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Background: Breast cancer is considered the number one killer of women both in China and abroad, and the leading cause of cancer death. It severely affects female health-related quality of life. Broad-complex, tramtrack, bric à brac (BTB) protein family was first discovered in drosophila as early as in 1993 by Godt D and peers, since then, more family members and their critical biological functions were uncovered. Moreover, researchers around the world have recently demonstrated that numerous signaling pathways connect BTB family members and human breast cancer. Purpose: In this review, we critically discuss these findings regarding the essential mechanisms and functions of the BTB protein family in mediating the organic processes of human breast cancer. Meanwhile, we summarize the signaling pathways the BTB protein family participates in. And we address that BTB proteins regulate the growth, apoptosis, and other behaviors of breast cancer cells. We also point out the future directions for further studies in this field. Methods: The relevant online literatures have been reviewed for this article. Conclusion: This review could offer an update on novel molecular targets for treating human breast cancer and new insights into BTB protein family research. [ABSTRACT FROM AUTHOR]

This study aims to investigate the knowledge and attitudes of participants and potential participants in clinical trials toward electronic informed consent. We conducted a survey-based cross-sectional study in Hunan Province, China in March 2021. A total of 547 respondents were included in this study. All questions in an 8-item survey section assessing participants' knowledge of electronic informed consent received correct answers from at least 70% of participants. In terms of attitude scores, most participants (86.3%) believed that electronic informed consent is more convenient than the paper-based version, and more than half (51.2%) believed that electronic informed consent could completely replace the paper-based version. Responses indicated that common concerns about electronic informed consent were its security and confidentiality, legal benefits, and implications for rights protection. [ABSTRACT FROM AUTHOR]

After giving a calculation formula for the g-derivative for a fuzzy-valued function with unilateral derivatives of the endpoint functions of level sets and characterizing the partial order relations between two fuzzy intervals by their generalized difference, we present the optimality conditions of weak LU-minimum solutions for fuzzy optimization problems by using the partial generalized differentiability and directional generalized differentiability. The optimization conditions obtained in this article extend the results in the literature. Examples are also given to illustrate the main theorems. [ABSTRACT FROM AUTHOR]

The present study aimed to study the efficacy and adverse effects of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in relapsed or refractory multiple myeloma. Patients were divided into three dose groups based on cell therapy concentration. After CAR-T cell therapy for 10 patients with recurrent or refractory multiple myeloma, the patients were monitored and evaluated regularly to observe the efficacy and adverse reactions of CAR-T cell therapy. At a median follow-up of 337 (253-504) days, one patient succumbed 24 days due to rapidly progressing disease. The overall response rate of nine patients was 88.9%, including 77.8% (7/9) with minimal residual disease negative complete remission (CR) and 11.1% (1/9) with partial remission. A total of three patients were maintained in remission state for more than a year and eight were maintained for more than six months. Among the three patients with extramedullary invasion, two extramedullary lesions disappeared and one was stable. The highest copy number of CAR-T cells in seven patients with CR was >1x105 copies/µl gDNA, and the best therapeutic effect can be achieved within 30 (7-30) days after the copy number of CAR-T cells reached 1x105 copies/µl genomic DNA. The median onset time in the nine patients was 43 (22-169) days, and the median progression-free survival was 337 (253-504). Among the 10 patients, nine (90%) had cytokine release syndrome, all of which were below grade II. There were nine (90%) patients with hematological adverse reactions, six (60%) patients with severe anemia, five (50%) patients with grade III and above leukopenia, five (50%) patients with granulocytopenia, four (40%) patients with grade III and above thrombocytopenia, and three (30%) patients with grade III and above pancytopenia. It was concluded that anti-BCMA CAR-T cell therapy is a promising treatment method for relapsed or refractory multiple myeloma and extramedullary invasion, with stable efficacy and controllable adverse effects. [ABSTRACT FROM AUTHOR]

Autophagy is a process in which cells degrade intracellular substances and play a variety of roles in cells, such as maintaining intracellular homeostasis, preventing cell overgrowth, and removing pathogens. It is highly conserved during the evolution of eukaryotic cells. So far, the study of autophagy is still a hot topic in the field of cytology. Ferroptosis is an iron‐dependent form of cell death, accompanied by the accumulation of reactive oxygen species and lipid peroxides. With the deepening of research, it has been found that ferroptosis, like autophagy, is involved in the occurrence and development of cardiovascular diseases. The relationship between autophagy and ferroptosis is complex, and the association between the two in cardiovascular disease remains to be clarified. This article reviews the mechanism of autophagy and ferroptosis and their correlation, and discusses the relationship between them in cardiovascular diseases, which is expected to provide new and important treatment strategies for cardiovascular diseases. Significance statement: Autophagy and ferroptosis are hot topics in the field of cell biochemistry, both of which are closely related to the occurrence and development of cardiovascular diseases. As the molecular mechanisms of autophagy and ferroptosis become more clear in cells, the two seem to intersect in some places, especially in related studies of cardiovascular diseases. If the interaction between autophagy and ferroptosis can be clarified, it will provide novel therapeutic strategies for alleviating related diseases. [ABSTRACT FROM AUTHOR]

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE−/− mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis. [Display omitted] • Endothelial NECC2 promotes the development of atherosclerosis. • NECC2 contributes to oxLDL-induced endothelial oxidative damage. • NECC2-induced Cav-1 phosphorylation via Tyk2 promotes oxLDL accumulation in VECs. • Compound YF-307 inhibits endothelial oxidative damage and atherosclerosis. [ABSTRACT FROM AUTHOR]

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR‐T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR‐T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR‐T cell therapy, and considers future outlooks for research development. Significance statement: The necessity and importance of chimeric antigen receptor (CAR) T cells and their therapeutic efficiency in treating diseases other than cancer, mainly cardiovascular diseases, have emerged in recent years. However, there is still room for advancement in the current models of CAR‐T cell therapy. This paper highlights the evolution and roadblocks of CAR‐T technology at different levels, from technical concerns to clinical outcomes, in an attempt to improve the therapeutic efficiency of CAR‐T cell therapy in this area. [ABSTRACT FROM AUTHOR]

In this paper, the mixed integer linear programming (MILP) for solving unit commitment (UC) problems in a hybrid power system containing thermal, hydro, and wind power have been studied. To promote its efficiency, an improved MILP approach has been proposed, while the symmetric problem in MILP formulas has been solved by reforming hierarchical constraints. Experiments on different scales have been conducted to demonstrate the effectiveness of the proposed approach. The results indicate a dramatic efficiency promotion compared to other popular MILP approaches in large scale power systems. Additionally, the proposed approach has been applied in UC problems of the hybrid power system. Two indexes, fluctuation degree and output degree, have been proposed to investigate the performance of renewable energy sources (RES). Several experiments are also implemented and the results show that the integration of pumped hydroelectric energy storage (PHES) can decrease the output of thermal units, as well as balance wind power fluctuation according to the load demand. [ABSTRACT FROM AUTHOR]

Potassium channels such as Kv2.1 are targeted to specific subcellular compartments to fulfill various functions. However, the mechanisms for their localization are poorly understood. Here, we show that KVS-4/Kv2.1 somatodendritic localization in Caenorhabditis elegans DA9 neuron requires UNC-101( AP-1 μ subunit). We define a bipartite sorting signal within KVS-4 consisting of a C-terminal EQMIL and N-terminal WNIIE motifs. The bipartite signal is sufficient to target nonpolarized transmembrane protein MIG-13 into DA9 somatodendritic compartments. Furthermore, we found that AP-1 interacts with the bipartite signal through UNC-101/ AP-1 μ N-terminal predicted Longin-like domain. Our results provide new insight into the mechanisms of Kv2.1 post-Golgi sorting and targeting. [ABSTRACT FROM AUTHOR]

Background: The most common materials of artificial blood vessels are polyethylene terephthalate and polytetrafluoroethylene. But polycarbonate polyurethane (PCU) is an ideal material for vascular prostheses because of their excellent characteristics. As far as we know, our artificial blood vessel is the first type of hybrid PCU/polyester three-layered large-diameter artificial blood vessel in the world. Objective: The purpose of this preclinical animal experiment is to evaluate the hemocompatibility, histocompatibility, effectiveness, and safety of the three-layered large-diameter artificial blood vessel in sheep. Methods: The artificial blood vessels took place of the initial segments of the sheep's thoracic aorta by end-to-end anastomosis. Results: All of the 14 sheep are male, their average body weight (BW) was 30.57 ± 3.95 kg. All 14 artificial blood vessels successfully replaced the thoracic aortas. 5 sheep did not survive to the end of the experiment, while the remaining 9 sheep did. After the surgery, the blood biochemical and blood routine indicators fluctuate slightly within the normal range. The angiography showed that the implanted artificial blood vessels were unobstructed without obvious stenosis or expansion. 24 weeks after surgery, the lumen surfaces of the artificial blood vessels were covered by endothelia in different degrees, and the average endothelialization rate was 69.44% (range: 20% to 100%). Conclusions: This artificial blood vessel is the first to use PCU in large-diameter artificial vascular grafts. It has excellent blood compatibility, wonderful biocompatibility, high endothelialization rate, and 100% patency. [ABSTRACT FROM AUTHOR]

Growing preclinical and clinical evidence has suggested the potential method of umbilical cord mesenchymal stem cell (UCMSC) therapy for diabetic foot. Thus, the authors provided an outline of the application of UCMSCs in the treatment of diabetic foot and further summarized the roles and mechanisms of this therapy. With no time limitations, the authors searched the Web of Science, Cochrane Central Register of Controlled Trials, and PubMed (MEDLINE) databases. 14 studies were included, including 9 preclinical experiments and 5 clinical trials (3 RCTs and 2 single-arm trials). The UCMSCs are of great efficacy and safety, and function mainly by reducing inflammation, regulating immunity, promoting growth factors, and enhancing the functions of vascular endothelial cells, fibroblasts, and keratinocytes. As a result, ulcer healing-related biological processes ensue, which finally lead to diabetic foot ulcer healing and clinical symptom improvement. UCMSC treatment enhances diabetic foot ulcer healing and has a safety profile. They function mainly by modulating immunity, promoting growth factor secretion, and enhancing cellular functions. More well-designed preclinical and clinical studies are needed to provide the most optimal protocol, the comprehensive molecular mechanisms, as well as to further evaluate the efficiency and safety profile of UCMSC treatment in diabetic foot patients. • The preclinical and clinical studies of UCMSC therapy for diabetic foot patients and animal models were first reviewed. • This review provides an initial summary of the roles and mechanisms of UCMSCs in the treatment of diabetic foot. • Quality control assays of UCMSC therapy for diabetic foot treatment were first summarized and evaluated. [ABSTRACT FROM AUTHOR]

For an effective medical application of therapeutic siRNA, a safe and an efficient delivery system are required. Herein, magnetic nanoparticles (MNPs) have been successfully used as siRNA delivery vehicles. Firstly, MNPs were coated with gold (Au) nanoparticles and then capped with PEI. To improve the biocompatibility of nanoparticles, hyaluronic acid (HA) was coated onto the surface of PEI-Au/Fe nanoparticles. The prepared HA-PEI-Au/Fe3O4 nanoparticles were characterized and found to be uniform and well segregated in TEM analysis. FTIR analysis confirmed that HA was successfully conjugated to PEI. The polymer content in these nanoparticles was relatively higher than PEG coated nanoparticles. Cell viability assay demonstrated that the nanoparticles were relatively biocompatible in nature. ADAM10 siRNA was loaded into the HA-PEI-Au/Fe3O4 nanoparticles and cytotoxicity to prostate cancer (PC3) cells was analyzed. The results indicate that ADAM10 siRNA loaded HA-PEI-Au/Fe3O4 suppress the PC3 cells growth in vitro. Clearly, it could be confirmed that HA-PEI coated Au/Fe3O4 nanoparticles with higher biocompatibility appear to be suitable for intracellular siRNA delivery. [ABSTRACT FROM AUTHOR]

Growing experience with engineered chimeric antigen receptor (CAR)‐T cells has revealed some of the challenges associated with developing patient‐specific therapy. The promising clinical results obtained with CAR‐T therapy nevertheless demonstrate the urgency of advancements to promote and expand its uses. There is indeed a need to devise novel methods to generate potent CARs, and to confer them and track their anti‐tumor efficacy in CAR‐T therapy. A potentially effective approach to improve the efficacy of CAR‐T cell therapy would be to exploit the benefits of nanotechnology. This report highlights the current limitations of CAR‐T immunotherapy and pinpoints potential opportunities and tremendous advantages of using nanotechnology to 1) introduce CAR transgene cassettes into primary T cells, 2) stimulate T cell expansion and persistence, 3) improve T cell trafficking, 4) stimulate the intrinsic T cell activity, 5) reprogram the immunosuppressive cellular and vascular microenvironments, and 6) monitor the therapeutic efficacy of CAR‐T cell therapy. Therefore, genetic and functional modifications promoted by nanotechnology enable the generation of robust CAR‐T cell therapy and offer precision treatments against cancer. [ABSTRACT FROM AUTHOR]

Different types of siRNA delivery vehicles including nanoparticles have been synthesized and utilized for prostate cancer gene therapy. However, one of the most common limitations being faced is the toxicity of cationic polymers toward the cells. In the current study, magnetic nanoparticles were prepared and conjugated with cationic polymer, polyethylenimine. Then polyethylene glycol was conjugated with polyethylenimine to improve the biocompatibility of nanoparticles. The transmission electron microscopy size of nanoparticles was found to be 15.82 (±9.07) nm, while hydrodynamic size was about 79.20 (±0.68) nm. Zeta potential analysis of polyethylenimine and polyethylene glycol-coated nanoparticles was +31.4 (±0.62) and +5.65 (±0.76) mV, respectively. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance confirmed the presence of polyethylene glycol and polyethylenimine polymers in magnetic nanoparticles. Cell viability test in mouse fibroblast NIH 3T3 and prostate cancer PC3 cells showed an increased in biocompatibility of functionally modified polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles. siRNA targeting a disintegrin and metalloproteinase 10 (ADAM10) was successfully loaded into the polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles and delivered to PC3 cells. The results clearly demonstrated a significant decrease in cell viability, which increased within a certain siRNA concentration. The inhibitory concentration (IC50) value for ADAM10 siRNA was calculated to be 15.83 nM after 72 h. Confocal microscopy confirmed the delivery of siRNA-loaded nanoparticles intracellularly to the tumor cells cytosol. This magnetic system can be used as a powerful platform to inhibit cancer cells progression. [ABSTRACT FROM AUTHOR]

• We proposed the method of constructing a fuzzy granular recurrence plot (FGRP method). • We designed an FGRP method based classification model. • The experiment shows the good performance of the FGRP method in reducing the influence of noise. • The experiment presents the good performance of the FGRP method based classification model. Recently, recurrence plot (RP) and its quantification techniques have become an important research tool in nonlinear analysis. In the existing researches, an RP is directly established on a time series ignoring the influence of noise on data, which will affect our judgement on the dynamic properties of a system. To tackle the problem there, this paper proposes a novel recurrence plot, namely fuzzy granular recurrence plot (FGRP). An FGRP of a time series is built not directly on the time series itself but on its corresponding granular time series which is composed of fuzzy information granules. With specific capability, fuzzy information granules are used as building blocks of an FGRP to achieve high-level, compact and understandable signal models. In order to apply the FGRP method to time series classification tasks, an FGRP based classification model is designed in this paper. Subsequent experiments show that the FGRP of a time series can reduce the effect of noise, and the FGRP based classification model can improve the classification performance. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA. [ABSTRACT FROM AUTHOR]

[Display omitted] • A gradient hydrophobic surface (GHS) was formed on pyrolytic carbon (PYC). • The GHS with parallel ridges was made by laser etching and fluorosilanization. • The GHS showed low flow resistance and spontaneous droplet motion. • The GHS showed much better blood compatibility than bare PYC. Effective surface modification to endow pyrolytic carbon (PYC) with long-term anti-thrombotic performance is highly demanded. In this work, a gradient hydrophobic surface on PYC was prepared by creating parallel ridges via the combination of laser etching technology and surface fluorosilanization. Scanning electron microscopy (SEM) observation confirms that the gradient hydrophobic surface is composed of a bare PYC region and four regions of parallel ridges with varying distances. The gradient hydrophobic surface is stable in air, phosphate buffer solution (PBS), and flowing PBS. Additionally, the gradient hydrophobic surface on PYC shows spontaneous droplet motion and much lower flow resistance than bare PYC. Compared to bare PYC, the gradient hydrophobic surface on PYC exhibits better blood compatibility and anti-adhesion performance. The results presented in this paper confirm that creating a gradient hydrophobic surface is an effective way of achieving long-lasting anti-thrombosis property. [ABSTRACT FROM AUTHOR]

Abstract: Two types of water-insoluble protein from Bombyx mori silkworm, degummed and undegummed superfine silk powders, were prepared through a physical method. Water-soluble superfine silk fibroin powder was obtained from salt-dissolved, dialyzed and freeze-dried silk fibroin. These three types of superfine silk powders were blended with solution of commercially available biomedical grade segmented polyurethane (PU) to prepare elastic biofiber by a wet-spinning process. The objective of the current study was to identify the feasibility of wet spinning of polyurethane/superfine silk powder blend elastic biofiber, and analyse and compare the mechanical properties of the as-spun biofibers. Superfine silk fibroin powders and PU were dispersed in dimethyl formamide (DMF) and the dope solution exhibited good fiber formation in a warm distilled water coagulation bath. The superfine silk powder/PU blend fiber had a smooth surface, dense structure, and considerably high strength with a circular cross-section. The future further investigation will be carried out to analyse in detail the structure and morphology of the as-spun fiber. The silk-inspired biomedical polyurethane biofiber showed potential as a biomaterial for small-diameter artificial vascular scaffolds. [Copyright &y& Elsevier]

Abstract: In order to blend the water-insoluble and biocompatible polyurethane (PU) with silk fibroin (SF) to prepare water-insoluble films as a biomaterial, the ionic liquid, 1-butyl-3-methylimidazolium chloride (BMIMCl), was used to prepare a SF/BMIMCl solution, which was directly blended with PU solution in N, N-dimethylformamide (DMF). Infrared spectroscopy indicated that the solution blending led to chemical bonding between the two polymers and a β-sheet structure was the main conformation of SF in the films. The hydrophilicity of the films increased with the content of SF, based on contact angle measurements. The composite showed good blood compatibility in coagulation time tests and has potential biomaterial applications. [Copyright &y& Elsevier]

Blood contacting materials with anti-thrombotic surfaces are highly demanded in clinics. Despite considerable research on surface modifications, limited progress has been made on effective prevention of thrombosis for artificial implants such as mechanical valve prosthesis. Herein, wettability gradient surface, which can ideally exhibit good hemocompatibility and low flow resistance, was developed for potential reduction of thrombosis. The wettability gradient surface on a model substrate of nickel-titanium (NiTi) alloy was prepared via a simple and economic method that combined laser microfabrication and surface stearic acid self-assembly approach. Scanning electron microscopy (SEM) observation confirmed that the wettability gradient surface was composed of a smooth NiTi region and three porous regions with different pore sizes and distances. Contact angle measurement revealed that, together with a low surface energy layer, the structural topography gradient could create a wettability gradient surface on NiTi alloy which could drive droplet motion. When compared with bare NiTi, such wettability gradient surface exhibited better anti-adhesion property, which was beneficial to the hemocompatibility and thus showing a lower hemolysis rate. Additionally, the wettability gradient surface also showed much lower flow resistance than bare NiTi. These results demonstrate that the developed wettability gradient surface may be used to reduce thrombosis. Unlabelled Image • The wettability gradient surface on NiTi alloy was formed by laser-induced method. • Such surface exhibited much better anti-adhesion property than bare NiTi. • Such surface showed much lower hemolysis rate than bare NiTi. • Such surface exhibited much lower flow resistance than bare NiTi. [ABSTRACT FROM AUTHOR]