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OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Infección de Heridas , Acinetobacter baumannii/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Antibacterianos/farmacología , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Modelos Animales de Enfermedad , Permeabilidad de la Membrana Celular/efectos de los fármacos , Humanos , ADN Bacteriano/genéticaRESUMEN
The regulation of circadian rhythms and the sleep-wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep-wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN-HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non-rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN-HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep-wake states regulation.
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Vías Eferentes , Optogenética , Núcleo Supraquiasmático , Animales , Núcleo Supraquiasmático/fisiología , Masculino , Ratones , Vías Eferentes/fisiología , Ratones Endogámicos C57BL , Fases del Sueño/fisiología , Prosencéfalo Basal/fisiología , Ritmo Circadiano/fisiología , ElectroencefalografíaRESUMEN
Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVNOXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVNOXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVNOXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVNOXT neurons through α2-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVNOXT neurons through the α2-adrenoceptor.
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Chemotherapy failure and resistance are the leading causes of mortality in patients with acute myeloid leukemia (AML). However, the role of m6A demethylase FTO and its inhibitor rhein in AML and AML drug resistance is unclear. Therefore, this study aimed to investigate the antileukemic effect of rhein on AML and explore its potential mechanisms underlying drug resistance. Bone marrow fluid was collected to assess FTO expression in AML. The Cell Counting Kit 8 reagent was used to assess cell viability. Migration assays were conducted to assess the cell migration capacity. Flow cytometry was used to determine the apoptotic effects of rhein and western blot analysis was used to detect protein expression. Online SynergyFinder software was used to calculate the drug synergy scores. The in-vivo antileukemic effect of rhein was assessed in an AML xenograft mouse model. We analyzed different types of AML bone marrow specimens to confirm that FTO is overexpressed in AML, particularly in cases of multidrug resistance. Subsequently, we conducted in-vivo and in-vitro investigations to explore the pharmacological activity and mechanism of rhein in AML and AML with multidrug resistance. The findings demonstrated that rhein effectively suppressed the proliferation and migration of AML cells in a time- and dose-dependent manner and induced apoptosis. Rhein targets FTO, inhibits the AKT/mTOR pathway, and exhibits synergistic antitumor effects when combined with azacitidine. This study elucidates the significant role of FTO and its inhibitor rhein in AML and AML with multidrug resistance, providing new insights for overcoming multidrug resistance in AML.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Antraquinonas , Apoptosis , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Animales , Ratones , Antraquinonas/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis/efectos de los fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Masculino , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones Desnudos , Persona de Mediana Edad , Ratones Endogámicos BALB C , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVES: The study aimed to explore the value of texture analysis of radiomics based on the short tau inversion recovery (STIR) sequence to evaluate the activity of bone marrow oedema of sacroiliac joints in early AS. METHODS: 43 patients with early AS whose data were randomly divided into the training cohort (n=116) and verification cohort (n=56) according to the ratio of 7:3. The optimal feature subsets were obtained by Mann-Whitney U-test, the minimum-Redundancy Maximum-Relevancy (mRMR), and then least absolute shrinkage and selection operator (LASSO) using these texture feature parameters, which were used to construct the final prediction model and obtained the Radscore. The ROC curve was performed to evaluate the performance of the model. The Spearman correlation test was used to analyse the correlation of various indicators. RESULTS: In the training cohort, to differentiate early AS sacroiliac joint bone marrow oedema between the active and stable groups, the AUCs of the Radscore, SPARCC and ADC were 0.81, 0.91, 0.78, respectively. In the validation cohort, the AUCs were 0.87, 0.89, 0.85. In the two cohorts, there were no significant differences in AUCs between values of the Radscore and SPARCC, ADC (p>0.05). There was a significant difference in AUC between SPARCC and ADC in the training cohort (p<0.05), with no statistical significance in the validation cohort (p>0.05). The correlations were all low between the Radscore values and the values of ESR, CRP, tI, ASDAS-ESR and ASDAS-CRP (p<0.05). CONCLUSIONS: Radiomics analysis based on STIR texture analysis has a good prediction for the evaluation of bone marrow oedema activity of sacroiliac joints in AS. It can be a new non-invasive and objective evaluation method for AS activity.
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Edema , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Articulación Sacroiliaca , Espondilitis Anquilosante , Humanos , Masculino , Femenino , Espondilitis Anquilosante/diagnóstico por imagen , Articulación Sacroiliaca/diagnóstico por imagen , Adulto , Edema/diagnóstico por imagen , Edema/etiología , Reproducibilidad de los Resultados , Persona de Mediana Edad , Enfermedades de la Médula Ósea/diagnóstico por imagen , Curva ROC , Médula Ósea/diagnóstico por imagen , Adulto Joven , Diagnóstico Precoz , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , RadiómicaRESUMEN
Three new homochiral metal bromides, namely, (l-Htp)2Cu2Br4 (1), (l-Htp)(l-tp)CdBr3 (2), and (l-tp)2ZnBr2 (3), were prepared using l-thioproline as the chiral template. These compounds feature dimeric, chainlike, and monomeric structures. Their second-harmonic-generation (SHG) efficiencies are 0.1, 0.3, and 2.0 times that of KH2PO4, respectively. Density functional theory calculations were performed to reveal the origin of the SHG response of compound 3.
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Three organic-inorganic metal iodides, namely, (NH4)(l-hp)ZnI3 (1), [Cd(l-hp)4]Cd3I8 (2), and (l-Hhp)(l-hp)PbI3 (3), have been synthesized using l-homoproline (l-hp) as the structure-directing agent. These compounds feature different noncentrosymmetric structures and optical properties. In particular, compound 3 shows a large second-harmonic-generation response of 3.4 times that of KH2PO4. Density functional theory calculations were performed to gain insight into its structure-property relationship.
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Ascites syndrome (AS) in broiler chickens, also known as pulmonary arterial hypertension (PAH), is a significant disease in the poultry industry. It is a nutritional metabolic disease that is closely associated with hypoxia-inducible factors and rapid growth. The rise in pulmonary artery pressure is a crucial characteristic of AS and is instrumental in its development. Hypoxia-inducible factor 1α (HIF-1α) is an active subunit of a key transcription factor in the oxygen-sensing pathway. HIF-1α plays a vital role in oxygen homeostasis and the development of pulmonary hypertension. Studying the effects of HIF-1α on pulmonary hypertension in humans or mammals, as well as ascites in broilers, can help us understand the pathogenesis of AS. Therefore, this review aims to (1) summarize the mechanism of HIF-1α in the development of pulmonary hypertension, (2) provide theoretical significance in explaining the mechanism of HIF-1α in the development of pulmonary arterial hypertension (ascites syndrome) in broilers, and (3) establish the correlation between HIF-1α and pulmonary arterial hypertension (ascites syndrome) in broilers. HIGHLIGHTSExplains the hypoxic mechanism of HIF-1α.Linking HIF-1α to pulmonary hypertension in broilers.Explains the role of microRNAs in pulmonary arterial hypertension in broilers.
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BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.
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Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Nomogramas , Humanos , Femenino , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Masculino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Estudios de Cohortes , Factores de Riesgo , Medición de Riesgo/métodosRESUMEN
This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.
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Envejecimiento , Medicamentos Herbarios Chinos , Riñón , Metabolómica , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Ratas , Riñón/efectos de los fármacos , Riñón/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Masculino , Transducción de Señal/efectos de los fármacosRESUMEN
Achieving tunable emissions spanning the spectrum, from blue to near-infrared (NIR) light, within a single component is a formidable challenge with significant implication, particularly in tailoring multicolor luminescence for anti-counterfeiting purposes. In this study, we demonstrate a broad spectrum of emissions, covering blue to red and extending into NIR light in [BPy]2CdX4 : xSb3+ (BPy=Butylpyridinium; X=Cl, Br; x=0 to 0.08) through precise multisite structural fine-tuning. Notably, the multicolor emissions from [BPy]2CdBr4 : Sb3+ manifest a distinctive pattern, transitioning from blue to yellow in tandem with the host [BPy]2CdBr4 and further extending from yellow to NIR with its homologous [BPy]2CdCl4 : Sb3+, resulting in the simultaneous presence of intersecting and independent emission colors. Detailed modulation of chemical composition enables partial luminescence switching, facilitating the creation of diverse patterns with multicolor luminescence by employing [BPy]2CdX4 : xSb3+ as phosphors. This study for the first time successfully implements several groups of tunable emission colors in a single matrix via multisite fine-tuning. Such an effective strategy not only develops the specific relationships between tunable emissions and adjustable compositions, but also introduces a cost-effective and straightforward approach to achieving unique, high-level, plentiful-color and multiple-information-storage labels for advanced anti-counterfeiting applications.
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Homochiral halide perovskites have gained increasing attention because of their fascinating optoelectronic properties and prospective applications in laser technologies. However, the limited choice of chiral organic templates severely restricts their structural diversity and second-harmonic generation (SHG) effects. Here, we present an in situ chiral template approach for the synthesis of one-dimensional (1D) homochiral lead iodides. A chiral imine (L-ipp) template was generated in situ by reacting L-proline (L-pro) and acetone under ambient conditions. Notably, L-ipp can cooperate with L-pro to direct the formation of a homochiral lead iodide with dual chiral templates, which is unprecedented in crystalline metal halides. The homochiral lead iodide containing both L-ipp and L-pro shows a strong SHG response of 8.0â times that of KH2 PO4 (8.0×KDP). The SHG efficiency is one of the largest values reported to date for any homochiral lead halides under 1064â nm laser irradiation. A comparative study shows that homochiral 1D lead iodides containing either L-ipp or L-pro exhibit relatively weak SHG responses (≤1.0×KDP). This work demonstrates the advantage of using two different chiral templates over a single chiral template in enhancing the SHG responses of halide materials.
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As an effective technique to extend the depth-of-field (DOF) of optical lenses, multi-focus image fusion has recently become an active topic in image processing community. However, a major problem remaining unsolved in this field is the lack of universal criteria in selecting objective evaluation metrics. Consequently, the metrics utilized in different studies often vary significantly, leading to high difficulties in achieving unbiased evaluation. To address this problem, this paper proposes a statistic-based approach for verifying the effectiveness of objective metrics in multi-focus image fusion. The core idea is to adopt statistical correlation measures to evaluate the performance consistency between a certain fusion metric and some popular full-reference image quality assessment models. In addition, a convolutional neural network (CNN)-based fusion metric is presented to measure the similarity between the source images and the fused image based on the semantic features at multiple abstraction levels. A comparative study is conducted to evaluate 20 existing fusion metrics using the proposed statistic-based approach on a large-scale, realistic and with-ground-truth multi-focus image fusion dataset recently released. Experimental results demonstrate the feasibility of the proposed approach in evaluating the effectiveness of objective metrics and the advantage of our CNN-based metric.
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OBJECTIVE: To construct a acute myeloid leukemia (AML) cell line in which HOXA5 gene is stably knocked out by CRISPR-Cas9-mediated gene editing technique, so as to clarify the effect of HOXA5 gene knockout on the proliferation of AML cells, and preliminarily explore the role of HOXA5 gene in the pathogenesis of AML. METHODS: The expression of HOXA5 in bone marrow mononuclear cells (BMMC) of non-tumor hematological patients and newly diagnosed AML patients was detected by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. The AML cell line KO-HOXA5-THP-1 was constructed in which HOXA5 gene was knocked out by CRISPR-Cas9-Mediated gene editing technique, and the knockout of HOXA5 gene was verified by qRT-PCR and Western blot, and the cell proliferation was detected by CCK-8 assay. RESULTS: Compared with non-tumor hematological patients, the levels of HOXA5 gene and protein in BMMC of newly diagnosed AML patients were significantly increased (P <0.05). The stable HOXA5 knockout cell line can be obtained by CRISPR-Cas9-Mediated gene editing technique, and the proliferation ability of THP-1 cells with HOXA5 gene knockout was significantly decreased (P <0.05). CONCLUSION: HOXA5 is highly expressed in AML cells, and knocking out HOXA5 can significantly affect the proliferation ability of AML cells, which provides a new potential therapeutic target for the precise treatment of AML.
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Edición Génica , Leucemia Mieloide Aguda , Humanos , Sistemas CRISPR-Cas , Leucemia Mieloide Aguda/metabolismo , Genes Homeobox , Línea Celular Tumoral , Proliferación Celular , Proteínas de Homeodominio/genéticaRESUMEN
Anatomical and functional image fusion is an important technique in a variety of medical and biological applications. Recently, deep learning (DL)-based methods have become a mainstream direction in the field of multi-modal image fusion. However, existing DL-based fusion approaches have difficulty in effectively capturing local features and global contextual information simultaneously. In addition, the scale diversity of features, which is a crucial issue in image fusion, often lacks adequate attention in most existing works. In this paper, to address the above problems, we propose a MixFormer-based multi-scale network, termed as MM-Net, for anatomical and functional image fusion. In our method, an improved MixFormer-based backbone is introduced to sufficiently extract both local features and global contextual information at multiple scales from the source images. The features from different source images are fused at multiple scales based on a multi-source spatial attention-based cross-modality feature fusion (CMFF) module. The scale diversity of the fused features is further enriched by a series of multi-scale feature interaction (MSFI) modules and feature aggregation upsample (FAU) modules. Moreover, a loss function consisting of both spatial domain and frequency domain components is devised to train the proposed fusion model. Experimental results demonstrate that our method outperforms several state-of-the-art fusion methods on both qualitative and quantitative comparisons, and the proposed fusion model exhibits good generalization capability. The source code of our fusion method will be available at https://github.com/yuliu316316.
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BACKGROUND: Type 2 diabetes accelerates the loss of muscle mass and strength. Sarcopenia is also one of the chronic complications of diabetes. OBJECTIVE: To investigate the clinical value of B mode ultrasound (BMUS) and shear wave elastography (SWE) for predicting type 2 diabetic sarcopenia. METHODS: We recorded Skeletal Muscle Mass Index (ASMI), grip strength, muscle thickness (MT), pinna angle (PA), fascicle length (FL), and the difference of Young's modulus in the relaxed states and tense states (ΔSWE). The correlations between clinical indicators and ultrasound characteristics were compared. A diagnostic model of sarcopenia was developed to assess the independent correlates and evaluate the diagnostic efficacy of sarcopenia. RESULTS: ASMI was significantly and positively correlated with MT and ΔSWE (râ=â0.826, 0.765, Pâ<â0.01), and grip strength was significantly and positively correlated with MT and ΔSWE (râ=â0.797, 0.818, Pâ<â0.01). MT was the most significant predictor of sarcopenia (ORâ=â4.576, Pâ<â0.001), and the cut-off value of MT was 11.4âmm (AUC: 0.952). CONCLUSION: BMUS and SWE can quantitatively assess muscle mass and strength, and are effective methods to predict the occurrence of sarcopenia in elderly patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Diagnóstico por Imagen de Elasticidad , Sarcopenia , Humanos , Sarcopenia/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/fisiopatología , Diagnóstico por Imagen de Elasticidad/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Ultrasonografía/métodos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiopatología , Fuerza de la ManoRESUMEN
Amatoxins are responsible for most fatal mushroom poisoning cases, as it causes both hepatotoxicity and nephrotoxicity. However, studies on amatoxin nephrotoxicity are limited. Here, we investigated nephrotoxicity over 4 days and nephrotoxicity/hepatotoxicity over 14 days in mice. The organ weight ratio, serological indices, and tissue histology results indicated that a nephrotoxicity mouse model was established with two stages: (1) no apparent effects within 24 h; and (2) the appearance of adverse effects, with gradual worsening within 2-14 days. For each stage, the kidney transcriptome revealed patterns of differential mRNA expression and significant pathway changes, and Western blot analysis verified the expression of key proteins. Amanitin-induced nephrotoxicity was directly related to RNA polymerase II because mRNA levels decreased, RNA polymerase II-related pathways were significantly enriched at the transcription level, and RNA polymerase II protein was degraded in the early poisoning stage. In the late stage, nephrotoxicity was more severe than hepatotoxicity. This is likely associated with inflammation because inflammation-related pathways were significantly enriched and NF-κB activation was increased in the kidney.
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Agaricales , Enfermedad Hepática Inducida por Sustancias y Drogas , Intoxicación por Setas , Masculino , Ratones , Animales , Alfa-Amanitina/toxicidad , Ratones Endogámicos ICR , ARN Polimerasa II/genética , Riñón , Inflamación , Perfilación de la Expresión Génica , ARN MensajeroRESUMEN
Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti3C2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport "bridge" (P-Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti3C2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O2 and H2O on the surfaces of Ti3C2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti3C2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli, respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti3C2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.
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Periodontitis , Fósforo , Titanio , Periodontitis/microbiología , Periodontitis/terapia , Fósforo/química , Titanio/química , Fototerapia , Antibacterianos/química , Antibacterianos/farmacología , Humanos , Staphylococcus aureus/efectos de los fármacos , Escherichia coli , Electricidad , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/química , Propiedades de Superficie , Animales , Transporte de Electrón , Pruebas de Sensibilidad MicrobianaRESUMEN
SLAMF8, the eighth member of the Signaling Lymphocytic Activation Molecule Family (SLAMF), functions in the regulation of the development and activity of diverse immune cells as a costimulatory receptor within the SLAMF family. Studies had revealed that SLAMF8 is expressed higher in several autoimmune inflammation diseases and tumors. Nevertheless, the connection between SLAMF8 and pan-cancer remains undisclosed. The research investigated the correlation between SLAMF8 and various factors including the immune microenvironment, microsatellite instability, immune novel antigen, gene mutation, immune regulatory factors, immune blockade TMB, and immune or molecular subtypes of SLAMF8 in verse cancer types. Immunohistochemistry was ultimately employed to validate the presence of the SLAMF8 gene in various tumor types including hepatocellular carcinoma, prostate adenocarcinoma, and kidney renal clear cell carcinoma. Furthermore, the relationship between SLAMF8 expression and the therapeutic efficacy of the PD1 blockade agent, Sintilimab, treatment in gastric cancer was validated. The result of differential analysis suggested that SLAMF8 was over-expressed in pan-cancer compared with paracancerous tissues. The analysis of survival indicated a connection between SLAMF8 and the overall prognosis in different types of cancers, where higher levels of SLAMF8 were found to be significantly linked to unfavorable outcomes in patients but favorable outcome of immunotherapy in gastric cancer. Significant correlations were observed between SLAMF8 levels and pan-cancer tumorigenesis, tumor metabolism, and immunity. As a result, SLAMF8 may become an important prognostic biomarker in the majority of tumors and a hopeful gene target for immunotherapy against gastric cancer.
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Inmunoterapia , Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismo , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Inmunoterapia/métodos , Pronóstico , Microambiente Tumoral/inmunología , Masculino , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión GénicaRESUMEN
Two new histidine-templated metal phosphate-oxalates (MPOs) were prepared under solvent-free conditions. Single-crystal X-ray diffraction analysis reveals that they have layered and chainlike structures, respectively. Under ultraviolet light irradiation, the two MPOs exhibit blue luminescence originating from histidine templates. Their proton-conducting properties were also investigated under different conditions.