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1.
Plant Biotechnol J ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087631

RESUMO

As a non-collinear expression form of genetic information, chimeric RNAs increase the complexity of transcriptome in diverse organisms. Although chimeric RNAs have been identified in plants, few common features have been revealed. Here, we systemically explored the landscape of chimeric RNAs across multi-accession and multi-tissue using pan-genome and transcriptome data of four plants: rice, maize, soybean, and Arabidopsis. Among the four species, conserved characteristics of breakpoints and parental genes were discovered. In each species, chimeric RNAs displayed a high level of diversity among accessions, and the clustering of accessions using chimeric events was generally concordant with clustering based on genomic variants, implying a general relationship between genetic variations and chimeric RNAs. Through mass spectrometry, we confirmed a fusion protein OsNDC1-OsGID1L2 and observed its subcellular localization, which differed from the original proteins. Phenotypic cues in transgenic rice suggest the potential functions of OsNDC1-OsGID1L2. Moreover, an intriguing chimeric event Os01g0216500-Os01g0216900, generated by a large deletion in basmati rice, also exists in another accession without the deletion, demonstrating its convergence in evolution. Our results illuminate the characteristics and hint at the evolutionary implications of plant chimeric RNAs, which serve as a supplement to genetic variations, thus expanding our understanding of genetic diversity.

2.
J Transl Med ; 22(1): 728, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103887

RESUMO

Cancer remains a leading cause of global mortality. The tumor microbiota has increasingly been recognized as a key regulator of cancer onset and progression, in addition to shaping tumor responses to immunotherapy. Microbes, including viruses, bacteria, fungi, and other eukaryotic species can impact the internal homeostasis and health of humans. Research focused on the gut microflora and the intratumoral microbiome has revolutionized the current understanding of how tumors grow, progress, and resist therapeutic interventions. Even with this research, however, there remains relatively little that is known with respect to the abundance of microbes and their effects on tumors and the tumor microenvironment. Engineered exosomes are a class of artificial extracellular nanovesicles that can actively transport small molecule drugs and nucleic acids, which have the broad prospects of tumor cell therapy. The present review offers an overview of recent progress and challenges associated with the intratumoral microbiome and engineered exosomes in the context of cancer research. These discussions are used to inform the construction of a novel framework for engineered exosome-mediated targeted drug delivery, taking advantage of intratumoral microbiota diversity as a strategic asset and thereby providing new opportunities to more effectively treat and manage cancer in the clinic.


Assuntos
Exossomos , Microbiota , Neoplasias , Humanos , Exossomos/metabolismo , Neoplasias/terapia , Neoplasias/microbiologia , Neoplasias/imunologia , Animais , Sistemas de Liberação de Medicamentos
3.
J Cosmet Dermatol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107974

RESUMO

OBJECTIVE: To investigate the repairing and anti-wrinkle efficacy of the facial cream enriched with C-xyloside, aiming at comprehensively evaluating its skin anti- aging effect and clarify its potential mechanism of action. METHODS: The repairing efficacy was studied on 3D epidermis skin model and the antiaging efficacy was studied on ex-vivo human skin. Two clinical studies were conducted with Chinese females. In the first study, 49 subjects aged between 30 and 50 with wrinkle concerns were recruited and instructed to apply the investigational cream containing C-xyloside for 8 weeks. Wrinkles attributes were assessed by dermatologist. Instrumental measurements on skin hydration, trans-epidermal water loss (TEWL), and skin elasticity were also conducted. In the second study, 30 subjects aged between 25 and 60 with self-declared sensitive skin and facial redness were recruited and instructed to apply the cream for 4 weeks. Biomarker analysis of the stratum corneum was conducted through facial tape strips. RESULTS: The cream improved the histomorphology of the 3D epidermis skin model after SLS stimulation, and significantly increase the expression of LOR and FLG. On human skin, the cream improved the histopathology induced by UV, and significantly increased the protein content of COL I and COL III, collagen density and the number of Ki-67 positive cell of skin compared with model group (n = 3, p < 0.01). The results from the first clinical study demonstrate a significant increased the skin hydration and elasticity by 21.90%, 13.08% (R2) and 12.30% (R5), respectively (n = 49, p < 0.05), and the TEWL values decreased by 33.94% (n = 49, p < 0.05), after 8 weeks application of the cream. In addition, the scores for nasolabial folds, glabellar wrinkle, underneath eye wrinkles, crow's feet wrinkle and forehead wrinkle in the volunteers exhibited a significant reduction of 34.02%, 43.34%, 50.03%, 33.64% and 55.81% respectively (n = 49, p < 0.05). The (rCE)/(fCE) ratio of volunteers based on tape stripping significant increased after using the sample cream (n = 30, p < 0.05). CONCLUSION: The cream containing C-xyloside showed improvement of skin wrinkles and enhancement of skin barrier function. These efficacies may be attributed to the fact that the sample cream can increase the expression of skin barrier related proteins LOR and FLG, promote the maturation of cornified envelope, enhance collagen I and III protein expression and stimulate skin cell proliferation, to provide sufficient evidence supporting its antiaging efficacy of skin.

4.
Free Radic Biol Med ; 223: 172-183, 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39097205

RESUMO

Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and aging-related diseases, its role in the regulation of human mesenchymal stem cell (MSC) senescence has not been investigated. This study aimed to determine the role of ALDH2 in regulating MSC senescence and illustrate the potential mechanisms. MSCs were isolated from young (YMSCs) and aged donors (AMSCs). Senescence-associated ß-galactosidase (SA-ß-gal) staining and Western blotting were used to assess MSC senescence. Reactive oxygen species (ROS) generation and mitochondrial membrane potential were determined to evaluate mitochondrial function. We showed that the expression of ALDH2 increased alongside cellular senescence of MSCs. Overexpression of ALDH2 accelerated YMSC senescence whereas down-regulation alleviated premature senescent phenotypes of AMSCs. Transcriptome and biochemical analyses revealed that an elevated ROS level and mitochondrial dysfunction contributed to ALDH2 function in MSC senescence. Using molecular docking, we identified interferon regulatory factor 7 (IRF7) as the potential target of ALDH2. Mechanistically, ectopic expression of ALDH2 led to mitochondrial dysfunction and accelerated senescence of MSCs by increasing the stability of IRF7 through a direct physical interaction. These effects were partially reversed by knockdown of IRF7. These findings highlight a crucial role of ALDH2 in driving MSC senescence by regulating mitochondrial homeostasis, providing a novel potential strategy against human aging-related diseases.

5.
J Obstet Gynaecol ; 44(1): 2393379, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39166780

RESUMO

BACKGROUND: Spinal anaesthesia is a common anaesthetic method for caesarean sections but often results in hypotension, posing potential risks to maternal and neonatal health. Norepinephrine, as a vasopressor, may be effective in preventing and treating this hypotension. This systematic review and meta-analysis aims to systematically evaluate the efficacy and safety of prophylactic norepinephrine infusion for the treatment of hypotension following spinal anaesthesia in caesarean sections. METHODS: Literature searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases for relevant studies on prophylactic administration of norepinephrine for the treatment of hypotension after spinal anaesthesia in caesarean delivery. Reference lists of included articles were also searched. The latest search update was on March 20, 2024. Meta-analysis was conducted using R software. The methods recommended by the Cochrane Handbook, Begge's and Egger's tests were used for risk of bias evaluation of the included literature. RESULTS: Nine studies were finally included in this study. The results showed that prophylactic administration of norepinephrine was superior to the control group in four aspects of treating hypotension after spinal anaesthesia in caesarean delivery: the incidence of hypotension was reduced [RR = 0.34, 95%CI (0.27-0.43), P < 0.01]; the incidence of severe hypotension was reduced [RR = 0.32, 95%CI (0.21-0.51), P < 0.01]; and maternal blood pressure was more stable with MDPE [MD = -5.00, 95%CI (-7.80--2.21), P = 0.06] and MDAPE [MD = 4.11, 95%CI (1.38-6.85), P < 0.05], the incidence of nausea and vomiting was reduced [RR = 0.52, 95%CI (0.35-0.77), P < 0.01]. On the other hand, the incidence of reactive hypertension was higher than the control group [RR = 3.58, 95%CI (1.94-6.58), P < 0.01]. There was no difference between the two groups in one aspects: newborn Apgar scores [MD = -0.01, 95%CI (-0.10-0.09, P = 0.85)]. CONCLUSION: Prophylactic administration of norepinephrine is effective in treating hypotension after spinal anaesthesia in caesarean delivery patients; however, it does not provide improved safety and carries a risk of inducing reactive hypertension.


Hypotension, or low blood pressure, after spinal anaesthesia can threaten the health of both mothers and their babies during caesarean sections. Norepinephrine is a drug that affects heart rate less and does not easily cross the placental barrier, which may reduce its potential negative effects on the baby. However, there are not many studies on using norepinephrine as a preventive measure. Our study systematically evaluated the use of prophylactic norepinephrine infusion to prevent hypotension in caesarean section patients. We found that it is effective in preventing low blood pressure but does not show improved safety and carries some risk of causing high pressure as a reaction.


Assuntos
Anestesia Obstétrica , Raquianestesia , Cesárea , Hipotensão , Norepinefrina , Vasoconstritores , Humanos , Cesárea/efeitos adversos , Raquianestesia/efeitos adversos , Raquianestesia/métodos , Feminino , Hipotensão/prevenção & controle , Hipotensão/etiologia , Hipotensão/tratamento farmacológico , Norepinefrina/administração & dosagem , Norepinefrina/uso terapêutico , Norepinefrina/efeitos adversos , Gravidez , Anestesia Obstétrica/efeitos adversos , Anestesia Obstétrica/métodos , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico , Adulto
6.
Plant Commun ; : 101066, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39169627

RESUMO

This study leveraged knowledge of the specific known cultivar progenitor "Nanjing11" of a weedy rice population from East China, and discovered that the landrace introgression greatly contributed to the recent feralization of modern cultivars, including the introduction of the Rc gene that confers key weedy traits such as red pericarp and seed dormancy.

7.
BMC Cancer ; 24(1): 1041, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174903

RESUMO

BACKGROUND AND PURPOSE: Ir192 vaginal brachytherapy (IBT) is commonly used for patients with postoperative endometrial cancer (EC). We devised a novel multichannel vaginal applicator that could be equipped with an electronic brachytherapy (EBT) device. We aimed to explore the differences in physical parameters between the EBT and IBT. MATERIALS AND METHODS: This retrospective study included 20 EC patients who received adjuvant IBT from March 1, 2023, to May 1, 2023. Multichannel vaginal cylinders were used, and three-dimensional plans were generated. We designed an electronic multichannel vaginal applicator model and simulated a three-dimensional EBT plan. In order to ensure comparability, D90 of the CTV for the EBT plan was normalized to be equivalent to that of the IBT plan for the same patient. RESULTS: Twenty EBT plans were compared with 20 IBT plans. Results showed, the mean D90 value of clinical target volume (CTV) was 536.1 cGy for both treatment plans. For the mean dose of CTV, the EBT was significantly greater (738.3 vs. 684.3 cGy, p = 0.000). There was no significant difference in CTV coverage between the EBT and IBT plans. For high-dose areas (V200% and V150%), the EBTs were significantly greater. There were no significant differences in the maximum doses to the vaginal mucosa between the EBT and IBT, whether at the apex or in the middle segment. For the bladder and rectum, both the low-dose area and high-dose area were significantly lower in the EBT plans. For the conformity index, there was no significant difference between the EBT and IBT plans. For the dose homogeneity index, the EBT value was lower. CONCLUSION: In conclusion, under the premise of a three-dimensional brachytherapy plan, for patients receiving multichannel vaginal applicator brachytherapy, compared with IBT, EBT could reduce the dose to the surrounding organs at risk while maintaining the dose in the target area.


Assuntos
Braquiterapia , Neoplasias do Endométrio , Radioisótopos de Irídio , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Feminino , Braquiterapia/métodos , Braquiterapia/instrumentação , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/patologia , Estudos Retrospectivos , Radioisótopos de Irídio/uso terapêutico , Planejamento da Radioterapia Assistida por Computador/métodos , Pessoa de Meia-Idade , Idoso , Radiometria , Órgãos em Risco/efeitos da radiação
8.
Rev Cardiovasc Med ; 25(7): 234, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39139413

RESUMO

Background: percutaneous coronary intervention (PCI) has become the mainstay of treatment for atherosclerotic cardiovascular disease (ASCVD). Inflammatory factors have been shown to be involved in the initiation and progression of ASCVD. After PCI, the persistence of inflammation, especially the inflammation released at the target lesion, may affect the stability of non-target lesion plaques. Interleukin-6 (IL-6) is one of the most common inflammatory factors, however studies about the influence of IL-6 on the progression of non-target lesions (NTLs) of coronary artery are limited. This study investigated whether serum IL-6 levels can affect the progression of NTLs after coronary stent implantation. Methods: We performed a retrospective cohort study including 441 patients undergoing coronary angiography (CAG) and stent implantation, who had at least one NTL, between January 2019 and December 2021. They underwent followup CAG 9 to 12 months after PCI. Quartile grouping was based on serum IL-6 levels following readmission. The relationship between serum IL-6 levels and the progression of NTLs after coronary stent implantation was analyzed by using logistic regression analysis and restricted cubic spline regression. Predictive value of IL-6 on NTL progression was evaluated using the receiver operating characteristic (ROC) curve. Results: When compared to the first quartile (Q1) group, the probability of NTL progression was increased in Q2 (adjusted odds ratio (aOR) 3.06, 95% CI 1.29-7.29), Q3 (aOR 3.55, 95% CI 1.52-8.26), and Q4 group (aOR 7.51, 95% CI 3.30-17.05), with a trend test p < 0.001. With the increase of IL-6 levels, the risk of progression of NTLs gradually increased, and there was a non-linear relationship between IL-6 and progression of NTLs (p < 0.001). The ROC curve showed that the critical value of the serum IL-6 level was 12.652 pg/mL (area under the curve is 0.673, sensitivity is 54.5%, specificity is 70.9%, p < 0.05). Conclusions: A high serum IL-6 level is an independent risk factor for the progression of NTLs after coronary stent implantation, and has certain predictive value for the progression of NTLs.

9.
ACS Nano ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39195723

RESUMO

Diagnostic and monitoring for drug-induced liver injury (DILI) predominantly rely on serum aminotransferases. However, owing to their widespread expression across multiple organs, a significant challenge emerges from the absence of reliable biomarkers for DILI diagnosis. Herein, we introduce a concept for DILI detection, circumventing the nonspecific elevation and delayed release of aminotransferases and then straightforwardly focusing on the core feature of DILI, abnormal gene expression caused by drug overdose. The developed full-scale platform integrates the properties of spherical nucleic acids with elaborately designed fluorescence in situ hybridization sequences, enabling the sensitive and specific profiling of drug-overdosed miR-122 expression alterations across molecular, cellular, organismal, and clinical scales and effectively bypassing the phenotypic features of disease. Furthermore, the diagnostic efficacies of serum and total RNA extracted from both mouse and human blood samples for DILI diagnosis were analyzed using the receiver operating characteristic curve and principal component analysis. We anticipate that this universal platform holds potential in facilitating DILI diagnosis, therapeutic evaluation, and prognosis.

10.
New Phytol ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135394

RESUMO

Understanding how life history shapes genetic diversity is a fundamental issue in evolutionary biology, with important consequences for conservation. However, we still have an incomplete picture of the impact of life history on genome-wide patterns of diversity, especially in long-lived semelparous plants. Puya raimondii is a high-altitude semelparous species from the Andes that flowers at 40-100 years of age. We sequenced the whole genome and estimated the nucleotide diversity of 200 individuals sampled from nine populations. Coalescent-based approaches were then used to infer past population dynamics. Finally, these results were compared with results obtained for the iteroparous species, Puya macrura. The nine populations of P. raimondii were highly divergent, highly inbred, and carried an exceptionally high genetic load. They are genetically depauperate, although, locally in the genome, balancing selection contributed to the maintenance of genetic polymorphism. While both P. raimondii and P. macrura went through a severe bottleneck during the Pleistocene, P. raimondii did not recover from it and continuously declined, while P. macrura managed to bounce back. Our results demonstrate the importance of life history, in particular generation time and reproductive strategy, in affecting population dynamics and genomic variation, and illustrate the genetic fragility of long-lived semelparous plants.

11.
Front Nutr ; 11: 1391023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39101008

RESUMO

Objective: This study aims to explore the association between niacin intake and stroke within a diverse, multi-ethnic population. Methods: A stringent set of inclusion and exclusion criteria led to the enrollment of 39,721 participants from the National Health and Nutrition Examination Survey (NHANES). Two interviews were conducted to recall dietary intake, and the USDA's Food and Nutrient Database for Dietary Studies (FNDDS) was utilized to calculate niacin intake based on dietary recall results. Weighted multivariate logistic regression was employed to examine the correlation between niacin and stroke, with a simultaneous exploration of potential nonlinear relationships using restricted cubic spline (RCS) regression. Results: A comprehensive analysis of baseline data revealed that patients with stroke history had lower niacin intake levels. Both RCS analysis and multivariate logistic regression indicated a negative nonlinear association between niacin intake and stroke. The dose-response relationship exhibited a non-linear pattern within the range of dietary niacin intake. Prior to the inflection point (21.8 mg) in the non-linear correlation between niacin intake and stroke risk, there exists a marked decline in the risk of stroke as niacin intake increases. Following the inflection point, the deceleration in the decreasing trend of stroke risk with increasing niacin intake becomes evident. The inflection points exhibit variations across diverse populations. Conclusion: This investigation establishes a negative nonlinear association between niacin intake and stroke in the broader American population.

12.
Angew Chem Int Ed Engl ; : e202410453, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037423

RESUMO

Thorium, a predominant actinide in the Earth's crust, presents significant environmental and health risks due to its radioactive nature. These risks are particularly pronounced during the mining and processing of monazite for rare earth elements (REEs), which contain substantial thorium concentrations. Current instrumental analysis methods for thorium, offer high accuracy but require laborious sample preparation and expensive instruments, making them unsuitable for on-site analysis. Herein, we present a class of color-tunable luminescent lanthanide-based metal-organic frameworks (Ln-MOFs) as fluorochromic sensors for Th4+ cations. Utilizing a heterobimetallic Eu3+/Tb3+ doping strategy, the luminescence colors of EuxTb1-x-BDC-OH can be finely tuned from red, to orange, and to green. More intriguingly, the higher Lewis acidity of Th4+ facilitates the transformation of EuxTb1-x-BDC-OH into a UiO-type Th-MOF via a dissolution-recrystallization mechanism. This process results in a gradual reduction of characteristic Ln3+ emissions and the emergence of blue color ligand-based fluorescence, thereby leading to selective fluorochromic responses with increasing Th4+ concentrations and enabling visible detection of Th4+ cations. Additionally, a custom-built portable optoelectronic device was fabricated, which directly converts luminescence colors into red-green-blue (RGB) values. This device enables easy quantification of Th4+ concentrations without the need for complex instrumentation.

13.
Science ; 385(6704): eadm8762, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38963845

RESUMO

Understanding how numerous quantitative trait loci (QTL) shape phenotypic variation is an important question in genetics. To address this, we established a permanent population of 18,421 (18K) rice lines with reduced population structure. We generated reference-level genome assemblies of the founders and genotyped all 18K-rice lines through whole-genome sequencing. Through high-resolution mapping, 96 high-quality candidate genes contributing to variation in 16 traits were identified, including OsMADS22 and OsFTL1 verified as causal genes for panicle number and heading date, respectively. We identified epistatic QTL pairs and constructed a genetic interaction network with 19 genes serving as hubs. Overall, 170 masking epistasis pairs were characterized, serving as an important factor contributing to genetic background effects across diverse varieties. The work provides a basis to guide grain yield and quality improvements in rice.


Assuntos
Epistasia Genética , Genoma de Planta , Oryza , Locos de Características Quantitativas , Oryza/genética , Sequenciamento Completo do Genoma , Mapeamento Cromossômico , Genes de Plantas , Genótipo , Redes Reguladoras de Genes , Fenótipo
14.
Radiat Oncol ; 19(1): 93, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049106

RESUMO

BACKGROUND: Conventional single-energy CT can only provide a raw estimation of electron density (ED) for dose calculation by developing a calibration curve that simply maps the HU values to ED values through their correlations. Spectral CT, also known as dual-energy CT (DECT) or multi-energy CT, can generate a series of quantitative maps, such as ED maps. Using spectral CT for radiotherapy simulations can directly acquire ED information without developing specific calibration curves. The purpose of this study is to assess the feasibility of utilizing electron density (ED) maps generated by a novel dual-layer detector spectral CT simulator for dose calculation in radiotherapy treatment plans. METHODS: 30 patients from head&neck, chest, and pelvic treatment sites were selected retrospectively, and all of them underwent spectral CT simulation. Treatment plans based on conventional CT images were transplanted to ED maps with the same structure set, including planning target volume (PTV) and organs at risk (OARs), and the dose distributions were then recalculated. The differences in dose and volume histogram (DVH) parameters of the PTV and OARs between the two types of plans were analyzed and compared. Besides, gamma analysis between these plans was performed by using MEPHYSTO Navigator software. RESULTS: In terms of PTV, the homogeneity index (HI), gradient index (GI), D2%, D98%, and Dmean showed no significant difference between conventional plans and ED plans. For OARs, statistically significant differences were observed in parotids D50%, brainstem in head&neck plans, spinal cord in chest plans and rectum D50% in pelvic plans, whereas the variance remained minor. For the rest, the DVH parameters exhibited no significant difference between conventional plans and ED plans. All of the mean gamma passing rates (GPRs) of gamma analysis were higher than 90%. CONCLUSION: Compared to conventional treatment plans relying on CT images, plans utilizing ED maps demonstrated similar dosimetric quality. However, the latter approach enables direct utilization in dose calculation without the requirements of establishing and selecting a specific Hounsfield unit (HU) to ED calibration curve, providing an advantage in clinical applications.


Assuntos
Elétrons , Estudos de Viabilidade , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Elétrons/uso terapêutico , Órgãos em Risco/efeitos da radiação , Radioterapia de Intensidade Modulada/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias/radioterapia , Neoplasias/diagnóstico por imagem , Masculino , Feminino
15.
Bioorg Med Chem Lett ; 110: 129862, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38944398

RESUMO

Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect, making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.


Assuntos
Analgésicos , Canal de Sódio Disparado por Voltagem NAV1.8 , Sulfonamidas , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Animais , Humanos , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Relação Estrutura-Atividade , Benzenossulfonamidas , Estrutura Molecular , Camundongos , Relação Dose-Resposta a Droga , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese química
16.
Nanomaterials (Basel) ; 14(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38921902

RESUMO

The corrosion behavior of 20G and TP347H materials was investigated in molten LiCl-NaCl-KCl salt. The corrosion rates of these materials in molten chloride salt are high and are strongly affected by the alloying surface oxide formation. The 20G shows uniform surface corrosion with almost no protective oxide formation on the surface. In contrast, the austenitic steel TP347H exhibits better corrosion resistance in molten chloride salts due to its high Cr content. Owing to the highly corrosive nature of molten chloride salts, the Cl- in molten salt could react with oxides and alloy, inducing intergranular corrosion of austenitic steel in molten chloride salt environments.

17.
Front Public Health ; 12: 1403409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38932782

RESUMO

Objective: There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study. Methods: This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status. Results: This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty. Conclusion: Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations.


Assuntos
Fragilidade , Inquéritos Nutricionais , Humanos , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Fragilidade/epidemiologia , Estados Unidos/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Fatores de Risco
18.
Med Dosim ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38910070

RESUMO

Respiratory motion management is the crucial challenge for safe and effective application of lung stereotactic body radiotherapy (SBRT). The present study implemented lung SBRT treatment in voluntary deep inspiration breath-hold (DIBH) with surface-guided radiotherapy (SGRT) system and evaluated the geometric and dosimetric benefits of DIBH to organs-at-risk (OARs), aiming to advising the choice between DIBH technology and conventional free breathing 4 dimensions (FB-4D) technology. Five patients of lung SBRT treated in DIBH with SGRT at our institution were retrospectively analyzed. CT scans were acquired in DIBH and FB-4D, treatment plans were generated for both respiratory phases. The geometric and dosimetry of tumor, ipsilateral lung, double lungs and heart were compared between the DIBH and FB-4D treatment plans. In terms of target coverage, utilizing DIBH significantly reduced the mean plan target volume (PTV) by 21.9% (p = 0.09) compared to FB-4D, the conformity index (CI) of DIBH and FB-4D were comparable, but the dose gradient index (DGI) of DIBH was higher. With DIBH expanding lung, the volumes of ipsilateral lung and double lungs were 2535.1 ± 403.0cm3 and 4864.3 ± 900.2cm3, separately, 62.2% (p = 0.009) and 73.1% (p = 0.009) more than volumes of ipsilateral lung (1460.03 ± 146.60cm3) and double lungs (2811.25 ± 603.64cm3) in FB-4D. The heart volume in DIBH was 700.0 ± 146.1cm3, 11.6% (p = 0.021) less than that in FB-4D. As for OARs protection, the mean dose, percent of volume receiving > 20Gy (V20) and percent of volume receiving > 5Gy (V5) of ipsilateral lung in DIBH were significantly lower by 33.2% (p = 0.020), 44.0% (p = 0.022) and 24.5% (p = 0.037) on average, separately. Double lungs also showed significant decrease by 31.1% (p = 0.019), 45.5% (p = 0.024) and 20.9% (p = 0.048) on average for mean dose, V20 and V5 in DIBH. Different from the lung, the mean dose and V5 of heart showed no consistency between DIBH and FB-4D, but lower maximum dose of heart was achieved in DIBH for all patients in this study. Appling lung SBRT in DIBH with SGRT was feasibly performed with high patient compliance. DIBH brought significant dosimetric benefits to lung, however, it caused more or less irradiated heart dose that depend on the patients' individual differences which were unpredictable.

19.
ACS Appl Mater Interfaces ; 16(26): 33723-33732, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38913623

RESUMO

LiFePO4 is widely used because of its high safety and cycle stability, but its inefficient electronic conductivity combined with sluggish Li+ diffusivity restricts its performance. To overcome this obstacle, applying a layer of conductive carbon onto the surface of LiFePO4 has the greatest improvement in electronic conductivity and Li+ diffusivity. However, the rate performance of carbon-coated LiFePO4 makes it difficult to meet the application requirements. Although nitrogen doping improves electrochemical performance by providing active sites and electronic conductivity, the N-doped carbon coating is prone to agglomeration, which causes a sharp decrease in capacity when the current rate increases. In this work, a synergistic N, Mn codoping strategy is implemented to overcome the aforementioned drawbacks by disrupting the large agglomeration of C-N bonds, improving the uniformity of the surface coating layer to enhance the completeness of the conductive network and increasing the number of Li+ diffusion channels, and thus accelerating the mass transfer rate under high-rate current. Consequently, this strategy effectively improves the rate capability (119 mA h g-1 at 10 C) while maintaining excellent cycling performance (88% capacity retention over 600 cycles at 5 C). This work improves the rate of ion diffusion and the rate capability of micrometer-sized LiFePO4, thus, enabling its wider application.

20.
Biochem Biophys Res Commun ; 726: 150259, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-38909535

RESUMO

Hypoxic-ischemic brain damage (HIBD) in the perinatal period is an important cause of cerebral damage and long-term neurological sequelae, and can place much pressure on families and society. Our previous study demonstrated that miRNA-326 reduces neuronal apoptosis by up-regulating the δ-opioid receptor (DOR) under oxygen-glucose deprivation in vitro. In the present study, we aimed to explore the neuroprotective effects of the miRNA-326/DOR axis by inhibiting apoptosis in HIBD using neonatal miRNA-326 knockout mice. Neonatal C57BL/6 mice, neonatal miRNA-326 knockout mice, and neonatal miRNA-326 knockout mice intraperitoneally injected with the DOR inhibitor naltrindole were treated with hypoxic-ischemia (HI). Neurological deficit scores, magnetic resonance imaging, terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling, and Caspase-3, Bax, and B-cell lymphoma 2 (Bcl-2) expression were evaluated on day 2 after HI. Neurobehavioral analyses were performed on days 2 and 28 after HI. Additionally, the Morris water maze test was conducted on days 28. Compared with HI-treated neonatal C57BL/6 mice, HI-treated neonatal miRNA-326 knockout mice had higher neurological deficit scores, smaller cerebral infarction areas, and improved motor function, reaction ability, and long-term spatial learning and memory. These effects were likely the result of inhibiting apoptosis; the DOR inhibitor reversed these neuroprotective effects. Our findings indicate that miRNA-326 knockout plays a neuroprotective effect in neonatal HIBD by inhibiting apoptosis via the target gene DOR.


Assuntos
Animais Recém-Nascidos , Apoptose , Hipóxia-Isquemia Encefálica , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs , Receptores Opioides delta , Animais , Masculino , Camundongos , Apoptose/genética , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptores Opioides delta/genética , Receptores Opioides delta/metabolismo
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