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Review question / Objective: The inclusion criteria for this study are based on the PICOS acronym: Participants (P): COVID-19 patients based on positive Coronavirus RT-PCR (reverse transcription-polymerase chain reaction) of nasopharyngeal and oropharyngeal swabs or a history of COVID-19 infection. Following previous research, the COVID-19 patients in this study will include the period of COVID-19 infection, symptom onset, recovery, and the onset of post-acute COVID-19 symptoms. Interventions (I): not applicable; Comparisons (C): healthy controls in comparative studies, or not applicable to epidemiological surveys; Outcome (O): the prevalence of poor sleep quality (PSQ) or available data could yield the prevalence of PSQ in COVID-19 patients. Sleep quality in COVID-19 patients will be assessed using standardized scales such as the Pittsburgh Sleep Quality Index (PSQI); Study design (S): epidemiological and comparative studies (only the baseline data of cohort study will be extracted).

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, TRAF3IP2-AS1, regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of TRAF3IP2-AS1 A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene E130307A14-Rik that is homologous to TRAF3IP2-AS1 and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing E130307A14-Rik or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17–related autoimmune diseases, such as psoriasis and multiple sclerosis.

WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC-TAK1-ATF2-TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca2+ pathway. It is also suggested that WNT-ANP signaling is implicated in cardiac physiology and pathophysiology.

Trefoil factor 3 (TFF3) is involved in cell adhesion, motility and apoptosis, regulates mucosal immunity and maintains the functional integrity of intestinal epithelia. The upregulation of TFF3 expression in the weaning rat intestine attracted our interest. The present study hypothesized that TFF3 may serve a role in preventing diarrhea in weaning piglets, which is an important consideration in the pig farming industry. Previous recombinant TFF3 protein expression yields obtained from Escherichia coli were too low and the bioactivity of the protein was poor. Hence, this expression system was unsuitable for industrial applications. The present study explored the production of recombinant sus scrofa TFF3 in a Brevibacillus choshinensis (B. choshinensis) expression system, aiming to enhance the expression level of bioactive protein. To achieve this, the sus scrofa TFF3-encoding gene fragment was fused into an E. coli-Brevibacillus shuttle vector pNCMO2. High levels of TFF3 (30 mg/l) were produced and secreted into the B. choshinensis culture medium in soluble form with a molecular mass of 13.6 kDa and high immunoreactivity in western blotting. Thus, Brevibacillus may be used to produce useful mucosal factors for biochemical analyses and mucosal protection, and in industrial applications to produce novel inhibitors of diarrhea.

Atrial natriuretic peptide (ANP), a canonical cardiac hormone, is mainly secreted from atrial myocytes and is involved in the regulation of body fluid, blood pressure homeostasis, and antioxidants. Cholecystokinin (CCK) is also found in cardiomyocytes as a novel cardiac hormone and induces multiple cardiovascular regulations. However, the direct role of CCK on the atrial mechanical dynamics and ANP secretion is unclear. The current study was to investigate the effect of CCK octapeptide (CCK-8) on the regulation of atrial dynamics and ANP secretion. Experiments were performed in isolated perfused beating rat atria. ANP was measured using radioimmunoassay. The levels of hydrogen peroxide (H

Silent information regulator factor 2‑related enzyme 1 (Sirt1) is involved in the regulation of cell senescence, gene transcription, energy balance and oxidative stress. However, the effect of Sirt1 on atrial natriuretic factor (ANF) secretion, especially under hypoxic conditions is unclear. The present study aimed to investigate the effect of Sirt1, regulated by NADPH oxidase 4 (NOX4), on ANF secretion in isolated beating rat atria during hypoxia. ANF secretion was analyzed using radioimmunoassays and protein expression levels were determined by western blotting and immunofluorescence staining. Intra‑atrial pressure was recorded using a physiograph. Hypoxia significantly upregulated Sirt1 and nuclear factor erythroid‑2‑related factor 2 (Nrf2) protein expression levels, together with significantly increased ANF secretion. Hypoxia‑induced protein expression of Sirt1 was significantly blocked by a NOX4 inhibitor, GLX351322, and Nrf2 protein expression levels were significantly abolished using the Sirt1 inhibitor, EX527. Hypoxia also significantly elevated the protein expression levels of phosphorylated‑Akt and sequestosome 1 and significantly downregulated Kelch‑like ECH‑associated protein 1 protein expression levels. These effects were significantly blocked by EX527, preventing hypoxia‑induced Nrf2 expression. An Nrf2 inhibitor, ML385, significantly abolished the hypoxia‑induced upregulation of activating transcription factor (ATF)3, ATF4, T cell factor (TCF)3 and TCF4/lymphoid enhancer factor 1 (LEF1) protein expression levels, and significantly attenuated hypoxia‑induced ANF secretion. These results indicated that Sirt1 and Nrf2, regulated by NOX4, can potentially stimulate TCF3 and TCF4/LEF1 signaling via ATF3 and ATF4 activation, thereby potentially participating in the regulation of ANF secretion in beating rat atria during hypoxia. In conclusion, intervening with the Sirt1/Nrf2/ATF signaling pathway may be an effective strategy for resisting oxidative stress damage in the heart during hypoxia.

Background: Associations between the microbiome–gut–brain axis and dementia have attracted considerable attention in research literature. This study examined the microbiome–gut–brain axis and dementia-related research from a bibliometric perspective. Methods: A search for original research and review articles on the microbiome–gut–brain axis and dementia was conducted in the Web of Science Core Collection (WOSCC) database. The R package “bibliometrix” was used to collect information on countries, institutions, authors, journals, and keywords. VOSviewer software was used to visualize the co-occurrence network of keywords. Results: Overall, 494 articles met the study inclusion criteria, with an average of 29.64 citations per article. Corresponding authors of published articles were mainly from China, the United States and Italy. Zhejiang University in China and Kyung Hee University in Korea were the most active institutions, while the Journal of Alzheimer’s Disease and Nutrients published the most articles in this field. Expected main search terms, “Parkinson disease” and “chain fatty-acids” were high-frequency keywords that indicate current and future research directions in this field. Conclusions: This bibliometric study helped researchers to identify the key topics and trends in the microbiome–gut–brain axis and dementia-related research. High-frequency keywords identified in this study reflect current trends and possible future directions in this field related to methodologies, mechanisms and populations of interest.

Background The urine protein/creatinine ratio (UPCR) is commonly used in current clinical practice. However, there are only few published clinical data on UPCR from large cohorts of Chinese adults. This study aimed to determine the overall and age‐ and sex‐specific UPCR reference values for healthy Dalian adults. Methods According to the Clinical & Laboratory Standards Institute EP28‐A3c guidelines, 1321 healthy Dalian adults (646 men and 675 women) aged 20–69 years were enrolled. Urine protein and creatinine levels were analyzed in the random morning spot urine samples, and UPCR was calculated. The 95th percentile of the UPCR was used as the normal upper limit. The Mann–Whitney U test was used to test differences among groups. Results The UPCR reference value was 141.7 mg/g for the entire cohort, 128.7 mg/g for men, and 150.8 mg/g for women. In addition, women had relatively higher UPCR values than men in the same age group. We also compared the UPCR reference values between different estimated glomerular filtration rate (eGFR) groups and found that women had significantly higher UPCR values than men in the normal eGFR groups. Conclusions This study provides the overall and age‐ and sex‐specific UPCR reference values for healthy Dalian adults., The urine protein/creatinine ratio (UPCR) reference value was 141.7 mg/g for the entire cohort, 128.7 mg/g for men, and 150.8 mg/g for women. In addition, women had relatively higher UPCR values than men in the same age group.

Metabolic reprogramming occurs in the clonal evolution of acute myeloid leukemia (AML), which contributes to cell survival under metabolic stress and the development of drug resistance. Leukemic cells exhibit various metabolic profiles, which involve multiple metabolic pathways due to the heterogeneity of AML. However, studies on metabolic targets for AML treatment are mostly focused on glycolysis at present. In this work, we established conditional knock-in AML mouse models harboring Dnmt3aR878H/WT, NrasG12D/WT, and both of the mutations, respectively. Transcriptomic analysis of Gr1+ cells from bone marrow was performed afterward to screen interested metabolic pathways and target genes. Candidate genes were studied using the CRISPR/Cas9 technique, quantitative real-time RT-PCR, and flow cytometric analyses. We revealed that multiple metabolic pathways were affected in AML mice, including lipid metabolism. Endothelial lipase (LIPG) was obviously upregulated in leukemic cells from AML mice with Dnmt3a mutation. We performed knockout of LIPG in OCI-AML3 cells carrying DNMT3A R882C mutation by using the CRISPR/Cas9 technique. Depletion of LIPG led to proliferation inhibition, apoptosis, damage of antioxidant capacity, and myeloid differentiation in OCI-AML3 cells. LIPG might serve as a potential metabolic target for the treatment of AML with abnormal lipid metabolism.

Background Our previous study had found that the abundance of Lactobacillaceae in stool of acute coronary syndrome patients was significantly decreased. Experiments have confirmed that Lactobacillus has the effects of anti-inflammation, regulating blood lipids and improving cardiac injury after myocardial infarction. Purpose To explore the relationship between Lactobacillus and prognosis of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention (PCI) and its possible mechanism. Methods Patients with AMI who received emergency PCI from July 2017 to December 2018 in department of CCU were enrolled.Stool and blood samples were collected from all patients. The fecal 16S rDNA gene sequencing data from subjects were analyzed and subjects were categorized into Low, Medium and High level groups according to stool Lactobacillus measurements. The primary endpoints were major adverse cardiac events (MACE). Univariate and multivariate Cox regression were used to analyze the relationship between Lactobacillus and prognosis. Kaplan-Meier survival curve was used to characterize the association between the risk of MACE and Lactobacillus levels. Spearman correlation analysis and trend test were used to assess the relationship between Lactobacillus and Clinical index. Results A total of 254 patients were included in the analysis. The age was 65.90±11.56 years old,and 152 (59.84%) were male. The follow-up time was 652 (548.25, 753) days. Multivariate Cox regression showed that patients with Lactobacillus >7.1 copies/g presented lower risk of MACE (HR=0.179, 95% CI 0.076–0.422, P Conclusion Lactobacillus can significantly reduce the risk of MACE in STEMI patients treated by PCI, especially for male smokers over 60 years old. The underlying mechanism may be related to the fact that Lactobacillus can reduce inflammatory reaction, lessen cardiac injury and improve cardiac function. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): the Key Project of Scientific and Technological Support Plan of Tianjin in 2020 Correlation analysis between LactobacillSubgroup analysis in different patients

DNMT3A mutations are frequently identified in acute myeloid leukemia (AML) and indicate poor prognosis. Previously, we found that the hotspot mutation DNMT3A R882H could upregulate CDK1 and induce AML in conditional knock-in mice. However, the mechanism by which CDK1 is involved in leukemogenesis of DNMT3A mutation-related AML, and whether CDK1 could be a therapeutic target, remains unclear. In this study, using fluorescence resonance energy transfer and immunoprecipitation analysis, we discovered that increased CDK1 could compete with EZH2 to bind to the PHD-like motif of DNMT3A, which may disturb the protein interaction between EZH2 and DNMT3A. Knockdown of CDK1 in OCI-AML3 cells with DNMT3A mutation markedly inhibited proliferation and induced apoptosis. CDK1 selective inhibitor CGP74514A (CGP) and the pan-CDK inhibitor flavopiridol (FLA) arrested OCI-AML3 cells in the G2/M phase, and induced cell apoptosis. CGP significantly increased CD163-positive cells. Moreover, the combined application of CDK1 inhibitor and traditional chemotherapy drugs synergistically inhibited proliferation and induced apoptosis of OCI-AML3 cells. In conclusion, this study highlights CDK1 overexpression as a pathogenic factor and a potential therapeutic target for DNMT3A mutation-related AML.

In the brain, AMPA receptors mediate fast excitatory neurotransmission, the dysfunction of which leads to neuropsychiatric disorders. Synaptic function of AMPA receptors is tightly controlled by a protein group called transmembrane AMPAR regulatory proteins (TARPs). TARP γ-8 (also known as CACNG8) preferentially expresses in the hippocampus, cortex and subcortical regions that are critical for emotion generation indicating its association with psychiatric disorders. Here, we identified rs10420324 (T/G), a SNP located in the human CACNG8 gene, regulated reporter gene expression in vitro and TARP γ-8 expression in the human brain. A guanine at the locus (rs10420324G) suppressed transcription likely through modulation of a local G-quadruplex DNA structure. Consistent with these observations, the frequency of rs10420324G was higher in patients with anti-social personality disorder (ASPD) than in controls, indicating that rs10420324G in CACNG8 is more voluntary for ASPD. We then characterized the behavior of TARP γ-8 knockout and heterozygous mice and found that consistent with ASPD patients who often exhibit impulsivity, aggression, risk taking, irresponsibility and callousness, a decreased γ-8 expression in mice displayed similar behaviors. Furthermore, we found that a decrease in TARP γ-8 expression impaired synaptic AMPAR functions in layer 2–3 pyramidal neurons of the prefrontal cortex, a brain region that inhibition leads to aggression, thus explaining, at least partially, the neuronal basis for the behavioral abnormality. Taken together, our study indicates that TARP γ-8 expression level is associated with ASPD, and that the TARP γ-8 knockout mouse is a valuable animal model for studying this psychiatric disease.

This article investigates an adaptive finite-time neural control for a class of strict feedback nonlinear systems with multiple objective constraints. In order to solve the main challenges brought by the state constraints and the emergence of finite-time stability, a new barrier Lyapunov function is proposed for the first time, not only can it solve multiobjective constraints effectively but also ensure that all states are always within the constraint intervals. Second, by combining the command filter method and backstepping control, the adaptive controller is designed. What is more, the proposed controller has the ability to avoid the ``singularity'' problem. The compensation mechanism is introduced to neutralize the error appearing in the filtering process. Furthermore, the neural network is used to approximate the unknown function in the design process. It is shown that the proposed finite-time neural adaptive control scheme achieves a good tracking effect. And each objective function does not violate the constraint bound. Finally, a simulation example of electromechanical dynamic system is given to prove the effectiveness of the proposed finite-time control strategy.

To determine the role of PPE25 in the infection ofIn MS-ppe25 group, PPE25 was expressed in non-pathogenic fast-growingPPE25 protein had no effect on MS growth, colony formation and the size of single colonies. MS-infected PMN had higher percentages of CFU and LDH release 2, 6, and 12 h after infections compared with the MS-vec group (PPE25 protein increases the survival of MS in PMN, induces cell necrosis, inhibits the expressions of ROS and NO, and changes the secretion of cytokines, which helps spread of the pathogen by evading host immunity.

Retinoic acid-inducible gene I (RIG-I) is up-regulated during granulocytic differentiation of acute promyelocytic leukemia (APL) cells induced by all- trans retinoic acid (ATRA). It has been reported that RIG-I recognizes virus-specific 5′-ppp-double-stranded RNA (dsRNA) and activates the type I interferons signaling pathways in innate immunity. However, the functions of RIG-I in hematopoiesis remain unclear, especially regarding its possible interaction with endogenous RNAs and the associated pathways that could contribute to the cellular differentiation and maturation. Herein, we identified a number of RIG-I–binding endogenous RNAs in APL cells following ATRA treatment, including the tripartite motif-containing protein 25 ( TRIM25 ) messenger RNA (mRNA). TRIM25 encodes the protein known as an E3 ligase for ubiquitin/interferon (IFN)-induced 15-kDa protein (ISG15) that is involved in RIG-I–mediated antiviral signaling. We show that RIG-I could bind TRIM25 mRNA via its helicase domain and C-terminal regulatory domain, enhancing the stability of TRIM25 transcripts. RIG-I could increase the transcriptional expression of TRIM25 by caspase recruitment domain (CARD) domain through an IFN-stimulated response element. In addition, RIG-I activated other key genes in the ISGylation pathway by activating signal transducer and activator of transcription 1 (STAT1), including the modifier ISG15 and several enzymes responsible for the conjugation of ISG15 to protein substrates. RIG-I cooperated with STAT1/2 and interferon regulatory factor 1 (IRF1) to promote the activation of the ISGylation pathway. The integrity of ISGylation in ATRA or RIG-I–induced cell differentiation was essential given that knockdown of TRIM25 or ISG15 resulted in significant inhibition of this process. Our results provide insight into the role of the RIG-I-TRIM25-ISGylation axis in myeloid differentiation.

Saphenous vein grafts disease (SVGD) is a common complication after coronary artery bypass graft (CABG) and usually treated by percutaneous coronary intervention (PCI). In this prospective cohort study, we performed virtual histology-intravascular ultrasound to investigate whether plaque composition and morphological characteristics were associated with post-PCI major adverse cardiac events (MACEs) and slow/no-reflow in patients with SVGD. Patients (n = 90) were studied (76.7% men, mean age 64.9 ± 8.2 years and mean duration of SVG 8.0 ± 3.6 years). There were 77.8% lesions with a plaque burden of at least 70%; 18 MACE incidences accumulated in 14 patients over 12 months post-PCI and slow/no-reflow was observed in 12 patients. On adjusted multivariate analysis, lesion length (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 1.01-1.08]); age of CABG (HR = 1.51 [95% CI: 1.11-2.05], and absolute necrotic core (NC) area (HR = 8.04 [95% CI: 1.86-34.73]) were independently associated with MACEs. Factors independently associated with slow/no-reflow post-PCI were preprocedure systolic blood pressure (odds ratio [OR] = 0.98; 95% CI: 0.96-0.99) and absolute NC area (OR = 2.47 (95% CI: 1.14-5.36). A cutoff value of absolute NC area at ≥1.1 mm2 may serve as a significant risk predictor for no-reflow after SVG-PCI. Factors associated with MACEs and the slow/no-reflow phenomenon following PCI of the SVG can be used in risk assessment of SVG.

Significance DNMT3A is a critical epigenetic modifier and tumor suppressor in the hematopoietic system. This gene is frequently mutated in hematopoietic malignancies, including acute myeloid leukemia (AML), with Dnmt3a R878H being the most common mutant. By using a conditional knockin approach, this study shows that Dnmt3a R878H is sufficient to initiate AML and recapitulate human leukemic features in mice. The leukemia-initiating cells are enriched in hematopoietic stem/progenitor cells. Through gene expression profiling, DNA methylation and histone modification analysis, and functional tests on important regulators for cell proliferation and differentiation in an animal model, this study has not only discovered mTOR pathway activation as a key player in the disease mechanism but also revealed the potential therapeutic effects of mTOR inhibition on DNMT3A mutation-related leukemia.

The adsorption and aggregation of mixed systems for ionic liquid (ILs) surfactants (1-decyl-3-methylimidazolium bromide, C 10 mimBr, 1-dodecyl-3-methylimidazolium bromide, C 12 mimBr, 1-hexadecyl-3-methylimidazolium bromide, C 16 mimBr) and non-ionic surfactant Triton X-100 in aqueous media have been investigated by surface tension measurements, electrical conductivity, 1 H NMR and FTIR technologies. Surface properties have been determined such as critical micelle concentration (CMC), surface saturation adsorption ( Γ max ), minimum surface area per surfactant molecule ( A min ), surface tension at the CMC (γ CMC ), adsorption efficiency ( pC 20 ), and surface pressure at the CMC ( Π CMC ) as well as thermodynamic parameters of micellization. The surface tension measurements revealed that the addition of Triton X-100 into ILs can decrease CMC of ILs, suggesting that it is beneficial to the mixed micelle formation. Consistent with the results of surface tension, electrical conductivity measurement demonstrate a small degree of counter-ion binding to form mixed micelles, which may increase with the addition of TX-100. The 1 H NMR data and FT-IR analysis demonstrated the presence of hydrogen-bond between the imidazolium cation of ILs and the PEO units of Triton X-100 and hydrophobic interactions between the alkyl chain of the imidazolium cation and the hydrophobic chain with phenyl of Triton X-100.

Accumulated studies have reported the prognostic significance of prealbumin in liver cancer, but the results were not conclusive. The aim of this study was to evaluate the association between pretreatment serum prealbumin and clinical outcome of liver cancer patients through a meta-analysis. We comprehensively searched EMBASE, PubMed, Web of Science and the Cochrane library to identify eligible studies. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were utilized to evaluate the prognostic value of pretreatment serum prealbumin in overall survival (OS) and recurrence-free survival (RFS) of liver cancer patients. A total of 3470 patients from 10 eligible studies were finally included for analysis. The combined effects of prealbumin on liver cancer patients' OS and RFS were HR = 1.83, 95% CI: 1.46-2.30

Homoharringtonine (HHT), a known protein synthesis inhibitor, has an anti-myeloid leukemia effect and potentiates the therapeutic efficacy of anthracycline/cytarabine induction regimens for acute myelogenous leukemia (AML) with favorable and intermediate prognoses, especially in the t(8;21) subtype. Here we provide evidence showing that HHT inhibits the activity of leukemia-initiating cells (Lin − /Sca-1 − /c-kit + ; LICs) in a t(8;21) murine leukemia model and exerts a down-regulating effect on MYC pathway genes in human t(8;21) leukemia cells (Kasumi-1). We discovered that NF-κB repressing factor (NKRF) is bound directly by HHT via the second double-strand RNA-binding motif (DSRM2) domain, which is the nuclear localization signal of NKRF. A series of deletion and mutagenesis experiments mapped HHT direct binding sites to K479 and C480 amino acids in the DSRM2 domain. HHT treatment shifts NKRF from the nucleus (including nucleoli) to the cytoplasm by occupying the DSRM2 domain, strengthens the p65–NKRF interaction, and interferes with p65-p50 complex formation, thereby attenuating the transactivation activity of p65 on the MYC gene. Moreover, HHT significantly decreases the expression of KIT , a frequently mutated and/or highly expressed gene in t(8;21) AML, in concert with MYC down-regulation. Our work thus identifies a mechanism of action of HHT that is different from, but acts in concert with, the known mode of action of this compound. These results justify further clinical testing of HHT in AML.

To determine the effect of NF-κB on cell proliferation and apoptosis, we investigate the expression of inflammation and apoptosis-related factors in the bovine mammary epithelial cell line, MAC-T. MAC-T cells were cultured in vitro and MTT and LDH assays used to determine the effects of lipopolysaccharide (LPS) on proliferation and cytotoxicity respectively. RT-PCR and western blotting were used to evaluate the effect of LPS and NF-κB inhibition [pyrrolidine dithiocarbamate (PDTC) treatment] on the expression of inflammation and apoptosis-related factors. LPS significantly inhibited MAC-T cell proliferation in a dose- and time-dependent manner. Furthermore, LPS promoted apoptosis while the NF-кB inhibitor PDTC attenuated this effect. After LPS treatment, the NF-кB signaling pathway was activated, and the expression of inflammation and apoptosis-related factors increased. When PDTC blocked NF-кB signaling, the expression of inflammation and apoptosis-related factors were decreased in MAC-T cells. LPS activates the TLR4/NF-κB signaling pathway, inhibits proliferation and promotes apoptosis in MAC-T cells. NF-кB inhibition attenuates MAC-T cell apoptosis and TLR4/NF-κB signaling pathway. NF-кB inhibitor alleviating MAC-T cell apoptosis is presumably modulated by NF-кB.

During the last decade, traffic injury rates of pedestrians who are elderly in Singapore were more than twice of those for pedestrians of all ages. This article aims to identify the factors and situations influencing the injury severity of pedestrians who are elderly involved in vehicle–pedestrian crashes. Six years of crash data from 2003 to 2008 containing about 805 crashes of pedestrians who are elderly were analyzed. The injury severity was modeled as a function of roadway characteristics, traffic features, environmental factors, as well as driver and pedestrian characteristics using a random-parameter ordered probit model that accounts for unobserved heterogeneities in the population. Results show that the likelihood of fatal injury is higher during night time. Although the probabilities of fatal or serious injury are higher along high-speed roads and at three-legged intersections, the corresponding probabilities are lower if the crash involving pedestrians who are elderly happens at signaliz...

β-cryptoxanthin (CX), a major carotenoid pigment, can inhibit inflammatory gene expression in mice with nonalcoholic steatohepatitis. In the present study, we examined the anti-inflammatory effects of CX on lipopolysaccharide (LPS)-induced inflammation in mouse primary Sertoli cells and the possible molecular mechanisms behind its effects. The results showed that CX significantly inhibited LPS-induced decreases in cell viability and in the percentage of apoptotic cells. Moreover, CX inhibited the LPS-induced up-regulation of tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in Sertoli cells. In addition, CX significantly limited the LPS-induced down-regulation of AR, HSF2, CREB, FSHR, INHBB and ABP in Sertoli cells. Western blot analysis showed that CX significantly suppressed NF-κB (p65) activation as well as MAPK phosphorylation. All the results suggested that CX suppressed inflammation, possibly associated with the NF-κB activation and MAPK of phosphorylation. Thus, CX may possess therapeutic potential against inflammation-related diseases.

β-cryptoxanthin (CRY), a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride (CdCl 2 )-induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal (i.p.) injections of corn oil and physiological saline. The other rats were i.p. injected with CRY (10 μg kg-1 ) every 8 h, beginning 8 h before CdCl 2 (2.0 mg kg-1 ) treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats. Furthermore, the Cd-induced decrease in the testicular testosterone (T) level was attenuated after CRY administration (P < 0.05). The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide (LPO) and malondialdehyde (MDA) levels (P < 0.01). The testicular antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.

BACKGROUND: Acute myeloid leukemia (AML) is a type of cancer that consists of a group of hematological malignancies with high heterogeneity. DNA methyltransferase 3A (DNMT3A)-mutated AML patients have a poor prognosis. Some long non-coding RNAs (lncRNAs) have been reported to enhance therapeutic sensitivity, and so could affect the overall survival rate of elderly cytogenetically normal acute myeloid leukemia (CN-AML) patients; however, studies on the lncRNA signature in DNMT3A-mutated AML are rare. METHOD: The DNMT3A R878H conditional knock-in mouse model was constructed to explore the lncRNAs of DNMT3A mutation by using the Cuffcomparison method. Cis and trans regulation networks were used to predict candidate genes. The expression levels in leukemic cell lines and the prognostic index of these candidate genes were analyzed with the Broad Institute Cancer Cell Line Encyclopedia (CCLE) and OncoLnc databases. The data for each sample were statistically analyzed using GraphPad Prism. RESULTS: In this study, we applied the DNMT3A R878H conditional knock-in mouse model to explore the lncRNA epigenetic landscape of DNMT3A mutation by using the Cuffcomparison method. Twenty-three differentially expressed lncRNAs were identified in Dnmt3a(R878H/WT)Mx1-Cre(+) mice. We next predicted the downstream targetable genes regulated by these lncRNAs through cis and trans regulation networks and found 124 candidate genes are related to these lncRNAs. In further analysis of 124 genes, we found that increased mRNA expression levels of interleukin 1 receptor type 2 (IL1R2), Krüppel-like factor 13 (KLF13), ATPase H+ transporting V1 subunit A (ATP6V1A), proteasome 26S Subunit, non-ATPase 3 (PSMD3), and pyrroline-5-carboxylate reductase 2 (PYCR2) were associated with poor prognosis in AML. Functional analysis of these genes demonstrated that the pathways involved in autophagy, cell cycle, and hematopoietic stem cell differentiation were more enriched in Dnmt3a(R878H/WT)Mx1-Cre(+) mice. CONCLUSION: Our study was the first to use DNMT3A R878H conditional knock-in mouse model to predict the specific lncRNAs regulated by the DNMT3A mutation in AML. Six candidate genes were found to be associated with DNMT3A mutation with poor prognosis. Our results provided a possible treatment strategy for this disease.

Biochar often refers to a carbon-rich product obtained by pyrolyzing biomass at relatively low temperatures (700 ℃). The increasing interest in the applications of biochar in soil amendment and environmental contaminant reduction has spurred many studies in recent years. Due to the high content of ash in biochar, the adsorption capacity of bichar is limited. The ash of biochar formed during pyrolysis has great influence on the structure characteristics and spectral characteristics of biochar. The ash of biochar is expected to enchance their efficacy and minimize their influence. For this purpose, the corn straw biochar made at two different temperatures (400 and 600 ℃) was used to study the effect on the structure characteristics of biochars under the acid elution. The samples were characterized with element analysis, Brunaner-Emmett-Teller-N2 surface areas, pore size distributions and micro infrared for structure analysis in this study. The result indicate that: the elution solvent could remove the by-products and improve the adsorptive capacity of biochars. (1)After acid elution, the carbon content, hydrophobicity and the aromatic functional group content were increased; the polarity of biochar was decreased. (2) After acid treated, the specific surface area of the biochars was significantly increased, the increment of two biochars was 3.46 times and 6.75 times; the pore volume and the mesoporous quantity were also enhanced. (3) After acid elution, the infrared analysis is similar, but the content of key functional groups was different significantly. The result of infrared analysis showed that, several absorbance peaks were decrease at 3 398~3 447, 2 924~3 056, 1 378~1 439 cm-1, and the acid treated can make the content of aliphatic chain char and hydroxyl reduce. (4) Biochar with low polarity and high aromaticity displayed a superior 2,4- dichlorophenoxyacetic acid adsorption capacity. Acid elution made the surface of biochar exposed more organic surface and porosity and it is one of the most important factors for the adsorption of biochar. The date with elemental analyzer, BET，FTIR techniques and batch experiment allowed us to develop a better understanding of evolution of biochar properties during the acid elution and these results have significant implications for using biochar as a soil additive for soil pollution.

Background DNMT3A R882H, a frequent mutation in acute myeloid leukemia (AML), plays a critical role in malignant hematopoiesis. Recent findings suggest that DNMT3A mutant acts as a founder mutation and requires additional genetic events to induce full-blown AML. Here, we investigated the cooperation of mutant DNMT3A and NRAS in leukemogenesis by generating a double knock-in (DKI) mouse model harboring both Dnmt3a R878H and Nras G12D mutations. Methods DKI mice with both Dnmt3a R878H and Nras G12D mutations were generated by crossing Dnmt3a R878H knock-in (KI) mice and Nras G12D KI mice. Routine blood test, flow cytometry analysis and morphological analysis were performed to determine disease phenotype. RNA-sequencing (RNA-seq), RT-PCR and Western blot were carried out to reveal the molecular mechanism. Results The DKI mice developed a more aggressive AML with a significantly shortened lifespan and higher percentage of blast cells compared with KI mice expressing Dnmt3a or Nras mutation alone. RNA-seq analysis showed that Dnmt3a and Nras mutations collaboratively caused abnormal expression of a series of genes related to differentiation arrest and growth advantage. Myc transcription factor and its target genes related to proliferation and apoptosis were up-regulated, thus contributing to promote the process of leukemogenesis. Conclusion This study showed that cooperation of DNMT3A mutation and NRAS mutation could promote the onset of AML by synergistically disturbing the transcriptional profiling with Myc pathway involvement in DKI mice.