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1.
Cell Mol Life Sci ; 81(1): 81, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38334797

RESUMEN

Papillary thyroid carcinoma (PTC) stands as the leading cancer type among endocrine malignancies, and there exists a strong correlation between thyroid cancer and obesity. However, the clinical significance and molecular mechanism of lipid metabolism in the development of PTC remain unclear. In this study, it was demonstrated that the downregulation of METTL16 enhanced lipid metabolism and promoted the malignant progression of PTC. METTL16 was expressed at lower levels in PTC tissues because of DNMT1-mediated hypermethylation of its promoter. Loss- and gain-of-function studies clarified the effects of METTL16 on PTC progression. METTL16 overexpression increased the abundance of m6A in SCD1 cells, increasing RNA decay via the m6A reader YTHDC2. The SCD1 inhibitor A939572 inhibited growth and slowed down lipid metabolism in PTC cells. These results confirm the crucial role of METTL16 in restraining PTC progression through SCD1-activated lipid metabolism in cooperation with YTHDC2. This suggests that the combination of METTL16 and anti-SCD1 blockade might constitute an effective therapy for PTC.


Asunto(s)
Metabolismo de los Lípidos , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Metabolismo de los Lípidos/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Metilación de ADN , Línea Celular Tumoral , Proliferación Celular , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismo , ARN Helicasas/genética , ARN Helicasas/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo
2.
Small ; : e2400599, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38860549

RESUMEN

Memristors are used in artificial neural networks owing to their exceptional integration capabilities and scalability. However, traditional memristors are hampered by limited resistance states and randomness, which curtails their application. The migration of metal ions critically influences the number of conductance states and the linearity of weight updates. Semi-metal filaments can provide subquantum conductance changes to the memristors due to the smaller single-atom conductance, such as Sb (≈0.01 G0 = 7.69 × 10-7 S). Here, a memristor featuring an active electrode composed of semi-metal Sb is introduced for the first time. This memristor demonstrates precise conductance control, a large on/off ratio, consistent switching, and prolonged retention exceeding 105 s. Density functional theory (DFT) calculations and characterization methods reveal the formation of Sb filaments during a set process. The interaction between Sb and O within the dielectric layer facilitates the Sb filaments' ability to preserve their morphology in the absence of electric fields.

3.
J Transl Med ; 22(1): 365, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632658

RESUMEN

BACKGROUND: Molecular subtyping is expected to enable precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE), we aimed to develop a novel TIDE-based subtyping strategy to guide personalized immunotherapy in the bladder cancer (BC). METHODS: Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns. Subsequently, consensus clustering was applied to classify BC patients based on TIDE marker-genes. Patients' clinicopathological, molecular features and signaling pathways of the different TIDE subtypes were well characterized. We also utilize the deconvolution algorithms to analyze the tumor microenvironment, and further explore the sensitivity and mechanisms of each subtype to immunotherapy. Furthermore, BC patient clinical information, real-world BC samples and urine samples were collected for the validation of our findings, which were used for RNA-seq analysis, H&E staining, immunohistochemistry and immunofluorescence staining, and enzyme-linked immunosorbent assay. Finally, we also explored the conservation of our novel TIDE subtypes in pan-cancers. RESULTS: We identified 69 TIDE biomarker genes and classified BC samples into three subtypes using consensus clustering. Subtype I showed the lowest TIDE status and malignancy with the best prognosis and highest sensitivity to immune checkpoint blockade (ICB) treatment, which was enriched of metabolic related signaling pathways. Subtype III represented the highest TIDE status and malignancy with the poorest prognosis and resistance to ICB treatment, resulting from its inhibitory immune microenvironment and T cell terminal exhaustion. Subtype II was in a transitional state with intermediate TIDE level, malignancy, and prognosis. We further confirmed the existence and characteristics of our novel TIDE subtypes using real-world BC samples and collected patient clinical data. This subtyping method was proved to be more efficient than previous known methods in identifying non-responders to immunotherapy. We also propose that combining our TIDE subtypes with known biomarkers can potentially improve the sensitivity and specificity of these biomarkers. Moreover, besides guiding ICB treatment, this classification approach can assist in selecting the frontline or recommended drugs. Finally, we confirmed that the TIDE subtypes are conserved across the pan-tumors. CONCLUSIONS: Our novel TIDE-based subtyping method can serve as a powerful clinical tool for BC and pan-cancer patients, and potentially guiding personalized therapy decisions for selecting potential beneficiaries and excluding resistant patients of ICB therapy.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Inmunoterapia , Biomarcadores de Tumor , Algoritmos , Análisis por Conglomerados , Microambiente Tumoral , Pronóstico
4.
Phys Rev Lett ; 132(18): 180201, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38759173

RESUMEN

Noise is, in general, inevitable and detrimental to practical and useful quantum communication and computation. Under the resource theory framework, resource distillation serves as a generic tool to overcome the effect of noise. Yet, conventional resource distillation protocols generally require operations on multiple copies of resource states, and strong limitations exist that restrict their practical utilities. Recently, by relaxing the setting of resource distillation to only approximating the measurement statistics instead of the quantum state, a resource-frugal protocol, "virtual resource distillation," is proposed, which allows more effective distillation of noisy resources. Here, we report its experimental implementation on a photonic quantum system for the distillation of quantum coherence (up to dimension four) and bipartite entanglement. We show the virtual distillation of the maximal superposed state of dimension four from the state of dimension two, an impossible task in conventional coherence distillation. Furthermore, we demonstrate the virtual distillation of entanglement with operations acting only on a single copy of the noisy Einstein-Podolsky-Rosen (EPR) pair and showcase the quantum teleportation task using the virtually distilled EPR pair with a significantly improved fidelity of the teleported state. These results illustrate the feasibility of the virtual resource distillation method and pave the way for accurate manipulation of quantum resources with noisy quantum hardware.

5.
Calcif Tissue Int ; 114(2): 182-199, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38055044

RESUMEN

In hyperlipidemia-induced osteoporosis, bone marrow mesenchymal stem cells (BMSCs) differentiate into more adipocytes than osteoblasts, leading to decreased bone formation. It is vital to elucidate the effects of hyperlipidemia on bone metabolism and seek new agents that regulate adipocyte-osteoblast lineage allocation. CoQ10, a rate-limiting coenzyme of the mitochondrial respiratory chain, has been reported to decrease oxidative stress and lipid peroxidation by functioning as a mitochondrial antioxidant. However, its effect on hyperlipidemia-induced osteoporosis remains unknown. Here, we analyzed the therapeutic mechanisms of CoQ10 on hyperlipidemia-induced osteoporosis by using high-fat diet (HFD)-treated ApoE-/- mice or oxidized low-density lipoprotein (ox-LDL)-treated BMSCs. The serum lipid levels were elevated and bone formation-related markers were decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, which could be reversed by CoQ10. Additionally, PGC-1α protein expression was decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, accompanied by mitochondrial dysfunction, decreased ATP content and overgeneration of reactive oxygen species (ROS), which could also be antagonized by CoQ10. Furthermore, PGC-1α knockdown in vitro promoted ROS generation, BMSC apoptosis, and adipogenic differentiation while attenuating osteogenic differentiation in BMSCs. Mechanistically, it suggested that the expression of PGC1-α protein was increased with miR-130b-3p inhibitor treatment in osteoporosis under hyperlipidemia conditions to improve mitochondrial function. Collectively, CoQ10 alleviates hyperlipidemia-induced osteoporosis in ApoE-/- mice and regulates adipocyte-osteoblast lineage allocation. The possible underlying mechanism may involve the improvement of mitochondrial function by modulating the miR-130b-3p/PGC-1α pathway.


Asunto(s)
Hiperlipidemias , MicroARNs , Osteoporosis , Ubiquinona/análogos & derivados , Ratones , Animales , Hiperlipidemias/complicaciones , Osteogénesis , Especies Reactivas de Oxígeno/metabolismo , Osteoporosis/prevención & control , Osteoporosis/tratamiento farmacológico , Diferenciación Celular , Mitocondrias/metabolismo , Apolipoproteínas E/farmacología , Apolipoproteínas E/uso terapéutico
6.
Anim Biotechnol ; 35(1): 2295928, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38174897

RESUMEN

Scrotal circumference is an important reproductive index of breeding rams, which has a high genetic correlation with ejaculation volume and semen quality. In this study, the scrotal circumference of 1353 male Hu sheep at different stages of development was measured and descriptive statistical analysis was performed. The results showed that the coefficient of variation of scrotal circumference at each stage was greater than 10%, and its heritability were moderately to high, ranging from 0.318 to 0.719. We used PCR amplification and Sanger sequencing to scan the polymorphisms of the IGFALS gene, and performed association analysis with the circumference of the scrotum at different stages. We identified a synonymous mutation g.918 G > C in exon 1 of the IGFALS gene, and this mutation was significantly associated with scrotal circumference at 100, 120, 140, 160 and 180 days (p < 0.05). Therefore, IGFALS gene polymorphism can be used as a molecular marker affecting scrotal circumference of Hu sheep, which can provide a reference for future molecular marker-assisted selection of scrotal circumference in sheep.


Asunto(s)
Escroto , Análisis de Semen , Ovinos/genética , Masculino , Animales , Análisis de Semen/veterinaria , Oveja Doméstica , Reproducción , Polimorfismo Genético/genética
7.
Anim Biotechnol ; 35(1): 2344207, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38669223

RESUMEN

As a crucial economic trait, fat deposition is directly related to carcass quality and feed efficiency in sheep. The purpose of this study was to investigate the polymorphisms of the FGB gene related to fat deposition and detect the expression features of the FGB gene in different adipose tissues of sheep by using Sanger sequencing, MassARRAY® SNP technique, and quantitative real-time PCR (qRT-PCR). Results showed that in the intron region of the FGB gene, a SNP g. 3378953 A > T has been identified, and significant association was found between perirenal fat weight, perirenal fat relative weight, mesenteric fat weight, and mesenteric fat relative weight (P < 0.05). Moreover, qRT-PCR analysis showed that FGB was expressed in all three adipose tissues, and FGB gene expression level in the AA genotype was significantly lower than that in the AT or TT genotypes (P < 0.05). Therefore, the FGB gene can be used as a candidate gene to reduce fat deposition in Hu sheep breeding, and the selection of the AA genotype in Hu sheep in production practice is more conducive to improving production efficiency.


Asunto(s)
Tejido Adiposo , Polimorfismo de Nucleótido Simple , Animales , Polimorfismo de Nucleótido Simple/genética , Tejido Adiposo/metabolismo , Ovinos/genética , Ovinos/fisiología , Genotipo , Oveja Doméstica/genética , Oveja Doméstica/fisiología , Masculino , Femenino , Cruzamiento
8.
Molecules ; 29(13)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38999190

RESUMEN

This paper systematically investigates the structure, stability, and electronic properties of niobium carbide clusters, NbmCn (m = 5, 6; n = 1-7), using density functional theory. Nb5C2 and Nb5C6 possess higher dissociation energies and second-order difference energies, indicating that they have higher thermodynamic stability. Moreover, ab initio molecular dynamics (AIMD) simulations are used to demonstrate the thermal stability of these structures. The analysis of the density of states indicates that the molecular orbitals of NbmCn (m = 5, 6; n = 1-7) are primarily contributed by niobium atoms, with carbon atoms having a smaller contribution. The composition of the frontier molecular orbitals reveals that niobium atoms contribute approximately 73.1% to 99.8% to NbmCn clusters, while carbon atoms contribute about 0.2% to 26.9%.

9.
Compr Rev Food Sci Food Saf ; 23(4): e13358, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38923121

RESUMEN

Low-cost, reliable, and efficient biosensors are crucial in detecting residual heavy metal ions (HMIs) in food products. At present, based on distance-induced localized surface plasmon resonance of noble metal nanoparticles, enzyme-mimetic reaction of nanozymes, and chelation reaction of metal chelators, the constructed optical sensors have attracted wide attention in HMIs detection. Besides, based on the enrichment and signal amplification strategy of nanomaterials on HMIs and the construction of electrochemical aptamer sensing platforms, the developed electrochemical biosensors have overcome the plague of low sensitivity, poor selectivity, and the inability of multiplexed detection in the optical strategy. Moreover, along with an in-depth discussion of these different types of biosensors, a detailed overview of the design and application of innovative devices based on these sensing principles was provided, including microfluidic systems, hydrogel-based platforms, and test strip technologies. Finally, the challenges that hinder commercial application have also been mentioned. Overall, this review aims to establish a theoretical foundation for developing accurate and reliable sensing technologies and devices for HMIs, thereby promoting the widespread application of biosensors in the detection of HMIs in food.


Asunto(s)
Técnicas Biosensibles , Contaminación de Alimentos , Metales Pesados , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Metales Pesados/análisis , Contaminación de Alimentos/análisis , Análisis de los Alimentos/métodos , Análisis de los Alimentos/instrumentación
10.
J Headache Pain ; 25(1): 72, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714978

RESUMEN

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.


Asunto(s)
Cefalea , Malformaciones Arteriovenosas Intracraneales , Humanos , Femenino , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/terapia , Masculino , Cefalea/etiología , Cefalea/terapia , Adulto , Estudios Retrospectivos , Factores de Riesgo , Persona de Mediana Edad , Adulto Joven , Tratamiento Conservador/métodos , Resultado del Tratamiento , Embolización Terapéutica/métodos , Adolescente
11.
Small ; 19(6): e2205797, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36461700

RESUMEN

Highly porous multi-responsive shape memory foams have unique advantages in designing 3D materials with lightweight for varied applications. Herein, a facile and efficient approach to fabricating a thermo-, electro-, and photo-responsive shape memory composite foam is demonstrated. A specific multi-step carbonization protocol is adopted for transforming commercial melamine sponge (MS) to highly porous carbon foam (CF) with robust elastic resilience, efficient electrothermal/photothermal conversions, and super-amphiphilicity. It is a novel proposal for CF to take the dual role of the elastic supporting framework and 3D energy conversion/transmission network without any functional fillers. The composite foam cPCL@CF incorporates the CF skeleton with in situ crosslinked polycaprolactone (PCL) layers, which exhibits high conductivity (≈140 S m-1 ) and excellent light absorption (≈97.7%) in the range of 250-2500 nm. By triggering the crystalline transition of PCL, the composite foam displays sensitive electro- and photo-induced shape memory effect (SME) with outstanding shape fixation ratio (Rf ) and recovery ratio (Rr ). Thanks to the super-amphiphilicity and high electrical conductivity, the cPCL@CF composite foam can give rapid and distinguishable electric signals upon tiny drips of salt solutions or lithium-ion battery (LIB) electrolytes, making it a new type of sensor for detecting electrolyte leakage.

12.
J Transl Med ; 21(1): 789, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37936202

RESUMEN

BACKGROUND: Prostate cancer (PCA) is the fifth leading cause of cancer-related deaths worldwide, with limited treatment options in the advanced stages. The immunosuppressive tumor microenvironment (TME) of PCA results in lower sensitivity to immunotherapy. Although molecular subtyping is expected to offer important clues for precision treatment of PCA, there is currently a shortage of dependable and effective molecular typing methods available for clinical practice. Therefore, we aim to propose a novel stemness-based classification approach to guide personalized clinical treatments, including immunotherapy. METHODS: An integrative multi-omics analysis of PCA was performed to evaluate stemness-level heterogeneities. Unsupervised hierarchical clustering was used to classify PCAs based on stemness signature genes. To make stemness-based patient classification more clinically applicable, a stemness subtype predictor was jointly developed by using four PCA datasets and 76 machine learning algorithms. RESULTS: We identified stemness signatures of PCA comprising 18 signaling pathways, by which we classified PCA samples into three stemness subtypes via unsupervised hierarchical clustering: low stemness (LS), medium stemness (MS), and high stemness (HS) subtypes. HS patients are sensitive to androgen deprivation therapy, taxanes, and immunotherapy and have the highest stemness, malignancy, tumor mutation load (TMB) levels, worst prognosis, and immunosuppression. LS patients are sensitive to platinum-based chemotherapy but resistant to immunotherapy and have the lowest stemness, malignancy, and TMB levels, best prognosis, and the highest immune infiltration. MS patients represent an intermediate status of stemness, malignancy, and TMB levels with a moderate prognosis. We further demonstrated that these three stemness subtypes are conserved across pan-tumor. Additionally, the 9-gene stemness subtype predictor we developed has a comparable capability to 18 signaling pathways to make tumor diagnosis and to predict tumor recurrence, metastasis, progression, prognosis, and efficacy of different treatments. CONCLUSIONS: The three stemness subtypes we identified have the potential to be a powerful tool for clinical tumor molecular classification in PCA and pan-cancer, and to guide the selection of immunotherapy or other sensitive treatments for tumor patients.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Pronóstico , Antagonistas de Andrógenos , Multiómica , Recurrencia Local de Neoplasia , Inmunoterapia , Microambiente Tumoral
13.
Clin Proteomics ; 20(1): 43, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853350

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement, especially the kidneys. However, the underlying mechanism remains unclear, and accurate biomarkers are still lacking. This study aimed to identify biomarkers to assess organ damage and disease activity in patients with SLE using quantitative proteomics. METHODS: Proteomic analysis was performed using mass spectrometry in 15 patients with SLE and 15 age-matched healthy controls. Proteomic profiles were compared in four main subtypes: SLE with proteinuria (SLE-PN), SLE without proteinuria (SLE-non-PN), SLE with anti-dsDNA positivity (SLE-DP), and SLE with anti-dsDNA negativity (SLE-non-DP). Gene ontology biological process analysis revealed differentially expressed protein networks. Cystatin C (CysC) levels were measured in 200 patients with SLE using an immunoturbidimetric assay. Clinical and laboratory data were collected to assess their correlation with serum CysC levels. RESULTS: Proteomic analysis showed that upregulated proteins in both the SLE-PN and SLE-DP groups were mainly mapped to neutrophil activation networks. Moreover, CysC from neutrophil activation networks was upregulated in both the SLE-PN and SLE-DP groups. The associations of serum CysC level with proteinuria, anti-dsDNA positivity, lower complement C3 levels, and SLE disease activity index score in patients with SLE were further validated in a large independent cohort. CONCLUSIONS: Neutrophil activation is more prominent in SLE with proteinuria and anti-dsDNA positivity, and CysC is a promising marker for monitoring organ damage and disease activity in SLE.

14.
BMC Gastroenterol ; 23(1): 374, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37915064

RESUMEN

OBJECTIVE: This paper aimed to assess the clinical efficacy, adverse reactions, and safety of employing PD-1 inhibitors in conjunction with chemotherapy as a treatment strategy for advanced gastric cancer (GC). METHODS: Ninety patients with advanced GC from January 2020 to December 2021 were divided into the research group (n = 45) and the control group (n = 45). The control group was treated with apatinib and tigio. The study group was treated with PD-1 inhibitor combined with apatinib and tigio. The remission rate (RR), disease control rate (DCR), overall survival (OS), Eastern Oncology Collaborative Group Physical Status Assessment (ECOG-PS) score, EORTCQLQ-C30 (v3.0) score, and incidence of adverse reactions were compared between the two groups. RESULTS: The research group exhibited improved outcomes in several key metrics relative to the control group. Specifically, the RR, DCR, and OS were notably higher in the research group. Additionally, the ECOG-PS score was significantly reduced, indicating better performance. At a median follow-up of 8.7 months, the research group's functional and total health scores on the EORTC QLQ-C30 (v3.0) scale had seen significant improvement compared to their initial scores and were also superior to the control group's scores. Importantly, both groups demonstrated comparable incidence rates for adverse reactions, with no significant difference observed (P > 0.05). CONCLUSION: PD-1 inhibitor combined with chemotherapy was more effective when treating patients with advanced GC. It was more beneficial to enhance the patient's condition, promote survival time, and improve physical status and life quality. In addition, the adverse reactions could be controlled.


Asunto(s)
Antineoplásicos , Neoplasias Gástricas , Humanos , Antineoplásicos/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Resultado del Tratamiento , Calidad de Vida
15.
J Nanobiotechnology ; 21(1): 103, 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36944946

RESUMEN

Osteosarcoma, the most common malignant tumor of the bone, seriously influences people's lives and increases their economic burden. Conventional chemotherapy drugs achieve limited therapeutic effects owing to poor targeting and severe systemic toxicity. Nanocarrier-based drug delivery systems can significantly enhance the utilization efficiency of chemotherapeutic drugs through targeting ligand modifications and reduce the occurrence of systemic adverse effects. A variety of ligand-modified nano-drug delivery systems have been developed for different targeting schemes. Here we review the biological characteristics and the main challenges of current drug therapy of OS, and further elaborate on different targeting schemes and ligand selection for nano-drug delivery systems of osteosarcoma, which may provide new horizons for the development of advanced targeted drug delivery systems in the future.


Asunto(s)
Antineoplásicos , Neoplasias Óseas , Nanopartículas , Osteosarcoma , Humanos , Sistema de Administración de Fármacos con Nanopartículas , Antineoplásicos/uso terapéutico , Ligandos , Osteosarcoma/tratamiento farmacológico , Neoplasias Óseas/tratamiento farmacológico , Portadores de Fármacos/uso terapéutico
16.
J Cardiothorac Vasc Anesth ; 37(6): 911-918, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36931906

RESUMEN

OBJECTIVE: To assess whether velocity-time integral (VTI) variation and peak velocity (Vpeak) variation of the left ventricular outflow tract (LVOT) accurately could predict fluid responsiveness in postoperative critically ill patients mechanically ventilated at low tidal volumes. DESIGN: A prospective, single-center, observational study. SETTING: A surgical intensive care unit at a tertiary hospital. PARTICIPANTS: Sixty postoperative critically ill patients with deep sedation and mechanical ventilation (tidal volume <8 mL/kg) were included in this study. INTERVENTIONS: Passive leg raising (PLR). MEASUREMENT AND MAIN RESULTS: Pulse pressure variation (PPV), VTI variation, and Vpeak variation were measured at baseline and after PLR by transthoracic echocardiography. The fluid responsiveness was defined as an increase (>10%) in stroke volume after PLR. Thirty-two (53.3%) patients were fluid responders. The areas under the receiver operating characteristic (AUROC) curves for PPV were 0.797, and the gray zone was large and included 58.3% of patients. Both VTI variation and Vpeak variation predicted fluid responsiveness with the AUROC of 0.919 and 0.905; meanwhile, the best cutoff values were 12.51% (sensitivity of 71.9%; specificity of 75.0%) and 11.76% (sensitivity of 81.3%; specificity of 89.3%). The gray zones of VTI variation and Vpeak variation were from 7.41% to 11.88% (contained 23.3% patients) and from 9.96% to 13.10% (contained 28.3% patients). CONCLUSIONS: In postoperative critically ill patients mechanically ventilated with tidal volume <8 mL/kg, the VTI variation and Vpeak variation of LVOT accurately could predict fluid responsiveness, and VTI variation showed more accuracy than Vpeak variation in predicting fluid responsiveness.


Asunto(s)
Enfermedad Crítica , Respiración Artificial , Humanos , Volumen de Ventilación Pulmonar , Velocidad del Flujo Sanguíneo , Estudios Prospectivos , Fluidoterapia , Presión Sanguínea , Volumen Sistólico , Hemodinámica
17.
BMC Musculoskelet Disord ; 24(1): 697, 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37653384

RESUMEN

OBJECTIVE: The present study is to evaluate the clinical outcomes of the sequential correction of severe and rigid kyphoscoliosis. METHODS: Between January 2014 and December 2020, 27 adults with severe and rigid kyphoscoliosis underwent sequential correction combined with posterior grade 4 or grade 5 spinal osteotomy. Radiological parameters, including the major curve Cobb angle, kyphotic angle, coronal imbalance, and sagittal vertical axis (SVA), were compared. Patient self-reported health-related quality of life (HRQOL) scores were used to evaluate clinical outcomes. RESULTS: The mean major curve Cobb angle improved from 134.30 ± 13.24° to 44.48 ± 9.34° immediately after surgery and to 46.11 ± 8.94° at the final follow-up. The mean kyphotic angle improved from 112.15 ± 20.28° to 38.63 ± 15.00° immediately after surgery and to 39.85 ± 14.92° at the final follow-up. The mean preoperative major curve Cobb angle of grade 5 spinal osteotomy group was higher than that of grade 4 spinal osteotomy group. Coronal imbalance and SVA slightly improved. The patient self-reported HRQOL scores improved postoperatively and at the final follow-up. Activity, appearance and total scores of the SRS-22 of the grade 5 spinal osteotomy group at the final follow-up were significantly better than those of the grade 4 spinal osteotomy group. CONCLUSIONS: Sequential correction combined with posterior grade 4 or grade 5 spinal osteotomies is an excellent and safe treatment for severe and rigid kyphoscoliosis in adults. Sequential correction combined with posterior grade 5 spinal osteotomies can be used to correct severe and rigid kyphoscoliosis with higher major curve Cobb angle.


Asunto(s)
Cifosis , Calidad de Vida , Adulto , Humanos , Cifosis/diagnóstico por imagen , Cifosis/cirugía , Procedimientos Neuroquirúrgicos , Osteotomía , Autoinforme
18.
Anim Biotechnol ; 34(2): 183-198, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34346280

RESUMEN

The present study aimed to investigate the relationship between growth performance, body composition, and fat deposition factors, and feed efficiency in growing lambs. We measured average daily feed intake (ADFI) and body weight (BW) from 653 Hu sheep that were fed a pellet diet. The residual feed intake (RFI) not significantly genetic and phenotypic correlated with the metabolic body weight (MBW) and average daily gain (ADG), but it was significantly genetic and phenotypic correlated with ADFI and the feed conversion ratio (FCR) (p < 0.01). However, the FCR was significantly associated with growth traits (p < 0.01). With the same ADG, body fat deposition was greater in animals with low feed efficiency compared with high feed efficiency. Therefore, excessive fat deposition can affect the feed efficiency of the body, and organ weight and gut-weight have a greater impact on the feed efficiency of lambs. The reticulum stomach and jejunum of lambs with a low RFI were smaller compared with that in the high RFI, indicating that lambs with a low RFI have less intake and a higher absorption rate. Small organs, such as the liver, of lambs with high FE might be associated with low energy expenditure and slow metabolism. This study provides a new perspective to study the biological processes responsible for feed efficiency variation in lambs.


Asunto(s)
Alimentación Animal , Ingestión de Alimentos , Ovinos , Animales , Alimentación Animal/análisis , Composición Corporal/genética , Dieta/veterinaria , Oveja Doméstica , Aumento de Peso
19.
Anim Biotechnol ; 34(4): 1626-1634, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34775926

RESUMEN

Hu sheep is an excellent short fat-tailed breed in China. Fat deposition in Hu sheep tail affects carcass quality and consumes a lot of energy, leading to an increase in feed cost. The objective of this study was to analyze the effects of HMGA1 polymorphism on tail fat weight in Hu sheep. Partial coding and non-coding sequences of HMGA1 were amplified with PCR and single nucleotide polymorphisms (SNP) of HMGA1 in 1163 Hu sheep were detected using DNA sequencing and KASPar technology. RT-qPCR analysis was performed to test HMGA1 expression in different tissues. The results showed that the expression of HMGA1 was higher in the duodenum, liver, spleen, kidney, and lung than in the heart, muscle, rumen, tail fat, and lymph. A mutation, g.5312 C > T, was detected in HMGA1; g.5312 C > T was significantly associated with tail fat weight, relative weight of tail fat (body weight), and relative weight of tail fat (carcass) (p < 0.05). The tail fat weight of the TT genotype was remarkably higher than that of the CC and TC genotypes. Therefore, HMGA1 can be used as a genetic marker for marker-assisted selection of tail fat weight in Hu sheep.


Asunto(s)
Proteína HMGA1a , Cola (estructura animal) , Ovinos/genética , Animales , Proteína HMGA1a/genética , Polimorfismo de Nucleótido Simple/genética , Secuencia de Bases , Genotipo
20.
Anim Biotechnol ; 34(4): 1132-1142, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34904532

RESUMEN

This study aimed to analyze the effects of polymorphisms in GP5 on blood physiological indices of 1065 sheep. The coefficients of variation of the red blood cell count (RBC), hemoglobin concentration (HGB), mean platelet volume (MPV), mean erythrocyte hemoglobin content (MCH), and red blood cell distribution-coefficient of variation (RDW-CV) were greater than 10%, and there was a very significant correlation between the main indices such as RBC, white blood cell, and platelet count (PLT) and most other indices (p < 0.01). qRT-PCR showed that GP5 was expressed in the heart, liver, spleen, lung, kidney, rumen, duodenum, muscle, tail fat, and lymph tissue, with significantly higher expression in the lymph. Subsequently, we detected single nucleotide polymorphisms (SNPs) in GP5 from group, which identified synonymous mutation g.657 T > C in the first exon of GP5. Association analysis showed significant correlations between the SNP and the physiological traits (p < 0.05), in which the RBC, neutrophilic granulocyte (NEUT) and RDW-CV values in sheep with the TC genotype and TT genotype were markedly lower than those in the CC genotype (p < 0.05). Thus, GP5 polymorphisms could be candidate biomarkers to screen blood physiological indices.


Asunto(s)
Hemoglobinas , Polimorfismo de Nucleótido Simple , Animales , Ovinos/genética , Recuento de Eritrocitos , Hemoglobinas/genética , Polimorfismo de Nucleótido Simple/genética , Biomarcadores , Exones
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