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1.
Chem Commun (Camb) ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946539

RESUMEN

Designing electrocatalysts for seawater splitting remains challenging. A Ru-Co alloy supported by an N-doped carbon substrate catalyst has been designed using etching and a low-temperature treatment method. Studies show that the superior performance of this catalyst is related to the hollow-structured N-doped carbon frame and surface reconstruction of the Ru-Co alloy.

2.
Heliyon ; 10(6): e28086, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38533007

RESUMEN

Wound healing is an intricate and fine regulatory process. In diabetic patients, advanced glycation end products (AGEs), excessive reactive oxygen species (ROS), biofilm formation, persistent inflammation, and angiogenesis regression contribute to delayed wound healing. Epigenetics, the fast-moving science in the 21st century, has been up to date and associated with diabetic wound repair. In this review, we go over the functions of epigenetics in diabetic wound repair in retrospect, covering transcriptional and posttranscriptional regulation. Among these, we found that histone modification is widely involved in inflammation and angiogenesis by affecting macrophages and endothelial cells. DNA methylation is involved in factors regulation in wound repair but also affects the differentiation phenotype of cells in hyperglycemia. In addition, noncodingRNA regulation and RNA modification in diabetic wound repair were also generalized. The future prospects for epigenetic applications are discussed in the end. In conclusion, the study suggests that epigenetics is an integral regulatory mechanism in diabetic wound healing.

3.
J Clin Med ; 13(3)2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38337466

RESUMEN

Background: Bladder cancer is a common urinary tract malignancy. Minimally invasive radical cystectomy has shown oncological outcomes comparable to the conventional open surgery and with advantages over the open procedure. However, outcomes of the two main minimally invasive procedures, robot-assisted and pure laparoscopic, have yet to be compared. This study aimed to compare in-hospital outcomes between these two techniques performed for patients with bladder cancer. Methods: This population-based, retrospective study included hospitalized patients aged ≥ 50 years with a primary diagnosis of bladder cancer who underwent robot-assisted or pure laparoscopic radical cystectomy. All patient data were extracted from the US National Inpatient Sample (NIS) database 2008-2018 and were analyzed retrospectively. Primary outcomes were in-hospital mortality, prolonged length of stay (LOS), and postoperative complications. Results: The data of 3284 inpatients (representing 16,288 US inpatients) were analyzed. After adjusting for confounders, multivariable analysis revealed that patients who underwent robot-assisted radical cystectomy had a significantly lower risk of in-hospital mortality (adjusted OR [aOR], 0.50, 95% CI: 0.28-0.90) and prolonged LOS (aOR, 0.63, 95% CI: 0.49-0.80) than those undergoing pure laparoscopic cystectomy. Patients who underwent robot-assisted radical cystectomy had a lower risk of postoperative complications (aOR, 0.69, 95% CI: 0.54-0.88), including bleeding (aOR, 0.73, 95% CI: 0.54-0.99), pneumonia (aOR, 0.49, 95% CI: 0.28-0.86), infection (aOR, 0.55, 95% CI: 0.36-0.85), wound complications (aOR, 0.33, 95% CI: 0.20-0.54), and sepsis (aOR, 0.49, 95% CI: 0.34-0.69) compared to those receiving pure laparoscopic radical cystectomy. Conclusions: Patients with bladder cancer, robot-assisted radical cystectomy is associated with a reduced risk of unfavorable short-term outcomes, including in-hospital mortality, prolonged LOS, and postoperative complications compared to pure laparoscopic radical cystectomy.

4.
Neurochem Res ; 49(3): 557-567, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38063946

RESUMEN

Stroke, the second-largest cause of death and the leading cause of disability globally, presents significant challenges in terms of prognosis and treatment. Identifying reliable prognosis biomarkers and treatment targets is crucial to address these challenges. Circular RNA (circRNA) has emerged as a promising research biomarkers and therapeutic targets because of its tissue specificity and conservation. However, the potential role of circRNA in stroke prognosis and treatment remains largely unexplored. This review briefly elucidate the mechanism underlying circRNA's involvement in stroke pathophysiology. Additionally, this review summarizes the impact of circRNA on different forms of strokes, including ischemic stroke and hemorrhagic stroke. And, this article discusses the positive effects of circRNA on promoting cerebrovascular repair and regeneration, maintaining the integrity of the blood-brain barrier (BBB), and reducing neuronal injury and immune inflammatory response. In conclusion, the significance of circRNA as a potential prognostic biomarker and a viable therapeutic target was underscored.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , ARN Circular/genética , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/terapia , Biomarcadores , Barrera Hematoencefálica
5.
Tissue Eng Part A ; 30(3-4): 107-114, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38019087

RESUMEN

Researchers have been exploring alternative methods for bone tissue engineering, as current management of critical bone defects may be a significant challenge for both patient and surgeon with conventional surgical treatments associated with several potential complications and drawbacks. Recent studies have shown mesenchymal stem cell sheets may enhance bone regeneration in different animal models. We investigated the efficacy of implanted scaffold-free bone marrow-derived mesenchymal stem cell (BMSC) sheets on bone regeneration of a critical bone defect in a weight-bearing rat model. BMSCs were isolated from the femora of male Sprague-Dawley rats 5-6 weeks of age and cell sheets were produced on temperature-responsive culture dishes. Nine male Sprague-Dawley rats 6-8 weeks of age were utilized. A bilateral femoral critical bone defect was created with a bridge plate serving as internal fixation. One side was randomly selected and BMSC sheets were implanted into the bone defect (BMSC group), with the contralateral side receiving no treatment (control). Rats were anesthetized and radiographs were performed at 2-week intervals. At the 8-week time point, rats were euthanized, femurs harvested, and microcomputed tomography and histological analysis was performed. We found a statistically significant increase in new bone formation and bone volume fraction compared with the control. Histomorphometry analysis revealed a larger percent of newly formed bone and a higher total histological score. Our results suggest that scaffold-free BMSC sheets may be used in the management of large weight-bearing bone defects to complement a different surgical technique or as a standalone approach followed by internal fixation. However, further research is still needed.


Asunto(s)
Células Madre Mesenquimatosas , Osteogénesis , Animales , Masculino , Ratas , Médula Ósea , Regeneración Ósea , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos , Microtomografía por Rayos X
6.
J Hematol Oncol ; 16(1): 123, 2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38110976

RESUMEN

Liquid-liquid phase separation (LLPS) is a novel principle for interpreting precise spatiotemporal coordination in living cells through biomolecular condensate (BMC) formation via dynamic aggregation. LLPS changes individual molecules into membrane-free, droplet-like BMCs with specific functions, which coordinate various cellular activities. The formation and regulation of LLPS are closely associated with oncogenesis, tumor progressions and metastasis, the specific roles and mechanisms of LLPS in tumors still need to be further investigated at present. In this review, we comprehensively summarize the conditions of LLPS and identify mechanisms involved in abnormal LLPS in cancer processes, including tumor growth, metastasis, and angiogenesis from the perspective of cancer hallmarks. We have also reviewed the clinical applications of LLPS in oncologic areas. This systematic summary of dysregulated LLPS from the different dimensions of cancer hallmarks will build a bridge for determining its specific functions to further guide basic research, finding strategies to intervene in LLPS, and developing relevant therapeutic approaches.


Asunto(s)
Neoplasias , Separación de Fases , Humanos , Transformación Celular Neoplásica , Carcinogénesis , Oncología Médica
7.
Front Neurosci ; 17: 1282558, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38027482

RESUMEN

Introduction: Epidural electrical stimulation (EES) has been shown to improve motor dysfunction after spinal cord injury (SCI) by activating residual locomotor neural networks. However, the stimulation current often spreads excessively, leading to activation of non-target muscles and reducing the accuracy of stimulation regulation. Objectives: Near-infrared nerve stimulation (nINS) was combined with EES to explore its regulatory effect on lower limb muscle activity in spinal-cord-transected rats. Methods: In this study, stimulation electrodes were implanted into the rats' L3-L6 spinal cord segment with T8 cord transected. Firstly, a series of EES parameters (0.2-0.6 mA and 20-60 Hz) were tested to determine those that specifically regulate the tibialis anterior (TA) and medial gastrocnemius (MG). Subsequently, to determine the effect of combined optical and electrical stimulation, near-infrared laser with a wavelength of 808 nm was used to irradiate the L3-L6 spinal cord segment while EES was performed. The amplitude of electromyography (EMG), the specific activation intensity of the target muscle, and the minimum stimulus current intensity to induce joint movement (motor threshold) under a series of optical stimulation parameters (power: 0.0-2.0 W; pulse width: 0-10 ms) were investigated and analyzed. Results: EES stimulation with 40 Hz at the L3 and L6 spinal cord segments specifically activated TA and MG, respectively. High stimulation intensity (>2 × motor threshold) activated non-target muscles, while low stimulation frequency (<20 Hz) produced intermittent contraction. Compared to electrical stimulation alone (0.577 ± 0.081 mV), the combined stimulation strategy could induce stronger EMG amplitude of MG (1.426 ± 0.365 mV) after spinal cord injury (p < 0.01). The combined application of nINS effectively decreased the EES-induced motor threshold of MG (from 0.237 ± 0.001 mA to 0.166 ± 0.028 mA, p < 0.001). Additionally, the pulse width (PW) of nINS had a slight impact on the regulation of muscle activity. The EMG amplitude of MG only increased by ~70% (from 3.978 ± 0.240 mV to 6.753 ± 0.263 mV) when the PW increased by 10-fold (from 1 to 10 ms). Conclusion: The study demonstrates the feasibility of epidural combined electrical and optical stimulation for highly specific regulation of muscle activity after SCI, and provides a new strategy for improving motor dysfunction caused by SCI.

8.
Acta Biochim Pol ; 70(4): 791-797, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37929666

RESUMEN

DMED is a common complication of diabetes, for which new treatment methods are urgently required. Focused on DMED, the pharmacological mechanism of simvastatin (Sim) was probed. A model of DMED was made in rats with streptozotocin and orally medicated with Sim. Lentiviral vectors that interfere with miR-9-5p or PDCD4 were injected, and the erectile function, histopathology of cavernous tissue, and α-SMA expression were evaluated. Cavernous smooth muscle cells (CMSCs) obtained from DMED rats were treated with Sim and transfected with the plasmid vector that interferes with miR-9-5p or PDCD4 to observe cell viability and apoptosis. The binding relationship between miR-9-5p and PDCD4 was checked. After 8-week treatment with Sim, erectile function was improved and the corpus cavernosum injury was alleviated. Upregulating miR-9-5p or downregulating PDCD4 further improved erectile function and cavernous injury in rats. miR-9-5p targeted regulation of PDCD4. In vitro cell experiment results showed that Sim induced proliferation and reduced apoptosis of CSMCs by enhancing miR-9-5p-targeted regulating PDCD4 in vitro. Sim attenuates DMED in rats via miR-9-5p/PDCD4.


Asunto(s)
Diabetes Mellitus Experimental , Disfunción Eréctil , MicroARNs , Masculino , Humanos , Ratas , Animales , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/genética , Ratas Sprague-Dawley , Simvastatina/farmacología , Simvastatina/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , MicroARNs/genética , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de Unión al ARN/genética
9.
Artículo en Inglés | MEDLINE | ID: mdl-37878252

RESUMEN

The coronavirus disease 2019 (COVID-19) epidemic has given a warning that it is important to explore the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical specimens or environmental samples for public health strategies and future variants. The surface-enhanced Raman spectroscopy (SERS) technique was demonstrated to achieve this goal. However, the consistency of signals originating from the poor compatibility of virions with SERS hotspots remains a key scientific challenge for the practical applications of SERS. Herein, we develop a SERS platform for the ultrasensitive and rapid detection of SARS-CoV-2 antigen within 20 min by the combination of a highly consistent SERS substrate and a supervised deep learning algorithm. A V-shaped resonant cavity array (VRC) substrate was fabricated to trap SARS-CoV-2 virions in the periodic V cavity array and stimulate the integral SERS signal of the virus via a resonance coupling effect. Benefiting from the unique architecture of the VRC substrate, we were able to directly detect the SARS-CoV-2 virus with high sensitivity and high consistency. These excellent performances enabled us to identify five different kinds of SARS-CoV-2 variants and detect SARS-CoV-2 from clinical and environmental samples with high accuracies.

10.
Nat Commun ; 14(1): 6469, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833289

RESUMEN

Niemann-Pick C1-like 1 (NPC1L1) is essential for intestinal cholesterol absorption. Together with the cholesterol-rich and Flotillin-positive membrane microdomain, NPC1L1 is internalized via clathrin-mediated endocytosis and transported to endocytic recycling compartment (ERC). When ERC cholesterol level decreases, NPC1L1 interacts with LIMA1 and moves back to plasma membrane. However, how cholesterol leaves ERC is unknown. Here, we find that, in male mice, intracellular bile acids facilitate cholesterol transport to other organelles, such as endoplasmic reticulum, in a non-micellar fashion. When cholesterol level in ERC is decreased by bile acids, the NPC1L1 carboxyl terminus that previously interacts with the cholesterol-rich membranes via the A1272LAL residues dissociates from membrane, exposing the Q1277KR motif for LIMA1 recruitment. Then NPC1L1 moves back to plasma membrane. This study demonstrates an intracellular cholesterol transport function of bile acids and explains how the substantial amount of cholesterol in NPC1L1-positive compartments is unloaded in enterocytes during cholesterol absorption.


Asunto(s)
Colesterol , Proteínas de Transporte de Membrana , Animales , Masculino , Ratones , Transporte Biológico , Membrana Celular/metabolismo , Colesterol/metabolismo , Absorción Intestinal , Proteínas de Transporte de Membrana/metabolismo
11.
Front Oncol ; 13: 1147805, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37681027

RESUMEN

Introduction: Immunogenic cell death (ICD) is a form of regulated cell death that activates an adaptive immune response in an immunocompetent host and is particularly sensitive to antigens from tumor cells. Kidney clear cell carcinoma (KIRC) is an immunogenic tumor with extensive tumor heterogeneity. However, no reliable predictive biomarkers have been identified to reflect the immune microenvironment and therapeutic response of KIRC. Methods: Therefore, we used the CIBERSORT and ESTIMATE algorithms to define three ICD clusters based on the expression of ICD-related genes in 661 KIRC patients. Subsequently, we identified three different ICD gene clusters based on the overlap of differentially expressed genes (DEGs) within the ICD clusters. In addition, principal component analysis (PCA) was performed to calculate the ICD scores. Results: The results showed that patients with reduced ICD scores had a poorer prognosis and reduced transcript levels of immune checkpoint genes regulated with T cell differentiation. Furthermore, the ICD score was negatively correlated with the tumor mutation burden (TMB) value of KICD. patients with higher ICD scores showed clinical benefits and advantages of immunotherapy, indicating that the ICD score is an accurate and valid predictor to assess the effect of immunotherapy. Discussion: Overall, our study presents a comprehensive KICD immune-related ICD landscape that can provide guidance for current immunotherapy and predict patient prognosis to help physicians make judgments about the patient's disease and treatment modalities, and can guide current research on immunotherapy strategies for KICD.

12.
iScience ; 26(6): 106784, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37378337

RESUMEN

Graph theory-based analysis describes the brain as a complex network. Only a few studies have examined modular composition and functional connectivity (FC) between modules in patients with spinal cord injury (SCI). Little is known about the longitudinal changes in hubs and topological properties at the modular level after SCI and treatment. We analyzed differences in FC and nodal metrics reflecting modular interaction to investigate brain reorganization after SCI-induced compensation and neurotrophin-3 (NT3)-chitosan-induced regeneration. Mean inter-modular FC and participation coefficient of areas related to motor coordination were significantly higher in the treatment animals than in the SCI-only ones at the late stage. The magnocellular part of the red nucleus may reflect the best difference in brain reorganization after SCI and therapy. Treatment can enhance information flows between regions and promote the integration of motor functions to return to normal. These findings may reveal the information processing of disrupted network modules.

13.
Sci Total Environ ; 892: 164662, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37277044

RESUMEN

Owing to its biotoxicity and inductive effect on photochemical pollution, atmospheric peroxyacetyl nitrate (PAN), which is a typical product of atmospheric photochemical reactions, has attracted much research attention. However, to the best of our knowledge, few comprehensive studies have been conducted on the seasonal variation and key influencing factors of PAN concentrations in southern China. In this study, PAN, ozone (O3), precursor volatile organic compound (VOC), and other pollutant concentrations were measured online for 1 year (from October 2021 to September 2022) in Shenzhen, a megacity in the Greater Bay Area of China. The average concentrations of PAN and peroxypropionyl nitrate (PPN) were 0.54 and 0.08 parts per billion (ppb), and the maximum hourly concentrations reached 10.32 and 1.01 ppb, respectively. The results of the generalized additive model (GAM) showed that the atmospheric oxidation capacity and precursor concentration were the most important factors affecting the PAN concentration. According to the steady-state model, the average cumulative contribution to the peroxyacetyl (PA) radical formation rate by six major carbonyl compounds was calculated at 4.2 × 106 molecules cm-3 s-1, and acetaldehyde (63.0 %) and acetone (13.9 %) contributed the most. Furthermore, the photochemical-age-based parameterization method was used to analyze the source contributions of carbonyl compounds and PA radicals. The results showed that although the primary anthropogenic (40.2 %), biogenic (27.8 %), and secondary anthropogenic (16.4 %) sources were the most important contributors of PA radicals, the biogenic and secondary anthropogenic source contributions both increased considerably in summer, and the cumulative proportion of both sources reached ~70 % in July. In addition, a comparison of PAN pollution processes in different seasons revealed that in summer and winter, the PAN concentration was predominantly limited by precursors and meteorological parameters, such as light intensity, respectively.


Asunto(s)
Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Estaciones del Año , Contaminantes Atmosféricos/análisis , China , Ozono/análisis , Compuestos Orgánicos Volátiles/análisis , Monitoreo del Ambiente
14.
World J Clin Cases ; 11(10): 2290-2300, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37122511

RESUMEN

BACKGROUND: Hypoparathyroidism, which can be sporadic or a component of an inherited syndrome, is the most common cause of hypocalcemia. If hypocalcemia is accompanied by other electrolyte disturbances, such as hypokalemia and hypomagnesemia, then the cause, such as renal tubular disease, should be carefully identified. CASE SUMMARY: An 18-year-old female visited our clinic because of short stature and facial deformities, including typical phenotypes, such as low ear position, depression of the nasal bridge, small hands and feet, and loss of dentition. The lab results suggested normal parathyroid hormone but hypocalcemia. In addition, multiple electrolyte disturbances were found, including hypokalemia, hypocalcemia and hypomagnesemia. The physical signs showed a short fourth metatarsal bone of both feet. The X-ray images showed cortical thickening of long bones and narrowing of the medulla of the lumen. Cranial computed tomography indicated calcification in the bilateral basal ganglia. Finally, the genetic investigation showed a de novo heterogenous mutation of "FAM111A" (c. G1706A:p.R569H). Through a review of previously reported cases, the mutation was found to be the most common mutation site in Kenny-Caffey syndrome type 2 (KCS2) cases reported thus far (16/23, 69.6%). The mutation was slightly more prevalent in females than in males (11/16, 68.8%). Except for hypocalcemia, other clinical manifestations are heterogeneous. CONCLUSION: As a rare autosomal dominant genetic disease of hypoparathyroidism, the clinical manifestations of KCS2 are atypical and diverse. This girl presented with short stature, facial deformities and skeletal deformities. The laboratory results revealed hypocalcemia as the main electrolyte disturbance. Even though her family members showed normal phenotypes, gene detection was performed to find the mutation of the FAM111A gene and confirmed the diagnosis of KCS2.

15.
Front Oncol ; 13: 1169876, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152007

RESUMEN

C-ros oncogene 1 (ROS1) fusion is a pathogenic driver gene in non-small cell lung cancer (NSCLC). Currently, clinical guidelines from the National Comprehensive Cancer Network (NCCN) have recommended molecular pathologic tests for patients with NSCLC, including the detection of the ROS1 gene. Crizotinib is a small molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and mesenchymal-epithelial transition (MET). In recent years, the efficacy of crizotinib in NSCLC patients with ROS1 fusion has been reported. Here, a 77-year-old woman was diagnosed with stage IVA lung adenocarcinoma harboring a novel low-density lipoprotein receptor (LDLR)-ROS1 fusion variant. This novel LDLR-ROS1 fusion was identified by targeted DNA next-generation sequencing (NGS) panel and then verified by RNA fusion panel based on amplicon sequencing. This patient benefited from subsequent crizotinib therapy and achieved progression-free survival of 15 months without significant toxic symptoms. Our case report recommended a promising targeted therapeutic option for patients with metastatic NSCLC with LDLR-ROS1 fusion and highlighted the importance of genetic testing for accurate treatment.

16.
Transplant Proc ; 55(4): 782-787, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37246131

RESUMEN

BACKGROUND: The aim of this study is to evaluate the impact of intraoperative allograft vascular flow on early kidney graft function. METHODS: A total of 159 patients underwent kidney transplantation from January 2017 to March 2022 at Linkou Chang Gung Memorial Hospital. Graft arterial and venous blood flow was measured separately with a transient time flowmeter (Transonic HT353; Transonic Systems, Inc, Ithaca, NY, United States) after ureteroneocystostomy. The early outcomes, including the postoperative creatinine level, were analyzed accordingly. RESULTS: There were 83 males and 76 females, with a mean age of 44.5 years. The mean graft arterial flow measured was 480.6 mL/min, and the mean venous flow was 506.2 mL/min. Delayed graft function (DGF) incidence was 36.5%, 32.5%, and 40.8% in total, living, and deceased donor groups, respectively. Living donor and deceased donor kidney transplantation were analyzed separately. In the DGF subgroup, there were lower graft venous flows, higher body mass index (BMI), and more male patients in the living kidney transplant group. Similarly, the deceased donor kidney transplantation group with delayed graft function tended to have higher body height, higher body weight, higher BMI, and more diabetes mellitus. The multivariate analysis showed that lower graft venous blood flow (odds ratio [OR] = 0.995, P = .008) and higher BMI (OR = 1.144, P = .042) were significantly correlated with delayed graft function in living donor kidney transplantations. In the deceased donor group, a multivariate analysis of risk factors showed that BMI had a significant correlation with delayed graft function (OR = 1.41, P = .039). CONCLUSIONS: Graft venous blood flow was significantly associated with delayed graft function in living donor kidney transplantation, and high BMI was correlated with DGF in all patients receiving kidney transplantation.


Asunto(s)
Funcionamiento Retardado del Injerto , Supervivencia de Injerto , Femenino , Humanos , Masculino , Adulto , Funcionamiento Retardado del Injerto/etiología , Funcionamiento Retardado del Injerto/epidemiología , Rechazo de Injerto/epidemiología , Estudios Retrospectivos , Donantes de Tejidos , Donadores Vivos , Factores de Riesgo
17.
Arterioscler Thromb Vasc Biol ; 43(7): 1219-1233, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37165876

RESUMEN

BACKGROUND: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported. METHODS: The study involved the whole-exome and target sequencing of college students from Uyghur and other ethnic groups in Xinjiang, China, for the association of PCSK9 loss-of-function mutations with low plasma levels of LDL-C. The mechanisms by which the identified mutations affect the function of PCSK9 were investigated in cultured cells using biochemical and cell assays. The causal effects of the identified PCSK9 mutations on LDL-C levels were verified in mice injected with adeno-associated virus expressing different forms of PCSK9 and fed a high-cholesterol diet. RESULTS: We identified 2 PCSK9 mutations-E144K and C378W-in Chinese Uyghurs with low plasma levels of LDL-C. The E144K and C378W mutations impaired the maturation and secretion of the PCSK9 protein, respectively. Adeno-associated virus-mediated expression of E144K and C378W mutants in Pcsk9 KO (knockout) mice fed a high-cholesterol diet also hampered PCSK9 secretion into the serum, resulting in elevated levels of LDL receptor in the liver and reduced levels of LDL-C in the serum. CONCLUSIONS: Our study shows that E144K and C378W are PCSK9 loss-of-function mutations causing low LDL-C levels in mice and probably in humans as well.


Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Hipercolesterolemia , Humanos , Ratones , Animales , Proproteína Convertasa 9/genética , LDL-Colesterol , Serina Endopeptidasas/genética , Proproteína Convertasas/genética , Proproteína Convertasas/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Ratones Noqueados , Aterosclerosis/genética , Aterosclerosis/prevención & control , Aterosclerosis/metabolismo , Mutación
18.
Basic Clin Androl ; 33(1): 12, 2023 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-37138233

RESUMEN

BACKGROUND: This study aimed to compare the clinical outcomes of non-transecting urethroplasty and lingual mucosal urethroplasty in the treatment of iatrogenic bulbar urethral stricture. RESULTS: A total of 25 patients with iatrogenic bulbar urethral stricture were enrolled, 12 of whom underwent lingual mucosal urethroplasty, 13 patients who underwent non-transecting urethroplasty. All patients were followed-up and evaluated at 3 postoperative months. Evaluations included urethrography, maximum urine flow rate (Qmax), nocturnal erectile function testing, International Index of Erectile Function (IIEF-5) assessment, and Anxiety Related Scale (SAS) assessment. In terms of operation time, there was a significant difference between non-transecting urethroplasty and lingual mucosal urethroplasty. However, there was no significant intergroup difference in intraoperative blood loss. Both techniques were associated with significantly improved Qmax relative to preoperative rates, but there was no significant difference between the groups in this regard over 3 months of postoperative follow-up. Nocturnal penile tumescence and rigidity results showed that there was no significant change in tip hardness after surgery in the non-transecting urethroplasty group. Moreover, IIEF-5 scores indicated that there was no significant intergroup difference in terms of subjective postoperative erectile function. According to the preliminary psychological evaluations during postoperative follow-up, the anxiety scores of patients undergoing non-transecting urethroplasty significantly improved, but there was no significant change in the mean SAS score among patients who underwent lingual mucosal urethroplasty. CONCLUSION: Both surgical methods can achieve the clinical goal of treating iatrogenic bulbar urethral stricture. Non-transecting urethroplasty has the characteristics of short operation time, relative technical simplicity, and retention of the original erectile function of most patients, and the surgical outcomes of non-transecting urethroplasty are not inferior to those of lingual mucosal urethroplasty, and it is a promising technique for widespread use to treat bulbar urethral strictures.


RéSUMé: CONTEXTE: Cette étude visait à comparer les résultats cliniques de l'urétroplastie non transectante et de l'urétroplastie avec greffe de  muqueuse linguale dans le traitement de la sténose urétrale bulbaire iatrogène. Un total de 25 patients présentant une sténose urétrale bulbaire iatrogène a été recruté, dont 12 ont subi une urétroplastie avec greffe de muqueuse buccale et 13 une urétroplastie non-transectante. Tous les patients ont été suivis et évalués à 3 mois postopératoires. Les évaluations comprenaient une uréthrographie, le débit urinaire maximal (Qmax), un test nocturne de la fonction érectile, l'évaluation de l'index international de la fonction érectile (IIEF5) et une évaluation de l'échelle d'anxiété. RéSULTATS: En termes de durée opératoire, il y avait une différence significative entre l'urétroplastie non-transectante et urétroplastie avec greffe de muqueuse buccale. Cependant, il n'y avait pas de différence significative entre les groupes en ce qui concerne la perte de sang peropératoire. Les deux techniques ont été associées à une amélioration significative du Qmax par rapport aux taux préopératoires, mais il n'y avait pas de différence significative entre les groupes à cet égard sur 3 mois de suivi postopératoire. Les résultats de la tumescence et de la rigidité nocturnes du pénis ont montré qu'il n'y avait pas de changement significatif de la dureté de l'extrémité du pénis après l'opération dans le groupe d'urétroplastie sans transsection. De plus, les scores IIEF-5 ont indiqué qu'il n'y avait pas de différence significative entre les groupes en termes de fonction érectile subjective postopératoire. Selon les évaluations psychologiques préliminaires au cours du suivi postopératoire, les scores d'anxiété des patients ayant subi une urétroplastie non-transectante se sont améliorés de manière significative, mais il n'y a pas eu de changement significatif du score moyen de l'échelle d'anxiété chez les patients ayant subi une urétroplastie avec greffe de muqueuse buccale. CONCLUSIONS: Les deux méthodes permettent d'atteindre l'objectif clinique du traitement de la sténose urétrale bulbaire iatrogène. L'urétroplastie sans transsection présente les caractéristiques suivantes: temps d'opération court, simplicité technique relative et maintien de la fonction érectile initiale chez la plupart des patients. Les résultats chirurgicaux de l'urétroplastie sans transsection ne sont pas inférieurs à ceux de l'urétroplastie avec greffe de muqueuse buccale et cette technique est prometteuse pour une utilisation généralisée dans le traitement des rétrécissements urétraux bulbaires.

20.
Opt Express ; 31(5): 7994-8004, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36859918

RESUMEN

We propose a scheme to realize robust optical entanglement in cavity optomagnonics, where two optical whispering gallery modes (WGMs) couple to a magnon mode in a yttrium iron garnet (YIG) sphere. The beam-splitter-like and two-mode squeezing magnon-photon interactions can be realized simultaneously when the two optical WGMs are driven by external fields. Entanglement between the two optical modes is then generated via their coupling with magnons. By exploiting the destructive quantum interference between the bright modes of the interface, the effects of initial thermal occupations of magnons can be eliminated. Moreover, the excitation of the Bogoliubov dark mode is capable of protecting the optical entanglement from thermal heating effects. Therefore, the generated optical entanglement is robust against thermal noise and the requirement of cooling the magnon mode is relaxed. Our scheme may find applications in the study of magnon-based quantum information processing.

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