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Abstract Background Previous research has suggested that engaging in regular physical activity (PA) can help to reduce symptoms of depression and anxiety in university students. However, there is a lack of evidence regarding the impact of reducing sedentary behavior (SB) and increasing light-intensity PA (LPA) on these symptoms. This study aims to address this gap by using isotemporal substitution (IS) models to explore how substituting SB with LPA or moderate-to-vigorous PA (MVPA) affects depression and anxiety symptoms among university students. Methods The study recruited 318 university students with a mean age of 21.13 years. Accelerometers were used to objectively measure the time spent on SB, LPA, and MVPA, while depression and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Self-rating Anxiety Scale (SAS). IS models using multivariable linear regression were employed to estimate the associations between different behaviors and depression and anxiety symptoms when 30 min of one behavior was substituted with another. Results In the single-activity model, less SB (β = 0.321, 95% CI: 0.089, 1.297) and more MVPA (β = −0.142, 95% CI: −1.496, − 0.071) were found to be significantly and negatively associated with depression scores, while less SB (β = 0.343, 95% CI: 0.057, 1.014), LPA (β = 0.132, 95% CI: 0.049, 1.023), and more MVPA (β = −0.077, 95% CI: −1.446, − 0.052) were significantly and negatively correlated with anxiety scores. The IS analysis revealed that substituting 30 min of SB with LPA (β = −0.202, 95% CI: −1.371, − 0.146) or MVPA (β = −0.308, 95% CI: −0.970, − 0.073) was associated with improvements in depressive symptoms. Substituting 30 min of SB with MVPA (β = −0.147, 95% CI: −1.863, − 0.034) was associated with reduced anxiety symptoms. Conclusion Replacing 30 min of SB with MVPA may alleviate depression and anxiety symptoms in university students. Further research is needed to explore the long-term effects of PA interventions on the mental health disorders of this population.

Abstract Background Although prior studies have demonstrated that children with high levels of fundamental movement skill (FMS) are more active throughout the day, little is known about children’s FMS and their physical activity (PA) during different segments of the school day (e.g., recess, lunch break, and physical education). The present study focused on FMS and moderate-to-vigorous PA (MVPA) during school day and identifies the association between children’s FMS and MVPA during different segments of the school day in China. Methods A total of 322 children (boys n = 163, girls n = 159; Mage = 8.12, SD = 1.22 years) from four elementary schools involved in this study. Children’s FMS and MVPA were measured using the Test of Gross Motor Development-2nd edition (TGMD-2) and hip-mounted accelerometers. Data such as height, weight, and socio-economic status (SES) were also obtained. Multilevel mixed regression models were used to examine the cross-sectional associations between FMS and MVPA. Models were adjusted for gender, age, standardized body mass index, and SES. Results Children engaged in 32.19 min of MVPA during the whole school day. Boys were more active than girls and had higher object-control skills competency. Locomotor skills were positively associated with children’s long recess (B = 1.063) and short recess time (B = 1.502) MVPA. Object-control skills were positively correlated with children’s MVPA time during long recess (B = 1.244) and physical education (PE) lessons (B = 1.171). Conclusion The findings highlight the importance of developing both locomotor and object-control skills in elementary schools to lead more MVPA engagement during different segments of the school day.

Objectives This study employed compositional data analysis to examine the association between 24-hour activity behaviours and emotional and behavioural problems among left-behind children (LBC).Design Cross-sectional analysis.Setting The research used a cross-sectional approach to analyse data collected from LBC living in Ningbo, Zhejiang Province, southern China, between February and May 2023.Participants A total of 275 LBC aged 9–15 years old were recruited.Outcome measures The measurement of 24-hour activity behaviour, incorporating sleep, sedentary behaviour (SED), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA), was accomplished using accelerometers. Emotional and behavioural problems were assessed through the application of the Strengths and Difficulties Questionnaire. Compositional data analysis was used to evaluate the potential relationship between the composition of 24-hour activity and emotional and behavioural problems.Results Changes in allocation, such as transferring time from SED to sleep and LPA, were associated with better internalising (β sleep=−0.53, 95% CI −0.60 to −0.46; β LPA=−0.46, 95% CI −0.55 to −0.38) and externalising problems (β sleep=−0.31, 95% CI −0.39 to −0.22; β LP =−0.23, 95% CI −0.32 to −0.13). Furthermore, reallocating time from LPA to MVPA was associated with reduced internalising problems (β=−0.40, 95% CI −0.84 to −0.12). Positive associations with prosocial behaviour were observed when the time was reallocated to MVPA from sleep (β=0.81, 95% CI 0.57 to 1.05), SED (β=0.75, 95% CI 0.51 to 0.99) and LPA (β=0.82, 95% CI 0.57 to 1.08).Conclusions The composition of 24-hour activity behaviours is correlated with emotional and behavioural problems in LBC. The findings indicate that redistributing time from SED to sleep and LPA is linked to improved internalisation and externalisation problem scores. Additionally, the substitution of MVPA for any other behaviours is positively associated with enhanced prosocial behaviours.

CBM well pattern optimization design and deployment is a key part of CBM development plan formulation. Reasonable well pattern deployment can not only optimize CBM production, but also reduce CBM development costs and improve economic benefits. In response to this problem, taking Daning block in the Ordos Basin as the research object, the coal seam conditions and coal reservoir characteristics in the study area were systematically analyzed, and the suitable well type and well pattern orientation for CBM development were determined. The results show that the No.5 coal seam of Shanxi Formation in the Daning block has the characteristics of large thickness, simple structure, high gas content and low permeability. The well type of CBM development should be mainly directional wells, supplemented by horizontal wells, with the corresponding well pattern for large-scale development, and the well pattern orientation is NE66°; using the CBM productivity numerical simulation software COMET3, the current use of the Daning block is analyzed. The productivity was predicted based on the well pattern and well spacing, and the productivity under the open scheme of different well pattern and well spacing was simulated and evaluated. Numerical simulation results show that the CBM recovery rate is only 19.03% after 3086 d of well pattern and well spacing used in the current CBM development in the Daning block, indicating a low degree of CBM resource production. When the well spacing is 300 m×80 m and 400 m×100 m (that is, the well spacing ratio is 4∶1), the cumulative gas production of a single well in the five-spot well pattern is the largest. That is, when the well row spacing ratio is 3∶1), the cumulative gas production of a single well in the rectangular well pattern is the largest. Therefore, it is considered that the five-point well pattern should be selected when setting the well row spacing ratio of 4∶1 in the Daning block, and the 3∶1 Rectangular well pattern should be selected for the well spacing ratio of 1. After the well pattern and well spacing are optimized, the CBM recovery rate reaches 44.18% and 36.85% respectively, and the CBM resource production degree is greatly improved.

Studies have shown that product scarcity appeals affect consumers’ perceived scarcity, willingness to pay, and other responses, and that scarcity appeal has the potential to cause consumers to pay higher attention to the product. However, there is a lack of research on the psychological responses of consumers to scarcity appeal from the perspective of perceived green washing. In this paper, three experiments are conducted to demonstrate the impact of product scarcity appeals on consumers’ purchase intentions. The research shows that when green products use product scarcity appeals as a strategy, consumers’ purchase intentions are affected, but consumers’ information processing about the product is the most important determinant. Perceived green washing mediates the negative effect of product scarcity appeals on green product purchase intentions. And impression management motives moderate the negative effect of product scarcity appeals on green product purchase intentions. The findings of the study not only help companies to effectively adopt the right advertising strategies to improve their marketing effectiveness, but also help them to explore the market for green products.

Abstract Adding adipose cells to cell-cultured meat can provide a distinctive aroma and juicy texture similar to real meat. However, a significant challenge still exists in obtaining seed cells that can be propagated for long periods, maintain their adipogenic potential, and reduce production costs. In this study, we present a cell strain derived from immortalized porcine preadipocytes that can be subculture for over 40 passages without losing differentiation capacity. This cell strain can be differentiated within 3D bioscaffolds to generate cell-cultured fat using fewer chemicals and less serum. Additionally, it can be expanded and differentiated on microcarriers with upscaled culture to reduce costs and labor. Moreover, it can co-differentiate with muscle precursor cells, producing a pattern similar to real meat. Therefore, our cell strain provides an exceptional model for studying and producing cell-cultured fat.

Abstract Objectives To evaluate the effect of different exercise interventions on depressive symptoms in children and adolescents. Methods Randomized controlled trials (RCT) published until May 2023 were screened in four databases. The Cochrane collaboration tool was used to assess the risk of bias for quality evaluation. Stata 16.0 software was used for both a pairwise meta-analysis and a series of frequentist network meta-analyses (NMA). Results A total of 35 RCTs and 5393 participants were included. Aerobic exercise had the most significant effect on depressive symptoms (66.2%), followed by group training (62.5%), resistance exercise (59.0%), and aerobic combined with resistance exercise (57.9%). Furthermore, children and adolescents younger than 15 years showed significant improvement in depressive symptoms (SMD=-0.41, 95% CI (-0.63, -0.19), P

Abstract Background Anxiety, depression, and stress are the most common mental health problems in childhood. Exercise interventions in childhood help to promote mental health. Objective To investigate the relationship between exercise interventions and improvement of negative emotions such as anxiety, depression, and stress in children (5–12 years). Methods Articles were searched in five electronic databases from their inception to January 2023. The meta-analysis was performed using Stata 16.0. Results Twenty-three intervention studies included 6830 children. 1) The exercise intervention group was significantly better than the control group in improving negative emotions (Standard Mean Difference SMD=-0.25, 95% Confidence Intervals CI: -0.34 to -0.15, P

Brown adipose tissue (BAT) dissipates energy as heat, contributing to temperature control, energy expenditure, and systemic homeostasis. In adult humans, BAT mainly exists in supraclavicular areas and its prevalence is associated with cardiometabolic health. However, the developmental origin of supraclavicular BAT remains unknown. Here, using genetic cell marking in mice, we demonstrate that supraclavicular brown adipocytes do not develop from the Pax3+/Myf5+ epaxial dermomyotome that gives rise to interscapular BAT (iBAT). Instead, the Tbx1+ lineage that specifies the pharyngeal mesoderm marks the majority of supraclavicular brown adipocytes. Tbx1Cre-mediated ablation of peroxisome proliferator-activated receptor gamma (PPARγ) or PR/SET Domain 16 (PRDM16), components of the transcriptional complex for brown fat determination, leads to supraclavicular BAT paucity or dysfunction, thus rendering mice more sensitive to cold exposure. Moreover, human deep neck BAT expresses higher levels of the TBX1 gene than subcutaneous neck white adipocytes. Taken together, our observations reveal location-specific developmental origins of BAT depots and call attention to Tbx1+ lineage cells when investigating human relevant supraclavicular BAT.

Previous studies have demonstrated that L. delbrueckii plays beneficial roles in modulating the gut microbiota, enhancing the intestinal barrier, and promoting animal growth. Postbiotics have a similar or even superior effect in protecting intestinal health compared to probiotics due to their excellent stability, extended shelf life, and safety. However, the protective effects and underlying mechanism of postbiotics from L. delbrueckii in intestinal inflammation remain unclear. In this study, we demonstrated the beneficial impact of postbiotics from L. delbrueckii on intestinal health by establishing a S. Typhimurium-induced intestinal inflammation model in mice, which included inactivated bacteria and supernatant. The results revealed that the probiotics and postbiotics from L. delbrueckii increased the survival rate and body weight of S. Typhimurium-induced mice, increased the level of IL-10, and decreased the levels of TNF-α and IL-6, thereby alleviating intestinal inflammation. Meanwhile, treatment with postbiotics decreased the levels of D-LA, DAO, and LPS and promoted the expression of Occludin, ZO-1, and Claudin-1 in the serum and jejunum, suggesting an improvement in intestinal barrier function by postbiotics. Additionally, the postbiotics modulated gut microbial diversity, increased the ratio of Firmicutes and Bacteroidetes, and restored the abundance of Muribaculaceae, Lachnospiraceae_NK4a136_groups, and Alloprevotella in S. Typhimurium-infected mice. Moreover, postbiotics from L. delbrueckii promoted the expansion of intestinal stem cells (ISCs) and increased the numbers of Paneth and Goblet cells. Taken together, these data revealed the beneficial role of postbiotics from L. delbrueckii in protecting against intestinal inflammation by promoting the expansion of ISCs.

Abstract Background Enhanced de novo lipogenesis is essential for hepatocellular carcinoma (HCC). Abnormally high cullin‐associated and neddylation‐dissociated 1 (CAND1) expression is associated with poor clinical prognosis in HCC. The SKP1‐Cullin‐1‐F‐box (SCF) complex consists of the SKP1, Cullin‐1 and F‐box proteins (FBPs) and performs multiple functions including adipogenesis. SCF complex was modulated by CAND1, but Whether and how the CAND1 promotes HCC by regulating SCF complex and lipogenesis are unknown. Methods HCC samples were used to analyze the correlations between CAND1 expression and clinicopathological characteristics such as survival and prognosis. The in vitro functions of CAND1, FBXO11 and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) were measured by cell proliferation, colony formation and migration assays. The in vivo functions were tested in multiple mouse liver cancer models including patient‐derived xenograft (PDX), cell line‐derived xenograft and AKT/NRASV12‐induced primary liver cancer models. Injections of adeno‐associated virus targeting CAND1 (AAV‐shCAND1) were performed to evaluate the therapeutic efficacy of targeting CAND1. RNA‐Seq and lipidomic assays followed by serial biochemical experiments including mass spectrometry, immunoprecipitation and GST pull‐down were performed to dissect the underlying mechanisms. Results CAND1 promoted the expression of lipid synthesis genes by disrupting SCF complex assembly and lipid accumulation. Furthermore, we identified hnRNPA2B1 as a novel F‐box protein 11 (FBXO11)‐binding partner. FBXO11 directly bound to hnRNPA2B1 and promoted hnRNPA2B1 ubiquitination and subsequent degradation. Our evaluations of the therapeutic efficacy of AAV‐shCAND1 injections confirmed that targeting the CAND1‐SCFFBXO11‐hnRNPA2B1A signalling axis was therapeutically effective. CAND1 downregulation significantly reduced the tumour burden in a primary mouse liver cancer model and a PDX model. Conclusions Our results highlight that CAND1 is associated with poor prognosis in HCC and regulates lipid metabolic reprogramming by dissociating the SCF complex. Targeting the CAND1‐SCFFBXO11‐hnRNPA2B1 axis may be a novel strategy for HCC treatment.

Introduction: Childhood and adolescent overweight and obesity are global public health issues. Previous studies on exercise and overweight and obese children have produced inconsistent findings and lacked comparisons between different exercise modalities and intensities. Therefore, a network meta-analysis is necessary to provide evidence-based intervention programs. This study aims to identify the effects of different exercise modalities and intensities on changes in body composition in overweight and obese children and adolescents.Methods: A search for randomized controlled trials was conducted on Web of Science, PubMed, Scopus, and Embase involving exercise interventions aimed at improving body composition (body fat percentage, BMI, fat mass, fat-free mass, body weight) in overweight and obese children and adolescents. A random effects network meta-analysis was performed using STATA 14.0 software within a frequentist framework. The literature quality was assessed using the Cochrane Risk of Bias Tool 2.0.Results: Thirty-two papers involving 1,452 participants were included. There were six types of intervention involved in the study, including moderate intensity aerobic exercise, high-intensity aerobic exercise, moderate intensity resistance exercise, high-intensity resistance exercise, moderate intensity combined exercise, and high-intensity combined exercise. The network meta-analysis results revealed that high-intensity combined exercise was the best exercise mode for improving BMI [mean difference in kg/m2 = −1.65, 95% CI (−3.27, −0.02)] and reducing fat mass [mean difference in kg = −2.87, 95% CI (−4.84, −0.91)]. Moderate intensity combined exercise was the best mode for weight loss [mean difference in kg = −4.58, 95% CI (−5.94, −3.22)] and improvement in body fat percentage [mean difference in% = −2.52, 95% CI (−3.83, −1.20)]. High-intensity resistance exercise had the optimal effect in increasing fat-free mass [mean difference in kg = 1.10, 95% CI (0.22, 1.99)].Conclusion: In conclusion, the study found that combined exercise, whether moderate or high intensity, was more effective than any other exercise modality in improving body fat percentage and BMI, reducing fat mass and weight. Resistance exercise was the most effective in increasing fat-free mass.

Sustainable ammonia is one of the leading candidates in the search for alternative clean fuels for marine applications. This paper aims to build a simulation model of a six-cylinder, four-stroke diesel engine to investigate the effects of increasing the ammonia proportion in methanol–ammonia fuel blends on engine performance and emissions. In the present study, the conditions of different speeds and different proportions of ammonia in fuel blends are investigated. The results show that the average effective pressure, brake power, and brake torque increase by about 5% with an increased ammonia substitution ratio. In terms of economic performance, the changes under medium and low speed conditions are not obvious. However, the change in high speed conditions is significant. The brake specific fuel consumption (BSFC) is reduced by 6.6%, and the brake thermal efficiency (BTE) is increased by 4%. It is found that the performance of the engine is best at medium speed. The best performance is achieved with higher efficiency and lower emissions. The present results can provide guidance for the optimization of ammonia–methanol blends and their applications in engines.

In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.

Abstract Background Dysregulated osteoclast activity due to altered osteoclast differentiation causes multiple bone diseases. Osteoclasts are multinucleated giant cells derived from hematopoietic stem cells and play a major role in bone absorption. However, the mechanisms underlying the tight regulation of osteoclast differentiation in multiple pathophysiological status remain unknown. Results We showed that Bhlhe40 upregulation is tightly associated with osteoclast differentiation and osteoporosis. Functionally, Bhlhe40 promoted osteoclast differentiation in vitro, and Bhlhe40 deficiency led to increased bone mass and decreased osteoclast differentiation in vivo. Moreover, Bhlhe40 deficient mice resisted estrogen deficiency and aging-induced osteoporosis. Mechanism study showed that the increase in bone mass due to Bhlhe40 deficiency was a cell intrinsic defect in osteoclast differentiation in these mice. BHLHE40 upregulated the gene expression of Fos and Nfatc1 by directly binding to their promoter regions. Notably, inhibition of Fos/Nfatc1 abrogated the enhanced osteoclast differentiation induced by BHLHE40 overexpression. Conclusions Our research reveals a novel Bhlhe40/c-Fos/Nfatc1 axis involved in regulating osteoclastogenesis and shows that osteoporosis caused by estrogen deficiency and aging can be rescued by regulating Bhlhe40 in mice. This may help in the development of a new strategy for the treatment of osteoporosis.

To address the issue of current garbage cleanup vessels being limited to performing garbage cleaning operations in the ocean, without the capability of transferring the garbage from the ocean to the land, this paper presents a spiral-propulsion amphibious intelligent robot for land garbage cleaning and sea garbage cleaning. The design solution is as follows. A mechanical structure based on a spiral drum is proposed. The interior of the spiral drum is hollow, providing buoyancy, allowing the robot to travel both on marshy, tidal flats and on the water surface, in conjunction with underwater thrusters. Additionally, a mechanical-arm shovel is designed, which achieves two-degrees-of-freedom movement through a spiral spline guide and servo, facilitating garbage collection. Our experimental results demonstrated that the robot exhibits excellent maneuverability in marine environments and on beach, marsh, and tidal flat areas, and that it collects garbage effectively.

Due to the untouchability of online shopping environment, image and text description, as two main ways of product information display, are important indicators for consumers to evaluate products. However, few studies have discussed the synergistic effects of image and text information on consumers. In the present study, in conjunction with the left-right position effect, we examine the expectation that horizontal placement of visual stimuli in different directions has a strong influence on consumers’ product evaluation preferences. This implicit assumption is based on consumers’ unconscious psychological need for closure when processing information. The authors conducted three studies to investigate the relative effects of image information and text statements at different locations in online shopping pages on consumer product evaluations. The results show that: (1) when the evaluation object is a search product, compared with the display mode of left text-right image, the display mode of left image-right text plays a more significant role in consumer product evaluation. The results of experiential products were just the opposite. The way of presenting the text declaration on the left and image on the right has a stronger impact on consumers’ evaluation preference for experiential products (Study 1 and Study 3). (2) The difference in consumers’ evaluation mode of different presentation sequences based on product attributes is driven by their visual information processing fluency (Study 2). These preferences are robust, and it is worth noting that only the order of graphic presentation has no significant influence on consumer product evaluation preference.

BackgroundThe development of a new strategy to overcome chemoresistance to hepatocellular carcinoma (HCC) treatment is a long-standing issue. We have previously found that upregulated SETD3 levels are closely correlated with HCC. This study aims to explore the mechanism underlying how upregulation of SETD3 promotes liver carcinogenesis.MethodsRNA-Sequencing analysis was used to explore the correlation of SETD3 with regulatory targets. In vitro assays including cell proliferation and migration were performed to study the oncogenic roles of SETD3 and PLK1. Western blotting, immunohistochemical staining, and blood biochemical assays were performed to examine protein expression or pathological index in tumor tissues and mice liver tissues. Luciferase reporter system and chromatin immunoprecipitation assays were used to explore the mechanism.ResultsWe revealed that SETD3 regulates gene expression in subgroups, including cell division, cell proliferation, and cell cycle, in hepatocellular tumor cells. We found that SETD3 upregulation is associated with elevated PLK1 level in both hepatic tumor cells and clinical liver tissues. We further showed that overexpression of SETD3 promoted tumor cell proliferation and migration, whereas inhibition of PLK1 activity attenuated these phenotypes caused by SETD3. By taking advantage of the Sleep Beauty transposase system, we confirmed that upregulated mouse Setd3 promoted hepatic carcinogenesis in situ, but knockdown of mouse Plk1 mitigated Setd3-promoted tumorigenesis in mice. Mechanistically, we showed that SETD3 could be recruited to the promoter of PLK1 gene to facilitate PLK1 transcription.ConclusionsOur data demonstrate that elevated SETD3 may promote HCC by enhancing PLK1 expression, which suggests that SETD3 may act as a potential drug target combined with PLK1 inhibition to treat HCC.

Abstract Background Forced polyploidization is an effective strategy for acute megakaryoblastic leukemia (AMKL) therapy and factors controlling polyploidization are potential targets for drug development. Although bone morphology protein 2-inducible kinase (BMP2K) has been implied to be a potential target for fasudil, a potent polyploidy-inducing compound, the function of BMP2K in megakaryopoiesis and AMKL remains unknown. This study aimed to investigate the role of BMP2K as a novel regulator in megakaryocyte polyploidization and differentiation and its implication in AMKL therapy. Results BMP2K upregulation was observed in human megakaryopoiesis and leukemia cells whereas BMP2K was downregulated in AMKL cells forced to undergo terminal differentiation. Functionally, BMP2K suppressed MLN8237-induced megakaryocytic differentiation in AMKL cells and dampened megakaryocyte differentiation in primary mouse fetal liver cells. Furthermore, BMP2K overexpression conferred resistance to multiple chemotherapy compounds in AMKL cells. Mechanistically, cyclin-dependent kinase 2 (CDK2) interacted with BMP2K and partially mediated its function. In transient MLN8237 and nocodazole challenge cell model, BMP2K reduced cell percentage of G2/M phase but increased G1 phase, suggesting a role of BMP2K antagonizing polyploidization and promoting mitosis by regulating cell cycle in megakaryopoiesis. Conclusions BMP2K negatively regulates polyploidization and megakaryocyte differentiation by interacting CDK2 and promoting mitosis in megakaryopoiesis. BMP2K may serve as a potential target for improvement of AMKL therapy.

Clinic therapy of acute myeloid leukemia (AML) remains unsatisfactory that urges for development of novel strategies. Recent studies identified ANP32A as a novel biomarker of unfavorable outcome of leukemia, which promoted leukemogenesis by increasing H3 acetylation and the expression of lipid metabolism genes. It is of great significance to investigate whether targeting ANP32A is a novel strategy for leukemia therapy. To target ANP32A, we identified a peptide that competed with ANP32A to bind to histone 3 (termed as H3-binding peptide, H3BP). Disrupting ANP32A and H3 interaction by the overexpression of H3BP-GFP fusion protein mimicked the effect of ANP32A knockdown, impaired H3 acetylation on multiple locus of target genes, reduced proliferation, and caused apoptosis in leukemia cells. Furthermore, a synthesized membrane-penetrating peptide TAT-H3BP effectively entered into leukemia cells and phenocopied such effect. In vivo, TAT-H3BP showed potent efficacy against leukemia: Intra-tumor injection of TAT-H3BP significantly reduced the volume of subcutaneous tumors in nude mice and recipient mice engrafted with TAT-H3BP-pretreated 6133/MPL W515L cells exhibited ameliorated leukemia burden and prolonged survival. Noticeably, TAT-H3BP efficiently suppressed proliferation and colony-forming unit of human primary AML cells without affecting normal cord blood cells. Our findings demonstrate that intervening the physical interaction of ANP32A with H3 impairs the oncogenicity of ANP32A and may be a promising therapeutic strategy against AML.

Consumers often feel embarrassed when buying products like condoms, hemorrhoid cream, and beriberi cream in crowded pharmacies. There is an interesting phenomenon in life: Some beriberi creams use the images of a “real foot”, while others use the images of a “cartoon foot.” Imagine if a young woman needed to go to a retail store for beriberi cream that would embarrass her, she would choose a “real foot image” or a “cartoon foot image” beriberi cream? It has been shown that the embarrassment of these products has a strong negative impact on consumer buying behavior. Previous researches have explored how changing packaging elements of embarrassing products (e.g., color/design/image placement) can effectively reduce consumer embarrassment. However, few have examined the impact of different image types of embarrassing product packaging (artificial vs. natural) with embarrassment. Therefore, this research explores the effect of image types (artificial vs. natural) on consumers’ willingness to purchase embarrassing products and reveals the mechanisms of the underlying effects. The results show that natural images can lead to lower purchase intention of embarrassing products when the advertisement uses first-person pronouns due to the mediating role played by negative body imagery. However, there is no significant difference in purchase intention between different image types in the third-person pronouns. Finally, this paper discusses its contributions and limitations.

Abstract Background Cell therapy remains the most promising approach against ischemic heart injury. However, poor survival of engrafted cells in ischemic sites diminishes its therapeutic efficacy. Follistatin-like 1 (Fstl1) is documented as a novel pro-survival cardiokine for cardiomyocytes, and it is protective during ischemic heart injury. In the present study, we characterize the potential of Fstl1 as an effective strategy to enhance hypoxia resistance of donor cells and optimize stem cell-based therapy. Methods Murine bone marrow-derived mesenchymal stem cells (MSCs) were expanded in monolayer culture and characterized by flow cytometry. MSCs were subjected to hypoxia to mimic cardiac ischemic environment. Expression of Fstl1 was monitored 0, 24, and 48 h following hypoxia. Constitutive expression of Fstl1 in MSCs was achieved by lentivirus-mediated Fstl1 overexpression. Genetically modified MSCs were further collected for cell death and proliferation assay following 48 h of hypoxic treatment. Acute myocardial infarction (MI) model was created by ligating the left anterior descending coronary artery, while control MSCs (MSCs-mCherry) or Fstl1-overexpressing MSCs (MSCs-Fstl1) were injected into the peri-infarct zone simultaneously. Subsequently, retention of the donor cells was evaluated on post-therapy 1, 3, & 7 days. Finally, myocardial function, infarct size, inflammation, and neovascularization of the infarcted hearts were calculated thereafter. Results Expression of Fstl1 in hypoxic MSCs declines dramatically in a time-dependent manner. In vitro study further demonstrated that Fstl1 promotes survival and proliferation of hypoxic MSCs. Moreover, Fstl1 significantly prolongs MSC survival/retention after implantation. Finally, transplantation with Fstl1-overexpressing MSCs significantly improves post-MI cardiac function by limiting scar formation, reducing inflammatory response, and enhancing neovascularization. Conclusions Our results suggest Fstl1 is an intrinsic cardiokine promoting survival and proliferation of MSCs, thereby optimizing their engraftment and therapeutic efficacy during cell therapy.

Objective: This study aimed to review and provide an informative synthesis of the findings from longitudinal studies that describe the relationship between sedentary behavior and various health outcomes among young adults. Methods: A literature search was conducted in Web of Science, PubMed, APA PsycInfo, MEDLINE, Embase, and the Cochrane Library for articles that examined the association between sedentary behavior and health outcomes among young adults aged 18–34 years. Two reviewers independently examined the articles and performed data extraction and quality assessment. The level of evidence was determined using the best-evidence synthesis. Results: A total of 34 studies were included in the analysis, 18 of which were high-quality studies. On the basis of inconsistency in the findings among studies, insufficient evidence was concluded for sedentary behavior and adiposity indicators, physical fitness, metabolic syndrome/cardiovascular disease risk factors, cognitive function, and mood disorders. Based on one high-quality study, moderate evidence for a negative relationship between sedentary behavior and physical fitness was observed. Conclusions: Given the trend toward increased time in sedentary behaviors and the inconsistent current findings, additional longitudinal studies of high methodologic quality are recommended to clarify the relationships between sedentary behavior and health outcomes among young adults.

In this paper, by using the critical point theory, some new results of the existence of at least two nontrivial periodic solutions with prescribed minimal period to a class of 2nth-order nonlinear discrete system are obtained. The main approach used in our paper is variational technique and the linking theorem. The problem is to solve the existence of periodic solutions with prescribed minimal period of 2nth-order discrete systems.

As the only renewable organic carbon source, abundant biomass has long been established and developed to mass-produce functionalized carbon materials. Herein, an extremely facile and green strategy was executed for the first time to in situ construct K-Fe3C@C nanohybrids directly by one-pot carbonizing the pomelo peel impregnated with Fe(NO3)3 solutions. The pyrolytically self-assembled nanohybrids were successfully applied in Fischer–Tropsch synthesis (FTS) and demonstrated high catalytic performance. Accordingly, the optimized K-Fe3C@C catalysts revealed excellent FTS activity (92.6% CO conversion) with highlighted C5+ hydrocarbon selectivity of 61.3% and light olefin (C2-4=) selectivity of 26.0% (olefin/paraffin (O/P) ratio of 6.2). Characterization results further manifest that the high performance was correlated with the in situ formation of the core-shell nanostructure consisting of Fe3C nanoparticles enwrapped by graphitized carbon shells and the intrinsic potassium promoter originated in pomelo peel during high-temperature carbonization. This work provided a facile approach for the low-cost mass-fabrication of high-performance FTS catalysts directly utilizing waste biomass without any chemical pre-treatment or purification.

Summary: Intestinal L cells regulate a wide range of metabolic processes, and L-cell dysfunction has been implicated in the pathogenesis of obesity and diabetes. However, it is incompletely understood how luminal signals are integrated to control the development of L cells. Here we show that food availability and gut microbiota-produced short-chain fatty acids control the posttranslational modification on intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) in intestinal epithelial cells. Via FOXO1 O-GlcNAcylation, O-GlcNAc transferase (OGT) suppresses expression of the lineage-specifying transcription factor Neurogenin 3 and, thus, L cell differentiation from enteroendocrine progenitors. Intestinal epithelial ablation of OGT in mice not only causes L cell hyperplasia and increased secretion of glucagon-like peptide 1 (GLP-1) but also disrupts gut microbial compositions, which notably contributes to decreased weight gain and improved glycemic control. Our results identify intestinal epithelial O-GlcNAc signaling as a brake on L cell development and function in response to nutritional and microbial cues.

Abstract Post‐translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O‐GlcNAcylation and the expression of O‐GlcNAc transferase (OGT), the enzyme adding the O‐GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical‐induced colitis. Paneth cell‐specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical‐induced colitis. On the other hand, the augmentation of O‐GlcNAc signaling by inhibiting O‐GlcNAcase, the enzyme removing O‐GlcNAcylation, alleviated chemical‐induced colitis. Our data reveal that protein O‐GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.

Abstract Background Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in fatty acid oxidation, was significantly upregulated in the early stage of the reprogramming process. Methods Mouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various fatty acid oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty acid oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation. Results We found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated fatty acid oxidation, also promoted reprogramming. In the early reprogramming process, fatty acid oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming. Conclusion We demonstrated that fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that fatty acid oxidation is crucial for the reprogramming efficiency.

Abstract Background Accumulating evidence demonstrates that the KRAB-ZNFs involve in various biological processes. As a typical member of KRAB-ZNFs, dysregulation of ZNF300 contributes to multiple pathologies such as leukemia and cancer. However, mechanisms underlying ZNF300 tight regulation and its pathophysiological function remain largely unknown. Methods The effect of ZNF300ZFR on gene transcriptional activity was measured by Dual luciferase reporter system. ChIP-PCR assay were performed to detect the enrichment of ZNF300 protein and H3K9Ac in the ZNF300 gene. Co-immunoprecipitation assays followed by western blot were performed to detect the interaction between ZNF300 and KAP1. The DNA methylation in the ZNF300 gene promoter was analyzed by BSP. ZNF300 function on K562 cell differentiation was analyzed by flow cytometry. Results In this study, we found that the zinc finger domain-encoding region (ZFR) of ZNF300 functioned as a repressor possibly by mediating DNA methylation and ZNF300 bound to its ZNF300ZFR, suggesting a potential auto-inhibition mechanism. To support this, DNA methylation inhibition upregulated ZNF300 expression and ZNF300 overexpression inhibited endogenous ZNF300 expression. More importantly, DNA methylation inhibition restored megakaryocyte differentiation in K562 cells suppressed by ZNF300 downregulation, suggesting an important role of DNA methylation in ZNF300 function. Interestingly, ZNF300 knockdown restored global H3K9Ac that was reduced in K562 cells undergoing megakaryocyte differentiation. Conclusions Our study revealed novel features of ZNF300 that possibly mediate its regulation and function by modulating epigenetic modifications.

Oncostatin M (OSM) is a secreted cytokine mainly involved in chronic inflammatory and cardiovascular diseases through binding to OSM receptor β (OSMR-β). Recent studies demonstrated that the presence of OSM contributed to the destabilization of atherosclerotic plaque. To investigate whether OSMR-β deficiency affects atherosclerosis, male OSMR-β−/−ApoE−/− mice were generated and utilized. Here we observed that OSMR-β expression was remarkably upregulated in both human and mouse atherosclerotic lesions, which were mainly located in macrophages. We found that OSMR-β deficiency significantly ameliorated atherosclerotic burden in aorta and aortic root relative to ApoE-deficient littermates and enhanced the stability of atherosclerotic plaques by increasing collagen and smooth muscle cell content, while decreasing macrophage infiltration and lipid accumulation. Moreover, bone marrow transplantation of OSMR-β−/− hematopoietic cells to atherosclerosis-prone mice displayed a consistent phenotype. Additionally, we observed a relatively reduced level of JAK2 and signal transducer and activator of transcription (STAT)3 in vivo and under Ox-LDL stimulation in vitro. Our findings suggest that OSMR-β deficiency in macrophages improved high-fat diet-induced atherogenesis and plaque vulnerability. Mech­anistically, the protective effect of OSMR-β deficiency on atherosclerosis may be partially attributed to the inhibition of the JAK2/STAT3 activation in macrophages, whereas OSM stimulation can activate the signaling pathway.

Hematopoiesis is dynamically regulated by metabolic cues in homeostatic and stressed conditions; however, the cellular and molecular mechanisms mediating the metabolic sensing and regulation remain largely obscure. Bone marrow adipose tissue remodels in various metabolic conditions and has been recently proposed as a niche for hematopoietic stem cells after irradiation. Here, we investigated the role of marrow adipose tissue-derived hematopoietic cytokine stem cell factor in unperturbed hematopoiesis by selectively ablating the Kitl gene from adipocytes and bone marrow stroma cells using Adipoq-Cre and Osx1-Cre, respectively. We found that both Adipoq-Kitl knockout (KO) and Osx1-Kitl KO mice diminished hematopoietic stem and progenitor cells and myeloid progenitors in the bone marrow and developed macrocytic anemia at the steady-state. The composition and differentiation of hematopoietic progenitor cells in the bone marrow dynamically responded to metabolic challenges including high fat diet, β3-adrenergic activation, thermoneutrality, and aging. However, such responses, particularly within the myeloid compartment, were largely impaired in Adipoq-Kitl KO mice. Our data demonstrate that marrow adipose tissue provides stem cell factor essentially for hematopoiesis both at the steady state and upon metabolic stresses.

TRAF6 is a ubiquitin E3 ligase regulating a number of biological processes. Here the authors show that ROS, generated during pathological cardiac stress, induces TRAF6 auto-ubiquitination and activation, promoting its interaction with and ubiquitination of TAK1 that contributes to development of cardiac hypertrophy.

BackgroundDickkopf‐3 (DKK3) is a negative regulator of the Wnt/β‐catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis. The aim of the present study was to define the role of DKK3 and its potential mechanism in the development of atherosclerosis. Methods and ResultsImmunofluorescence analysis showed that DKK3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice. The expression level was significantly increased in atherogenesis. DKK3−/−ApoE−/− mice exhibited a significant decrease in atherosclerotic lesions in the entire aorta, aortic sinus, and brachiocephalic arteries. Transplantation of bone marrow from DKK3−/−ApoE−/− mice into lethally irradiated ApoE−/− recipients resulted in a reduction of atherosclerotic lesions, compared with the lesions in recipients transplanted with ApoE−/− donor cells, suggesting that the effect of DKK3 deficiency was largely mediated by bone marrow–derived cells. A reduction in the necrotic core size, accompanied by increased collagen content and smooth muscle cells and decreased accumulation of macrophages and lipids, contributed to the stability of plaques in DKK3−/−ApoE−/− mice. Furthermore, multiple proinflammatory cytokines exhibited marked decreases in DKK3−/−ApoE−/− mice. Finally, we observed that DKK3 ablation increased β‐catenin expression in the nuclei of macrophages both in vivo and in vitro. ConclusionsDKK3 expression in macrophages is involved in the pathogenesis of atherosclerosis through modulation of inflammation and inactivation of the Wnt/β‐catenin pathway.

BackgroundVinexin β is a novel adaptor protein that regulates cellular adhesion, cytoskeletal reorganization, signal transduction, and transcription; however, the exact role that vinexin β plays in atherosclerosis remains unknown. Methods and ResultsImmunoblot analysis showed that vinexin β expression is upregulated in the atherosclerotic lesions of both patients with coronary heart disease and hyperlipemic apolipoprotein E–deficient mice and is primarily localized in macrophages indicated by immunofluorescence staining. The high‐fat diet–induced double‐knockout mice exhibited lower aortic plaque burdens than apolipoprotein E−/− littermates and decreased macrophage content. Vinexin β deficiency improved plaque stability by attenuating lipid accumulation and increasing smooth muscle cell content and collagen. Moreover, the bone marrow transplant experiment demonstrated that vinexin β deficiency exerts atheroprotective effects in hematopoietic cells. Consistent with these changes, the mRNA expression of proinflammatory cytokines were downregulated in vinexin β−/− apolipoprotein E−/− mice, whereas the anti‐inflammatory M2 macrophage markers were upregulated. The immunohistochemical staining and in vitro experiments showed that deficiency of vinexin β inhibited the accumulation of monocytes and the migration of macrophages induced by tumor necrosis factor α–stimulated human umbilical vein endothelial cells as well as macrophage proliferation. Finally, the inhibitory effects exerted by vinexin β deficiency on foam cell formation, nuclear factor κB activation, and inflammatory cytokine expression were largely reversed by constitutive Akt activation, whereas the increased expression of the nuclear factor κB subset promoted by adenoviral vinexin β was dramatically suppressed by inhibition of AKT. ConclusionsVinexin β deficiency attenuates atherogenesis primarily by suppressing vascular inflammation and inactivating Akt–nuclear factor κB signaling. Our data suggest that vinexin β could be a therapeutic target for the treatment of atherosclerosis.

BackgroundAtherosclerosis is a chronic disease that is closely related to inflammation and macrophage apoptosis, which leads to secondary necrosis and proinflammatory responses in advanced lesions. Caspase‐activated DNase (CAD) is a double‐strand specific endonuclease that leads to the subsequent degradation of chromosome DNA during apoptosis. However, whether CAD is involved in the progression of atherosclerosis remains elusive. Methods and ResultsCAD−/−ApoE−/− and ApoE−/− littermates were fed a high‐fat diet for 28 weeks to develop atherosclerosis. Human specimens were collected from coronary heart disease (CHD) patients who were not suitable for transplantation. CAD expression was increased in the atheromatous lesions of CHD patients and high‐fat diet‐treated ApoE‐deficient mice. Further investigation demonstrated that CAD deficiency inhibited high‐fat diet‐induced atherosclerosis, as evidenced by decreased atherosclerotic plaques, inhibited inflammatory response, and macrophage apoptosis, as well as enhanced stability of plaques in CAD−/−ApoE−/− mice compared to the ApoE−/− controls. Bone marrow transplantation verified the effect of CAD on atherosclerosis from macrophages. Mechanically, the decrease in the phosphorylated levels of mitogen‐activated protein kinase (MAPK) kinase/extracellular signal‐regulated kinase 1 and 2 (MEK‐ERK1/2) that resulted from CAD knockout and the activation of nuclear factor kappa B signaling mediated by CAD stimulation that was suppressed by inhibiting ERK1/2 phosphorylation revealed the potential association between the role of CAD in atherosclerosis and the MAPK signaling pathway. ConclusionsIn conclusion, CAD deficiency protects against atherosclerosis through inhibiting inflammation and macrophage apoptosis, which is partially through inactivation of the MEK‐ERK1/2 signaling pathway. This finding provides a promising therapeutic target for treating atherosclerosis.

The original article [1] mistakenly omitted a source of funding, and the authors would like to rectify this by acknowledging the additional support of the Natural Science Foundation in Jiangsu Province (BK20150687).

This study investigates dynamics of the melt conveying process in a novel extruder in which a polymer experiences a primarily elongational deformation field. The working principle of the novel extruder is completely different from that of conventional screw extruders. At the last stage of polymer processing in the proposed novel extruder, melt is conveyed through feeding and discharging processes. Here we present a mathematical model to analyze dynamics in the melt conveying process. Melt extrusion is primarily influenced by the position of vane chamber and the structural parameters of the novel extruder such as eccentricity.

Previously, we reported that ZNF300 might play a role in leukemogenesis. In this study, we further investigated the function of ZNF300 in K562 cells undergoing differentiation. We found that ZNF300 upregulation in K562 cells coincided with megakaryocytic differentiation induced by phorbol-12-myristate-13-acetate (PMA) or erythrocytic differentiation induced by cytosine arabinoside (Ara-C), respectively. To further test whether ZNF300 upregulation promoted differentiation, we knocked down ZNF300 and found that ZNF300 knockdown effectively abolished PMA-induced megakaryocytic differentiation, evidenced by decreased CD61 expression. Furthermore, Ara-C-induced erythrocytic differentiation was also suppressed in ZNF300 knockdown cells with decreased γ-globin expression and CD235a expression. These observations suggest that ZNF300 may be a critical factor controlling distinct aspects of K562 cells. Indeed, ZNF300 knockdown led to increased cell proliferation. Consistently, ZNF300 knockdown cells exhibited an increased percentage of cells at S phase accompanied by decreased percentage of cells at G0/G1 and G2/M phase. Increased cell proliferation was further supported by the increased expression of cell proliferation marker PCNA and the decreased expression of cell cycle regulator p15 and p27. In addition, MAPK/ERK signaling was significantly suppressed by ZNF300 knockdown. These findings suggest a potential mechanism by which ZNF300 knockdown may impair megakaryocytic and erythrocytic differentiation.

Multiple nuclear localization domains have been identified in nuclear proteins, and they finely control nuclear import and functions of those proteins. ZNF268 is a typical KRAB-containing zinc finger protein (KRAB-ZFP), and previous studies have shown that the KRAB domain reinforces nuclear localization of KRAB-ZFPs by interacting with KAP1. In this study, we find that some of 24 zinc fingers of ZNF268 also possess nuclear localization activity. Results of mutagenesis studies suggest that KRAB and zinc fingers are both necessary, and they function both independently and cooperatively for the nuclear localization of ZNF268. However, the subnuclear targeting activities of KRAB and zinc fingers are different. KRAB targets proteins in nucleoplasm, but not in the nucleolus, which is mediated by interaction with KAP1, while zinc fingers target proteins in the whole nucleus uniformly. The cooperative activities of KAP1-KRAB-zinc fingers result in the precise nucleoplasmic, but not nucleolar localization of KRAB-ZFPs. Our studies reveal a novel mechanism for the subcellular localization of KRAB-ZFPs and may help us to further explore their biological functions.

The hERG potassium channel can modulate the proliferation of the chronic myelogenous leukemic K562 cells, and its role in the erythroid differentiation of K562 cells still remains unclear.The hERG potassium channel blockage by a new 36-residue scorpion toxin BmKKx2, a potent hERG channel blocker with IC50 of 6.7 ± 1.7 nM, enhanced the erythroid differentiation of K562 cells. The mean values of GPA (CD235a) fluorescence intensity in the group of K562 cells pretreated by the toxin for 24 h and followed by cytosine arabinoside (Ara-C) treatment for 72 h were about 2-fold stronger than those of K562 cells induced by Ara-C alone. Such unique role of hERG potassium channel was also supported by the evidence that the effect of the toxin BmKKx2 on cell differentiation was nullified in hERG-deficient cell lines. During the K562 cell differentiation, BmKKx2 could also suppress the expression of hERG channels at both mRNA and protein levels. Besides the function of differentiation enhancement, BmKKx2 was also found to promote the differentiation-dependent apoptosis during the differentiation process of K562 cells. In addition, the blockage of hERG potassium channel by toxin BmKKx2 was able to decrease the intracellular Ca(2+) concentration during the K562 cell differentiation, providing an insight into the mechanism of hERG potassium channel regulating this cellular process.Our results revealed scorpion toxin BmKKx2 could enhance the erythroid differentiation of leukemic K562 cells via inhibiting hERG potassium channel currents. These findings would not only accelerate the functional research of hERG channel in different leukemic cells, but also present the prospects of natural scorpion toxins as anti-leukemic drugs.

MicroRNAs (miRNAs), approximately 22-nucleotide non-coding RNA molecules, regulate a variety of pivotal physiological or pathological processes, including embryonic development and tumorigenesis. To obtain comprehensive expression profiles of miRNAs in human embryos, we characterized miRNA expression in weeks 4-6 of human embryonic development using miRNA microarrays and identified 50 human-embryo-specific miRNAs (HES-miRNAs). Furthermore, we selected three non-conserved or primate-specific miRNAs, hsa-miR-638, -720, and -1280, and examined their expression levels in various normal and tumor tissues. The results show that expression of most miRNAs is extremely low during early human embryonic development. In addition, the expression of some non-conserved or primate-specific miRNAs is significantly different between tumor and the corresponding normal tissue samples, suggesting that the miRNAs are closely related to the pathological processes of various tumors. This study presents the first comprehensive overview of miRNA expression during human embryonic development and offers immediate evidence of the relationship between human early embryonic development and tumorigenesis.