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1.
ISA Trans ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38782639

RESUMEN

Autonomous race driving poses a complex control challenge as vehicles must be operated at the edge of their handling limits to reduce lap times while respecting physical and safety constraints. This paper presents a novel reinforcement learning (RL)-based approach, incorporating the action mapping (AM) mechanism to manage state-dependent input constraints arising from limited tire-road friction. A numerical approximation method is proposed to implement AM, addressing the complex dynamics associated with the friction constraints. The AM mechanism also allows the learned driving policy to be generalized to different friction conditions. Experimental results in our developed race simulator demonstrate that the proposed AM-RL approach achieves superior lap times and better success rates compared to the conventional RL-based approaches. The generalization capability of driving policy with AM is also validated in the experiments.

2.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1017-1028, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38658145

RESUMEN

Brassica juncea (mustard) is a vegetable crop of Brassica, which is widely planted in China. The yield and quality of stem mustard are greatly influenced by the transition from vegetative growth to reproductive growth, i.e., flowering. The WRKY transcription factor family is ubiquitous in higher plants, and its members are involved in the regulation of many growth and development processes, including biological/abiotic stress responses and flowering regulation. WRKY71 is an important member of the WRKY family. However, its function and mechanism in mustard have not been reported. In this study, the BjuWRKY71-1 gene was cloned from B. juncea. Bioinformatics analysis and phylogenetic tree analysis showed that the protein encoded by BjuWRKY71-1 has a conserved WRKY domain, belonging to class Ⅱ WRKY protein, which is closely related to BraWRKY71-1 in Brassica rapa. The expression abundance of BjuWRKY71-1 in leaves and flowers was significantly higher than that in roots and stems, and the expression level increased gradually along with plant development. The result of subcellular localization showed that BjuWRKY71-1 protein was located in nucleus. The flowering time of overexpressing BjuWRKY71-1 Arabidopsis plants was significantly earlier than that of the wild type. Yeast two-hybrid assay and dual-luciferase reporter assay showed that BjuWRKY71-1 interacted with the promoter of the flowering integrator BjuSOC1 and promoted the expression of its downstream genes. In conclusion, BjuWRKY71-1 protein can directly target BjuSOC1 to promote plant flowering. This discovery may facilitate further clarifying the molecular mechanism of BjuWRKY71-1 in flowering time control, and creating new germplasm with bolting and flowering tolerance in mustard.


Asunto(s)
Flores , Regulación de la Expresión Génica de las Plantas , Planta de la Mostaza , Proteínas de Plantas , Factores de Transcripción , Planta de la Mostaza/genética , Planta de la Mostaza/metabolismo , Planta de la Mostaza/crecimiento & desarrollo , Flores/genética , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Filogenia , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética
3.
Plant Cell Physiol ; 65(1): 68-78, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-37814936

RESUMEN

Reprograming of chromatin structures and changes in gene expression are critical for plant male gamete development, and epigenetic marks play an important role in these processes. Histone variant H3.3 is abundant in euchromatin and is largely associated with transcriptional activation. The precise function of H3.3 in gamete development remains unclear in plants. Here, we report that H3.3 is abundantly expressed in Arabidopsis anthers and its knockout mutant h3.3-1 is sterile due to male sterility. Transcriptome analysis of young inflorescence has identified 2348 genes downregulated in h3.3-1 mutant, among which 1087 target genes are directly bound by H3.3, especially at their 3' ends. As a group, this set of H3.3 targets is enriched in the reproduction-associated processes including male gamete generation, pollen sperm cell differentiation and pollen tube growth. The function of H3.3 in male gamete development is dependent on the Anti-Silencing Factor 1A/1B (ASF1A/1B)-Histone regulator A (HIRA)-mediated pathway. Our results suggest that ASF1A/1B-HIRA-mediated H3.3 deposition at its direct targets for transcription activation forms the regulatory networks responsible for male gamete development.


Asunto(s)
Arabidopsis , Histonas , Histonas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Semillas/metabolismo , Fertilidad , Células Germinativas/metabolismo , Cromatina/metabolismo
4.
Signal Transduct Target Ther ; 8(1): 436, 2023 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-38016957

RESUMEN

Despite the remarkable success of immune checkpoint inhibitors (ICIs), primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment (TME). Oncolytic viruses (OVs) can overcome the immunosuppressive TME and promote systemic antitumor immunity in hosts. Engineered OVs armed with ICIs would likely have improved effectiveness as a cancer therapy. According to the diverse immune cell landscapes among different types of tumors, we rationally and precisely generated three recombinant oncolytic adenoviruses (OAds): OAd-SIRPα-Fc, OAd-Siglec10-Fc and OAd-TIGIT-Fc. These viruses were designed to locally deliver SIRPα-Fc, Siglec10-Fc or TIGIT-Fc fusion proteins recognizing CD47, CD24 or CD155, respectively, in the TME to achieve enhanced antitumor effects. Our results suggested that OAd-SIRPα-Fc and OAd-Siglec10-Fc both showed outstanding efficacy in tumor suppression of macrophage-dominated tumors, while OAd-TIGIT-Fc showed the best antitumor immunity in CD8+ T-cell-dominated tumors. Importantly, the recombinant OAds activated an inflammatory immune response and generated long-term antitumor memory. In addition, the combination of OAd-Siglec10-Fc with anti-PD-1 significantly enhanced the antitumor effect in a 4T1 tumor model by remodeling the TME. In summary, rationally designed OAds expressing ICIs tailored to the immune cell landscape in the TME can precisely achieve tumor-specific immunotherapy of cancer.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Adenoviridae/genética , Virus Oncolíticos/genética , Neoplasias/genética , Neoplasias/terapia , Viroterapia Oncolítica/métodos , Receptores Inmunológicos/genética , Microambiente Tumoral/genética
5.
Artículo en Inglés | MEDLINE | ID: mdl-37729569

RESUMEN

In this article, a reinforcement learning (RL)-based strategy for unmanned surface vehicle (USV) path following control is developed. The proposed method learns integrated guidance and heading control policy, which directly maps the USV's navigation states to motor control commands. By introducing a twin-critic design and an integral compensator to the conventional deep deterministic policy gradient (DDPG) algorithm, the tracking accuracy and robustness of the controller can be significantly improved. Moreover, a pretrained neural network-based USV model is built to help the learning algorithm efficiently deal with unknown nonlinear dynamics. The self-learning and path following capabilities of the proposed method were validated in both simulations and real sea experiments. The results show that our control policy can achieve better performance than a traditional cascade control policy and a DDPG-based control policy.

6.
Front Genet ; 14: 1232117, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37554402

RESUMEN

Antimicrobial peptides are present ubiquitously in intra- and extra-biological environments and display considerable antibacterial and antifungal activities. Clinically, it has shown good antibacterial effect in the treatment of diabetic foot and its complications. However, the discovery and screening of antimicrobial peptides primarily rely on wet lab experiments, which are inefficient. This study endeavors to create a precise and efficient method of predicting antimicrobial peptides by incorporating novel machine learning technologies. We proposed a deep learning strategy named AMP-EBiLSTM to accurately predict them, and compared its performance with ensemble learning and baseline models. We utilized Binary Profile Feature (BPF) and Pseudo Amino Acid Composition (PSEAAC) for effective local sequence capture and amino acid information extraction, respectively, in deep learning and ensemble learning. Each model was cross-validated and externally tested independently. The results demonstrate that the Enhanced Bi-directional Long Short-Term Memory (EBiLSTM) deep learning model outperformed others with an accuracy of 92.39% and AUC value of 0.9771 on the test set. On the other hand, the ensemble learning models demonstrated cost-effectiveness in terms of training time on a T4 server equipped with 16 GB of GPU memory and 8 vCPUs, with training durations varying from 0 to 30 s. Therefore, the strategy we propose is expected to predict antimicrobial peptides more accurately in the future.

7.
ISA Trans ; 137: 222-235, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36801140

RESUMEN

This paper investigates visual navigation and control of a cooperative unmanned surface vehicle (USV)-unmanned aerial vehicle (UAV) system for marine search and rescue. First, a deep learning-based visual detection architecture is developed to extract positional information from the images taken by the UAV. With specially designed convolutional layers and spatial softmax layers, the visual positioning accuracy and computational efficiency are improved. Next, a reinforcement learning-based USV control strategy is proposed, which could learn a motion control policy with an enhanced ability to reject wave disturbances. The simulation experiment results show that the proposed visual navigation architecture can provide stable and accurate position and heading angle estimation in different weather and lighting conditions. The trained control policy also demonstrates satisfactory USV control ability under wave disturbances.

8.
IEEE Trans Neural Netw Learn Syst ; 34(10): 7145-7157, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35025751

RESUMEN

Existing approaches to constrained-input optimal control problems mainly focus on systems with input saturation, whereas other constraints, such as combined inequality constraints and state-dependent constraints, are seldom discussed. In this article, a reinforcement learning (RL)-based algorithm is developed for constrained-input optimal control of discrete-time (DT) systems. The deterministic policy gradient (DPG) is introduced to iteratively search the optimal solution to the Hamilton-Jacobi-Bellman (HJB) equation. To deal with input constraints, an action mapping (AM) mechanism is proposed. The objective of this mechanism is to transform the exploration space from the subspace generated by the given inequality constraints to the standard Cartesian product space, which can be searched effectively by existing algorithms. By using the proposed architecture, the learned policy can output control signals satisfying the given constraints, and the original reward function can be kept unchanged. In our study, the convergence analysis is given. It is shown that the iterative algorithm is convergent to the optimal solution of the HJB equation. In addition, the continuity of the iterative estimated Q -function is investigated. Two numerical examples are provided to demonstrate the effectiveness of our approach.

9.
Sci Rep ; 12(1): 18752, 2022 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-36335144

RESUMEN

Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan-Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb < 30 g/L, antibiotic use, diuretic use, NSAID use and proton pump inhibitor use were independent risk factors for AKI development in patients treated with ICIs. Stage 2 or 3 AKI was an independent risk factor for nonrecovery of renal function after AKI onset. Multivariate Cox regression analysis showed that anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs, while high baseline BMI, other tumor types, ACEI/ARB use, and chemotherapy use were protective factors for patient death. AKI occurs in 7.1% of patients treated with ICIs. Anemia, Alb < 30 g/L, and combined medication use are independent risk factors for AKI in patients treated with ICIs. Anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs.


Asunto(s)
Lesión Renal Aguda , Inhibidores de Puntos de Control Inmunológico , Humanos , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Incidencia , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Factores de Riesgo , Pronóstico , Diuréticos/efectos adversos
10.
Blood Purif ; : 1-11, 2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-35952629

RESUMEN

INTRODUCTION: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. METHODS: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (ß2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of ß2M and PTH, while the secondary outcome was the reduction of the pruritus score. RESULTS: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of ß2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. CONCLUSION: The long-term HP + HD can reduce ß2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

11.
Sheng Wu Gong Cheng Xue Bao ; 38(8): 3029-3040, 2022 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-36002429

RESUMEN

Brassica juncea is a yearly or biennial vegetable in Brassica of Cruciferae. The yield and quality of its product organs are affected by flowering time. WRKY proteins family can respond to biological and abiotic stresses, developmental regulation and signal transduction. WRKY75 is an important member of WRKY family which can regulate flowering, but the flowering regulation mechanism in B. juncea has not been reported. In this study, a gene BjuWRKY75 in B. juncea was cloned, and the encoded-protein belonged to the group Ⅱ of WRKY protein with highly conserved domain. BjuWRKY75 had the highest homology with BriWRKY75 of Brassica nigra. The relative expression level of BjuWRKY75 in flowers was significantly higher than that in leaves and stems, and it was expressed stably in leaves. BjuWRKY75 protein was localized in the nucleus and interacted with the promoter of the flowering integrator BjuFT, which contained the W-box response element for the interaction between protein and DNA. Thus, it could transcriptionally activate the expression of the downstream genes. The overexpression of BjuWRKY75 in Arabidopsis led to earlier flowering significantly. In conclusion, BjuWRKY75 could directly target the promoter of BjuFT and accelerate flowering. These results may facilitate further study on the regulation of flowering molecules of BjuWRKY75.


Asunto(s)
Arabidopsis , Planta de la Mostaza , Arabidopsis/genética , Flores/genética , Regulación de la Expresión Génica de las Plantas , Planta de la Mostaza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas
12.
J Adv Res ; 42: 41-53, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35933090

RESUMEN

INTRODUCTION: Polyploidy is a major force in plant evolution and the domestication of cultivated crops. OBJECTIVES: The study aimed to explore the relationship and underlying mechanism between three-dimensional (3D) chromatin organization and gene transcription upon rice genome duplication. METHODS: The 3D chromatin structures between diploid (2C) and autotetraploid (4C) rice were compared using high-throughput chromosome conformation capture (Hi-C) analysis. The study combined genetics, transcriptomics, whole-genome bisulfite sequencing (WGBS-seq) and 3D genomics approaches to uncover the mechanism for DNA methylation in modulating gene transcription through 3D chromatin architectures upon rice genome duplication. RESULTS: We found that 4C rice presents weakened intra-chromosomal interactions compared to its 2C progenitor in some chromosomes. In addition, we found that changes of 3D chromatin organizations including chromatin compartments, topologically associating domains (TADs), and loops, are uncorrelated with gene transcription. Moreover, DNA methylations in the regulatory sequences of genes in compartment A/B switched regions and TAD boundaries are unrelated to their expression. Importantly, although there was no significant difference in the methylation levels in transposable elements (TEs) in differentially expressed gene (DEG) and non-DEG promoters between 2C and 4C rice, we found that the hypermethylated TEs across genes in compartment A/B switched regions and TAD boundaries may suppress the expression of these genes. CONCLUSION: The study proposed that the rice genome doubling might modulate TE methylation to buffer the effects of chromatin architecture on gene transcription in compartment A/B switched regions and TAD boundaries, resulting in the disconnection between 3D chromatin structure alteration and gene transcription upon rice genome duplication.


Asunto(s)
Elementos Transponibles de ADN , Oryza , Elementos Transponibles de ADN/genética , Oryza/genética , Metilación de ADN , Duplicación de Gen , Cromatina/genética , Transcripción Genética/genética
13.
Front Genet ; 13: 792183, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35251124

RESUMEN

X-linked hypophosphataemia (XLH) is an X-linked dominant rare disease that refers to the most common hereditary hypophosphatemia (HH) caused by mutations in the phosphate-regulating endopeptidase homolog X-linked gene (PHEX; OMIM: * 300550). However, mutations that have already been reported cannot account for all cases of XLH. Extensive genetic analysis can thus be helpful for arriving at the diagnosis of XLH. Herein, we identified a novel heterozygous mutation of PHEX (NM_000444.5: c.1768G > A) in a large Chinese family with XLH by whole-exome sequencing (WES). In addition, the negative effect of this mutation in PHEX was confirmed by both bioinformatics analysis and in vitro experimentation. The three-dimensional protein-model analysis predicted that this mutation might impair normal zinc binding. Immunofluorescence staining, qPCR, and western blotting analysis confirmed that the mutation we detected attenuated PHEX protein expression. The heterozygous mutation of PHEX (NM_000444.5: c.1768G > A) identified in this study by genetic and functional experiments constitutes a novel genetic cause of XLH, but further study will be required to expand its use in clinical and molecular diagnoses of XLH.

14.
Stem Cell Res Ther ; 13(1): 128, 2022 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-35337372

RESUMEN

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for acute kidney injury (AKI). However, the optimal route of MSC transplantation remains controversial, and there have been no comparisons of the therapeutic benefits of MSC administration through different delivery routes. METHODS: In this study, we encapsulated MSCs into a collagen matrix to help achieve local MSC retention in the kidney and assessed the survival of MSCs in vitro and in vivo. After transplanting collagen matrix-encapsulated-MSCs (Col-MSCs) under the renal capsule or into the parenchyma using the same cell dose and suspension volume in an ischemia/reperfusion injury model, we evaluated the treatment efficacy of two local transplantation routes at different stages of AKI. RESULTS: We found that Col-MSCs could be retained in the kidney for at least 14 days. Both local MSC therapies could reduce tubular injury, promote the proliferation of renal tubular epithelial cells on Day 3 and alleviate renal fibrosis on Day 14 and 28. MSC transplantation via the subcapsular route exerts better therapeutic effects for renal functional and structural recovery after AKI than MSC administration via the parenchymal route. CONCLUSIONS: Subcapsular MSC transplantation may be an ideal route of MSC delivery for AKI treatment, and collagen I can provide a superior microenvironment for cell-cell and cell-matrix interactions to stabilize the retention rate of MSCs in the kidney.


Asunto(s)
Lesión Renal Aguda , Trasplante de Células Madre Mesenquimatosas , Insuficiencia Renal Crónica , Lesión Renal Aguda/terapia , Animales , Colágeno , Femenino , Humanos , Riñón , Masculino , Ratones , Resultado del Tratamiento
15.
NPJ Vaccines ; 6(1): 75, 2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-34016984

RESUMEN

The development of adjuvants has been an empirical process. Efforts to develop a new design and evaluation system for novel adjuvants are not only desirable but also necessary. Moreover, composite adjuvants that contain two or more types of adjuvants to synergistically enhance the immune response are important for adjuvant and vaccine design. Innate defense regulator peptides (IDRs) are promising adjuvants for clinical immunotherapy because they exhibit multifaceted immunomodulatory capabilities. However, the rational design and discovery of IDRs that have improved immunomodulatory activities have been hampered by the lack of screening techniques and the great challenges in the identification of their interaction partners. Here, we describe a screening and evaluation system for IDR design. On the basis of in vitro screening, the optimized IDR DP7 recruited neutrophils, monocytes and macrophages to the site of infection. The adjuvant, comprising the DP7 and CpG oligonucleotide (CpG), induced chemokine/cytokine expression, enhanced the antigen uptake by dendritic cells and upregulated surface marker expression in dendritic cells. Vaccination with the NY-ESO-1 or OVA antigens combined with the adjuvant alum/CpG/DP7 strongly suppressed tumor growth in mice which was due to the improvement of antigen-specific humoral and cellular immunity. Regarding the mechanism of action, GPR35 may be the potential interaction partner of DP7. Our study revealed the potential application of the screening and evaluation system as a strategy for rationally designing effective IDRs or composite adjuvants and identifying their mechanism of action.

16.
Sheng Wu Gong Cheng Xue Bao ; 37(1): 142-148, 2021 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-33501796

RESUMEN

WRKY transcription factors are one of the largest families of transcription factors in higher plants and involved in regulating multiple and complex growth and development processes in plants. WRKY12 is a typical member of WRKY family. This article summarizes recent research progresses on the regulatory mechanism of WRKY12 in multiple growth and development processes, and analyzes the functional differences between WRKY12 and WRKY13. It provides a useful reference for further studying the molecular mechanism of WRKY12 in plant complex developments. It also provides clearer research ideas and reference strategies for exploring the self-regulation of other WRKY member and the mutual regulatory relationships between different WRKY family genes.


Asunto(s)
Desarrollo de la Planta , Proteínas de Plantas , Regulación de la Expresión Génica de las Plantas , Humanos , Filogenia , Desarrollo de la Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Estrés Fisiológico , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
17.
Drug Des Devel Ther ; 15: 209-222, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33488068

RESUMEN

PURPOSE: This study aimed to describe a novel cancer vaccine developed using H2O2-inactivated Salmonella typhimurium RE88 [with deletions of AroA (the first enzyme in the aromatic amino acid biosynthesis pathway) and DNA adenine methylase] as the carrier. METHODS: The pVLT33 plasmid was used to engineer an RE88 strain induced to express ovalbumin (OVA) by isopropylthiogalactoside (RE88-pVLT33-OVA). The immune responses and anticancer effects of H2O2-inactivated RE88-pVLT33-OVA were compared with those of non-inactivated RE88-pVLT33-OVA and OVA (positive control) in mice carrying OVA-expressing tumors (EG7-OVA) cells. RESULTS: Anti-ovalbumin IgG (immunoglobulin G) titer following vaccination with H2O2-inactivated RE88-pVLT33-OVA was higher for subcutaneous than for intragastric vaccination. When subcutaneous administration was used, H2O2-inactivated RE88-pVLT33-OVA (2 × 109 CFU (colony forming units)/mouse) achieved an anti-ovalbumin IgG titer higher than that for the same dose of RE88-pVLT33-OVA and comparable to that for 10 µg ovalbumin (positive control). The binding of mouse serum antibodies to EG7-OVA cells was stronger for H2O2-inactivated RE88-pVLT33-OVA (2 × 109 CFU/mouse) than for 10 µg ovalbumin. Furthermore, subcutaneous vaccination with H2O2-inactivated RE88-pVLT33-OVA (2 × 109 CFU/mouse) induced greater activation of splenic T cells and more extensive tumor infiltration with CD4+/CD8+ T cells compared with 10 µg ovalbumin (positive control). The mice vaccinated subcutaneously with H2O2-inactivated RE88-pVLT33-OVA at a dose of 2 × 108 or 6 × 108 CFU/mouse had smaller tumors compared with mice in the negative control groups. Tumor weight in mice vaccinated with H2O2-inactivated RE88-pVLT33-OVA at a dose of 2 × 109 CFU/mouse was significantly lower than that in both negative control groups (P < 0.05) and decreased with the increasing dose of H2O2-inactivated RE88-pVLT33-OVA. H2O2-inactivated RE88-pVLT33-OVA was potentially safer than the non-inactivated strain, could carry exogenous antigens, and had specific epitopes that could be exploited as natural adjuvants to facilitate the induction of cellular and humoral immune responses. CONCLUSION: It was anticipated that H2O2-inactivated RE88-pVLT33-OVA could be used as a novel delivery system for new cancer vaccines.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Modelos Animales de Enfermedad , Peróxido de Hidrógeno/química , Neoplasias/terapia , Salmonella typhimurium/efectos de los fármacos , Animales , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Femenino , Peróxido de Hidrógeno/farmacología , Ratones , Ratones Endogámicos C57BL , Neoplasias/inmunología , Ovalbúmina/inmunología
18.
Ann Transl Med ; 9(23): 1739, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35071433

RESUMEN

BACKGROUND: To evaluate the effect of proliferating cell nuclear antigen (PCNA) and p53 in patients with oral squamous cell carcinoma (OSCC). METHODS: Multiple databases, including PubMed, Embase, Cochrane library, and China National Knowledge Database, were searched for relevant studies and full-text articles that evaluated the effect of PCNA and p53 in patients with OSCC. Review Manager 5.2 was adopted to estimate the impact of the results among the selected articles. Forest plots, NOS table, sensitivity analysis, and bias analysis were also conducted. RESULTS: In total, nine eligible studies satisfied the included criteria. High PCNA expression (>50%) was significantly more prevalent in OSCC than low PCNA expression (<50%) (OR =3.88; 95% CI: 2.04-7.37; P<0.0001; I2=0%). However, there was no significant difference between p53 and OSCC (OR =1.60; 95% CI: 0.18-14.63; P=0.68; I2=86%). Low PCNA expression had a higher 5-year overall survival in OSCC patients than high PCNA expression (OR =0.47; 95% CI: 0.27-0.80; P=0.005; I2=41%). Meanwhile, p53 negative had a higher 5-year overall survival than p53 positive (OR =0.20; 95% CI: 0.10-0.42; P<0.0001; I2=0%). There was no difference between high and low PCNA in terms of metastasis (OR =0.80 with 95% CI: 0.18-3.45, I2=63%, P of over effect =0.76). The overall results showed no difference between p53 and metastasis (OR =0.38 with 95% CI: 0.13-1.10, I2=0%, P of over effect =0.07). DISCUSSION: PCNA and p53 might be suitable for prognostic and survival evaluation in OSCC patients.

19.
Medicine (Baltimore) ; 99(30): e20942, 2020 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-32791674

RESUMEN

BACKGROUND: To compare clinical effect between Er: YAG and CO2 laser in treatment of oral tumorous lesions. METHODS: A comprehensive search was conducted from 2000 to 2019. The quality assessment was performed by the QUADAS-2 tool (The Cochrane Collaboration, 2011). The clinical value of comparison between Er: YAG and CO2 laser was evaluated by using the pooled estimate of sensitivity and specificity. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results. RESULTS: Finally, 268 patients were enrolled in 6 studies and ultimately met the eligibility criteria. The Er: YAG and CO2 groups were 141 and 127, respectively. The meta-analysis showed significant difference in success (risk ratio  = 21.29, 95% confidence interval [1.09, 1.52], P = .002; P for Heterogeneity = .99, I = 0%) and time of surgery ((P of heterogeneity = .29, I = 20%, Z = 25.69, P of over effect < .00001). The recurrence and complications of CO2and Er: YAG groups had no difference. CONCLUSION: Er: YAG laser had better effects than CO2 laser in eliminating oral tumorous lesions while it needed longer operation time than CO2 laser.


Asunto(s)
Láseres de Gas/uso terapéutico , Láseres de Estado Sólido/uso terapéutico , Leucoplasia Bucal/terapia , Humanos
20.
Chin Med J (Engl) ; 130(8): 885-891, 2017 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-28397716

RESUMEN

BACKGROUND: Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death. METHODS: Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality. RESULTS: In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis. CONCLUSIONS: Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.


Asunto(s)
Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Adulto , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo
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