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1.
Neural Regen Res ; 20(3): 821-835, 2025 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38886955

RESUMEN

JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/ß-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

2.
Sheng Li Xue Bao ; 76(3): 496-506, 2024 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-38939943

RESUMEN

Hemoglobinopathies are one of the most common single-gene genetic disorders globally, with approximately 1% to 5% of the global population carrying the mutated gene for thalassemia. Thalassemia are classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia based on the need for blood transfusion. Traditional treatment modalities include blood transfusion, splenectomy, hydroxyurea therapy, and iron chelation therapy, which are now widely used for clinical treatment and constitute the main methods recommended in the ß-thalassemia treatment guidelines. However, there are multiple barriers and limitations to the application of these approaches, and there is an urgent need to explore new therapeutic approaches. With the in-depth study of the pathophysiological process of ß-thalassemia, a deeper understanding of the pathogenesis of the disease has been gained. It has been demonstrated that the pathogenesis of thalassemia is closely related to ineffective erythropoiesis (IE), imbalance in the ratio of α/ß-globin protein chains and iron overload. New therapeutic approaches are emerging for different pathogenic mechanisms. Among them, new drugs for the treatment of IE mainly include activin receptor II trap ligands, Janus kinase 2 inhibitors, pyruvate kinase activators, and glycine transporter protein 1 inhibitors. Correcting the imbalance in the hemoglobin chain is mainly due to emerging technologies such as bone marrow transplantation and gene editing. Measures in reducing iron overload are associated with inhibiting the activity of transferrin and hepcidin. These new approaches provide new ideas and options for the treatment and management of ß-thalassemia.


Asunto(s)
Terapia Genética , Talasemia beta , Talasemia beta/terapia , Talasemia beta/genética , Humanos , Terapia Genética/métodos , Transfusión Sanguínea , Janus Quinasa 2/genética , Receptores de Activinas Tipo II/genética , Esplenectomía , Edición Génica , Quelantes del Hierro/uso terapéutico , Trasplante de Médula Ósea/métodos , Sobrecarga de Hierro/terapia , Eritropoyesis , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de Fusión
3.
BMC Oral Health ; 24(1): 742, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937712

RESUMEN

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, characterized by high morbidity, high mortality, and poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) has been shown to be highly expressed in various cancers. However, its biological functions, potential role as a biomarker, and its relationship with immune infiltrates in HNSCC remain unclear. Our principal objective was to analyze CTHRC1 expression, its prognostic implications, biological functions, and its effects on the immune system in HNSCC patients using bioinformatics analysis. METHODS: The expression matrix was obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). CTHRC1 expression in HNSCC was analyzed between tumor and adjacent normal tissues, different stages were compared, and its impact on clinical prognosis was assessed using Kaplan-Meier analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA) were employed for enrichment analysis. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to analyze protein-protein interactions. Pearson correlation tests were used to investigate the association between CTHRC1 expression and immune checkpoints. The correlation between CTHRC1 and immune infiltration was investigated using CIBERSORT, TIMER, and ESTIMATE. RESULTS: Compared to adjacent normal tissues, CTHRC1 was found to be highly overexpressed in tumors. Increased expression of CTHRC1 was more evident in the advanced stage of HNSCC and predicted a poor prognosis. Most genes related to CTHRC1 in HNSCC were enriched in physiological functions of Extracellular matrix(ECM) and tumor. Furthermore, several immune checkpoints, such as TNFSF4 and CD276 have been shown to be associated with CTHRC1 expression. Notably, the level of CTHRC1 expression correlated significantly with immune infiltration levels, particularly activated macrophages in HNSCC. CONCLUSIONS: High expression of CTHRC1 predicts poor prognosis and is associated with immune infiltration in HNSCC, confirming its utility as a tumor marker for HNSCC. TRIAL REGISTRATION: Not applicable. All data are from public databases and do not contain any clinical trials.


Asunto(s)
Biomarcadores de Tumor , Proteínas de la Matriz Extracelular , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Biomarcadores de Tumor/metabolismo , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Biología Computacional , Masculino
4.
J Nanobiotechnology ; 22(1): 377, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937768

RESUMEN

BACKGROUND: Efficient monitoring of glucose concentration in the human body necessitates the utilization of electrochemically active sensing materials in nonenzymatic glucose sensors. However, prevailing limitations such as intricate fabrication processes, lower sensitivity, and instability impede their practical application. Herein, ternary Cu-Co-Ni-S sulfides nanoporous network structure was synthesized on carbon fiber paper (CP) by an ultrafast, facile, and controllable technique through on-step cyclic voltammetry, serving as a superior self-supporting catalytic electrode for the high-performance glucose sensor. RESULTS: The direct growth of free-standing Cu-Co-Ni-S on the interconnected three-dimensional (3D) network of CP boosted the active site of the composites, improved ion diffusion kinetics, and significantly promoted the electron transfer rate. The multiple oxidation states and synergistic effects among Co, Ni, Cu, and S further promoted glucose electrooxidation. The well-architected Cu-Co-Ni-S/CP presented exceptional electrocatalytic properties for glucose with satisfied linearity of a broad range from 0.3 to 16,000 µM and high sensitivity of 6829 µA mM- 1 cm- 2. Furthermore, the novel sensor demonstrated excellent selectivity and storage stability, which could successfully evaluate the glucose levels in human serum. Notably, the novel Cu-Co-Ni-S/CP showed favorable biocompatibility, proving its potential for in vivo glucose monitoring. CONCLUSION: The proposed 3D hierarchical morphology self-supported electrode sensor, which demonstrates appealing analysis behavior for glucose electrooxidation, holds great promise for the next generation of high-performance glucose sensors.


Asunto(s)
Técnicas Biosensibles , Fibra de Carbono , Cobalto , Cobre , Técnicas Electroquímicas , Electrodos , Níquel , Sulfuros , Cobre/química , Níquel/química , Catálisis , Humanos , Cobalto/química , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Sulfuros/química , Fibra de Carbono/química , Glucosa/análisis , Glucosa/química , Nanoporos , Oxidación-Reducción , Glucemia/análisis
5.
Bioresour Technol ; 406: 131031, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925402

RESUMEN

The sustainable management of agricultural waste is essential for curtailing environmental contamination. To address the shortcomings of single treatment methods, this study evaluated the feasibility of combining membrane-covered composting (MC) with vermicomposting. Based on this, the integrated effects of different biochar addition strategies on the combined process were investigated. The aim was to improve the efficiency of vermicomposting while eliminating the negative effects of biochar on earthworms. Addition of biochar before membrane-covered composting increased total earthworm biomass by 25.6 - 31.4 % and reproduction rate by 13.4 - 23.9 %. Specifically, the electrical conductivity (EC) (1061.0 - 1112.0 uS/cm) of the vermicompost was significantly reduced, while the total nutrient content (42.3 - 42.6 mg/g) and germination index (GI) (103.9 - 108.4 %) were maximized. Additionally, reductions in the carbon-to-nitrogen ratio and volatile content were observed. Overall, combination process is a promising approach to improve the quality of vermicomposting. The study's results offer a novel perspective on the value-added treatment of agricultural waste.

6.
Materials (Basel) ; 17(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38893998

RESUMEN

A high strength and ductile Mg-Gd-Y-Zn-Zr alloy was designed and fabricated. The local strain evolution of the alloys during plastic deformation was analyzed using high-resolution digital image correlation (DIC). The results showed that the ß particles, nano-sized γ' phases, and LPSO phases were distributed in the as-extruded alloy and a bimodal microstructure was exhibited, including elongated un-dynamic recrystallized grains and fine dynamic recrystallized grains. With increasing extrusion ratio, the grain size remained, with the volume fraction of dynamic recrystallization of the as-extruded alloy increasing from 30% to 75%, and the as-extruded alloy exhibited a high strength-ductility synergy, which is attributed to the grain refinement, extensive ß particles, and elongated block-shaped LPSO phases. The strain evolution analysis showed that a strain-transfer from un-DRXed regions to adjacent DRXed regions and LPSO phases can promote uniform plastic deformation, which tends to improve the ductility of the alloy.

7.
Front Bioeng Biotechnol ; 12: 1400614, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887613

RESUMEN

Background and objective: Our group has developed a novel artificial cervical joint complex (ACJC) as a motion preservation instrument for cervical corpectomy procedures. Through finite element analysis (FEA), this study aims to assess this prosthesis's mobility and stability in the context of physiological reconstruction of the cervical spine. Materials and methods: A finite element (FE)model of the subaxial cervical spine (C3-C7) was established and validated. ACJC arthroplasty, anterior cervical corpectomy and fusion (ACCF), and two-level cervical disc arthroplasty (CDA) were performed at C4-C6. Range of motion (ROM), intervertebral disc pressure (IDP), facet joint stress (FJS), and maximum von Mises stress on the prosthesis and vertebrae during loading were compared. Results: Compared to the intact model, the ROM in all three surgical groups demonstrated a decline, with the ACCF group exhibiting the most significant mobility loss, and the highest compensatory motion in adjacent segments. ACJC and artificial cervical disc prosthesis (ACDP) well-preserved cervical mobility. In the ACCF model, IDP and FJS in adjacent segments increased notably, whereas the index segments experienced the most significant FJS elevation in the CDA model. The ROM, IDP, and FJS in both index and adjacent segments of the ACJC model were intermediate between the other two. Stress distribution of ACCF instruments and ACJC prosthesis during the loading process was more dispersed, resulting in less impact on the adjacent vertebrae than in the CDA model. Conclusion: The biomechanical properties of the novel ACJC were comparable to the ACCF in constructing postoperative stability and equally preserved physiological mobility of the cervical spine as CDA without much impact on adjacent segments and facet joints. Thus, the novel ACJC effectively balanced postoperative stability with cervical motion preservation.

8.
J Hepatocell Carcinoma ; 11: 1095-1112, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887684

RESUMEN

Background: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown. Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed. Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial-mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment. Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients.

9.
Sci Adv ; 10(25): eadj8650, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38896624

RESUMEN

Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells. However, the mechanisms sustaining stemness and chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we demonstrate that Bicaudal C homolog 1 (BICC1), an RNA binding protein regulating numerous cytoplasmic mRNAs, facilitates chemoresistance and stemness in PDAC. Mechanistically, BICC1 activated tryptophan catabolism in PDAC by up-regulating indoleamine 2,3-dioxygenase-1 (IDO1) expression, a tryptophan-catabolizing enzyme. Increased levels of tryptophan metabolites contribute to NAD+ synthesis and oxidative phosphorylation, leading to a stem cell-like phenotype. Blocking BICC1/IDO1/tryptophan metabolism signaling greatly improves the gemcitabine (GEM) efficacy in several PDAC models with high BICC1 level. These findings indicate that BICC1 is a critical tryptophan metabolism regulator that drives the stemness and chemoresistance of PDAC and thus a potential target for combinatorial therapeutic strategy against chemoresistance.


Asunto(s)
Resistencia a Antineoplásicos , Células Madre Neoplásicas , Neoplasias Pancreáticas , Triptófano , Triptófano/metabolismo , Humanos , Resistencia a Antineoplásicos/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Línea Celular Tumoral , Animales , Ratones , Regulación Neoplásica de la Expresión Génica , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/genética
10.
Dalton Trans ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38910547

RESUMEN

Bioinspired by the active sites of multicopper oxidases (MCOs), bi/multinuclear copper complexes have attracted great attention in promoting catalytic activity for the oxygen reduction reaction (ORR). Herein, we report the preparation of a Cu-N-C electrocatalyst Cu-BPOZ@CNB-400 for efficient ORR, which was obtained by low temperature pyrolysis of a dinuclear 2,5-bis(2-pyridyl)-1,3,4-oxadiazole (BPOZ) copper complex loaded on a N-doped carbon support at 400 °C. Cu-BPOZ@CNB-400 exhibited a half-wave potential (E1/2) of 0.86 V vs. RHE for the ORR in 0.1 M KOH solution, which was significantly higher than that of the Cu-BPOZ@CNB-800 (E1/2 = 0.83 V) catalyst treated under high temperature (at 800 °C) and the control catalyst Cu-Phen@CNB-400 (E1/2 = 0.82 V) derived from low-temperature-treatment (at 400 °C) of a mononuclear phenanthroline-coordinated-Cu complex loaded on a N-doped carbon support. When Cu-BPOZ@CNB-400 was applied as the cathode catalyst in zinc-air batteries a maximum power density (Pmax) of 127 mW cm-2 could be achieved, demonstrating comparable catalyst performance to the commercial 20 wt% Pt/C (Pmax = 122 mW cm-2) and the control Cu-Phen@CNB-400 catalyst (Pmax = 105 mW cm-2) under similar experimental conditions. Low-temperature pyrolysis of dinuclear copper complexes on a carbon support improved the charge transfer efficiency, inhibited metal aggregation, and could produce highly dispersed Cu-N-C catalysts with dinuclear copper sites for promoting the 4e--reduction selectivity of the ORR. It thus provides a cost-effective approach for the controllable fabrication of efficient ORR catalysts to be applied for energy conversion devices.

11.
Cleft Palate Craniofac J ; : 10556656241260481, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839107

RESUMEN

OBJECTIVE: The aim of this study was to cephalometrically evaluate the pharyngeal morphology in adults with unoperated Submucous Cleft Palate (SMCP), adults with unoperated Overt Cleft Palate (OCP), and adults without clefts. DESIGN: This study employed a retrospective cross-sectional design. Lateral cephalometric radiography was performed on three groups of adults: 1) 29 with unrepaired SMCP; 2) 41 with unrepaired OCP; and 3) 39 without clefts, who served as controls. One-way ANOVA and rank-sum tests were used for intergroup comparisons. P value was set at .05. RESULTS: The soft palate length and the ratio of soft palate length to pharyngeal depth were significantly lower in subjects with unoperated SMCP and OCP than in non-cleft controls. Significant differences were also observed in pharyngeal depth, nasopharyngeal depth, and posterior pharyngeal wall thickness between subjects with unoperated OCP and non-cleft controls. CONCLUSIONS: Pharyngeal morphology differs significantly between individuals with and without clefts, particularly in soft palate length and the ratio of soft palate length to pharyngeal depth.

12.
Clin Transl Immunology ; 13(6): e1515, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835955

RESUMEN

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

13.
PhytoKeys ; 242: 161-227, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38854497

RESUMEN

This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photiniamicrophylla (J.E.Vidal) B.B.Liu and Weniomelesatropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.

14.
Front Vet Sci ; 11: 1359547, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855411

RESUMEN

Introduction: Porcine deltacoronavirus (PDCoV), an emerging swine enteropathogenic coronavirus with worldwide distribution, mainly infects newborn piglets with severe diarrhea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. However, the underlying pathogenic mechanisms of PDCoV infection and the effects of PDCoV infection on host transcripts and metabolites remain incompletely understood. Methods: This study investigated a combined transcriptomic and metabolomic analysis of porcine intestinal epithelial cells (IPEC-J2) following PDCoV infection by LC/MS and RNA-seq techniques. A total of 1,401 differentially expressed genes and 254 differentially accumulated metabolites were detected in the comparison group of PDCoV-infected vs. mock-infected. Results and discussion: We found that PDCoV infection regulates gene sets associated with multiple signaling pathways, including the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, MAPK signaling pathway, chemokine signaling pathway, ras signaling pathway and so on. Besides, the metabolomic results showed that biosynthesis of cofactors, nucleotide metabolism, protein digestion and absorption, and biosynthesis of amino acid were involved in PDCoV infection. Moreover, integrated transcriptomics and metabolomics analyses revealed the involvement of ferroptosis in PDCoV infection, and exogenous addition of the ferroptosis activator erastin significantly inhibited PDCoV replication. Overall, these unique transcriptional and metabolic reprogramming features may provide a better understanding of PDCoV-infected IPEC-J2 cells and potential targets for antiviral treatment.

15.
Biochem Biophys Res Commun ; 725: 150232, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38897042

RESUMEN

Molecular processes are orchestrated by various proteins that promote early endosomes to become late endosomes and eventually fuse with lysosomes, guaranteeing the degradation of the content. Rab7, which is localized to late endosomes, is one of the most well-known GTPases. ORP1L is recruited by Rab7 to facilitate the fusion of late endosomes and lysosomes. Here, we present the structure of GDP-bound Rab7 Q67L with ORP1L. Structural analysis, supported by biochemical and ITC binding experiments, not only provides structural insight into the interactions between the ORP1L ANK domain and Rab7 but also suggests that the GTPase activity of Rab7 does not interfere with its ORP1L-binding capacity.

17.
IMA Fungus ; 15(1): 15, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38863028

RESUMEN

In the present study, three mitogenomes from the Bipolaris genus (Bipolaris maydis, B. zeicola, and B. oryzae) were assembled and compared with the other two reported Bipolaris mitogenomes (B. oryzae and B. sorokiniana). The five mitogenomes were all circular DNA molecules, with lengths ranging from 106,403 bp to 135,790 bp. The mitogenomes of the five Bipolaris species mainly comprised the same set of 13 core protein-coding genes (PCGs), two rRNAs, and a certain number of tRNAs and unidentified open reading frames (ORFs). The PCG length, AT skew and GC skew showed large variability among the 13 PCGs in the five mitogenomes. Across the 13 core PCGs tested, nad6 had the least genetic distance among the 16 Pleosporales species we investigated, indicating that this gene was highly conserved. In addition, the Ka/Ks values for all 12 core PCGs (excluding rps3) were < 1, suggesting that these genes were subject to purifying selection. Comparative mitogenomic analyses indicate that introns were the main factor contributing to the size variation of Bipolaris mitogenomes. The introns of the cox1 gene experienced frequent gain/loss events in Pleosporales species. The gene arrangement and collinearity in the mitogenomes of the five Bipolaris species were almost highly conserved within the genus. Phylogenetic analysis based on combined mitochondrial gene datasets showed that the five Bipolaris species formed well-supported topologies. This study is the first report on the mitogenomes of B. maydis and B. zeicola, as well as the first comparison of mitogenomes among Bipolaris species. The findings of this study will further advance investigations into the population genetics, evolution, and genomics of Bipolaris species.

18.
Artículo en Inglés | MEDLINE | ID: mdl-38824095

RESUMEN

BACKGROUND: In patients with hilar cholangiocarcinoma (HCCA), radical resection can be achieved by resection and reconstruction of the vasculature. However, whether vascular reconstruction (VR) improves long-term and short-term prognosis has not been demonstrated comprehensively. METHODS: This was a retrospective multicenter study of patients who received surgery for HCCA with or without VR. Variables associated with overall survival (OS) and recurrence-free survival (RFS) were identified based on Cox regression. Kaplan-Meier curves were used to explore the impact of VR. Restricted mean survival time (RMST) was used for comparisons of short-term survival between the groups. Patients' intraoperative and postoperative characteristics were compared. RESULTS: Totally 447 patients were enrolled. We divided these patients into 3 groups: VR with radical resections (n = 84); non-VR radical resections (n = 309) and non-radical resection (we pooled VR-nonradical and non-VR nonradical together, n = 54). Cox regression revealed that carbohydrate antigen 242 (CA242), vascular invasion, lymph node metastasis and poor differentiation were independent risk factors for OS and RFS. There was no significant difference of RMST between the VR and non-VR radical groups within 12 months after surgery (10.18 vs. 10.76 mon, P = 0.179), although the 5-year OS (P < 0.001) and RFS (P < 0.001) were worse in the VR radical group. The incidences of most complications were not significantly different, but those of bile leakage (P < 0.001) and postoperative infection (P = 0.009) were higher in the VR radical group than in the non-VR radical group. Additionally, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) up to 7 days after surgery tended to decrease in all groups. There was no significant difference in the incidence of postoperative liver failure between the VR and non-VR radical groups. CONCLUSIONS: Radical resection can be achieved with VR to improve the survival rate without worsening short-term survival compared with resection with non-VR. After adequate assessment of the patient's general condition, VR can be considered in the resection.

19.
Clin Oral Investig ; 28(7): 384, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888691

RESUMEN

OBJECTIVES: The study was to explore the causal effects of sleep characteristics on temporomandibular disorder (TMD)-related pain using Mendelian randomization (MR) analysis. MATERIALS AND METHODS: Five sleep characteristics (short sleep, insomnia, chronotype, snoring, sleep apnea) were designated as exposure factors. Data were obtained from previous publicized genome-wide association studies and single nucleotide polymorphisms (SNPs) strongly associated with them were utilized as instrumental variables (IVs). TMD-related pain was designed as outcome variable and sourced from the FinnGens database. MR analysis was employed to explore the causal effects of the five sleep characteristics on TMD-related pain. The causal effect was analyzed using the inverse variance-weighted (IVW), weighted median, and MR-Egger methods. Subsequently, sensitivity analyses were conducted using Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. RESULTS: A causal effect of short sleep on TMD-related pain was revealed by IVW (OR: 1.60, 95% CI: 1.06-2.41, P = 0.026). No causal relationship was identified between other sleep characteristics (insomnia, chronotype, snoring, sleep apnea) and TMD-related pain. CONCLUSIONS: Our study suggests that short sleep may increase the risk of TMD-related pain, while there was no causal relationship between other sleep characteristics and TMD-related pain. Further studies are warranted to deepen and definitively clarify their relationship. CLINICAL RELEVANCE: These findings reveal that the short sleep may be a risk factor of TMD-related pain and highlight the potential therapeutical effect of extending sleep time on alleviating TMD-related pain.


Asunto(s)
Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Trastornos de la Articulación Temporomandibular , Humanos , Trastornos de la Articulación Temporomandibular/genética , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Ronquido , Trastornos del Sueño-Vigilia/genética , Síndromes de la Apnea del Sueño/genética
20.
Acad Radiol ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38890032

RESUMEN

RATIONALE AND OBJECTIVES: The aim of this study was to ascertain whether the utilization of multiple b-value diffusion-weighted habitat imaging, a technique that depicts tumor heterogeneity, could aid in identifying breast cancer patients who would derive substantial benefit from neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This prospective study enrolled 143 women (II-III breast cancer), who underwent multi-b-value diffusion-weighted imaging (DWI) in 3-T magnetic resonance (MR) before NAC. The patient cohort was partitioned into a training set (consisting of 100 patients, of which 36 demonstrated a pathologic complete response [pCR]) and a test set (featuring 43 patients, 16 of whom exhibited pCR). Utilizing the training set, predictive models for pCR, were constructed using different parameters: whole-tumor radiomics (ModelWH), diffusion-weighted habitat-imaging (ModelHabitats), conventional MRI features (ModelCF), along with combined models ModelHabitats+CF. The performance of these models was assessed based on the area under the receiver operating characteristic curve (AUC) and calibration slope. RESULTS: In the prediction of pCR, ModelWH, ModelHabitats, ModelCF, and ModelHabitats+CF achieved AUCs of 0.733, 0.722, 0.705, and 0.756 respectively, within the training set. These scores corresponded to AUCs of 0.625, 0.801, 0.700, and 0.824 respectively in the test set. The DeLong test revealed no significant difference between ModelWH and ModelHabitats (P = 0.182), between ModelHabitats and ModelHabitats+CF (P = 0.113). CONCLUSION: The habitat model we developed, incorporating first-order features along with conventional MRI features, has demonstrated accurate predication of pCR prior to NAC. This model holds the potential to augment decision-making processes in personalized treatment strategies for breast cancer.

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