Land-use change interacts with island biogeography to alter bird community assembly.

Anthropogenic activities have reshaped biodiversity on islands worldwide. However, it remains unclear how island attributes and land-use change interactively shape multiple facets of island biodiversity through community assembly processes. To answer this, we conducted bird surveys in various land-use types (mainly forest and farmland) using transects on 34 oceanic land-bridge islands in the largest archipelago of China. We found that bird species richness increased with island area and decreased with isolation, regardless of the intensity of land-use change. However, forest-dominated habitats exhibited lower richness than farmland-dominated habitats. Island bird assemblages generally comprised species that share more similar traits or evolutionary histories (i.e. functional and/or phylogenetic clustering) than expected if assemblages were randomly assembled. Contrary to our expectations, we observed that bird assemblages in forest-dominated habitats were more clustered on large and close islands, whereas assemblages in farmland-dominated habitats were more clustered on small islands. These contrasting results indicate that land-use change interacts with island biogeography to alter the community assembly of birds on inhabited islands. Our findings emphasize the importance of incorporating human-modified habitats when examining the community assembly of island biota, and further suggest that agricultural landscapes on large islands may play essential roles in protecting countryside island biodiversity.

Identifying patterns of multidimensional self-compassion in Chinese young adults: implications for longitudinal mental health outcomes during the pandemic.

BACKGROUND: Self-compassion (SC), reflecting self-attitude and self-connectedness, has proven to be a modifiable factor in promoting mental health outcomes. Increasingly, SC is recognized as a multidimensional construct consisting of six dimensions, rather than a single dimension. OBJECTIVES: First, this study adopted a person-centered approach to explore profiles of SC dimensions in Chinese young adults. Second, the study examined the predictive effects of SC profiles on mental health outcomes. METHODS: In February 2020, young adults (N = 1164) were invited to complete the 26-item Neff's Self-Compassion Scale online. Three months later, the same subjects (N = 1099) reported their levels of depressive symptoms, posttraumatic stress disorder (PTSD) symptoms, and posttraumatic growth (PTG). RESULTS: After controlling for retrospective ACEs, four classes best characterized the profiles: self-compassionate (26.7%, N = 294), self-uncompassionate (12.3%, N = 135), average (55.9%, N = 614), and detached groups (5.1%, N = 56). Young adults in the self-compassionate group adjusted the best (with the highest level of PTG and the lowest levels of depressive and PTSD symptoms). Adults in the self-uncompassionate group demonstrated the poorest mental health outcomes (with the lowest level of PTG and the highest levels of depressive and PTSD symptoms). Young adults in the average group obtained more PTG than adults in the detached group (p < .01), but did not differ significantly in depressive and PTSD symptoms (p > .05). CONCLUSION: The compassionate profile is the most adaptable for young adults among all groups. This study highlights the limitations of representing the relative balance of SC with a composite score.

CO2 -Mediated Photocatalytic Chlorine Production Over Bismuth Oxychloride in Chloride Solution.

As one of the most commonly bulky chemicals, chlorine is conventionally manufactured by electrolysis of NaCl solution in the chlor-alkali process, which requires a huge supply of electrical energy. The photocatalytic route to produce chlorine by using solar energy and NaCl solution offers a promising strategy to reduce energy consumption and bring economic benefits. Herein, it was found that the introduction of CO2 would enhance the productivity of Cl2 from 8.24 µmol⋅h-1 to 39.6 µmol⋅h-1 in NaCl solution over BiOCl. Experimental studies reveal that the CO2 species (CO3 2- ) entered into the crystal texture of BiOCl and the interlayer space between [Bi2 O2 ]2+ slabs were increased and distorted, accelerating the cycle of Cl species. Besides, the cycle of carbonate species also existed and accelerated the reaction efficiency of Cl- oxidation to Cl2 . This work provides a new feasible method of using abundant CO2 resources to accelerate the process of chlorine production via photocatalysis.

Nearby large islands diminish biodiversity of the focal island by a negative target effect.

The Equilibrium Theory of Island Biogeography postulates that larger and closer islands support higher biodiversity through the dynamic balance of colonization and extinction processes. The negative diversity-isolation (i.e. the distance to the mainland) relationship is derived based on the assumption that the mainland is the only source pool for island biotas. However, nearby islands could also act as species sources for focal islands via a source effect. In this study, we move a further step and hypothesize that nearby islands may reduce bird colonizers of the focal island and diminish its biodiversity, resulting in a negative target effect. To test our hypothesis, we assessed the effects of island area and isolation (metrics considering both the mainland and nearby islands) on taxonomic (i.e. species richness), functional and phylogenetic diversity of terrestrial breeding birds on 42 islands in the largest archipelago of China, the Zhoushan Archipelago. Furthermore, we compared the predictive power of the distance to the large island under a set of relative area thresholds and the relative area of nearby islands on species richness under a set of distance thresholds to explore the role of nearby islands as a source and/or target island. We found that island area had a positive effect on species richness, phylogenetic diversity and functional diversity, while the distance to the mainland had a negative effect only on species richness. Species richness on the focal island increased with increasing distance to the nearest larger island, indicating the negative target effect. Furthermore, the negative target effect depended on the area of nearby islands relative to the area of the focal island. Our finding of the negative target effect suggests islands located between the mainland and the focal island can be not only sources or stepping stones, but also colonization targets. This result demonstrates the importance of considering multiple geographical attributes of islands in island biogeographic studies, especially the characteristics related to source and/or target effects.

Age and spatial distribution of the world's oldest trees.

Extremely old trees have important roles in providing insights about historical climatic events and supporting cultural values. Yet there has been limited work on the global distribution and conservation of these trees. We extracted information on 197,855 tree cores at 4,854 sites, and combined it with other tree age data from a further 156 sites, to determine the age of the world's oldest trees and quantify the factors influencing their global distribution. We found that extremely old trees >1,000 years are rare. Among 30 individual trees that exceeded 2,000 years old, 27 occurred in high mountains. Our model suggests that many of the existing oldest trees occur in high-elevation, cold and arid mountains with limited human disturbance. This pattern is markedly different from that of the tallest trees, which are more likely to occur in more mesic and productive locations. Global warming and expansion of human activities may induce rapid population declines of extremely old trees. New strategies, including targeted establishment of conservation reserves in remote regions, especially those in western Table 1 parts of China and USA, are required to protect these trees. This article is protected by copyright. All rights reserved.

Septin 9 methylation analysis of lymph node micrometastases for predicting relapse of colorectal cancer.

BACKGROUND: Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC. METHODS: We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR). RESULTS: Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001). CONCLUSION: Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.

Emulsifying and whipping properties of mixing polysaccharide dispersions: effect of ratio between insoluble soybean fiber and hydroxypropyl methylcellulose.

BACKGROUND: The interactions between various food colloids in different systems (e.g., dispersions, emulsions, creams) have a bearing on the processing and characteristics of food systems. Hydrophilic polysaccharides have been proven to have the potential to fabricate the above systems. In the present work, hydroxypropyl methylcellulose (HPMC) was partially replaced by the insoluble soybean fiber (ISF) extracted from defatted okara to prepare mixing dispersions, oil-in-water emulsions and whipped creams. RESULTS: The presented work showed that as the proportion of ISF increased, the foaming properties of ISF/HPMC dispersions were enhanced, the absolute value of the ζ-potential and the particle size of the emulsions increased, while the heat stability and centrifugal stability first increased and then decreased. Upon whipping, the loss angle (tan δ) decreased first and then increased, while the overrun, foam stability and cream stability, as well as the elastic modulus (G'), presented the opposite trend. CONCLUSION: These results indicated that an appropriate amount (40-60%) of ISF in the ISF/HPMC systems enhanced the foaming and emulsifying capacities of mixtures and the stability of the resultant emulsion; subsequently, the whipping performance and whipped cream network structure were strengthened, suggesting that ISF has great potential for application in whipped cream as a 'green' and safe food ingredient. © 2022 Society of Chemical Industry.

Evodiamine inhibits vasculogenic mimicry in HCT116 cells by suppressing hypoxia-inducible factor 1-alpha-mediated angiogenesis.

Evodiamine (Evo), a quinazoline alkaloid and one of the most typical polycyclic heterocycles, is mainly isolated from Evodia rugulosa. Vasculogenic mimicry (VM) is a newly identified way of angiogenesis during tumor neovascularization, which is prevalent in a variety of highly invasive tumors. The purpose of this study was to investigate the effect and mechanism of Evo on VM in human colorectal cancer (CRC) cells. The number of VM structures was calculated by the three-dimensional culture of human CRC cells. Wound-healing was used to detect the migration of HCT116 cells. Gene expression was detected by reverse transcription-quantitative PCR assay. CD31/PAS staining was used to identify VM. Western blotting and immunofluorescence were used to detect protein levels. The results showed that Evo inhibited the migration of HCT116 cells, as well as the formation of VM. Furthermore, Evo reduced the expression of hypoxia-inducible factor 1-alpha (HIF-1α), VE-cadherin, VEGF, MMP2, and MMP9. In a model of subcutaneous xenotransplantation, Evo also inhibited tumor growth and VM formation. Our study demonstrates that Evo could inhibit VM in CRC cells HCT116 and reduce the expression of HIF-1α, VE-cadherin, VEGF, MMP2, and MMP9.

Decomposing peer effects in pro-environmental behaviour: Evidence from a Chinese nationwide survey.

We explore potential peer effects in pro-environmental behaviour using Chinese General Social Survey 2013, where individual participations in ten pro-environmental activities are recorded. Instrumental variable regressions suggest that individual pro-environmental behaviour is positively and significantly affected by that of neighbourhood peers. Such effects are robust against alternative estimation procedures and falsification tests. Results further show that, while identified peer effects do function through social networks, such mediation explains only a small portion of the peer effects, which may largely occur among strangers living in the neighbourhood through observation and mimicry. These findings imply that peer effects should be seriously considered in neighbourhood-level interventions to stimulate pro-environmental behaviour more cost-effectively.

Understanding food westernisation and other contemporary drivers of adult, adolescent and child nutrition quality in urban Vietnam.

OBJECTIVE: To examine the association between consumption of western foods purchased and consumed away from home and measures of nutrition quality: average daily caloric intake and macronutrient (carbohydrates, fat and protein) shares, for urban consumers in Vietnam, a country undergoing economic transition. DESIGN: Cross-sectional observational data were collected using household surveys and 24-h food diaries. Outcome variables were individual average daily caloric intake and shares of calories from macronutrients: carbohydrates, fat and protein. The key explanatory variable was individual daily share of calories from western food purchased and consumed away from home. Ordinary least squares and multivariate regression analyses were used to examine the association between the outcome variables: caloric intake and macronutrient shares and the share of calories from western food consumed away from home. SETTING: Hanoi and Ho Chi Minh City in Vietnam. PARTICIPANTS: In total, 1685 households and 4997 individuals, including adults (aged $$ \ge $$ 18 years), adolescents (aged 10-17 years) and children (aged 0-9 years). RESULTS: The share of calories from western food away from home was significantly associated with higher caloric intake among male and female adults (P < 0·01), adolescents (P < 0·01) and male children (P < 0·10) and was associated with higher shares of fat for male and female adults (P < 0·01), adolescents (P < 0·01) and male children (P < 0·01). CONCLUSIONS: Policymakers must be conscious of the numerous factors associated with poor nutrition quality, especially in younger Vietnamese individuals. Relevant interventions targeting at risk groups are required if nutrition improvement is a long-term goal.

Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1.

Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5'monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2.

The removal of Rhodamine B by H2O2 or ClO2 combined with hydrodynamic cavitation.

Rhodamine B (RhB), widely used as an industrial dye, is a toxic organic that is hazardous to human health and can cause water pollution. In this study, the removal rate of RhB was investigated by the following methods: hydrodynamic cavitation (HC) operated individually, and HC combined with oxidants H2O2 or ClO2. The effect of different operating parameters including pressure (2-6 bar) and initial pH (2-8) on the extent of degradation was investigated using an orifice plate as the cavitation device to achieve maximum removal of RhB. Under the parameters of HC, the effect of different loadings was investigated: H2O2 (n(RhB):n(H2O2) was varied from 1:17.60 to 1:211.28) and ClO2 (n(RhB):n(ClO2) was varied from 1:8.87 to 1:177.53). A combination of cavitation and H2O2 or ClO2 resulted in degradations of 80.6% and 95.3%. The results indicated that the combination of HC and oxidants was better than the individual HC process for the degradation of RhB. When combining HC with H2O2 or ClO2, the synergistic coefficients of 62.54 and 74.79 were obtained. The combination of HC and ClO2 was proven to be more effective for the removal of RhB compared to HC alone and the hybrid process of HC and H2O2.

Reverse Reconstruction and Bioprinting of Bacterial Cellulose-Based Functional Total Intervertebral Disc for Therapeutic Implantation.

The degradation of intervertebral discs (IVD), a typical hierarchical structured tissue, causes serious neck and back pain. The current methods cannot fully reconstitute the unique structure and function of native IVD. In this study, by reverse reconstruction of the structure of native IVD and bioprinting bacterial cellulose (BC) nanofibers with a high-throughput optimized micropattern screening microchip, a total IVD is created that contained type II collagen-based nucleus pulposus (NP) and hierarchically organized and micropatterned BC-based annulus fibrosus (AF), mimicking native IVD tissue. The artificial NP contains rat NP cells, whereas the AF contains concentrically arranged BC layers with aligned micropatterns and attached AF cells in +/-30° alternate directions between adjacent layers. Long-term (3 months) implantation experiments on rats demonstrate the excellent structural (shape maintenance, hydration, tissue integration) and functional (mechanical support and flexibility) performance of the artificial IVD. This study provides a novel strategy for creating highly sophisticated artificial tissues.

The importance of accounting for imperfect detection when estimating functional and phylogenetic community structure.

Incorporating imperfect detection when estimating species richness has become commonplace in the past decade. However, the question of how imperfect detection of species affects estimates of functional and phylogenetic community structure remains untested. We used long-term counts of breeding bird species that were detected at least once on islands in a land-bridge island system, and employed multi-species occupancy models to assess the effects of imperfect detection of species on estimates of bird diversity and community structure by incorporating species traits and phylogenies. Our results showed that taxonomic, functional, and phylogenetic diversity were all underestimated significantly as a result of species' imperfect detection, with taxonomic diversity showing the greatest bias. The functional and phylogenetic structure calculated from observed communities were both more clustered than those from the detection-corrected communities due to missed distinct species. The discrepancy between observed and estimated diversity differed according to the measure of biodiversity employed. Our study demonstrates the importance of accounting for species' imperfect detection in biodiversity studies, especially for functional and phylogenetic community ecology, and when attempting to infer community assembly processes. With datasets that allow for detection-corrected community structure, we can better estimate diversity and infer the underlying mechanisms that structure community assembly, and thus make reliable management decisions for the conservation of biodiversity.

Land ownership and technology adoption revisited: Improved maize varieties in Ethiopia.

The lack of land ownership can discourage agricultural technology adoption, yet there is scarce evidence of the impact of land rental contracts on the adoption of improved crop varieties in developing countries. The current study investigates such impact using a nationally representative survey of Ethiopian maize farmers. In contrast to many previous studies, we show in a simple model that cash-renters are as likely to adopt improved maize varieties as owner-operators, while sharecroppers are more likely to adopt given that such varieties are profitable. Empirical analysis reveals a significant impact of sharecropping on improved maize variety adoption, and no significant impact from cash-rental, lending support to the above hypotheses. These results imply that improvements in land rental markets can potentially enhance household welfare through crop variety adoption in agrarian economies where land sales markets are incomplete or missing.

Functional and phylogenetic structure of island bird communities.

Biodiversity change in anthropogenically transformed habitats is often nonrandom, yet the nature and importance of the different mechanisms shaping community structure are unclear. Here, we extend the classic Theory of Island Biogeography (TIB) to account for nonrandom processes by incorporating species traits and phylogenetic relationships into a study of faunal relaxation following habitat loss and fragmentation. Two possible mechanisms can create nonrandom community patterns on fragment islands. First, small and isolated islands might consist of similar or closely related species because they are environmentally homogeneous or select for certain shared traits, such as dispersal ability. Alternatively, communities on small islands might contain more dissimilar or distantly related species than on large islands because limited space and resource availability result in greater competitive exclusion among species with high niche overlap. Breeding birds were surveyed on 36 islands and two mainland sites annually from 2010 to 2014 in the Thousand Island Lake region, China. We assessed community structure of breeding birds on these subtropical land-bridge islands by integrating species' trait and evolutionary distances. We additionally analysed habitat heterogeneity and variance in size ratios to distinguish biotic and abiotic processes of community assembly. Results showed that functional-phylogenetic diversity increased with island area, and decreased with isolation. Bird communities on the mainland were more diverse and generally less clustered than island bird communities and not different than randomly assembled communities. Bird communities on islands tend to be functionally similar and phylogenetically clustered, especially on small and isolated islands. The nonrandom decline in species diversity and change in bird community structure with island area and isolation, along with the relatively homogeneous habitats on small islands, support the environmental filtering hypothesis. Our study demonstrates the importance of integrating multiple forms of diversity for understanding the effects of habitat loss and fragmentation, and further reveals that TIB could be extended to community measures by moving beyond assumptions of species equivalency in colonisation rates and extinction susceptibilities.

ZLN005 protects cardiomyocytes against high glucose-induced cytotoxicity by promoting SIRT1 expression and autophagy.

Diabetic cardiomyopathy increases the risk for the development of heart failure independent of coronary artery disease and hypertension. Either type 1 or type 2 diabetes is often accompanied by varying degrees of hyperglycemia, which has been proven to induce myocardial apoptosis in animal models. Recently, a novel small molecule, ZLN005, has been reported to show antidiabetic efficacy in a mouse model, possibly by induction of PGC-1α expression. In this study, we investigated whether ZLN005 protects cardiomyocytes against high glucose-induced cytotoxicity and the mechanisms involved. Neonatal mouse cardiomyocytes were incubated with media containing 5.5 or 33mM glucose for 24h in the presence or absence of ZLN005. ZLN005 treatment led to ameliorated cardiomyocyte oxidative injury, enhanced cell viability, and reduced apoptosis in the high glucose environment. Western blot analysis revealed that high glucose suppressed cardiomyocyte autophagy, whereas ZLN005 increased the expression of autophagy marker proteins ATG5, beclin1, and LC3 II/LC3 I; this increase was accompanied by increased expression of SIRT1. Furthermore, EX527, a SIRT1-specific inhibitor, weakened the protective effects of ZLN005 on cardiomyocytes subjected to high glucose. Taken together, these results suggest that ZLN005 suppresses high glucose-induced cardiomyocyte injury by promoting SIRT1 expression and autophagy.

Co-culture with neonatal cardiomyocytes enhances the proliferation of iPSC-derived cardiomyocytes via FAK/JNK signaling.

BACKGROUND: We previously reported that the pluripotent stem cells can differentiate into cardiomyocytes (CMs) by co-culture with neonatal CMs (NCMs) in vitro. However, the involving mechanism is not clear. METHODS: Mouse induced pluripotent stem cells (iPSCs) were cultured in hanging drops to form embryoid bodies (EBs) and to induce myocardial differentiation. Co-culture of EBs and NCMs was established in a transwell insert system, while EBs grown alone in the wells were used as controls. RESULTS: Co-culture with NCMs markedly increased the generation of functional CMs from iPSCs. The focal adhesion kinase (FAK) phosphorylation, and c-Jun N-terminal kinase (JNK) phosphorylation in co-culture were higher than that in EBs grown alone. Treating FAK small interfering RNA (FAK siRNA) or specific inhibitor for JNK (SP600125) to iPSCs significantly reduced the phosphorylation of JNK and the expressions of Mef2c and Bcl-2. The expressions of cTnT and MLC-2V were also decreased. Our results revealed that co-culture with NCMs significantly enhance the differentiation ability of iPSCs by increasing Mef2c and Bcl-2 expressions concomitantly with a marked augment on cell proliferation through JNK signaling pathways. CONCLUSIONS: These findings indicated that co-culture of EBs with NCMs induces genes expressed in a mature pattern and stimulates the proliferation of iPSC-derived CMs (iPS-CMs) by activating FAK/JNK signaling.

Three-dimensional poly-(ε-caprolactone) nanofibrous scaffolds directly promote the cardiomyocyte differentiation of murine-induced pluripotent stem cells through Wnt/ß-catenin signaling.

BACKGROUND: Environmental factors are important for stem cell lineage specification, and increasing evidence indicates that the nanoscale geometry/topography of the extracellular matrix (ECM) directs stem cell fate. Recently, many three-dimensional (3D) biomimetic nanofibrous scaffolds resembling many characteristics of the native ECM have been used in stem cell-based myocardial tissue engineering. However, the biophysical role and underlying mechanism of 3D nanofibrous scaffolds in cardiomyocyte differentiation of induced pluripotent stem cells (iPSCs) remain unclear. RESULTS: Here, we fabricated a 3D poly-(ε-caprolactone) (PCL) nanofibrous scaffold using the electrospinning method and verified its nanotopography and porous structure by scanning electron microscopy. We seeded murine iPSCs (miPSCs) directly on the 3D PCL nanofibrous scaffold and initiated non-directed, spontaneous differentiation using the monolayer method. After the 3D PCL nanofibrous scaffold was gelatin coated, it was suitable for monolayer miPSC cultivation and cardiomyocyte differentiation. At day 15 of differentiation, miPSCs differentiated into functional cardiomyocytes on the 3D PCL nanofibrous scaffold as evidenced by positive immunostaining of cardiac-specific proteins including cardiac troponin T (cTnT) and myosin light chain 2a (MLC2a). In addition, flow cytometric analysis of cTnT-positive cells and cardiac-specific gene and protein expression of cTnT and sarcomeric alpha actinin (α-actinin) demonstrated that the cardiomyocyte differentiation of miPSCs was more efficient on the 3D PCL nanofibrous scaffold than on normal tissue culture plates (TCPs). Furthermore, early inhibition of Wnt/ß-catenin signaling by the selective antagonist Dickkopf-1 significantly reduced the activity of Wnt/ß-catenin signaling and decreased the cardiomyocyte differentiation of miPSCs cultured on the 3D PCL nanofibrous scaffold, while the early activation of Wnt/ß-catenin signaling by CHIR99021 further increased the cardiomyocyte differentiation of miPSCs. CONCLUSION: These results indicated that the electrospun 3D PCL nanofibrous scaffolds directly promoted the cardiomyocyte differentiation of miPSCs, which was mediated by the activation of the Wnt/ß-catenin signaling during the early period of differentiation. These findings highlighted the biophysical role of 3D nanofibrous scaffolds during the cardiomyocyte differentiation of miPSCs and revealed its underlying mechanism involving Wnt/ß-catenin signaling, which will be helpful in guiding future stem cell- and scaffold-based myocardium bioengineering.

Mutation in the first Ig-like domain of Kit leads to JAK2 activation and myeloproliferation in mice.

Myeloproliferative neoplasms constitute a group of hematopoietic neoplasms at the myeloid stem cell level. Although mutations in the receptor tyrosine kinase KIT have been identified in patients with myeloproliferative neoplasm, the functional causality is unknown because of a lack of animal models. Here, we describe a mouse strain harboring a point mutation in the first Ig-like domain of Kit. Intriguingly, the mutant mice develop a myeloproliferative disorder with typical loss-of-function phenotypes in other tissues. The mutant Kit is incompletely N-glycosylated, shows compromised receptor dimerization, and down-regulates Akt and extracellular signal-regulating kinase 1/2 signaling. However, the mutation increases the association of Kit to Janus kinase (JAK)2 and hence the activation of JAK2. The ß common receptor of the gp140 family interacts and synergizes with Kit to promote JAK2 phosphorylation, which is further enhanced by the Kit mutation. Inhibition of JAK2 suppresses the proliferation of hematopoietic progenitors in vitro and partially rescues myeloproliferation in mice. Our data suggest that overactivation of JAK2 leads to myeloproliferation in Kit mutant mice and provide mechanistic insights for the diagnosis and treatment of myeloproliferative neoplasms in humans.