Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent ...differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.
Regarding the issue of information freshness in systems that aid in data collection using unmanned aerial vehicles (UAVs), a data collection algorithm that is based on freshness and UAV assistance is ...proposed. Under the limitations of wireless sensor node communication distance and UAV parameters, the optimization problem of minimizing the average spatial correlation age of information (SCAoI) of all nodes in the area is set up. This problem is solved by optimizing the number of clusters, UAV flight trajectories, and the order of data collection from cluster member nodes. The maximum communication distance of the nodes is used as the cluster formation radius, and the maximum-minimum distance clustering algorithm is used to cluster the nodes in the region to obtain the minimum number of clusters. After it has been proven that the trajectory optimization problem in this study is NP-hard, the ant colony algorithm is applied to obtain the minimum flight time and the corresponding trajectory. By using the greedy algorithm to determine the member nodes in the sequence of data collection for a cluster, the instantaneous SCAoI of the UAV arriving at the cluster head is solved. Simulation results show that the proposed algorithm in this paper can effectively improve the freshness of data and reduce the average SCAoI of the system compared with the algorithm in the comparative literature, reducing the average SCAoI by about 61%.
Maize leaf disease detection is an essential project in the maize planting stage. This paper proposes the convolutional neural network optimized by a Multi-Activation Function (MAF) module to detect ...maize leaf disease, aiming to increase the accuracy of traditional artificial intelligence methods. Since the disease dataset was insufficient, this paper adopts image pre-processing methods to extend and augment the disease samples. This paper uses transfer learning and warm-up method to accelerate the training. As a result, three kinds of maize diseases, including maculopathy, rust, and blight, could be detected efficiently and accurately. The accuracy of the proposed method in the validation set reached 97.41%. This paper carried out a baseline test to verify the effectiveness of the proposed method. First, three groups of CNNs with the best performance were selected. Then, ablation experiments were conducted on five CNNs. The results indicated that the performances of CNNs have been improved by adding the MAF module. In addition, the combination of Sigmoid, ReLU, and Mish showed the best performance on ResNet50. The accuracy can be improved by 2.33%, proving that the model proposed in this paper can be well applied to agricultural production.
Emerging evidence indicates gut microbes and their products could activate the autonomic nervous system (ANS), which plays important roles in the initiation and maintenance of atrial fibrillation ...(AF). Trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes, is associated with cardiovascular diseases. The present study aimed to investigate the role of TMAO in the progression of AF.
In part 1: TMAO or saline was locally injected into 4 major atrial ganglionated plexi (GP) to clarify its effect on cardiac ANS and AF inducibility in normal canines. In part 2: TMAO or saline was injected into 4 major atrial GP to test its effect on AF progression in a rapid atrial pacing (RAP)-induced AF model.
In part 1: Local injection of TMAO significantly increased anterior right GP (ARGP) function and neural activity, shortened ERP values. In part 2, compared with the control group, 6-hour RAP significantly shortened the ERP, widened the ∑WOV, enhanced the ARGP function and neural activity, increased the NGF and c-fos expression, and up-regulated the inflammatory cytokines. TMAO aggravated all of these changes by activating the proinflammatory p65 NF-κB signaling pathway.
TMAO could increase the instability of atrial electrophysiology in normal canines and aggravate the acute electrical remodeling in a RAP-induced AF model by exacerbating autonomic remodeling. The increased inflammatory cytokines in the GP due to the activation of p65 NF-κB signaling may contribute to these effects.
•Trimethylamine N-oxide (TMAO) facilitate the progression of atrial fibrillation (AF).•The mechanism relies on the activation of cardiac autonomic nervous system (CANS).•Gut microbes may participate in the progression of AF via regulating CANS by TMAO.
Peanuts are one of the most common allergenic foods in the world and can cause severe allergic reactions. Ara h 2 is the most allergenic components of peanut allergens. Although critical amino acids ...at the epitopes were identified, the effect of their physicochemical properties remained unclear. The critical amino acids in epitopes of Ara h 2 (epitope 1: 26ELQGDRRCQSQLER39 and epitope 2: 62RDPYSPSQDPYSPS75). The critical amino acids were substituted by amino acid with different physicochemical properties. Then, the potential allergenicity of those peptides was assessed by IgE binding and cell model. Changing the properties of amino acids by mutation affects potential sensitisation. The charge distribution and molecular weight of critical amino acids in the epitope affected the IgE binding capacity significantly. The conclusion based on peptide might be different from that on whole protein, and our study provided direction of amino acids mutation in desensitisation therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias ...(VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K + Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.
Lithium–sulfur (Li–S) batteries are promising alternatives of conventional Li‐ion batteries attributed to their remarkable energy densities and high sustainability. However, the practical ...applications of Li–S batteries are hindered by the shuttling effect of lithium polysulfides (LiPSs) on cathode and the Li dendrite formation on anode, which together leads to inferior rate capability and cycling stability. Here, an advanced N‐doped carbon microreactors embedded with abundant Co3O4/ZnO heterojunctions (CZO/HNC) are designed as dual‐functional hosts for synergistic optimization of both S cathode and Li metal anode. Electrochemical characterization and theoretical calculations confirm that CZO/HNC exhibits an optimized band structure that effectively facilitates ion diffusion and promotes bidirectional LiPSs conversion. In addition, the lithiophilic nitrogen dopants and Co3O4/ZnO sites together regulate dendrite‐free Li deposition. The S@CZO/HNC cathode exhibits excellent cycling stability at 2 C with only 0.039% capacity fading per cycle over 1400 cycles, and the symmetrical Li@CZO/HNC cell enables stable Li plating/striping behavior for 400 h. Remarkably, Li‐S full cell using CZO/HNC as both cathode and anode hosts shows an impressive cycle life of over 1000 cycles. This work provides an exemplification of designing high‐performance heterojunctions for simultaneous protection of two electrodes, and will inspire the applications of practical Li–S batteries.
An advanced microreactor embedded with Co3O4/ZnO heterojunctions (CZO/HNC) is designed as dual‐functional hosts for synergistic optimization of both S cathode and Li anode. Electrochemical characterization and theoretical calculations confirm that CZO/HNC exhibits an optimized band structure that effectively facilitates ion diffusion and promotes polysulfides conversion. In addition, the lithiophilic nitrogen dopants and Co3O4/ZnO sites together regulate dendrite‐free Li deposition.
Proliferation and migration of vascular smooth muscle cells (VSMCs) play pivotal roles in the development of restenosis after angioplasty and oxidative stress involves both processes. Naringenin, a ...flavanone compound found in citrus fruits, has been widely evaluated for antioxidant activity. This study was designed to explore whether naringenin could inhibit angiotensin II-induced VSMCs proliferation and migration and decrease neointimal hyperplasia in balloon injured rat carotid arteries. VSMCs were treated with or without naringenin before stimulation with 1 µ M angiotensin II and twenty-four rats were subjected to carotid arteries injury and the carotid arteries were harvested at 14 d after balloon injury. The results showed naringenin led to a significant inhibition of angiotensin II-induced VSMCs proliferation and migration. Naringenin significantly attenuated the reactive oxygen species production, increased the superoxide dismutase activity and decreased the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reduced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) and the nuclear translocation of nuclear factor (NF)-κB p65 in angiotensin II-treated VSMCs. Moreover, naringenin decreased the ratio of neointima to media by 63.8% in balloon injured rat carotid arteries, and the serum level of 8-iso-prostaglandin F2α in naringenin-treated rats was significantly decreased. These results indicated naringenin exhibited antioxidant activity on angiotensin II-treated VSMCs and balloon injured rat carotid arteries and could be a potential protective agent for restenosis after angioplasty.
Vagus Nerve Stimulation and Myocardial Ischemia‐Reperfusion Injury
Background
Low‐level vagus nerve stimulation (LL‐VNS) has been demonstrated to protect myocardium against acute ischemia/reperfusion ...(I/R) injury. However, the underlying mechanism of this protective effect remains unknown.
Objective
This study aimed to test the hypothesis that LL‐VNS exerts cardioprotective effect on acute I/R injury in canines via antioxidative stress and antiapoptosis reactions.
Method
Thirty anesthetized mongrel dogs were randomly divided into three groups: I/R group (N = 12, the left anterior descending coronary artery was occluded for 1 hour following by 1 hour reperfusion), LL‐VNS group (N = 9, I/R plus LL‐VNS), and sham group (N = 9, sham surgery without LL‐VNS). The voltage threshold was set at 80% of the voltage required to slow the sinus rate. Infarct size was assessed with Evans Blue and triphenyltetrazolium chloride. Activity assays, TUNEL staining, and western blotting were performed to determine markers of oxidative stress and apoptosis.
Results
LL‐VNS significantly decreased the incidence of ventricular arrhythmias, increased vagal tone, as confirmed by heart rate viability, and reduced infarct size compared with the I/R group. This improvement was associated with a reduction in myocardial neutrophil infiltration, the inhibition of oxidative stress, and the suppression in cardiomyocyte apoptosis. In contrast, the lack of LL‐VNS in the I/R group induced the opposite effect compared with the sham group.
Conclusion
LL‐VNS exerts protective effects on myocardial I/R injury. Its potential mechanisms involve the suppression of oxidative stress and cellular apoptosis.
Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the ...interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity.