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Soybean is a major crop that provides essential protein and oil for food and feed. Since its origin in China over 5000 years ago, soybean has spread throughout the world, becoming the second most important vegetable oil crop and the primary source of plant protein for global consumption. From early domestication and artificial selection through hybridization and ultimately molecular breeding, the history of soybean breeding parallels major advances in plant science throughout the centuries. Now, rapid progress in plant omics is ushering in a new era of precision design breeding, exemplified by the engineering of elite soybean varieties with specific oil compositions to meet various end-use targets. The assembly of soybean reference genomes, made possible by the development of genome sequencing technology and bioinformatics over the past 20 years, was a great step forward in soybean research. It facilitated advances in soybean transcriptomics, proteomics, metabolomics, and phenomics, all of which paved the way for an integrated approach to molecular breeding in soybean. In this review, we summarize the latest progress in omics research, highlight novel findings made possible by omics techniques, note current drawbacks and areas for further research, and suggest that an efficient multi-omics approach may accelerate soybean breeding in the future. This review will be of interest not only to soybean breeders but also to researchers interested in the use of cutting-edge omics technologies for crop research and improvement.

Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumours. The function and mechanism of apatinib in oesophageal squamous cell carcinoma (ESCC) remain unknown. In present study, we found that the development of ESCC in patients was controlled by treatment of combination of apatinib and a chemotherapeutic drug. Moreover, apatinib efficiently promotes cell apoptosis, inhibits cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and activity of the Akt/mTOR pathway in ESCC cells. Western blot analysis showed that apatinib significantly increased vimentin protein levels, decreased Bcl2, matrix metalloproteinase 9 (MMP9), E-cadherin, p-Akt and p-mTOR protein levels in ESCC cells. Furthermore, apatinib enhanced chemosensitivity of cytotoxic drugs paclitaxel (TAX), 5-fluorouracil (5-FU) and cisplatin (DDP) by upregulating expression of vimentin protein, and downregulating expression of Bcl2, MMP9 and E-cadherin protein in vitro. Compared with single-agent groups, the combination of apatinib with each chemotherapeutic drug significantly repressed tumour growth and angiogenesis through blocking the expression of Ki67 and VEGFR-2 in vivo. Taken together, apatinib efficiently inhibits cell growth through blocking Bcl2 and Akt/mTOR pathway, and suppresses metastasis via inhibiting MMP9 and EMT in ESCC cells. Apatinib promoted antitumour effect of chemotherapeutic agents through promoting cell apoptosis and inhibiting EMT and angiogenesis in ESCC., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: This study is aimed at exploring the association between autophagy and tumor immune infiltration (TII) in colorectal cancer (CRC)., Methods and Materials: We downloaded the transcriptome profiling and clinical data for CRC from The Cancer Genome Atlas (TCGA) database and obtained the normal colon transcriptome profiling data from Genotype-Tissue Expression Project (GTEx) database. The list of autophagy-related signatures was obtained from the Human Autophagy Database. We isolated the autophagy-related genes from the CRC gene expression matrix and constructed an autophagy-related prognostic (ARP) risk model. Then, we constructed a multiROC curve to validate the prognostic ability of the ARP risk model. CIBERSORT was used to determine the fractions of 22 immune cells in each CRC sample, and the association between these TII cells and CRC clinical variables was further investigated. Finally, we estimated the association of 3 hub-ARP signatures and 20 different types of TII cell distribution., Results: We classified 447 CRC patients into 224 low-risk and 223 high-risk patients using the median ARP risk score. According to the univariate survival test results, except for gender ( P = 0.672), age ( P = 0.008), cancer stage, and pathological stage T, M, and N were closely correlated with the prognosis of CRC patients ( P < 0.001). Multivariate survival analysis results indicate that age and rescore were the only independent prognostic indicators with significant differences ( P < 0.05). After merging the immune cell distribution (by CIBERSORT) with the CRC clinical data, the results indicate that activated macrophage M0 cells exhibited the highest clinical response, which included cancer stage and stage T, N, and M. Additionally, six immune cells were closely associated with cancer stage, including regulatory T cells (Tregs), gamma delta T cells, follicular helper T cells, activated memory CD4 T cells, activated NK cells, and resting dendritic cells. Finally, we evaluated the correlation of ARP signatures with TII cell distribution. Compared with the other correlation, NRG1 and plasma cells (↑), risk score and macrophage M1 (↑), NRG1 and dendritic cell activated (↑), CDKN2A and T cell CD4 memory resting (↓), risk score and T cell CD8 (↑), risk score and T cell CD4 memory resting (↓), and DAPK1 and T cell CD4 memory activated (↓) exhibited a stronger association ( P < 0.0001)., Conclusions: In summary, we explored the correlation between the risk of autophagy and the TII microenvironment in CRC patients. Furthermore, we integrated different CAR signatures with tumor-infiltrating immune cells and found robust associations between different levels of CAR signature expression and immune cell infiltrating density., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yu Bian-fang et al.)

Ovarian cancer has the most mortality of all gynecologic malignancies. High-grade serous ovarian carcinoma (HGSOC) is the most common and deadly type of ovarian cancer. Tumor recurrence occurs due to the emergence of chemotherapy resistance. Thus, searching for new therapeutic strategies is essential for the management of ovarian cancer. Deregulation of iron metabolism can be used by ovarian cancer cells to survive, proliferate and metastasize. Here we report that sodium molybdate, a soluble molybdenum (Mo) compound, induces the elevation of the labile iron pool (LIP) in ovarian cancer cells, correlated with the down-regulation of genes involved in extracellular matrix organization. Sodium molybdate also induces depletion of glutathione (GSH) through mediating the production of nitric oxide (NO). Elevation of LIP and depletion of GSH promote the ferroptosis of ovarian cancer cells. Meanwhile, nitric oxide induces mitochondrial damage through inhibiting mitochondrial aconitase activity, ATP production, and mitochondrial membrane potential, leading to apoptosis of ovarian cancer cells. In vivo study shows that sodium molybdate reduces tumor burden in nude mice. Xenografts treated with sodium molybdate are characterized by obvious iron accumulation, increased expression of the iron storage protein ferritin, and lipid peroxide product 4-hydroxynonenal. In addition, an elevated percentage of apoptotic cells is observed in xenografts treated with sodium molybdate. Taken together, these results demonstrate that sodium molybdate can induce both ferroptosis and apoptosis of ovarian cancer cells, making it a potential therapeutic candidate for ovarian cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In response to DNA double-strand breaks (DSBs), DNA damage repair factors are recruited to DNA lesions and form nuclear foci. However, the underlying molecular mechanism remains largely elusive. Here, by analyzing the localization of DSB repair factors in the XY body and DSB foci, we demonstrate that pre-ribosomal RNA (pre-rRNA) mediates the recruitment of DSB repair factors around DNA lesions. Pre-rRNA exists in the XY body, a DSB repair hub, during meiotic prophase, and colocalizes with DSB repair factors, such as MDC1, BRCA1 and TopBP1. Moreover, pre-rRNA-associated proteins and RNAs, such as ribosomal protein subunits, RNase MRP and snoRNAs, also localize in the XY body. Similar to those in the XY body, pre-rRNA and ribosomal proteins also localize at DSB foci and associate with DSB repair factors. RNA polymerase I inhibitor treatment that transiently suppresses transcription of rDNA but does not affect global protein translation abolishes foci formation of DSB repair factors as well as DSB repair. The FHA domain and PST repeats of MDC1 recognize pre-rRNA and mediate phase separation of DSB repair factors, which may be the molecular basis for the foci formation of DSB repair factors during DSB response., (© 2022. The Author(s), under exclusive licence to Center for Excellence in Molecular Cell Science, CAS.)

Butorphanol, a partial agonist of opioid receptor κ 1 receptor, can and is widely used as an analgesic drug to relieve moderate and severe pain in clinic. Osteosarcoma is one of the most common malignant bone tumor in adolescents under the age of 20. To our knowledge no study has investigated the effect of butorphanol on the proliferation of osteosarcoma cells. In this study, The proliferation of osteosarcoma cells was measured by CCK-8 and colony formation assays, and the migration of osteosarcoma cells were detected by scratch and transwell assays. The expression of piRNA was detected by RNA sequencing and real-time PCR. PiRNA mimics or inhibitors have been used to upregulate or inhibit piRNA expression in osteosarcoma cells, respectively. We found that butorphanol, at the concentration of 10ug/ml or higher, could significantly inhibit the proliferation and migration of osteosarcoma cells. Our resuslts indicated that butorphanol promoted the expression of piRNA hsa&#95;piR&#95;006613 and overexpression of piRNA hsa&#95;piR&#95;006613 inhibited the proliferation and migration of osteosarcoma cells. our study also showed that inhibition of the expression of piRNA hsa&#95;piR&#95;006613 could promote the proliferation and migration of osteosarcoma cells. Butorphanol played the regulatory role on osteosarcoma cells in dependent of piRNA hsa&#95;piR&#95;006613. Butorphanol was found to inhibit the proliferation and migration of osteosarcoma cells by promoting piRNA hsa&#95;piR&#95;006613 expression. Bioinformatics analysis showed that hsa&#95;piR&#95;006613 downregulated FN1 protein expression by binding with 3'-UTR of FN1 mRNA. In all, the present research indicated that butorphanol suppresses the proliferation of osteosarcoma by promoting the expression of piRNA hsa&#95;piR&#95;006613, which downregulated the expression of FN1. Has&#95;piR&#95;006613 may become a new therapeutic target for osteosarcoma., 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 © 2022 Cui, Xin, Li, Deng and Gao.)

The environmental fate of 3-nitro-1,2,4-triazol-5-one (NTO) and other insensitive munitions constituents (MCs) is of significant concern due to their high water solubility and mobility relative to legacy MCs. Plant-based biochars have been shown to possess a considerable electron storage capacity (ESC), which enables them to undergo reversible electron transfer reactions. We hypothesized biochar can act as a rechargeable electron donor to effect abiotic reduction of MCs repeatedly through its ESC. To test this hypothesis, MC reduction experiments were performed using wood-derived biochars that were oxidized with dissolved oxygen or reduced with dithionite. Removal of aqueous NTO, an anion at circumneutral pH, by oxidized biochar was minimal and occurred through reversible adsorption. In contrast, NTO removal by reduced biochar was much more pronounced and occurred predominantly through reduction, with concomitant formation of 3-amino-1,2,4-triazol-5-one (ATO). Mass balance and electron recovery with ferricyanide further showed that (1) the amount of NTO reduced to ATO was relatively constant (85-100 μmol per gram of biochar) at pH 6-10; (2) the fraction of biochar ESC reactive toward NTO was ca . 30% of that toward ferricyanide; (3) the NTO-reactive fraction of the ESC was regenerable over multiple redox cycles. We also evaluated biochar transformation of other MCs, including nitroguanidine (NQ), 2,4-dinitroanisole (DNAN), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). While mass and electron balances could not be established due to sorption, DNAN and RDX reduction by reduced biochar was confirmed via detection of multiple reduction products. In contrast, NQ was not reduced under any of the conditions tested. This study is the first demonstration of organic contaminant degradation through biochar's rechargeable ESC. Our results indicate biochar is a regenerable electron storage medium and sorbent that can remove MCs from water through concurrent reduction and sorption, and is thus potentially useful for pollution control and remediation at military facilities.

The study investigated the changes in IgE binding capacity, protein profiles and peptide compositions after soybeans were boiled and autoclaved. The results of ELISA showed that the IgE binding capacity of soybean was reduced by 69.3% and 88.9% after boiling and autoclaving, respectively. Above 43 and 10 kDa proteins disappeared in boiled and autoclaved soybeans from SDS-PAGE, respectively. A Venn diagram and heat map showed that there was no change in allergen types and a reduction in allergen contents in the boiled and autoclaved soybeans. The changes in peptide compositions were also observed in the boiled and autoclaved soybeans through Venn diagram, PCA and heat map. LC/MS-MS and peptide mapping analysis demonstrated that boiling and autoclaving masked many epitopes in Gly m 4 and Gly m 5, such as ALVTDADNVIPK, SVENVEGNGGPGTIKK and KITFLEDGETK of Gly m 4 and VEKEECEEGEIPRPRPRPQHPER of Gly m 5, resulting in a reduction of IgE binding capacity in the extracted proteins. By contrast, the exposure of many epitopes in Gly m 6 was observed in boiled and autoclaved soybeans, which might be mainly responsible for the existing IgE binding capacity in the treated soybean proteins. Interestingly, the IgE binding capacity of soybeans showed a positive correlation with the total contents and number of peptides in Gly m 4-Gly m 6.

Ascorbic acid (AscA) and gallic acid (GalA) are common electron donors and their boosting effect on lytic polysaccharide monooxygenases (LPMO) has been studied extensively. However, their influence on cellulase hydrolytic action has been ignored. In this work, the effect of AscA and GalA on cellulases hydrolytic action was evaluated. It was found that AscA could increase the hydrolysis of cellulose by cellulases, while GalA showed no effect on cellulases' hydrolytic action. The effect of AscA differed for the monocomponent cellulases: it showed a special boosting effect on cellobiohydrolase, rather than endoglucanase and β-glucosidase. This promoting effect could be another mechanism behind the boosting effect of the AscA-driven LPMO system on cellulose saccharification. These findings thus advance the understanding of the role of electron donors on cellulose saccharification and offer important clues on how to evaluate the feasibility of electron donors from a new perspective., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Metal halide perovskite and its derivatives show great promise in X-ray detection. However, large-scale fabrication of high-quality thick perovskite films is still full of challenges due to the complicated crystal nucleation process that always introduces lots of cracks or pinholes in the final perovskite film. Here, a MA 3 Bi 2 I 9 film was fabricated by the cost-effective, scalable spraying process, and MACl was used as an additive to effectively tune the crystallization process. As a result, a dense MA 3 Bi 2 I 9 film constituted by large grains was obtained, which has a high carrier mobility of ∼1 cm 2 V -1 s -1 and a large activation energy ( E a ) for ion migration of 0.91 eV. Thanks to the outstanding optoelectronic characteristics, X-ray detectors with a configuration of ITO/MA 3 Bi 2 I 9 /Au show a sensitivity of 35 μC Gy air -1 cm -2 and a limit of detection (LoD) of 0.14 μGy air s -1 , which is outstanding compared with commercial α-Se detectors.

Background: Mycoplasma pneumoniae is a leading cause of community-acquired respiratory infections. Infantile Feire Kechuan Oral Solution (IFKOS) is effective for treatment of M. pneumoniae infection. The aim of this study was to explore the potential mechanism of IFKOS against M. pneumoniae infection in basal epithelial human lung adenocarcinoma A549 cells., Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the effects of IFKOS on the viability of A549 cells infected with M. pneumoniae. Optical microscopy was used to observe cell morphology and a Muse cell analyzer was used to assess apoptosis and the cell cycle phase. Enzyme-linked immunosorbent assays were employed to assess the expression levels of interleukin (IL)-4, IL-6, IL-8, IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-α, and IFN-γ., Results: Under certain conditions, M. pneumoniae infection reduced the viability and inhibited the proliferation of A549 cells, promoted early apoptosis, and arrested cells in the G0/G1 phase, thus shortening the S and G2/M phases (all p < 0.05). M. pneumoniae also upregulated expression of IL-8 and TNF-α and downregulated that of IL-6 (p < 0.05), which switched the immune balance of Th1/Th2 to Th1 cells. IFKOS (5.531 mg/mL) improved the viability and proliferation of M. pneumoniae-infected A549 cells, mitigated early apoptosis, and reversed cell cycle arrest in the G0/G1 phase, thereby extending the S and G2/M phases (all, p < 0.05). IFKOS downregulated expression of IL-8 and TNF-α and upregulated that of IL-6 (p < 0.01), thereby reversing the immune imbalance of Th1/Th2. Secretion of IL-4, IL-17, IFN-α, and IFN-γ was not observed., Conclusion: IFKOS played a protective role in the regulation of cell viability, apoptosis, the cell cycle, and Th1/Th2 immune imbalance induced by M. pneumoniae infection and conveyed an anti-inflammatory effect in A549 cells., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The aim of the study was to investigate the relationship between myopic severity and the retinal microvasculature based on quantitative variables using optical coherence tomography angiography (OCTA) and to identify OCTA indicators of microvascular network loss in myopia., Methods: This cross-sectional study included 123 eyes of 123 myopic subjects. The included eyes were divided into three groups according to the spherical equivalent (SE) and axial length (AL): low myopia (LM) (-3.00 D ≤ SE ≤ -0.50 D), moderate myopia (MM) (-6.00 D ≤ SE < -3.00 D), and high myopia (HM) (-9.00 D ≤ SE < -6.00 D or AL >26 mm). All the eyes underwent OCTA scans. The densities and thicknesses of the macular and peripapillary zones, including the foveal avascular zone (FAZ) area, superficial vascular plexus (SVP) density, deep vascular plexus (DVP) density, ganglion cell complex (GCC) thickness, full retinal thickness, radial peripapillary capillary plexus (RPCP) density, and retinal nerve fiber layer (RNFL) thickness, were automatically exported., Results: Compared to the LM or MM group, the HM group had a significantly reduced FAZ area (p < 0.05). In most sectors of the parafoveal and perifoveal areas, the HM group had significantly lower DVP density and higher retinal thickness than the LM and MM groups (all p < 0.05). However, significant differences among the three groups in only one or several sectors were observed with regard to SVP density, GCC thickness, and RNFL thickness, and no significant differences among the three groups in any sector were noticed in RPCP density. Perifoveal DVP density and perifoveal full retinal thickness were positively associated with SE and negatively associated with AL in stepwise multiple linear regression analyses adjusted for sex and age., Conclusion: DVP density was closely related to myopic severity. Reduced perifoveal DVP density may serve as an indicator of microvascular network loss in myopia. OCTA may provide useful and crucial information for monitoring the progression of myopia., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objectives: To investigate the effects of β-ecdysterone on fracture healing and the underlying mechanism., Methods: MTT assay was used to detect the cell viability. AO/PI and flow cytometry assays were used to determine the apoptotic rate. The expression level of RunX2, ATG7 and LC3 was evaluated by qRT-PCR and Western blot assays. X-ray and HE staining were conducted on the fractured femur. Immunohistochemical assay was used to detect the expression level of Beclin-1 and immunofluorescence assay was used to measure the expression level of LC3 in the fractured femurs. Western blot was utilized to determine the expression level of PI3K, p-AKT1, AKT1, p-mTOR, mTOR, p-p70S6K, and p70S6K., Results: The ALP activity and the expression of RunX2 in fractured osteoblasts were significantly elevated, the apoptotic rate was suppressed by rapamycin, 60, and 80 μM β-ecdysterone. The state of autophagy both in fractured osteoblasts and femurs was facilitated by rapamycin and β-ecdysterone. Compared to control, Garrett score was significantly promoted in rapamycin and β-ecdysterone groups, accompanied by ameliorated pathological state. Lastly, the PI3K/AKT/mTOR pathway both in fractured osteoblasts and femurs was inhibited by rapamycin and β-ecdysterone., Conclusion: β-ecdysterone might facilitate fracture healing by activating autophagy through suppressing PI3K/AKT/mTOR signal pathway., (© 2021. The Author(s).)

The rice seed setting rate (RSSR) is an important component in calculating rice yields and a key phenotype for its genetic analysis. Automatic calculations of RSSR through computer vision technology have great significance for rice yield predictions. The basic premise for calculating RSSR is having an accurate and high throughput identification of rice grains. In this study, we propose a method based on image segmentation and deep learning to automatically identify rice grains and calculate RSSR. By collecting information on the rice panicle, our proposed image automatic segmentation method can detect the full grain and empty grain, after which the RSSR can be calculated by our proposed rice seed setting rate optimization algorithm (RSSROA). Finally, the proposed method was used to predict the RSSR during which process, the average identification accuracy reached 99.43%. This method has therefore been proven as an effective, non-invasive method for high throughput identification and calculation of RSSR. It is also applicable to soybean yields, as well as wheat and other crops with similar characteristics., 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 Guo, Li, Zhang, Li, Hu, Xin, Chen, Wang and Zhu.)

Osteoarthritis (OA) is a chronic degenerative disease that significantly impacts the quality of life of the elderly population. Recently, the pathogenesis of OA has been reported to involve autophagy in chondrocytes. Intriguingly, icariin, one of the main components of epimedium, exerts multiple pharmacological effects, including a protective effect against chondrocyte damage. Thus, we aimed to investigate the therapeutic effect of icariin on OA and its potential underlying mechanism by using a rat model of OA. After treatment with icariin or an autophagy activator (rapamycin) or inhibitor (3-methyladenine), OA chondrocyte viability was measured using the CCK-8 assay, apoptosis in the chondrocytes was evaluated using the acridine orange-propidium iodide assay and flow cytometry, and OA tissue pathological state was assessed using micro-CT scanning and safranin O staining. Furthermore, immunohistochemical staining was used to measure the expression level of Beclin-1 and immunofluorescence labeling was used to visualize LC3 expression, and western blotting was used to determine the expression levels of autophagy proteins and key proteins in the PI3K signaling pathway. The apoptotic rate of OA chondrocytes was markedly elevated by 3-methyladenine and suppressed by rapamycin and icariin; autophagy genes were drastically downregulated in the 3-methyladenine group and upregulated in the rapamycin and icariin groups; and the PI3K/AKT/mTOR signaling pathway was activated by 3-methyladenine and inhibited by rapamycin and icariin. Notably, following treatment with rapamycin and icariin, the severe pathological state in OA cartilage tissues was substantially alleviated, and this was accompanied by activated autophagy and inhibited PI3K signaling in the cartilage tissues. Taken together, these findings indicate that icariin alleviates OA by regulating the autophagy of chondrocytes by mediating PI3K/AKT/mTOR signaling.

Acute myeloid leukemia (AML) was confirmed to be associated with hematopoietic insufficiency, as well as abnormal proliferation, differentiation or survival of myeloid progenitors. Multiple studies reported that microRNA-204 (miR-204) and Hepatocyte growth factor (HGF) played important roles in types of cancers. However, the potential molecular regulatory mechanism between miR-204 and HGF in AML remains to be further defined. Real-time PCR (RT-PCR) was adopted to detect the expression of miR-204 and HG. Relative protein levels were detected by western blot assay. The viability, cell cycle, apoptosis, migration, and invasion were analyzed by MTT, flow cytometry, and transwell assays. Moreover, the target relationship between miR-204 and HGF was predicted by MiRcode website and confirmed by luciferase reporter, RNA pull-down, and western blot assays. Our data suggested that miR-204 was downregulated in AML serum samples and cells. MiR-204 overexpression repressed cell proliferation, migration, invasion, and induced cell apoptosis in AML cells. HGF was upregulated in AML samples and cells, and HGF knockdown inhibited the malignancy of AML cells. In addition, HGF was directly targeted by miR-204. HGF overexpression reversed the effects of miR-204 mimic on AML cell proliferation, apoptosis, migration, and invasion. Besides, miR-204 regulated the c-Met signaling by targeting HGF, thereby regulating the downstream protein levels related to cell proliferation, apoptosis, migration, and invasion in AML cells. In conclusion, miR-204 could regulate AML progression through regulating the HGF/c-Met pathway.

The three-seeded pod number is an important trait that positively influences soybean yield. Soybean variety with increased three-seeded pod number contributes to the seed number/plant and higher yield. The candidate genes of the three-seeded pod may be the key for improving soybean yield. In this study, identification and validation of candidate genes for three-seeded pod has been carried out. First, a total of 36 quantitative trait locus (QTL) were detected from the investigation of recombinant inbred lines including 147 individuals derived from a cross between Charleston and Dongning 594 cultivars. Five consensus QTLs were integrated. Second, an introgressed line CSSL-182 carrying the target segment for the trait from the donor parent was selected to verify the consensus QTL based on its phenotype. Third, a secondary group was constructed by backcrossing with CSSL-182, and two QTLs were confirmed. There were a total of 162 genes in the two QTLs. The mining of candidate genes resulted in the annotation of eight genes with functions related to pod and seed sets. Finally, haplotype analysis and quantitative reverse transcriptase real-time PCR were carried to verify the candidate genes. Four of these genes had different haplotypes in the resource group, and the differences in the phenotype were highly significant. Moreover, the differences in the expression of the four genes during pod and seed development were also significant. These four genes were probably related to the development process underlying the three-seeded pod in soybean. Herein, we discuss the past and present studies related to the three-seeded pod trait in soybean., 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, Jiang, Li, Liu, Qi, Wu, Zhang, Hu, Zhu, Guo, Wang, Zheng, Zhang, Zhao, Wang, Shan, Xin, Luan and Chen.)

Purpose: To characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response., Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6. In an in vivo assay, we used a model established with NPIdKO™ mice, which have a reconstituted immune system generated by transplanting PBMCs through intravenous injection, to evaluate the effect of metformin on tumors., Results: The TCGA esophageal cancer data showed that IL-6 expression was positively correlated with PD-L1 expression and that patients with high IL-6 expression had a significantly lower overall survival rate than patients with low IL-6 expression. PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway. In the coculture system, the metformin pretreatment group showed higher T cell activation and better T cell killing function than the control group. Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response., Conclusions: Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response., 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 Lu, Xin, Guan, Xu, Yang, Chen, Yang, Wang-Gillam, Wang, Zong and Wang.)

Soybean [ Glycine max (L.) Merr.] is an important grain and oil crop in the world, and it is the main source of high-quality protein. The number of four-seeded pods is a quantitative trait in soybean and is closely related to yield in terms of breeding. Therefore, it is of great significance to study the inheritance of four-seed pods and to excavate related genes for improving soybean yield. In this study, individuals with high ratio of four-seed pods which from chromosome segment substitution lines (CSSLs) that can be stably inherited were selected as the parent, and Suinong 14 (SN14) was used as recurrent parent to construct secondary mapping population via marker-assisted selection. From 2006 to 2017, QTL analysis was performed using secondary mapping populations, and the initial QTL mapping interval was 0.67 Mb and was located on Gm07. Based on the initial QTL mapping results, individuals that were heterozygous at the interval (36,116,118-37,399,738 bp) were screened in 2018, and the heterozygous individuals were subjected to inbreeding to obtain 13 F 3 populations, with a target interval of 321 kb. Gene annotation was performed on the fine mapping interval, and 27 genes were obtained. Among 27 genes, Glyma.07G200900 and Glyma.07G201200 were identified as candidate genes. qRT-PCR was used to measure the expression of the 2 candidate genes at different developmental stages of soybean, and the expression levels of the 2 candidate genes in terms of cell division (axillary buds, COTs, EMs) were higher than those in terms of cell expansion (MM, LM), and these genes play a positive regulatory role in the formation of four-seeded pods. Haplotype analysis of 2 candidate genes which shows that Glyma.07G201200 has two excellent haplotypes, and the significance level between the two excellent haplotypes at p  < 0.05. Those results provide the information for gene map-based cloning and molecular marker-assisted breeding of the number of four-seeded pod in soybean., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01265-6., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

Auxin/indoleacetic acid (Aux/IAA) proteins play an important regulatory role in the developmental process of plants and their responses to stresses. A previous study has shown that constitutive expression of OsIAA18 , an Aux/IAA transcription factor gene of rice improved salt and osmotic tolerance in transgenic Arabidopsis plants. However, little work is known about the regulatory functions of the OsIAA18 gene in regulating the abiotic stress tolerance of rice. In this study, the OsIAA18 gene was introduced into the rice cultivar, Zhonghua 11 and the OsIAA18 overexpression in rice plants exhibited significantly enhanced salt and drought tolerance compared to the wild type (WT). Moreover, overexpression of OsIAA18 in rice increased endogenous levels of abscisic acid (ABA) and the overexpression of OsIAA18 in rice plants showed hypersensitivity to exogenous ABA treatment at both the germination and postgermination stages compared to WT. Overexpression of OsIAA18 upregulated the genes involved in ABA biosynthesis and signaling pathways, proline biosynthesis pathway, and reactive oxygen species (ROS)-scavenging system in the overexpression of OsIAA18 in rice plants under salt and drought stresses. Proline content, superoxide dismutase (SOD), and peroxidase (POD) activities were significantly increased, whereas malonaldehyde (MDA), hydrogen peroxide (H 2 O 2 ), and superoxide anion radical (O 2 - ) content were significantly decreased in the transgenic plants under salt and drought stresses. Taken together, we suggest that OsIAA18 plays a positive role in drought and salt tolerance by regulating stress-induced ABA signaling. The OsIAA18 gene has a potential application in genetically modified crops with enhanced tolerance to abiotic stresses., 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 Wang, Niu, Xin, Long, Wang, Liu, Li, Zhang, Qi, Ye, Wang, Pei, Hu, Yuan and Chen.)

This study aimed to explore the value of magnetic resonance imaging (MRI) features based on deep learning super-resolution algorithms in evaluating the value of propofol anesthesia for brain protection of patients undergoing craniotomy evacuation of the hematoma. An optimized super-resolution algorithm was obtained through the multiscale network reconstruction model based on the traditional algorithm. A total of 100 patients undergoing craniotomy evacuation of hematoma were recruited and rolled into sevoflurane control group and propofol experimental group. Both were evaluated using diffusion tensor imaging (DTI) images based on deep learning super-resolution algorithms. The results showed that the fractional anisotropic image (FA) value of the hind limb corticospinal tract of the affected side of the internal capsule of the experimental group after the operation was 0.67 ± 0.28. The National Institute of Health Stroke Scale (NIHSS) score was 6.14 ± 3.29. The oxygen saturation in jugular venous (SjvO 2 ) at T4 and T5 was 61.93 ± 6.58% and 59.38 ± 6.2%, respectively, and cerebral oxygen uptake rate (CO 2 ER) was 31.12 ± 6.07% and 35.83 ± 7.91%, respectively. The difference in jugular venous oxygen (Da-jvO 2 ) at T3, T4, and T5 was 63.28 ± 10.15 mL/dL, 64.89 ± 13.11 mL/dL, and 66.03 ± 11.78 mL/dL, respectively. The neuron-specific enolase (NSE) and central-nerve-specific protein (S100 β ) levels at T5 were 53.85 ± 12.31 ng/mL and 7.49 ± 3.16 ng/mL, respectively. In terms of the number of postoperative complications, the patients in the experimental group were better than the control group under sevoflurane anesthesia, and the differences were substantial ( P  < 0.05). In conclusion, MRI images based on deep learning super-resolution algorithm have great clinical value in evaluating the degree of brain injury in patients anesthetized with propofol and the protective effect of propofol on brain nerves., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Deqian Xin et al.)

Objective: To investigate the clinical application of perioperative nursing care for patients with osteosarcoma of the distal femur who received artificial knee replacement., Methods: A total of 80 patients with osteosarcoma of the distal femur admitted to our hospital from March 2019 to March 2020 were selected as research subjects and divided into the control group and the study group according to their admission sequence. The control group was given routine nursing care, while the study group was given perioperative nursing care. The negative emotions, sleep quality, limb function, pain, complication rate, and nursing satisfaction of the two groups of patients after nursing care were analyzed., Results: After nursing care, (1) the Hamilton depression rating scale (HAMD) and Hamilton anxiety scale (HAMA) scores of the study group were both lower than those of the control group; (2) the sleep quality score of the study group was lower than that of the control group (P < 0.001); (3) the study group obtained higher limb function score and excellent-and-good rate than the control group (P < 0.05); (4) the pain score of the study group was lower than that of the control group (P < 0.05), and the time to functional exercise and length of hospital stay of the study group were shorter than those of the control group (P < 0.05); (5) patients in the study group had a lower complication rate than those in the control group (P=0.02); (6) the nursing satisfaction rating of the study group was higher than that of the control group (P < 0.001)., Conclusion: For patients with osteosarcoma of the distal femur treated by artificial knee replacement, in addition to the amelioration of negative emotions and sleep quality, perioperative nursing also improves the patients' limb function and satisfaction and mitigates pain and complications., Competing Interests: None., (AJTR Copyright © 2021.)

Insulin-like growth factor 2 mRNA-binding protein 2 ( IGF2BP2 , also called IMP2 ) plays an essential role in the development and maturation of germ cells and embryos and is a candidate gene for goat litter size, based on a previous genome-wide selective sweep analysis. In this study, the mRNA expression level of IGF2BP2 was found to be significantly higher in a single-lamb group than in a multi-lamb group. Insertions/deletions (indels) within the goat IGF2BP2 gene, including P4-Ins-13bp and P5-Del-12bp, were verified in 918 Shaanbei White Cashmere (SBWC) female goats. The minor allelic frequencies (MAFs) of P4-Ins-13bp and P5-Del-12bp loci were 0.349 and 0.295, respectively. Analysis using the Chi-square ( χ 2 ) test showed that the genotype ( χ 2 =14.479, P= 0.006) distribution of P4-Ins-13bp was significantly different between the single-lamb and multi-lamb groups. Correlation analysis demonstrated that P4-Ins-13bp was significantly associated with goat litter size ( P= 0.022), and individual goats with the homozygous deletion/deletion (DD) genotype produced more litters than other goats. Therefore, considered as a potential molecular marker significantly related to lambing traits, the P4-Ins-13bp mutation of the goat IGF2BP2 gene can be used in goat breeding with practical molecular marker-assisted selection (MAS) to optimize female reproduction and improve economic efficiency in the goat industry.

Objective: This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE)., Methods: Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2., Results: Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells., Conclusion: miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression., (© 2021. The Author(s).)

Background: After non-contact co-culture of bone marrow mesenchymal stem cells (BMSCs) with nucleus pulposus cells (NPCs), exosomes secreted by BMSCs were able to ameliorate the degree of disc degeneration. The reason for this is, at least in part, that exosomes from BMSCs achieve by affecting the level of autophagy in NPCs, while the components in exosomes are diverse and their specific mechanism of action is still unclear., Purpose: Here, we aimed to explore the therapeutic effect of co-culture of BMSCs and NPCs on NPCs and explore its specific mechanism of action., Study Design/setting: In vitro study., Methods: Rat NPCs and BMSCs were isolated and cultured in vitro. The serum deprivation experiment (using oxygen, glucose, and serum deprivation [OGD]) simulates the pathological state of low blood supply of the intervertebral disc in vivo. We used apoptotic cell staining and flow cytometry to study the effect of BMSCs on the apoptosis rate of rat NPCs, and the apoptotic proteins active-caspase-3, active-caspase-9, autophagy marker proteins LC3 and Beclin 1 were further detected using Western blot analysis. The expression levels of the pro-apoptotic protein Bax and the apoptosis-inhibiting protein Bcl2 were measured. The differentially expressed miRNAs were screened in a gene expression profiling chip. Then qRT-PCR was used to detect the effect of different treatment methods on miR-155 expression. The effect of anti-miR-155 antibodies on autophagy was studied by flow cytometry and transmission electron microscopy. A luciferase reporter assay was used to study the direct interaction between miR-155 and BACH1 mRNA, which was analyzed by TargetScan software, and the results were verified by Western blotting., Results: Compared with the OGD group, the expression level of miR-155 and the NPC autophagy level significantly increased; the HO-1 protein expression increased; and the Bach1 protein expression, degeneration index, and apoptosis index all significantly decreased in the co-culture group. After BMSCs transfected with anti-miR-155 were co-cultured with NPCs, the miR-155 expression in the cells was significantly reduced, the HO-1 protein expression and the level of cell autophagy was reduced. However, Bach1 protein expression, NPC degeneration index, and apoptosis index increased. After being inhibited by the autophagy inhibitor wortmannin, the cell degeneration index and apoptosis rate significantly improved., Conclusion: In the OGD model, BMSCs can significantly increase the viability, the level of autophagy, and reduce the level of apoptosis in rat NPCs. BMSC exosomes increase miR-155 expression in NPCs, which targets Bach1 and in turn upregulates HO-1 expression, activates autophagy in NPCs, inhibits the apoptosis level, and improves intervertebral disc degeneration., Clinical Significance: Our experiment shows that it is maybe feasible to treat disc degeneration with drugs. At the same time, compared with BMSC injection method of treatment, side effects of drug therapy are smaller, and can be controlled, it also provides a new way for intervertebral disc degeneration drug treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Optimal adjustment of cardiac preload is essential for improving left ventricle stroke volume (LVSV) and tissue perfusion. Changes in LVSV caused by central venous pressure (CVP) are the most important concerns in the treatment of critically ill patients. Objectives: This study aimed to clarify the changes in LVSV after negative fluid balance in patients with elevated CVP, and to elucidate the relationship between the parameters of right ventricle (RV) filling state and LVSV changes. Methods: This prospective cohort study included patients with high central venous pressure (CVP) (≥8 mmHg) within 24 h of ICU admission in the Critical Medicine Department of Peking Union Medical College Hospital. Patients were classified into two groups based on the LVSV changes after negative fluid balance. The cutoff value was 10%. The hemodynamic and echo parameters of the two groups were recorded at baseline and after negative fluid balance. Results: A total of 71 patients included in this study. Forty in VI Group (LVOT VTI increased ≥10%) and 31 in VNI Group (LVOT VTI increased <10%). Of all patients, 56.3% showed increased LVSV after negative fluid balance. In terms of hemodynamic parameters at T0, patients in VI Group had a higher CVP ( p < 0.001) and P(v-a)CO 2 ( p < 0.001) and lower ScVO 2 ( p < 0.001) relative to VNI Group, regarding the echo parameters at T0, the RV D /LV D ratio ( p < 0.001), DIVC end-expiratory ( p < 0.001), and ΔLVOT VTI ( p < 0.001) were higher, while T0 LVOT VTI ( p < 0.001) was lower, in VI Group patients. The multifactor logistic regression analysis suggested that a high CVP and RV D /LV D ratio ≥0.6 were significant associated with LVSV increase after negative fluid balance in critically patients. The AUC of CVP was 0.894. A CVP >10.5 mmHg provided a sensitivity of 87.5% and a specificity of 77.4%. The AUC of CVP combined with the RV D /LV D ratio ≥0.6 was 0.926, which provided a sensitivity of 92.6% and a specificity of 80.4%. Conclusion: High CVP and RV D /LV D ratio ≥0.6 were significant associated with RV stressed in critically patients. Negative fluid balance will not always lead to a decrease, even an increase, in LVSV in these patients., 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 Hua, Xin, Xiaoting and Dawei.)

Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of Tet1 results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking Tet1 in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport. Tet1-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene, Itpr2, impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice., (© 2021. The Author(s).)

The halide perovskite X-ray detector can meet the urgent needs of low-dose medical imaging by X-rays. However, there is still a pressing challenge in lacking robust methods for large-scale fabrication of high-quality perovskite films with tunable thickness. Here we report a laminated fabrication of polycrystalline MAPbI 3 by using solvent-free liquid perovskite molten-salt (PMS), that offers reduced toxic issue, scalable fabrication, and highly tunability in film thickness. Nylon membrane was chosen as a scaffold for the infiltration of PMS, which simultaneously acts as a physical barrier to suppress the ionic migration in the MAPbI 3 -nylon composite (denoted as MAPbI 3 -LLP). The enhanced material properties result in good stability and high performance of X-ray detectors that show low detection limit and high sensitivity. Additionally, single gamma-ray photon detection was realized by MAPbI 3 -LLP detectors. The promising performance characteristics of such polycrystalline detectors can accelerate the adoption of polycrystalline perovskites in X-ray imaging and gamma-ray detection.

A novel bacterial strain, designated C23 T , was isolated from a soil sample obtained from King George Island, Antarctica. Phenotypic, phylogenetic, chemotaxonomic and molecular analyses were performed on the new isolate. Strain C23 T formed orange colonies on agar plates and was Gram-stain-positive. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain C23 T was a member of the genus Planococcus and was closely related to Planococcus salinarum DSM 23802 T (98.5% sequence similarity), Planococcus halotolerans SCU63 T (98.3%), Planomicrobium okeanokoites IFO 12526 T (98.3%), Planococcus donghaensis DSM 22276 T (98.3%) and Planococcus maitriensisi S1 T (98.2%). This organism grew at 2-38 °C (optimum, 25-30 °C), pH 6.0-12.0 (optimum, pH 7.5) and 0-14% (w/v) NaCl (optimum, 2%). The predominant menaquinone was MK-8. The major cellular fatty acids were anteiso-C 15:0 , iso-C 14:0 and C 16:1 ω7c alcohol. The whole genome DNA of C23 T was deposited in the GenBank database under accession number WXYN00000000. According to the whole genome, the DNA G + C content of strain C23 T was determined to be 46.8 mol%; the average nucleotide identity (ANI) of strain C23 T and P. salinarum DSM 23802 T , P. halotolerans SCU63 T , P. okeanokoites IFO 12526 T , P. donghaensis DSM 22276 T and P. maitriensis S1 T were 74.1%, 74.3%, 74.1%, 78.8 and 73.6%; the digital DNA-DNA hybridization (dDDH) values between strain C23 T and the five closely related species were 19.7%, 19.6%, 19.5%, 22.4 and 18.6%; the average amino acid identity (AAI) values between strain C23 T and the five closely related species were 73.9%, 74.5%, 74.4%, 84.6 and 74.5%. All data were below the threshold range for species determination. Based on the polyphasic taxonomic study, we considered that strain C23 T represented a novel species of the genus Planococcus for which the name Planococcus soli sp. nov. is proposed. The type strain is C23 T (= KCTC 33644 T  = CGMCC 1.15115 T ).

Objective: To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC). Methods: The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC. Results: Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group ( P <0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4(+) T lymphocytes in ESCC ( r ( s )=0.259, P =0.020), but not correlated with the content of B lymphocytes, CD8(+) T lymphocytes, neutrophils, macrophages or dendritic cells ( P >0.05). Conclusions: S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4(+) T lymphocytes in ESCC tissue.

There is growing interest in expanding the production of soybean oils (mainly triacylglycerol, or TAG) to meet rising feed demand and address global energy concerns. We report that a plastid-localized glycerol-3-phosphate dehydrogenase (GPDH), encoded by GmGPDHp1 gene, catalyzes the formation of glycerol-3-phosphate (G3P), an obligate substrate required for TAG biosynthesis. Overexpression of GmGPDHp1 increases soybean seed oil content with high levels of unsaturated fatty acids (FAs), especially oleic acid (C18:1), without detectably affecting growth or seed protein content or seed weight. Based on the lipidomic analyses, we found that the increase in G3P content led to an elevated diacylglycerol (DAG) pool, in which the Kennedy pathway-derived DAG was mostly increased, followed by PC-derived DAG, thereby promoting the synthesis of TAG containing relatively high proportion of C18:1. The increased G3P levels induced several transcriptional alterations of genes involved in the glycerolipid pathways. In particular, genes encoding the enzymes responsible for de novo glycerolipid synthesis were largely upregulated in the transgenic lines, in-line with the identified biochemical phenotype. These results reveal a key role for GmGPDHp1-mediated G3P metabolism in enhancing TAG synthesis and demonstrate a strategy to modify the FA compositions of soybean oils for improved nutrition and biofuel., (© 2021 Institute of Botany, Chinese Academy of Sciences.)

Organolead trihalide perovskite single crystals (SCs) offer unprecedented opportunity for X-ray and visible light detection. Nevertheless, it remains a challenge to keep simultaneous high-performance and stability at a high-temperature working mode. Herein, formamidinium lead bromide (FAPbBr 3 ) SCs are developed to successfully address these issues. Low-temperature crystallized induced FAPbBr 3 SCs possess an excellent mobility-lifetime product and an ultralow surface charge recombination velocity, thus exhibiting an X-ray dose rate as low as 0.3 μGy air s -1 as a sensitive radiation detector. Furthermore, it also contributes a specific detectivity as high as 3.5 × 10 12 cm Hz 1/2 W -1 , keeping stable at high-temperature of 460 K as a photodetector. A prototype of an imaging system with diffuse reflection mode is constructed using detectors as receivers, enabling defined scanning images in a high temperature environment. The bifunctional FAPbBr 3 SC detectors will motivate new strategies for stable detection in an extreme space environment.

Background: Compound Xueshuantong capsule (CXC) and Hexuemingmu tablet (HXMMT) are two important Chinese patent medicines (CPMs) frequently used to treat proliferative diabetic retinopathy (PDR), especially when complicated with vitreous hemorrhage (VH). However, a network pharmacology approach to understand the therapeutic mechanisms of these two CPMs in PDR has not been applied., Objective: To identify differences in the active ingredients between CXC and HXMMT and to comparatively predict and further analyze the molecular targets shared by these CPMs and PDR. Materials and methods . The differentially expressed messenger RNAs (mRNAs) between normal retinal tissues in healthy individuals and active fibrovascular membranes in PDR patients were retrieved from the Gene Expression Omnibus database. The active ingredients of CXC and HXMMT and the targets of these ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. The intersections of the CPM (CXC and HXMMT) targets and PDR targets were determined. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, and the ingredient-target networks, protein-protein interaction networks, and KEGG-target (KEGG-T) networks were constructed., Results: CXC contains 4 herbs, and HXMMT contains 19. Radix salviae is the only herb common to both. CXC had 34 potential therapeutic targets in PDR, while HXMMT had these 34 and 10 additional targets. Both CPMs shared the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessel diameter and size, vasoconstriction, smooth muscle contraction, hemostasis, and blood coagulation. The shared pathways included the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, and IL-17 signaling pathway., Conclusions: Both CXC and HXMMT include components effective at treating PDR and affect the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessels, and blood coagulation. Radix salviae , the only herb common to both CPMs, contains many useful active ingredients. The PDR-CXC and PDR-HXMMT networks shared 34 common genes (RELA, HSPA8, HSP90AA, HSP90AB1, BRCA, EWSR1, CUL7, HNRNPU, MYC, CTNNB1, MDM2, YWHAZ, CDK2, AR, FN1, HUWE1, TP53, TUBB, EP300, GRB2, VCP, MCM2, EEF1A1, NTRK1, TRAF6, EGFR, PRKDC, SRC, HDAC5, APP, ESR1, AKT1, UBC, and COPS5), and the PDR-HXMMT network has 10 additional genes (RNF2, VNL, RPS27, COPS5, XPO1, PARP1, RACK1, YWHAB, and ITGA4). The top 5 pathways with the highest gene ratio in both networks were the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, IL-17 signaling pathway, and focal adhesion. Additional pathways such as neuroactive ligand-receptor interaction, chemokine signaling pathway, and AMPK signaling pathway were enriched with HXMMT targets. Thus, HXMMT has more therapeutic targets shared by different active ingredients and more abundant gene functions than CXC, which may be two major reasons why HXMMT is more strongly recommended than CXC as an auxiliary treatment for new-onset VH secondary to PDR. However, the underlying mechanisms still need to be further explored., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Hongyan Yao et al.)

We previously reported that L-Cysteine, H 2 S donor, remarkably attenuated neuroinflammation following hypoxia-ischemia (HI) brain injury in neonatal mice. However, its anti-inflammatory mechanism for HI insult is still unknown. The study focus on the effects of L-Cysteine on immune cell populations, Ca 2+ mobilization and phagocytosis after neonatal HI. We found that L-Cysteine treatment skewed CD11b + /CD45 low microglia and CD11b + /CD45 high brain monocytes/macrophages towards a more anti-inflammatory property 72 h after HI-injured brain. Moreover, L-Cysteine treatment reduced cerebral infiltration of CD4 T cells 7 days following HI insult. Furthermore, CD4 T cell subset analysis revealed that L-Cysteine treatment decreased Th1 and Th2 counts, while increased Th17/Th2 ratio. Moreover, L-Cysteine treatment suppressed LPS-induced cytosolic Ca 2+ and LPS-stimulated phagocytosis in primary microglia. The anti-inflammatory effect of L-Cysteine was associated with improving neurobehavioral impairment following HI insult. Our results demonstrate L-Cysteine treatment suppressed the invasion of peripheral immune cells, increasing [Ca 2+ ]i and excessive phagocytosis to improve neurobehavioral deficits following hypoxia-ischemia injury in neonatal mice by H 2 S release., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Direct X-ray detectors based on metal halide perovskites and their derivatives exhibit high sensitivity and low limit of detection (LoD). Compared with three-dimensional (3D) hybrid lead halide perovskites, low-dimensional A 3 Bi 2 I 9 perovskite derivatives (A = Cs, Rb, NH 4 , CH 3 NH 3 (MA)) present better stability, greater environmental friendliness, and comparable X-ray detection performance. Here, we report FA 3 Bi 2 I 9 (FA= CH(NH 2 ) 2 ) single crystals (SCs) as a new member of the A 3 Bi 2 I 9 series for X-ray detection, which were prepared by the nucleation-controlled secondary solution constant temperature evaporation (SSCE) method. Centimeter-sized FA 3 Bi 2 I 9 SCs show a full width at half-maximum (fwhm) of 0.0096°, which is superior to that of recently reported Cs 3 Bi 2 I 9 (0.058°) and MA 3 Bi 2 I 9 SCs (0.024°) obtained by inverse temperature crystallization (ITC). The as-grown FA 3 Bi 2 I 9 SC shows a large resistivity of 7.8 × 10 10 Ω cm and a high ion migration activation energy ( E a ) of 0.56 eV, which can guarantee a low noise level and good operational stability under a large external bias. The FA 3 Bi 2 I 9 SC detector exhibits a LoD of 0.2 μGy air s -1 , a sensitivity of 598.1 μC Gy air -1 cm -2 , and an X-ray detection efficiency of 33.5%, which are much better than those of the commercialized amorphous selenium detector. Results presented here will provide a new lead-free perovskite-type material to achieve green, sensitive, and stable X-ray detectors.

Introduction: Catheter ablation for atrial fibrillation (AF-CA) in patients with situs inversus dextrocardia (SID) can be challenging because of the contrary anatomy and associated anomalies. Cases and literature regarding AF-CA in SID are rare and provide little information. Our study aims to present an improved procedure, ablation strategies, and evaluate the safety and outcomes of AF-CA in patients with AF and SID., Methods: A total of 10 patients with AF-SID (mean age, 60.4 ± 15.7 years; six paroxysmal AF, four persistent atrial fibrillation [PeAF]) were enrolled. For the improved procedure, images obtained by preacquired computed tomography and three-dimensional electroanatomical mapping, integrating intracardiac echocardiography, and x-ray imaging data are necessary to optimize the transseptal puncture and ablation procedure., Results: All patients successfully underwent 13 AF-CA procedures without complications, including three patients received repeat procedures. However, two PeAF patients presented sick sinus syndrome (SSS) after the AF-CA procedure, and one underwent permanent pacemaker implantation therapy during hospitalization. During the follow-up period (6-72 months), the outcomes were not favorable: three patients (30%) maintained sinus rhythm (SR) after the initial procedure; after repeated procedures, the overall SR rate was 40% (four patients)., Conclusion: With the improved strategy, AF-CA can be safely and effectively performed with low radiation exposure in patients with SID. However, the long-term outcomes were not favorable, even when managed at a tertiary center by a team of specialists. Moreover, patients with PeAF might also have masked SSS, which should be carefully considered., (© 2020 Wiley Periodicals LLC.)

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) significantly suppressed hypoxia-ischemia (HI)-induced neuroinflammation in neonatal mice. However, its underlying mechanism is still unknown. Osteopontin (OPN) is one of the key molecules involved in neuroinflammation. We demonstrate here for the first time a key role of OPN in EVs-mediated neuroinflammation following HI. Firstly, HI exposure upregulated OPN expression in Iba-1 + / TMEM119 + microglia and Iba-1 + /TMEM119 - monocytes/macrophages. Blocking OPN mRNA expression with LV-shOPN attenuated edema, infarct volumes, and the levels of inflammatory cytokines following HI exposure. MSCs-EVs treatment remarkably restored synaptic reorganization and up-regulated synaptic protein expression post-HI, concomitant with reducing OPN levels. Moreover, MSCs-EVs treatment rescued microglial phagocytosis of viable neurons following HI, concomitant with decreasing OPN expression. In addition, blocking NF-κB activation with pyrrolidine dithiocarbamate (PDTC, NF-κB inhibitor) or MSCs-EVs attenuated HI-induced OPN expression in the ipsilateral cortex. This study demonstrates that upregulation of OPN expression in cerebral immune cells aggravated brain damage and inflammation following HI insult. MSCs-EVs suppressed neuroinflammation, synaptic damage and microglial phagocytosis after HI injury by preventing NF-κB-mediated OPN expression in neonate mice., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Subarachnoid hemorrhage (SAH) is an acute and severe disease with high disability and mortality. Inflammatory reactions have been proven to occur throughout SAH. Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) have shown broad potential for the treatment of brain dysfunction and neuroprotective effects through neurogenesis and angiogenesis after stroke. However, the mechanisms of EVs in neuroinflammation during the acute phase of SAH are not well known. Our present study was designed to investigate the effects of MSCs-EVs on neuroinflammation and the polarization regulation of microglia to the M2 phenotype and related signaling pathways after SAH in rats. The SAH model was induced by an improved method of intravascular perforation, and MSCs-EVs were injected via the tail vein. Post-SAH assessments included neurobehavioral tests as well as brain water content, immunohistochemistry, PCR and Western blot analyses. Our results showed that MSCs-EVs alleviated the expression of inflammatory cytokines in the parietal cortex and hippocampus 24 h and 48 h after SAH and that MSCs-EVs inhibited NF-κB and activated AMPK to reduce inflammation after SAH. Furthermore, MSC-EVs regulated the polarization of microglia toward the M2 phenotype by downregulating interleukin-1β, cluster of differentiation 16, cluster of differentiation 11b, and inducible nitric oxide synthase and upregulating the expression of cluster of differentiation 206 and arginase-1. Additionally, MSCs-EVs inhibited the neuroinflammatory response and had neuroprotective effects in the brain tissues of rats after SAH. This study may support their use as a potential treatment strategy for early SAH in the future., (Copyright © 2020. Published by Elsevier Masson SAS.)

We previously reported that preconditioning of mesenchymal stem cells (MSCs) with hydrogen sulfide (H 2 S) improved their therapeutic potential in cerebral ischemia. However, the mechanisms involved with this effect have not been determined. As one approach to address this issue, we focused on a neuroprotective role of modification of MSCs-derived extracellular vesicles (EVs) with H 2 S treatment, and further examined the underlying mechanisms during hypoxia-ischemia (HI) injury in neonatal mice. At 24 h following HI insult, neonatal mice received either systemically administered EVs (derived from MSCs) or H 2 S-EVs (derived from NaHS-preconditioned MSCs). Both treatments reached the injured region of the ipsilateral hemisphere within 2 h after administration and were incorporated into microglia and neurons. Mice receiving H 2 S-EVs exhibited substantially lower amounts of brain tissue loss, decreased levels of pro-inflammatory mediators, and a skewed distribution of CD45 low microglia and CD45 high brain mononuclear phagocytes toward a more anti-inflammatory condition as compared with that in mice receiving only EVs. Moreover, these neuroprotective and anti-inflammatory effects of H 2 S-EVs were accompanied with long-term preservation of cognitive and memory functions, in contrast to the functional deficits observed in mice receiving only EVs. This H 2 S preconditioning upregulated miR-7b-5p levels in EVs as determined with next-generation sequencing, while knockdown analyses revealed that inducing miR-7b-5p expression and targeting FOS in the ipsilateral cortex were essential for the neuroprotective and anti-inflammatory effects of H 2 S-EVs following HI exposure. Taken together, these results demonstrate that miR-7b-5p transferred by H 2 S-EVs into the ipsilateral hemisphere further induced miR-7b-5p expression, which promoted CD45 low microglia and CD45 high brain mononuclear phagocytes toward a beneficial phenotype and improved HI-induced cognitive impairments in neonatal mice., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To investigate the therapeutic effects of β-ecdysterone on osteoarthritis (OA) and the underlying mechanism., Methods: OA model was established on rats by injecting MIA. ELSA was used to determine the concentration of IL-1β, IL-6, NO and TNF-α in the chondrocytes and cartilage tissues. Immunofluorescence assay was used to determine the expression of collagen II in the chondrocytes. The survival rate of chondrocytes was evaluated by MTT assay. The apoptosis of chondrocytes was checked by AO/PI staining and flow cytometry assay. The expression level of Atg7, PI3K and caspase-3 was evaluated by qRT-PCR. Western Blot was used determine the expression of PI3K, p-AKT1, AKT1, p-mTOR, mTOR, p70S6K, p-p70S6K, LC3I, LC3II and caspase-3. HE staining was used to check the pathological state of cartilage tissues., Results: Chondrocytes were tolerable to rapamycin, 3-methyladenine and β-ecdysterone at the concentration of 10 mM, 100 nM and 40 μM, respectively. The apoptosis of chondrocytes was inhibited by rapamycin and β-ecdysterone, and induced by 3-methyladenine. PI3K, p-AKT1, p-mTOR, p-p70S6K and caspase-3 were down-regulated by rapamycin and β-ecdysterone, and up-regulated by 3-methyladenine in both the chondrocytes and the cartilage tissues. The expression of Atg7 and LC3II/LC3I were regulated in a opposite way. The inflammation state was improved by rapamycin and β-ecdysterone both the chondrocytes and the cartilage tissues. HE staining results showed that the pathological state of cartilage tissues was alleviated by β-ecdysterone., Conclusion: β-ecdysterone might alleviate osteoarthritis by activating autophagy in chondrocytes through regulating PI3K/AKT/mTOR signal pathway., Competing Interests: None., (AJTR Copyright © 2020.)

Background: Cell proliferation and migration are the determinants of malignant tumor progression, and a better understanding of related genes will lead to the identification of new targets aimed at preventing the spread of cancer. Some studies have shown that KIAA1199 (CEMIP) is a transmembrane protein expressed in many types of noncancerous cells and cancer cells. However, the potential role of KIAA1199 in the progression of cholangiocarcinoma (CCA) remains unclear., Results: Analysis of cancer-related databases showed that KIAA1199 is overexpressed in CCA. ELISA, immunohistochemistry, Western blotting and qPCR indicated high expression levels of KIAA1199 in serum, CCA tissues and CCA cell lines. In the serum (n = 41) and large sample validation (n = 177) cohorts, higher KIAA1199 expression was associated with shorter overall survival and disease-free survival times. At the cellular level, KIAA1199 overexpression (OE) promoted CCA growth and metastasis. Subcutaneous tumor xenograft experiments showed that KIAA1199 enhances CCA cell proliferation. Additionally, the expression levels of components in the EMT-related TGF-β pathway changed significantly after KIAA1199 upregulation and silencing., Conclusion: KIAA1199 is a promising new diagnostic molecule and therapeutic target in CCA. The serum KIAA1199 level can be used as a promising clinical tool for predicting the overall postoperative outcomes of patients with CCA., Methods: CCA-related KIAA1199 data were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. To assess the prognostic impact of KIAA1199, an enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of KIAA1199 in 41 patients who underwent surgical resection. Immunohistochemical staining, Western blotting and qPCR were used to verify and retrospectively review the expression levels of KIAA1199 in cancer tissue specimens from 177 CCA patients. The effect of KIAA1199 on CCA was evaluated by cell-based functional assays and subcutaneous tumor xenograft experiments. The expression levels of proteins associated with epithelial-mesenchymal transition (EMT) and activation of relevant signaling pathways were measured via Western blotting.

The synthesis of mitochondrial DNA (mtDNA) is a complex process that involves the formation and resolution of unusual nucleic acid structures, such as RNA:DNA hybrids. However, little is known about the enzymes that regulate these processes. RECQ4 is a DNA replication factor important for mtDNA maintenance, and here, we unveil a role of human RECQ4 in regulating the formation and resolution of mitochondrial RNA:DNA hybrids. Mitochondrial membrane protein p32 can block mtDNA synthesis by restricting RECQ4 mitochondrial localization via protein-protein interaction. We found that the interaction with p32 was disrupted not only by the previously reported cancer-associated RECQ4 mutation, del(A420-A463), but also by a clinical mutation of the adjacent residue, P466L. Surprisingly, although P466L mutant was present in the mitochondria at greater levels, unlike del(A420-A463) mutant, it failed to enhance mtDNA synthesis due to the accumulation of RNA:DNA hybrids throughout the mtDNA. Biochemical analysis revealed that P466L mutation enhanced RECQ4 annealing activity to generate RNA:DNA hybrids at the same time reduced its unwinding activity to resolve this structure. Hence, P466L mutation led to a reduced efficiency in completing mtDNA synthesis due to unresolved RNA:DNA hybrids across mtDNA.

The poor attenuation capability of high-energy X-ray photons hinders the application of X-ray detectors in medical and astrophysical areas. Halide-based perovskites are promising candidates for X-ray detection because of their improved sensitivity. However, their inferior attenuation coefficient is still unsatisfactory for broadband X-ray detection. Here, a new kind of X-ray detection material, AgBi 2 I 7 rudorffite single crystal (SC), is prepared and applied in X-ray detection for the first time, and it shows a higher attenuation coefficient than halide-based perovskites, commercialized a-Se, and the currently outstanding Cd 0.9 Zn 0.1 Te (CZT). The AgBi 2 I 7 rudorffite SCs possess outstanding electric properties and excellent stability. AgBi 2 I 7 -SC detectors demonstrate a limit of detection (LoD) of 72 nGy air s -1 and a sensitivity of 282.5 μC Gy air -1 cm -2 to X-rays and show only a slight performance degradation after ontinuous X-ray irradiation with a total dose of 58 Gy air . This work opens up a new perspective and broad opportunities for halide rudorffite in X-ray detection.

Background: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country., Methods: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline., Findings: The notified number of TB patients decreased sharply in the 1 st week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19., Interpretation: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established., Funding: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180)., Competing Interests: The authors have no competing interests., (© 2020 The Authors. Published by Elsevier Ltd.)

Objective: To evaluate the precision of the robot-assisted sacroiliac screw placement for posterior pelvis injury and the impacting factors. Methods: The clinical data of twenty-four cases of posterior pelvic fractures treated by percutaneous sacroiliac screw placement in Yantai shan Hospital from August 2016 to May 2018 were studied retrospectively. There were 17 males and 7 females with a mean age of 44.1 years (ranged from 17 to 71 years). According to AO classification, 17 cases were type B fractures (9 cases of type B1 and 8 type B2), and 7 cases were type C factures (3 cases of type C1, 2 type C2 and 2 type C3). All cases were treated by robot-assisted percutaneous sacroiliac screw placement (AO cannulated screws with a diameter of 7.3 mm). In the posterior pelvic surgeries for the 24 cases, 26 S(1) sacroiliac screws fixations and 18 S(2) sacroiliac screw fixations were placed in total, with single S(1) segmental fixation in 8 cases, single S(2) segmental fixation in 3 cases, S(1) and S(2) combined fixation in 13 cases, S(1) unidirectional one-sided fixation in 18 cases, S(1) bidirectional two-sided fixation in 3 cases, S(2) unidirectional one-sided fixation in 14 cases, S(2) bidirectional two-sided fixation in 2 cases and S(1) unidirectional double screws fixation in 2 cases. X-ray and CT examinations were taken for all 24 cases after operation. The visual analogue scale (VAS) of pain were performed before and after the operation. Results: All the sacroiliac screws were successfully implanted at once as planned with the assistance of the robot. The postoperative X-ray films and CT showed that none of the sacroiliac screws broke through the sacral body and the contralateral sacral wing's frontal cortex nor did they stray into the sacral canal and the intervertebral space. In 3 cases, the sacroiliac screws went closely against and wore out the front edge of iliac cortical density line and sacral alar slope and finally re-entered the sacral body. In 3 cases, sacroiliac screws touched upon the sacral nerve canals but did not break through the nerve canals. The mean VAS of pain was improved from 7.1 points (4-10 points) before the operation to 1.9 points (0-3 points) after. Conclusions: The robot-assisted sacroiliac screw placement shows high precision, and hence is worthy of clinical promotion; however the primary role of the surgeon could not be replaced.

A methodology for deconvolution of fast exchange equilibrium states in NMR spectroscopy (DFEQNMR) was developed based on DFT-GIAO NMR chemical shift prediction and a probability theory algorithm. Proof-of-concept studies were performed to estimate the protonation state of N-containing organic molecules involving fast proton exchange equilibrium and evaluate the solution tautomerism of a purine derivative. DFT-GIAO calculations were optimized to achieve good accuracy in 13 C, 1 H and 15 N chemical shift prediction for protonated species. The probability theory algorithm enabled the determination of solution species ratios and yielded 95% confidence regions by comparing experimental and simulated chemical shift data sets. The calculation showed good accuracy for model partial salts with various functionalities and application in structure elucidation of complex natural product partial salts was also demonstrated. This method showed promising potential in acquisition of important insight into fast exchange equilibrium systems with only one experimental NMR chemical shift data set.

Introduction: We have reported previously that hydrogen-rich saline (HS) plays a neuroprotective role in hypoxia-ischemia (HI) brain damage in newborn mice. However, the mechanisms for this neuroprotection resulting from HS remain unknown. In this study, we examined the potential for HS to exert effects upon microglial phagocytosis via involvement of the Akt signaling pathway as one of the neuroprotective mechanisms in response to neonatal HI., Methods: The HI brain injury model was performed on postnatal day (PND) 7 (modified Vannucci model). The acute brain damage was detected at 3 days after HI exposure. The behavioral and functional screening of the pups at PND11 and PND13 and their long-term outcomes (PND35, 28-days post-HI) were evaluated sensorimotor performance and cognitive functions, respectively., Results: The result showed that HS administration alleviated HI-induced edema, infract volume and cellular apoptosis within the cortex of neonatal mice. Accompanying these indices of neuroprotection from HS were reductions in HI-induced phagocytosis in microglia as demonstrated in vivo and in vitro, effects that were associated with increasing levels of Akt phosphorylation and improvements in neurobehavioral responses. These beneficial effects of HS were abolished in mice treated with an Akt inhibitor., Discussion: These results demonstrate that HS treatment attenuates neurobehavioral deficits and apoptosis resulting from HI, effects which were associated with reductions in phagocytosis and appear to involve the Akt signaling pathway., Competing Interests: The authors have no financial, personal, or other conflicts of interest to disclose for this work., (© 2020 Ke et al.)

Objective: The aim of this study is to investigate the expression levels of circRNA&#95;100782 in gastric cancer tissues, and its function of regulating tumor suppressor gene Rb by absorbing miR-574-3p in a sponge form., Patients and Methods: qRT-PCR was performed to detect the expressions of circRNA&#95;100782 at different stages during gastric cancer tissues. CCK-8 assay was performed to evaluate the osteoclast proliferation and differentiation. The correlation between miR-574-3p and circRNA&#95;100782 was detected by statistical analysis. Bioinformatics and Luciferase assay were performed to explore the interaction and binding site of circRNA&#95;100782 and miR-574-3p. The mice Rb 3'-UTR were cloned into the Luciferase reporter vector and miR-574-3p binding mutants were constructed to validate the inhibited regulation of miR-574-3p to the expression of Rb., Results: In the current study, compared with adjacent non-cancerous normal tissues, the expressions of circRNA&#95;100782 and Rb were both downregulated in human gastric cancer cells. Through qRT-PCR and CCK-8 assay, we found that the expression of circRNA&#95;100782 is related to the proliferation of gastric cancer cells. Besides, we also found that circRNA&#95;100782 regulated the migration ability of gastric cancer cells through transwell assay. The bioinformatics prediction and luciferase assay demonstrated that circRNA&#95;100782 can serve as a molecular sponge to further regulate the expression of Rb by sponging with miR-574-3p; moreover, circRNA&#95;100782 can serve as a ceRNA for miR-574-3p to further regulate the expression of Rb., Conclusions: In this research, we discovered that circRNA&#95;100782 was downregulated in gastric cancer cells and is associated with cell proliferation and invasion by inhibiting tumor suppressor gene Rb by interacting with miR-574-3p.