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Objective. Naringin is a flavonoid derived from Chinese herbs. According to earlier studies, naringin may have the potential to alleviate aging-induced cognitive dysfunction. Therefore, this study attempted to explore the protective effect and underlying mechanism of naringin on aging rats with cognitive dysfunction. Methods. After the construction of a model of aging rats with cognitive dysfunction through subcutaneous injection of D-galactose (D-gal; 150 mg/kg), intragastric administration of naringin (100 mg/kg) was performed for treatment. Behavioral tests, including Morris water maze test (MWM), novel object recognition test (NORT), and fear conditioning test, were used to measure the cognitive function; ELISA and biochemical tests were used to determine the levels of interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the hippocampus of rats in each group, respectively; H&E staining was used to observe the pathological changes in the hippocampus; Western blot was used to examine the expression of toll-like receptor 4 (TLR4)/NF-κB pathway-related proteins and endoplasmic reticulum (ER) stress-related proteins in the hippocampus. Results. The model was successfully constructed by subcutaneous injection of D-gal (150 mg/kg). The behavioral test results showed that naringin could ameliorate the cognitive dysfunction and alleviate the histopathological damage of hippocampus. Moreover, naringin significantly improve the inflammatory response (the levels of IL-1β, IL-6, and MCP-1 were decreased), oxidative stress response (MDA level was increased while GSH-Px activity was decreased), and ER stress (the expression of glucose-regulated protein 78 (GRP78), C/-EBP homologous protein (CHOP), and transcription factor 6 (ATF6) expression was downregulated), and increased the levels of neurotrophic factors BDNF and NGF in D-gal rats. Besides, further mechanistic studies revealed the downregulation of naringin on TLR4/NF-κB pathway activity. Conclusion. Naringin may inhibit inflammatory response, oxidative stress, and ER stress by downregulating TLR4/NF-κB pathway activity, thereby improving cognitive dysfunction and alleviating histopathological damage of hippocampus in aging rats. Briefly, naringin is an effective drug for the treatment of cognitive dysfunction.

Background: It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive.Methods: The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells.Results: The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells.Conclusion: Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.

Background aims Despite the great advances in immunosuppressive therapy for severe aplastic anemia (SAA), most patients are not completely cured. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been recommended as an alternative treatment in adult SAA patients. However, haplo-HSCT presents a higher incidence of graft failure and graft-versus-host disease (GVHD). The authors designed a combination of haplo-HSCT and umbilical cord-derived mesenchymal stem cells (UC-MSCs) for treatment of SAA in adult patients and evaluated its effects. Methods Adult patients (≥18 years) with SAA (N = 25) were given HLA-haploidentical hematopoietic stem cells (HSCs) combined with UC-MSCs after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin and intensive GVHD prophylaxis, including cyclosporine, basiliximab, mycophenolate mofetil and short-term methotrexate. Additionally, the effects of the protocol in adult SSA patients were compared with those observed in juvenile SAA patients (N = 75). Results All patients achieved myeloid engraftment after haplo-HSCT at a median of 16.12 days (range, 11–26). The median time of platelet engraftment was 28.30 days (range, 13–143). The cumulative incidence of grade II acute GVHD (aGVHD) at day +100 was 32.00 ± 0.91%. No one had grade III–IV aGVHD at day +100. The cumulative incidence of total chronic GVHD was 28.00 ± 0.85%. The overall survival was 71.78 ± 9.05% at a median follow-up of 42.08 months (range, 2.67–104). Promisingly, the protocol yielded a similar curative effect in both young and adult SAA patients. Conclusions The authors’ data suggest that co-transplantation of HLA-haploidentical HSCs and UC-MSCs may provide an effective and safe treatment for adult SAA.

Growth hormone secretagogue receptor 1a (GHS-R1a) is an important G protein-coupled receptor (GPCR) that regulates a variety of functions by binding to ghrelin. It has been shown that the dimerization of GHS-R1a with other receptors also affects ingestion, energy metabolism, learning and memory. Dopamine type 2 receptor (D2R) is a GPCR mainly distributed in the ventral tegmental area (VTA), substantia nigra (SN), striatum and other brain regions. In this study we investigated the existence and function of GHS-R1a/D2R heterodimers in nigral dopaminergic neurons in Parkinson’s disease (PD) models in vitro and in vivo. By conducting immunofluorescence staining, FRET and BRET analyses, we confirmed that GHS-R1a and D2R could form heterodimers in PC-12 cells and in the nigral dopaminergic neurons of wild-type mice. This process was inhibited by MPP+ or MPTP treatment. Application of QNP (10 μM) alone significantly increased the viability of MPP+-treated PC-12 cells, and administration of quinpirole (QNP, 1 mg/kg, i.p. once before and twice after MPTP injection) significantly alleviated motor deficits in MPTP-induced PD mice model; the beneficial effects of QNP were abolished by GHS-R1a knockdown. We revealed that the GHS-R1a/D2R heterodimers could increase the protein levels of tyrosine hydroxylase in the SN of MPTP-induced PD mice model through the cAMP response element binding protein (CREB) signaling pathway, ultimately promoting dopamine synthesis and release. These results demonstrate a protective role for GHS-R1a/D2R heterodimers in dopaminergic neurons, providing evidence for the involvement of GHS-R1a in PD pathogenesis independent of ghrelin.

Background: Readout-segmented echo-planar imaging (rs-EPI) with simultaneous multislice (SMS) technology has been successfully applied to tumor research in many organs, but no feasibility study in rectal cancer has been reported, and the optimal acceleration of SMS with rs-EPI in rectal cancer has not been well determined yet. Objective: To investigate the feasibility of SMS rs-EPI of rectal cancer with different acceleration factors (AFs) and its influence on image quality, acquisition time and apparent diffusion coefficients (ADCs) in comparison to conventional sequences. Methods: All patients underwent rs-EPI and SMS rs-EPI with AFs of 2 and 3 (2 × SMS rs-EPI and 3 × SMS rs-EPI, respectively) using a 3T scanner. Acquisition times of the three rs-EPI sequences were measured. Image qualitative parameters (5-point Likert scale), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), geometric distortion, and apparent diffusion coefficient (ADC) values of the three sequences were compared. Results: A total of eighty-three patients were enrolled in our study. rs-EPI and 2 × SMS rs-EPI offered equivalently high overall image quality with a scan time reduction to nearly half (rs-EPI: 137 s, 2 × SM rs-EPI: 60 s). 3 × SMS rs-EPI showed significantly poorer image quality (p < 0.05). ADC values were significantly lower in 3 × SMS rs-EPI compared to rs-EPI in rectal tumors and normal tissue (tumor tissue: rs-EPI 1.19 ± 0.21 × 10−3 mm2/s, 3 × SMS rs-EPI 1.10 ± 0.26 × 10−3 mm2/s, p < 0.001; normal tissue: rs-EPI 1.68 ± 0.13 × 10−3 mm2/s, 3 × SMS rs-EPI 1.54 ± 0.20 × 10−3 mm2/s, p < 0.001). Conclusions: SMS rs-EPI using an AF of 2 is feasible for rectal MRI resulting in substantial reductions in acquisition time while maintaining diagnostic image quality and similar ADC values to those of rs-EPI when the slice distance and number of shots are the same among three rs-EPI sequences.

One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production.

119 p. The functional scope of unconscious visual information processing and its implementation in the human brain remains a highly contested issue in cognitive neuroscience. The influential global workspace and higher-order theories predict that unconscious visual processing is restricted to representations in the visual cortex, which are not read-out further by frontoparietal areas. The present thesis employs fMRI and computational approaches to develop a high-precision, within-subject framework in order to define the properties of the brain representations of unconscious content associated with null perceptual sensitivity. Machine learning models were used to read-out multivariate unconscious content from fMRI signals throughout the ventral visual pathway, and model-based representational similarity analysis examined the properties of both conscious and unconscious representations. Finally, feedforward convolutional neural network (FCNN) models were used to simulate the fMRI results, namely, to probe the existence of informative representations of visual objects with null perceptual sensitivity in artificial networks. The results show that even when human observers display null perceptual sensitivity at a behavioral level, there are neural representations of unconscious content widely distributed throughout the cortex, and these are not only contained in visual regions but also extend to higher-order regions in the ventral visual pathway, parietal and even prefrontal areas. The computational simulations with different FCNN models trained to perform the same visual task with noisy images demonstrated that even when the FCNN models failed to classify the category of the noisy images, the hidden representation of the FCNN models contained an informative representation that allowed for decoding of the image class. The implications of the results for models of visual consciousness are discussed

Objective: This study aimed to investigate the nurse-patient trust among in-patients in the context of the coronavirus disease (COVID-19) epidemic; it further analyzed the related influencing factors, which will provide a theoretical basis for developing corresponding measures. Methods: This study employed a mixed-method design and analyzed 149 patients at the Hongqi Hospital, affiliated with Mudanjiang Medical University, from December 2020 to February 2021. Quantitative analysis was carried out using the “Nurse Patient Trust Scale,” and qualitative analysis was performed using a semi-structured interview with in-patients. Results: The average score on the scale was 46.65 ± 2.83, and the scores of the 2 dimensions were: 23.24 ± 1.51 for ability and peace of mind, and 23.32 ± 1.53 for attitude and care. According to the interview data, the factors included 3 aspects: a comfortable hospital environment and humane management measures; the nurse’s own competence; and effective communication with patients. Conclusion: During the COVID-19 epidemic, there are still many factors affecting patients’ trust in nurses that can be addressed by taking different measures. All these factors must be considered by the relevant managers and clinical nursing staff to maintain a better nurse-patient trust relationship.

Results of slow spindles (10-12 Hz) and fast spindles (12-14 Hz)

1) load data, 2) ICA correcting data, 3) visualize data and power spectral density of data, 4) detection spindles.

Sleep researchers classify critical neural events called spindles that are related to memory consolidation via scalp electroencephalography (EEG). Manual classification is time consuming and is susceptible to low inter-rater agreement. This could be addressed using an automated approach. The current study presents an optimized filter based and thresholding pipeline to set up a baseline for comparison to evaluate machine learning models using naïve features, such as raw signals, peak frequency, and dominant power. Filter based and thresholding pipelines allow us to formally define sleep spindles using signal processing but may miss examples most human scorers would agree were spindles. Machine learning methods, in theory should be able to approach human performance but they require a large quantity of scored data, proper feature representation, intensive feature engineering, and model selection. We evaluate both a pipeline based signal processing and machine learning with naïve features. We show that the machine learning models learned from our pipeline improve classification. An automated approach designed for the current data was applied to the DREAMS dataset. With one of the expert’s annotation as a gold standard, our pipeline yields an excellent sensitivity that is close to a second expert’s scores and with the advantage that it can classify spindles based on multiple channels if more channels are available. More importantly, our pipeline could be modified as a guide to aid manual annotation of sleep spindles based on multiple channels quickly (6-10 seconds for processing a 40-minute EEG recording) making it faster and more objective.

Background Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. Methods The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan–Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods. Results NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis. Conclusions NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

AIM: To investigate the clinical effect of canaliculotomy joint novel R-S lacrimal tube implantation under lacrimal endoscope for canaliculitis.METHODS: Thirty-one patients(thirty-two eyes)diagnosed as canaliculitis were investigated from July 2016 to September 2019 in our department. All patients have treated with canaliculotomy joint lacrimal tube implantation under lacrimal endoscope. The patients were randomly divided into two groups. Group A was treated with novel R-S lacrimal tube for 15 cases 15 eyes, and group B was treated with annular silicone tube. They were removed the lacrimal tube after 2-3mo, and followed postoperatively for at least 1a. The treatment results were comparatively analyzed.RESULTS: The effective rate was 93% in group A and 94% in group B(P>0.05). The mean time of lacrimal tube implantation of group A was 2.27±1.335min, and group B was 5.29±1.404min. The total rate of complications was 7% in group A and 47% in group B. The rate of foreign body sensation in nasal cavity was 7% in group A and 41% in group B. The rate of increased nasal secretions was 0 in group A and 29% in group B. The difference of the mean time of lacrimal tube implantation, the rate of complications, the rate of foreign body sensation in nasal cavity and the rate of increased nasal secretions between two groups was statistically significant(P

With the development of social media, advertising has migrated from traditional media to social media. Marketers are increasingly using social media’s brand pages to actively create humorous dialogue interactions with other brands for brand communication to achieve positive business outcomes. Especially brand-to-brand’s aggressive humor dialogue can also be an effective brand communication strategy. Based on benign violation theory, we have studied the influence mechanism and boundary condition of the brand-to-brand’s aggressive humor styles (low-aggressive and high-aggressive) on consumer engagement behavioral intention in social media context. Through experiments, it is indicated that low-aggressive humor could promote consumer engagement behavioral intention more than high-aggressive humor. Benign appraisal mediates the relationship between low-aggressive humor and consumer engagement behavioral intention. Furthermore, brand personality not only moderates the effect of low-aggressive humor on consumer engagement behavioral intention, but also moderates the mediating role of benign appraisal between low-aggressive humor and consumer engagement behavior intention.

Background Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. But the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. Methods The expression of NAPSB in pan-cancer and HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in HCC using Zhongnan cohort. Kaplan-Meier analyses, univariate and multivariate Cox regression were conducted to determine the predictive value of NAPSB on HCC prognosis. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed. Results NAPSB was downregulated in HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), T cell inflamed score, and cancer immunity cycles and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis (PANoptosis). Conclusions NAPSB was correlated with an immuno-hot and inflamed TME and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

Background: Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih (PTLCS) belongs to the family Compositae, which is a perennial medicinal plant mainly distributed in the Qinghai-Tibet Plateau of China. This review provides a comprehensive summary of the ethnopharmacology, phytochemistry, and pharmacology of PTLCS. This review offers valuable references and guidance for researching PTLCS in depth. Methods: The related references of PTLCS were retrieved from an online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. Results: PTLCS is widely reported for treating headaches, head injuries, traumatic injuries, anabrosis, impetigo, hepatitis, and other diseases in the medical field. Phytochemical research revealed that this plant contained flavonoid aglycones, flavonoid glycosides, xanthones, triterpenoids, coumarins, polyacetylenes, volatile oils, and other compounds. Meanwhile, PTLCS exhibited extensive pharmacological activities including anti-cardiac ischemia, anti-hypoxia, hepatoprotective, anti- inflammatory and analgesic, and antioxidant activities. Conclusions: PTLCS is widely used as a Tibetan medicine, which has a variety of chemicals with diverse bioactivities. Therefore, further studies are necessary to perform on the PTLCS to assay biological activities, discover their bioactive constituents, and reveal pharmacological mechanisms. This review may supply an important theoretical basis and valuable reference for in-depth research and exploitations of PTLCS.

Customer citizenship behavior has attracted widespread attention from scholars due to its capacity of enabling enterprises to gain competitive advantages of low costs and high efficiency by giving full play to the initiative of customers. Based on the S-O-R Model, we have established the theoretical model to study the influence imposed by social support of online travel platform enterprises on customer citizenship behavior against the backdrop of the sharing economy. This research tests the fitting of the theoretical model and its fundamental hypotheses using 626 samples acquired from the investigation with SPSS26.0 and AMOS25.0. Results indicate that the social support has a positive influence on customer citizenship behavior. Social support could have a positive influence on positive emotions. Social support has no significant negative effect on negative emotions. Positive emotions have a positive influence on customer citizenship behavior. Negative emotions have a negative influence on customer citizenship behavior. Positive emotions play a mediating effect in the positive influence of social support on customer citizenship behavior. Social support could have a positive influence on customer satisfaction. Customer satisfaction has a positive influence on customer citizenship behavior. Customer satisfaction plays a mediating effect in the positive effect of social support on customer citizenship behavior. Positive emotions and customer satisfaction play a chain mediating effect in the positive effect of social support on customer citizenship behavior.

Background Though accumulated evidence has demonstrated visceral organ involvement in acute graft-versus-host disease (aGVHD), how aGVHD influences the bone marrow (BM) niche and the reconstitution of hematopoiesis post-hematopoietic stem cell transplantation remains largely unknown. Methods In the current study, the cell morphology, immunophenotype, multi-differentiation capacity, self-renewal capacity, and hematopoiesis promotion of the MSCs from aGVHD and non-aGVHD patients were investigated. Additionally, the stemness and hematopoiesis-promoting property of healthy donor-derived MSCs were evaluated in the presence of BM supernatant from aGVHD patients. Mechanistically, antibodies targeting inflammatory cytokines involved in aGVHD were added into the MSC culture. Furthermore, a recombinant human tumor necrosis factor (TNF-α) receptor-Ig fusion protein (rhTNFR:Fc) was used to protect healthy donor-derived MSCs. Moreover, mRNA sequencing was performed to explore the underlying mechanisms. Results The aGVHD MSCs exhibited morphological and immunophenotypic characteristics that were similar to those of the non-aGVHD MSCs. However, the osteogenic and adipogenic activities of the aGVHD MSCs significantly decreased. Additionally, the colony formation capacity and the expression of self-renewal-related genes remarkably decreased in aGVHD MSCs. Further, the hematopoiesis-supporting capacity of aGVHD MSCs significantly reduced. The antibody neutralization results showed that TNF-α contributed to the impairment of MSC properties. Moreover, rhTNFR:Fc exhibited notable protective effects on MSCs in the aGVHD BM supernatants. The mRNA sequencing results indicated that the TNF-α pathway and the Toll-like receptor pathway may be activated by TNF-α. Conclusions Thus, our data demonstrate MSCs as cellular targets of aGVHD and suggest a potential role of TNF-α blockage in maintaining the BM niche of aGVHD patients.

Although thymus-independent donor-derived T cell expansion may determine the occurrence of graft-versus-host disease (GVHD) and relapse after transplantation, the characteristics and dynamics of the expansion process remain unclear. To address this issue, we monitored T cell receptor β repertoire at day 0, day 28, and day 61 after transplantation in 30 patients with hematologic malignancies by next-generation sequencing. The clonality index showed an increasing clonality over time (P = .001). The top 200 clonotypes accounted for more than half of the total clonotypes (median frequency, 63.55%) at day 61, and there was a remarkable overlapping between the top 200 clonotypes of each repertoire and its former repertoire (50%). A normalized index, called the T Cell Response Index (TCRI), was designed on the basis of rank-shift analysis to quantify antigen-driven expansion. The TCRI during the first month was not related to relapse or GVHD (P.05), whereas the TCRI during the second month was related to relapse (P = .006). Recipients with a TCRI below 1.0 during the second month had a higher cumulative relapse rate (31.25% versus 0%, P = .0323) and had a lower 1-year survival rate (56.25% versus 78.57%, P = .281). The clonotypes with strong competitiveness in the second month in the nonrelapse group preferentially used TRBV2, TRBV12-3, TRBJ1-1 and TRBJ1-5 segments (P.01). In conclusion, homeostatic expansion predominates in the first month due to nonspecific T cell proliferation, whereas antigen-driven expansion predominates in the second month and results in a graft-versus-tumor (GvT) effect. Moreover, TCRI could serve as a quantitative indicator of GvT against relapse within the first year. The difference in V and J segment usage reveals that T cells responsible for potent GvT effect are similar among patients.

Hematopoietic Stem and Progenitor Cells In article number 2103838, Xiao‐Ming Yang, Chang‐Yan Li and co‐workers identify a critical regulator‐HEMGN, that is required for hematopoietic stem and progenitor cells (HSPCs) homing, survival, and reconstitution of blood cells during bone marrow transplantation (BMT). HEMGN acts as a protector which limits interferon‐γ (IFN‐γ) signaling by suppressing nuclear Stat1 tyrosine phosphorylation and assists HSPCs to combat the transplantation stress. Targeted Hemgn may be used to improve conditioning regimens and engraftment during bone marrow transplantation. [Image: see text]

Background: Highland barley Monascus purpureus Went, a traditional Tibetan medicine with food functions, which is fermented by Monascus purpureus with highland barley as substrate. It possesses various medical functions of promoting blood circulation and removing blood stasis, invigorating spleen and promoting digestion in folk of the Qinghai-Tibet Plateau in China. This review provides a comprehensive overview of ethnopharmacology, phytochemistry, and pharmacology of highland barley Monascus purpureus Went. Methods: The references of highland barley Monascus purpureus Went were retrieved from the online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. Results: Phytochemical research revealed that highland barley Monascus purpureus Went contained multiple chemical components, including Monascus pigments, monacolins, lactones, and other compounds. The reported pharmacological activities of highland barley Monascus purpureus Went included hypolipidemic, anti-nonalcoholic fatty liver disease, and hepatoprotective activities. Conclusions: In a word, botany, ethnopharmacology, phytochemistry and pharmacology of highland barley Monascus purpureus Went were reviewed comprehensively in this paper. In the future, highland barley Monascus purpureus Went needs further study, such as paying more attention to quality control and utilization of medicine. Therefore, this review may provide a theoretical basis and valuable data for future studies and exploitations on highland barley Monascus purpureus Went.

Nonalcoholic Fatty Liver Disease (NAFLD) is a serious problem endangering human health in the world. The pathogenesis of this disease is often accompanied by lipid metabolism disorder and can cause liver lipid accumulation. Highland barley Monascus purpureus Went extract (HBMPWE) can inhibit the liver lipid accumulation caused by a high-fat, high-fructose, high-cholesterol diet. However, it is not clear what changes have taken place in the process of liver lipid metabolism after HBMPWE administration. To fill this knowledge gap and to support the findings published in the companion research article entitled “Highland Barley Monascus purpureus Went Extract Ameliorates High-Fat, High-Fructose, High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism in Golden Hamsters” [1], we provided important information related to the liver differential metabolites and identified twenty-one differential metabolites of liver metabolism. In the model group, the levels of lactate, linoleic acid, and malic acid increased significantly. After HBMPWE treatment, the expressions of these metabolites reduced significantly. Therefore, these liver differential metabolites could be used as biological signatures reflecting the severity of NAFLD and HBMPWE treatment outcomes.

Although haploidentical stem cell transplantation (haplo-HSCT) offers almost all acute lymphoblastic leukaemia (ALL) patients an opportunity for immediate transplantation, it exhibits a higher incidence of graft failure and graft versus host disease (GVHD). Mesenchymal stem cells (MSCs) are characterised by their haematopoiesis-promoting and immunomodulatory capacity. Thus, we designed a combination of haplo-HSCT and MSCs for ALL patients. ALL patients (n = 110) were given haploidentical HSCs combined with allogenic MSCs, and ALL patients without MSC infusion (n = 56) were included as controls. The 100-day cumulative incidences of grade ≥2 acute GVHD (aGVHD) and grade ≥3 aGVHD were 40.00% and 9.09% compared to 42.32% (P = 0.79) and 22.79% (P = 0.03) in patients without MSC infusion, respectively. The 3-year cumulative incidences of chronic GVHD (cGVHD) and extensive cGVHD were 22.27% and 10.27% compared to 32.14% (P = 0.19) and 22.21% (P = 0.04) in patients without MSC infusion, respectively. No significant differences in the 3-year relapse incidence, nonrelapse mortality, leukaemia-free survival or overall survival in groups with and without MSC cotransplantation were observed. Multivariate analysis showed that MSC infusion contributed to a lower risk of developing extensive cGVHD. Our data suggested that haplo-HSCT combined with MSCs may provide an effective and safe treatment for ALL patients.

To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen.Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed.Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P0.05). The mobilization failure rate of lymphoma patients was 42.1%, which was significantly higher than 7.1% of multiple myeloma patients (P=0.026). The mobilization failure rate was higher in the group with chemotherapy courses≥5 before mobilization (P=0.016). Age, gender, dose of rhG-CSF, and chemotherapy regimen had no significant correlation with mobilization failure rate (P0.05).Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.淋巴瘤与多发性骨髓瘤患者自体外周血造血干细胞动员影响因素分析.分析淋巴瘤和多发性骨髓瘤患者自体外周血造血干细胞动员的影响因素，为优化自体造血干细胞动员方案提供参考。.收集2015年1月至2018年12月本中心收治的33例多发性骨髓瘤及淋巴瘤行自体造血干细胞动员患者的临床资料，分析性别、年龄、动员前化疗疗程、重组人粒细胞集落刺激因子用量、疾病类型及化疗方案与动员失败率的相关性。.疾病类型和动员前化疗疗程可影响造血干细胞动员的失败率（P0.05）；淋巴瘤患者动员失败率为42.1%，显著高于多发性骨髓瘤患者（7.1%）（P=0.026）；采集前化疗疗程≥5个组失败率显著增高（P=0.016）。年 龄、性别、重组人粒细胞集落刺激因子用量及化疗方案与干细胞动员失败率无显著相关性（P0.05）。.采集前多疗程化疗及淋巴瘤患者是自体造血干细胞动员的不良因素。.

One new ionone glycoside, named centrantheroside F (

Hepatocyte lipid accumulation is the main feature in the early stage of nonalcoholic fatty liver disease (NAFLD). Highland barley Monascus purpureus Went (HBMPW), a fermentation product of Hordeum vulgare Linn. var. nudum Hook. f. has traditionally been used as fermented foods in Tibet with the effect of reducing blood lipid in folk medicine.This study investigated the protective effects and molecular mechanism of highland barley Monascus purpureus Went extract (HBMPWE) on NAFLD in syrian golden hamster fed with high-fat, high-fructose, high-cholesterol diet (HFFCD).HFFCD-induced NAFLD golden hamster model was established and treated with HBMPWE. Liver index, biochemical index, and hematoxylin and eosin (HE) staining were observed. Liver metabolomics and western blot analysis were employed.Our study found that HBMPWE ameliorated HFFCD induced dyslipidemia, weight gain and elevated the liver index. In addition, HBMPWE treatment significantly attenuated lipid accumulation in the liver and modulated lipid metabolism (sphingolipid, glycerophospholipid). Our data demonstrated that HBMPWE not only regulated the expression of proteins related to fatty acid synthesis and decomposition (SREBP-1/ACC/FAS/AceS1, PPARα/ACSL/CPT1/ACOX1), but also regulated the expression of proteins related to cholesterol synthesis and clearance (HMGCR, LDLR, CYP7A1).HBMPWE improved NAFLD through multiple pathways and multiple targets in body metabolism and could be used as a functional food to treat NAFLD and other lipid metabolic disorders.

Wound healing may be disrupted by lipopolysaccharide (LPS)-induced mitochondrial dysfunction, inflammation, and excessive oxidative stress, which can lead to undesirable consequences. The haematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) is a mitochondrial matrix protein that regulates mitochondrial function. This study aimed to comprehensively identify the role of HAX-1 in the inhibition of LPS-induced mitochondrial dysfunction and apoptosis in human dermal fibroblasts (HDFs). HAX-1 expression was assessed in the HDF-a cell line using real-time polymerase chain reaction, western blotting, and immunohistochemical staining. The viability, migration, and apoptosis of HDF-a cells were evaluated using the water-soluble tetrazolium-1 assay, transwell assay, and flow cytometry analysis, respectively. Mitochondrial function was evaluated based on reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm). Our results demonstrated that LPS stimulation markedly repressed HAX-1 expression in HDFs and silencing of HAX-1 led to mitochondrial ROS accumulation, ΔΨm disruption, and abnormal mitochondrial morphology. Accordingly, overexpression of HAX-1 or administration of metformin enhanced mitochondrial fusion and normalized mitochondrial dynamics, thereby reversing LPS-induced mitochondrial dysfunction, fibroblast apoptosis, and viability and migration inhibition in HDF-a cells. These data support a mechanism wherein HAX-1 plays a crucial role in LPS-induced fibroblast apoptosis in a mitochondria-dependent manner.

Generally, in the laser measurement of gears, the laser beam passes through the center of the gear, and the laser displacement sensor reads the spatial distance from the gear involute tooth surface to the laser displacement sensor. However, in this method, the angle between the laser beam and the normal vector of the measured tooth surface is too large, which affects the accuracy of the measurement and the stability of the data. This paper proposes an offset laser measurement method. The laser beam is offset from the center of the gear by a certain distance to form a larger incident angle with the tooth surface, which can effectively improve the problem and increase the measurement accuracy. Through the discussion of selecting the optimal offset distance, the range of optimal offset measurement position is obtained and clarified by experiments. We solved the data conversion problem caused by the change of measuring position, and measured the pitch deviation and helix angle of the gear to confirm the feasibility of this method. Based on theoretical calculation and experimental verification, it is found that this method has the advantages of better measurement accuracy and less measurement data fluctuations. It is suitable for precision gear measurement.

Aberrant expression or genomic mutations of microRNA have been reported to be associated with a variety of human diseases. This study is aimed to analyze the association between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 Chinese subjects. All these ten SNPs are on or near mature microRNAs which are expressed in the brain. To illustrate the function of miR-27a, we constructed a miR-27a knockout (KO) astrocytoma cell line U-251MG. By comparing the differentially expressed genes in wild-type and KO U-251MG, we determined several candidate target genes of miR-27a and then verified ICAM-1 as a target gene of miR-27a. We identified the association between the T/C polymorphism at rs895819 and bipolar disorder. Ectopic expression of miR-27a in NPCs showed that the T to C mutation at rs895819 reduced the suppressive effects of miR-27a on the expression of its target genes. Further studies revealed that the T/C polymorphism on miR-27a led to differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Our study highlighted the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.

The aberrant expression or genomic mutations of microRNA are associated with several human diseases. This study analyzes the relationship between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 subjects. All these ten SNPs were on or near mature microRNAs. We identified the association between bipolar disorder and the T/C polymorphism at rs895819. To illustrate the function of miR-27a, we constructed several miR-27a knockout (KO) cell lines, determined candidates of miR-27a, and then verified NCAM1 as a target gene of miR-27a. Further studies revealed that the T/C polymorphism on miR-27a led to the differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Furthermore, the C mutation on pre-miR-27a suppresses cell migration and dopamine expression levels. Our study highlights the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.

Background To explore the mechanism of Maxing Shigan Decoction in the treatment of myocardial injury and lung injury through network pharmacology and molecular docking technology. Methods In Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and the Comparative Toxicogenomics Database, National Center for Biotechnology Information database, Online Mendelian Inheritance in Man database, the compounds and targets of each drug in Maxing Shigan Decoction and the targets of “acute lung intervention” and “myocardial injury” diseases were searched. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed by the DAVID database. GOLD 5.1 was used for molecular docking. Results Maxing Shigan Decoction includes 327 compounds and 2722 targets, including 30 key targets. 2125 items were obtained by GO enrichment analysis, including 2047 items of Biological Process, 28 items of Cell Composition and 50 items of Molecular Function. The KEGG pathway was enriched to obtain 149 pathways. The results of molecular docking showed that Gancaonin H and Licorice Glycoside E were well combined with Angiotensin-Converting Enzyme 2-A (ACE2-A) and Angiotensin-Converting Enzyme 2-B (ACE2-B), respectively, and Licorice was well combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin 6 (IL-6). Supraene is an active compound of Ephedra. It has good binding with ACE2-A, ACE2-B, GM-CSF and IL-6, respectively. (6Z, 10E, 14E, 18E)-2, 6, 10, 15, 19, 23- hexamethyletracosa-2, 6, 10, 14, 18, 22- hexaene are the active compounds of Almond, which are well combined with ACE2-A, ACE2-B, GM-CSF and IL-6. Conclusion Maxing Shigan Decoction may act on ACE2, GM-CSF and IL-6 targets through the active compounds Supraene of Ephedra, and Almond (6Z, 10E, 14E, 18E)-2, 6, 10, 15, 19, 23-hexamethyletracosa-2, 6, 10, 14, 18, 22-hexaene. Gancainin H and licorice Glycide E are the active compounds of Licorice, act on A and B sites of ACE2 respectively, and Glycyrin acts on GM-CSF and IL-6 targets, coordinating multiple signal pathways to play anti-inflammatory and antiviral roles to prevent and treat lung and heart injury caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

A modified Schelling model was established to study the mixing law and coalescence distribution characteristics of droplets formed under the stirring condition of oil-water system. The model was mathematically solved, and the effects of threshold and oil-water ratio on droplets distribution is simulated. The following conclusions are obtained: Firstly, The material with good hydrophilicity can maintain its full mixing result after full mixing, and the final coalescence effect of the semi-hydrophilic material is the most obvious, and the material with strong hydrophobicity will fluctuate and cannot spontaneously aggregate. Secondly, with the increase of the number of iterations, the system approaches the local optimum rapidly under the appropriate threshold, but with the further increase of the number of iterations, the overall change speed of the system is slow; Furthermore, the convergence degree of different size Schelling model is different, if the model is too large, it is easy to fall into local optimum and can't reduce P value further.; lastly, the more the oil-water ratio deviates from 1, the better the aggregation effect is.

How the brain representation of conceptual knowledge vary as a function of processing goals, strategies and task-factors remains a key unresolved question in cognitive neuroscience. Here, we asked how the brain representation of semantic categories is shaped by the depth of processing during mental simulation. Participants were presented with visual words during functional magnetic resonance imaging (fMRI). During shallow processing, participants had to read the items. During deep processing, they had to mentally simulate the features associated with the words. Multivariate classification, informational connectivity and encoding models were used to reveal how the depth of processing determines the brain representation of word meaning. Decoding accuracy in putative substrates of the semantic network was enhanced when the depth processing was high, and the brain representations were more generalizable in semantic space relative to shallow processing contexts. This pattern was observed even in association areas in inferior frontal and parietal cortex. Deep information processing during mental simulation also increased the informational connectivity within key substrates of the semantic network. To further examine the properties of the words encoded in brain activity, we compared computer vision models—associated with the image referents of the words—and word embedding. Computer vision models explained more variance of the brain responses across multiple areas of the semantic network. These results indicate that the brain representation of word meaning is highly malleable by the depth of processing imposed by the task, relies on access to visual representations and is highly distributed, including prefrontal areas previously implicated in semantic control.

This study presents a novel phase field method (PFM) - lattice Boltzmann method (LBM) coupled model that describes the ice crystal growth in sea water freezing. Sea water frozen crystalisation impacted by flow and heterogeneous nucleation was numerically and experimentally investigated. The PFM-LBM model was established to conduct simulation. A microscope observation experimental system was built to conduct verification. The results show that flow of sea water effectively promotes the diffusion of discharged salt and the growth of ice crystals, and reduces the probability of dendrite closure. In the directional competitive growth of ice crystals, the salt content trapped in the ice crystals decreased by 17.4% at 0.025 m/s and 21.9% at 0.05 m/s, while the existence of heterogeneous particles resulted in a narrower the brine channel and higher ice crystal growth rate, of which the ice crystal area increased by 10.8% and the trapped salt content in the ice crystals decreased by 14.8%. The study provides both a methodology of numerically simulate sea ice crystallisation which includes the phase change, solute migration, heat transfer and flow, and a feasible controlling approach to improve desalination efficiency of sea water frozen crystallisation.

Objective: To investigate the effect of budesonide and montelukast on airway function and serum inflammatory factors in children with asthma. Methods: A total of 72 children with bronchial asthma were selected as the subjects, and randomly divided into the observation group (36 cases) and the control group (36 cases). The children in the control group were treated with Budesonide Aerosol, and the observation group was treated with montelukast sodium on the basis of the control group. The airway function and the level of inflammatory factors were detected and compared between the two groups. Results: Before treatment, there was no significant difference in TEF25%, TEF50%, TEF75% and FEV1/FVC between the two groups; After treatment, the TEF25%, TEF50%, TEF75% and FEV1/FVC of the two groups were improved before treatment, and the indexes in the observation group were higher than those in the control group, the difference was statistically significant. Before treatment, the IL-4, IL-6, IL-8, IL-17, TNF- alpha levels in the two groups were not statistically different; After treatment, the levels of IL-4, IL-6, IL-8, IL-17 and TNF- in the two groups were lower than those before the treatment, and the indexes in the observation group were lower than those in the control group, and the differences were statistically significant. Conclusion: Budesonide inhalation combined with montelukast can improve the airway function and inflammatory factors in children with asthma.

Hematopoietic stem and progenitor cells (HSPCs) possess the remarkable ability to regenerate the whole blood system in response to ablated stress demands. Delineating the mechanisms that maintain HSPCs during regenerative stresses is increasingly important. Here, it is shown that Hemgn is significantly induced by hematopoietic stresses including irradiation and bone marrow transplantation (BMT). Hemgn deficiency does not disturb steady‐state hematopoiesis in young mice. Hemgn−/‐ HSPCs display defective engraftment activity during BMT with reduced homing and survival and increased apoptosis. Transcriptome profiling analysis reveals that upregulated genes in transplanted Hemgn−/− HSPCs are enriched for gene sets related to interferon gamma (IFN‐γ) signaling. Hemgn−/− HSPCs show enhanced responses to IFN‐γ treatment and increased aging over time. Blocking IFN‐γ signaling in irradiated recipients either pharmacologically or genetically rescues Hemgn−/‐ HSPCs engraftment defect. Mechanistical studies reveal that Hemgn deficiency sustain nuclear Stat1 tyrosine phosphorylation via suppressing T‐cell protein tyrosine phosphatase TC45 activity. Spermidine, a selective activator of TC45, rescues exacerbated phenotype of HSPCs in IFN‐γ‐treated Hemgn−/− mice. Collectively, these results identify that Hemgn is a critical regulator for successful engraftment and reconstitution of HSPCs in mice through negatively regulating IFN‐γ signaling. Targeted Hemgn may be used to improve conditioning regimens and engraftment during HSPCs transplantation.

A new conductive aggregate was prepared by the calcination of magnetically separated fly ash and used to form a mortar containing carbon fiber. The electrical resistivity, electro-thermal properties, and Seebeck effect of the mortar were studied. The prepared mortar has good electrical conductivity and electro-thermal effects, which facilitate its use as a thermal actuator. Furthermore, the greater Seebeck effect would allow the mortar to be used as a temperature sensor. Based on these properties of the mortar, a smart self-heating and self-sensing system was fabricated, which was found to be capable of measuring temperature accurately, maintaining a set temperature, and operating reliably.

The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching 90%, while the prognosis of adults remains poor due to the limited therapeutic approaches. In order to identify new targets for ALL, we performed whole-exome sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two cases exhibited A639G and P960S mutations separately. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice. Moreover, a high sensitivity to the JAK1/2 inhibitor ruxolitinib was observed in S646P mutant model. Exploration in a total of 209 ALL cases showed that JAK1 mutations occur at a frequency of 10.5% in T-ALL (2/19) and 1.6% in B-ALL (3/190). Collectively, our results suggested that JAK1 S646P is an activating mutation in vitro and in vivo. JAK-STAT pathway might represent a promising therapeutic target for ALL.

To explore the role of bone marrow niche in the chemotherapy resistance of patient with acute myeloid leukemia (AML), and to investigate the effects of the MSCs on the apoptosis of HL-60 cell and its underlying mechanisms.MSCs were derived from the bone marrow of newly diagnosed AML patients (AML-MSCs) and health donors(MSCs) were co-cultured with HL-60 cells respectively. The apoptosis of HL-60 cells in the presence/absence of MSCs and/or Daunorubicin were determined by flow cytometry with Annexin V/PI double staining. In addition, the morphological features of HL-60 cells were observed by Wright-Giemsa staining, and the ratio of blasts and differentiated cells were counted. Furthermore, the expressions of apoptosis-related factors including Caspase-3, Caspase-8,Caspase-9 and Survivin were detected by Western blot.The flow cytometry showed that there was no significant change in apoptosis of HL-60 cells co-cultured with MSC derived from healthy donors or AML patients. After adding Daunorubicin into different cultural systems, the apoptotic rates of HL-60, HL-60 co-cultured with normal MSCs and HL-60 co-cultured with AML-MSCs were (49.57±7.44)%, (30.72±4.05)% and (22.99±4.08)%, respectively, which showed that normal MSCs and AML-MSCs could remarkably supress Daunorubicin-induced HL-60 apoptosis, however, there was no statistically significant difference of apoptosis between HL-60 co-cultured with normal MSCs and HL-60 co-cultured with AML-MSCs. Wright-Giemsa staining showed that most of the HL-60 cells co-cultured with AML-MSCs were primitive, and cell differentiation was unusual. In AML-MSCs co-cultured group, the cell apoptosis and differentiation caused by DNR was significant decreased, and most of HL-60 cells were initial. Western blot showed that the cleavage activity of Caspase-3 of HL-60 in AML-MSCs and normal MSCs co-cultured group was decreased, compared with HL-60 in single cultured group, moreover, the decrease was significantly in AML-MSC group. Additionally, the expression of survivin in AML-MSCs and normal MSCs co-cultured group was increased, compared with that in single cultured group, and increase was significant in AML-MSCs group.MSCs can suppress Daunorubicin-induced HL-60 apoptosis via inhibiting Caspase-3 and maintaining survivin level.初诊急性髓系白血病患者来源的骨髓间充质干细胞通过调节Caspase-3/survivin抑制DNR诱导的HL-60细胞凋亡.探讨急性髓系白血病（AML）患者的骨髓微环境在化疗耐药中的作用，观察骨髓间充质干细胞（MSC）对柔红霉素（DNR）诱导的AML细胞HL-60凋亡的影响，并探索其初步作用机制.分别将健康供者和初诊AML患者来源的骨髓MSC与 HL-60细胞共培养，不同的实验组添加或者不添加DNR，采用流式细胞术检测Annexin Ⅴ/PI标记的HL-60细胞凋亡；通过瑞氏-吉姆萨染色观察各组HL-60细胞形态，统计原始和分化细胞所占的比例；采用Western blot 检测凋亡相关蛋白Caspase-3、Caspase-8、Caspase-9和Survivin的表达情况.流式细胞术显示，健康供者MSC以及初诊AML患者来源MSC分别与HL-60细胞共培养未见HL-60细胞的凋亡情况有显著变化。加入DNR后，HL-60细胞凋亡率为（49.57±7.44）％，健康供者MSC共培养加药组和初诊AML患者来源的MSC共培养加药组凋亡率显著降低，分别为（30.72±4.05）％（P0.01）和（22.99±4.08）%（P0.01），但健康供者MSC组与初诊AML患者来源MSC组对DNR诱导HL-60细胞凋亡的抑制作用无统计学差别（P0.05）。瑞氏-吉姆萨染色结果显示，初诊AML患者来源MSC共培养的HL-60细胞绝大多数处于原始状态，极少见到细胞分化。初诊AML患者来源MSC共培养组中，DNR引起的细胞凋亡和分化明显减少，HL-60细胞大多数处于原始状态。Western blot 检测结果表明，初诊AML患者来源MSC和健康供者MSC共培养组的HL-60细胞内Caspase-3活性剪切均较HL-60细胞单独培养组下降，且初诊AML患者来源MSC组显著降低。此外，初诊AML患者来源MSC和健康供者MSC共培养的HL-60细胞Survivin的表达较单独药物作用组表达更高，且初诊AML患者来源MSC组表达显著增高.初诊的AML患者骨髓中存在的MSC与健康人骨髓MSC可以抑制DNR诱导的HL-60细胞凋亡，其作用机制可能与抑制了HL-60细胞内Caspase-3活性，提高了Survivin的表达有关.

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.

How the brain representation of conceptual knowledge vary as a function of processing goals remains unclear. We hypothesized that the brain representation of semantic categories is shaped by the depth of processing. Participants were presented with visual words during functional MRI. During shallow processing, participants had to read the items. During deep processing, they had to mentally simulate the features associated with the words. Multivariate classification, informational connectivity and encoding models were used to reveal how the depth of processing determines the brain representation of word meaning. Decoding accuracy in putative substrates of the semantic network was enhanced when the depth processing was high, and the brain representations were more generalizable in semantic space relative to shallow processing contexts. This pattern was observed even in association areas in inferior frontal and parietal cortex. Deep information processing during mental simulation also increased the informational connectivity within key substrates of the semantic network. To further examine the properties of the words encoded in brain activity, we compared computer vision models - associated with the image referents of the words - and word embeddings. Computer vision models explained more variance of the brain responses across multiple areas of the semantic network. These results indicate that the brain representation of word meaning is highly malleable by the depth of processing imposed by the task, relies on access to visual representations and is highly distributed, including prefrontal areas previously implicated in semantic control.

To study the influence of acute myeloid leukemia (AML) microenvironment on mesenchymal stem cells (MSCs).MSCs were isolated from the bone marrow of newly diagnosed AML patients (AML-MSCs) and were cultured. The morphology of MSC was observed by inverted microscopy, the immunophenotypes of MSC were detected by flow cytometry, the proliferation ability of MSC was detected by using MTT method, the multi-differentation ability of MSC was assayed by osteogenic, lipogenic and chrondrogenic induction. The morphologic features, immunophenotypic characteristics, cell proliferation, and multipotential differentiation capability were compared between the MSC derived from normal healthy donors and AML patients.AML-MSCs presented the morphological features similar to the normal MSCs. In addition, AML-MSCs highly expressed CD29, CD44, CD73, CD105 and HLA-ABC. Meanwhile, they were homogenously negative for CD14，CD31, CD34, CD45, CD80, CD86 and HLA-DR. Further-more, AML-MSCs showed cell proliferation ability similar to normal MSCs. Notably, AML-MSCs exerted increased osteogenic-differentiation capacity as compared with normal MSCs.AML-MSCs possess typical MSC phenotypes but displayed enhanced osteogenic-differentiation capacity.初诊急性髓系白血病患者来源的骨髓间充质干细胞成骨分化能力增强.探讨急性髓系白血病(AML)患者骨髓微环境对间充质干细胞(MSC)生物学特性的影响.从初诊的AML患者骨髓中分离得到MSC，在倒置显微镜下观察细胞形态，采用流式细胞术测定其免疫学表型，MTT法检测其增殖能力，以成骨、成脂肪和成软骨诱导检测MSC的多向分化能力.从初诊AML病患者骨髓中分离得到的MSC呈现出经典的成纤维细胞样形态；其细胞表面高表达CD29, CD44, CD73, CD105和HLA-ABC，低表达CD14，CD31, CD34, CD45, CD80, CD86和HLA-DR。与健康人骨髓MSC相比，其增殖能力未见显著差别，但是其成骨细胞分化的能力显著增强.初诊的AML患者骨髓中存在的MSC具有与健康人骨髓MSC相似的细胞形态、免疫表型和增殖能力，但是其成骨分化能力显著增强.