Adipose-derived stem cells (ASCs) secrete many cytokines, proteins, growth factors, and extracellular vesicles with beneficial outcomes that can be used in regenerative medicine. It has great potential, and the development of new treatment strategies using the ASCs secretome is of global interest. Besides cytokines, proteins, and growth factors, the therapeutic effect of secretome is hidden in non-coding RNAs such as miR-21, miR-24, and miR-26 carried via exosomes secreted by adequate cells. The whole secretome, including ASC-derived exosomes (ASC-exos) has been proven in many studies to have immunomodulatory, proangiogenic, neurotrophic, and epithelization activity and can potentially be used for neurodegenerative, cardiovascular, respiratory, inflammatory, and autoimmune diseases as well as wound healing treatment. Due to limitations in the use of stem cells in cell-based therapy, its secretome with emphasis on exosomes seems to be a reasonable and safer alternative with increased effectiveness and fewer side effects. Moreover, the great advantage of cell-free therapy is the possibility of biobanking the ASCs secretome. In this review, we focus on the current state of knowledge on the use of the ASCs secretome in stem cell-free therapy. Full article

A deep-learning architecture, dubbed as the 2D-ADMM-Net (2D-ADN), is proposed in this article. It provides effective high-resolution 2D inverse synthetic aperture radar (ISAR) imaging under scenarios of low SNRs and incomplete data, by combining model-based sparse reconstruction and data-driven deep learning. Firstly, mapping from ISAR images to their corresponding echoes in the wavenumber domain is derived. Then, a 2D alternating direction method of multipliers (ADMM) is unrolled and generalized to a deep network, where all adjustable parameters in the reconstruction layers, nonlinear transform layers, and multiplier update layers are learned by an end-to-end training through back-propagation. Since the optimal parameters of each layer are learned separately, 2D-ADN exhibits more representation flexibility and preferable reconstruction performance than model-driven methods. Simultaneously, it is able to better facilitate ISAR imaging with limited training samples than data-driven methods owing to its simple structure and small number of adjustable parameters. Additionally, benefiting from the good performance of 2D-ADN, a random phase error estimation method is proposed, through which well-focused imaging can be acquired. It is demonstrated by experiments that although trained by only a few simulated images, the 2D-ADN shows good adaptability to measured data and favorable imaging results with a clear background can be obtained in a short time. Full article

Background and Objectives—Direct current cardioversion (DCCV) is a safe and useful treatment for atrial tachyarrhythmias. In the past, the energy delivered in DCCV was decided upon empirically, based only on the type of tachyarrhythmia. This conventional method does not consider individual factors and may lead to unnecessary electrical damage. Materials and Methods—We performed DCCV in patients with atrial tachyarrhythmias. The impedance and electrical current at the moment of shock were measured. The human thoracic impedance between both defibrillator patches and the electric current that was used were measured. Results—A total of 683 DCCVs were performed on 466 atrial tachyarrhythmia patients. The average impedance was 64 ± 11 Ω and the average successful current was 23 ± 6 mA. The magnitude of the electrical current that was successful depended upon the human impedance (linear regression, B = −0.266, p < 0.001) and the left atrial diameter (B = 0.092, p < 0.001). Impedance was directly proportional to body mass index (BMI) (B = 1.598, p < 0.001) and was higher in females than in males (77 ± 15 Ω vs. 63 ± 11 Ω, p < 0.001). Notably, the high-impedance (>70 Ω) group had a higher BMI (27 ± 4 kg/m² vs. 25 ± 3 kg/m², p < 0.001) and a higher proportion of females (37% vs. 9%, p < 0.001) than the low-impedance group (<70 Ω). However, thoracic impedance was not an independent predictor for successful DCCV. Conclusions—Human thoracic impedance was one of the factors that impacted the level of electrical current required for successful DCCV in patients with atrial arrhythmias. In the future, it will be helpful to consider individual predictors, such as BMI and gender, to minimize electrical damage during DCCV. Full article

Sildenafil citrate, a widely-used oral therapy for erectile dysfunction, is a cytochrome P3A4 (CYP3A4) enzyme substrate. Studies have reported that this substrate has an inhibitory effect on CYP3A4 enzymes in long-term cigarette and cannabis smokers, which predominantly mediate the hepatic elimination of sildenafil. Cigarette and/or cannabis smoking could therefore alter the exposure of sildenafil. The aim of this study was to examine the effect of smoking cigarettes and/or cannabis on the pharmacokinetics, pharmacodynamics, safety and tolerability of sildenafil. Thirty-six healthy human subjects were equally divided into three groups: non-smokers, cigarette smokers and cannabis smokers. Each group was administered a single dose of sildenafil (50 mg tablets). The primary outcome measures included the maximum concentration of sildenafil in plasma (C_max), the elimination half-life (t1/2) and the area under the plasma concentration time curve from zero to time (AUC_0–t). The pharmacodynamics were assessed by the International Index of Erectile Function (IIEF-5). The exposure of sildenafil (AUC_0–t) showed a statistically significant increase in cigarette smokers (1156 ± 542 ng·h/mL) of 61% (p < 0.05) while in cannabis smokers (967 ± 262 ng·h/mL), a non-significant increase in AUC_0–t of 35% (p > 0.05) was observed relative to non-smokers (717 ± 311 ng·h/mL). Moreover, the C_max of sildenafil increased by 63% (p < 0.05) and 22% (p > 0.05) in cigarette smokers and cannabis smokers, respectively. Cigarette smoking increases the exposure of sildenafil to a statistically significant level with no effect on its pharmacodynamics, safety and tolerability. Full article

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases. Full article

This meta-analysis was conducted to assess the efficacy and adverse events associated with S-1 chemotherapy combined with radiotherapy for patients with head and neck cancer. The PubMed, Embase, and Cochrane Library databases were searched up to 10 February 2021. Eligible studies included clinical trials using S-1 chemotherapy combined with radiotherapy for head and neck cancer patients that measured tumor response, local control rate, overall survival, and grade 3/4 adverse events. A meta-analysis was performed using a random effects model. Twelve trials involving 378 patients met the selection criteria. The objective response and clinical benefit rate (complete/partial response and stable disease) of S-1 chemotherapy with radiotherapy were 86.3% (95% confidence interval (CI), 60.3–96.3) and 88.3% (95% CI, 70.1–96.1), respectively. The median 3-year local control rate, 3-year overall survival rate, and grade 3/4 adverse event rate were 84.0% (95% CI, 71.4–91.7), 69.6% (95% CI, 54.9–81.1), and 42.0% (95% CI, 36.2–48.0), respectively. S-1 combined with radiotherapy for patients with head and neck squamous cell carcinoma results in a good tumor response, favorable survival rate, and low toxicity. A prospective randomized, double-blind trial is required to assess the efficacy and safety of S-1 combined with radiotherapy to treat HNSCC. Full article

(1) Introduction: Stigmatization is a multi-level process leading to depreciation of particular social groups. It is particularly visible among people suffering from mental illnesses. Patient stigmatization is a serious problem in psychiatric care; thus, a reliable assessment of its level is important in the context of effective medical interventions. The aim of this paper is to assess the level of stigmatization of psychiatric patients among doctors. (2) Methods: An online, quantitative, CAWI (Computer Assisted Web Interview) study was conducted in the form of an anonymous, voluntary survey addressed to doctors working in Poland. The questionnaire questions included a socio-geographic assessment and questions assessing the level of stigmatization. A standardized psychometric tool, the MICA-4 Scale for doctors, was also used. The results obtained were compared with the evaluation of the existing reports on stigmatization among Polish society. (3) Results: 501 doctors of various specialties and at various stages of career participated in the study. Most of the respondents were women (75%). The average score of MICA-4 obtained by the respondents was 40.26 (minimum 17; maximum 67; SD 8.93). The women’s score was lower than the men’s (p = 0.034). (4) Conclusions: Stigmatization of psychiatric patients is a common phenomenon among doctors. The type of performed work and career stage has an impact on the perception of psychiatric patients. Specialists scored highest in the MICA-4 Scale, similarly to physicians of surgical fields. Due to the prevalence of the phenomenon of stigmatization, especially among people who are meant to provide patients with help, there is an urgent need to implement anti-stigma programs. Full article

It is now well established that the tumor microenvironment plays a key role in determining cancer growth, metastasis and drug resistance. Thus, it is fundamental to understand how cancer cells interact and communicate with their stroma and how this crosstalk regulates disease initiation and progression. In this setting, 3D cell cultures have gained a lot of interest in the last two decades, due to their ability to better recapitulate the complexity of tumor microenvironment and therefore to bridge the gap between 2D monolayers and animal models. Herein, we present an overview of the 3D systems commonly used for studying tumor–stroma interactions, with a focus on recent advances in cancer modeling and drug discovery and testing. Full article

A countershaft brake is used as a transmission brake (TB) to realize synchronous shifting by reducing the automated mechanical transmission (AMT) input shaft’s speed rapidly. This process is performed to reduce shifting time and improve shifting quality for heavy-duty vehicles equipped with AMT without synchronizer. To improve controlled synchronous shifting, the AMT input shaft’s equivalent resistance torque and the TB’s characteristic parameters are studied. An AMT dynamic model under neutral gear position is analyzed during the synchronous control interval. A dynamic model of the countershaft brake is discussed, and its control flow is given. The parameter identification method of the AMT input shaft’s equivalent resistance torque is given on the basis of the least squares algorithm. The parameter identification of the TB’s characteristic parameters is proposed on the basis of the recursive least squares method (RLSM). Experimental results show that the recursive estimations of the TB’s characteristic parameters under different duty cycles of the TB solenoid valve, including brake torque estimation, estimation accuracy, and braking intensity estimation, can be effectively estimated. The research provides some reliable evidence to further study the synchronous shifting control schedule for heavy-duty vehicles with AMT. Full article

This case study introduces an innovation and development concept for agile software tools for the improvement of the productivity and customer experience of forest services. This need was recognized in the context of the opening of forest data and the development of service platforms for a forest-based bioeconomy in Finland. The forest services that were studied covered a continuum from a single type of work, e.g., soil preparation and young stand management through timber procurement, to comprehensive forest property management services. The study concentrated on the needs of micro-, small, and medium-sized enterprises (SMEs), which provide either retail- or business to business (B2B) services as sub-contractors. In addition, the challenges and bottlenecks in service processes detected by other stakeholders were considered. The prevailing service processes were conceptually modelled in order to search for opportunities for improvements in business and ecosystem services, i.e., agile software concepts. For example, we examined whether it would be possible to create opportunities for flexible operational models for precision, resilience, and protection of valuable microsites in forests. These software concepts were developed and evaluated in co-operation with the stakeholders in a co-creative workshop. The technological feasibility and commercial viability of the concepts, as well as the desirability for the customer were considered. The results of this business development process—i.e., agile software concepts and their anticipated benefits—were provided for further evaluation. In addition to the practical implications of this kind of innovation process tested, the potential of these kinds of agile tools for the further development of knowledge-intensive service processes was further discussed. Full article

In this study, recycled fine aggregate (RFA), also known as recycled brick micro-powder (RBM), was used to completely replace quartz sand for the preparation of green, low-cost ecological engineered cementitious composites (ECO-ECC). RFA was used to replace ultrafine silica sand in the range of 0–100%. Firstly, the optimal replacement rate of RFA was determined, and the test results showed that the ECO-ECC prepared by fully replacing quartz sand with RFA as fine aggregate had strain hardening and multiple cracks, and the tensile strain of the specimens could reach 3%. Then the effects of fiber volume fraction and size effect on the mechanical properties of ECO-ECC were systematically investigated. The results showed that the fiber volume fraction has some influence on the mechanical properties of ECO-ECC. With the increase of fiber volume fraction, the ultimate deflection of the material keeps increasing up to 44.87 mm and the ultimate strain up to 3.46%, with good ductility and toughness. In addition, the compressive strength of the material has a good size effect, and there is a good linear relationship between different specimen sizes and standard sizes. It provides a good basis for engineering applications. Microscopic experimental results also showed that fibers play an important bridging role in the material, and the fiber pull-out and pull-break damage effects are significant. Full article

Background: With the outbreak and spread of the COVID-19 epidemic, online teaching time has been extended continuously. The changes in teaching methods, teaching conditions, and teaching environment have brought great pressure and difficulties in adjustment to teachers, which have led to a series of physical and mental problems such as negativity, lack of confidence, and depression. The long-term accumulation of these problems makes teachers’ turnover intention increasingly serious. Methods: Based on these premises, this study took 449 high school teachers in China as research objects and investigated the relationship between high school teachers’ resilience, job burnout, and turnover intention in the context of the COVID-19 epidemic. Results: The resilience of high school teachers had a significant negative predictive effect on job burnout and turnover intention (r = −0.473, p < 0.05; r = −0.283, p < 0.05), while job burnout had a significant positive predictive effect on turnover intention (r = 0.485, p < 0.05). At the same time, job burnout played a moderating role between resilience and turnover intention (λ = −0.019, p < 0.001). Discussion: This study suggests that society, schools, families, and individuals should adopt various strategies to improve teachers’ adaptability and relieve teachers’ job burnout, so as to solve the practical problem of teachers’ high turnover intention and ensure continuous improvement and healthy development of online teaching. Full article

This paper provides several error estimations for total variation (TV) type regularization, which arises in a series of areas, for instance, signal and imaging processing, machine learning, etc. In this paper, some basic properties of the minimizer for the TV regularization problem such as stability, consistency and convergence rate are fully investigated. Both a priori and a posteriori rules are considered in this paper. Furthermore, an improved convergence rate is given based on the sparsity assumption. The problem under the condition of non-sparsity, which is common in practice, is also discussed; the results of the corresponding convergence rate are also presented under certain mild conditions. Full article

The problems of chronic or noncommunicable diseases (NCD) that now kill around 40 million people each year require multiparametric combinatorial diagnostics for the selection of effective treatment tactics. This could be implemented using the biosensor principle based on peptide aptamers for spatial recognition of corresponding protein markers of diseases in biological fluids. In this paper, a low-cost label-free principle of biomarker detection using a biosensor system based on fluorometric registration of the target proteins bound to peptide aptamers was investigated. The main detection principle considered includes the re-emission of the natural fluorescence of selectively bound protein markers into a longer-wavelength radiation easily detectable by common charge-coupled devices (CCD) using a specific luminophore. Implementation of this type of detection system demands the reduction of all types of stray light and background fluorescence of construction materials and aptamers. The latter was achieved by careful selection of materials and design of peptide aptamers with substituted aromatic amino acid residues and considering troponin T, troponin I, and bovine serum albumin as an example. The peptide aptamers for troponin T were designed in silico using the «Protein 3D» (SPB ETU, St. Petersburg, Russia) software. The luminophore was selected from the line of ZnS-based solid-state compounds. The test microfluidic system was arranged as a flow through a massive of four working chambers for immobilization of peptide aptamers, coupled with the optical detection system, based on thick film technology. The planar optical setup of the biosensor registration system was arranged as an excitation-emission cascade including 280 nm ultraviolet (UV) light-emitting diode (LED), polypropylene (PP) UV transparent film, proteins layer, glass filter, luminophore layer, and CCD sensor. A laboratory sample has been created. Full article

Inflammation is an old concept that has started to be considered as an important factor in infection and chronic diseases. The role of leukocytes, the plasmatic components, then of the mediators such as prostaglandins, cytokines, and, in recent decades, of the endothelium has completed the concept of the inflammation process. The function of the endothelium appeared to be crucial as a regulator or the initiator of the inflammatory process. Culture of human endothelial cells and experimental systems made it possible to define the molecular basis of inflammation in vascular diseases, in diabetes mellitus, atherosclerosis, vasculitis and thromboembolic complications. Advanced glycation end product receptor (RAGE), present on endothelial cells (ECs) and monocytes, participates in the activation of these cells in inflammatory conditions. Inflammasome is a cytosolic multiprotein that controls the response to diverse microorganisms. It is positively regulated by stimulator of interferon response CGAMP interactor-1 (STING1). Angiogenesis and thrombotic events are dysregulated during inflammation. ECs appear to be a protector, but also a possible initiator of thrombosis. Full article

The paper explores a tandem configuration of three-blade impellers in a stirred reactor. The working fluid is a liquid-solid mixture and the stirring mechanism fitted with the two impellers must prevent the sedimentation of solid particles while homogenously dispersing them in the bulk liquid. The present numerical investigation, performed with the expert software Ansys^® Fluent, Release 16, employs the Eulerian multiphase model along with the RNG k–ε turbulence model to simulate the free-surface liquid–solid flows in the baffled stirred reactor. A sliding mesh approach is used to model the impellers rotation. The tandem configuration is clearly superior to a single impeller, while the existing electrical motor that drives the stirring mechanism still provides the necessary power. Full article

Empagliflozin, an established treatment for type 2 diabetes (T2DM), has shown beneficial effects on liver steatosis and fibrosis in animals and in humans with T2DM, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). However, little is known about the effects of empagliflozin on liver function in advanced NASH with liver fibrosis and without diabetes. This study aimed to assess the effects of empagliflozin on hepatic and metabolic outcomes in a diet-induced obese (DIO) and insulin-resistant but non-diabetic biopsy-confirmed mouse model of advanced NASH. Male C57BL/6JRj mice with a biopsy-confirmed steatosis and fibrosis on AMLN diet (high fat, fructose and cholesterol) for 36-weeks were randomized to receive for 12 weeks: (a) Empagliflozin (10 mg/kg/d p.o.), or (b) vehicle. Metabolic outcomes, liver pathology, markers of Kupffer and stellate cell activation and lipidomics were assessed at the treatment completion. Empagliflozin did not affect the body weight, body composition or insulin sensitivity (assessed by intraperitoneal insulin tolerance test), but significantly improved glucose homeostasis as assessed by oral glucose tolerance test in DIO-NASH mice. Empagliflozin improved modestly the NAFLD activity score compared with the vehicle, mainly by improving inflammation and without affecting steatosis, the fibrosis stage and markers of Kupffer and stellate cell activation. Empagliflozin reduced the hepatic concentrations of pro-inflammatory lactosylceramides and increased the concentrations of anti-inflammatory polyunsaturated triglycerides. Empagliflozin exerts beneficial metabolic and hepatic (mainly anti-inflammatory) effects in non-diabetic DIO-NASH mice and thus may be effective against NASH even in non-diabetic conditions. Full article

Cucurbita moschata Duchesne (Cucurbitaceae) is a plant food highly appreciated for the content of nutrients and bioactive compounds, including polyphenols and carotenoids, which contribute to its antioxidant and antimicrobial capacities. The purpose of this study was to identify phenolic acids and flavonoids of Cucurbita moschata Duchesne using high-performance liquid chromatography–diode array detection–electrospray ionization tandem mass spectrometry (HPLC–DAD–ESI-MS) at different ripening stages (young, mature, ripened) and determine its antioxidant and antimicrobial activities. According to the results, phenolic acids and flavonoids were dependent on the maturity stage. The mature fruits contain the highest total phenolic and flavonoids contents (97.4 mg GAE. 100 g⁻¹ and 28.6 mg QE. 100 g⁻¹).A total of 33 compounds were identified. Syringic acid was the most abundant compound (37%), followed by cinnamic acid (12%) and protocatechuic acid (11%). Polyphenol extract of the mature fruits showed the highest antioxidant activity when measured by DPPH (0.065 μmol TE/g) and ABTS (0.074 μmol TE/g) assays. In the antimicrobial assay, the second stage of ripening had the highest antibacterial activity. Staphylococcus aureus was the most sensitive strain with an inhibition zone of 12 mm and a MIC of 0.75 mg L⁻¹. The lowest inhibition zone was obtained with Salmonella typhimurium (5 mm), and the MIC value was 10 mg L⁻¹. Full article

The luxury goods industry and holography have a lengthy history together. In this article, we review the applications of holography to the industry and the relevant technical requirements, in particular when the hologram itself is the luxury item, when the hologram is used to promote luxury items, and when the hologram is used for authentication of luxury items. We then explore some possible scenarios for the evolution of this relationship. Full article

Dacarbazine (DAC) 5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide is an imidazole-carboxamide derivative that is structurally related to purines. DAC belongs to the triazene compounds, which are a group of alkylating agents with antitumor and mutagenic properties. DAC is a non-cell cycle specific drug, active in all phases of the cellular cycle. In the frame of this work the 3d metal complexes (cobalt and copper) with dacarbazine were synthesized. Their spectroscopic properties by the use of FT-IR, FT-Raman, and ¹HNMR were studied. The structures of dacarbazine and its complexes with copper(II) and cobalt(II) were calculated using DFT methods. The effect of metals on the electronic charge distribution of dacarbazine was discussed on the basis of calculated NBO atomic charges. The reactivity of metal complexes in relation to ligand alone was estimated on the basis of calculated energy of HOMO and LUMO orbitals. The aromaticity of the imidazole ring in dacarbazine and the complexes were compared (on the basis of calculated geometric indices of aromaticity). Thermal stability of the investigated 3d-metal complexes with dacarbazine and the products of their thermal decomposition were analyzed. Full article