/metabolismo , Helicobacter pylori/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Helicobacter/metabolismo , Interleucina-8/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Gastrite/patologia , Interleucina-12/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Mucosa Gástrica/metabolismo
5.
J Fungi (Basel) ; 10(4)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38667951

RESUMO

The crucial functional arbuscular mycorrhizal fungi (AMF) and diazotrophs play pivotal roles in nutrient cycling during vegetation restoration. However, the impact of managed vegetation restoration strategies on AMF and diazotroph communities remains unclear. In this study, we investigated the community structure and diversity of AMF and diazotrophs in a karst region undergoing managed vegetation restoration from cropland. Soil samples were collected from soils under three vegetation restoration strategies, plantation forest (PF), forage grass (FG), and a mixture of plantation forest and forage grass (FF), along with a control for cropland rotation (CR). The diversity of both AMF and diazotrophs was impacted by managed vegetation restoration. Specifically, the AMF Shannon index was higher in CR and PF compared to FF. Conversely, diazotroph richness was lower in CR, PF, and FG than in FF. Furthermore, both AMF and diazotroph community compositions differed between CR and FF. The relative abundance of AMF taxa, such as Glomus, was lower in FF compared to the other three land-use types, while Racocetra showed the opposite trend. Among diazotroph taxa, the relative abundance of Anabaena, Nostoc, and Rhizobium was higher in FF than in CR. Soil properties such as total potassium, available potassium, pH, and total nitrogen were identified as the main factors influencing AMF and diazotroph diversity. These findings suggest that AMF and diazotroph communities were more sensitive to FF rather than PF and FG after managed vegetation restoration from cropland, despite similar levels of soil nutrients among PF, FG, and FF. Consequently, the integration of diverse economic tree species and forage grasses in mixed plantations notably altered the diversity and species composition of AMF and diazotrophs, primarily through the promotion of biocrust formation and root establishment.

6.
Acta Biomater ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679405

RESUMO

Diabetic wound management remains a significant challenge in clinical care due to bacterial infections, excessive inflammation, presence of excessive reactive oxygen species (ROS), and impaired angiogenesis. The use of multifunctional wound dressings has several advantages in diabetic wound healing. Moreover, the balance of macrophage polarization plays a crucial role in promoting skin regeneration. However, few studies have focused on the development of multifunctional wound dressings that can regulate the inflammatory microenvironment and promote diabetic wound healing. In this study, an extracellular matrix-inspired glycopeptide hydrogel composed of glucomannan and polypeptide was proposed for regulating the local microenvironment of diabetic wound sites. The hydrogel network, which was formed via Schiff base and hydrogen bonding interactions, effectively inhibited inflammation and promoted angiogenesis during wound healing. The hydrogels exhibited sufficient self-healing ability and had the potential to scavenge ROS and to activate the mannose receptor (MR), thereby inducing macrophage polarization toward the M2 phenotype. The experimental results confirm that the glycopeptide hydrogel is an effective tool for managing diabetic wounds by showing antibacterial, ROS scavenging, and anti-inflammatory effects, and promoting angiogenesis to facilitate wound repair and skin regeneration in vivo. STATEMENT OF SIGNIFICANCE: •The designed wound dressing combines the advantage of natural polysaccharide and polypeptide. •The hydrogel promotes M2-polarized macrophages, antibacterial, scavenges ROS, and angiogenesis. •The multifunctional glycopeptide hydrogel dressing could accelerating diabetic wound healing in vivo.

8.
J Exp Clin Cancer Res ; 43(1): 108, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600610

RESUMO

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Neoplasias Colorretais , Mupirocina , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/antagonistas & inibidores , Sistema y+ de Transporte de Aminoácidos , Carcinogênese , Morte Celular , Transformação Celular Neoplásica , Neoplasias Colorretais/tratamento farmacológico
10.
Exp Cell Res ; 437(1): 113994, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479704

RESUMO

m6A modification has been studied in tumors, but its role in host anti-tumor immune response and TAMs polarization remains unclear. The fatty acid oxidation (FAO) process of TAMs is also attracting attention. A co-culture model of colorectal cancer (CRC) cells and macrophages was used to simulate the tumor microenvironment. Expression changes of m6A demethylase genes FTO and ALKBH5 were screened. ALKBH5 was further investigated. Gain-of-function experiments were conducted to study ALKBH5's effects on macrophage M2 polarization, CRC cell viability, proliferation, migration, and more. Me-RIP and Actinomycin D assays were performed to study ALKBH5's influence on CPT1A, the FAO rate-limiting enzyme. AMP, ADP, and ATP content detection, OCR measurement, and ECAR measurement were used to explore ALKBH5's impact on macrophage FAO level. Rescue experiments validated ALKBH5's mechanistic role in macrophage M2 polarization and CRC malignant development. In co-culture, CRC cells enhance macrophage FAO and suppress m6A modification in M2 macrophages. ALKBH5 was selected as the gene for further investigation. ALKBH5 mediates CPT1A upregulation by removing m6A modification, promoting M2 macrophage polarization and facilitating CRC development. These findings indicate that ALKBH5 enhances fatty acid metabolism and M2 polarization of macrophages by upregulating CPT1A, thereby promoting CRC development.


Assuntos
Neoplasias Colorretais , Macrófagos , Humanos , Regulação para Cima/genética , Macrófagos/metabolismo , Neoplasias Colorretais/patologia , Ácidos Graxos/metabolismo , Microambiente Tumoral , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo
11.
Lung Cancer ; 190: 107541, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38531154

RESUMO

OBJECTIVE: Metabolic reprogramming is an important coordinator of tumor development and resistance to therapy, such as the tendency of tumor cells to utilize glycolytic energy rather than oxidative phosphorylation, even under conditions of sufficient oxygen. Therefore, targeting metabolic enzymes is an effective strategy to overcome therapeutic resistance. MATERIALS AND METHODS: We explored the differential expression and growth-promoting function of MDH2 by immunohistochemistry and immunoblotting experiments in lung cancer patients and lung cancer cells. Pentose phosphate pathway-related phenotypes (including ROS levels, NADPH levels, and DNA synthesis) were detected intracellularly, and the interaction of malate and proteinase 6PGD was detected in vitro. In vivo experiments using implanted xenograft mouse models to explore the growth inhibitory effect and pro-chemotherapeutic function of dimethyl malate (DMM) on lung cancer. RESULTS: We found that the expression of malate dehydrogenase (MDH2) in the tricarboxylic acid cycle (TCA cycle) was increased in lung cancer. Biological function enrichment analysis revealed that MDH2 not only promoted oxidative phosphorylation, but also promoted the pentose phosphate pathway (PPP pathway). Mechanistically, it was found that malate, the substrate of MDH2, can bind to the PPP pathway metabolic enzyme 6PGD, inhibit its activity, reduce the generation of NADPH, and block DNA synthesis. More importantly, DMM can improve the sensitivity of lung cancer to the clinical drug cisplatin. CONCLUSION: We have identified malate as a natural inhibitor of 6PGD, which will provide new leads for the development of 6PGD inhibitors. In addition, the metabolic enzyme MDH2 and the metabolite malate may provide a backup option for cells to inhibit their own carcinogenesis, as the accumulated malate targets 6PGD to block the PPP pathway and inhibit cell cycle progression.


Assuntos
Neoplasias Pulmonares , Animais , Humanos , Camundongos , DNA , Neoplasias Pulmonares/genética , Malatos/farmacologia , NADP/metabolismo
12.
J Environ Manage ; 356: 120664, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508006

RESUMO

Continuous discharge of wastewater, emissions, and solid wastes from steelworks poses environmental risks to ecosystems. However, the role of keystone taxa in maintaining multifunctional stability during environmental disturbances remains poorly understood. To address this, we investigated the community diversity, assembly mechanisms, and soil multifunctionality of soils collected from within the steelworks (I), within 2.5 km radius from the steelworks (E), and from an undisturbed area (CK) in Jiangsu Province, China, via 16 S rRNA sequencing. Significant differences were found in the Chao1 and the richness indexes of the total taxa (p < 0.05), while the diversity of keystone taxa was not significant at each site (p > 0.05). The deterministic processes for total taxa were 42.9%, 61.9% and 47.7% in CK, E, and I, respectively. Steelworks stress increased the deterministicity of keystone taxa from 52.3% in CK to 61.9% in E and I soils. The average multifunctionality indices were 0.518, 0.506 and 0.513 for CK, E and I, respectively. Although the soil multifunctionality was positive correlated with α diversity of both the total and keystone taxa, the average degree of keystone taxa in functional network increased significantly (79.96 and 65.58, respectively), while the average degree of total taxa decreased (44.59 and 51.25, respectively) in the E and I. This suggests keystone taxa contribute to promoting the stability of ecosystems. With increasing disturbance, keystone taxa shift their function from basic metabolism (ribosome biogenesis) to detoxification (xenobiotics biodegradation, metabolism, and benzoate degradation). Here we show that keystone taxa are the most important factor in maintaining stable microbial communities and functions, providing new insights for mitigating pollution stress and soil health protection.


Assuntos
Microbiota , Solo , Microbiologia do Solo , Bactérias/genética , Poluição Ambiental
13.
Adv Healthc Mater ; : e2304386, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373601

RESUMO

Tissue engineering at single-cell resolution has enhanced therapeutic efficacy. Droplet microfluidics offers a powerful platform that allows deterministic single-cell encapsulation into aqueous droplets, yet the direct encapsulation of cells into microgels remains challenging. Here, the design of a microfluidic device that is capable of single-cell encapsulation within polyethylene glycol norbornene (PEGNB) hydrogels on-chip is reported. Cells are first ordered in media within a straight microchannel via inertial focusing, followed by the introduction of PEGNB solution from two separate, converging channels. Droplets are thoroughly mixed by passage through a serpentine channel, and microgels are formed by photo-photopolymerization. This platform uniquely enables both single-cell encapsulation and excellent cell viability post-photo-polymerization. More than 90% of singly encapsulated mesenchymal stromal cells (MSCs) remain alive for 7 days. Notably, singly encapsulated MSCs have elevated expression levels in genes that code anti-inflammatory cytokines, for example, IL-10 and TGF-ß, thus enhancing the secretion of proteins of interest. Following injection into a mouse model with induced inflammation, singly encapsulated MSCs show a strong retention rate in vivo, reduce overall inflammation, and mitigate liver damage. These translational results indicate that deterministic single-cell encapsulation could find use in a broad spectrum of tissue engineering applications.

14.
Plant Cell Rep ; 43(3): 63, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340191

RESUMO

KEY MESSAGE: To establish a sterile culture system and protoplast regeneration system for Bryum argenteum, and to establish and apply CRISPR/Cas9 system in Bryum argenteum. Bryum argenteum is a fascinating, cosmopolitan, and versatile moss species that thrives in various disturbed environments. Because of its comprehensive tolerance to the desiccation, high UV and extreme temperatures, it is emerging as a model moss for studying the molecular mechanisms underlying plant responses to abiotic stresses. However, the lack of basic tools such as gene transformation and targeted genome modification has hindered the understanding of the molecular mechanisms underlying the survival of B. argenteum in different environments. Here, we reported the protonema of B. argenteum can survive up to 95.4% water loss. In addition, the genome size of B. argenteum is approximately 313 Mb by kmer analysis, which is smaller than the previously reported 700 Mb. We also developed a simple method for protonema induction and an efficient protoplast isolation and regeneration protocol for B. argenteum. Furthermore, we established a PEG-mediated protoplast transient transfection and stable transformation system for B. argenteum. Two homologues of ABI3(ABA-INSENSITIVE 3) gene were successfully cloned from B. argenteum. To further investigate the function of the ABI3 gene in B. argenteum, we used the CRISPR/Cas9 genetic editing system to target the BaABI3A and BaABI3B gene in B. argenteum protoplasts. This resulted in mutagenesis at the target in about 2-5% of the regenerated plants. The isolated abi3a and abi3b mutants exhibited increased sensitivity to desiccation, suggesting that BaABI3A and BaABI3B play redundant roles in desiccation stress. Overall, our results provide a rapid and simple approach for molecular genetics in B. argenteum. This study contributes to a better understanding of the molecular mechanisms of plant adaptation to extreme environmental.


Assuntos
Briófitas , Bryopsida , Edição de Genes , Bryopsida/genética , Briófitas/genética , Estresse Fisiológico/genética , Transformação Genética , Sistemas CRISPR-Cas/genética , Protoplastos
15.
Acta Pharmacol Sin ; 45(5): 1044-1059, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38326625

RESUMO

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.


Assuntos
Antineoplásicos , Proliferação de Células , Neoplasias Colorretais , Depsipeptídeos , Compostos Macrocíclicos , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Depsipeptídeos/farmacologia , Depsipeptídeos/uso terapêutico , Depsipeptídeos/química , Depsipeptídeos/síntese química , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Br J Ophthalmol ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38237954

RESUMO

PURPOSE: To describe the pattern of MRI changes in the pregeniculate visual pathway in Leber hereditary optic neuropathy (LHON). METHOD: This retrospective observational study enrolled 60 patients with LHON between January 2015 and December 2021. The abnormal MRI features seen in the pregeniculate visual pathway were investigated, and then correlated with the causative mitochondrial DNA (mtDNA) mutation, the distribution of the MRI lesions and the duration of vision loss. RESULT: The cohort included 48 (80%) males and 53 (88%) had bilateral vision loss. The median age of onset was 17.0 years (range 4.0-58.0). 28 (47%) patients had the m.11778G>A mutation. 34 (57%) patients had T2 hyperintensity (HS) in the pregeniculate visual pathway and 13 (22%) patients with chiasmal enlargement. 20 patients (71%) carrying the m.11778G>A mutation had T2 HS, significantly more than the 14 patients (44%) with T2 HS in the other LHON mutation groups (p=0.039). Furthermore, significantly more patients in the m.11778G>A group (16 patients (57%)) had T2 HS in optic chiasm (OCh)/optic tract (OTr) than the other LHON mutation groups (7 patients (22%), p=0.005). Optic chiasmal enlargement was more common in patients with vision loss duration <3 months compared with those ≥3 months (p=0.028). CONCLUSION: T2 HS in the pregeniculate visual pathway is a frequent finding in LHON. Signal changes in the OCh/OTr and chiasmal enlargement, in particular within the first 3 months of visual loss, were more commonly seen in patients carrying the m.11778G>A mtDNA mutation, which may be of diagnostic significance.

17.
J Colloid Interface Sci ; 660: 953-960, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38281476

RESUMO

Inanimate motors, driven by the difference in surface tension, provide platforms for studying the physics of characteristic motion and mimicking the complex behaviors of biological systems. However, it is challenging to endow inanimate motors with high autonomy, with an emphasis on simulating the behavior of living organisms in response to external stimuli. Herein, by applying sodium chloride (NaCl) as an external stimulus, we achieve the regulation of motion mode and chemotaxis in a self-propelled camphor system. We present a comprehensive surface/interface understanding of motion bifurcation with the increase of concentration NaCl, i.e., continuous motion to no motion via oscillatory motion. The features of motions (the speed and frequency) and the mechanisms are elucidated depending on the concentrations of NaCl and sodium dodecyl sulfate (SDS). Furthermore, the characteristic motion and chemotaxis to the salt stimulus are correlated to the dynamic breaking/reforming of the surface tension balance and gradient-type distribution phenomenon triggered by dynamic camphor dissolution, surfactant adsorption /diffusion and camphor-surfactant interaction. This work sheds light on the typical motions of inanimate motors and scrutinizes the synergy between dual additives, which will boost the design of advanced self-propelled systems with nonlinear characteristic motion.

18.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167013, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38199515

RESUMO

Inflammatory bowel disease (IBD) is an incurable and disabling bowel disease driven by multiple risk factors that severely limit patients' quality of life. We integrated the RNA-sequencing data of 1238 IBD patients, and investigated the pathogenesis of IBD by combining transcriptional element prediction analysis and immune-related analysis. Here, we first determined that KIAA1109 is inhibited in IBD patients. The expression of KIAA1109 and NOD2, the key receptor of NOD-like receptors, showed a negative correlation. The NOD-like receptor signaling pathway is activated and exerts transcriptional regulation on the chemokines CXCL1 and CXCL2 through the activation of the transcription factors NFκB and AP1. Analysis of immune infiltration revealed that the expression of chemokines CXCL1 and CXCL2 may regulate the inflammatory response induced by immune cells. These findings suggest that the KIAA1109-NOD2-NFκB/AP1-CXCL1/CXCL2 regulatory axis is the molecular mechanism of IBD pathogenesis, which will provide a new perspective for the diagnosis, treatment and management of IBD patients.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Qualidade de Vida , Doenças Inflamatórias Intestinais/genética , Marcadores Genéticos , Perfilação da Expressão Gênica , Quimiocinas/genética
19.
Dalton Trans ; 53(8): 3559-3572, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38284391

RESUMO

A bifunctional catalyst used for urea oxidation-assisted hydrogen production can efficiently catalyze the urea oxidation reaction (UOR) and hydrogen evolution reaction (HER) simultaneously, thus simplifying electrolytic cell installation and reducing the cost. Constructing the heterointerface of two components or species and doping heteroatom are effective strategies to improve the performance of electrocatalysts, which could regulate the local electronic structure of the catalysts at their interface region, adjust their orbital overlap, and achieve enhanced catalytic performance. In this study, a simple hydrothermal method was studied for the preparation of B-doped Ni5P4/Ni2P heterostructures on nickel foam (B-Ni5P4/Ni2P@NF). Under 1 M KOH at a current density of 10 mA cm-2, an overpotential of 76 mV was obtained for the HER. When 0.3 M urea was added to 1 M KOH, the performance of the prepared catalyst was greatly improved. When the current density reached 10 mA cm-2, the potential was only 1.35 V. In addition, urea-assisted overall water splitting voltage was only 1.41 V. Thus, the B-Ni5P4/Ni2P catalyst possess excellent electrocatalytic activity. The main reason for the excellent properties of the electrocatalyst is the construction of heterostructure, which regulates the electronic structure of the catalyst at its interface and generates a new efficient active site. In addition, the doping of B atoms further promotes the charge transfer rate, thus strengthening the interaction between two phases and improving the catalytic performance. This study provides a simple, environmentally friendly, and rapid design method to prepare an active bi-functional electrocatalyst that has a positive effect on urea-assisted overall water splitting.

20.
Small ; 20(19): e2308453, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38221691

RESUMO

Despite great efforts on economical and functionalized carbon materials, their scalable applications are still restricted by the unsatisfying energy storage capability under high-rate conditions. Herein, theoretical and methodological insights for surface-to-bulk engineering of multi-heteroatom-doped hollow porous carbon (HDPC), with subtly designed Zn(OH)F nanoarrays as the template are presented. This fine-tuned HDPC delivers an ultrahigh-rate energy storage capability even at a scan rate of 3000 mV s-1 (fully charged within 0.34 s). It preserves a superior capacitance of 234 F g-1 at a super-large current density of 100 A g-1 and showcases an ultralong cycling life without capacitance decay after 50 000 cycles. Through dynamic and theoretical analysis, the key role of in situ surface-modified heteroatoms and defects in decreasing the K+-adsorption/diffusion energy barrier is clarified, which cooperates with the porous conductive highways toward enhanced surface-to-bulk activity and kinetics. In situ Raman aids in visualizing the reversibly dynamic adsorption/releasing of the electrolyte ions on the tailored carbon structure during the charge/discharge process. The potential of the design concept is further evidenced by the enhanced performances in water-in-salt electrolytes. This surface-to-bulk nanotechnology opens the path for developing high-performance energy materials to better meet the practical requirements in the future.

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