RESUMO
Dyslipidemia may induce chronic kidney disease and trigger both ferroptosis and endoplasmic reticulum (ER) stress, but the instigating factors are incompletely understood. We tested the hypothesis that different models of dyslipidemia engage distinct kidney injury mechanisms. Wild-type (WT) or proprotein-convertase subtilisin/kexin type-9 (PCSK9)-gain-of-function (GOF) Ossabaw pigs were fed with a 6-months normal (ND) or high-fat (HFD) diet (n=5-6 each). Renal function and fat deposition were studied in-vivo using CT, and blood and kidney tissue studied ex-vivo for lipid profile, systemic and renal vein free fatty acids (FFA) levels, and renal injury mechanisms including lipid peroxidation (LPO), ferroptosis, and ER stress. Compared with WT-ND pigs, both HFD and PCSK9-GOF elevated triglyceride levels, which were highest in WT-HFD, whereas total and low-density lipoprotein (LDL) cholesterol levels rose only in PCSK9-GOF pigs, particularly in PCSK9-GOF/HFD. The HFD groups had worse kidney function than ND. The WT-HFD kidneys retained more FFA than other groups, but all kidneys developed fibrosis. Furthermore, HFD-induced ferroptosis in WT-HFD indicated by increased free iron, and LPO, and decreased glutathione peroxidase-4 mRNA expression, while PCSK9-GOF induced ER stress with upregulated GRP94 and CHOP protein expression. In vitro, PK1 cells treated with palmitic acid (PA) and oxidized-LDL to mimic HFD and PCSK9-GOF showed similar trends to those observed in vivo. Taken together, HFD-induced hypertriglyceridemia promotes renal FFA retention and ferroptosis, whereas PCSK9-GOF-induced hypercholesterolemia elicits ER stress, both resulting in renal fibrosis. These observations suggest different targets for preventing and treating renal fibrosis in subjects with specific types of dyslipidemia.
RESUMO
Numerical models of electromyography (EMG) signals have provided a huge contribution to our fundamental understanding of human neurophysiology and remain a central pillar of motor neuroscience and the development of human-machine interfaces. However, while modern biophysical simulations based on finite element methods (FEMs) are highly accurate, they are extremely computationally expensive and thus are generally limited to modeling static systems such as isometrically contracting limbs. As a solution to this problem, we propose to use a conditional generative model to mimic the output of an advanced numerical model. To this end, we present BioMime, a conditional generative neural network trained adversarially to generate motor unit (MU) activation potential waveforms under a wide variety of volume conductor parameters. We demonstrate the ability of such a model to predictively interpolate between a much smaller number of numerical model's outputs with a high accuracy. Consequently, the computational load is dramatically reduced, which allows the rapid simulation of EMG signals during truly dynamic and naturalistic movements.
RESUMO
Objective.Brain switches provide a tangible solution to asynchronized brain-computer interface, which decodes user intention without a pre-programmed structure. However, most brain switches based on electroencephalography signals have high false positive rates (FPRs), resulting in less practicality. This research aims to improve the operating mode and usability of the brain switch.Approach.Here, we propose a novel virtual physical model-based brain switch that leverages periodic active modulation. An optimization problem of minimizing the triggering time subject to a required FPR is formulated, numerical and analytical approximate solutions are obtained based on the model.Main results.Our motor imagery (MI)-based brain switch can reach 0.8FP/h FPR with a median triggering time of 58 s. We evaluated the proposed brain switch during online device control, and their average FPRs substantially outperformed the conventional brain switches in the literature. We further improved the proposed brain switch with the Common Spatial Pattern (CSP) and optimization method. An average FPR of 0.3 FPs/h was obtained for the MI-CSP-based brain switch, and the average triggering time improved to 21.6 s.Significance.This study provides a new approach that could significantly reduce the brain switch's FPR to less than 1 Fps/h, which was less than 10% of the FPR (decreasing by more than a magnitude of order) by other endogenous methods, and the reaction time was comparable to the state-of-the-art approaches. This represents a significant advancement over the current non-invasive asynchronous BCI and will open widespread avenues for translating BCI towards clinical applications.
Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Imaginação , Humanos , Imaginação/fisiologia , Eletroencefalografia/métodos , Encéfalo/fisiologia , Modelos Neurológicos , Movimento/fisiologiaRESUMO
Neuromechanical studies investigate how the nervous system interacts with the musculoskeletal (MSK) system to generate volitional movements. Such studies have been supported by simulation models that provide insights into variables that cannot be measured experimentally and allow a large number of conditions to be tested before the experimental analysis. However, current simulation models of electromyography (EMG), a core physiological signal in neuromechanical analyses, remain either limited in accuracy and conditions or are computationally heavy to apply. Here, we provide a computational platform to enable future work to overcome these limitations by presenting NeuroMotion, an open-source simulator that can modularly test a variety of approaches to the full-spectrum synthesis of EMG signals during voluntary movements. We demonstrate NeuroMotion using three sample modules. The first module is an upper-limb MSK model with OpenSim API to estimate the muscle fibre lengths and muscle activations during movements. The second module is BioMime, a deep neural network-based EMG generator that receives nonstationary physiological parameter inputs, like the afore-estimated muscle fibre lengths, and efficiently outputs motor unit action potentials (MUAPs). The third module is a motor unit pool model that transforms the muscle activations into discharge timings of motor units. The discharge timings are convolved with the output of BioMime to simulate EMG signals during the movement. We first show how MUAP waveforms change during different levels of physiological parameter variations and different movements. We then show that the synthetic EMG signals during two-degree-of-freedom hand and wrist movements can be used to augment experimental data for regressing joint angles. Ridge regressors trained on the synthetic dataset were directly used to predict joint angles from experimental data. In this way, NeuroMotion was able to generate full-spectrum EMG for the first use-case of human forearm electrophysiology during voluntary hand, wrist, and forearm movements. All intermediate variables are available, which allows the user to study cause-effect relationships in the complex neuromechanical system, fast iterate algorithms before collecting experimental data, and validate algorithms that estimate non-measurable parameters in experiments. We expect this modular platform will enable validation of generative EMG models, complement experimental approaches and empower neuromechanical research.
Assuntos
Biologia Computacional , Eletromiografia , Movimento , Músculo Esquelético , Eletromiografia/métodos , Humanos , Movimento/fisiologia , Músculo Esquelético/fisiologia , Redes Neurais de Computação , Fenômenos Biomecânicos/fisiologia , Simulação por Computador , Potenciais de Ação/fisiologia , Modelos NeurológicosRESUMO
Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.
Assuntos
Tecido Adiposo , Diferenciação Celular , Epigênese Genética , Células-Tronco Mesenquimais , Mitocôndrias , Obesidade , Humanos , Células-Tronco Mesenquimais/metabolismo , Obesidade/metabolismo , Obesidade/genética , Obesidade/patologia , Mitocôndrias/metabolismo , Tecido Adiposo/metabolismo , Diferenciação Celular/genética , Feminino , Masculino , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Adulto , Pessoa de Meia-Idade , Proliferação de CélulasRESUMO
In recent years, the rotational Doppler effect (RDE) has been widely used in rotational motion measurement. However, the performance of existing detection systems based on the RDE are generally limited by the drastic reduction of signal-to-noise ratio (SNR) due to the influence of atmospheric turbulence, partial obscuration of the vortex beam (VB) during propagation, and misalignment between the optical axis of VB and the rotational axis of the object, which poses a challenge for practical applications. In this paper, we proposed a coherent detection method of the RDE measurement based on triple Fourier transform. First, the weak RDE signal in backscattered light is amplified by using the balanced homodyne detection method, and the amplified signal still retains the same characteristic of severe broadening in the frequency domain as the original signal. Furthermore, we proposed the triple Fourier transform to extract the broadened RDE frequency shift signal after the coherent amplification. The proposed method significantly improves the SNR of RDE measurement and facilitates the accurate extraction of rotational speed, which helps to further improve the RDE detection range and promote its practical application.
RESUMO
The aim of this study was to explore the dynamic changes in the physicochemical properties of Laiyang pear residue polysaccharide (LPP) during in vitro digestion, as well as its protective effect on the intestines. Monosaccharide composition and molecular weight analysis showed that there was no significant change in LPP during the oral digestion stage. However, during the gastric and intestinal digestion stages, the glycosidic bonds of LPP were broken, leading to the dissociation of large molecular aggregates and a significant increase in reducing sugar content (CR) accompanied by a decrease in molecular weight. In addition, LPP exerted the intestinal protective ability via inhibiting gut inflammation, improving intestinal barrier, and regulating intestinal flora in DSS-induced mice. Specifically, LPP mitigated DSS-induced intestinal pathological damage of mice via enhancing intestinal barrier integrity and upregulating expressions of TJ proteins, and suppressed inflammation by inhibiting NF-κB signaling axis. Furthermore, LPP decreased the ratio of Firmicutes/Bacteroidetes, increased the relative abundance of Lactobacillus, and altered the diversity and the composition of gut microbiota in DSS-induced mice. Therefore, LPP had the potential to be a functional food that improved gut microbiota environment to enhance health and prevent diseases, such as a prebiotic.
Assuntos
Sulfato de Dextrana , Microbioma Gastrointestinal , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Camundongos , Sulfato de Dextrana/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Pyrus/química , Inflamação/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Digestão/efeitos dos fármacos , Masculino , NF-kappa B/metabolismoRESUMO
IL-36 is known to mediate inflammation and fibrosis. Nevertheless, IL-36 signalling axis has also been implicated in cancer, although understanding of exact contribution of IL-36 to cancer progression is very limited, partly due to existence of multiple IL-36 ligands with agonistic and antagonistic function. Here we explored the role of IL-36 in oral squamous cell carcinoma (OSCC). Firstly, we analyzed expression of IL-36 ligands and receptor and found that the expression of IL-36γ was significantly higher in head and neck cancer (HNSCC) than that of normal tissues, and that the high expression of IL-36γ predicted poor clinical outcomes. Secondly, we investigated the direct effect of IL-36γ on OSCC cells and found that IL-36γ stimulated proliferation of OSCC cells with high expression of IL-36R expression. Interestingly, IL-36γ also promoted migration of OSCC cells with low to high IL-36R expression. Critically, both proliferation and migration of OSCC cells induced by IL-36γ were abrogated by anti-IL-36R mAb. Fittingly, RNA sequence analysis revealed that IL-36γ regulated genes involved in cell cycle and cell division. In summary, our results showed that IL-36γ can be a tumor-promoting factor, and targeting of IL-36R signalling may be a beneficial targeted therapy for patients with abnormal IL-36 signalling.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Interleucina-1/metabolismo , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proliferação de Células , Linhagem Celular TumoralRESUMO
Three Parallel Rivers is one of the world's biodiversity hotspots. However, the research on myxomycetes diversity is scarce in this area. Random sampling was used to investigate myxomycetes' diversity and distribution characteristics in this area. One hundred and seventeen species, including three varieties, were obtained, belonging to 28 genera, nine families, and six orders, with Arcyria cinerea and Physarum viride being the dominant species. Moreover, four species and one variety were first reported in China. Twenty-six species and one variety were first reported in Yunnan Province. The species' most commonly utilized substrate for fruiting bodies was decaying wood, and Cribraria was the dominant genus. The species diversity was most abundant in mixed broadleaf-conifer forests. Species similarity between coniferous and broad-leaved forests was much higher than the pairwise comparison of other forest types. NMDS analysis shows that substrate and forest types had insignificant effects on myxomycetes communities, while river valley had a significant effect. The myxomycetes community similarity between river valleys is unrelated to geographical proximity.
Assuntos
Mixomicetos , Traqueófitas , Humanos , Rios , China , Florestas , Biodiversidade , ÁrvoresRESUMO
Renal artery stenosis (RAS) is a major cause of ischemic kidney disease, which is largely mediated by inflammation. Mapping the immune cell composition in ischemic kidneys might provide useful insight into the disease pathogenesis and uncover therapeutic targets. We used mass cytometry (CyTOF) to explore the single-cell composition in a unique data set of human kidneys nephrectomized due to chronic occlusive vascular disease (RAS, n = 3), relatively healthy donor kidneys (n = 6), and unaffected sections of kidneys with renal cell carcinoma (RCC, n = 3). Renal fibrosis and certain macrophage populations were also evaluated in renal sections. Cytobank analysis showed in RAS kidneys decreased cell populations expressing epithelial markers (CD45-/CD13+) and increased CD45+ inflammatory cells, whereas scattered tubular-progenitor-like cells (CD45-/CD133+/CD24+) increased compared with kidney donors. Macrophages switched to proinflammatory phenotypes in RAS, and the numbers of IL-10-producing dendritic cells (DC) were also lower. Compared with kidney donors, RAS kidneys had decreased overall DC populations but increased plasmacytoid DC. Furthermore, senescent active T cells (CD45+/CD28+/CD57+), aged neutrophils (CD45+/CD15+/CD24+/CD11c+), and regulatory B cells (CD45+/CD14-/CD24+/CD44+) were increased in RAS. RCC kidneys showed a distribution of cell phenotypes comparable with RAS but less pronounced, accompanied by an increase in CD34+, CD370+, CD103+, and CD11c+/CD103+ cells. Histologically, RAS kidneys showed significantly increased fibrosis and decreased CD163+/CD141+ cells. The single-cell platform CyTOF enables the detection of significant changes in renal cells, especially in subsets of immune cells in ischemic human kidneys. Endogenous pro-repair cell types in RAS warrant future study for potential immune therapy.NEW & NOTEWORTHY The single-cell platform mass cytometry (CyTOF) enables detection of significant changes in one million of renal cells, especially in subsets of immune cells in ischemic human kidneys distal to renal artery stenosis (RAS). We found that pro-repair cell types such as scattered tubular-progenitor-like cells, aged neutrophils, and regulatory B cells show a compensatory increase in RAS. Immune cell phenotype changes may reflect ongoing inflammation and impaired immune defense capability in the kidneys.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Obstrução da Artéria Renal , Humanos , Idoso , Carcinoma de Células Renais/patologia , Obstrução da Artéria Renal/patologia , Artéria Renal , Rim/patologia , Isquemia/patologia , Fenótipo , Inflamação/patologia , Neoplasias Renais/patologiaRESUMO
Vortex beams (VBs) with orbital angular momentum have shown great potential in the detection of transverse rotational motion of spatial targets which is undetectable in the classical radar scheme. However, most of the reported rotational Doppler measurements based on VBs can only be realized under ideal experimental conditions. The long-range detection is still a challenge. The detection distance based on rotational Doppler effect (RDE) is mainly limited by the scattered signal's signal-to-noise ratio (SNR). In this work, we investigated the influence of multi-ring vortex beams (MVBs) on the rotational Doppler frequency spectrum of scattered light from an object based on RDE and proposed a method of SNR enhancement of RDE signal. Firstly, different types of MVBs composed of a set of single-ring VBs with the same topological charge and different radii are designed, including multi-ring Laguerre Gaussian beam (MLGB), multi-ring perfect vortex beams (MPVB), and high-order Laguerre Gaussian beam (HLGB). Then, the influence of the number of rings and radial radius interval on the intensity profiles of MVBs and rotational Doppler frequency spectra under aligned and misaligned conditions is studied in detail. And the reasons why different types of MVBs lead to different SNR enhancement effectiveness with the increase of rings are also analyzed theoretically. Finally, proof-of-concept experiments were conducted to verify the effectiveness of the SNR enhancement method for RDE signals. The results showed that the amplitudes of the Doppler spectra generated by the MLGB and MPVB are improved substantially with the increase of rings, but the enhancement effect caused by the former is superior to the latter. The gain of HLGB on the RDE signal is the lowest. This study provides a useful reference for the optimization of rotational Doppler detection systems and may be of great application value in telemetry, long-range communication and optical imaging.
RESUMO
The rotational Doppler effect of the vortex beam is a recently emerged promising application of the optical vortex with orbital angular momentum. In this paper, we combine the method of the micro-Doppler effect of the traditional radar and the rotational Doppler effect of the vortex beam and propose an approach of rotational micro-Doppler effect, realizing the simultaneous measurement of spin and precession. We firstly analyze the rotational micro-Doppler characteristic introduced by precession under the illuminating of vortex beam and calculate the rotational micro-Doppler parameters related to the spin and precession. Then we conduct an experiment of using the vortex beam to detect a spinning object with precession and the rotational micro-Doppler frequency is successfully observed. By extracting the rotational micro-Doppler parameters, the simultaneous and independent measurement of spin and precession is realized. Both the theoretical analysis and experimental results indicate that the rotational micro-Doppler effect is an effective extension of the rotational Doppler effect and is also a feasible application of the vortex beam detection.
RESUMO
The typical semi conductivity and few active sites of hydrogen evolution of 2H MoSe2 severely restrict its electrocatalytic hydrogen evolution performance. At the same time, the 1T MoSe2 has metal conductivity and plentiful hydrogen evolution sites, making it feasible to optimize the electrocatalytic hydrogen evolution behavior of MoSe2 using phase engineering. In this study, we, through a simple one-step hydrothermal method, composed 1T/2H MoSe2, and then used newly emerging transition metal carbides with several atomic-layer thicknesses Ti3C2Tx to improve the conductivity of a MoSe2-based electrocatalyst. Finally, MoSe2@Ti3C2Tx was successfully synthesized, according to the control of the additional amount of Ti3C2Tx, to form a proper MoSe2/ Ti3C2Tx heterostructure with a better electrochemical HER performance. As obtained MoSe2@4 mg-Ti3C2Tx achieved a low overpotential, a small Tafel slope and this work offers additional insight into broadened MoSe2 and MXenes-based catalyst's electrochemical application.
RESUMO
High-fat diets (HFD) could cause obesity, trigger lipid accumulation, and induce oxidative stress and inflammation, leading to kidney damage. This study aimed to elucidate the protective effects of nuciferine on HFD-caused nephrotoxicity and explore the underlying mechanisms in Kunming mice and palmitic acid-exposed HK-2 cells. In obese mice, nuciferine notably alleviated HFD-induced chronic renal dysfunction and delayed renal fibrosis progression and podocyte apoptosis, as evidenced by the increased expressions of renal function factors BUN, CRE, and UA and the decreased expressions of key protein factors TGF-ß1, p-Samd3, Wnt-1, and ß-catenin. Nuciferine also effectively attenuated HFD-induced renal lipid accumulation via the AMPK-mediated regulation of FAS and HSL expressions and suppressed inflammation and oxidative stress via the AMPK-mediated Nrf-2/HO-1 and TLR4/MyD88/NF-κB pathways. In addition, consistent with the results of animal experiments, nuciferine remarkably reversed cell damage and attenuated lipid accumulation, inflammation, and oxidative stress in palmitic acid-exposed HK-2 cells through the AMPK-mediated signaling pathway. Therefore, nuciferine could be a new food-derived protective agent to offset obesity and correlative kidney damage.
Assuntos
Proteínas Quinases Ativadas por AMP , Antioxidantes , Camundongos , Animais , Antioxidantes/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Ácido Palmítico/efeitos adversos , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , NF-kappa B/genética , NF-kappa B/metabolismo , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/complicações , Estresse Oxidativo , Dieta Hiperlipídica/efeitos adversosRESUMO
Introduction: Diquat poisoning leads to kidney injury, hepatotoxicity, rhabdomyolysis, gastrointestinal hemorrhage, and respiratory failure. Diquat has high mortality and no specific antidote. The pathology of acute kidney injury caused by diquat poisoning has been mainly investigated in animal studies and autopsies, and typically shows renal tubular necrosis. To our knowledge, antemortem renal biopsy has not been reported in humans.Case reports: Two males and one female presented following deliberate diquat self-poisoning. Their main clinical manifestations were abdominal pain, nausea, and emesis. All developed acute kidney injury. Kidney biopsy was performed in two cases which showed acute tubular necrosis with renal interstitial edema and multifocal inflammatory cell infiltration. Treatments given included gastric lavage, catharsis, early hemoperfusion combined with continuous kidney replacement therapy or hemodialysis, administration of glucocorticoids, and antioxidant therapy. All patients survived.Discussion: Despite potentially lethal ingestions three patients survived oral diquat poisoning with intensive supportive care. No clear relationship can be made between any of the therapies given and patient outcome.Conclusions: Kidney biopsy in these patients confirmed proximal renal tubular injury was the major pathological finding although interstitial injury was also present. The role of therapies that address renal pathology requires further study.
Assuntos
Injúria Renal Aguda , Intoxicação , Masculino , Animais , Humanos , Feminino , Diquat , Rim , Diálise Renal , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Necrose , Intoxicação/terapiaRESUMO
Steady-state visual evoked potential (SSVEP) based brain-computer interfaces (BCIs) have achieved an information transfer rate (ITR) of over 300 bits/min, but abundant training data is required. The performance of SSVEP algorithms deteriorates greatly under limited data, and the existing time-shift data augmentation method fails to improve it because the phase-locked requirement between training samples is violated. To address this issue, this study proposes a novel augmentation method, namely phase-locked time-shift (PLTS), for SSVEP-BCI. The similarity between epochs at different time moments was evaluated, and a unique time-shift step was calculated for each class to augment additional data epochs in each trial. The results showed that the PLTS significantly improved the classification performance of SSVEP algorithms on the BETA SSVEP datasets. Moreover, under the condition of one calibration block, by slightly prolonging the calibration duration (from 48 s to 51.5 s), the ITR increased from 40.88±4.54 bits/min to 122.61±7.05 bits/min with the PLTS. This study provides a new perspective on augmenting data epochs for training-based SSVEP-BCI, promotes the classification accuracy and ITR under limited training data, and thus facilitates the real-life applications of SSVEP-based brain spellers.
Assuntos
Interfaces Cérebro-Computador , Humanos , Potenciais Evocados Visuais , Eletroencefalografia/métodos , Estimulação Luminosa , Encéfalo/fisiologia , AlgoritmosRESUMO
The optical vortex (OV) carries unique orbital angular momentum (OAM) and experiences a Doppler frequency shift when backscattered from a spinning object. This rotational Doppler effect (RDE) has provided a solution for the non-contact detection of rotating motion. The reported RDE researches mainly use a single OV that generates frequency shifts proportional to its topological charge and has low robustness to light incidence. Here, we show the distinctive RDE of superimposed optical vortex array (SOVA). We analyze the holistic OAM of SOVA which is represented in terms of a superposition of azimuthal harmonics and displays a unique modal gathering effect. In the experiment of RDE, the frequency shift signals of SOVA show a precise mapping to the OAM modes and the modal gathering effect contributes to enhance the amplitude of signals, which has the potential to enhance robustness against non-coaxial incidence. This finding provides a new aspect of RDE and a pioneered example for introducing various SOVAs into rotation detection.
RESUMO
Introduction: Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) are paracrine vectors with therapeutic functions comparable to their parent cells. However, it remains unclear if donor obesity affects their therapeutic functions. We tested the hypothesis that the curative effect of human adipose tissue-derived MSC-EVs (A-MSC-EVs) is blunted by obesity. Methods: MSC-EVs were isolated by ultracentrifugation from mesenchymal stem/stromal cells (MSCs) collected from abdominal subcutaneous fat of obese and lean human subjects (obese and lean-MSC-EVs, respectively) and injected into the aorta of mice 2 weeks after renal artery stenosis (RAS) induction. Magnetic resonance imaging studies were conducted 2 weeks after MSC-EVs delivery to determine renal function. The effect of MSC-EVs on tissue injury was assessed by histology and gene expression of inflammatory factors, including interleukin (IL)-1ß, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α). Oxidative damage, macrophage infiltration, plasma renin, and hypoxia inducible factor-1α (HIF-1α) were also assessed. Results: Tracking showed that MSC-EVs localized in the kidney tissue, including glomeruli and tubules. All MSC-EVs decreased systolic blood pressure (SBP) and plasma renin and improved the poststenotic kidney (STK) volume, but obese-MSC-EVs were less effective than lean-MSC-EVs in improving medullary hypoxia, fibrosis, and tubular injury. Lean-MSC-EVs decreased inflammation, whereas obesity attenuated this effect. Only lean-MSC-EVs decreased STK cortical HIF-1α expression. Conclusion: Obesity attenuates the antihypoxia, antifibrosis, antiinflammation, and tubular repair functions of human MSC-EVs in chronic ischemic kidney disease. These observations may have implications for the self-repair potency of obese subjects and for the use of autologous MSC-EVs in regenerative medicine.
RESUMO
BACKGROUND: Several interleukin (IL)-17 inhibitors have been approved for the treatment of moderate-to-severe plaque psoriasis (PsO). There is still scope for the development of affordable treatments for PsO. OBJECTIVES: To assess, in a phase Ia study, the safety, tolerability and pharmacokinetics (PK) of HB0017, a humanized monoclonal antibody that targets IL-17A, in healthy participants and patients with moderate-to-severe plaque PsO; and, in a phase Ib study, to assess the efficacy of HB0017 in patients with moderate-to-severe plaque PsO. METHODS: The phase Ia study (NCT04505033) was a randomized double-blind placebo-controlled dose-escalation study in healthy participants. Each cohort of 10 volunteers was randomly assigned to receive either a single dose of HB0017 (50â mg, 150â mg, 300â mg or 450â mg) or the matching placebo at a ratio of 4 : 1. The phase Ib study (NCT05442788) was a randomized double-blind placebo-controlled dose-escalation study in enrolled patients with moderate-to-severe plaque PsO. Each cohort of 10 patients was randomly assigned to receive either multiple doses of HB0017 (150â mg, 300â mg or 450â mg) or the matching placebo at a ratio of 4 : 1. RESULTS: HB0017 demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. In the phase Ia and Ib studies, participants in both the HB0017 and placebo groups experienced treatment-emergent adverse events (69% vs. 87%, 96% vs. 100%, respectively). HB0017 demonstrated clinically meaningful effects in patients with moderate-to-severe plaque PsO. PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and static Physician Global Assessment (sPGA) 0/1 (i.e. 'clear' or 'almost clear') responses were 100% for the HB0017 300-mg group, with maximal improvements (100% or near 100% reductions from baseline) in PASI score observed at week 12, while the duration of effect was evident up to week 20. There was no clinical response in any participant in the placebo group in the phase Ib study. CONCLUSIONS: Overall, HB0017 showed acceptable safety and tolerability in both healthy participants and patients with moderate-to-severe plaque PsO. An encouraging signal of efficacy with a longer half-life provides HB0017 with the potential to be added to the currently available range of biologics targeting IL-17A.