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1.
J Chem Inf Model ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385334

RESUMO

Current DNA storage schemes lack flexibility and consistency in processing highly redundant and correlated image data, resulting in low sequence stability and image reconstruction rates. Therefore, according to the characteristics of image storage, this paper proposes storing images in DNA via base128 encoding (DNA-base128). In the data writing stage, data segmentation and probability statistics are carried out, and then, the data block frequency and constraint encoding set are associated with achieving encoding. When the image needs to be recovered, DNA-base128 completes internal error correction by threshold setting and drift comparison. Compared with representative work, the DNA-base128 encoding results show that the undesired motifs were reduced by 71.2-90.7% and that the local guanine-cytosine content variance was reduced by 3 times, indicating that DNA-base128 can store images more stably. In addition, the structural similarity index (SSIM) and multiscale structural similarity (MS-SSIM) of image reconstruction using DNA-base128 were improved by 19-102 and 6.6-20.3%, respectively. In summary, DNA-base128 provides image encoding with internal error correction and provides a potential solution for DNA image storage. The data and code are available at the GitHub repository: https://github.com/123456wk/DNA_base128.

2.
Comput Biol Med ; 171: 108103, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38335822

RESUMO

Ultrasound imaging, as a portable and radiation-free modality, presents challenges for accurate segmentation due to the variability of lesions and the similar intensity values of surrounding tissues. Current deep learning approaches leverage convolution for extracting local features and self-attention for handling global dependencies. However, traditional CNNs are spatially local, and Vision Transformers lack image specific bias and are computationally demanding. In response, we propose the Global-Local Fusion Network (GLFNet), a hybrid structure addressing the limitations of both CNNs and Vision Transformers. The GLFNet, featuring Global-Local Fusion Blocks (GLFBlocks), integrates global semantic information with local details to improve segmentation. Each GLFBlock comprises Global and Local Branches for feature extraction in parallel. Within the Global and Local Branches, we introduce the Self-Attention Convolution Fusion Block (SACFBlock), which includes a Spatial-Attention Module and Channel-Attention Module. Experimental results show that our proposed GLFNet surpasses its counterparts in the segmentation tasks, achieving the overall best results with an mIoU of 79.58% and Dice coefficient of 74.62% in the DDTI dataset, an mIoU of 76.61% and Dice coefficient of 71.04% in the BUSI dataset, and an mIoU of 86.77% and Dice coefficient of 87.38% in the BUID dataset. The fusion of local and global features contributes to enhanced performance, making GLFNet a promising approach for ultrasound image segmentation.

3.
Carbohydr Polym ; 330: 121822, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368103

RESUMO

Hydroxypropyl cellulose (HPC) is a sustainable cellulose derivative valued for its excellent biocompatibility and solubility and is widely used in various fields. Recent scientific research on high-substituted HPC mainly focused on its efficient preparation and phase transition behavior. Herein, a novel strategy of high-substituted HPC synthesis was demonstrated by employing DMSO/TBAF·3H2O as a cellulose solvent, exhibiting more efficiency than traditional approaches. High-substituted HPC prepared has remarkable thermal stability, exceptional hydrophilicity, and satisfactory solubility. Phase transition behavior of HPC with varying molar degrees of substitution (MS) was delved and a notable negative correlation between MS and cloud point temperature (TCP), was revealed, particularly evident at an MS of 12.3, where the TCP drops to 33 °C. Moreover, a unique self-assembly behavior featuring structural color and responsiveness to force in a solvent-free environment emerged when the MS exceeded 10.4. These insights comprehensively strengthen the understanding and knowledge of high-substituted HPC, simultaneously paving the way for further HPC investigation and exploitation.

4.
J Nutr Health Aging ; 28(4): 100168, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341967

RESUMO

OBJECTIVES: Frailty is an age-related syndrome associated with poor health outcomes. Studies in developed countries indicate that the dietary inflammatory index (DII) and dietary total antioxidant capacity (DTAC) are important dietary factors influencing the risk of frailty in older adults. However, few studies have explored the association between DII, DTAC, and frailty among older Chinese adults. The objective of the current study was to examine whether DII and DTAC were associated with pre-frailty or frailty among older Chinese adults. DESIGN: A cross-sectional study. SETTING: Community-based. PARTICIPANTS: We included 6414 participants aged ≥60 years. MEASUREMENTS: Dietary intake was assessed using a validated food frequency questionnaire (FFQ). The DII and energy-adjusted DII (E-DII) were calculated using food parameters. DTAC was estimated using two widely adopted antioxidant scores: DTAC based on ferric reducing antioxidant power and dietary antioxidant quality score (DAQS) obtained from vitamins (vitamins A, C, and E) and minerals (zinc and selenium) with antioxidant functions. Frailty was assessed using the frailty index (FI) calculated from 28 health-related deficits. Individuals were classified as robust (FI ≤ 0.10), pre-frailty (FI > 0.10 to <0.25), or frailty (FI ≥ 0.25). Multiple logistic regression models were used to evaluate the associations of DII and DTAC with pre-frailty and frailty. RESULTS: After adjusting for confounding factors, individuals in the highest DII quintile (Q5) were more likely to have pre-frailty (odds ratio [OR] = 1.56; 95% confidence interval [CI]: 1.25-1.93; P for trend <0.001) than those in the lowest Q1. A similar positive association was detected for E-DII and pre-frailty. A significant association was found between DII and frailty. Compared with the lowest Q1, the highest Q5 of DTAC was negatively correlated with pre-frailty (OR = 0.66; 95% CI: 0.52-0.84; P for trend <0.001) and frailty (OR = 0.71; 95% CI: 0.50-0.1.03; P for trend <0.001). The DAQS yielded results similar to pre-frailty results (OR = 0.72; 95% CI: 0.58-0.89; P < 0.001). There was no evidence suggesting an association between DAQS and frailty. CONCLUSIONS: More proinflammatory diets were linked to higher pre-frailty risk, whereas higher levels of dietary antioxidants were associated with lower pre-frailty and frailty risk among older Chinese adults.

5.
Org Lett ; 26(6): 1154-1159, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38323790

RESUMO

The direct functionalization of ß-C(sp2)-H bonds in enamides has garnered increasing attention within the realm of organic synthesis. However, these remarkable advancements are predominantly dependent on transition metals; limited success has been achieved via organocatalytic catalysis. Herein, we report a CPA-catalyzed ß-C(sp2)-H functionalization of enamides cascade intramolecular cyclization to synthesize the chiral dihydropyrimido[1,6-a]indoles bearing gem-difluoromethylene. Moreover, this methodology enables the synthesis of diverse chiral dihydropyrimido[1,6-a]indoles with outstanding enantioselectivities in moderate to high yields.

6.
Medicine (Baltimore) ; 103(5): e36458, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306562

RESUMO

This study aimed to elucidate the potential causative links between inflammatory biomarkers and gastric cancer risk via a two-sample Mendelian randomization approach. Leveraging genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization analysis. Instrumental variable selection for inflammatory markers - namely, tissue factor, monocyte chemotactic protein-1, E-selectin, interleukin 6 receptor, and fatty acid-binding protein 4 - was informed by SNP data from the IEU database. Strongly associated SNPs served as instrumental variables. We applied a suite of statistical methods, including Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), MR-Egger, and mode-based estimates, to compute the odds ratios (ORs) that articulate the impact of these markers on gastric cancer susceptibility. The IVW method revealed that the interleukin 6 receptor was inversely correlated with gastric cancer progression (OR = 0.86, 95% CI = 0.74-0.99, P = .03), whereas fatty acid-binding protein 4 was found to elevate the risk (OR = 1.21, 95% CI = 1.05-1.39, P = .03). Instrumental variables comprised 5, 4, 7, 2, and 3 SNPs respectively. Convergent findings from WME, MR-Egger, and mode-based analyses corroborated these associations. Sensitivity checks, including heterogeneity, horizontal pleiotropy assessments, and leave-one-out diagnostics, affirmed the robustness and reliability of our instruments across diverse gastric malignancy tissues without substantial bias. Our research suggests that the interleukin 6 receptor potentially mitigates, while fatty acid-binding protein 4 may contribute to the pathogenesis of gastric cancer (GC). Unraveling the intricate biological interplay between inflammation and oncogenesis offers valuable insights for preemptive strategies and therapeutic interventions in gastric malignancy management.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Reprodutibilidade dos Testes , Biomarcadores , Proteínas de Ligação a Ácido Graxo , Receptores de Interleucina-6
7.
Neurospine ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38317559

RESUMO

Objective: This study aimed to evaluate the effects of two endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods: Based on CT images of a healthy adult volunteer, six finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate six physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the six models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the two surgical models for the six motion states. N1 showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4-L5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion: In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

8.
J Agric Food Chem ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38303158

RESUMO

The leaf skeletonizer, Pyrausta machaeralis (Lepidoptera: Crambidae), is a serious insect pest of teak (Tectona grandis) in China. The application of insect pheromones is widely applied as an environmentally friendly technology for integrated pest management (IPM). In the present study, crude extracts of sex pheromone glands of calling P. machaeralis females were collected and then analyzed using gas chromatography/electroantennographic detection (GC/EAD) and gas chromatography-mass spectrometry (GC-MS). The combination of infrared spectroscopy (IR) and nuclear magnetic resonance (NMR) spectrometry was used for structure identification. Afterward, their electrophysiological and behavioral activity was evaluated in the laboratory and field. Herein, we eventually determined two active components, E-11-tetradecenyl acetate (E11-14:Ac) and Z-11-tetradecenyl acetate (Z11-14:Ac), at a ratio of 96:4, as the sex pheromone of P. machaeralis. The identification of sex pheromones would facilitate the development of efficient strategies for monitoring and controlling the field populations of P. machaeralis.

9.
Blood Adv ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359367

RESUMO

HCMBL is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL. We sequenced DNA from 371 HCMBL individuals using a targeted sequencing panel of 59 recurrently mutated genes in CLL to identify high-impact mutations. We compared the sequencing results to that of our treatment-naïve CLL cohort(N=855) and employed Cox regression to estimate hazard ratios and 95% confidence intervals (CI) for associations with TTFT. Compared to CLL, the frequencies of any mutated genes were lower in HCMBL (70% versus 52%). At 10-years, 37% of HCMBL individuals with any mutated gene had progressed requiring treatment compared to 10% among HCMBL individuals with no mutations; this led to 5.4-fold shorter TTFT (95%CI:2.6-11.0) among HCMBL with any mutated gene versus none, independent of CLL-IPI. When considering individuals with low-risk of progression according to CLL-IPI, HCMBL individuals with any mutations had 4.3-fold shorter TTFT (95%CI:1.6-11.8) versus those with none. Finally, when considering both CLL-IPI and any mutated gene status, we observed HCMBL individuals who were high-risk for both prognostic factors with worse prognosis compared to low-risk CLL patients (i.e., 5-year progression rate of 32% versus 21%, respectively). Among HCMBL, the frequency of somatically mutated genes at diagnosis is lower than that of CLL. Accounting for both the number of mutated genes and CLL-IPI can identify HCMBL individuals with more aggressive clinical course.

10.
Pathol Res Pract ; 254: 155154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38286054

RESUMO

The serine/threonine kinase (STK) 33 plays a key role in cancer cell proliferation and metastasis. Abnormal STK33 expression is closely related to malignancy of numerous cancers. This study suggests the important role of STK33 in the pathogenesis and metastatic progression of esophageal squamous cell carcinoma (ESCC). STK33 expression in human ESCC tissues was detected by immunohistochemical technique. Further, we analyzed the relationship between STK33 and clinical and pathological factors as well as the prognosis of patients. ECa109 cell line was cultured and transfected with STK33-RNAi lentiviral vector to perform Hochest33342 & PI and metastasis experiments. The TCGA database was used to analyze the STK33 expression level in ESCC. All statistical analyses were performed in SPSS 23.0 software. Differences with P < 0.05 were considered statistically significant. In human ESCC specimens, STK33 was overexpressed and associated with poor prognosis. Silencing STK33 expression suppressed ESCC proliferation, migration, invasion, and tumor growth. STK33 also mediated angiogenesis, TGFß, and inflammatory response in ESCC. Mechanistic investigations revealed that STK33 regulates ESCC through multiple complex pathways. Dysregulated STK33 signaling promotes ESCC growth and progression. Thus, our findings identified STK33 as a candidate treatment target that improves ESCC therapy.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Linhagem Celular Tumoral , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proliferação de Células/genética , Serina/metabolismo , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica/genética
11.
Insect Sci ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214204

RESUMO

The gregarious lifestyle of lepidopteran larvae is diverse and shaped by a complex interplay of ecological and evolutionary factors. Our review showed that the larval-aggregation behavior has been reported in 23 lepidopteran families, indicating multiple evolution of this behavior. Some larvae live in sibling groups throughout all larval instars and even pupation stages, which may result from the kin-selection. In contrast, group fusion may occur among different sibling or foraging groups of larvae and form larger aggregates, and the gregariousness of these species might be driven by the group-selection. While group size and foraging patterns vary greatly across species, it is generally associated with improved larval survivorship and accelerated development. However, the advantages of group living, such as facilitating feeding activities, adjusting the temperature, and defending natural enemies, may diminish along with development, with strong intraspecific competition occurring at later instars, even when food is abundant. Therefore, the group sizes and fission-fusion dynamics of certain gregarious lepidopteran larvae may be a consequence of their cost-benefit balance depending on various biotic and abiotic factors. Trail and aggregation pheromones, silk trails, or body contact contribute to collective movement and group cohesion of gregarious lepidopteran larvae. However, frequent contact among group members may cause the horizontal transmission of pathogens and pesticides, which may bring an integrated pest management strategy controlling gregarious lepidopteran pests.

12.
Mol Med ; 30(1): 7, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200442

RESUMO

BACKGROUND: Intervertebral disc degeneration (IDD) is considered an important pathological basis for spinal degenerative diseases. Tissue engineering is a powerful therapeutic strategy that can effectively restore the normal biological properties of disc units. In this study, hydrogels loaded with growth/differentiation factor 5 (GDF5) and stem cells were combined to provide an effective strategy for nucleus pulposus regeneration. METHODS: Nucleus pulposus stem cells (NPSCs) were obtained by low-density inoculation and culture, and their stem cell characteristics were verified by flow cytometry and a tri-lineage-induced differentiation experiment. A decellularized nucleus pulposus matrix (DNPM) and chitosan hybrid hydrogel was prepared, and GDF5-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres were incorporated into the hydrogels to obtain a composite hydrogels with GDF5-loaded microspheres. Taking bone marrow mesenchymal stem cells (BMSCs) as a reference, the effect of composite hydrogels with GDF5-loaded microspheres on the chondrogenic differentiation of NPSCs was evaluated. A model of intervertebral disc degeneration induced by acupuncture on the tail of rats was constructed, and the repair effect of composite hydrogels with GDF5-loaded microspheres combined with NPSCs on IDD was observed. RESULTS: Stem cell phenotype identification, stemness gene expression and tri-lineage-induced differentiation confirmed that NPSCs had characteristics similar to those of BMSCs. The rat DNPM and chitosan hybrid hydrogels had good mechanical properties, and the GDF5-loaded microspheres sustainably released GDF5. NPSCs grew normally in the composite hydrogels and gradually expressed a chondrocyte phenotype. Animal experiments showed that the composite hydrogels with GDF5-loaded microspheres combined with NPSCs effectively promoted nucleus pulposus regeneration and that the effect of the hydrogels on the repair of IDD was significantly better than that of BMSCs. CONCLUSION: GDF5-loaded microspheres combined with DNPM/chitosan composite hydrogels can effectively promote the differentiation of NPSCs into nucleus pulposus-like cells and effectively preventIDD.


Assuntos
Quitosana , Degeneração do Disco Intervertebral , Núcleo Pulposo , Animais , Ratos , Hidrogéis , Degeneração do Disco Intervertebral/terapia , Microesferas , Células-Tronco
13.
Small ; : e2309906, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38221704

RESUMO

On-site hydrogen production from liquid organic hydrogen carriers e.g., methanol provides an emerging strategy for the safe storage and transportation of hydrogen. Herein, a catalytic architecture consisting of nickel-cobalt nanoclusters dispersed on gallium nitride nanowires supported by silicon for light-driven hydrogen production from methanol is reported. By correlative microscopic, spectroscopic characterizations, and density functional theory calculations, it is revealed that NiCo nanoclusters work in synergy with GaN nanowires to enable the achievement of a significantly reduced activation energy of methanol dehydrogenation by switching the potential-limiting step from *CHO → *CO to *CH3 O → *CH2 O. In combination with the marked photothermal effect, a high hydrogen rate of 5.62 mol·gcat-1·h-1 with a prominent turnover frequency of 43,460 h-1 is achieved at 5 Wcm-2 without additional energy input. Remarkably, the synergy between Co and Ni, in combination with the unique surface of GaN, renders the architecture with outstanding resistance to sintering and coking. The architecture thereby exhibits a high turnover number of >16,310,000 over 600 h. Outdoor testing validates the viability of the architecture for active and robust hydrogen evolution under natural concentrated sunlight. Overall, this work presents a promising architecture for on-site hydrogen production from CH3 OH by virtually unlimited solar energy.

14.
Langmuir ; 40(3): 1902-1908, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38194665

RESUMO

Self-assemblies of two fluorenone-based derivatives (FE and FEC) consisting of a central 2,7-diphenyl-9-fluorenone polar moiety but differing in the flexible terminal groups were investigated by scanning tunneling microscopy (STM) at the 1-octanoic acid/HOPG interface under different concentrations and density functional theory calculation (DFT). STM results reveal a concentration-dependent polymorphic self-assembly behavior for FE, but without the presence of co-adsorbed solvents. As the concentration decreases, the dimer, bracket-like, and ribbon-like self-assembled structures were observed. On the contrary, FEC molecules assemble into only a type of oval-shaped morphology by the intermolecular N···H-O hydrogen bonds with the solvent molecules. Combined with DFT calculations, it can be deduced that the intermolecular van der Waals forces, dipole-dipole interactions, and hydrogen bonding are the main driving forces to stabilize the molecular packing of fluorenone-based polycatenars with strong polarity. Our work is of significance at the molecular level to further clarify the intermolecular interactions and conformational effects on the formation of molecular packing structures with liquid crystal property.

15.
Sci Rep ; 14(1): 79, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168491

RESUMO

Water can be redistributed physically and virtually. We explored water allocation optimization to mitigate water stresses by constructing a physical-virtual dual water system and optimizing the 1987 Yellow River water allocation scheme. We calculated the virtual water volume, identified the virtual in-basin, out-of-basin, and export water volumes, and compared the total regional water demand (i.e., combined physical and virtual water volumes) with regional water planetary boundaries to optimize basin water allocation schemes. Virtual water accounted for > 90% of the total regional demands, whereas physical flows did not significantly impact them. Moreover, allocation quotas for Qinghai and Inner Mongolia should be reduced by 0.113 and 1.005 billion m3, respectively, for sustainability. Furthermore, improving the efficiency of water-intensive sectors and limiting virtual water outflows from heavy industry to out-of-basin sectors are vital to water intensification. Increased attention should be directed toward physical-virtual water demands than the current focus on supply-oriented water allocation.

16.
J Org Chem ; 89(3): 1515-1523, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38253015

RESUMO

Radical cascade cyclization via the cracking of alkenyl C-H has emerged as an attractive and remarkable tool for the rapid construction of ring frameworks with endocyclic double bonds. We developed a cascade reaction of 3-aza-1,5-enynes with sulfur dioxide and cycloketone oxime esters to access cyanoalkylsulfonylated 1,2-dihydropyridines, which can be easily converted to pyridine derivatives. This protocol involves radical addition to the C≡C bond and 6-endo cyclization and features high regioselectivity and a broad substrate scope.

17.
Int Immunopharmacol ; 128: 111398, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38171054

RESUMO

Liver fibrosis, a progression of chronic liver disease, is a significant concern worldwide due to the lack of effective treatment modalities. Recent studies have shown that natural products play a crucial role in preventing and treating liver fibrosis. Isobavachalcone (IBC) is a chalcone compound with anti-inflammatory, antioxidant, and anti-cancer properties. However, its potential antifibrotic effects remain to be elucidated. This study aimed to investigate the antifibrotic effects of IBC on liver fibrosis and its underlying mechanisms in rats. The results showed that IBC significantly ameliorated the pathological damage and collagen deposition in liver tissues; it also reduced the levels of hydroxyproline (HYP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). In addition, IBC activated Nuclear factor E2-associated factor 2/Hemeoxygenase-1 (Nrf2/HO-1) signaling, leading to the nuclear translocation of Nrf2. This translocation subsequently increased the levels of superoxide dismutase (SOD) and glutathione (GSH) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), thereby alleviating oxidative stress-induced damage. Moreover, it inhibited the expression of nuclear factor kappa B (NF-κB), which further reduced the levels of downstream inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta (IL-1ß), thereby suppressing the activation of HSCs and weakening liver fibrosis. In HSC-T6 cell experiments, changes observed in inflammatory responses, oxidative stress indicators, and protein expression were consistent with the in vivo results. Furthermore, the Nrf2 inhibitor (ML385) attenuated the effect of IBC on inhibiting the activation of quiescent HSCs. Consequently, IBC could alleviate liver fibrosis by activating Nrf2/ HO-1 signaling.


Assuntos
Chalconas , Animais , Ratos , Chalconas/farmacologia , Chalconas/uso terapêutico , Glutationa/metabolismo , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo
18.
Tissue Cell ; 86: 102298, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181584

RESUMO

BACKGROUND AND AIMS: The specific mechanisms underlying the inhibition of hepatocellular carcinoma (HCC) proliferation and metastasis by mitochondrial apoptosis are not yet fully understood. However, it plays a vital role in suppressing HCC's ability to proliferate and spread. The involvement of MRPL21, a member within the family of mitochondrial ribosomal proteins (MRPs), is well-documented in both cellular apoptosis and energy metabolism. This study aims to explore and unravel the underlying mechanisms through which MRPL21 contributes to mitochondrial apoptosis and resistance against apoptosis in HCC. METHODS: To evaluate the level of MRPL21 expression at the gene and protein expression levels, analysis was performed on human liver samples and blood using techniques for quantification. A knockdown plasmid targeting MRPL21 was constructed to investigate its impact on the growth and apoptosis of hepatocellular carcinoma (HCC). To evaluate the impact of MRPL21 knockdown on hepatocellular carcinoma (HCC) cell proliferation and apoptosis, various assays were performed including CCK-8 assays, flow cytometry analysis, detection of reactive oxygen species (ROS), and assessment of mitochondrial membrane potential (MMP). Furthermore, the role of MRPL21 in TP53 mutation was examined using Nutlin-3. RESULTS: In HCC tissues and blood samples, an upregulation of MRPL21 expression was observed when compared to samples obtained from healthy individuals, and it is correlated with a poor prognosis for HCC. Silencing MRPL21 can effectively suppress Hep3B and HCCLM3 cells proliferation by modulating the mitochondrial membrane potential, it triggers the generation of reactive oxygen species (ROS), thereby leading to G0/G1 cell cycle arrest and initiation of early apoptosis. Furthermore, by inhibiting P53 activity, Nutlin-3 treatment can enhance MRPL21-deficiency-mediated apoptosis in Hep3B and HCCLM3 cells. CONCLUSION: Through its influence on TP53 mutation, MRPL21 promotes HCC proliferation and progression while conferring resistance to apoptosis. These findings suggest that MRPL21 holds promise as a valuable biomarker for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Mutação , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
19.
Int Immunopharmacol ; 128: 111562, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38244515

RESUMO

Ankylosing spondylitis (AS), is known as a chronic inflammatory autoimmune disease, there is evidence to suggest that gut microbiota disorders may be related to the occurrence and development of AS. Studies have shown that 6-formylindolo[3, 2-b]carbazole (FICZ) has the ability to modulate intestinal homeostasis and inhibit inflammatory responses. The purpose of this work is to evaluate the protective role of FICZ in treating AS and elucidate potential mechanisms. FICZ was administered to the proteoglycan (PG)-induced AS mice for 7 consecutive weeks. The effects of FICZ on AS mice were evaluated by the disease severity, intestinal histopathology, proinflammatory cytokine levels, and intestinal mucosal barrier function. The gut microbiota compositions were profiled through 16S rDNA high-throughput sequencing. We found that FICZ significantly reduced the severity of AS and resulted in the downregulating of TNF-α and IL-17A inflammatory cytokines. Moreover, FICZ ameliorated pathological changes in the ileal and improved intestinal mucosal barrier function. Furthermore, FICZ altered the composition of the gut microbiota by increasing the Bacteroidetes/Firmicutes phylum ratio and enriched the genes related to "glycan biosynthesis and metabolism", thus reversing the process of AS. In conclusion, FICZ suppressed the progression of AS and altered gut microbiota in AS mice, which provided new insight into AS therapy strategy.


Assuntos
Microbioma Gastrointestinal , Espondilite Anquilosante , Camundongos , Animais , Citocinas/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Carbazóis/farmacologia
20.
Heliyon ; 10(2): e24347, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293528

RESUMO

In this study, a novel heterogeneous double-wire arc additive manufacturing method was used for the in-situ synthesis of a novel Ti-Ni-Al-V alloy wall. The results indicated that the synthesis wall was composed of the NiTi2, B2, and Ni4Ti3 phases from the bottom to the top. With an increase in deposition layers, the Ti2Ni content decreased. The hardness at the bottom was ∼685.4 HV0.2, while that of the middle and stable regions was 553 HV0.2. The maximum compressive strength was 2100 MPa. The fracture morphology was brittle. After cyclic compression, the recoverable and unrecoverable strains were 4.79 % and 1.21 %, respectively, indicating excellent recovery characteristics.

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