Search

Background: Lactate dehydrogenase (LDH) is one of the important enzyme systems for glycolysis and gluconeogenesis. It can catalyze the reduction and oxidation reaction between propionic acid and L-lactic acid, which is usually overexpressed in cancer cells. Therefore, inhibiting the activity of LDH is a promising way for the treatment of cancer. In this study, an effective method based on ligand fishing and ultra performance liquid chromatography-mass spectrum (UPLC-MS) was established to screen and identify active ingredients from Selaginella doederleinii with potential inhibitory activity for LDH., Methods: Firstly, LDH was immobilized on the magnetic nanoparticles (MNPs), three immobilization parameters including LDH concentration, immobilization time and pH were optimized by single factor and response surface methodology for maximum (max) immobilization yield. Then, a mixed model of galloflavin and chlorogenic acid (inhibitors and non-inhibitors of LDH) was used to verify the specificity of immobilized LDH ligand fishing, and the conditions of ligand fishing were further optimized. Finally, combined with UPLC-MS, immobilized LDH was used to simultaneously screen and identify potential LDH inhibitors from the ethyl acetate extract of Selaginella doederleinii ., Results: The prepared fishing material was comprehensively characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) and fourier transform infrared spectrometer (FT-IR). The optimal immobilization conditions were obtained as LDH concentration of 0.7 mg/mL, pH value of 4.5, and immobilization time of 3.5 h. Under these conditions, the max immobilization yield was (3.79 ± 0.08) × 103 U/g. The specificity analysis showed that immobilized LDH could recognize and capture ligands, and the optimal ligand fishing conditions included that the incubation time was 30 min, the elution time was 20 min, and the concentration of methanol as eluent was 80%. Finally, two LDH inhibitors, amentoflavone and robustaflavone, were screened by immobilized LDH from the ethyl acetate extract of Selaginella doederleinii ., Conclusions: The study provided a meaningful evidence for discovering the bioactive constituents in ethyl acetate extract of Selaginella doederleinii related to cancer treatment, and this ligand fishing method was feasible for screening enzyme inhibitors from similar complex mixtures., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Zinc is an essential trace element for bone growth and bone homeostasis in the human body. Bone mesenchymal stem cells (BMSCs) are multipotent progenitors existing in the bone marrow stroma with the capability of differentiating along multiple lineage pathways. Zinc plays a paramount role in BMSCs, which can be spurred differentiating into osteoblasts, chondrocytes, or adipocytes, and modulates the formation and activity of osteoclasts. The expression of related genes also changed during the differentiation of various cell phenotypes. Based on the important role of zinc in BMSC differentiation, using zinc as a therapeutic approach for bone remodeling will be a promising method. This review explores the role of zinc ion in the differentiation of BMSCs into various cell phenotypes and outlines the existing research on their molecular mechanism.

The ability of articular cartilage to repair itself is limited because it lacks blood vessels, nerves, and lymph tissue. Once damaged, it can lead to joint swelling and pain, accelerating the progression of osteoarthritis. To date, complete regeneration of hyaline cartilage exhibiting mechanical properties remains an elusive goal, despite the many available technologies. The inflammatory milieu created by cartilage damage is critical for chondrocyte death and hypertrophy, extracellular matrix breakdown, ectopic bone formation, and progression of cartilage injury to osteoarthritis. In the inflammatory microenvironment, mesenchymal stem cells (MSCs) undergo aberrant differentiation, and chondrocytes begin to convert or dedifferentiate into cells with a fibroblast phenotype, thereby resulting in fibrocartilage with poor mechanical qualities. All these factors suggest that inflammatory problems may be a major stumbling block to cartilage repair. To produce a milieu conducive to cartilage repair, multi-dimensional management of the joint inflammatory microenvironment in place and time is required. Therefore, this calls for elucidation of the immune microenvironment of cartilage repair after injury. This review provides a brief overview of: (1) the pathogenesis of cartilage injury; (2) immune cells in cartilage injury and repair; (3) effects of inflammatory cytokines on cartilage repair; (4) clinical strategies for treating cartilage defects; and (5) strategies for targeted immunoregulation in cartilage repair. STATEMENT OF SIGNIFICANCE: Immune response is increasingly considered the key factor affecting cartilage repair. It has both negative and positive regulatory effects on the process of regeneration and repair. Proinflammatory factors are secreted in large numbers, and necrotic cartilage is removed. During the repair period, immune cells can secrete anti-inflammatory factors and chondrogenic cytokines, which can inhibit inflammation and promote cartilage repair. However, inflammatory factors persist, which accelerate the degradation of the cartilage matrix. Furthermore, in an inflammatory microenvironment, MSCs undergo abnormal differentiation, and chondrocytes begin to transform or dedifferentiate into fibroblast-like cells, forming fibrocartilage with poor mechanical properties. Consequently, cartilage regeneration requires multi-dimensional regulation of the joint inflammatory microenvironment in space and time to make it conducive to cartilage regeneration., Competing Interests: Declaration of Competing Interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans., Methods: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient., Results: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion., Conclusion: Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Individuals can perceive the mean emotion or mean identity of a group of faces. It has been considered that individual representations are discarded when extracting a mean representation; for example, the "element-independent assumption" asserts that the extraction of a mean representation does not depend on recognizing or remembering individual items. The "element-dependent assumption" proposes that the extraction of a mean representation is closely connected to the processing of individual items. The processing mechanism of mean representations and individual representations remains unclear. The present study used a classic member-identification paradigm and manipulated the exposure time and set size to investigate the effect of attentional resources allocated to individual faces on the processing of both the mean emotion representation and individual representations in a set and the relationship between the two types of representations. The results showed that while the precision of individual representations was affected by attentional resources, the precision of the mean emotion representation did not change with it. Our results indicate that two different pathways may exist for extracting a mean emotion representation and individual representations and that the extraction of a mean emotion representation may have higher priority. Moreover, we found that individual faces in a group could be processed to a certain extent even under extremely short exposure time and that the precision of individual representations was relatively poor but individual representations were not discarded., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Ji, Li and Chen.)

The Mildew Resistance Locus O (MLO) gene family has been investigated in many species. However, there are few studies on chrysanthemum MLO genes. We report in this study that CmMLO17 in Chrysanthemum morifolium was upregulated after Alternaria alternata infection. Silencing of CmMLO17 by artificial microRNA resulted in reduced susceptibility of chrysanthemum to A. alternata infection. Genes in the abscisic acid (ABA) and Ca 2+ signaling pathways were upregulated in the CmMLO17-silenced line R20 compared to the wild-type plants. We speculated that CmMLO17-silenced plants had a faster and stronger defense response that was mediated by the ABA and Ca 2+ signaling pathways, resulting in reduced susceptibility of chrysanthemum to A. alternata infection. In addition, a candidate gene, CmKIC, that may interact with CmMLO17 was discovered by the yeast two-hybrid assay. The interaction between CmMLO17 and CmKIC was confirmed using the yeast two-hybrid assay and bimolecular fluorescence complementation (BiFC) analysis. CmMLO17 and CmKIC were both located on the plasma membrane, and CmKIC was also located on the nucleus. CmKIC overexpression increased the susceptibility of chrysanthemum to A. alternata, whereas CmKIC silencing resulted in reduced susceptibility. Therefore, CmMLO17 and CmKIC may work together in C. morifolium to support the growth of A. alternata. The results of this study will provide insight into the potential function of MLO and improve the understanding of plant defense responses to necrotrophic pathogens.

Genetic factors play a key role in the pathogenesis of autoimmune diseases, whereas the disease-causing variants remain largely unknown. Herein, we performed an exome-wide association study of systemic sclerosis in a Han Chinese population. In the discovery stage, 527 patients with systemic sclerosis and 5,024 controls were recruited and genotyped. In the validation study, an independent sample set of 479 patients and 1,096 controls were examined. In total, we found that four independent signals reached genome-wide significance. Among them, rs7574865 (P combined  = 3.87 × 10 -12 ) located within signal transducer and activator of transcription 4 gene was identified previously using samples of European ancestry. Additionally, another signal including three SNPs in linkage disequilibrium might be unreported susceptibility loci located in the epidermis differentiation complex region. Furthermore, two SNPs located within exon 3 of IGHM (rs45471499, P combined  = 1.15 × 10 -9 ) and upstream of LRP2BP (rs4317244, P combined  = 4.17 × 10 -8 ) were found. Moreover, rs4317244 was identified as an expression quantitative trait locus for LRP2BP that regulates tight junctions, cell cycle, and apoptosis in endothelial cell lines. Collectively, our results revealed three signals associated with systemic sclerosis in Han Chinese and suggested the importance of LRP2BP in systemic sclerosis pathogenesis. Given the limited sample size and discrepancies between previous results and our study, further studies in multiethnic populations are required for verification., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This meta-analysis aimed to compare the clinical symptoms of COVID-19 pneumonia in children., Methods and Analysis: Electronic databases including PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI) database, Wanfang Database, and Chinese Biomedical Literature Database (CBM) were searched from its inception to June 21, 2020. We only included studies that reported clinical symptoms of COVID pneumonia in children. Quality of the included studies was assessed by 2 authors. Pooled results were summarized by STATA 12.0 software.The heterogeneity was measured by I2 tests (I2 < 50 indicates little heterogeneity, I2≥50 indicates high heterogeneity). Publication bias was performed by funnel plot and statistically assessed by Begg test (P > .05 as no publication bias)., Results: Results will be shown as figures or tables., Conclusion: Our study aims to systematically present the clinical symptoms of COVID-19 pneumonia patients in children, so as to further provide guidance for clinical management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

In this study, K417G Ni-based superalloy with a 20-mm gap was successfully bonded at 1200 °C using powder metallurgy with a powder mixture. The results indicated that the microstructure and mechanical properties of the as-bonded alloy were highly dependent on the brazing time (15-45 min), mainly due to the precipitation and distribution characteristics of M 3 B 2 boride particles. Specifically, alloy brazed for 30 min exhibited desirable mechanical properties, such as a high tensile ultimate strength of 971 MPa and an elongation at fracture of 6.5% at room temperature, exceeding the balance value (935 MPa) of the base metal. The excellent strength and plasticity were mainly due to coherent strengthening and dispersion strengthening of the in situ spherical and equiaxed M 3 B 2 boride particles in the γ + γ' matrix. In addition, the disappearance of dendrites and the homogenization of the microstructure are other factors that cannot be excluded. This powder metallurgy technique, which can avoid the eutectic transformation of traditional brazing, provides a new effective method for wide-gap repair of alloy materials.

Through an analysis of data gathered from Chinese firms surveyed by the Carbon Disclosure Project (CDP), this paper studies the motivations of Chinese firms to respond to the CDP. The results indicate that (1) Chinese firms are more inclined to respond to the CDP survey for the sense-making motivation; (2) Chinese firms are less inclined to respond to the CDP survey due to the existence of proprietary costs for information disclosure; (3) self-interested political motivation is a negative motivation for Chinese firms to respond to the CDP survey; state-owned enterprises (SOEs) are less inclined to respond to the CDP survey than are non-SOEs; and (4) Chinese firms did not consider a financing motivation when deciding whether to respond to the CDP survey. However, the results of our further research show that if firms actively respond to the CDP survey, their financing constraints can be significantly reduced. This paper studies the four motivations for Chinese firms to respond to the CDP survey, contributing to the research of carbon emission disclosure. This paper highlights the importance of corporate carbon awareness for carbon emission disclosure, builds an understanding of the internal driving forces of response to the CDP survey among Chinese firms, and thus promotes the increase of Chinese corporate disclosure of carbon emission.

Sediment resuspension plays an important role to provide nutrient release for algal growth in large shallow lakes. The settling velocity (w s ) is the key parameter for understanding the suspended sediment transport. In this paper, acoustic Doppler velocimeter (ADV) and optical backscatter sensor (OBS) instruments were used to measure in situ velocities and suspended sediment concentration (SSC) simultaneously without affecting the ambient turbulence in the bottom layer of Lake Taihu. The results showed that (1) ADV echo intensity (EI) could be transferred into SSC successfully by using a simple logarithmic relationship with a strong correlation of 0.87. (2) Three methods from a balance of settling and diffusive flux gradients for calculating settling velocities were applied, including Reynolds concentration flux, estimation of eddy diffusivity using the von-Karman Prandtl equation, and Kwon's power equation. The average settling velocity during the observation period was 0.11 mm/s for Lake Taihu. (3) The fitted power function, w s  = 1.85 × 10 -3 C 1.04 , could be used to estimate w s according to SSC. (4) Settling velocity changes with SSC, vertical velocities, and wind speed, which describes suspended sediment instantaneous and continuous motions. This paper provides an effective approach for estimating the settling velocity, provides a reference value of settling velocity for hydrodynamic model, and supports a better understanding of sediment transport process and nutrient release in large shallow lakes.

Chrysanthemum is an important ornamental plant which is increasingly being monocropped. Monocropping is known to affect both fungal abundance and species diversity. Here, quantitative PCR allied with DGGE analysis was used to show that fungi were more abundant in the rhizosphere than in the bulk soil and that the fungal populations changed during the growth cycle of the chrysanthemum. The majority of amplified fragments appeared to derive from Fusarium species, and F. oxysporum and F. solani proved to be the major pathogenic species which are built up by monocropping.

Objective: To study the transdermal absorbability of gentiopicroside, naringin and protosappanin B contained in Xuanbi gel plaster., Method: The Franz diffusing cells method was adopted for the in vitro model of rat belly skins. Three indexes, gentiopicroside, naringin and protosappanin B, residued in the accept liquid, skins and plaster were determined by HPLC., Result: The penetration rates of gentiopicroside, naringin and protosappanin B were respectively 3.47, 1.59, 2.13 microg x cm(-2) x h(-1). After 24 h, their penetration rates were 25.42%, 11.73%, 17.78%, respectively. The residual quantities of gentiopieroside, naringin and protosappanin B in skin were 0.231, 0.593, 0.568 microg x cm(-2), ith the retention rates of 0.027%, 0.227%, 0.475%, respectively. The amount of residue of gentiopicroside, naringin and protosappanin B in plaster were 2179, 674, 278 microg, with the retention rates of 81.36%, 81.92%, 73.83%, respectively., Conclusion: The in vitro transdermal behavior of Xuanbi gel plaster is close to a zero-order process. The residual quantity the retention rate in skins is much lower than the penetration rate and the residual rate in plaster.