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1.
J Plast Surg Hand Surg ; 59: 102-107, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39246152

RESUMEN

PURPOSE: This study aims to investigate whether contrast-enhanced ultrasound (CEUS) could be used to reveal the status of blood supply of the superficial flap of rat model in the early postoperative stage. METHODS: One viable and one ischemic random-pattern flap were prepared on the left and right back of the same rat respectively with a number of 40. CEUS examinations were applied within 12 h and 7 days postoperatively, and the quantitative measurements of microvascular blood volume (BV) of the base and the end of both flaps were expressed using acoustic intensity as a ratio to that of the healthy skin. RESULTS: Within 12 h post operation, there was a smaller BV value of the ischemic ends than that of both the ischemic bases and viable ends (p < 0.001), while no difference was indicated between ischemic bases and viable bases or between viable bases and viable ends. The same result was provided 7 days post operation. CONCLUSION: Microcirculation of superficial tissues such as random-pattern flaps in this rat model can be assessed quantitatively by CEUS. It could sensitively and accurately reveal the objective status of tissue perfusion in the early postoperative stage.


Asunto(s)
Medios de Contraste , Microcirculación , Colgajos Quirúrgicos , Ultrasonografía , Animales , Colgajos Quirúrgicos/irrigación sanguínea , Microcirculación/fisiología , Masculino , Ratas Sprague-Dawley , Ratas , Isquemia/diagnóstico por imagen , Periodo Posoperatorio , Volumen Sanguíneo
2.
Front Pharmacol ; 15: 1411459, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239642

RESUMEN

Introduction: Graves' disease (GD) is the most common cause of hyperthyroidism and can affect multiple systems of the body. Currently, commonly-used treatment methods for GD have a series of shortcomings. In contrast, traditional Chinese medicine has been proven to be effective in inhibiting the progression of GD and is expected to become a key direction for the development of new drugs in the future. Therefore, a network meta-analysis was performed to compare the impacts of different traditional Chinese medicines on the curative effect, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) and thyrotropin receptor antibody (TRAb) in patients with GD. Methods: PubMed, Embase, Cochrane Library, Web of Science, WanFang, Weipu, and CNKI were searched for the randomized controlled trials of traditional Chinese medicine on GD patients up to 19 December 2023. The quality of the included studies was evaluated regarding the risk of bias, and the data were analyzed by R software. Results: Thirty-five articles were included in the analysis, involving 2828 GD patients and traditional Chinese medicines including Bailing Capsule, Jinshuibao Capsule, Astragalus injection, Jiakangling Tablet, Jiakangling Capsule, Tripterygium Wilfordii, Sanjie Xiaoying Decoction, Prunella vulgaris (L.) Oral Liquid, P. vulgaris (L.) Granules, Xiehuo Xiaoying Recipe, Xiehuo Yangyin Powder, Yikang Pill and Yinjia Pellet. The results of network meta-analysis suggested that for GD patients, Bailing Capsule, Jiakangling Capsule, Tripterygium wilfordii, P. vulgaris (L.) Oral Liquid and Yinjia Pellet had better curative effect compared with Western medicine. Prunella vulgaris (L.) Granules and Yikang Pill could improve the TSH level. Prunella vulgaris (L.) Granules, P. vulgaris (L.) Oral Liquid and Yikang Pill could reduce FT3 level. Jiakangling Capsule, P. vulgaris (L.) Granules, P. vulgaris (L.) Oral Liquid and Yikang Pill could reduce the FT4 level. Prunella vulgaris (L.) Oral Liquid can reduce the level of TPOAb and TRAb. Besides, Yinjia Pellet was the most helpful in improving the curative effect. Yikang Pill could best improve TSH. Prunella vulgaris (L.) Granules had the best effect on reducing FT3. Prunella vulgaris (L.) Granules performed best in reducing FT4. Prunella vulgaris (L.) Oral Liquid had the most favorable effect on reducing TPOAb and TRAb. Conclusion: Based on the current research, it is safe to conclude that Chinese medicine can improve the curative effect and TSH level of patients with GD, and reduce the levels of FT3, FT4, TPOAb and TRAb. Besides, Yinjia Pellet is the most helpful in improving the curative effect. Yikang Pill can best improve TSH. Prunella vulgaris (L.) Granules have the best effect on reducing FT3. Prunella vulgaris (L.) Granules perform best in reducing FT4. Prunella vulgaris (L.) Oral Liquid has the most favorable effect on reducing TPOAb and TRAb. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42024521912.

3.
Photoacoustics ; 39: 100638, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39221436

RESUMEN

Metallurgical defects in metal laser additive manufacturing (LAM) are inevitable due to complex non-equilibrium thermodynamics. A laser ultrasonic system was designed for detecting surface/near-surface defects in the layer-by-layer LAM process. An approach was proposed for ultrasonic imaging of defects based on variable time window intensity mapping with adaptive 2σ threshold denoising. The Gaussian mixture model hypothesis and expectation-maximization algorithm can automatically differentiate between components dominated by defects and background noises, thereby providing an adaptive threshold that accommodates detection environments and surface roughness levels. Results show that the ultrasonic wave reflection at defect boundaries diminishes far-field ultrasonic intensity upon pulsed laser irradiation on surface defects, enabling defect size and location characterization. This method is applicable to LAM samples with a significant surface roughness of up to 37.5 µm. It can detect superficial and near-surface defects down to 0.5 mm in diameter and depth, making it significant for online defect detection in additive manufacturing.

4.
Br J Cancer ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223303

RESUMEN

BACKGROUND: This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency. RESULTS: Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43-1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27-0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates. CONCLUSIONS: Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients.

6.
J Multidiscip Healthc ; 17: 4373-4382, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39262823

RESUMEN

Purpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies. Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA. Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA's place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05). Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.

7.
Genes Dis ; 11(6): 101117, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39263535

RESUMEN

Renal fibrosis is a complex and multifactorial process that involves inflammation, cell proliferation, collagen, and fibronectin deposition in the kidney, ultimately leading to chronic kidney disease and even end-stage renal disease. The main goal of treatment is to slow down or halt the progression of fibrosis and to improve or preserve kidney function. Despite significant progress made in understanding the underlying mechanisms of renal fibrosis, current therapies have limited renal protection as the disease progresses. Exosomes derived from stem cells are a newer area of research for the treatment of renal fibrosis. Exosomes as nano-sized extracellular vesicles carry proteins, lipids, and nucleic acids, which can be taken up by local or distant cells, serving as mediators of intercellular communication and as drug delivery vehicles. Exosomes deliver molecules that reduce inflammation, renal fibrosis and extracellular matrix protein production, and promote tissue regeneration in animal models of kidney disease. Additionally, they have several advantages over stem cells, such as being non-immunogenic, having low risk of tumor formation, and being easier to produce and store. This review describes the use of natural and engineered exosomes containing therapeutic agents capable of mediating anti-inflammatory and anti-fibrotic processes during both acute kidney injury and chronic kidney disease. Exosome-based therapies will be compared with stem cell-based treatments for tissue regeneration, with a focus on renal protection. Finally, future directions and strategies for improving the therapeutic efficacy of exosomes are discussed.

8.
Phys Chem Chem Phys ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39279742

RESUMEN

The BiFeO3-BaTiO3 solid solution exhibits enhanced electric properties due to its modified phase structure with relaxor characteristics and reduced leakage current. Despite these advancements, the underlying mechanism behind the phase transition from a ferroelectric to a relaxor state in BF-BT ceramics remains largely unexplored. Here, the evolution of strain in (0.67 - x)BiFeO3-0.33BaTiO3-xBi(Mg0.5Zr0.5)O3 ceramics is investigated, with a focus on the strain transition from a ferroelectric to a relaxor phase. A strengthening of relaxor behavior is observed in the modified rhombohedral (R) and pseudocubic (PC) phase structure, resulting in optimal strain (Suni = 0.25%, Spos = 0.24%) at x = 0.04. The enhanced strain is attributed to the promotion of domain switching and the presence of strong random fields, with polar nanoregions integrating into a long-range ordered matrix. Furthermore, a gradual increase in strain with rising temperature is noted, driven by increased polarization and the expansion of ferroelectric domains. This study underscores the critical role of structural modifications in augmenting the electric response of BF-BT ceramics, thereby advancing the development of lead-free piezoelectric materials.

9.
Front Immunol ; 15: 1442673, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234249

RESUMEN

The interplay between immune components and the epithelium plays a crucial role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Natural killer (NK) cells, one of the main tumor-killing immune cell populations, have received increasing attention in HNSCC immunotherapy. In this review, we explore the mechanism underlying the interplay between NK cells and HNSCC. A series of immune evasion strategies utilized by cancer cells restrict HNSCC infiltration of NK cells. Overcoming these limitations can fully exploit the antineoplastic potential of NK cells. We also investigated the tumor-killing efficacy of NK cell-based immunotherapies, immunotherapeutic strategies, and new results from clinical trials. Notably, cetuximab, the most essential component of NK cell-based immunotherapy, inhibits the epidermal growth factor receptor (EGFR) signaling pathway and activates the immune system in conjunction with NK cells, inducing innate effector functions and improving patient prognosis. In addition, we compiled information on other areas for the improvement of patient prognosis using anti-EGFR receptor-based monoclonal antibody drugs and the underlying mechanisms and prognoses of new immunotherapeutic strategies for the treatment of HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Células Asesinas Naturales , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Células Asesinas Naturales/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Inmunoterapia/métodos , Animales , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/inmunología , Escape del Tumor/efectos de los fármacos , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Transducción de Señal , Cetuximab/uso terapéutico , Cetuximab/farmacología
10.
J Org Chem ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240699

RESUMEN

Herein, a visible-light-promoted radical cascade cyclization of heterocyclic ketene aminals (HKAs) and thiocyanates was developed to access functionalized fused 2-iminothiazolines. This novel cascade reaction can be realized under only visible-light irradiation without the help of external photocatalysts, oxidants, and additives. These multicomponent cascade reactions demonstrate excellent selectivity for the Z-isomers and ensure the formation of the products only in their isomeric form. Preliminary mechanism investigations demonstrated that HKAs and thiocyanates can form electron donor-acceptor complexes for harvesting the energy of visible light to activate substrates and generate reactive radicals. This protocol can be used for synthesizing various natural-like products such as fused 2-iminothiazolines. This approach demonstrates multiple advantages such as commercially available substrates, convenient operation, environmentally friendly, mild conditions, and an efficient multicomponent reaction (2A + B).

11.
Commun Biol ; 7(1): 1075, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223298

RESUMEN

Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr-/- mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFß2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFß receptor I/II complex by interacting with unglycosylated TGFß receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFß2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.


Asunto(s)
Carnitina O-Palmitoiltransferasa , Fibrosis , Degeneración Macular , Mitocondrias , Receptores de LDL , Epitelio Pigmentado de la Retina , Factor de Crecimiento Transformador beta2 , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Animales , Degeneración Macular/metabolismo , Degeneración Macular/patología , Degeneración Macular/genética , Ratones , Mitocondrias/metabolismo , Mitocondrias/patología , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/deficiencia , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/genética , Receptores de LDL/metabolismo , Receptores de LDL/genética , Receptores de LDL/deficiencia , Humanos , Ratones Noqueados , Transición Epitelial-Mesenquimal , Metabolismo Energético , Ratones Endogámicos C57BL
12.
Nat Commun ; 15(1): 7700, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227599

RESUMEN

Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

13.
Inorg Chem ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266252

RESUMEN

Pollution of surface water by heavy metal hexavalent chromium ions poses a serious threat to human health; herein, a two-dimensional (2D) cationic breathing Ni-MOF with free nitrate ions between the layers was designed and synthesized according to the characteristics of hexavalent chromium ions, {[Ni(L)2](NO3)2·5H2O}n (L = 1,3,5-tris[4-(imidazol-1-yl)phenyl]benzene). The flexible layer spacing of the 2D breathing Ni-MOF allows the exchange of NO3- by CrO42- without destroying the original structure. Electrostatic and hydrogen bonding interactions between CrO42- and Ni-MOF facilitate its exchange with NO3-. Moreover, CrO42- exhibits a higher binding energy with Ni-MOF compared to NO3-, and the hydrophobic channels of Ni-MOF favor CrO42- trapping due to its lower hydration energy. Consequently, Ni-MOF demonstrates both effective sorption and electrochemical sensing of Cr(VI), achieving a sensitivity of 2.091 µA µM-1 and a detection limit of 0.07 µM.

14.
Commun Biol ; 7(1): 1135, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271748

RESUMEN

Genome differential positioning within interphase nuclei remains poorly explored. We extended and validated Tyramide Signal Amplification (TSA)-seq to map genomic regions near nucleoli and pericentric heterochromatin in four human cell lines. Our study confirmed that smaller chromosomes localize closer to nucleoli but further deconvolved this by revealing a preference for chromosome arms below 36-46 Mbp in length. We identified two lamina associated domain subsets through their differential nuclear lamina versus nucleolar positioning in different cell lines which showed distinctive patterns of DNA replication timing and gene expression across all cell lines. Unexpectedly, active, nuclear speckle-associated genomic regions were found near typically repressive nuclear compartments, which is attributable to the close proximity of nuclear speckles and nucleoli in some cell types, and association of centromeres with nuclear speckles in human embryonic stem cells (hESCs). Our study points to a more complex and variable nuclear genome organization than suggested by current models, as revealed by our TSA-seq methodology.


Asunto(s)
Nucléolo Celular , Centrómero , Heterocromatina , Humanos , Heterocromatina/metabolismo , Heterocromatina/genética , Nucléolo Celular/metabolismo , Nucléolo Celular/genética , Centrómero/metabolismo , Centrómero/genética , Línea Celular
15.
Animals (Basel) ; 14(17)2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39272256

RESUMEN

This experiment aimed to study the effects of tannin supplementation on growth performance, rumen fermentation characteristics, apparent digestibility and serum biochemistry, and antioxidant and immune indexes in fattening lambs. A total of 36 male Hu sheep lambs (body weight = 15.83 ± 0.48 kg and days of age = 55 ± 2 d) were fed a high-concentrate diet and randomly divided into one of three groups of 12 animals each: control with no tannin (CON) and tannin treatments (TA1, 3 g/d per lamb; TA2, 6 g/d per lamb). The feeding experiment lasted for 60 d. The results showed that the average daily gain and ruminal propionate content of lambs in the TA1 group were higher (p < 0.05) than those in the CON group. Lambs fed tannin had significantly increased (p < 0.05) microbial protein and decreased (p < 0.05) ammonia nitrogen concentrations in the rumen. In addition, the crude protein and neutral detergent fiber digestibility of the TA2 group were significantly decreased (p < 0.05) as compared with the TA1 and CON groups, respectively. The serum concentrations of triglyceride, immunoglobulin A, and catalase and the total antioxidant capacity were higher (p < 0.05) in the TA1 group that those in the CON group, whereas an opposite trend of urea nitrogen, interleukin-1ß, and malondialdehyde was found between the two groups. Also, tannin supplementation increased (p < 0.05) Lactobacillus and decreased (p < 0.05) Salmonella counts in the feces of lambs. Taken together, tannin supplementation can improve the growth performance, immunity, and antioxidant ability of fattening lambs fed a high-concentrate diet.

16.
Materials (Basel) ; 17(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39274608

RESUMEN

This study focuses on the calcined coal gangue (CCG)-blended cements containing Stöber nano-SiO2 (SNS) particles. The effects of SNS particles on the workability, hydration behaviour, mechanical properties and microstructure evolution of the blended cements were comprehensively investigated at curing ages ranging from 1 to 28 d. The hydration behaviour was studied via isothermal calorimetry test, X-ray diffraction (XRD) and thermogravimetric (TG) tests. The microstructural evolution was studied using mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). The results show that the incorporation of SNS led to a significant reduction in fluidity, particularly at an SNS content of 3%. The SNS significantly increased the compressive strength of the CCG-blended cement at all curing ages, and the optimum SNS content was found to be 2%. SNS significantly accelerated not only the early cement hydration but also the pozzolanic reaction of CCG at later curing ages, resulting in a decrease in portlandite, as evidenced by the isothermal calorimetry, XRD and TG analysis. Microstructural analysis shows that the incorporation of SNS effectively refined the pore structure of the CCG-blended cement, resulting in the formation of a dense microstructure. All these beneficial effects of SNS provides advantages in the development of the compressive strength of the CCG-blended cement at all curing ages.

18.
Plant Cell Environ ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39222021

RESUMEN

Cobalt (Co) contamination in soils potentially affects human health through the food chain. Although rice (Oryza sativa) as a staple food is a major dietary source of human Co intake, it is poorly understood how Co is taken up by the roots and accumulated in rice grain. In this study, we physiologically characterized Co accumulation and identified the transporter for Co2+ uptake in rice. A dose-dependent experiment showed that Co mainly accumulated in rice roots. Further analysis with LA-ICP-MS showed Co deposited in most tissue of the roots, including exodermis, endodermis and stele region. Co accumulation analysis using mutants defective in divalent cation uptake showed that Co2+ uptake in rice is mediated by the Mn2+/Cd2+/Pb2+ transporter OsNramp5, rather than OsIRT1 for Fe2+ and OsZIP9 for Zn2+. Knockout of OsNramp5 enhanced tolerance to Co toxicity. Heterologous expression of OsNramp5 showed transport activity for Co2+ in Saccharomyces cerevisiae. Co2+ uptake was inhibited by either Mn2+ or Cd2+ supply. At the reproductive stage, the Co concentration in the straw and grains of the OsNramp5 knockout lines was decreased by 41%-48% and 28%-36%, respectively, compared with that of the wild-type rice. The expression level of OsNramp5 in the roots was not affected by Co2+. Taken together, our results indicate that OsNramp5 is a major transporter for Co2+ uptake in rice, which ultimately mediates Co accumulation in the grains.

19.
J Cell Mol Med ; 28(16): e70013, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39199011

RESUMEN

Crohn's disease (CD) presents with diverse clinical phenotypes due to persistent inflammation of the gastrointestinal tract. Its global incidence is on the rise. Neutrophil extracellular traps (NETs) are networks released by neutrophils that capture microbicidal proteins and oxidases targeting pathogens. Research has shown that NETs are implicated in the pathogenesis of several immune-mediated diseases such as rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease. The goal of this study was to identify a panel of NET-related genes to construct a diagnostic and therapeutic model for CD. Through analysis of the GEO database, we identified 1950 differentially expressed genes (DEGs) associated with CD. Gene enrichment and immune cell infiltration analyses indicate that neutrophil infiltrates and chemokine-related pathways are predominantly involved in CD, with other immune cells such as CD4 and M1 macrophages also playing a role in disease progression. Utilizing weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks, we identified six hub genes (SPP1, SOCS3, TIMP1, IRF1, CXCL2 and CD274). To validate the accuracy of our model, we performed external validation with statistical differences(p < 0.05). Additionally, immunohistochemical experiments demonstrated higher protein expression of the hub genes in colonic tissues from CD patients compared to healthy subjects (p < 0.05). In summary, we identified six effective hub genes associated with NETs as potential diagnostic markers for CD. These markers not only offer targets for future research but also hold promise for the development of novel therapeutic interventions for CD.


Asunto(s)
Biología Computacional , Enfermedad de Crohn , Trampas Extracelulares , Redes Reguladoras de Genes , Mapas de Interacción de Proteínas , Humanos , Enfermedad de Crohn/genética , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/patología , Biología Computacional/métodos , Trampas Extracelulares/metabolismo , Trampas Extracelulares/genética , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica , Neutrófilos/metabolismo , Neutrófilos/inmunología , Regulación de la Expresión Génica , Biomarcadores , Bases de Datos Genéticas
20.
Nat Methods ; 21(8): 1454-1461, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39122941

RESUMEN

Recent advances in machine learning have enabled the development of next-generation predictive models for complex computational biology problems, thereby spurring the use of interpretable machine learning (IML) to unveil biological insights. However, guidelines for using IML in computational biology are generally underdeveloped. We provide an overview of IML methods and evaluation techniques and discuss common pitfalls encountered when applying IML methods to computational biology problems. We also highlight open questions, especially in the era of large language models, and call for collaboration between IML and computational biology researchers.


Asunto(s)
Biología Computacional , Aprendizaje Automático , Biología Computacional/métodos , Humanos , Algoritmos
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