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1.
Cell ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38968937

RESUMO

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.

2.
Nat Chem Biol ; 20(6): 710-720, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38200110

RESUMO

Biomolecular condensates have been proposed to mediate cellular signaling transduction. However, the mechanism and functional consequences of signal condensates are not well understood. Here we report that LATS2, the core kinase of the Hippo pathway, responds to F-actin cytoskeleton reduction and forms condensates. The proline-rich motif (PRM) of LATS2 mediates its condensation. LATS2 partitions with the main components of the Hippo pathway to assemble a signalosome for LATS2 activation and for its stability by physically compartmentalizing from E3 ligase FBXL16 complex-dependent degradation, which in turn mediates yes-associated protein (YAP)-transcriptional coactivator with PDZ-binding motif (TAZ) recruitment and inactivation. This oncogenic FBXL16 complex blocks LATS2 condensation by binding to the PRM region to promote its degradation. Disruption of LATS2 condensation leads to tumor progression. Thus, our study uncovers that the signalosomes assembled by LATS2 condensation provide a compartmentalized and reversible platform for Hippo signaling transduction and protein stability, which have potential implications in cancer diagnosis and therapeutics.


Assuntos
Via de Sinalização Hippo , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Proteínas Supressoras de Tumor , Proteínas Serina-Treonina Quinases/metabolismo , Humanos , Proteínas Supressoras de Tumor/metabolismo , Células HEK293 , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular Tumoral , Camundongos , Proteínas de Sinalização YAP/metabolismo , Fatores de Transcrição/metabolismo
3.
Stem Cells ; 42(6): 540-553, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38393342

RESUMO

Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we showed that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG bound to and stabilized HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encoded E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.


Assuntos
Processamento Alternativo , Ribonucleoproteína Nuclear Heterogênea A1 , Células-Tronco Embrionárias Humanas , RNA Longo não Codificante , Humanos , Processamento Alternativo/genética , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/citologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/genética , Autorrenovação Celular/genética , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Diferenciação Celular/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
4.
Nano Lett ; 24(33): 10337-10347, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39120122

RESUMO

Breast cancer (BC) is the most common tumor worldwide and requires crucial molecular typing for treatment and prognosis assessment. Currently, approaches like pathological staining, immunohistochemistry (IHC), and immunofluorescence (IF) face limitations due to the low signal-to-background ratio (SBR) and high tumor heterogeneity, resulting in a high misdiagnosis rate. Fluorescent assay in the second near-infrared region (NIR-II, 1000-1700 nm) exhibits ultrahigh SBR owing to diminished scattering and tissue autofluorescence. Here, we present a NIR-II strategy for accurate BC molecular typing and three-dimensional (3D) visualization based on the atomically precise fluorescent Au24Pr1 clusters. Single-atom Pr doping results in 3.9-fold fluorescence enhancement and long-term photostability. The Au24Pr1 clusters possess high fluorescence centered at ∼1100 nm and the SBR on pathological section diagnosis was 4 times higher than that of NIR-I imaging. This enables high spatial resolution 3D visualization of biopsy specimens, which can surmount tissue heterogeneity for clinical diagnosis of BC.


Assuntos
Neoplasias da Mama , Imageamento Tridimensional , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Imageamento Tridimensional/métodos , Imagem Óptica/métodos , Ouro/química , Corantes Fluorescentes/química
5.
J Mol Cell Cardiol ; 187: 51-64, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38171043

RESUMO

Senescence of vascular smooth muscle cells (VSMCs) is a key contributor to plaque vulnerability in atherosclerosis (AS), which is affected by endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production. However, the crosstalk between ER stress and ROS production in the pathogenesis of VSMC senescence remains to be elucidated. ER-associated degradation (ERAD) is a complex process that clears unfolded or misfolded proteins to maintain ER homeostasis. HRD1 is the major E3 ligase in mammalian ERAD machineries that catalyzes ubiquitin conjugation to the unfolded or misfolded proteins for degradation. Our results showed that HRD1 protein levels were reduced in human AS plaques and aortic roots from ApoE-/- mice fed with high-fat diet (HFD), along with the increased ER stress response. Exposure to cholesterol in VSMCs activated inflammatory signaling and induced senescence, while reduced HRD1 protein expression. CRISPR Cas9-mediated HRD1 knockout (KO) exacerbated cholesterol- and thapsigargin-induced cell senescence. Inhibiting ER stress with 4-PBA (4-Phenylbutyric acid) partially reversed the ROS production and cell senescence induced by HRD1 deficiency in VSMCs, suggesting that ER stress alone could be sufficient to induce ROS production and senescence in VSMCs. Besides, HRD1 deficiency led to mitochondrial dysfunction, and reducing ROS production from impaired mitochondria partly reversed HRD1 deficiency-induced cell senescence. Finally, we showed that the overexpression of HDR1 reversed cholesterol-induced ER stress, ROS production, and cellular senescence in VSMCs. Our findings indicate that HRD1 protects against senescence by maintaining ER homeostasis and mitochondrial functionality. Thus, targeting HRD1 function may help to mitigate VSMC senescence and prevent vascular aging related diseases. TRIAL REGISTRATION: A real-world study based on the discussion of primary and secondary prevention strategies for coronary heart disease, URL:https://www.clinicaltrials.gov, the trial registration number is [2022]-02-121-01.


Assuntos
Aterosclerose , Músculo Liso Vascular , Animais , Humanos , Camundongos , Aterosclerose/metabolismo , Senescência Celular , Estresse do Retículo Endoplasmático/fisiologia , Degradação Associada com o Retículo Endoplasmático , Mamíferos/metabolismo , Músculo Liso Vascular/metabolismo , Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
6.
Curr Issues Mol Biol ; 46(6): 6284-6299, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38921046

RESUMO

Dracocephalum moldavica is widely used as an ornamental, medicine, and perfume in industry. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) is widely and accurately utilized for gene expression evaluations. Selecting optimal reference genes is essential for normalizing RT-qPCR results. However, the identification of suitable reference genes in D. moldavica has not been documented. A total of 12 reference genes in D. moldavica were identified by PEG6000 (15%) treatment under hypertonia conditions in different tissues (roots, stem, leaves, flower, seeds and sepal) and during three stages of flower development, then used to validate the expression stability. There were four algorithms (delta Ct, geNorm, NormFinder, and BestKeeper) used to analyze the stability. Finally, the RefFinder program was employed to evaluate the candidate reference genes' stability. The results showed that ACTIN, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and EF1α (elongation factor-1α) were stable reference genes under the PEG6000 treatment. Heat shock protein 70 (HSP70) was the most stable gene across different flower development stages. ADP-ribosylation factor (ARF) was the most stable gene in different tissues and total samples. This study provides reliable gene expression studies for future research in D. moldavica.

7.
Anal Chem ; 96(19): 7353-7359, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38690857

RESUMO

Accurate detection of multiple cardiovascular biomarkers is crucial for the timely screening of acute coronary syndrome (ACS) and differential diagnosis from acute aortic syndrome (AAS). Herein, an antibody microarray-based metal-enhanced fluorescence assay (AMMEFA) has been developed to quantitatively detect 7 cardiovascular biomarkers through the formation of a sandwich immunoassay on the poly(glycidyl methacrylate-co-2-hydroxyethyl methacrylate)-decorated GNR-modified slide (GNR@P(GMA-HEMA) slide). The AMMEFA exhibits high specificity and sensitivity, the linear ranges span 5 orders of magnitude, and the limits of detection (LODs) of cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), C-reactive protein (CRP), copeptin, myoglobin, D-Dimer, and N-terminal pro-brain natriuretic peptide (NT-proBNP) reach 0.07, 0.2, 65.7, 0.6, 0.2, 8.3, and 0.3 pg mL-1, respectively. To demonstrate its practicability, the AMMEFA has been applied to quantitatively analyze 7 cardiovascular biomarkers in 140 clinical plasma samples. In addition, the expression levels of cardiovascular biomarkers were analyzed by the least absolute shrinkage and selector operator (LASSO) regression, and the area under receiver operator characteristic curves (AUCs) of healthy donors (HDs), ACS patients, and AAS patients are 0.99, 0.98, and 0.97, respectively.


Assuntos
Biomarcadores , Humanos , Biomarcadores/sangue , Biomarcadores/análise , Análise Serial de Proteínas/métodos , Limite de Detecção , Imunoensaio/métodos , Fluorescência
8.
Anal Chem ; 96(3): 1138-1146, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38165811

RESUMO

Fast-paced pharmaceutical process developments (e.g., high-throughput experimentation, directed evolution, and machine learning) involve the introduction of fast, sensitive, and accurate analytical assays using limited sample volumes. In recent years, acoustic droplet ejection (ADE) coupled with an open port interface has been invented as a sampling technology for mass spectrometry, providing high-throughput nanoliter analytical measurements directly from the standard microplates. Herein, we introduce an ADE-multiple reaction monitoring-mass spectrometry (ADE-MRM-MS) workflow to accelerate pharmaceutical process research and development (PR&D). This systematic workflow outlines the selection of MRM transitions and optimization of assay parameters in a data-driven manner using rapid measurements (1 sample/s). The synergy between ADE sampling and MRM analysis enables analytical assays with excellent sensitivity, selectivity, and speed for PR&D reaction screenings. This workflow was utilized to develop new ADE-MRM-MS assays guiding a variety of industrial processes, including (1) screening of Ni-based catalysts for C-N cross-coupling reaction at 1 Hz and (2) high-throughput regioisomer analysis-enabled enzyme library screening for peptide ligation reaction. ADE-MRM-MS assays were demonstrated to deliver accurate results that are comparable to conventional liquid chromatography (LC) experiments while providing >100-fold throughput enhancement.


Assuntos
Desenvolvimento de Medicamentos , Acústica , Espectrometria de Massas/métodos , Peptídeos , Fluxo de Trabalho
9.
J Comput Chem ; 45(20): 1737-1743, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38622788

RESUMO

We present a comprehensive investigation of the electronic properties of fluorinated monolayer violet phosphorus using first-principles calculations. Our results reveal a strong dependence of the electronic properties on the different fluorine coverages of fluorination. As the fluorine coverage increases, monolayer violet phosphorus undergoes a significant transition from a wide direct bandgap semiconductor to a narrow indirect bandgap semiconductor. Moreover, both semi-fluorinated and fully fluorinated monolayer violet phosphorus exhibit advantageous semiconducting characteristics, with a tunable bandgap of 0.50 ~ 1.04 eV under biaxial strain ranging from -6% to 6%. Notably, the fully fluorinated monolayer violet phosphorus demonstrates a higher coefficient of light absorption within the visible range. Therefore, our findings highlight the tunability of monolayer violet phosphorus properties through the absorption of various fluorine coverages, providing valuable insights for the design and development of novel semiconductor devices based on this material.

10.
Cell Commun Signal ; 22(1): 275, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755602

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. METHODS: We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. RESULTS: We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. CONCLUSION: In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.


Assuntos
Proteína Rica em Cisteína 61 , Retinopatia Diabética , Armadilhas Extracelulares , Neutrófilos , Animais , Feminino , Humanos , Masculino , Camundongos , Proteína Rica em Cisteína 61/metabolismo , Proteína Rica em Cisteína 61/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/patologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/genética , Armadilhas Extracelulares/genética , Armadilhas Extracelulares/metabolismo , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Retina/patologia , Retina/metabolismo
11.
Inorg Chem ; 63(2): 1274-1287, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38165643

RESUMO

A series of Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors were successfully prepared by the high-temperature solid-phase method. The phase and morphology of the phosphors were studied by means of Rietveld refinement and scanning electron microscopy. The results show that the phase is pure, and the crystal structure is the Ia3̅d space group. In the Ca3Al2Ge3O12: xDy3+ phosphors, using 380 nm excitation, phosphors showed blue (4F9/2 → 6H15/2) and yellow (4F9/2 → 6H13/2) emission peaks at 481 and 581 nm, respectively. In Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors, the energy transfer was inferred by the spectrum overlap of Dy3+ and Eu3+, and the lifetime attenuation was analyzed from the perspective of dynamics; finally, the band gap structure of the phosphors was analyzed by combining diffuse reflection spectra with the first principle, and the energy transfer mechanism and luminescence mechanism were elaborated by combining theory and practice. The transition from blue white light to red light can be achieved by tuning the range of y in Ca3Al2Ge3O12: 0.015Dy3+, yEu3+. Wherein, when y = 0.07, phosphors, the chromaticity coordinate of warm white CIE is (0.3932, 0.3203), the color temperature is 3093 K, and the warm white light is synthesized. The thermal stability of the synthesized warm white phosphors is 90.1% (423 K), the thermal sensing factors are Samax = 5.51 × 10-4 K-1 (303 K) and Srmax = 0.0359% K-1 (303 K), and the actual quantum efficiency is IQE = 52.48%. These results prove that Ca3Al2Ge3O12: Dy3+, Eu3+ have good application prospects as single-component warm w-LED devices.

12.
Phys Chem Chem Phys ; 26(4): 3375-3388, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38204322

RESUMO

LiYGeO4 phosphors doped with Dy3+ and Eu3+ ions were synthesized using the solid phase method, and their color characteristics were adjustable. The bandgap value of LiYGeO4 calculated by diffuse reflection data is very close to the theoretical value of 3.669 eV, indicating that LiYGeO4 is an ideal candidate for doped rare earth activated ions. The analysis of the emission spectra and fluorescence attenuation curves of Dy3+ and Eu3+ co-doped LiYGeO4 phosphors revealed a clear energy transfer process: energy transfer from Dy3+ to Eu3+. Analysis of emission spectra and fluorescence attenuation curves revealed a transfer of energy from Dy3+ to Eu3+. This transfer mechanism is attributed to the dipole-dipole interactions. In addition, by constantly adjusting the doping levels of Dy3+ and Eu3+, a warm white phosphor with a color temperature of 3881 K was obtained. Finally, the emission intensity of the LiYGeO4:0.015Dy3+,0.02Eu3+ phosphor at 423 K was 86%, indicating that the phosphor has excellent thermal stability and 40% internal quantum efficiency, which proves the potential application of the LiYGeO4 phosphor in white light-emitting diodes (w-LEDs).

13.
J Nat Prod ; 87(4): 1059-1066, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38561238

RESUMO

Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (1-7), were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 cultivated with heat-killed Pseudomonas aeruginosa. The structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data. The relative configurations were established by J-based configuration analysis and acetonide derivatization. The absolute configurations were elucidated by the Mosher ester method and ECD calculations. The structures of acremosides E-G (5-7) featured the linear sesquiterpene skeleton with a tetrahydrofuran moiety attached to a sugar alcohol. Acremosides A (1) and C-E (3-5) showed significant inhibitory activities against hepatitis C virus (EC50 values of 4.8-8.8 µM) with no cytotoxicity (CC50 of >200 µM).


Assuntos
Acremonium , Sesquiterpenos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Animais , Estrutura Molecular , Acremonium/química , Antivirais/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Poríferos/química , Hepacivirus/efeitos dos fármacos , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos
14.
J Nat Prod ; 87(2): 365-370, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38276888

RESUMO

Violaceotides B-E (1-4), four new cyclic tetrapeptides, along with seven known compounds, were identified from the sponge-associated Aspergillus insulicola IMB18-072 co-cultivated with the marine-derived Alternaria angustiovoidea IMB20-805. Their structures were elucidated by extensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and MS/MS data. The absolute configurations were determined by the advanced Marfey's method. Compounds 2, 3, and violaceotide A (5) displayed selective antimicrobial activities against the aquatic pathogenic bacteria Edwardsiella tarda and E. ictaluri. In addition, compounds 1-5 showed inhibitory activities against the LPS-induced expression of the inflammatory mediator IL-6 in RAW264.7 cells at a concentration of 10 µM.


Assuntos
Anti-Infecciosos , Espectrometria de Massas em Tandem , Técnicas de Cocultura , Espectroscopia de Ressonância Magnética , Anti-Inflamatórios/farmacologia , Estrutura Molecular , Fungos , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química
15.
Cryobiology ; 115: 104895, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38616031

RESUMO

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.


Assuntos
Glândulas Suprarrenais , Criopreservação , Hidrocortisona , Transplante Heterólogo , Animais , Glândulas Suprarrenais/metabolismo , Transplante Heterólogo/métodos , Criopreservação/métodos , Suínos , Hidrocortisona/sangue , Ratos , Glicemia/metabolismo , Glicemia/análise , Aldosterona/sangue , Aldosterona/metabolismo , Masculino , Glicogênio/metabolismo , Ressuscitação/métodos , Preservação de Órgãos/métodos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia
16.
Am J Emerg Med ; 84: 111-119, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39111099

RESUMO

BACKGROUND: A nomogram is a visualized clinical prediction models, which offer a scientific basis for clinical decision-making. There is a lack of reports on its use in predicting the risk of arrhythmias in trauma patients. This study aims to develop and validate a straightforward nomogram for predicting the risk of arrhythmias in trauma patients. METHODS: We retrospectively collected clinical data from 1119 acute trauma patients who were admitted to the Advanced Trauma Center of the Affiliated Hospital of Zunyi Medical University between January 2016 and May 2022. Data recorded included intra-hospital arrhythmia, ICU stay, and total hospitalization duration. Patients were classified into arrhythmia and non-arrhythmia groups. Data was summarized according to the occurrence and prognosis of post-traumatic arrhythmias, and randomly allocated into a training and validation sets at a ratio of 7:3. The nomogram was developed according to independent risk factors identified in the training set. Finally, the predictive performance of the nomogram model was validated. RESULTS: Arrhythmias were observed in 326 (29.1%) of the 1119 patients. Compared to the non-arrhythmia group, patients with arrhythmias had longer ICU and hospital stays and higher in-hospital mortality rates. Significant factors associated with post-traumatic arrhythmias included cardiovascular disease, catecholamine use, glasgow coma scale (GCS) score, abdominal abbreviated injury scale (AIS) score, injury severity score (ISS), blood glucose (GLU) levels, and international normalized ratio (INR). The area under the receiver operating characteristic curve (AUC) values for both the training and validation sets exceeded 0.7, indicating strong discriminatory power. The calibration curve showed good alignment between the predicted and actual probabilities of arrhythmias. Decision curve analysis (DCA) indicated a high net benefit for the model in predicting arrhythmias. The Hosmer-Lemeshow goodness-of-fit test confirmed the model's good fit. CONCLUSION: The nomogram developed in this study is a valuable tool for accurately predicting the risk of post-traumatic arrhythmias, offering a novel approach for physicians to tailor risk assessments to individual patients.

17.
BMC Geriatr ; 24(1): 195, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38408957

RESUMO

BACKGROUND: Loneliness is a negative emotional state that can lead to physical and mental health problems. This study's objective was to acquire an in-depth understanding of the heterogeneity and the predictors of loneliness among older adults in rural China and provide valuable references for practical interventions. METHODS: Older rural adults in China (N = 680) were recruited between January and April 2023. Latent profile analysis (LPA) was employed to identify subgroups of loneliness among participants. Single-factor and multinomial logistic regression analyses were conducted to investigate predictors of loneliness. RESULTS: The loneliness of rural older adults could be divided into three subgroups: low interaction loneliness group (55.0%), moderate emotional loneliness group (31.8%), and high loneliness group (13.2%). The subgroup predictors included age, gender, religious beliefs, marital status, living alone, number of chronic diseases, and smartphone use (P < 0.05). CONCLUSION: This study identified a classification pattern for loneliness among older adults in rural areas of China, revealed the characteristics of different demographic variables in loneliness categories, and highlighted the heterogeneity of loneliness in this population. It serves as a theoretical reference for formulating intervention plans aimed at addressing various loneliness categories for local rural older adults. CLINICAL TRIAL REGISTRATION: ChiCTR2300071591.


Assuntos
Emoções , Solidão , Humanos , Idoso , Solidão/psicologia , Estado Civil , População Rural , China/epidemiologia
18.
BMC Geriatr ; 24(1): 49, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212725

RESUMO

BACKGROUND: This study explores the effect of sensory-based static balance training on the balance ability, aging attitude, and perceived stress of older adults in the community. It provides a practical basis for the in-depth implementation and revision of the community health management model. METHODS: A randomized controlled intervention study was conducted from 2022 to 2023. A total of 72 older adults were recruited and randomly divided into an intervention group (36 individuals) and a control group (36 individuals). Balance ability (measured by the Short Physical Performance Battery and One Leg Stand Test), aging attitudes, and perceived stress were assessed at baseline and at the 12-week and 24-week follow-ups. Repeated-measures ANOVA and generalized estimating equations were used to compare outcome measures. RESULTS: Sensory-based static balance training was beneficial for balance ability and aging attitude among participants in the intervention group. At the end of the intervention, participants in the intervention group showed significant improvements in SPPB scores and OLST scores compared with the control group (FSPPB = 12.347, P = 0.001, Waldχ2OLST = 45.530, P < 0.001), as well as significant differences in aging attitudes (FAAQ = 18.549, P < 0.001). Multiple comparisons at different time points in the intervention group reveal a significant intervention effect (FSPPB = 29.211, Waldχ2OLST = 80.428, FAAQ = 45.981, all P < 0.05). However, the difference in perceived stress before and after the intervention was not significant (FCPSS = 2.876, P = 0.095). CONCLUSIONS: Sensory-based static balance training significantly improved balance ability and aging attitudes among older adults in the community. The effect on perceived stress among older adults in the community was not significant. TRIAL REGISTRATION: Registered in the Chinese Clinic on 04/06/2022. The registration number is ChiCTR2200060541.


Assuntos
Terapia por Exercício , Equilíbrio Postural , Humanos , Idoso , Envelhecimento , Estresse Psicológico/terapia
19.
Sensors (Basel) ; 24(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38400261

RESUMO

In the field of inter-satellite laser communication, achieving high-quality communication and compensating for the Doppler frequency shift caused by relative motion necessitate lasers with narrow linewidths, low phase noise, and the ability to achieve mode-hop-free tuning within a specific range. To this end, this paper investigates a novel external cavity diode laser (ECDL) with a frequency-selective F-P etalon structure, leveraging the external cavity F-P etalon structure in conjunction with an auxiliary filter to achieve single longitudinal mode selection. The laser undergoes linewidth testing using a delayed self-heterodyne beating method, followed by the testing of its phase noise and frequency noise characteristics using a noise analyzer, yielding beat spectra and noise power spectral density profiles. Furthermore, the paper introduces an innovative bidirectional temperature-scanning laser method to achieve optimal laser-operating point selection and mode-hop-free tuning. The experimental results showcase that the single longitudinal mode spectral side-mode suppression ratio (SMSR) is around 70 dB, and the output power exceeds 10 mW. Enhancing the precision of the F-P etalon leads to a more pronounced suppression of low-frequency phase noise, reducing the Lorentzian linewidth from the initial 10 kHz level to a remarkable 5 kHz level. The bidirectional temperature-scanning laser method not only allows for the selection of the optimal operating point but also enables mode-hop-free tuning within 160 pm.

20.
J Stroke Cerebrovasc Dis ; 33(4): 107616, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316284

RESUMO

OBJECTIVE: The clinical characteristics and mechanisms of stroke caused by anterior circulation atherosclerotic plaques (ACAPs) and posterior circulation atherosclerotic plaques (PCAPs) are distinct. We aimed to compare the differences in vulnerability, morphology, and distribution between ACAPs and PCAPs based on hign-resolution magnetic resonance imaging (HR-MRI). MATERIALS AND METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang database were retrieved from inception through May 2023. Meta-analysis was performed by R 4.2.1 software. The quality of the literature was assessed by the Agency for Healthcare Research and Quality (AHRQ). Subgroup analysis was conducted to explore the heterogeneity of the pooled results. RESULTS: There were a total of 13 articles, including 1194 ACAPs and 1037 PCAPs. The pooled estimates demonstrated that the incidence of intraplaque hemorrhage in the PCAPs was higher (OR 1.72, 95%CI 1.35-2.18). The plaque length (SMD 0.23, 95%CI 0.06-0.39) and remodeling index (SMD 0.29, 95%CI 0.14-0.44) of PCAPs were larger than those in ACAPs. However, there were no evident differences in significant enhancement or stenosis degree between the two groups. CONCLUSION: There were more unstable features in PCAPs, highlighting an elevated risk of recurrent ischemic stroke in the posterior circulation. Furthermore, PCAPs were prone to developing penetrating artery disease due to their wider distribution. Nevertheless, posterior circulation arteries exhibited a greater propensity for outward remodeling, which may lead treatment team to miss the optimal intervention stage by being overlooked on angiographic detection.


Assuntos
Circulação Cerebrovascular , Arteriosclerose Intracraniana , Imageamento por Ressonância Magnética , Placa Aterosclerótica , Valor Preditivo dos Testes , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Fatores de Risco , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Medição de Risco , Ruptura Espontânea , Prognóstico , Artéria Cerebral Posterior/diagnóstico por imagem , Artéria Cerebral Posterior/fisiopatologia , Artéria Cerebral Anterior/diagnóstico por imagem , Artéria Cerebral Anterior/fisiopatologia , Idoso de 80 Anos ou mais
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