Search

Abstract Little is known about the prognostic value of left atrial strain by four-dimensional speckle-tracking echocardiography in end-stage renal disease patients with preserved left ventricular ejection fraction. This prospective study collected clinical and echocardiographic data from 80 stable dialysis patients (mean age 57 ± 10 years; 62.5% men). All patients underwent the dedicated four-dimensional speckle-tracking echocardiography to measure LASr (peak longitudinal strain of reservoir function), LAScd (peak longitudinal strain of conduit function), LASct (peak longitudinal strain of contractile function), LASr_c (peak circumferential strain of reservoir function), LAScd_c (peak circumferential strain of conduit function) and LASct_c (peak circumferential strain of contractile function). These patients were enrolled from August 2021 to August 2023 and followed-up for 19 months (interquartile-range 15 to 20 months). The primary outcome was a composite of all-cause mortality or major adverse cardiovascular events (MACEs). The study patients were classified into event (developed mortality or MACEs) and event-free group according to the primary outcome. Multivariate Cox regression analysis was used to investigate risk factors for all-cause mortality or MACEs. The event group had lower LASr (16.4% vs. 21.2%, P = 0.0003), LASct (8.2% vs. 11.2%, P = 0.01), LASr_c (25.2% vs. 35.0%, P = 0.0004) and LASct_c (14.9% vs. 20.9%, P = 0.001) than the event-free group. Using optimal cut-off value determined by ROC curve, the less LASr (LASr

Abstract Background Organic phosphorus insecticides (OPPs) are a class of environmental pollutants widely used worldwide with potential human health risks. We aimed to assess the association between exposure to OPPs and osteoarthritis (OA) particularly in participants with atherosclerotic cardiovascular disease (ASCVD). Methods Participants’ information was obtained from data in the National Health and Nutrition Examination (NHANES). Weighted logistic regression models were utilized to detect associations between OPPs metabolites and OA. Restricted cubic spline plots (RCS) were drawn to visualize the dose-response relationship between each metabolite and OA prevalence. Weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR), were applied to investigate the joint effect of mixtures of OPPs on OA. Results A total of 6871 samples were included in our study, no significant associations between OPPs exposure and OA incidence were found in whole population. However, in a subset of 475 individuals with ASCVD, significant associations between DMP (odds ratio [OR] as a continuous variable = 1.22, 95% confidence interval [CI]: 1.07,1.28), DEP ((odds ratio [OR] of the highest tertile compared to the lowest = 2.43, 95% confidence interval [CI]: 1.21,4.86), and OA were observed. DMP and DEP showed an increasing dose-response relationship to the prevalence of OA, while DMTP, DETP, DMDTP and DEDTP showed a nonlinear relationship. Multi-contamination modeling revealed a 1.34-fold (95% confidence intervals:0.80, 2.26) higher prevalence of OA in participants with high co-exposure to OPPs compared to those with low co-exposure, with a preponderant weighting (0.87) for the dimethyl dialkyl phosphate metabolites (DMAPs). The BKMR also showed that co-exposure of mixed OPPs was associated with an increased prevalence of OA, with DMP showing a significant dose-response relationship. Conclusion High levels of urine dialkyl phosphate metabolites (DAP) of multiple OPPs are associated with an increased prevalence of OA in patients with ASCVD, suggesting the need to prevent exposure to OPPs in ASCVD patients to avoid triggering OA and further avoid the occurrence of cardiovascular events caused by OA.

Phase transition generates rapid changes of transport parameters and poor mechanical property, and thus restricts the application of thermoelectric materials. AgBiSe2 exhibits cubic phase at above 580 K with high-symmetry structure and low lattice thermal conductivity, indicating the potentiality of high thermoelectric performances. In this work, the cubic structure of AgBiSe2 was achieved at ambient conditions by alloying with PbS, enhancing the configurational entropy at both cationic and anionic sites. The cubic structure was rather stable after several measurement cycles. Nb substitution at cationic sites effectively reduced band gap, and increased both carrier concentration and effective mass. All samples exhibited relatively low lattice thermal conductivity (0.68–0.34 W/(m·K)) in the temperature range of 300–773 K, due to the nanoscale inhomogeneity and the random distribution of multiple species at some atomic sites. A maximum zT of 0.65 at 773 K was obtained for (Ag0.99Nb0.01BiSe2)0.8(PbS)0.2 sample. The entropy-driven structural stabilization is a promising strategy to achieve stable structure for practical thermoelectric applications.

Osteoporosis is a common chronic metabolic bone disorder. Recently, increasing numbers of studies have demonstrated that Toll-like receptor 4 (TLR4, a receptor located on the surface of osteoclasts and osteoblasts) plays a pivotal role in the development of osteoporosis. Herein, we performed a comprehensive review to summarize the findings from the relevant studies within this topic. Clinical data showed that TLR4 polymorphisms and aberrant TLR4 expression have been associated with the clinical significance of osteoporosis. Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying the pathological processes of osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. In vivo and in vitro studies demonstrate that many promising substances or agents (i.e., methionine, dioscin, miR-1906 mimic, artesunate, AEG-1 deletion, patchouli alcohol, and Bacteroides vulgatus) have been able to improve bone metabolism (i.e., inhibits bone resorption and promotes bone formation), which may partially attribute to the inhibition of TLR4 expression. The present review highlights the important role of TLR4 in the clinical significance and the pathogenesis of osteoporosis from the aspects of inflammation and immunity. Future therapeutic strategies targeting TLR4 may provide a new insight for osteoporosis treatment.

In this paper, we first use an L2−discrepancy bound to give the expected uniform integration approximation for functions in the Sobolev space H1(K) equipped with a reproducing kernel. The concept of stratified sampling under general equal measure partition is introduced into the research. For different sampling modes, we obtain a better convergence order O(N−1−1d) for the stratified sampling set than for the Monte Carlo sampling method and the Latin hypercube sampling method. Second, we give several expected uniform integration approximation bounds for functions equipped with boundary conditions in the general Sobolev space Fd,q∗, where 1p+1q=1. Probabilistic Lp−discrepancy bound under general equal measure partition, including the case of Hilbert space-filling curve-based sampling are employed. All of these give better general results than simple random sampling, and in particular, Hilbert space-filling curve-based sampling gives better results than simple random sampling for the appropriate sample size.

AbstractObjectives Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model.Methods Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET).Results Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET).Conclusion Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Objective: In order to reuse the Areca catechu by-product—A. catechu pedicle, and improve the quality of mycelium of edible fungi, the effect of the pedicle aqueous extract on the liquid fermentation of edible fungi was investigated. Methods: Pleurotus ostreatus, Pleurotus citrinopileatus Singer, and Flammulina velutiper were selected as the test strains, and the effects of the addition of A. catechu pedicle aqueous extract on the quality of mycelium and the activity of enzymes related to the growth and metabolism of the three strains were investigated, by using mycelial growth rate, biomass, mycelial active ingredients and antioxidant activity as indicators. Results: The best growth effect was observed on the P. ostreatus, P. citrinopileatus and F. velutiper when 6.4, 4.8 and 4.8 mg/mL A. catechu pedicle aqueous extract was added, respectively. Compared with the control group, when adding 4.8～6.4 mg/mL A. catechu pedicle aqueous extract, the mycelium active ingredient content was significantly increased, and the mycelium triterpene content of P. ostreatus, P. citrinopileatus, and F. velutiper were increased by 95.24%, 70.91% and 75.00%, respectively. Moreover, A. catechu pedicle aqueous extract increased the antioxidant activity of mycelium, and the antioxidant capacity of mycelium was in the following order: P. citrinopileatus＞F. velutiper＞P. ostreatus; A. catechu pedicle aqueous extract increased the activities of amylase, cellulase, xylanase and laccase of the three strains to some extent, but the effect on the trend of enzyme activity was not significant. Conclusion: Adding the proper amount of aqueous extract of A. catechu pedicle can effectively improve the mycelial quality and the antioxidant activity of the three strains.

Abstract Background Dynesys stabilization (DS) is utilized to preserve mobility at the instrumental segments and prevent adjacent segment pathology in clinical practice. However, the advantages of DS method in medium and long-term follow-up remain controversial. Objective To compare the radiographic and clinical outcomes between DS and instrumented fusion in the treatment of degenerative lumbar spine disease with or without grade I spondylolisthesis with a minimum follow-up period of 2 years. Methods We conducted a comprehensive search of PubMed, EMBASE, Cochrane, and Web of Science databases, Chinese National Knowledge Databases, and Wanfang Database for potentially eligible articles. Clinical outcomes were assessed in terms of VAS and ODI scores, screw loosening and breakage, and surgical revision. Radiographic outcomes were assessed in terms of postoperative range of movement (ROM) and disc heigh. Moreover, adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) were evaluated. Results Seventeen studies with 1296 patients were included in the meta-analysis. The DS group was associated with significantly lower postoperative VAS scores for low-back and leg pain, and lower rate of surgical revision than the fusion group. Moreover, the Dynesys group showed significantly less ASDeg than the fusion group but showed no significant advantage over the fusion group in terms of preventing ASDis. Additionally, the ROM at the stabilized segments of the fusion group decreased significantly and that at the adjacent segments increased significantly compared with those of the DS group. Conclusion DS showed comparable clinical outcomes and provided benefits in preserving the motion at the stabilized segments, thus limiting the hypermobility at the adjacent segments and preventing ASDeg compared with the fusion method in degenerative disease with or without grade I spondylolisthesis.

Keloids, a pathological scar that is induced by the consequence of aberrant wound healing, is still a major global health concern for its unsatisfactory treatment outcomes. HIF-1α, a main regulator of hypoxia, mainly acts through some proteins or signaling pathways and plays important roles in a variety of biological processes. Accumulating evidence has shown that HIF-1α played a crucial role in the process of keloid formation. In this review, we attempted to summarize the current knowledge on the association between HIF-1α expression and the development and progression of keloids. Through a comprehensive analysis, the molecular mechanisms underlying HIF-1α in keloids were shown to be correlated to the proliferation of fibroblasts, angiogenesis, and collagen deposits. The affected proteins and the signaling pathways were multiple. For instance, HIF-1α was reported to promote keloids formation by enhancing angiogenesis, fibroblast proliferation, and collagen deposition through the activation of periostin PI3K/Akt, TGF‐β/Smad and TLR4/MyD88/NF-κB pathway. However, the specific effects of HIF-1α on keloids keloid illnesses in clinical practice is are entirely unclear, and further studies in clinical trials are still warranted. Therefore, an in-depth understanding of the biological mechanisms of HIF-1α in keloid formation is significant to develop promising therapeutic targets for the treatment of keloids in clinical practice.

Abstract Objective To determine the rates and risk factors of pedicle screw placement accuracy and the proximal facet joint violation (FJV) using TINAVI robot-assisted technique. Methods Patients with thoracolumbar fractures or degenerative diseases were retrospectively recruited from June 2018 and June 2020. The pedicle penetration and proximal FJV were compared in different instrumental levels to identify the safe and risk segments during insertion. Moreover, the factors were also assessed using univariate and multivariate analyses. Results A total of 72 patients with 332 pedicle screws were included in the current study. The optimal and clinically acceptable screw positions were 85.8% and 93.4%. Of the 332 screws concerning the intra-pedicular accuracy, 285 screws (85.8%) were evaluated as Grade A according to the Gertzbein and Robbins scale, with the remaining 25 (7.6%), 10 (3.0%), 6 (1.8%), and 6 screws (1.8%) as Grades B, C, D, and E. Moreover, in terms of the proximal FJV, 255 screws (76.8%) screws were assessed as Grade 0 according to the Babu scale, with the remaining 34 (10.3%), 22 (6.6%), and 21 screws (6.3%) as Grades 1, 2, and 3. Furthermore, the univariate analysis showed significantly higher rate of penetration for patients with age

N6-methyladenosine (m6A), as the most abundant modification of mammalian messenger RNAs, is essential for tissue development and pathogenesis. However, the biological significance of m6A methylation in cardiac differentiation and development remains largely unknown. Here, we identify that the downregulation of m6A demethylase ALKBH5 is responsible for the increase of m6A methylation and cardiomyocyte fate determination of human embryonic stem cells (hESCs) from mesoderm cells (MESs). In contrast, ALKBH5 overexpression remarkably blocks cardiomyocyte differentiation of hESCs. Mechanistically, KDM5B and RBBP5, the components of H3K4 modifying enzyme complexes, are identified as downstream targets for ALKBH5 in cardiac-committed hESCs. Loss of function of ALKBH5 alters the expression of KDM5B and RBBP5 through impairing stability of their mRNAs, which in turn promotes the transcription of GATA4 by enhancing histone H3 Lys4 trimethylation (H3K4me3) at the promoter region of GATA4. Taken together, we reveal a previously unidentified role of m6A demethylase ALKBH5 in determining cardiac lineage commitment of hESCs.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has extremely high morbidity and mortality. Although many existing studies have focused on the identification of biomarkers, little information has been uncovered regarding the PBMC RNA profile of HCC. We attempted to create a profile throughout using expression of peripheral blood mononuclear cell (PBMC) RNA using RNA-seq technology and compared the transcriptome between HCC patients and healthy controls. Seventeen patients and 17 matched healthy controls were included in this study, and PBMC RNA was sequenced from all samples. Sequencing data were analyzed using bioinformatics tools, and quantitative reverse transcription PCR (qRT-PCR) was used for selected validation of DEGs. A total of 1,578 dysregulated genes were found in the PBMC samples, including 1,334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies revealed that HCC is closely linked to differentially expressed genes (DEGs) implicated in the immune response. Expression of 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) was confirmed by qRT-PCR, and higher sensitivity and specificity were obtained by ROC analysis of the 6 genes. CALM1 was found to gradually decrease as tumors enlarged. Nearly the opposite expression modes were obtained when compared to tumor sequencing data. Immune cell populations exhibited significant differences between HCC and controls. These findings suggest a potential biomarker for the diagnosis of HCC. This study provides new perspectives for liver cancer development and possible future successful clinical diagnosis.

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate peroxisome proliferator-activated receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD+/SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been suggested to possess the capacity to differentiate into different cell lineages. Maintaining a balanced stem cell differentiation program is crucial to the bone microenvironment and bone development. MicroRNAs (miRNAs) have played a critical role in regulating the differentiation of BMSCs into particular lineage. However, the role of miR-149-3p in the adipogenic and osteogenic differentiation of BMSCs has not been extensively discovered. In this study, we aimed to detect the expression levels of miR-149-3p during the differentiation of BMSCs and investigate whether miR-149-3p participated in the lineage choice of BMSCs or not. Compared with mimic-negative control (NC), miR-149-3p mimic decreased the adipogenic differentiation potential of BMSCs and increased the osteogenic differentiation potential. Further analysis revealed that overexpression of miR-149-3p repressed the expression of fat mass and obesity-associated (FTO) gene through binding to the 3ʹ UTR of the FTO mRNA. Also, the role of miR-149-3p mimic in inhibiting adipogenic lineage differentiation and potentiating osteogenic lineage differentiation was mainly through targeting FTO, which also played an important role in regulating body weight and fat mass. In addition, BMSCs treated with miR-149-3p anti-miRNA oligonucleotide (AMO) exhibited higher potential to differentiate into adipocytes and lower tendency to differentiate into osteoblasts compared with BMSCs transfected with NC. In summary, our results detected the effects of miR-149-3p in cell fate specification of BMSCs and revealed that miR-149-3p inhibited the adipogenic differentiation of BMSCs via a miR-149-3p/FTO regulatory axis. This study provided cellular and molecular insights into the observation that miR-149-3p was a prospective candidate gene for BMSC-based bone tissue engineering in treating osteoporosis. Keywords: miRNA, osteoporosis, osteogenesis, adipogenesis, BMSC, differentiation, FTO

Abstract Large variations in crown shape are observed across the globe, from plants with wide and deep crowns to those with leaves clustered at the top. While there have been advances in the large‐scale monitoring of forests, little is known about factors driving variations in crown shape with environmental conditions. Previous theoretical research suggests a gradient in crown shape with latitude, due to the effects of sun angle. Yet, it remains unclear whether such changes are also predicted under competition. Using a size‐structured forest‐growth model that incorporates self‐shading from plants and competitive shading from their neighbors, we investigate how changes in site productivity and sun angle shape crown evolution. We consider evolution in two traits describing the top‐heaviness and width‐to‐height ratio of crowns, shaped by trade‐offs reflecting the costs and benefits of alternative architectures. In top‐heavy trees, most of the leaves are at the top half of the trunk. We show that, contrary to common belief, the angle of sun beams per se has only a weak influence on crown shapes, except at low site productivity. By contrast, reduced site productivity has a strong effect, with trees growing in less productive sites keeping their leaves closer to the ground. The crown width‐to‐height ratio is generally higher at a lower site productivity, but this trait is not strongly influenced by any environmental factor. This theoretical analysis brings into question established beliefs about the effects of latitude on crown shapes. By introducing geometry‐related growth constraints caused by shading from both the surrounding forest and the tree on itself, and costs for constructing and maintaining a three‐dimensional crown, our analysis suggests crown shapes may vary with latitude, mostly via effects on overall site productivity, and less because of the angle of the sun.

Background/Aims: Melatonin possesses many biological activities such as antioxidant and anti-aging. Cardiac progenitor cells (CPCs) have emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the low survival of transplanted CPCs in infarcted myocardium limits the successful use in treating MI. In the present study, we aimed to investigate if melatonin protects against oxidative stress-induced CPCs damage and enhances its therapeutic efficacy for MI. Methods: TUNEL assay and EdU assay were used to detect the effects of melatonin and miR-98 on H2O2-induced apoptosis and proliferation. MI model was used to evaluate the potential cardioprotective effects of melatonin and miR-98. Results: Melatonin attenuated H2O2-induced the proliferation reduction and apoptosis of c-kit+ CPCs in vitro, and CPCs which pretreated with melatonin significantly improved the functions of post-infarct hearts compared with CPCs alone in vivo. Melatonin was capable to inhibit the increase of miR-98 level by H2O2 in CPCs. The proliferation reduction and apoptosis of CPCs induced by H2O2 was aggravated by miR-98. In vivo, transplantation of CPCs with miR-98 silencing caused the more significant improvement of cardiac functions in MI than CPCs. MiR-98 targets at the signal transducer and activator of the transcription 3 (STAT3), and thus aggravated H2O2-induced the reduction of Bcl-2 protein. Conclusions: Pre-treatment with melatonin protects c-kit+ CPCs against oxidative stress-induced damage via downregulation of miR-98 and thereby increasing STAT3, representing a potentially new strategy to improve CPC-based therapy for MI.

Therapeutic efficiency of cardiac progenitor cells (CPCs) transplantation is limited by its low survival and retention in infarcted myocardium. Autophagy plays a critical role in regulating cell death and apoptosis, but the role of microRNAs (miRNAs) in oxidative stress-induced autophagy of CPCs remains unclear. This study aimed to explore if miRNAs mediate autophagy of c-kit+ CPCs. We found that the silencing of miR-143 promoted the autophagy of c-kit+ CPCs in response to H2O2, and the protective effect of miR-143 inhibitor was abrogated by autophagy inhibitor 3-methyladenine (3-MA). Furthermore, autophagy-related gene 7 (Atg7) was identified as the target gene of miR-143 by dual luciferase reporter assays. In vivo, after transfection with miR-143 inhibitor, c-kit+ CPCs from green fluorescent protein transgenic mice were more observed in infarcted mouse hearts. Moreover, transplantation of c-kit+ CPCs with miR-143 inhibitor improved cardiac function after myocardial infarction. Take together, our study demonstrated that miR-143 mediates oxidative stress-induced autophagy to enhance the survival of c-kit+ CPCs by targeting Atg7, which will provide a complementary approach for improving CPC-based heart repair. Keywords: Autophagy, Atg7, Cardiac progenitor cells, MicroRNAs, MI

Abstract In this paper, we consider a free boundary problem describing the invasion of a generalist predator into a prey population. We analytically derive the conditions guaranteeing the existence and uniqueness of the classical solution by means of the Schauder fixed point theorem, and further study the long-time behaviours of these two species. Finally, we numerically investigate the dynamical behaviour during the early invasion stage. Numerical results show that generalist predators are more likely to succeed in alien invasion by reducing the threshold size of the spatial domain of initial invasion, below which invasion fails.

Background/Aims: Blue light emitting diodes (LEDs) have been proven to affect the growth of several types of cells. The effects of blue LEDs have not been tested on bone marrow-derived mesenchymal stem cells (BMSCs), which are important for cell-based therapy in various medical fields. Therefore, the aim of this study was to determine the effects of blue LED on the proliferation, apoptosis and osteogenic differentiation of BMSCs. Methods: BMSCs were irradiated with a blue LED light at 470 nm for 1 min, 5 min, 10 min, 30 min and 60 min or not irradiated. Cell proliferation was measured by performing cell counting and EdU staining assays. Cell apoptosis was detected by TUNEL staining. Osteogenic differentiation was evaluated by ALP and ARS staining. DCFH-DA staining and γ-H2A.X immunostaining were used to measure intracellular levels of ROS production and DNA damage. Results: Both cell counting and EdU staining assays showed that cell proliferation of BMSCs was significantly reduced upon blue LED irradiation. Furthermore, treatment of BMSCs with LED irradiation was followed by a remarkable increase in apoptosis, indicating that blue LED light induced toxic effects on BMSCs. Likewise, BMSC osteogenic differentiation was inhibited after exposure to blue LED irradiation. Further, blue LED irradiation was followed by the accumulation of ROS production and DNA damage. Conclusions: Taken together, our study demonstrated that blue LED light inhibited cell proliferation, inhibited osteogenic differentiation, and induced apoptosis in BMSCs, which are associated with increased ROS production and DNA damage. These findings may provide important insights for the application of LEDs in future BMSC-based therapies.

Background/Aims: It is well documented that myocardial hypertrophy is associated with low ambient temperature. Atorvastatin (Atv) has been shown to protect against atherosclerosis, cardiac fibrosis, ischemia/reperfusion injury, etc. In this study, we aim to determine whether atorvastatin is effective in the treatment of myocardial hypertrophy induced by cold exposure and to shed light on underlying mechanism. Methods: The mice aged 4-week were randomized to Control (Ctl) group (raised at room temperature), Cold group (raised at 3-5ºC) and Atv treatment group (raised at 3-5ºC followed by 10mg/kg/day Atv infusion). Echocardiography (ECG), HE, TUNEL and Masson’s trichrome staining, and Transmission electronic microscopy were performed to analyze cardiac function, myocardial hypertrophy, cardiac fibrosis, apoptosis and cardiomyocyte ultrastructure, respectively. Western blot was carried out to determine the involvement of MAPK and apoptosis pathways. Results: Exposure of mice to low temperature induced myocardial hypertrophic growth characterized by the elevation of heart/body weight index and heart weight /tibia length index, compared with control mice. Atv treatment attenuated cardiac hypertrophy induced by cold exposure; Atv also attenuated the increase of cross-sectional area of cardiomyocytes and cardiac collagen content fraction in mice exposed to cold. ECG showed that the decline of cardiac functions including the elevated left ventricular systolic/diastolic internal dimension (LVIDs/d) and fractional shortening (FS) in mice with cold exposure was also inhibited by Atv treatment. Transmission electronic microscopy uncovered that Atv attenuated mitochondrial injury induced by cold exposure in mice. In addition, systolic blood pressure was gradually increased in mice exposed to cold temperature, and Atv treatment significantly inhibited the elevation of blood pressure in cold-treated mice. Mechanistically, mitogen-activated protein kinase (MAPK) signal was not altered in mice exposed to cold, and Atv did not affect MAPK signal in cold-treated mice. But Atv mitigated the reduction of Bcl-2/Bax level in heart of cold-treated mice. Conclusion: Atv attenuated myocardial hypertrophy induced by cold exposure through inhibiting the downregulation of Bcl-2 in heart. It may provide a novel strategy for low temperature-induced myocardial hypertrophy treatment.

Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS) is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Methods: BMSCs were exposed to ferric ammonium citrate (FAC) with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, β-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS) level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. Results: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 μg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. Conclusion: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.

The stem cell-based therapy has emerged as the promising therapeutic strategies for cardiovascular diseases (CVDs). Recently, increasing evidence suggest stem cell-derived active exosomes are important communicators among cells in the heart via delivering specific substances to the adjacent/distant target cells. These exosomes and their contents such as certain proteins, miRNAs and lncRNAs exhibit huge beneficial effects on preventing heart damage and promoting cardiac repair. More importantly, stem cell-derived exosomes are more effective and safer than stem cell transplantation. Therefore, administration of stem cell-derived exosomes will expectantly be an alternative stem cell-based therapy for the treatment of CVDs. Furthermore, modification of stem cell-derived exosomes or artificial synthesis of exosomes will be the new therapeutic tools for CVDs in the future. In addition, stem cell-derived exosomes also have been implicated in the diagnosis and prognosis of CVDs. In this review, we summarize the current advances of stem cell-derived exosome-based treatment and prognosis for CVDs, including their potential benefits, underlying mechanisms and limitations, which will provide novel insights of exosomes as a new tool in clinical therapeutic translation in the future.

The problem of water shortage needs to be solved urgently. The membrane-embedded microchannel structure based on the ion concentration polarization (ICP) desalination effect is a potential portable desalination device with low energy consumption and high efficiency. The electroosmotic flow in the microchannel of the cation exchange membrane and the desalination effect of the system are numerically analyzed. The results show that when the horizontal electric field intensity is 2 kV/m and the transmembrane voltage is 400 mV, the desalting efficiency reaches 97.3%. When the electric field strength increases to 20 kV/m, the desalination efficiency is reduced by 2%. In terms of fluid motion, under the action of the transmembrane voltage, two reverse eddy currents are formed on the surface of the membrane due to the opposite electric field and pressure difference on both sides of the membrane, forming a pumping effect. The electromotive force in the channel exhibits significant pressure-flow characteristics with a slip boundary at a speed approximately six times that of a non-membrane microchannel.