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1.
Plant Genome ; : e20435, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38348504

RESUMO

The rhomboid-like (RBL) gene encodes serine protease, which plays an important role in the response to cell development and diverse stresses. However, genome-wide identification, expression profiles, and haplotype analysis of the RBL family genes have not been performed in wheat (Triticum aestivum L.). This study investigated the phylogeny and diversity of the RBL family genes in the wheat genome through various approaches, including gene structure analysis, evolutionary relationship analysis, promoter cis-acting element analysis, expression pattern analysis, and haplotype analysis. The 41 TaRBL genes were identified and divided into five subfamilies in the wheat genome. RBL family genes were expanded through segmented duplication and purification selection. The cis-element analysis revealed their involvement in various stress responses and plant development. The results of RNA-seq and quantitative real-time-PCR showed that TaRBL genes displayed higher expression levels in developing spike/grain and were differentially regulated under polyethylene glycol, NaCl, and abscisic acid treatments, indicating their roles in grain development and abiotic stress response. A kompetitive allele-specific PCR molecular marker was developed to confirm the single nucleotide polymorphism of TaRBL14a gene in 263 wheat accessions. We found that the elite haplotype TaRBL14a-Hap2 showed a significantly higher 1000-grain weight than TaRBL14a-Hap11 in at least three environments, and the TaRBL14a-Hap2 was positively selected in wheat breeding. The findings will provide a good insight into the evolutionary and functional characteristics of the TaRBL genes family in wheat and lay the foundation for future exploration of the regulatory mechanisms of TaRBL genes in plant growth and development, as well as their response to abiotic stresses.

2.
BMC Genomics ; 25(1): 32, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177998

RESUMO

BACKGROUND: γ-glutamylcyclotransferase (GGCT), an enzyme to maintain glutathione homeostasis, plays a vital role in the response to plant growth and development as well as the adaptation to various stresses. Although the GGCT gene family analysis has been conducted in Arabidopsis and rice, the family genes have not yet been well identified and analyzed at the genome-wide level in wheat (Triticum aestivum L.). RESULTS: In the present study, 20 TaGGCT genes were identified in the wheat genome and widely distributed on chromosomes 2A, 2B, 2D, 3A, 4A, 5A, 5B, 5D, 6A, 6B, 6D, 7A, 7B, and 7D. Phylogenetic and structural analyses showed that these TaGGCT genes could be classified into three subfamilies: ChaC, GGGACT, and GGCT-PS. They exhibited similar motif compositions and distribution patterns in the same subgroup. Gene duplication analysis suggested that the expansion of TaGGCT family genes was facilitated by segmental duplications and tandem repeats in the wheat evolutionary events. Identification of diverse cis-acting response elements in TaGGCT promoters indicated their potential fundamental roles in response to plant development and abiotic stresses. The analysis of transcriptome data combined with RT-qPCR results revealed that the TaGGCTs genes exhibited ubiquitous expression across plant organs, with highly expressed in roots, stems, and developing grains. Most TaGGCT genes were up-regulated after 6 h under 20% PEG6000 and ABA treatments. Association analysis revealed that two haplotypes of TaGGCT20 gene displayed significantly different Thousand-kernel weight (TKW), Kernel length (KL), and Kernel width (KW) in wheat. The geographical and annual distribution of the two haplotypes of TaGGCT20 gene further revealed that the frequency of the favorable haplotype TaGGCT20-Hap-I was positively selected in the historical breeding process of wheat. CONCLUSION: This study investigated the genome-wide identification, structure, evolution, and expression analysis of TaGGCT genes in wheat. The motifs of TaGGCTs were highly conserved throughout the evolutionary history of wheat. Most TaGGCT genes were highly expressed in roots, stems, and developing grains, and involved in the response to drought stresses. Two haplotypes were developed in the TaGGCT20 gene, where TaGGCT20-Hap-I, as a favorable haplotype, was significantly associated with higher TKW, KL, and KW in wheat, suggesting that the haplotype is used as a function marker for the selection in grain yield in wheat breeding.


Assuntos
Triticum , gama-Glutamilciclotransferase , gama-Glutamilciclotransferase/genética , Filogenia , Melhoramento Vegetal , Regiões Promotoras Genéticas , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Proteínas de Plantas/genética
3.
Zhongguo Zhong Yao Za Zhi ; 48(18): 4981-4992, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802840

RESUMO

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.


Assuntos
Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Terapia Fototérmica , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Peptídeos Catiônicos Antimicrobianos , Imunoterapia/métodos , Linhagem Celular Tumoral , Fototerapia/métodos , Nanopartículas/química
4.
Adv Healthc Mater ; 12(23): e2300524, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37269141

RESUMO

Vaccination immunotherapy has revolutionized cancer treatment modalities. Although the immunomodulatory adjuvant generally employs for potentiating vaccine response, systemic administration may drive immune-related side effects, even immune tolerance. Therefore, tunable immunoadjuvants are highly desirable to simultaneously stimulate the immune response and mitigate systemic toxicity. Self-immolated nanoadjuvants are herein reported to potentiate vaccination immunotherapy of cancer. The nanoadjuvants are engineered by co-assembling an intracellular acidity-ionizable polymeric agonist of toll-like receptor 7/8 resiquimod (R848) and polymeric photosensitizer pyropheophorbide a (PPa). The resultant nanoadjuvants specifically accumulate at the tumor site via passive targeting and are dissociated in the acidic endosome versicles to activate PPa via protonation of the polymer backbone. Upon 671 nm laser irradiation, PPa performed photodynamic therapy to induce immunogenic cell death of tumor cells and subsequently releases R848 in a customized manner, which synergistically activates dendritic cells (DCs), promotes antigen cross-presentation, and eventually recruits cytotoxic T lymphocytes for tumor regression. Furthermore, the synergistic in situ vaccination immunotherapy with immune checkpoint blockade induce sustained immunological memory to suppress tumor recurrence in the rechallenged colorectal tumor model.


Assuntos
Neoplasias Colorretais , Células Dendríticas , Humanos , Células Dendríticas/metabolismo , Imunoterapia , Linfócitos T Citotóxicos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/metabolismo , Adjuvantes Imunológicos , Vacinação
6.
Artigo em Inglês | MEDLINE | ID: mdl-37216250

RESUMO

Sleep apnea (SA) is a common sleep-related breathing disorder that tends to induce a series of complications, such as pediatric intracranial hypertension, psoriasis, and even sudden death. Therefore, early diagnosis and treatment can effectively prevent malignant complications SA incurs. Portable monitoring (PM) is a widely used tool for people to monitor their sleep conditions outside of hospitals. In this study, we focus on SA detection based on single-lead electrocardiogram (ECG) signals which are easily collected by PM. We propose a bottleneck attention based fusion network named BAFNet, which mainly includes five parts of RRI (R-R intervals) stream network, RPA (R-peak amplitudes) stream network, global query generation, feature fusion, and classifier. To learn the feature representation of RRI/RPA segments, fully convolutional networks (FCN) with cross-learning are proposed. Meanwhile, to control the information flow between RRI and RPA networks, a global query generation with bottleneck attention is proposed. To further improve the SA detection performance, a hard sample scheme with k-means clustering is employed. Experiment results show that BAFNet can achieve competitive results, which are superior to the state-of-the-art SA detection methods. It means that BAFNet has great potential to be applied in the home sleep apnea test (HSAT) for sleep condition monitoring. The source code is released at https://github.com/Bettycxh/Bottleneck-Attention-Based-Fusion-Network-for-Sleep-Apnea-Detection.

7.
J Drug Target ; 31(6): 555-568, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37216425

RESUMO

Melanoma is the most aggressive form of skin cancer and there is a need for the development of effective anti-melanoma therapies as it shows high metastatic ability and low response rate. In addition, it has been identified that traditional phototherapy could trigger immunogenic cell death (ICD) to activate antitumor immune response, which could not only effectively arrest primary tumour growth, but also exhibit superior effects in terms of anti-metastasis, anti-recurrence for metastatic melanoma treatment. However, the limited tumour accumulation of photosensitizers/photothermal agents and immunosuppressive tumour microenvironment severely weaken the immune effects. The application of nanotechnology facilitates a higher accumulation of photosensitizers/photothermal agents at the tumour site, which can thus improve the antitumor effects of photo-immunotherapy (PIT). In this review, we summarise the basic principles of nanotechnology-based PIT and highlight novel nanotechnologies that are expected to enhance the antitumor immune response for improved therapeutic efficacy.


Assuntos
Melanoma , Neoplasias , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/terapia , Melanoma/tratamento farmacológico , Fototerapia , Imunoterapia , Nanotecnologia , Microambiente Tumoral , Linhagem Celular Tumoral
8.
RSC Adv ; 13(17): 11450-11456, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37063735

RESUMO

This study introduces a new method for the synthesis of silver nanoparticles on a cotton fabric surface by an in situ method. Reactive hyperbranched polymer (EPDA-HBP) was synthesized using epoxy chloropropane dimethylamine and amino hyperbranched polymer. Then, the fabric was modified with reactive hyperbranched polymer to obtain the amino-grafted fabric. The prepared fiber can complex Ag+ and convert Ag+ to Ag0 through the reducibility of amino acids. EPDA-HBP-grafted cotton fibers and silver nanoparticle-coated fibers were then characterized by FTIR, antibacterial, FE-SEM, EDS, and XPS methods. FE-SEM, EDS, and XPS indicated that Ag NPs were uniformly coated on the cotton fabric. FTIR results confirmed that EPDA-HBP was grafted onto the surface of cotton fiber. When the Ag content was more than 180 mg kg-1, the treated cotton fabric showed above 99.9% bacterial reduction against Escherichia coli and Staphylococcus aureus.

9.
Entropy (Basel) ; 25(3)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36981298

RESUMO

Millimeter-wave (mmWave) communication is considered a promising technology for fifth-generation (5G) wireless communications systems since it can greatly improve system throughput. Unfortunately, because of extremely high frequency, mmWave transmission suffers from the signal blocking problem, which leads to the deterioration of transmission performance. In this paper, we solve this problem by the combination of ultra-dense network (UDN) and user-centric virtual cell architecture. The deployment of dense small base stations (SBSs) in UDN can reduce transmission distance of signals. The user-centric virtual cell architecture mitigates and exploits interference to improve throughput by using coordinated multipoint (CoMP) transmission technology. Nonetheless, the backhaul burden is heavy and interbeam interference still severe. Therefore, we propose a novel iterative backhaul capacity-limited joint user association and power allocation (JUAPA) scheme in ultra-dense mmWave networks under user-centric virtual cell architecture. To mitigate interference and satisfy quality of service (QoS) requirements of users, a nonconvex system throughput optimization problem is formulated. To solve this intractable optimization problem, we divide it into two alternating optimization subproblems, i.e., user association and power allocation. During each iteration, a many-to-many matching algorithm is designed to solve user association. Subsequently, we perform power allocation optimization using a successive convex approximation (SCA) algorithm. The results confirm that the performance of the proposed scheme is close to that of the exhaustive searching scheme, which greatly reduces complexity, and clearly superior to that of traditional schemes in improving system throughput and satisfying QoS requirements.

10.
Small Methods ; 7(5): e2200888, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36446643

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal and resistant to conventional therapies, including chemo-, radio-, and immunotherapy. In this study, it is first determined that a combination of dihydroartemisinin (DHA) and RSL-3 (a glutathione peroxidase 4 (GPX4) inhibitor) markedly induced ferroptosis of PDAC tumor cells. A mechanistic study revealed that DHA can react with iron ions to generate carbon radicals and deplete intracellular glutathione, thereby cumulatively triggering the lipid peroxidation of tumor cells with RSL-3-mediated GPX4 inhibition. A DHA-conjugated amphiphilic copolymer is subsequently synthesized, and intracellular acidity and oxidation dual-responsive DHA nanoparticles are further engineered for the tumor-specific co-delivery of DHA and RSL-3. The resultant nanoparticles (PDBA@RSL-3) efficiently induce ferroptosis of tumor cells in the Panc02 tumor-bearing immune-deficient mouse model, and elicit T-cell-based antitumor immunity in the immune-competent mouse model. The combination of PDBA@RSL-3 nanoparticles and programmed death ligand 1 blockade therapy efficiently inhibits PDAC tumor growth in the immune-competent mouse models. This study may provide novel insights for treatment of PDAC with ferroptosis-based immunotherapy.


Assuntos
Carcinoma Ductal Pancreático , Nanopartículas , Neoplasias Pancreáticas , Camundongos , Animais , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Oxirredução , Neoplasias Pancreáticas
11.
Gels ; 8(12)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36547353

RESUMO

The traditional two-dimensional (2D) cell culture methods have a long history of mimicking in vivo cell growth. However, these methods cannot fully represent physiological conditions, which lack two major indexes of the in vivo environment; one is a three-dimensional 3D cell environment, and the other is mechanical stimulation; therefore, they are incapable of replicating the essential cellular communications between cell to cell, cell to the extracellular matrix, and cellular responses to dynamic mechanical stimulation in a physiological condition of body movement and blood flow. To solve these problems and challenges, 3D cell carriers have been gradually developed to provide a 3D matrix-like structure for cell attachment, proliferation, differentiation, and communication in static and dynamic culture conditions. 3D cell carriers in dynamic culture systems could primarily provide different mechanical stimulations which further mimic the real in vivo microenvironment. In this review, the current advances in 3D dynamic cell culture approaches have been introduced, with their advantages and disadvantages being discussed in comparison to traditional 2D cell culture in static conditions.

12.
Bull Environ Contam Toxicol ; 110(1): 10, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36512068

RESUMO

The nano-zero valence iron (nZVI) via green synthesis for heavy metal remediation has attracted many attentions due to its low-cost, environmental-safety, relative reproductivity, and high stability. However, influence of synthesis conditions on the physiochemical properties of nZVI via green tea extracts and the responding suspensibility, which is required for high reactivity, has not been fully elucidated. In this study, we investigated the zeta potentials, sedimentation and lead (Pb2+) removal capacity of various nZVIs synthesized using green tea extracts. The results showed that the tea extracts extracted at 80oC presented an excellent activity, which contributed to the outstanding suspensibility and reaction activity of nZVI synthesized in a volume ratio of 1:1 (tea extraction versus Fe2+ solution). Thus, the optimized nZVI was successfully prepared with a Pb2+ removal capacity (377.3 mg/g), which was seven times stronger than 50.31 mg/g of traditional chemical synthesized nZVI.


Assuntos
Recuperação e Remediação Ambiental , Poluentes Químicos da Água , Ferro/química , Chá/química , Chumbo , Poluentes Químicos da Água/análise , Adsorção
13.
J Clin Med ; 11(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36362626

RESUMO

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL > 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II > 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II < 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR > 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.

14.
Entropy (Basel) ; 24(9)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36141205

RESUMO

In the context of "double carbon", as a traditional high energy consumption industry, the textile industry is facing the severe challenges of energy saving and emission reduction. To improve production efficiency in the textile industry, we propose the use of content-based image retrieval technology to shorten the fabric production cycle. However, fabric retrieval has high requirements for results, which makes it difficult for common retrieval methods to be directly applied to fabric retrieval. This paper presents a novel method for fabric image retrieval. Firstly, we define a fine-grained similarity to measure the similarity between two fabric images. Then, a convolutional neural network with a compact structure and cross-domain connections is designed to narrow the gap between fabric images and similarities. To overcome the problems of probabilistic missing and difficult training in classical hashing, we introduce a variational network module and structural module into the hashing model, which is called DVSH. We employ list-wise learning to perform similarity embedding. The experimental results demonstrate the superiority and efficiency of the proposed hashing model, DVSH.

15.
Tissue Eng Part C Methods ; 28(11): 610-622, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36127859

RESUMO

Large-scale mammalian cell culture is essential in cell therapy, vaccine production, and the manufacturing of therapeutic protein drugs. Due to the adherent growth characteristic of most mammalian cell types, the combination of cell carrier and bioreactor is a common choice in large-scale mammalian cell culture. Current cell carriers developed by polymer crosslinking, lithography, or emulsion drops are unable to obtain a structure with uniformed porous structure and porous interior design, which results in an inhomogeneous culture condition for cells and therefore cannot ensure an optimal dynamic culture condition for cell proliferation, matrix production, and cell differentiation. In addition, the fluidic shear stress (a standard mechanical stimulation in bioreactor culture) and inner-carrier velocity (to ensure nutrient transport and waste exchange), which influence cell viability and growth, are not well-controlled/analyzed due to an irregular porous structure with these traditionally synthesized cell carriers. To solve these problems, we designed four types of hollow porous spheres (HPS, 1.0 cm diameter) with different porous structures. To investigate the impacts of porous structure on surface shear stress and inner velocity, computational fluid dynamics (CFD) simulations were conducted to analyze the liquid flow behavior in HPSs, based on which an optimal structure with minimal surface shear stress and best inner velocity was obtained and fabricated using fused deposition modeling three-dimensional (3D) printing technology. Inspired by the industrial large-scale culture system, a novel 3D dynamic culture system was then established using HPSs to seed the cells, which were then placed in a mini bioreactor on a tube roller. CFD analysis showed that under 0.1 m/s water flow, the shear stress at most surface areas from four HPSs was lower than 20 dynes/cm2, which suggests that the HPSs should provide protection against physical stress to the cells living on the scaffold surface. A dynamic cell seeding was developed and refined using the 3D culture system, which increased the 32% seeding efficiency of MC3T3 cells compared to the traditional static cell seeding method. The cell proliferation analysis demonstrated that HPSs could speed up cell growth in dynamic cell culture. The HPS with a honeycomb-like structure showed the highest inner pore velocity (CFD analysis) and achieved the fastest cell proliferation and the highest cell viability. Overall, our study, for the first time, developed a 3D printed HPS cell culture device with a uniformed porous structure, which can effectively facilitate cell adhesion and proliferation in the dynamic cultural environment, thereby could be considered an ideal carrier candidate.


Assuntos
Engenharia Tecidual , Tecidos Suporte , Animais , Porosidade , Engenharia Tecidual/métodos , Tecidos Suporte/química , Células Cultivadas , Técnicas de Cultura de Células/métodos , Reatores Biológicos , Impressão Tridimensional , Mamíferos
16.
Sensors (Basel) ; 22(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35808215

RESUMO

The traditional manual defect detection method has low efficiency and is time-consuming and laborious. To address this issue, this paper proposed an automatic detection framework for fabric defect detection, which consists of a hardware system and detection algorithm. For the efficient and high-quality acquisition of fabric images, an image acquisition assembly equipped with three sets of lights sources, eight cameras, and a mirror was developed. The image acquisition speed of the developed device is up to 65 m per minute of fabric. This study treats the problem of fabric defect detection as an object detection task in machine vision. Considering the real-time and precision requirements of detection, we improved some components of CenterNet to achieve efficient fabric defect detection, including the introduction of deformable convolution to adapt to different defect shapes and the introduction of i-FPN to adapt to defects of different sizes. Ablation studies demonstrate the effectiveness of our proposed improvements. The comparative experimental results show that our method achieves a satisfactory balance of accuracy and speed, which demonstrate the superiority of the proposed method. The maximum detection speed of the developed system can reach 37.3 m per minute, which can meet the real-time requirements.


Assuntos
Algoritmos
17.
Theranostics ; 12(7): 3456-3473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547769

RESUMO

Rationale: Scarce tumor mutation burden and neoantigens create tremendous obstacles for an effective immunotherapy of colorectal cancer (CRC). Oncolytic peptides rise as a promising therapeutic approach that boosts tumor-specific immune responses by inducing antigenic substances. However, the clinical application of oncolytic peptides has been hindered because of structural instability, proteolytic degradation, and undesired toxicity when administered systemically. Methods: Based on wasp venom peptide, an optimized stapled oncolytic peptide MP9 was developed with rigid α-helix, protease-resistance, and CRC cell cytotoxicity. By incorporating four functional motifs that include D-peptidomimetic inhibitor of PD-L1, matrix metalloproteinase-2 (MMP-2) cleavable spacer, and MP9 with 4-arm PEG, a novel peptide-polymer conjugate (PEG-MP9-aPDL1) was obtained and identified as the most promising systemic delivery vehicle with PD-L1 targeting specificity and favorable pharmacokinetic properties. Results: We demonstrated that PEG-MP9-aPDL1-driven oncolysis induces a panel of immunogenic cell death (ICD)-relevant damage-associated molecular patterns (DAMPs) both in vitro and in vivo, which are key elements for immunotherapy with PD-L1 inhibitor. Further, PEG-MP9-aPDL1 exhibited prominent immunotherapeutic efficacy in a CRC mouse model characterized by tumor infiltration of CD8+ T cells and induction of cytotoxic lymphocytes (CTLs) in the spleens. Conclusion: Our findings suggest that PEG-MP9-aPDL1 is an all-in-one platform for oncolytic immunotherapy and immune checkpoint blockade (ICB).


Assuntos
Antígeno B7-H1 , Neoplasias Colorretais , Animais , Camundongos , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/terapia , Inibidores de Checkpoint Imunológico , Fatores Imunológicos , Imunoterapia , Metaloproteinase 2 da Matriz , Peptídeos , Polímeros
18.
Sensors (Basel) ; 22(5)2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35270890

RESUMO

Future network services must adapt to the highly dynamic uplink and downlink traffic. To fulfill this requirement, the 3rd Generation Partnership Project (3GPP) proposed dynamic time division duplex (D-TDD) technology in Long Term Evolution (LTE) Release 11. Afterward, the 3GPP RAN#86 meeting clarified that 5G NR needs to support dynamic adjustment of the duplex pattern (transmission direction) in the time domain. Although 5G NR provides a more flexible duplex pattern, how to configure an effective duplex pattern according to services traffic is still an open research area. In this research, we propose a distributed multi-agent deep reinforcement learning (MARL) based decentralized D-TDD configuration method. First, we model a D-TDD configuration problem as a dynamic programming problem. Given the buffer length of all UE, we model the D-TDD configuration policy as a conditional probability distribution. Our goal is to find a D-TDD configuration policy that maximizes the expected discount return of all UE's sum rates. Second, in order to reduce signaling overhead, we design a fully decentralized solution with distributed MARL technology. Each agent in MARL makes decisions only based on local observations. We regard each base station (BS) as an agent, and each agent configures uplink and downlink time slot ratio according to length of intra-BS user (UE) queue buffer. Third, in order to solve the problem of overall system revenue caused by the lack of global information in MARL, we apply leniency control and binary LSTM (BLSTM) based auto-encoder. Leniency controller effectively controls Q-value estimation process in MARL according to Q-value and current network conditions, and auto-encoder makes up for the defect that leniency control cannot handle complex environments and high-dimensional data. Through the parallel distributed training, the global D-TDD policy is obtained. This method deploys the MARL algorithm on the Mobile Edge Computing (MEC) server of each BS and uses the storage and computing capabilities of the server for distributed training. The simulation results show that the proposed distributed MARL converges stably in various environments, and performs better than distributed deep reinforcement algorithm.

19.
Entropy (Basel) ; 24(2)2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-35205594

RESUMO

Energy Harvesting (EH) is a promising paradigm for 5G heterogeneous communication. EH-enabled Device-to-Device (D2D) communication can assist devices in overcoming the disadvantage of limited battery capacity and improving the Energy Efficiency (EE) by performing EH from ambient wireless signals. Although numerous research works have been conducted on EH-based D2D communication scenarios, the feature of EH-based D2D communication underlying Air-to-Ground (A2G) millimeter-Wave (mmWave) networks has not been fully studied. In this paper, we considered a scenario where multiple Unmanned Aerial Vehicles (UAVs) are deployed to provide energy for D2D Users (DUs) and data transmission for Cellular Users (CUs). We aimed to improve the network EE of EH-enabled D2D communications while reducing the time complexity of beam alignment for mmWave-enabled D2D Users (DUs). We considered a scenario where multiple EH-enabled DUs and CUs coexist, sharing the full mmWave frequency band and adopting high-directive beams for transmitting. To improve the network EE, we propose a joint beamwidth selection, power control, and EH time ratio optimization algorithm for DUs based on alternating optimization. We iteratively optimized one of the three variables, fixing the other two. During each iteration, we first used a game-theoretic approach to adjust the beamwidths of DUs to achieve the sub-optimal EE. Then, the problem with regard to power optimization was solved by the Dinkelbach method and Successive Convex Approximation (SCA). Finally, we performed the optimization of the EH time ratio using linear fractional programming to further increase the EE. By performing extensive simulation experiments, we validated the convergence and effectiveness of our algorithm. The results showed that our proposed algorithm outperformed the fixed beamwidth and fixed power strategy and could closely approach the performance of exhaustive search, particle swarm optimization, and the genetic algorithm, but with a much reduced time complexity.

20.
Echocardiography ; 39(2): 278-285, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35066909

RESUMO

AIM: To evaluate the prognostic utility of red blood cell distribution width (RDW) and maximum left ventricular wall thickness (MLVWT) in patients with hypertrophic cardiomyopathy (HCM). PATIENTS AND METHODS: This study is a retrospective cohort analysis. Patients diagnosed with HCM at the First Affiliated Hospital of Sun Yat-sen University from March 2014 to March 2019 were included. HCM patients were stratified into two groups based on the occurrence of major adverse cardiac events (MACE). Receiver operating characteristic (ROC) curves were then constructed and Cox regression models were employed to gauge the prognostic relevance of RDW and MLVWT for HCM patients. Kaplan-Meier analysis evaluated the survival and MACE-free rate in patients with different level of RDW and MLVWT. RESULTS: A total of 300 patients with HCM were enrolled in this study and followed up for 40.56±18.33 months. Among them, 117 MACE (39.00%), 40 all-cause deaths (13.33%), and 29 cardiovascular deaths (9.67%). The level of RDW, MLVWT, creatinine (Cr), and B-type pro-brain natriuretic peptide (NT-ProBNP) were statistically different between the MACE group and non-MACE group (P < .05). Multivariate analysis showed that after adjusting for confounding factors, RDW and MLVWT were independent predictors of all-cause mortality and MACE in HCM patients. ROC showed that RDW > .13 and MLVWT > 23 mm are the cut-off value to predict all-cause mortality and MACE. The area under the ROC curve AUC of the combination predicting the occurrence of all-cause mortality and MACE are .823 and .820, respectively. Kaplan-Meier analysis showed that the survival rate and MACE-free survival rate of group 1 (RDW≦.13 and MLVWT≦23 mm) were significantly higher than group 2 (RDW > .13 or MLVWT > 23 mm), and group 3 (RDW > .13 and MLVWT > 23 mm) (P = .000). CONCLUSION: We determined that increased RDW and MLVWT was independently associated with MACE incidence and risk of mortality in HCM patients. Combined evaluation of RDW and MLVWT yielded a more accurate predictive model of HCM patient outcomes relative to the use of either of these metrics in isolation. Our research can provide a theoretical basis in the occurrence of MACE for the high-risk HCM and intervene them properly and timely.


Assuntos
Cardiomiopatia Hipertrófica , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Índices de Eritrócitos , Eritrócitos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos
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