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1.
Adv Sci (Weinh) ; : e2401685, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664981

RESUMO

The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value-added epoxides. However, due to the competitive reaction of water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br-/HOBr-mediated method is developed to achieve a near-quantitative selectivity and ≈100% FE of styrene oxide on α-Fe2O3, in which low concentration of Br- as mediator and locally generated acidic micro-environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH-dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38662557

RESUMO

Fine-grained image recognition is a longstanding computer vision challenge that focuses on differentiating objects belonging to multiple subordinate categories within the same meta-category. Since images belonging to the same meta-category usually share similar visual appearances, mining discriminative visual cues is the key to distinguishing fine-grained categories. Although commonly used image-level data augmentation techniques have achieved great success in generic image classification problems, they are rarely applied in fine-grained scenarios, because their random editing-region behavior is prone to destroy the discriminative visual cues residing in the subtle regions. In this paper, we propose diversifying the training data at the feature-level to alleviate the discriminative region loss problem. Specifically, we produce diversified augmented samples by translating image features along semantically meaningful directions. The semantic directions are estimated with a covariance prediction network, which predicts a sample-wise covariance matrix to adapt to the large intra-class variation inherent in fine-grained images. Furthermore, the covariance prediction network is jointly optimized with the classification network in a meta-learning manner to alleviate the degenerate solution problem. Experiments on four competitive fine-grained recognition benchmarks (CUB-200-2011, Stanford Cars, FGVC Aircrafts, NABirds) demonstrate that our method significantly improves the generalization performance on several popular classification networks (e.g., ResNets, DenseNets, EfficientNets, RegNets and ViT). Combined with a recently proposed method, our semantic data augmentation approach achieves state-of-the-art performance on the CUB-200-2011 dataset. The source code will be released.

3.
J Adv Res ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38653371

RESUMO

INTRODUCTION: Myocardial ischemia-reperfusion (IR) injury is a common medical issue contributing to the onset and progression of ischemic heart diseases (IHD). Growth arrest-specific gene 6 (GAS6) is vitamin K-dependent secretory protein, to promote cell proliferation and inhibit inflammation and apoptosis through binding with Tyro3, Axl, and Mertk (TAM) receptors. OBJECTIVES: Our study aimed to examine the effect of GAS6 pathways activation as a potential new treatment in myocardial ischemia-reperfusion (IR) injury. METHODS: Gain- and loss-of-function experiments were utilized to determine the roles of GAS6 in the pathological processes of myocardial IR injury. RESULTS: Our results revealed down-regulated levels of GAS6, Axl, and SIRT1 in murine hearts subjected to IR injury, and cardiomyocytes challenged with hypoxia reoxygenation (HR). GAS6 overexpression significantly improved cardiac dysfunction in mice subjected to myocardial IR injury, accompanied by reconciled mitochondrial dysfunction, oxidative stress, and apoptosis. In vitro experiments also observed a protective effect of GAS6 in cardiomyocytes. SIRT1 was found to function as a downstream regulator for GAS6/Axl signaling axis. Through screening a natural product library, a polyphenol natural compound catechin was identified to exhibit a protective effect by turning on GAS6/Axl-SIRT1 cascade. CONCLUSIONS: Together, our findings indicate that GAS6 emerges as a potential novel target in the management of myocardial IR injury and other related anomalies.

4.
IEEE Trans Cybern ; PP2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630570

RESUMO

This article focuses on distributed nonconvex optimization by exchanging information between agents to minimize the average of local nonconvex cost functions. The communication channel between agents is normally constrained by limited bandwidth, and the gradient information is typically unavailable. To overcome these limitations, we propose a quantized distributed zeroth-order algorithm, which integrates the deterministic gradient estimator, the standard uniform quantizer, and the distributed gradient tracking algorithm. We establish linear convergence to a global optimal point for the proposed algorithm by assuming Polyak- [Formula: see text] ojasiewicz condition for the global cost function and smoothness condition for the local cost functions. Moreover, the proposed algorithm maintains linear convergence at low-data rates with a proper selection of algorithm parameters. Numerical simulations validate the theoretical results.

5.
Int J Biol Macromol ; 267(Pt 1): 131512, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608972

RESUMO

Two-dimensional (2D) transition metal carbides (Ti3C2Tx MXene) have gained significant attention for their potential in constructing diverse functional materials, However, MXene is easily oxidized and weakly bound to the cellulose matrix, which pose challenges in developing MXene-decorated non-woven fabric with strong bonding and stable thermal management properties. Herein, we successfully prepared deep eutectic supramolecular polymer (DESP) functionalized MXene to address these issues. MXene can be wrapped with DESP to be insulated from water and protected from being oxidized. Subsequently, we achieved an efficient in-situ deposition of DESP-functionalized MXene onto fibers through a combination of dip coating and photopolymerization technique. The resulting nonwoven fabric (CNs-DESP@M) exhibited excellent photothermal conversion properties along with rapid thermal response and functional stability. Interestingly, the interface bonding between MXene and the fiber surface was significantly enhanced due to the abundant pyrogallol groups in DESP, resulting in the composite textile exhibiting commendable mechanical properties (2.68 MPa). Moreover, the as-prepared textile demonstrates outstanding bactericidal efficacy against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The multifunctional textile, created through a facile and efficient approach, demonstrates remarkable potential for applications in smart textiles, catering to the diverse needs of individuals in the future.

6.
Heliyon ; 10(7): e29001, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596018

RESUMO

Kidney renal clear cell carcinoma (KIRC), one of the most prevalent form of kidney carcinoma, is highly aggressive cancer known for significant immune infiltration and high mortality rates. The absence of sensitivity to traditional therapy has spurred the search for new treatments. Protein Tyrosine Kinase 6 (PTK6) is implicated in promoting cancer growth, spread, and metastasis. Our review of The Cancer Genome Atlas database revealed PTK6 overexpression in KIRC, though its specific role in this cancer type was unclear. We investigated PTK6's cancer-promoting roles in KIRC using the database and confirmed our findings with patient-derived tissues. Our analysis showed that elevated PTK6 expression is linked to worse outcomes and higher levels of immune infiltration. It also correlates positively with neo-antigens (NEO) and DNA ploidy changes in KIRC. This research delves into PTK6's role in KIRC development, suggesting PTK6 as a possible biomarker for prognosis and treatment in KIRC.

7.
J Environ Manage ; 358: 120818, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599086

RESUMO

Hydrometallurgy is a primary method for recovering cathode electrode materials from spent lithium-ion batteries (LIBs). Most of the current research materials are pure cathode electrode materials obtained through manual disassembly. However, the spent LIBs are typically broken as a whole during the actual industrial recycling which makes the electrode materials combined with the collector fluid. Therefore, the competitive leaching between metal collector fluid and electrode material was examined. The pyrolysis characteristics of the electrode materials were analyzed to determine the pyrolysis temperature. The electrode sheet was pyrolyzed and then crushed for competitive leaching. The effect of pyrolysis was analyzed by XPS. The competitive leaching behavior was studied based on leaching agent concentration, leaching time and leaching temperature. The composition and morphology of the residue were determined to prove the competitive leaching results by XRD-SEM. TG results showed that 500 °C was the suitable pyrolysis temperature. XPS analysis demonstrated that pyrolysis can completely remove PVDF. Li and Co were preferentially leached during the competitive leaching while the leaching rates were 90.10% and 93.40% with 50 min leaching at 70 °C. The Al and Cu had weak competitive leachability and the leaching rate was 29.10% and 0.00%. XRD-SEM analysis showed that Li and Co can be fully leached with residual Al and Cu remaining. The results showed that the mixed leaching of electrode materials is feasible based on its excellent selective leaching properties.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38622370

RESUMO

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month. The patients with poor clinical outcomes showed significantly lower EOS count within 8 days after surgery. The time-dependent ROC analysis showed that EOS recovery days predicted 1-month death with an AUC of 0.886 and a cutoff of 6 days. EOS recovery within 6 days was associated with a lower incidence of postoperative infection, a poorer prognosis, and a lower risk of 1-month and 6-month mortality than those requiring more recovery days. Collectively, postoperative early recovery of EOS predicted lower mortality and better prognosis and may be applied as an effective, rapid, and simple tool for the risk stratification and prognostic prediction of patients with TA-AAD.Clinical trial registration number: NCT05409677.

10.
Sensors (Basel) ; 24(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38610271

RESUMO

Detecting transportation pipeline leakage points within chemical plants is difficult due to complex pathways, multi-dimensional survey points, and highly dynamic scenarios. However, hexapod robots' maneuverability and adaptability make it an ideal candidate for conducting surveys across different planes. The path-planning problem of hexapod robots in multi-dimensional environments is a significant challenge, especially when identifying suitable transition points and planning shorter paths to reach survey points while traversing multi-level environments. This study proposes a Particle Swarm Optimization (PSO)-guided Double Deep Q-Network (DDQN) approach, namely, the PSO-guided DDQN (PG-DDQN) algorithm, for solving this problem. The proposed algorithm incorporates the PSO algorithm to supplant the traditional random selection strategy, and the data obtained from this guided approach are subsequently employed to train the DDQN neural network. The multi-dimensional random environment is abstracted into localized maps comprising current and next level planes. Comparative experiments were performed with PG-DDQN, standard DQN, and standard DDQN to evaluate the algorithm's performance by using multiple randomly generated localized maps. After testing each iteration, each algorithm obtained the total reward values and completion times. The results demonstrate that PG-DDQN exhibited faster convergence under an equivalent iteration count. Compared with standard DQN and standard DDQN, reductions in path-planning time of at least 33.94% and 42.60%, respectively, were observed, significantly improving the robot's mobility. Finally, the PG-DDQN algorithm was integrated with sensors onto a hexapod robot, and validation was performed through Gazebo simulations and Experiment. The results show that controlling hexapod robots by applying PG-DDQN provides valuable insights for path planning to reach transportation pipeline leakage points within chemical plants.

11.
Huan Jing Ke Xue ; 45(3): 1468-1479, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471862

RESUMO

Pharmaceuticals and personal care products (PPCPs) are a group of emerging contaminants causing detrimental effects on aquatic living organisms even at low doses. To investigate the contamination characteristics and ecological risks of PPCPs in drains flowing into the Yellow River of Ningxia, 21 PPCPs were detected and analyzed using solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry in this study. All 21 targeted compounds were detected in the drains, with total concentrations ranging from 47.52 to 1 700.96 ng·L-1. Ciprofloxacin, acetaminophen, benzophenone-3, and diethyltoluamide were the more commonly detected compounds, with detection frequencies exceeding 80%. The five highest-concentration PPCPs were acetaminophen, diethyltoluamide, caffeine, benzophenone-3, and levofloxacin, with the maximum concentrations of 597.21, 563.23, 559.00, 477.28, and 473.07 ng·L-1, respectively. Spatial analysis showed that the pollution levels of PPCPs in the drains of the four cities were different, with average concentrations of ∑PPCPs in the order of Yinchuan>Shizuishan>Wuzhong>Zhongwei. The total concentration of PPCPs before flowing into the Yellow River ranged from 124.82 to 1 046.61 ng·L-1. Source analysis showed that livestock and poultry breeding wastewater was the primary source for sulfadiazine and oxytetracycline, whereas medical wastewater was the primary source for levofloxacin and ciprofloxacin. The primary sources of triclocarban and triclosan were domestic sewage and industrial wastewater, whereas the primary source of caffeine and diethyltoluamide was domestic sewage. The pollution of diciofenac, cimetidine, triclocarban, and triclosan in the drains was positively correlated with the regional population and economic development level. The ecological risk assessment indicated that levofloxacin, diclofenac, gemfibrozil, benzophenone-3, and triclocarban posed high risks to aquatic organisms in drains flowing into the Yellow River. It is worthwhile to consider the mixture risk of the PPCPs that exhibited high risk at most sampling sites.


Assuntos
Benzofenonas , Carbanilidas , Cosméticos , Triclosan , Poluentes Químicos da Água , Acetaminofen , Organismos Aquáticos , Cafeína/análise , Ciprofloxacina , Cosméticos/análise , Monitoramento Ambiental/métodos , Levofloxacino/análise , Preparações Farmacêuticas , Medição de Risco , Rios/química , Esgotos/análise , Águas Residuárias , Poluentes Químicos da Água/análise
12.
Int J Biol Macromol ; 266(Pt 2): 131080, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537850

RESUMO

Despite the tremendous efforts on developing antibacterial wearable textile materials containing Ti3C2Tx MXene, the singular antimicrobial mechanism, poor antibacterial durability, and oxidation susceptibility of MXene limits their applications. In this context, flexible multifunctional cellulosic textiles were prepared via layer-by-layer assembly of MXene and the in-situ synthesis of zeolitic imidazolate framework-8 (ZIF-8). Specifically, the introduction of highly conductive MXene enhanced the interface interactions between the ZIF-8 layer and cellulose fibers, endowing the green-based materials with outstanding synergistic photothermal/photodynamic therapy (PTT/PDT) activity and adjustable electromagnetic interference (EMI) shielding performance. In-situ polymerization formed a MXene/ZIF-8 bilayer structure, promoting the generation of reactive oxygen species (ROS) while protecting MXene from oxidation. The as-prepared smart textile exhibited excellent bactericidal efficacy of >99.99 % against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) after 5 min of NIR (300 mW cm-2) irradiation which is below the maximum permissible exposure (MPE) limit. The sustained released Zn2+ from the ZIF-8 layer achieved a bactericidal efficiency of over 99.99 % within 48 h without NIR light. Furthermore, this smart textile also demonstrated remarkable EMI shielding efficiency (47.7 dB). Clearly, this study provides an elaborate strategy for designing and constructing multifunctional cellulose-based materials for a variety of applications.

13.
Meat Sci ; 213: 109504, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555738

RESUMO

This study investigated how lipid metabolism in the longissimus thoracis is influenced by the diet supplemented with grape seed procyanidins (GSPs) in growing-finishing pigs. Forty-eight crossbred pigs were randomly assigned to four groups, each receiving a basal diet, or basal diet added with 150, 200, and 250 mg/kg GSPs. Transcriptomics and metabolomics were employed to explore differential gene and metabolite regulation. The expression of key lipid metabolism-related genes was tested via qRT-PCR, and the lipid and fatty acid composition of the longissimus thoracis were determined. Dietary GSPs at different concentrations upregulated lipoprotein lipase (LPL), which is involved in lipolysis, and significantly increased the mRNA expression levels of carnitine palmitoyltransferase-1B (CPT1B) and cluster of differentiation 36 (CD36), implicated in transmembrane transport of fatty acids. Dietary supplementation of GSPs at 200 or 250 mg/kg markedly reduced total cholesterol and triglyceride content in longissimus thoracis. Dietary GSPs significantly decreased the contents of low-density lipoprotein cholesterol and saturated fatty acids, while increasing unsaturated fatty acids. In conclusion, GSPs may regulate lipid metabolism, reducing cholesterol level, and improving fatty acid composition in the longissimus thoracis of growing-finishing pigs. Our findings provide evidence for the beneficial effects of GSPs as pig feed additives for improving lipid composition.

14.
Antibiotics (Basel) ; 13(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38534697

RESUMO

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

15.
Heliyon ; 10(6): e27678, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533058

RESUMO

Background: Aortic dissection refers to the true and false two-lumen separation of the aortic wall, in which the blood in the aortic lumen enters the aortic mesomembrane from the tear of the aortic intima to separate the mesomembrane and expand along the long axis of the aorta. Purpose: In view of the problems of individual differences, complex complications and many small targets in clinical aortic dissection detection, this paper proposes a convolution neural network MFF-FPN (Multi-scale Feature Fusion based Feature Pyramid Network) for the detection of aortic dissection complications. Methods: The proposed model uses Resnet50 as the backbone for feature extraction and builds a pyramid structure to fuse low-level and high-level feature information. We add an attention mechanism to the backbone network, which can establish inter-dependencies between feature graph channels and enhance the representation quality of CNN. Results: The proposed method has a mean average precision (MAP) of 99.40% in the task of multi object detection for aortic dissection and complications, which is higher than the accuracy of 96.3% on SSD model and 99.05% on YoloV7 model. It greatly improves the accuracy of small target detection such as cysts, making it more suitable for clinical focus detection. Conclusions: The proposed deep learning model achieves feature reuse and focuses on local important information. By adding only a small number of model parameters, we are able to greatly improve the detection accuracy, which is effective in detecting small target lesions commonly found in clinical settings, and also performs well on other medical and natural datasets.

16.
Diabetes Metab Res Rev ; 40(3): e3796, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38529788

RESUMO

AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Criança , Humanos , Adulto Jovem , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/epidemiologia , Estudos Retrospectivos , Estudos Prospectivos , China/epidemiologia , Sistema de Registros
17.
Waste Manag Res ; : 734242X241231393, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500349

RESUMO

Thermal phase separation technology is a new comprehensive treatment technology, which heats oil-based cuttings to a certain temperature to vaporize oil and water components. Based on a large oil-based drilling cuttings comprehensive utilization project, the engineering design and application effect of thermal phase separation technology were analysed. The practice shows that thermal phase separation technology can reduce the oil content of purified residue to 0.1-0.2%, the average recovery rate of base oil is 94.12% and the annual recovery of base oil is about 4800 t; the purified residue does not have corrosive, leaching toxicity and other dangerous characteristics, and can be used for making bricks or building materials. Thermal phase separation technology is a comprehensive utilization and treatment technology with excellent engineering and environmental benefits, which has a high promotion value.

18.
J Appl Biomed ; 22(1): 23-32, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505967

RESUMO

Dictyophora indusiata, commonly known as bamboo fungus, is a type of edible mushroom that is highly popular worldwide for its rich flavor and nutritional value. It is also recognized for its pharmaceutical efficacy, with medicinal benefits attributed to its consumption. One of the most important components of Dictyophora indusiata is polysaccharide, which has been acknowledged as a promising regulator of biological response due to its immunostimulatory and anti-inflammatory properties. However, the specific roles of polysaccharide in modulating the NOD-like receptor protein 3 (NLRP3) inflammasome activation within macrophages remain relatively under-researched. To investigate this further, the mechanism by which Dictyophora indusiata polysaccharide (DIP) exerts its immunostimulatory activity in RAW 264.7 macrophages was analyzed. Results indicated that DIP has the potential to facilitate the priming of NLRP3 inflammasome activation by enhancing TLR4 expression, phosphorylation of IκB-α, and nuclear translocation of NF-κB p65 subunit. It was noted that DIP was unable to mediate the second step of NLRP3 inflammasome activation. The findings of this study provide compelling evidence that DIP has immunomodulatory effects by modulating the NLRP3 inflammasome in RAW264.7 macrophages.


Assuntos
Basidiomycota , Inflamassomos , NF-kappa B , NF-kappa B/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas NLR , Transdução de Sinais , Polissacarídeos/farmacologia
19.
Diabetol Metab Syndr ; 16(1): 71, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515175

RESUMO

BACKGROUND: Regulatory T cells (Tregs) are involved in the maintenance of immune homeostasis and immune regulation. Clinical trials on the adoptive transfer of Tregs have been ongoing for > 10 years. However, many unresolved issues remain in the production of readymade Treg products and selection of patients. Hence, this study aimed to develop a method to expand off-the-shelf Tregs derived from umbilical cord blood (UCB-Tregs) in vitro without changing their phenotype and inhibitory function. In addition, the study intended to design an approach to precisely select patients who are more likely to benefit from the adoptive Treg transfer therapy. METHODS: UCB-Tregs were isolated and cultured in a medium containing human recombinant IL-2 and rapamycin and then multiply restimulated with human T-activator CD3/CD28 dynabeads. The phenotype and suppressive capacity of Tregs were assessed on days 18 and 42. The relationship between the suppressive function of UCB-Tregs in vitro and clinical indicators was analyzed, and the ability of the in vitro suppressive capacity to predict the in vivo therapeutic effects was evaluated. RESULTS: UCB-Tregs expanded 123-fold and 5,981-fold at 18 and 42 days, respectively. The suppressive function of UCB-Tregs on the proliferation of immune cells at 42 days was not significantly different compared with that of UCB-Tregs obtained at 18 days. The suppression rate of UCB-Tregs to PBMCs was negatively correlated with the course of diabetes. Moreover, the high-suppression group exhibited a better treatment response than the low-suppression group during the 12-month follow-up period. CONCLUSIONS: Multiply restimulated UCB-Tregs expanded at a large scale without any alterations in their classical phenotypic features and inhibitory functions. The suppressive function of Tregs in vitro was negatively correlated with the disease duration. The present study revealed the possibility of predicting the in vivo therapeutic effects via the in vitro inhibition assay. Thus, these findings provided a method to obtain off-the-shelf Treg products and facilitated the selection of patients who are likely to respond to the treatment, thereby moving toward the goal of precision treatment.

20.
Am J Cancer Res ; 14(1): 390-402, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323280

RESUMO

ZW10 interacting kinetochore protein (ZWINT), an essential part of the kinetochore complex, plays a crucial role in maintaining genome stability by correcting improper attachments between the kinetochore and microtubules. An initial analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases revealed that ZWINT is significantly expressed across a diverse range of tumor types. We subsequently investigated the influence of ZWINT on clinical outcomes and potential signaling pathways. A multidimensional analysis of ZWINT revealed significant statistical associations between ZWINT expression and clinical outcomes, as well as the E2F1 oncogenic signature. Experimental validation confirmed the increased expression of ZWINT in both pancreatic cancer cell lines and pancreatic adenocarcinoma tissues. Furthermore, our findings indicate that ZWINT promotes the proliferation of PANC-1 cells through cell cycle regulation. This comprehensive analysis of ZWINT suggests a strong correlation between its expression and various types of tumors, especially pancreatic adenocarcinoma (PAAD), indicating its potential oncogenic role. These findings enhance our understanding of the function of ZWINT in carcinogenesis.

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