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BACKGROUND: The pathological results obtained from endoscopic forceps biopsy (EFB) do not always align with the findings of postoperative endoscopic submucosal dissection (ESD). Furthermore, as ESD becomes more widespread, the number of noncurative endoscopic cases increases; thus, an accurate preoperative diagnosis and an appropriate treatment method are crucial. The purpose of this study was to explore the risk factors for postoperative pathological upgrading and noncurative resection and to gather experience in clinical and pathological diagnosis. METHODS: From March 2016 to November 2023, 292 ESD specimens were collected from 262 patients with gastric mucosal lesions. Clinicopathological information, the coincidence rate of pathological diagnosis between EFB and ESD specimens, and risk factors related to noncurative resection were analyzed retrospectively. RESULTS: The overall upgraded pathological diagnosis rate between EFB and ESD was 26.4%. The independent predictors for the upgraded group included proximal stomach lesions, lesion size > 2 cm, surface ulceration, and surface nodules. Twenty of the 235 early gastric cancer (EGC) patients underwent noncurative ESD resection. Multivariate analysis showed that undifferentiated carcinoma and tumor infiltration into the submucosa were significantly associated with noncurative resection. CONCLUSION: Biopsy cannot fully represent the lesions of gastric intraepithelial neoplasia (GIN). When a suspected epithelial dysplasia is suspected, a careful endoscopic examination should be conducted to evaluate the lesion site, size, and surface characteristics to ensure an accurate diagnosis. Noncurative endoscopic resection is associated with undifferentiated carcinoma and submucosal infiltration. Clinicians must be familiar with these predictive factors for noncurative resection and select the appropriate treatment for their patients.
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Resección Endoscópica de la Mucosa , Mucosa Gástrica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Femenino , Masculino , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Factores de Riesgo , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Biopsia/métodos , Gastroscopía/métodos , Adulto , Anciano de 80 o más AñosRESUMEN
Chiral assemblies have become one of the most active research areas due to their versatility, playing an increasingly important role in bio-detection, imaging and therapy. In this work, chiral UCNPs/CuxOS@ZIF nanoprobes are prepared by encapsulating upconversion nanoparticles (UCNPs) and CuxOS nanoparticles (NPs) into zeolitic imidazolate framework-8 (ZIF-8). The novel excited-state energy distribution-modulated upconversion nanostructure (NaYbF4@NaYF4: Yb, Er) is selected as the fluorescence source and energy donor for highly efficient fluorescence resonance energy transfer (FRET). CuxOS NP is employed as chiral source and energy acceptor to quench upconversion luminescence (UCL) and provide circular dichroism (CD) signal. Utilizing the natural adsorption and sorting advantages of ZIF-8, the designed nanoprobe can isolate the influence of other common disruptors, thus achieve ultra-sensitive and highly selective UCL/CD dual-mode quantification of H2S in aqueous solution and in living cells. Notably, the nanoprobe is also capable of in vivo intra-tumoral H2S tracking. Our work highlights the multifunctional properties of chiral nanocomposites in sensing and opens a new vision and idea for the preparation and application of chiral nanomaterials in biomedical and biological analysis.
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BACKGROUND: The chemokine receptor CXCR6 is critical for sustained tumor control mediated by CD8+ cytotoxic T cells (CTLs) in tumors. Previous studies have shown that ionizing radiation induces an inflamed immune contexture by upregulating CXCR6. However, the clinical significance of CXCR6 expression in triple-negative breast cancer (TNBC) and its correlation with radiotherapy remains unknown. This study aimed to clarify the prognostic value of CXCR6 and its role in the breast tumor microenvironment (TME). METHODS: The messenger RNA and protein expression of CXCR6 in human TNBC and their association with survival were analyzed. The role of CXCR6 in the immune context was investigated using a combination of single-cell RNA sequencing, bulk transcriptome sequencing data, and fluorescence-based multiplex immunohistochemistry (mIHC) techniques. RESULTS: Elevated CXCR6 expression correlated with better clinical outcomes and superior response to adjuvant radiotherapy and immunotherapy in TNBC. CXCR6 fostered an immunostimulatory microenvironment characterized by upregulated cytotoxic markers. We also found that CXCR6 plays a crucial role in regulating the differentiation of CD8+ T cells and the intercellular communication of immune cell subtypes, thus shaping the TME. CONCLUSIONS: This study highlights the emerging role of CXCR6 in shaping the TME and targeting CXCR6 may be a promising strategy for improving the effectiveness of radiotherapy and immunotherapy in TNBC.
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Receptores CXCR6 , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Humanos , Neoplasias de la Mama Triple Negativas/radioterapia , Neoplasias de la Mama Triple Negativas/inmunología , Femenino , Microambiente Tumoral/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Pronóstico , Inmunoterapia/métodos , Radioterapia AdyuvanteRESUMEN
Accurate on-site detection of nitrite in complex matrices remains a significant challenge. Herin, we construct a self-ratio optical bimodal portable kit via co-assembling NaErF4:0.5%Tm@NaYF4@NaYbF4:0.5%Tm@NaYF4 (Er:Tm@Yb:Tm) and nitrogen-doped carbon platinum nanomaterials (Pt/CN) in sodium alginate (SA) hydrogel. Pt/CN nanomaterials are synthesized by high-temperature sintering using a zinc-based zeolite imidazolium framework as a sacrificial template. The Pt/CN nanozyme possesses excellent oxidase-like activity to produce the oxidation state 3,3',5,5'-tetramethylbenzidine (oxTMB). Nitrite mediates diazotization of oxTMB to trigger the change of absorption signals, accompanying the ratio fluorescence response of the Er:Tm@Yb:Tm. Crucially, Er:Tm@Yb:Tm and Pt/CN are embedded in SA hydrogel to fabricate a portable kit with efficient and sensitive performance. An image processing algorithm is used to analyze the nitrite-induced signal change of the portable hydrogel kit, resulting in detection limits of 0.63 µM. This method has great potential for point-of-care applications due to its reliability, long-term stability, accuracy, sensitivity, and portability.
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Técnicas Biosensibles , Hidrogeles , Límite de Detección , Nitritos , Teléfono Inteligente , Técnicas Biosensibles/métodos , Nitritos/análisis , Hidrogeles/química , Humanos , Bencidinas/química , Nanoestructuras/química , Platino (Metal)/químicaRESUMEN
N-succinyl-L-phenylalanine (SP) has been identified as a taste-active contributor in an array of foods. Despite its recognized importance, the understanding of its synthesis and taste enhancement properties remains rudimentary. The study examined the enzymatic synthesis of SP with 45.58 ± 1.95% yield. This was achieved under optimized conditions: 0.3 mol/L L-phenylalanine, 0.9 mol/L succinic acid, 30,000 U/L of the AY 50C, pH 4 and 55 °C for 24 h. Sensory evaluation and electronic tongue revealed that the incorporation of a mere 1 mg/L SP substantially increased the kokumi, umami, and saltiness intensities, indicating the potential of SP as a potent taste enhancer. Moreover, time-intensity (TI) results demonstrated a significant increase of umami duration in samples containing 1 mg/L of SP (210.0 ± 0 s), a significant extension compared to the control group (150.0 ± 0 s). Notably, the intensity of umami and saltiness in the SP sample were consistently higher than that of control group. The sigmoid curve analysis further confirmed that SP exhibited a synergistic effect on umami and saltiness perceptions. Moreover, the study also illuminated interaction of SP with T1R1, T1R3, TMC4, TRPV1, and CaSR receptors, resulting in significant enhancement in umami, saltiness, and kokumi.
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Polyimide polymer membranes have become critical materials in gas separation and storage applications due to their high selectivity and excellent permeability. However, with over 107 known types of polyimides, relying solely on experimental research means potential high-performance candidates are likely to be overlooked. This study employs a deep learning method optimized by negative correlation ensemble techniques to predict the gas permeability and selectivity of polyimide structures, enabling rapid and efficient material screening. We propose a deep neural network model based on negative correlation deep ensemble methods (DNN-NCL), using Morgan molecular fingerprints as input. The DNN-NCL model achieves an R2 value of approximately 0.95 on the test set, which is a 4% improvement over recent model performance, and effectively mitigates overfitting with a maximum discrepancy of less than 0.03 between the training and test sets. High-throughput screening of over 8 million hypothetical polymers identified hundreds of promising candidates for gas separation membranes, with 14 structures exceeding the Robeson upper bound for CO2/N2 separation. Visualization of high-throughput predictions shows that although the Robeson upper bound was never explicitly used as a model constraint, the majority of predictions are compressed below this limit, demonstrating the deep learning model's ability to reflect real-world physical conditions. Reverse analysis of model predictions using SHAP analysis achieved interpretability of the deep learning model's predictions and identified three key functional groups deemed important by the deep neural network for gas permeability: carbonyl, thiophene, and ester groups. This established a bridge between the structure and properties of polyimide materials. Additionally, we confirmed that two polyimide structures predicted by the model to have excellent CO2/N2 selectivity, namely 6-methylpyrimidin-5-amine and 1,4,5,6-tetrahydropyrimidin-2-amine, have been experimentally validated in previous studies. This research demonstrates the feasibility of using deep learning methods to explore the vast chemical space of polyimides, providing a powerful tool for discovering high-performance gas separation membranes.
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Background: Traumatic vascular injuries in the pediatric patient population are uncommon, especially firecracker blast injuries. Extremities are more frequently affected. Vascular lesions in children have unique characteristics compared to adults, including small vessel diameters, continued growth and development, and susceptibility to vasospasm. There are no clear guidelines for vascular repair and postoperative drug therapy. This may present some challenges during treatment. The study's purpose is to retrospectively analyze a case of femoral artery and vein injuries in a child due to firecracker explosion, and to summarize the characteristics of femoral artery and vein rupture in children and the diagnostic and therapeutic experience. Case Description: We reported a 9-year-old boy with a firecracker injury to the perineum resulting in a left femoral artery and femoral vein rupture. In particular, the wound from firecracker explosion is located at the point of body projection of the spermatic cord, rather than the femoral artery and femoral vein. Emergency compression of the wound to stop bleeding provided an opportunity for subsequent surgical treatment. The intraoperative exploration revealed that the left femoral artery was mostly dissected along a 3-cm long section with a disfigured wall, and the left femoral vein was partially dissected with its anterior wall partially disrupted and missing. The child was subjected to left femoral artery autologous great saphenous vein interposition and left femoral vein repair with patch plasty. The patient had a successful surgery with good follow-up. Conclusions: Pediatric femoral arteriovenous injury is a rare and complex condition, often associated with critical complications, challenging surgical interventions, and a high risk of mortality and disability. The location of body wounds may contribute to delayed diagnosis of the condition, emphasizing the importance of timely physical examination for early diagnosis. Timely and accurate vascular repair is paramount for saving lives and minimizing the risk of limb amputation. Long-term postoperative follow-up is necessary to monitor the patency of the repaired vessels and promptly detect any complications.
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To satisfy the demands of the food industry, innovative flavor enhancers need to be developed urgently to increase the food flavor. In our work, N-lauroyl phenylalanine (LP) was prepared from phenylalanine (l-Phe) and lauric acid (Lau) in water through the use of commercial enzymes (Promatex, Sumizyme FP-G, and Trypsin), and its flavor-presenting properties and mechanism were investigated. The highest LP yields obtained under one-factor optimized conditions were 61.28, 63.43, and 77.58%, respectively. Sensory assessment and an e-tongue test revealed that 1 mg/L LP enhanced the kokumi, saltiness, and umami of the simulated chicken broth solution and attenuated the bitterness of the l-isoleucine solution. The molecular simulation results suggested that the mechanisms of LP enhancement of kokumi and umami were related to hCaSR and hT1R1-hT1R3, and that hydrophobic forces and hydrogen bonds were involved in the binding of LP to taste receptors. The results implied that LP is a potential flavor enhancer for food applications.
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BACKGROUND: Postoperative delirium remains prevalent despite extensive research through randomised trials aimed at reducing its incidence. Understanding trial characteristics associated with interventions' effectiveness facilitates data interpretation. METHODS: Trial characteristics were extracted from eligible trials identified through two systematic literature searches. Multivariable meta-regression was used to investigate trial characteristics associated with effectiveness estimated using odds ratios. Meta-analysis was used to investigate pooled effectiveness. RESULTS: We identified 201 eligible trials. Compared with China, trials from the USA/Canada (ratio of odds ratio, 1.89; 95% confidence interval, 1.45-2.45) and Europe/Australia/New Zealand (1.67; 1.29-2.18) had an 89% and 67% higher odds ratio, respectively, suggesting reduced effectiveness. The effectiveness was enhanced when the incidence of postoperative delirium increased (0.85; 0.79-0.92, per 10% increase). Trials with concerns related to deviations from intended interventions reported increased effectiveness compared with those at low risk (0.69; 0.53-0.90). Compared with usual care, certain interventions appeared to have reduced the incidence of postoperative delirium in low-risk trials with low-to-moderate certainty of evidence. However, these findings should be considered inconclusive because of challenges in grouping heterogeneous interventions, the limited number of eligible trials, the prevalence of small-scale studies, and potential publication bias. CONCLUSIONS: The effectiveness of postoperative delirium trials varied based on the region of trial origin, the incidence of delirium, and the risk of bias. The limitations caution against drawing definitive conclusions from different bodies of evidence. These findings highlight the imperative need to improve the quality of research on a global scale. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023413984).
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Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Delirio/prevención & control , Delirio/epidemiología , Delirio del Despertar/prevención & control , Delirio del Despertar/epidemiologíaRESUMEN
BACKGROUND: Understanding the mechanisms through which interferon (IFN) signaling is negatively regulated is crucial for preserving the equilibrium of innate immune reactions, as the innate immune system functions, such as the original barrier, combat threats to the host. Although the function of the encephalomyocarditis virus (EMCV) viral proteins in antagonizing innate immunity has been related to earlier studies, the precise mechanism underlying the role of viral protein 3 (VP3) in type I IFN has yet to be fully illuminated. METHODS: VP3 expression and many other adaptor molecules belonging to type I IFN pathway expression levels were evaluated using Western blotting. The IFN and other antiviral genes, such as interferon-stimulated genes (ISGs) 15 and 56, were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). A 50% tissue culture infectious dose (TCID50) assay was utilized to explore the effect of VP3 on EMCV proliferation in human embryonic kidney (HEK293) cells. Co-immunoprecipitation (Co-IP) assays and confocal microscope analysis were used to investigate the underlying mechanisms mediated by VP3. RESULTS: We discovered that the VP3 of EMCV acts as a suppressor of innate immune reactions. Increased levels of VP3 enhance viral reproduction through modulation of innate immune signaling pathways and suppression of antiviral responses. Additional information indicated that during viral infection, the VP3 of EMCV enhances autophagy and interacts specifically with mitochondrial antiviral signaling protein (MAVS), leading to its degradation in an autophagy pathway that relies on p62. CONCLUSIONS: Our findings showed that EMCV developed a tactic to combat host antiviral defenses by using autophagy to break down a protein that controls the innate immune response following a viral infection of the host. Notably, VP3 plays an important role in this process. Overall, these discoveries may provide a novel therapeutic target for EMCV.
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Proteínas Adaptadoras Transductoras de Señales , Autofagia , Virus de la Encefalomiocarditis , Interferón Tipo I , Transducción de Señal , Humanos , Virus de la Encefalomiocarditis/inmunología , Virus de la Encefalomiocarditis/metabolismo , Autofagia/inmunología , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Células HEK293 , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Inmunidad Innata , ProteolisisRESUMEN
Background: Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer (NSCLC). The atypical mitogen-activated protein kinase 4 (MAPK4) has been shown to be involved in the pathogenesis of various diseases. However, the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear. Methods: Adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group, respectively. The cell proliferation was analyzed with flow cytometry and immunofluorescence staining. The vascular density in tumor mass was analyzed by immunofluorescence staining. The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining, and so on. Results: We found that the expression of MAPK4, which was dominantly expressed in local endothelial cells (ECs), was correlated with tumor angiogenesis of NSCLC. Furthermore, MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs (HUVECs). Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways, and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2 (ERK1/2) pathway but not Akt and c-Jun n-terminal kinase pathways. Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant, which was accompanied with increased transduction of the ERK1/2 pathway. Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC. Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo. Conclusion: Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC. MAPK4 may thus represent a new target for NSCLC.
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Background: Hypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension. Methods: This is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored. Results: Sixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1-23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury. Conclusion: Perioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.
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Covalent organic frameworks (COFs), at the forefront of porous materials, hold tremendous potential in membrane separation; however, achieving high continuity in COF membranes remains crucial for efficient gas separation. Here, we present a unique approach termed assembly-dissociation-reconstruction for fabricating COF membranes tailored for CO2/N2 separation. A parent COF is designed from two-node aldehyde and three-node amine monomers and dissociated to high-aspect-ratio nanosheets. Subsequently, COF nanosheets are orderly reconstructed into a crack-free membrane by surface reaction under water evaporation. The membrane exhibits high crystallinity, open pores and a strong affinity for CO2 adsorption over N2, resulting in CO2 permeance exceeding 1060 GPU and CO2/N2 selectivity surpassing 30.6. The efficacy of this strategy offers valuable guidance for the precise fabrication of gas-separation membranes.
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PURPOSE: To report optical coherence tomography findings of presumed veterinary anthelmintic drugs (VADs)-induced retinal toxicity that may aid in understanding potential pathogenic mechanisms. METHODS: This is a retrospective observational case series analysis of patients with vision abnormalities following the accidental or intentional consumption of veterinary anthelmintic drugs. All cases underwent a thorough ophthalmological examination. Moreover, medical records, as well as the initial and follow-up optical coherence tomography images, were thoroughly scrutinized. RESULTS: Four patients were identified (3 men; mean [range] age, 36.5 [22-52] years). Each patient overdosed on one or two of the following VADs: closantel, triclabendazole, praziquantel, pyrantel pamoate, and niclofolan. The most characteristic optical coherence tomography finding was diffuse, granular, hyperreflective lesions throughout the outer retina, which were initially identified in the ellipsoid zone in two cases. At follow-up, optical coherence tomography exhibited regression of hyperreflective lesions and extensive loss of the outer retinal elements in two patients. In addition, the subfoveal outer retinal layers may be partially preserved. CONCLUSION: Some veterinary anthelmintic drugs could be detrimental to the human retina if overdosed, resulting in visual disturbances. Optical coherence tomography revealed the mitochondria-enriched ellipsoid zone where outer retinal damage first appeared on, implying that these medications may harm the retina by inhibiting mitochondrial energy metabolism, as they do to eliminate parasites.
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Antihelmínticos , Enfermedades de la Retina , Tomografía de Coherencia Óptica , Tomografía de Coherencia Óptica/métodos , Humanos , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Masculino , Antihelmínticos/toxicidad , Femenino , Adulto Joven , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Drogas Veterinarias/toxicidad , Retina/efectos de los fármacos , Retina/patología , Agudeza Visual , Salicilanilidas/toxicidad , Triclabendazol , Praziquantel/toxicidadRESUMEN
Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.
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Cartílago , Ratones Endogámicos C57BL , Ratones Noqueados , Estrés Oxidativo , Selenoproteínas , Animales , Selenoproteínas/metabolismo , Selenoproteínas/genética , Ratones , Cartílago/metabolismo , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Condrocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Línea CelularRESUMEN
Organophosphorus flame retardants (OPFRs) such as triphenyl phosphate (TPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to impair cardiac function in fish. However, limited information is available regarding their cardiotoxic mechanisms. Using rare minnow (Gobiocypris rarus) as a model, we found that both TPHP and TDCIPP exposures decreased heart rate at 96 h postfertilization (hpf) in embryos. Atropine (an mAChR antagonist) can significantly attenuate the bradycardia caused by TPHP, but only marginally attenuated in TDCIPP treatment, suggesting that TDCIPP-induced bradycardia is independent of mAChR. Unlike TDCIPP, although TPHP-induced bradycardia could be reversed by transferring larvae to a clean medium, the inhibitory effect of AChE activity persisted compared to 96 hpf, indicating the existence of other bradycardia regulatory mechanisms. Transcriptome profiling revealed cardiotoxicity-related pathways in treatments at 24 and 72 hpf in embryos/larvae. Similar transcriptional alterations were also confirmed in the hearts of adult fish. Further studies verified that TPHP and TDCIPP can interfere with Na+/Ca2+ transport and lead to disorders of cardiac excitation-contraction coupling in larvae. Our findings provide useful clues for unveiling the differential cardiotoxic mechanisms of OPFRs and identifying abnormal Na+/Ca2+ transport as one of a select few known factors sufficient to impair fish cardiac function.
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Cardiotoxicidad , Cyprinidae , Retardadores de Llama , Animales , Retardadores de Llama/toxicidad , Embrión no Mamífero/efectos de los fármacos , Compuestos Organofosforados/toxicidad , Organofosfatos/toxicidadRESUMEN
To reconstruct a 3D human surface from a single image, it is crucial to simultaneously consider human pose, shape, and clothing details. Recent approaches have combined parametric body models (such as SMPL), which capture body pose and shape priors, with neural implicit functions that flexibly learn clothing details. However, this combined representation introduces additional computation, e.g. signed distance calculation in 3D body feature extraction, leading to redundancy in the implicit query-and-infer process and failing to preserve the underlying body shape prior. To address these issues, we propose a novel IUVD-Feedback representation, consisting of an IUVD occupancy function and a feedback query algorithm. This representation replaces the time-consuming signed distance calculation with a simple linear transformation in the IUVD space, leveraging the SMPL UV maps. Additionally, it reduces redundant query points through a feedback mechanism, leading to more reasonable 3D body features and more effective query points, thereby preserving the parametric body prior. Moreover, the IUVD-Feedback representation can be embedded into any existing implicit human reconstruction pipeline without requiring modifications to the trained neural networks. Experiments on the THuman2.0 dataset demonstrate that the proposed IUVD-Feedback representation improves the robustness of results and achieves three times faster acceleration in the query-and-infer process. Furthermore, this representation holds potential for generative applications by leveraging its inherent semantic information from the parametric body model.
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Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.
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COVID-19 , Selenoproteínas , Humanos , Selenoproteínas/genética , Selenoproteínas/metabolismo , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2 , Mapas de Interacción de Proteínas/genéticaRESUMEN
BACKGROUND: Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture. METHODS: Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed. RESULTS: Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture. CONCLUSIONS: The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.
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Inyecciones Espinales , Atrofia Muscular Espinal , Oligonucleótidos , Escoliosis , Humanos , Escoliosis/tratamiento farmacológico , Escoliosis/diagnóstico por imagen , Atrofia Muscular Espinal/tratamiento farmacológico , Atrofia Muscular Espinal/diagnóstico por imagen , Femenino , Masculino , Inyecciones Espinales/métodos , Oligonucleótidos/administración & dosificación , Oligonucleótidos/uso terapéutico , Niño , Adolescente , Punción Espinal/métodos , Adulto , Adulto Joven , PreescolarRESUMEN
Lake ecosystems confront escalating challenges to their stability and resilience, most intuitively leading to biodiversity loss, necessitating effective preservation strategies to safeguard aquatic environments. However, the complexity of ecological processes governing lake biodiversity under multi-stressor interactions remains an ongoing concern, primarily due to insufficient long-term bioindicator data, particularly concerning macroinvertebrate biodiversity. Here we utilize a unique, continuous, and in situ biomonitoring dataset spanning from 2011 to 2019 to investigate the spatio-temporal variation of macroinvertebrate communities. We assess the impact of four crucial environmental parameters on Lake Dongting and Lake Taihu, i.e., water quality, hydrology, climate change, and land use. These two systems are representative of lakes with Yangtze-connected and disconnected subtropical floodplains in China. We find an alarming trend of declining taxonomic and functional diversities among macroinvertebrate communities despite improvements in water quality. Primary contributing factors to this decline include persistent anthropogenic pressures, particularly alterations in human land use around the lakes, including intensified nutrient loads and reduced habitat heterogeneity. Notably, river-lake connectivity is pivotal in shaping differential responses to multiple stressors. Our results highlight a strong correlation between biodiversity alterations and land use within a 2-5 km radius and 0.05-2.5 km from the shorelines of Lakes Dongting and Taihu, respectively. These findings highlight the importance of implementing land buffer zones with specific spatial scales to enhance taxonomic and functional diversity, securing essential ecosystem services and enhancing the resilience of crucial lake ecosystems.