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Liquid crystal elastomers (LCEs), consisting of polymer networks and liquid crystal mesogens, show a reversible phase change under thermal stimuli. However, the kinetic performance is limited by the inherently low thermal conductivity of the polymers. Transforming amorphous bulk into a fiber enhances thermal conductivity through the alignment of polymer chains. Challenges are present due to their rigid networks, while cross-links are crucial for deformation. Here, we employ hydrodynamic alignment to orient the LCE domains assisted by controlled in situ cross-linking and to remarkably reduce the diameter to submicrons. We report that the intrinsic thermal conductivity of LCE fibers at room temperature reaches 1.44 ± 0.32 W/m-K with the sub-100 nm diameter close to the upper limit determined in the quasi-1D regime. Combining the outstanding thermal conductivity and thin diameters, we anticipate these fibers to exhibit a rapid response and high force output in thermomechanical systems. The fabrication method is expected to apply to other cross-linked polymers.
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Monascus has the ability to produce secondary metabolites, such as monacolin K (MK), known for its physiological functions, including lipid-lowering effects. Widely utilized in industries such as health food and medicine, MK is a significant compound derived from Monascus. Quinoa, recognized by the Food and Agriculture Organization of the United Nations as "the only plant food that can meet human basic nutritional needs by itself", possesses dual advantages of high nutritional value and medicinal food homology. This study employed animal experiments to investigate the hypolipidemic activity of Monascus-fermented quinoa (MFQ) and explored the molecular mechanism underlying the lipid-lowering effect of MFQ on hyperlipidemic mice through transcriptomic and metabolomic analyses. The results demonstrated that high-dose MFQ intervention (1600 mg kg-1 d-1) effectively decreased weight gain in hyperlipidemic mice without significant changes in cardiac index, renal index, or spleen index. Moreover, hepatic steatosis in mice was significantly improved. Serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol were markedly reduced, demonstrating that the lipid-lowering effect of MFQ was comparable to the drug control lovastatin. Conversely, both low-dose MFQ (400 mg kg-1 d-1) and unfermented quinoa exhibited no significant lipid-lowering effect. Integrated analysis of the transcriptome and metabolome suggested that MFQ may regulate amino acid levels in hyperlipidemic mice by influencing metabolic pathways such as phenylalanine, tyrosine, and tryptophan metabolism. This regulation alleviates hyperlipidemia induced by a high-fat diet, resulting in a significant reduction in blood lipid levels in mice.
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Melatonin plays an important role in plant growth and development. However, little information is available about melatonin regulating rice panicle structure and yield. This study explored the regulatory effects and mechanisms of melatonin spraying before the panicle differentiation stage on rice panicle structure and grain quality. The results showed that spraying melatonin before panicle differentiation increased rice yield, which was mainly reflected in the increase in spikelets per panicle and the percentage of filled grains. In addition, melatonin treatment significantly increased the panicle length. The results of panicle structure analysis showed that the increase in spikelets per panicle caused by melatonin was attributed to the significant increase in the number of secondary branches, total number of secondary branch spikelets, and number of spikelets per secondary branch. The results showed that melatonin can increase the content of zeatin, auxin, and gibberellin, and reduce the content of abscisic acid. These results showed that melatonin affected panicle structure by regulating hormone content, thereby improving yield. In addition, melatonin improves the processing quality, appearance quality, and nutritional quality of secondary branch grains. The above results indicate that application of melatonin improves the number of secondary branches and the quality of grainss on secondary branches.
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Melatonina , Oryza , Melatonina/farmacología , Melatonina/administración & dosificación , Oryza/efectos de los fármacos , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Grano Comestible/efectos de los fármacos , Grano Comestible/crecimiento & desarrollo , Giberelinas/farmacologíaRESUMEN
As a two-dimensional (2D) material, palladium diselenide (PdSe2) has attracted extensive research attention due to its unique asymmetric crystal structure and extraordinary optoelectronic properties, showing great potential in electronic, optoelectronic, and other application fields. Thinner PdSe2 exhibits semiconductor properties, while the photoresponse of the photodetectors based on this film is weaker. Although increasing the thickness of the PdSe2 film can improve the photoresponse, thicker PdSe2 exhibits metallic-like properties, which is not conducive to the formation of the heterojunction. In this work, a PdSe2 2D material with a quantum island structure is prepared by a simple thermal-assisted conversion method. A new type of photodetector with a PdSe2/n--Si/n+-Si vertical PIN-like structure is innovatively proposed. Broad spectral absorption from 532 to 2200 nm and a high rectification ratio (106) of the device are achieved. The introduced n--Si layer concentrates the electric field in the depletion region, thereby shortening the transit time and accelerating the separation and collection of the carriers, resulting in the enhancement of the responsivity and 3 dB frequency compared to the traditional device with a PN structure. A recorded highest 3 dB frequency of â¼25 kHz is achieved for the PdSe2 2D-3D PIN-like device.
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BACKGROUND: PDAC, also known as pancreatic ductal adenocarcinoma, is often diagnosed at a late stage due to nonspecific symptoms and a distinct lack of reliable biomarkers for timely diagnosis. Ferroptosis, a novel non-apoptotic cell death mode discovered in recent years, is strongly linked to the progression of PDAC and the evasion of the immune system. The objective of this study is to discover a novel ceRNA biomarker associated with ferroptosis and investigate its possible molecular mechanisms and therapeutic potential in PDAC. METHODS: Based on the FerrDb and TCGA databases, the R survival package was used to screen for ferroptosis-related mRNAs associated with PDAC prognosis. The ferroptosis-related ceRNA network was identified by miRTarBase, miRNet, and starBase and visualized using Cytoscape. The LASSO regression analysis was used to build a risk model associated with ceRNA. Additionally, we investigated the correlation between the ceRNA axis and the infiltration of immune cells in PDAC by employing the ssGSEA algorithm. Spearman correlation analysis was used to investigate the association between the ceRNA network and the expression levels of immune checkpoint genes in PDAC. The prediction of potential medications for PAAD patients with high risk scores was conducted using the R package oncoPredict and the Genomics of Drug Sensitivity in Cancer (GDSC) repository. Expression levels of LINC02535 in clinical specimens and PDAC cell lines were determined using qRT-PCR. CCK-8, colony formation, EdU, wound healing, and transwell assays were performed to assess the impact of reducing LINC02535 on the growth, migration, and invasion of PDAC cell lines BxPC3 and PANC1. RESULTS: We first discovered a new LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis and created a prognostic nomogram for predicting overall survival. Meanwhile, the risk scores of the LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis were linked to immune subtypes in PDAC. The high immune infiltration subtype exhibited elevated ceRNA risk scores and EIF2S1 expression. The correlation analysis revealed a positive correlation between ceRNA risk scores and four immune cells, namely Activated CD4 T cell, Memory B cell, Neutrophil, and Type 2â¯T helper cell, as well as four immune checkpoint genes, namely CD274, HAVCR2, PDCD1LG2, and TIGIT. The analysis of drug sensitivity indicated that individuals with a high-risk score may exhibit greater sensitivity to inhibitors targeting MEK1/2 compared to those with a low-risk score. In our validation experiments, it was observed that the expression of LINC02535 was increased in both PDAC tissues and cell lines. Additionally, the inhibition of LINC02535 resulted in decreased proliferation, migration, and invasion of PDAC cells. Rescue experiments demonstrated that LINC02535 promoted PDAC cell growth and metastasis by upregulating EIF2S1 expression. CONCLUSION: To summarize, a novel ferroptosis-associated LINC02535/miR-30c-5p/EIF2S1 ceRNA network for PDAC patients was established. The analysis of this network's functionality offers potential insights for clinical decision-making and the advancement of precision medicine.
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OBJECTIVE: Disorders of lipid oxidation play an important role in organ damage, and lipid metabolites are associated with inflammation and coagulation dysfunction in sepsis. However, the specific molecular mechanism by which lipid metabolism-related proteins regulate sepsis is still unclear. The aim of this study is to investigate the role of mortality factor 4-like protein 1 (MORF4L1, also called MRG15), a hepatic lipid metabolism related gene, in sepsis-induced liver injury. METHODS: In the mouse sepsis models established by cecal ligation and puncture (CLP) and lipopolysaccharide (LPS), the impact of pretreatment with the MRG15 inhibitor argatroban on sepsis-related liver injury was investigated. In the LPS-induced hepatocyte sepsis cell model, the effects of MRG15 overexpression or knockdown on hepatic inflammation and lipid metabolism were studied. Additionally, in a co-culture system of hepatocytes and macrophages, the influence of MRG15 knockdown in hepatocytes on the synthesis and secretion of inflammation-related protein PCSK9 as well as its effect on macrophage activation were examined. RESULTS: Studies have shown that MRG15 expression was increased in septicemia mice and positively correlated with lipid metabolism and inflammation. However, knockdown of MRG15 ameliorates sepsis-induced hepatocyte injury. Increased MRG15 in LPS-stimulated hepatocytes promotes PCSK9 synthesis and secretion, which induces macrophage M1 polarization and exacerbates the inflammatory response. Agatroban, an inhibitor of MRG15, ameliorates sepsis-induced liver injury in mice by inhibiting MRG15-induced lipid metabolism disorders and inflammatory responses. CONCLUSIONS: In sepsis, increased MRG15 expression in hepatocytes leads to disturbed hepatic lipid metabolism and induces macrophage M1 polarization by secreting PCSK9, ultimately exacerbating liver injury.
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BACKGROUND: The quality of low-light endoscopic images involves applications in medical disciplines such as physiology and anatomy for the identification and judgement of tissue structures. Due to the use of point light sources and the constraints of narrow physiological structures, medical endoscopic images display uneven brightness, low contrast, and a lack of texture information, presenting diagnostic challenges for physicians. METHODS: In this paper, a nonlinear brightness enhancement and denoising network based on Retinex theory is designed to improve the brightness and details of low-light endoscopic images. The nonlinear luminance enhancement module uses higher-order curvilinear functions to improve overall brightness; the dual-attention denoising module captures detailed features of anatomical structures; and the color loss function mitigates color distortion. RESULTS: Experimental results on the Endo4IE dataset demonstrate that the proposed method outperforms existing state-of-the-art methods in terms of Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Learned Perceptual Image Patch Similarity (LPIPS). The PSNR is 27.2202, SSIM is 0.8342, and the LPIPS is 0.1492. It provides a method to enhance image quality in clinical diagnosis and treatment. CONCLUSIONS: It offers an efficient method to enhance images captured by endoscopes and offers valuable insights into intricate human physiological structures, which can effectively assist clinical diagnosis and treatment.
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Relación Señal-Ruido , Humanos , Endoscopía/métodos , Aumento de la Imagen/métodos , Algoritmos , Dinámicas no Lineales , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
We present a novel time-of-flight resolved Bessel light bullet-enabled stimulated Raman scattering (B2-SRS) microscopy for deeper tissue 3D chemical imaging with high resolution without a need for mechanical z-scanning. To accomplish the tasks, we conceive a unique method to enable optical sectioning by generating the counter-propagating pump and Stokes Bessel light bullets in the sample, in which the group velocities of the Bessel light bullets are made ultraslow (e.g., vg ≈ 0.1c) and tunable by introducing programmable angular dispersions with a spatial light modulator. We theoretically analyze the working principle of the collinear multicolor Bessel light bullet generations and velocity controls with the relative time-of-flight resolved detection for SRS 3D deep tissue imaging. We have also built the B2-SRS imaging system and present the first demonstration of B2-SRS microscopy with Bessel light bullets for 3D chemical imaging in a variety of samples (e.g., polymer bead phantoms, biological samples such as spring onion tissue and porcine brain) with high resolution. The B2-SRS technique provides a > 2-fold improvement in imaging depth in porcine brain tissue compared to conventional SRS microscopy. The method of optical sectioning in tissue using counter-propagating ultraslow Bessel light bullets developed in B2-SRS is generic and easy to perform and can be readily extended to other nonlinear optical imaging modalities to advance 3D microscopic imaging in biological and biomedical systems and beyond.
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The long-term performance of anaerobic digestion (AD) often decreases substantially when treating swine wastewater contaminated with heavy metals. However, the toxicological characteristics and mechanisms of continuous exposure to heavy metals under different organic loading rates (OLR) are still poorly understood. In these semi-continuous AD experiments, it was found that zinc concentrations of 40 mg/L only deteriorated the reductive environments of AD. In comparison, a concentration of 2.0 mg/L probably facilitated the reproduction of microorganisms in the operating digesters with a constant OLR of 0.51 g COD/(L·d). Nevertheless, when the OLR was increased to 2.30 g COD/(L·d), 2.0 mg/L zinc inhibited various life activities of microorganisms at the molecular level within only 10 days. Hence, even though 2.0 mg/L zinc could promote AD performances from a macroscopic perspective, it had potential inhibitory effects on AD. Therefore, this study deepens the understanding of the inhibitions caused by heavy metals on AD and the metabolic laws of anaerobic microorganisms in swine wastewater treatment. These results could be referred to for enhancing AD in the presence of zinc in practical swine wastewater treatment.
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Reactores Biológicos , Eliminación de Residuos Líquidos , Aguas Residuales , Zinc , Animales , Aguas Residuales/química , Zinc/toxicidad , Anaerobiosis , Porcinos , Eliminación de Residuos Líquidos/métodos , Reactores Biológicos/microbiología , Contaminantes Químicos del Agua/toxicidad , Metales Pesados/toxicidadRESUMEN
Purpose: Phosphorus Magnetic Resonance Spectroscopy (31P MRS) enables non-invasive assessment of energy metabolism, yet its application is hindered by sensitivity limitations. To overcome this, often high magnetic fields are used, leading to challenges such as spatial B 1 + inhomogeneity and therefore the need for accurate flip angle determination in accelerated acquisitions with short repetition times T R ) . In response to these challenges, we propose a novel short T R and look-up table-based Double-Angle Method for fast 3D 31P B 1 + mapping (fDAM). Methods: Our method incorporates 3D weighted stack of spiral gradient echo acquisitions and a frequency-selective pulse to enable efficient B 1 + mapping based on the phosphocreatine signal at 7T. Protocols were optimised using simulations and validated through phantom experiments. The method was validated in phantom experiments and skeletal muscle applications using a birdcage 1H/31P volume coil. Results: The results of fDAM were compared to the classical DAM (cDAM). A good correlation (r=0.94) was obtained between the two B 1 + maps. A 3D 31P B 1 + mapping in the human calf muscle was achieved in about 10 min using a birdcage volume coil, with a 20% extended coverage relative to that of the cDAM (24 min). fDAM also enabled the first full brain coverage 31P 3D B 1 + mapping in approx. 10 min using a 1 Tx/ 32 Rx coil. Conclusion: fDAM is an efficient method for 31P 3D B 1 + mapping, showing promise for future applications in rapid 31P MRSI.
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Persistent organic pollutants seriously affect the growth and development of crops. 1,2,4-Trichlorobenzene (TCB), as one of the most widely used chlorobenzenes, can affect the yield of japonica rice. However, existing research on the effect of TCB on japonica rice yield is not in-depth, and a basic understanding of commonality has not yet been formed. In this study, 28 conventional japonica rice varieties were selected to investigate the effects of TCB stress on their yield, yield composition, and TCB accumulation. This study also evaluated the efficiency of conventional tolerance indices in evaluating the TCB stress tolerance of japonica rice. The results showed that TCB caused sustained inhibition of the growth of japonica rice, which was considerably manifested in plant height, root length, soil plant analysis development (SPAD), and dry weight at different growth stages. Under TCB stress, TCB accumulation in various tissues of japonica rice increased sharply. TCB stress reduces the yield of japonica rice by reducing the number of panicles per hill, the number of spikelets per panicle, the grain filling percentage, and the grain weight. Overall, the results of this study indicate that TCB stress can cause a decrease in the yield of japonica rice, and the decrease in panicle number is the main reason. The conventional tolerance index can effectively evaluate the tolerance of japonica rice to TCB. The results of this study are substantial for the breeding and cultivation of japonica rice.
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The vast neuronal diversity in the human neocortex is vital for high-order brain functions, necessitating elucidation of the regulatory mechanisms underlying such unparalleled diversity. However, recent studies have yet to comprehensively reveal the diversity of neurons and the molecular logic of neocortical origin in humans at single-cell resolution through profiling transcriptomic or epigenomic landscapes, owing to the application of unimodal data alone to depict exceedingly heterogeneous populations of neurons. In this study, we generated a comprehensive compendium of the developing human neocortex by simultaneously profiling gene expression and open chromatin from the same cell. We computationally reconstructed the differentiation trajectories of excitatory projection neurons of cortical origin and inferred the regulatory logic governing lineage bifurcation decisions for neuronal diversification. We demonstrated that neuronal diversity arises from progenitor cell lineage specificity and postmitotic differentiation at distinct stages. Our data paves the way for understanding the primarily coordinated regulatory logic for neuronal diversification in the neocortex.
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In the ongoing arms race between bacteria and bacteriophages, bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas systems. Recently, AcrIIA25.1 and AcrIIA32 have been found to effectively inhibit the activity of SpyCas9 both in bacterial and human cells. However, their molecular mechanisms remain elusive. Here, we report the cryo-electron microscopy structures of ternary complexes formed by AcrIIA25.1 and AcrIIA32 bound to SpyCas9-sgRNA. Using structural analysis and biochemical experiments, we revealed that AcrIIA25.1 and AcrIIA32 recognize a novel, previously-unidentified anti-CRISPR binding site on SpyCas9. We found that both AcrIIA25.1 and AcrIIA32 directly interact with the WED domain, where they spatially obstruct conformational changes of the WED and PI domains, thereby inhibiting SpyCas9 from recognizing protospacer adjacent motif (PAM) and unwinding double-stranded DNA. In addition, they may inhibit nuclease activity by blocking the dynamic conformational changes of the SpyCas9 surveillance complex. In summary, our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins, provide new strategies for the modulation of SpyCas9 activity, and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.
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The pavement asphalt properties are susceptible to deterioration under environmental factors, and the deterioration product will affect its surrounding aqueous environment. For this reason, the idealized asphalt-aggregate mixture was treated with coupled temperature, ultraviolet and aqueous solutions based on self-made multifactorial coupled simulation device. Subsequently, the deterioration of asphalt chemical properties was analyzed by fourier transform infrared spectroscopy and saturate-aromatic-resin-asphaltene tests. Meanwhile, the effect of environmental factors on leachate properties was explored based on organic matter contents and chemical elements. Based on that, the grey correlation method was adopted to correlate asphalt chemical properties and leachate properties. The results clearly showed that environmental factors increased the sulfoxide and carbonyl group content of asphalt and transformed the chemical components within it into polar substances. The asphalt chemical properties were gradually improved when coupling ultraviolet with sodium carbonate, sodium chloride and distilled water sequentially. Compared to neutral solution, alkaline solution exacerbated the effect of asphalt precipitates on leachate properties. The environmental factors increased the organic matter contents and chemical elements of leachate with time. The interaction mechanism between asphalt and aqueous environment involved the deterioration of asphalt properties caused by the presence of water, as well as the release of precipitates from aged asphalt into surrounding aqueous environment.
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Alzheimer's disease (AD), the most common form of dementia, has gotten considerable attention. Previous studies have demonstrated that clioquinol (CQ) as a metal chelator is a potential drug for the treatment of AD. However, the mode of action of CQ in AD is still unclear. In our study, the antioxidant effects of CQ on yeast cells expressing Aß42 were investigated. We found that CQ could reduce Aß42 toxicity by alleviating reactive oxygen species (ROS) generation and lipid peroxidation level in yeast cells. These alterations were mainly attributable to the increased reduced glutathione (GSH) content and independent of activities of superoxide dismutase (SOD) and/or catalase (CAT). CQ could affect antioxidant enzyme activity by altering the transcription level of related genes. Interestingly, it was noted for the first time that CQ could combine with antioxidant enzymes to reduce their enzymatic activities by molecular docking and circular dichroism spectroscopy. In addition, CQ restored Aß42-mediated disruption of GSH homeostasis via regulating YAP1 expression to protect cells against oxidative stress. Our findings not only improve the current understanding of the mechanism of CQ as a potential drug for AD treatment but also provide ideas for subsequent drug research and development.
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Péptidos beta-Amiloides , Antioxidantes , Clioquinol , Glutatión , Estrés Oxidativo , Especies Reactivas de Oxígeno , Saccharomyces cerevisiae , Estrés Oxidativo/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo , Clioquinol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , Antioxidantes/farmacología , Peroxidación de Lípido/efectos de los fármacos , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Fragmentos de Péptidos/metabolismo , Simulación del Acoplamiento Molecular , Catalasa/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismoRESUMEN
Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.
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Fondo de Ojo , Tomografía de Coherencia Óptica , Animales , Masculino , Femenino , Modelos Animales de Enfermedad , Disco Óptico/patología , Disco Óptico/diagnóstico por imagen , Atrofia Óptica/patología , Atrofia Óptica/epidemiología , Presión Intraocular/fisiología , Miopía Degenerativa/patología , Miopía Degenerativa/epidemiología , Fibras Nerviosas/patología , Longitud Axial del Ojo/patología , Células Ganglionares de la Retina/patología , Miopía/patología , Miopía/epidemiología , Miopía/veterinariaRESUMEN
Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.
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Ácidos Aminoisobutíricos , Ganglios Espinales , Hiperalgesia , Ovariectomía , Receptores Acoplados a Proteínas G , Transducción de Señal , Animales , Femenino , Hiperalgesia/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ratones , Transducción de Señal/efectos de los fármacos , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Ácidos Aminoisobutíricos/farmacología , Ácidos Aminoisobutíricos/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
A palladium-catalyzed regio- and stereo-selective phosphination of cyclic biarylsulfonium salts (racemic) with HPAr3Ar4 for straightforward synthesis of atropoisomeric phosphines (P,S-ligands) bearing a stereogenic axis or both a stereogenic axis and a P-stereogenic center is reported. The high reactivity and regio- and stereo-selectivity originate from the torsional strain release and palladium catalysis, and the construction of a P-stereogenic center is enabled by an efficient dynamic kinetic resolution. The high performance of the nascent P,S-ligands has been demonstrated in palladium-catalyzed asymmetric allylic substitutions, indicating the great potential of the present methodology.
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BACKGROUND AND PURPOSE: As a crucial diagnostic and prognostic biomarker, telomerase reverse transcriptase (TERT) promoter mutation holds immense significance for personalized treatment of patients with glioblastoma (GBM). In this study, we developed a radiomics nomogram to determine the TERT promoter mutation status and assessed its prognostic efficacy in GBM patients. METHODS: The study retrospectively included 145 GBM patients. A comprehensive set of 3736 radiomics features was extracted from preoperative magnetic resonance imaging, including T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1WI, and fluid-attenuated inversion recovery. The construction of the radiomics model was based on integrating the radiomics signature (rad-score)with clinical features. Receiver-operating characteristic curve analysis was employed to evaluate the discriminative ability of the prediction model, and the risk score was used to stratify patient outcomes. RESULTS: The least absolute shrinkage and selection operator classifier identified 10 robust features for constructing the prediction model, and the radiomics nomogram exhibited excellent performance in predicting TERT promoter mutation status, with area under the curve values of.906 (95% confidence interval [CI]:.850-.963) and.899 (95% CI:.708-.966) in the training and validation sets, respectively. The clinical utility of the radiomics nomogram is further supported by calibration curve and decision curve analyses. Additionally, the radiomics nomogram effectively stratified GBM patients with significantly different prognoses (HR = 1.767, p = .019). CONCLUSION: The radiomics nomogram holds promise as a modality for evaluating TERT promoter mutations and prognostic outcomes in patients with GBM.