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1.
J Gastrointest Oncol ; 15(4): 1674-1685, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39279925

RESUMEN

Background: The regulation of cancer stem cells (CSCs) is influenced by RNA-binding proteins (RBPs). The present study sought to investigate the role of NOVA2 in the processes of self-renewal, carcinogenesis, and lenvatinib resistance in liver CSCs. Methods: Neuro-oncological ventral antigen 2 (NOVA2) expression in liver CSCs was examined by real-time polymerase chain reaction (PCR). In vitro experiments were used to assess the effects of NOVA2 on liver CSC expansion and lenvatinib resistance. Results: In our study, the expression of the RBP NOVA2 was higher in CSCs. NOVA2 also increased the capacity for self-renewal and carcinogenesis of the liver CSCs via the Wnt pathway. Further, suppressing the Wnt pathway leads to desensitization of the hepatocellular carcinoma (HCC) cells that overexpress NOVA2 to apoptosis caused by lenvatinib. Analyzing patient data confirmed reduced levels of NOVA2 and therefore we speculate that NOVA2 may serve as a potential indicator for response to lenvatinib in patients with HCC. Methyltransferase-like 3 (METTL3) and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1)-dependent N6-methyladenosine (m6A) methylation were linked to upregulation of NOVA2 in HCC. Furthermore, it was shown that the expression of METTL3 was elevated in cellular models of type 2 diabetes mellitus (T2DM). Conclusions: NOVA2 is involved in the process of liver CSC self-renewal and carcinogenesis. In addition, NOVA2 expression may help identify patients with a higher chance of benefiting from lenvatinib treatment and can be a promising therapeutic target for HCC.

2.
J Thorac Oncol ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39306192

RESUMEN

INTRODUCTION: An increasing number of early-stage lung adenocarcinoma (LUAD) are detected as lung nodules. The radiological features related to LUAD progression remain further investigation. Exploration is required to bridge the gap between radiomics features and molecular characteristics of lung nodules. METHODS: Consensus clustering was applied to the radiomics features of 1,212 patients to establish stable clustering. Clusters were illustrated using clinicopathological and next-generation sequencing (NGS). A classifier was constructed to further investigate the molecular characteristic in patients with paired CT and RNA-seq data. RESULTS: Patients were clustered into 4 clusters. Cluster 1 was associated with a low consolidation-to-tumor ratio (CTR), pre-invasion, grade I disease and good prognosis. Clusters 2 and 3 showed increasing malignancy with higher CTR, higher pathological grade and poor prognosis. Cluster 2 possessed more spread through air spaces (STAS) and cluster 3 showed higher proportion of pleural invasion. Cluster 4 had similar clinicopathological features with cluster 1 except higher proportion of grade II disease. RNA-seq indicated that cluster 1 represented nodules with indolent growth and good differentiation, whereas cluster 4 showed progression in cell development but still had low proliferative activity. Nodules with high proliferation were classified into clusters 2 and 3. Additionally, the radiomics classifier distinguished cluster 2 as nodules harboring an activated immune environment, while cluster 3 represented nodules with a suppressive immune environment. Furthermore, gene signatures associated with the prognosis of early-stage LUAD were validated in external datasets. CONCLUSION: Radiomics features can manifest molecular events driving progression of lung adenocarcinoma. Our study provides a molecular insight into radiomics features and assists in the diagnosis and treatment of early stage LUAD.

3.
Am J Clin Exp Immunol ; 13(4): 195-201, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39310122

RESUMEN

OBJECTIVE: To evaluate the clinical effectiveness of surface electromyography combined with a spine 3D data system. METHODS: 10 idiopathic scoliosis patients (age: 12.90±3.67 years, height: 155.90±20.07 cm, weight: 48.00±12.86 kg, 6 major thoracic lateral bends and 4 lumbar bends) who were selected to attend the outpatient clinic of Ruijin Rehabilitation Hospital, First diagnosed as scoliosis by imaging examination (EOS system), evaluation by using the surface electromyography monitoring system, the radiation-free 3D spine data acquisition and analysis system, the surface electromyography of the paravertebral muscles (root mean square value (RMS) of the resting standing and action position of the spine) and the Cobb angle of scoliosis were recorded. RESULTS: The RMS of the convex side was larger than that of the concave side in the two postures (P<0.05), and The RMS value of bilateral action position was significantly higher than that of rest position (P<0.05). There was no correlation between RMS ratio and Cobb angle in two positions of thoracic scoliosis (P>0.05). There was a significant correlation between the RMS ratio at rest position of lumbar scoliosis and Cobb angle. At rest, the RMS value of convex side was significantly correlated with the Cobb angle measured by the EOS system and the 3D data system (P<0.05, of which P<0.01). The Cobb angle measured by 3D data system and the EOS system was significantly correlated (P<0.01). CONCLUSION: Surface EMG can be used to evaluate the motor function of paravertebral muscles on both sides of scoliosis patients. The new 3D data system has high accuracy in evaluating scoliosis. The combination of the two can dynamically evaluate scoliosis, which is more clinically effective.

4.
Am J Ophthalmol ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218388

RESUMEN

BACKGROUND: Keratoconus (KC) is a corneal ectasia disease in which the vision of some patients cannot achieve satisfaction by spectacle corrections. However, not everyone can embrace contact lenses to achieve better vision. Perceptual learning (PL) is a potential treatment for vision improvement in such patients. PURPOSE: To investigate the effectiveness and maintenance of PL on vision improvement in KC patients corrected with spectacles. DESIGN: Randomized, double-blind clinical trial. PARTICIPANTS: Thirty-five non-progressive KC patients aged 9 years or older with unsatisfied spectacle-corrected vision were enrolled. METHODS: Non-progressive KC patients with best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life questionnaires were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat (ITT) principle. RESULTS: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs. 0.02 ± 0.06 logMAR; P = 0.0006). Eight out of seventeen (47.06 %) patients in the PL group reached CDVA improvement ≥ 2 lines (P=0.0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs. 0.01 ± 0.07 logMAR; P = 0.0011). The increase of CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = 0.009). No side effects were observed and no subjects quit because of training difficulties. CONCLUSION: Three-month perceptual learning improved vision in KC patients and the improvement maintained after 3 months of treatment cessation. The results indicate that perceptual learning may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity.

5.
Oncogene ; 43(38): 2868-2884, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39154122

RESUMEN

The dysregulation of long non-coding RNAs (lncRNAs) are involved in regulating tumor progression in multiple manner. However, little is known about whether lncRNA is involved in the translation regulation of proteins. Here, we identified that the suppressor of inflammatory macrophage apoptosis lncRNA (SIMALR) was highly expressed in nasopharyngeal carcinoma (NPC) tissues by analyzing the lncRNA microarray. Clinically, the high expression of SIMALR served as an independent predictor for inferior prognosis in NPC patients. SIMALR functioned as an oncogenic lncRNA that promoted the proliferation and metastasis of NPC cells in vitro and in vivo. Mechanistically, SIMALR served as a critical accelerator of protein synthesis by binding to eEF1A2 (eukaryotic translation elongation factor 1 alpha 2), one of the most crucial regulators in the translation machinery of the eukaryotic cells, and enhancing its endogenous GTPase activity. Furthermore, SIMALR mediated the activation of eEF1A2 phosphorylation to accelerate the translation of ITGB4/ITGA6, ultimately promoting the malignant phenotype of NPC cells. In addition, N-acetyltransferase 10 (NAT10) enhanced the stability of SIMALR and caused its overexpression in NPC through the N4-acetylcytidine (ac4C) modification. In sum, our results illustrate SIMALR functions as an accelerator for protein translation and highlight the oncogenic role of NAT10-SIMALR-eEF1A2-ITGB4/6 axis in NPC.


Asunto(s)
Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Factor 1 de Elongación Peptídica , ARN Largo no Codificante , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factor 1 de Elongación Peptídica/genética , Factor 1 de Elongación Peptídica/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/metabolismo , Animales , Ratones , Proliferación Celular/genética , Línea Celular Tumoral , Biosíntesis de Proteínas , Femenino , Masculino , Pronóstico , Ratones Desnudos
6.
Nat Mater ; 23(9): 1169-1178, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39215155

RESUMEN

Recent discoveries of Mott insulating and unconventional superconducting states in twisted bilayer graphene with moiré superlattices have not only reshaped the landscape of 'twistronics' but also sparked the rapidly growing fields of moiré photonic and phononic structures. These innovative moiré structures have opened new routes of exploration for classical wave physics, leading to intriguing phenomena and robust control of electromagnetic and mechanical waves. Drawing inspiration from the success of twisted bilayer graphene, this Perspective describes an overarching framework of the emerging moiré photonic and phononic structures that promise novel classical wave devices. We begin with the fundamentals of moiré superlattices, before highlighting recent studies that exploit twist angle and interlayer coupling as new ingredients with which to engineer and tailor the band structures and effective material properties of photonic and phononic structures. Finally, we discuss the future directions and prospects of this emerging area in materials science and wave physics.

7.
Comput Biol Med ; 179: 108835, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38996550

RESUMEN

Gene regulatory networks (GRNs) are crucial for understanding organismal molecular mechanisms and processes. Construction of GRN in the epithelioma papulosum cyprini (EPC) cells of cyprinid fish by spring viremia of carp virus (SVCV) infection helps understand the immune regulatory mechanisms that enhance the survival capabilities of cyprinid fish. Although many computational methods have been used to infer GRNs, specialized approaches for predicting the GRN of EPC cells following SVCV infection are lacking. In addition, most existing methods focus primarily on gene expression features, neglecting the valuable network structural information in known GRNs. In this study, we propose a novel supervised deep neural network, named MEFFGRN (Matrix Enhancement- and Feature Fusion-based method for Gene Regulatory Network inference), to accurately predict the GRN of EPC cells following SVCV infection. MEFFGRN considers both gene expression data and network structure information of known GRN and introduces a matrix enhancement method to address the sparsity issue of known GRN, extracting richer network structure information. To optimize the benefits of CNN (Convolutional Neural Network) in image processing, gene expression and enhanced GRN data were transformed into histogram images for each gene pair respectively. Subsequently, these histograms were separately fed into CNNs for training to obtain the corresponding gene expression and network structural features. Furthermore, a feature fusion mechanism was introduced to comprehensively integrate the gene expression and network structural features. This integration considers the specificity of each feature and their interactive information, resulting in a more comprehensive and precise feature representation during the fusion process. Experimental results from both real-world and benchmark datasets demonstrate that MEFFGRN achieves competitive performance compared with state-of-the-art computational methods. Furthermore, study findings from SVCV-infected EPC cells suggest that MEFFGRN can predict novel gene regulatory relationships.


Asunto(s)
Enfermedades de los Peces , Redes Reguladoras de Genes , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Rhabdoviridae/genética , Enfermedades de los Peces/genética , Enfermedades de los Peces/virología , Infecciones por Rhabdoviridae/genética , Infecciones por Rhabdoviridae/virología , Carpas/genética , Carpas/virología , Biología Computacional/métodos , Redes Neurales de la Computación , Cyprinidae/genética
8.
Cell Discov ; 10(1): 70, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38937452

RESUMEN

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

9.
Nat Commun ; 15(1): 5300, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38906860

RESUMEN

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.


Asunto(s)
Docetaxel , Resistencia a Antineoplásicos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Piroptosis , Ubiquitina-Proteína Ligasas , Ubiquitinación , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Docetaxel/farmacología , Docetaxel/uso terapéutico , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Dinaminas/metabolismo , Dinaminas/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Gasderminas , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/genética , Fosforilación/efectos de los fármacos , Piroptosis/efectos de los fármacos , Piroptosis/genética , Especies Reactivas de Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Angew Chem Int Ed Engl ; : e202407037, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767062

RESUMEN

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket-dependent small-molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket-independent STING-activating agonists (piSTINGs), which act through multivalency-driven oligomerization to activate STING. Additionally, a piSTING-adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING-based vaccine combination with aPD-1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists.

11.
Sci Total Environ ; 927: 172391, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608899

RESUMEN

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.


Asunto(s)
Ansiedad , Microbioma Gastrointestinal , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Animales , Microbioma Gastrointestinal/fisiología , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ondas de Radio/efectos adversos , Inflamasomas/metabolismo , Neuronas , Masculino , Conducta Animal/efectos de la radiación
12.
J Clin Neurosci ; 124: 20-26, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38640804

RESUMEN

OBJECTIVE: To investigate the relationship between short-term changes in quantitative myasthenia gravis score (QMGS) after thymectomy and postoperative recurrence in myasthenia gravis (MG) patients without thymoma. METHODS: A retrospective observational cohort study. The QMGS of 44 patients with non-thymomatous MG were evaluated before and 1 month after thymectomy, and the frequency and time of postoperative recurrence were recorded. The reduction rate of QMGS (rr-QMGS) was defined as (QMGS one week before thymectomy - QMGS one month after thymectomy)/ QMGS one week before thymectomy × 100 %, as an indicator of short-term symptom change after thymectomy. The receiver operating characteristic (ROC) curve was established to determine an appropriate cut-off value of rr-QMGS for distinguishing postoperative recurrence. Multivariate Cox regression analysis was applied to predict postoperative recurrence. RESULTS: Postoperative recurrence occurred in 21 patients (30 times in total) during follow-up. The mean annual recurrence rate was 3.98 times/year preoperatively and 0.30 times/year postoperatively. ROC analysis determined the cut-off value of rr-QMGS was 36.7 % (sensitivity 90.5 %, specificity 52.2 %). Multivariate Cox regression analysis showed that rr-QMGS<36.7 % (hazard rate[HR]6.251, P = 0.014) is positive predictor of postoperative recurrence. Kaplan-Meier analysis showed that postoperative recurrence time was earlier in the low rr-QMGS group than in the high rr-QMGS group (12.62 vs. 36.60 months, p = 0.005). CONCLUSIONS: Low rr-QMGS is associated with early postoperative recurrence. Rr-QMGS can be used to predict postoperative recurrence of non-thymomatous MG.


Asunto(s)
Miastenia Gravis , Recurrencia , Timectomía , Humanos , Miastenia Gravis/cirugía , Miastenia Gravis/diagnóstico , Timectomía/efectos adversos , Timectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Adulto Joven , Curva ROC , Estudios de Seguimiento
13.
Artículo en Inglés | MEDLINE | ID: mdl-38607211

RESUMEN

Objective: To explore the application value of transabdominal ultrasonography in the diagnosis of gastrointestinal malignant tumors. Methods: This study retrospectively analyzed the transabdominal ultrasound imaging data of 284 patients with gastrointestinal tumors admitted to our hospital from April 2019 to March 2022 and assessed the accuracy of transabdominal ultrasound in diagnosing different types of gastrointestinal tumor diseases. The diagnostic accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was calculated. Results: The sensitivity and specificity of transabdominal ultrasonography in the diagnosis of gastric cancer were (82.40% and 83.72%, respectively), colon cancer (77.78% and 88.35%, respectively), gastric stromal tumor (95.45% and 93.65%, respectively), gastric lymphoma (72.22% and 94.66%, respectively), colorectal lymphoma (80.00% and 95.42%, respectively), gastric mucosal hypertrophy (85.71% and 96.69%, respectively), and pyloric hypertrophy (92.59% and 97.79%, respectively). Among the 284 patients included, 152 patients had malignant tumors, including 34 patients with stage I, 30 patients with stage II, 51 patients with stage III, and 37 patients with stage IV. The accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was 85.53% (130/152). Conclusion: Transabdominal ultrasonography shows promise as a diagnostic tool for gastrointestinal malignant tumors; however, it is recommended to be used in conjunction with other detection methods such as fibrous gastrointestinal tract examination to minimize the risk of missed diagnoses and misdiagnoses. The study highlights the potential of transabdominal ultrasonography as a non-invasive and accessible diagnostic method for gastrointestinal malignancies. Further research and advancements in imaging technologies are crucial for enhancing diagnostic capabilities and improving patient outcomes in the future.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38591775

RESUMEN

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).


Asunto(s)
Ácidos Grasos , Marinobacter , Ácidos Grasos/química , Fosfolípidos/química , Agua de Mar/microbiología , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Composición de Base , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana
15.
Sci Rep ; 14(1): 7998, 2024 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580689

RESUMEN

There are millions of patients experiencing infertility in China, but assisted reproductive technology (ART) is performed at the patient's expense and is difficult to afford. With the sharp decline in China's birth rate, there is a growing controversy over the inclusion of ART in medical insurance (MI). This study aims to explore the feasibility of ART coverage by MI for the first time. We obtained basic data such as the prevalence of infertility, the cost of ART, and the success rate in China with the method of meta-analysis and consulting the government bulletin. Then, we calculated the number of infertile couples in China and the total financial expenditure of MI covering ART. Finally, we discussed the feasibility of coverage, and analyzed the population growth and economic benefits after coverage. According to our research results, it was estimated that there were 4.102-11.792 million infertile couples in China, with an annual increase of 1.189-1.867 million. If MI covered ART, the fund would pay 72.313-207.878 billion yuan, accounting for 2-6% of the current fund balance, and the subsequent annual payment would be 20.961-32.913 billion yuan, accounting for 4-7% of the annual fund balance. This was assuming that all infertile couples would undergo ART, and the actual cost would be lower. The financial input‒output ratio would be 13.022. Benefiting from the inclusion of ART in MI coverage, there would be 3.348-9.624 million new live infants, and 8-13% newborns would be born every year thereafter, which means that by 2050, 37-65 million people would be born. Due to its affordable cost, high cost-effectiveness and favourable population growth, it may be feasible to include ART in MI.


Asunto(s)
Infertilidad , Resultado del Embarazo , Embarazo , Femenino , Recién Nacido , Humanos , Estudios de Factibilidad , Vigilancia de la Población , Técnicas Reproductivas Asistidas , China/epidemiología , Infertilidad/epidemiología , Infertilidad/terapia
16.
J Cardiovasc Pharmacol ; 84(1): 118-123, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38547516

RESUMEN

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF, and LAA-v values were greater and LAD and LAAD mean values were lower in the effective ( P < 0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A, and LAA-v with anticoagulant efficacy ( P < 0.05). The efficacy of rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A, and LAA-v. Multivariate logistic regression analysis further revealed LAEF [odds ratio (OR) 1.7, 95% confidence interval (CI), 0.45-16.9, P = 0.008], 3D-EF (OR 6.4, 95% CI, 1.06-16.9, P = 0.039) and left ventricular global longitudinal strain (OR 18.0, 95% CI, 1.38-35.68, P = 0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of rivaroxaban as an anticoagulation agent.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Ecocardiografía Tridimensional , Inhibidores del Factor Xa , Rivaroxabán , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/diagnóstico , Femenino , Masculino , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/fisiopatología , Apéndice Atrial/efectos de los fármacos , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Trombosis/fisiopatología , Valor Predictivo de las Pruebas , Función del Atrio Izquierdo/efectos de los fármacos , Terapia Trombolítica , Función Ventricular Izquierda/efectos de los fármacos , Factores de Tiempo
17.
Heliyon ; 10(6): e27873, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38533040

RESUMEN

Background: Ovarian cancer, as a highly malignant tumor, features the critical involvement of tumor-associated fibroblasts in the ovarian cancer tissue microenvironment. However, due to the apparent heterogeneity within fibroblast subpopulations, the specific functions of these subpopulations in the ovarian cancer tissue microenvironment remain insufficiently elucidated. Methods: In this study, we integrated single-cell sequencing data from 32 ovarian cancer samples derived from four distinct cohorts and 3226 bulk RNA-seq data from GEO and TCGA-OV cohorts. Utilizing computational frameworks such as Seurat, Monocle 2, Cellchat, and others, we analyzed the characteristics of the ovarian cancer tissue microenvironment, focusing particularly on fibroblast subpopulations and their differentiation trajectories. Employing the CIBERSORTX computational framework, we assessed various cellular components within the ovarian cancer tissue microenvironment and evaluated their associations with ovarian cancer prognosis. Additionally, we conducted Mendelian randomization analysis based on cis-eQTL to investigate causal relationships between gene expression and ovarian cancer. Results: Through integrative analysis, we identified 13 major cell types present in ovarian cancer tissues, including CD8+ T cells, malignant cells, and fibroblasts. Analysis of the tumor microenvironment (TME) cell proportions revealed a significant increase in the proportion of CD8+ T cells and CD4+ T cells in tumor tissues compared to normal tissues, while fibroblasts predominated in normal tissues. Further subgroup analysis of fibroblasts identified seven subgroups, with the MMP11+Fib subgroup showing the highest activity in the TGFß signaling pathway. Single-cell analysis suggested that oxidative phosphorylation could be a key pathway driving fibroblast differentiation, and the ATRNL1+KCN + Fib subgroup exhibited chromosomal copy number variations. Prognostic analysis using a large sample size indicated that high infiltration of MMP11+ fibroblasts was associated with poor prognosis in ovarian cancer. SMR analysis identified 132 fibroblast differentiation-related genes, which were linked to pathways such as platinum drug resistance. Conclusions: In the context of ovarian cancer, fibroblasts expressing MMP11 emerge as the primary drivers of the TGF-beta signaling pathway. Their presence correlates with an increased risk of adverse ovarian prognoses. Additionally, the genetic regulation governing the differentiation of fibroblasts associated with ovarian cancer correlates with the emergence of drug resistance.

18.
Adv Sci (Weinh) ; 11(15): e2303403, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38348559

RESUMEN

Communication with hand gestures plays a significant role in human-computer interaction by providing an intuitive and natural way for humans to communicate with machines. Ultrasound-based devices have shown promising results in contactless hand gesture recognition without requiring physical contact. However, it is challenging to fabricate a densely packed wearable ultrasound array. Here, a stretchable ultrasound array is demonstrated with closely packed transducer elements fabricated using surface charge engineering between pre-charged 1-3 Lead Zirconate Titanate (PZT) composite and thin polyimide film without using a microscope. The array exhibits excellent ultrasound properties with a wide bandwidth (≈57.1%) and high electromechanical coefficient (≈0.75). The ultrasound array can decipher gestures up to 10 cm in distance by using a contactless triboelectric module and identify materials from the time constant of the exponentially decaying impedance based on their triboelectric properties by utilizing the electrostatic induction phase. The newly proposed metric of the areal-time constant is material-specific and decreases monotonically from a highly positive human body (1.13 m2 s) to negatively charged polydimethylsiloxane (PDMS) (0.02 m2 s) in the triboelectric series. The capability of the closely packed ultrasound array to detect material along with hand gesture interpretation provides an additional dimension in the next-generation human-robot interaction.


Asunto(s)
Ingeniería , Gestos , Humanos , Ultrasonografía , Impedancia Eléctrica
19.
iScience ; 27(3): 109116, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38384839

RESUMEN

The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p < 0.0001) and disease-free survival (p = 0.004) in HCC patients. Enhanced expression of PPM1G increases the cell proliferation rate, and knockdown of PPM1G led to a significant reduction in tumor volume in vivo. Further experiments illustrated that upregulated-PPM1G expression increased the protein expression of gain-of-function (GOF) mutant p53. Besides, the immunoprecipitation analysis revealed a direct interaction between PPM1G and GOF mutant p53. Collectively, PPM1G can be a powerful prognostic predictor and potential drug-target molecule.

20.
Clin Interv Aging ; 19: 219-227, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38352273

RESUMEN

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes. Methods: In this retrospective propensity score-matched cohort study, older adult patients undergoing major non-cardiac surgeries were selected, 1837 receiving NA infusion during surgery, and 1072 not receiving NA. The propensity score matching was conducted with a 1:1 ratio and 1072 patients were included in each group. The primary outcomes were postoperative in-hospital mortality and complications. Results: Intraoperative NA administration reduced postoperative urinary tract infection (OR:0.124, 95% CI:0.016-0.995), and had no effect on other postoperative complications and mortality, it reduced intraoperative crystalloid infusion (OR:0.999, 95% CI:0.999-0.999), blood loss (OR: 0.998, 95% CI: 0.998-0.999), transfusion (OR:0.327, 95% CI: 0.218-0.490), but increased intraoperative lactate production (OR:1.354, 95% CI:1.051-1.744), and hospital stay (OR:1.019, 95% CI:1.008-1.029). Conclusion: Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and mortality, and can be safely used in older adult patients undergoing major non-cardiac surgeries.


Asunto(s)
Norepinefrina , Procedimientos Quirúrgicos Operativos , Anciano , Humanos , Estudios de Cohortes , Norepinefrina/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Puntaje de Propensión , Estudios Retrospectivos , Infecciones Urinarias/complicaciones
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