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Macrophage migration inhibitory factor (MIF) is a multifunctional protein that possesses cytokine, enzyme, and endocrine activities and acts as a chaperone-like molecule. Owing to its immune-inflammatory regulatory properties, the role of MIF has long been an attractive target in research on various autoimmune and inflammatory disorders. MIF is also widely expressed in the central nervous system (CNS), and its potential roles in CNS disorders have become a focus to elucidate the physiological and pathological effects of MIF and to explore its potential significance in the treatment of CNS diseases. Previously, the majority of work on MIF functional regulation was focused on MIF tautomerase inhibitors. However, mounting information has indicated that the functions of MIF extend far beyond its tautomerase activity. Here, we review the recent advances in understanding the complex roles of MIF in the pathogenesis of CNS disorders as well as the discovery and design of small molecules targeted to tautomerase and nuclease of MIF.

Abstract Ruthenium (Ru) is widely recognized as a low-cost alternative to iridium as anode electrocatalyst in proton-exchange membrane water electrolyzers (PEMWE). However, the reported Ru-based catalysts usually only operate within tens of hours in PEMWE because of their intrinsically high reactivity of lattice oxygen that leads to irrepressible Ru leaching and structural collapse. Herein, we report a design concept by employing large-sized and acid-resistant lattice lead (Pb) as a second element to induce a pinning effect for effectively narrowing the moving channels of oxygen atoms, thereby lowering the reactivity of lattice oxygen in Ru oxides. The Pb-RuO2 catalyst presents a low overpotential of 188 ± 2 mV at 10 mA cm−2 and can sustain for over 1100 h in an acid medium with a negligible degradation rate of 19 μV h−1. Particularly, the Pb-RuO2-based PEMWE can operate for more than 250 h at 500 mA cm−2 with a low degradation rate of only 17 μV h−1. Experimental and theoretical calculation results reveal that Ru-O covalency is reduced due to the unique 6s−2p−4d orbital hybridization, which increases the loss energy of lattice oxygen and suppresses the over-oxidation of Ru for improved long-term stability in PEMWE.

Abstract Precisely modulating the Ru-O covalency in RuOx for enhanced stability in proton exchange membrane water electrolysis is highly desired. However, transition metals with d-valence electrons, which were doped into or alloyed with RuOx, are inherently susceptible to the influence of coordination environment, making it challenging to modulate the Ru-O covalency in a precise and continuous manner. Here, we first deduce that the introduction of lanthanide with gradually changing electronic configurations can continuously modulate the Ru-O covalency owing to the shielding effect of 5s/5p orbitals. Theoretical calculations confirm that the durability of Ln-RuOx following a volcanic trend as a function of Ru-O covalency. Among various Ln-RuOx, Er-RuOx is identified as the optimal catalyst and possesses a stability 35.5 times higher than that of RuO2. Particularly, the Er-RuOx-based device requires only 1.837 V to reach 3 A cm−2 and shows a long-term stability at 500 mA cm−2 for 100 h with a degradation rate of mere 37 μV h−1.

AIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.

Abstract Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple‐negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti‐cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the ubiquitin E3 ligase βTRCP in the form of molecular glue. C1 significantly inhibits the proliferation and metastasis of TNBC cells both in vitro and in vivo and in TNBC patient‐derived organoids, and these antitumor effects are attributed to the degradation of eEF2K by C1. Additionally, combination treatment of C1 with paclitaxel, a commonly used chemotherapeutic drug, exhibits synergistic anti‐tumor effects against TNBC. This study not only generates a powerful research tool to investigate the therapeutic potential of targeting eEF2K, but also provides a promising lead compound for developing novel drugs for the treatment of TNBC and other cancers.

This research intended to identify effective teaching styles that nurture "creativity" in the teaching of dance choreography in Korea. This research is based on the first phase of research that identified choreographic knowledge as educational content aiming to cultivate creativity in the teaching and learning of dance choreography in universities. A literature review covering various fields, including Aristotle's theory of knowledge, education, creativity, and choreographic pedagogy, was conducted. This research utilises qualitative research methods through the grounded theory approach. The data were collected from choreographers and their creative process in a doctorate inquiry completed in 2013 investigating choreographic pedagogy focused on cultivating creativity. The identified teaching styles primarily promote reflection and aim to provide learner agency to experience behaviours, thoughts and emotions that can be engaged during the choreographic process through a learner-centred approach.

Abstract Background As the direct organ of villus, hair follicles have obvious seasonal cycles. The hair follicle cycle is orchestrated by multiple cell types that together direct cell renewal and differentiation. But the regulation property of hair follicle cells from anagen to catagen in yak is still unknown. Results In this study, single-cell RNA sequencing was performed on 24,124 single cells of the scapular skin from white yak. Based on tSNE cluster analysis, the cell types of IFE-DC, epidermal cell lines, fibroblasts, keratinocytes, IRS, DS, INFU, and other cells in yak hair follicles during anagen and catagen were successfully identified, and the gene expression profiles were described. The GO enrichment analysis indicated the different cells characteristic genes to be mainly enriched in the epidermal development, epithelial cell differentiation and wound healing pathways. The pseudotime trajectory analysis described the differentiation trajectory of the epidermal lineage and dermal lineage of the hair follicle during anagen and catagen. Moreover, the dynamic changes of the genes like LHX2, KRT25, and KRT71 were found to be highly expressed in HS and IRS, but not in the IFE-DC, INFU, and keratinocyte during differentiation. Conclusions Our results analyzed the time-varying process of gene expression in the dermal cell lineage and epidermal cell lineage of hair follicles during anagen and catagen during fate differentiation was expounded at the single cell level, revealing the law of fate specialization of different types of cells. In addition, based on the enrichment analysis, the transcriptional regulatory factors involved in the different cell fates were also revealed. These results will help to enhance our understanding of yak hair follicle cycle and promote the development and utilization of yak villus.

The morphogenesis of hair follicle structure is accompanied by the differentiation of skin tissue. Mammalian coats are produced by hair follicles. The formation of hair follicles requires signal transmission between the epidermis and dermis. However, knowledge of the transcriptional regulatory mechanism is still lacking. We used single-cell RNA sequencing to obtain 26,573 single cells from the scapular skin of yaks at hair follicle telogen and anagen stages. With the help of known reference marker genes, 11 main cell types were identified. In addition, we further analyzed the DP cell and dermal fibroblast lineages, drew a single-cell map of the DP cell and dermal fibroblast lineages, and elaborated the key genes, signals, and functions involved in cell fate decision making. The results of this study provide a very valuable resource for the analysis of the heterogeneity of DP cells and dermal fibroblasts in the skin and provide a powerful theoretical reference for further exploring the diversity of hair follicle cell types and hair follicle morphogenesis.

Background Shenqi Fuzheng injection (SQFZ) combined with chemotherapy can sensitize tumour cells. However, the mechanisms underlying SQFZ’s effects remain unknown. In human breast cancer cell lines and M2 macrophages, we showed that SQFZ was a significantly potent agent of sensitization. Methods The human breast cancer cell line, MDA-MB-231/DDP, and the human acute leukaemia mononuclear cell line, THP-1, were used. MDA-MB-231/DDP breast cancer xenografts were established to monitor tumour growth. Resistance-associated proteins were examined by western blotting. Levels of cytokines and chemokines were detected by ELISA. Cell viability was measured using the MTT assay. Apoptosis was detected by flow cytometric analysis. Results SQFZ significantly enhanced the capability of cisplatin to reduce tumour mass. SQFZ and cisplatin decreased the expression of CD206 by 1.89-fold and increased that of CD86 by 1.76-fold as compared to cisplatin alone. The levels of PGE2, IL-6, and CCL1 decreased significantly, and the activation of p-PI3K and the expressions of P-gp and ABCG2 were also inhibited by SQFZ in combination with cisplatin treatment in vivo. The survival following cisplatin administration of 60 μM and 120 μM reduced significantly in the presence of SQFZ in MDA-MB-231/DDP and M2 co-cultured cells. IGF-1, a PI3K activator, combined with SQFZ weakened the effects of SQFZ-induced apoptosis from 28.7% to 10.5%. The effects of IGF-1 on increasing the expressions of P-gp, ABCG2, and Bcl-2, and decreasing that of Bax were reversed by SQFZ. Conclusion Our findings provide evidence that SQFZ is a potential therapeutic drug for cancer therapy.

The popularity and development of social media have made it more and more convenient to spread rumors, and it has become especially important to detect rumors in massive amounts of information. Most of the traditional rumor detection methods use the rumor content or propagation structure to mine rumor characteristics, ignoring the fusion characteristics of the content and structure and their interaction. Therefore, a novel rumor detection method based on heterogeneous convolutional networks is proposed. First, this paper constructs a heterogeneous map that combines both the rumor content and propagation structure to explore their interaction during rumor propagation and obtain a rumor representation. On this basis, this paper uses a deep residual graph convolutional neural network to construct the content and structure interaction information of the current network propagation model. Finally, this paper uses the Twitter15 and Twitter16 datasets to verify the proposed method. Experimental results show that the proposed method has higher detection accuracy compared to the traditional rumor detection method.

The psycho-lexical approach can be effectively used to explore the structure of sports culture. Based on a lexical list of adjective vocabulary reflecting sports culture and through an item analysis, 87 discriminating objectives were selected representing sports culture.ObjectiveTo explore the structure of sports culture from the objectives lexicons.MethodsItem analysis and factor analysis were adopted to abstract the structure of sports culture.ResultsThrough a principal component analysis, a structure of six factors including extroversion-activity, diligence-progression, experience, independence-excellence, enjoyment, and body culture was extracted. Through a second-order factor analysis, a psychological structure of sports culture consisting of six dimensions and 12 factors was extracted, and result of the reliability analysis revealed good Cronbach α coefficient and test–retest reliability coefficient.ConclusionThe psycho-lexical structure of sports culture can be used to understand structure of sports culture.

Here adsorption studies were proposed on a carboxylated sludge biochar (CSB) material modified by HNO3 to assess its capacity in the removal of cobalt from aqueous solution. The as-prepared sludge biochar material was characterized by Brunauer-Emmett-Teller (BET) analysis, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), energy-dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The isotherm process could be well described by the Langmuir isotherm model. The adsorption kinetics indicated that cobalt adsorption followed a pseudo-second-order kinetics model. The mechanism between Co(II) and biochar involved electrostatic interaction, ion exchange, surface complexation and physical function. The adsorption capacity on CSB was as high as 72.27 mg·g−1, surpassing original sludge biochar (SB) as CSB had abundant oxygen-containing functional groups and many hydroxyls, plus the BET surface areas increased when SB was modified by HNO3, which stimulated adsorption effect. Therefore, this work shows that CSB could be used as an efficient adsorbent to remove Co(II) in wastewater. Highlights The material has abundant oxygen-containing functional groups, which are beneficial for binding Co(II).; The isotherm process could be well described by the Langmuir isotherm model and pseudo-second-order kinetic model.; The adsorbent has an efficient adsorption capacity for Co(II), as high as 72.27 mg·g−1.;

α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. To develop novel α-glucosidase inhibitors, a series of 5-fluoro-2-oxindole derivatives (3a ∼ 3v) were synthesized, and their α-glucosidase inhibitory activities were investigated. Biological assessment results showed that most synthesized compounds presented potential inhibition on α-glucosidase. Among them, compounds 3d, 3f, and 3i exhibited much better inhibitory activity with IC50 values of 49.89 ± 1.16 μM, 35.83 ± 0.98 μM, and 56.87 ± 0.42 μM, respectively, which were about 10 ∼ 15 folds higher than acarbose (IC50 = 569.43 ± 43.72 μM). A kinetic mechanism study revealed that compounds 3d, 3f, and 3i inhibited the α-glucosidase in a reversible and mixed manner. Molecular docking was carried out to simulate the affinity between the compound and α-glucosidase.

Objective: The purpose of this review was to evaluate the effectiveness of Qigong in improving the quality of life and relieving fatigue, sleep disturbance, and cancer-related emotional disturbances (distress, depression, and anxiety) in women with breast cancer. Methods: The PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Sinomed, Wanfang, VIP, and China National Knowledge Infrastructure databases were searched from their inceptions to March 2020 for controlled clinical trials. Two reviewers selected relevant trials that assessed the benefit of Qigong for breast cancer patients independently. A methodological quality assessment was conducted according to the criteria of the 12 Cochrane Back Review Group for risk of bias independently. A meta-analysis was performed by Review Manager 5.3. Results: This review consisted of 17 trials, in which 1236 cases were enrolled. The quality of the included trials was generally low, as only five of them were rated high quality. The results showed significant effectiveness of Qigong on quality of life (n = 950, standardized mean difference (SMD), 0.65, 95 % confidence interval (CI) 0.23–1.08, P = 0.002). Depression (n = 540, SMD = −0.32, 95 % CI −0.59 to −0.04, P = 0.02) and anxiety (n = 439, SMD = −0.71, 95 % CI −1.32 to −0.10, P = 0.02) were also significantly relieved in the Qigong group. There was no significant benefit on fatigue (n = 401, SMD = −0.32, 95 % CI 0.71 to 0.07, P = 0.11) or sleep disturbance relief compared to that observed in the control group (n = 298, SMD = −0.11, 95 % CI 0.74 to 0.52, P = 0.73). Conclusion: This review shows that Qigong is beneficial for improving quality of lifeand relieving depression and anxiety; thus, Qigong should be encouraged in women with breast cancer.

Abstract Introduction The traditional treatment of myocardial infarction with ventricular septal rupture is surgical treatment. For the elderly patients with cardiac insufficiency, surgical treatment is very risky. The successful treatment of this case by interventional occlusion is a new method. No relevant literature reports have been found. Case A 77-year-old man with a past medical history of old myocardial infarction presented to the physician with sudden onset of palpitation and shortness of breath. Echocardiography showed thinning of the interventricular septum near the apex and bulging toward the right ventricular side with “paradoxical motion”, on which a rupture of about 8 mm in diameter was seen. CDFI: left ventricular blood shunted to the right ventricle through the rupture.Echocardiographic diagnosis: old left ventricular anteroseptal myocardial infarction with ventricular septal rupture. Due to the older age of the patient and reduced left ventricular function, surgical repair of the ventricular septal rupture site was more difficult. After multidisciplinary discussion, it was agreed that the patient could not afford thoracotomy and was not suitable for thoracotomy, and echocardiography guided interventional occlusion of the ruptured interventricular septum could be performed. Conclusion Transesophageal echocardiography-guided interventional occlusion of myocardial infarction with ventricular septal rupture in elderly patients with cardiac insufficiency is a new attempt, the successful treatment of this case shows that this method is feasible, for some patients is an appropriate treatment.

Abstract Background Professor Xinfang Wang first introduced the clinical application of trans nose pharynx esophagus echocardiography (TNPEE) in 2014. Subsequently, we developed the technology. In the present study we assess the feasibility of TNPEE in the ultrasonic diagnosis. Methods Select patients suitable for TNPEE examination. After obtaining written consent of patients or their families, oral dacronin hydrochloride gel local anesthesia was given 10–15 min before examination. The nostrils were disinfected and then smeared with tetracaine hydrochloride gel, which acted as local anesthesia and lubrication. The probe was inserted gently through the nostrils and entered the esophagus through the nasal cavity and pharynx. TNPEE is similar to transoral esophagus echocardiography (TOEE) after the probe reaches the esophagus. Results TNPEE was performed in 103 patients. Forty-five patients (43.7%) underwent the examination successfully, 46 patients (44.7%) failed because of objective reasons, 12 patients midway refused to accept the examination and cancelled the examination, accounting for 11.6%, 11 patients (12.1%) suffered from epistaxis. Of all the patients with epistaxis, 9 had taken anticoagulant drugs, accounting for 82% of the patients with epistaxis. The vital signs of all patients were stable and no serious complications occurred. Conclusion Compared with TOEE, TNPEE can cause less nausea and vomiting reaction, and patients take longer time to undergo examination, which is conducive to more detailed examination. However, TNPEE has a high requirement for the probe, and its success rate is relatively low. It is easy to cause nasal bleeding in patients, so its wide clinical application is limited.

Decomposition-based evolutionary algorithms are popular with solving multi-objective optimization problems. It uses weight vectors and aggregate functions to keep the convergence and diversity. However, it is hard to balance diversity and convergence in high-dimensional objective space. In order to discriminate solutions and equilibrate the convergence and diversity in high-dimensional objective space, a two-archive many-objective optimization algorithm based on D-dominance and decomposition (Two Arch-D) is proposed. In Two Arch-D, the method of D-dominance and adaptive strategy adjusting parameter are used to apply selection pressure on the population to identify better solutions. Then, it uses the two archives’ strategy to equilibrate convergence and diversity, and after classifying solutions in convergence archive, the improved Tchebycheff function is used to evaluate the solution set and retain the better solutions. For the diversity archive, the diversity is maintained by making any two solutions as far apart and different as possible. Finally, the Two Arch-D is compared with other four multi-objective evolutionary algorithms on 45 many-objective test problems (including 5, 10 and 15 objectives). Good performance of the algorithm is verified by the description and analysis of the experimental results.

In this study, a temperature imaging method based on a magnetic nanoparticle thermometer is proposed and evaluated. We first constructed a new model for finding the single temperature of magnetic nanoparticles with core size distribution. Specifically, we employed an air-core coil as a magnetic probe, which measured the magnetization of magnetic nanoparticles (MNPs). We then constructed a relation between the output signal of an air-core coil in the direction of the geometric center axis and the magnetization of the MNPs in a 2-D imaging area based on the magnetic dipole theory. Once this was achieved, we established a temperature imaging model by utilizing Green function as the convolution kernel, which describes the distance relationship between MNPs and the geometric center axis of the air-cored coil. After this, we calculated the harmonic distribution by a deconvolution algorithm and determined the temperature of the MNPs at different positions based on the model of harmonic amplitude and temperature, resulting in the 2-D temperature distribution. The simulation proved that the model and method of 2-D temperature distribution measurement could theoretically be acceptable. In the experiment, the 2-D temperature distribution of multi-chip power LEDs was measured accurately by a homemade system, thus demonstrating the feasibility of the proposed method for temperature imaging. This method is expected to provide a new solution for measuring the internal temperature distribution of opaque objects under extreme conditions.