Bioactive glass 1393 promotes angiogenesis and accelerates wound healing through ROS/P53/MMP9 signaling pathway.

Compared to bioactive glass 45S5, bioactive glass 1393 has shown greater potential in activating tissue cells and promoting angiogenesis for bone repair. Nevertheless, the effect of bioactive glass 1393 in the context of wound healing remains extensively unexplored, and its mechanism in wound healing remains unclear. Considering that angiogenesis is a critical stage in wound healing, we hypothesize that bioactive glass 1393 may facilitate wound healing through the stimulation of angiogenesis. To validate this hypothesis and further explore the mechanisms underlying its pro-angiogenic effects, we investigated the impact of bioactive glass 1393 on wound healing angiogenesis through both in vivo and in vitro studies. The research demonstrated that bioactive glass 1393 accelerated wound healing by promoting the formation of granulation, deposition of collagen, and angiogenesis. The results of Western blot analysis and immunofluorescence staining revealed that bioactive glass 1393 up-regulated the expression of angiogenesis-related factors. Additionally, bioactive glass 1393 inhibited the expression of ROS and P53 to promote angiogenesis. Furthermore, bioactive glass 1393 stimulated angiogenesis through the P53 signaling pathway, as evidenced by P53 activation assays. Collectively, these findings indicate that bioactive glass 1393 accelerates wound healing by promoting angiogenesis via the ROS/P53/MMP9 signaling pathway.

The TRIM21-FOXD1-BCL-2 axis underlies hyperglycaemic cell death and diabetic tissue damage.

Chronic hyperglycaemia is a devastating factor that causes diabetes-induced damage to the retina and kidney. However, the precise mechanism by which hyperglycaemia drives apoptotic cell death is incompletely known. Herein, we found that FOXD1, a FOX family transcription factor specifically expressed in the retina and kidney, regulated the transcription of BCL-2, a master regulator of cell survival. Intriguingly, the protein level of FOXD1, which responded negatively to hyperglycaemic conditions, was controlled by the TRIM21-mediated K48-linked polyubiquitination and subsequent proteasomal degradation. The TRIM21-FOXD1-BCL-2 signalling axis was notably active during diabetes-induced damage to murine retinal and renal tissues. Furthermore, we found that tartary buckwheat flavonoids effectively reversed the downregulation of FOXD1 protein expression and thus restored BCL-2 expression and facilitated the survival of retinal and renal tissues. In summary, we identified a transcription factor responsible for BCL-2 expression, a signalling axis (TRM21-FOXD1-BCL-2) underlying hyperglycaemia-triggered apoptosis, and a potential treatment for deleterious diabetic complications.

Genetic and epigenetic regulators of retinal Müller glial cell reprogramming.

Background: Retinal diseases characterized with irreversible loss of retinal nerve cells, such as optic atrophy and retinal degeneration, are the main causes of blindness. Current treatments for these diseases are very limited. An emerging treatment strategy is to induce the reprogramming of Müller glial cells to generate new retinal nerve cells, which could potentially restore vision. Main text: Müller glial cells are the predominant glial cells in retinae and play multiple roles to maintain retinal homeostasis. In lower vertebrates, such as in zebrafish, Müller glial cells can undergo cell reprogramming to regenerate new retinal neurons in response to various damage factors, while in mammals, this ability is limited. Interestingly, with proper treatments, Müller glial cells can display the potential for regeneration of retinal neurons in mammalian retinae. Recent studies have revealed that dozens of genetic and epigenetic regulators play a vital role in inducing the reprogramming of Müller glial cells in vivo. This review summarizes these critical regulators for Müller glial cell reprogramming and highlights their differences between zebrafish and mammals. Conclusions: A number of factors have been identified as the important regulators in Müller glial cell reprogramming. The early response of Müller glial cells upon acute retinal injury, such as the regulation in the exit from quiescent state, the initiation of reactive gliosis, and the re-entry of cell cycle of Müller glial cells, displays significant difference between mouse and zebrafish, which may be mediated by the diverse regulation of Notch and TGFß (transforming growth factor-ß) isoforms and different chromatin accessibility.

cGAS-STING signaling in cell death: Mechanisms of action and implications in pathologies.

Cyclic GMP-AMP synthase (cGAS) monitors dsDNA in the cytosol in response to pathogenic invasion or tissue injury, initiating cGAS-STING signaling cascades that regulate various cellular physiologies, including IFN /cytokine production, autophagy, protein synthesis, metabolism, senescence, and distinct types of cell death. cGAS-STING signaling is crucial for host defense and tissue homeostasis; however, its dysfunction frequently leads to infectious, autoimmune, inflammatory, degenerative, and cancerous diseases. Our knowledge regarding the relationships between cGAS-STING signaling and cell death is rapidly evolving, highlighting their essential roles in pathogenesis and disease progression. Nevertheless, the direct control of cell death by cGAS-STING signaling, rather than IFN/NF-κB-mediated transcriptional regulation, remains relatively unexplored. This review examines the mechanistic interplays between cGAS-STING cascades and apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagic/lysosomal cell death. We will also discuss their pathological implications in human diseases, particularly in autoimmunity, cancer, and organ injury scenarios. We hope that this summary will stimulate discussion for further exploration of the complex life-or-death responses to cellular damage mediated by cGAS-STING signaling.

Mitochondrial control of innate immune responses.

Mitochondria are versatile organelles and essential components of numerous biological processes such as energy metabolism, signal transduction, and cell fate determination. In recent years, their critical roles in innate immunity have come to the forefront, highlighting impacts on pathogenic defense, tissue homeostasis, and degenerative diseases. This review offers an in-depth and comprehensive examination of the multifaceted mechanisms underlying the interactions between mitochondria and innate immune responses. We will delve into the roles of healthy mitochondria as platforms for signalosome assembly, the release of mitochondrial components as signaling messengers, and the regulation of signaling via mitophagy, particularly to cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling and inflammasomes. Furthermore, the review will explore the impacts of mitochondrial proteins and metabolites on modulating innate immune responses, the polarization of innate immune cells, and their implications on infectious and inflammatory diseases.

Fucoidan promotes angiogenesis and accelerates wound healing through AKT/Nrf2/HIF-1α signalling pathway.

After skin injury, wound repair involves a complex process in which angiogenesis plays a crucial role. Previous research has indicated that fucoidan may aid in wound healing; we therefore hypothesised that fucoidan may speed up the process by promoting angiogenesis. In this study, we investigated the potential molecular mechanism underlying fucoidan's ability to accelerate wound healing by promoting angiogenesis. Using a full-cut wound model, we observed that fucoidan significantly intensified wound closure and promoted granulation formation and collagen deposition. Immunofluorescence staining revealed that fucoidan also promoted wound angiogenesis, specifically by accelerating the migration of new blood vessels to the middle area of the wound. Furthermore, fucoidan demonstrated the ability to enhance the proliferation of human umbilical vein endothelial cells (HUVECs) damaged by hydrogen peroxide (H2 O2 ) and to improve the formation of endothelial tubes. Mechanistic studies revealed that fucoidan upregulated the protein levels of the AKT/Nrf2/HIF-1α signalling pathway, which plays a crucial role in angiogenesis. This was further confirmed using the inhibitor LY294002, which reversed the promotion of endothelial tube formation by fucoidan. Overall, our findings suggest that fucoidan can promote angiogenesis via the AKT/Nrf2/HIF-1α signalling pathway and accelerate wound healing.

Rutin alleviates colon lesions and regulates gut microbiota in diabetic mice.

Diabetes is a common metabolic disorder that has become a major health problem worldwide. In this study, we investigated the role of rutin in attenuating diabetes and preventing diabetes-related colon lesions in mice potentially through regulation of gut microbiota. The rutin from tartary buckwheat as analyzed by HPLC was administered intragastrically to diabetic mice, and then the biochemical parameters, overall community structure and composition of gut microbiota in diabetic mice were assayed. The results showed that rutin lowered serum glucose and improved serum total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride concentrations, tumor necrosis factor-α, interleukin-6, and serum insulin in diabetic mice. Notably, rutin obviously alleviated colon lesions in diabetic mice. Moreover, rutin also significantly regulated gut microbiota dysbiosis and enriched beneficial microbiota, such as Akkermansia (p < 0.05). Rutin selectively increased short-chain fatty acid producing bacteria, such as Alistipes (p < 0.05) and Roseburia (p < 0.05), and decreased the abundance of diabetes-related gut microbiota, such as Escherichia (p < 0.05) and Mucispirillum (p < 0.05). Our data suggested that rutin exerted an antidiabetic effect and alleviated colon lesions in diabetic mice possibly by regulating gut microbiota dysbiosis, which might be a potential mechanism through which rutin alleviates diabetes-related symptoms.

A novel circ_0018553 protects against angiotensin-induced cardiac hypertrophy in cardiomyocytes by modulating the miR-4731/SIRT2 signaling pathway.

Due to the complicated pathophysiology of cardiac hypertrophy, there are no effective therapies for the treatment of pathological cardiac hypertrophy. Accumulating evidence has demonstrated that circRNAs participate in the pathophysiology of cardiac hypertrophy. In this study, we investigated the regulatory mechanisms of the novel circ_0018553 in angiotensin II (Ang II)-induced cardiac hypertrophy. Circ_0018553 was enriched in endothelial progenitor cell (EPC)-derived exosomes, and circ_0018553 expression was downregulated in a cellular model of Ang II-induced cardiac hypertrophy. Silencing circ_0018553 promoted cardiac hypertrophy in the Ang II-induced cardiac hypertrophy cellular model, while overexpression of circ_0018553 significantly attenuated Ang II-induced cardiac hypertrophy in cardiomyocytes. Moreover, mechanistic studies revealed that circ_0018553 acted as a sponge for miR-4731 and that miR-4731 repressed sirtuin 2 (SIRT2) expression by targeting the 3'UTR of SIRT2. MiR-4731 overexpression promoted cardiac hypertrophy in the Ang II-induced cardiac hypertrophy cellular model, while inhibition of miR-4731 significantly attenuated Ang II-induced cardiac hypertrophy in cardiomyocytes. The rescue experiments showed that miR-4731 overexpression attenuated the protective effects of circ_0018553 overexpression on the cardiac hypertrophy induced by Ang II; SIRT2 silencing also attenuated the protective effects of miR-4731 inhibition on the Ang II-induced cardiac hypertrophy. In conclusion, our results indicated that EPC-derived exosomal circ_0018553 protected against Ang II-induced cardiac hypertrophy by modulating the miR-4731/SIRT2 signaling pathway.

Tartary Buckwheat Flavonoids Improve Colon Lesions and Modulate Gut Microbiota Composition in Diabetic Mice.

Tartary buckwheat flavonoids (TBFs) exhibit diverse biological activities, with antioxidant, antidiabetes, anti-inflammatory, and cholesterol-lowering properties. In this study, we investigated the role of TBFs in attenuating glucose and lipid disturbances in diabetic mice and hence preventing the occurrence of diabetes-related colon lesions in mice by regulating the gut microbiota. The results showed that TBFs (1) reversed blood glucose levels and body weight changes; (2) improved levels of serum total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and fasting insulin; and (3) significantly reduced diabetes-related colon lesions in diabetic mice. In addition, TBFs also affected the diabetes-related imbalance of the gut microbiota and enriched beneficial microbiota, including Akkermansia and Prevotella. The TBF also selectively increased short-chain fatty acid-producing bacteria, including Roseburia and Odoribacter, and decreased the abundance of the diabetes-related gut microbiota, including Escherichia, Mucispirillum, and Bilophila. The correlation analysis indicated that TBFs improved metabolic parameters related to key communities of the gut microbiota. Our data suggested that TBFs alleviated glucose and lipid disturbances and improved colon lesions in diabetic mice, possibly by regulating the community composition of the gut microbiota. This regulation of the gut microbiota composition may explain the observed effects of TBFs to alleviate diabetes-related symptoms.

Association between trimethylamine N-oxide and prognosis of patients with acute myocardial infarction and heart failure.

AIMS: This study aimed to investigate the association between trimethylamine N-oxide (TMAO) and the prognosis and association between high-sensitivity C-reactive protein (hsCRP) and TMAO-associated cardiovascular risk in patients with acute myocardial infarction (AMI) complicated by heart failure (HF). METHODS AND RESULTS: A total of 985 patients presenting with AMI and HF were consecutively enrolled at the Fuwai Hospital between March 2017 and January 2020. Patients were stratified into groups according to tertiles of TMAO levels and the median hsCRP levels. The primary endpoint was major adverse cardiac events (MACE), including all-cause death, recurrence of myocardial infarction, and rehospitalization due to HF. During a median follow-up of 716 days, 138 (14.0%) patients experienced MACE. Cox regression analyses showed that the adjusted hazard ratio (HR) for MACE was higher in patients in tertile 3 [TMAO > 9.52 µmol/L, HR: 1.85, 95% confidence interval (CI): 1.18-2.89; P = 0.007] than in tertile 1 (TMAO < 4.74 µmol/L), whereas no significant differences were detected between the patients in tertiles 1 and 2 (TMAO = 4.74-9.52 µmol/L, HR: 0.96, 95% CI: 0.59-1.58; P = 0.874). Restricted cubic spline regression depicted an S-shaped association between TMAO and MACE (P for nonlinearity = 0.012). In the setting of hsCRP above the median level (6.68 mg/L), per unit increase of TMAO was associated with a 20% increase of MACE risk (HR: 1.20, 95% CI: 1.05-1.37, P = 0.009); increasing tertiles of TMAO were significantly associated with a higher risk of MACE (adjusted P = 0.007 for interaction; P < 0.001 for trend across tertiles). The Kaplan-Meier analysis indicated that patients in tertile 3 had a significantly lower event-free survival (P = 0.001) when the hsCRP level was above the median level. No similar association between TMAO and MACE was observed when the hsCRP level was below the median level. CONCLUSIONS: High plasma TMAO levels were independently correlated with poor prognosis in patients with AMI complicated by HF, especially in those with higher hsCRP levels. There was an S-shaped relationship between TMAO and HR for MACE.

High-Risk Culprit Plaque Predicts Cardiovascular Outcomes Independently of Plaque Rupture in ST-Segment Elevation Myocardial Infarction: Insight From Optical Coherence Tomography.

The present study explored the predictive value of culprit high-risk plaque (HRP) detected by optical coherence tomography (OCT) for predicting major adverse cardiovascular events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI). HRP was defined as the simultaneous presence of four criteria: minimum lumen area <3.5 mm2, fibrous cap thickness <75 µm, lipid plaque with lipid arc extension >180°, and presence of macrophages. Patients (n = 274) were divided into non-HRP group (n = 206) and HRP group (n = 68). MACEs were defined as a composite of all-cause death, myocardial infarction, stroke, and revascularization. During a mean follow-up of 2.2 years, 47 (17.5%) MACEs were observed: 28 (13.6%) in the non-HRP group and 19 (27.9%) in the HRP group (log-rank P = .005). Patients with HRP were 2.05 times more likely to suffer from a MACE than those without HRP (hazards ratio: 2.05, 95% confidence interval: 1.04-4.02, P = .038); MACE risk was comparable between plaque rupture and plaque erosion. In conclusion, HRP was present in 24.8% of STEMI patients and associated with higher cardiovascular risk independent of plaque rupture, suggesting that HRP detected by OCT may help identify patients at high risk of future cardiac events.

A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis.

Innate DNA sensing via the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) mechanism surveys microbial invasion and cellular damage and thus participates in various human infectious diseases, autoimmune diseases and cancers. However, how DNA sensing rapidly and adaptively shapes cellular physiology is incompletely known. Here we identify the STING-PKR-like endoplasmic reticulum kinase (PERK)-eIF2α pathway, a previously unknown cGAS-STING mechanism, enabling an innate immunity control of cap-dependent messenger RNA translation. Upon cGAMP binding, STING at the ER binds and directly activates the ER-located kinase PERK via their intracellular domains, which precedes TBK1-IRF3 activation and is irrelevant to the unfolded protein response. The activated PERK phosphorylates eIF2α, forming an inflammatory- and survival-preferred translation program. Notably, this STING-PERK-eIF2α pathway is evolutionarily primitive and physiologically critical to cellular senescence and organ fibrosis. Pharmacologically or genetically targeting this non-canonical cGAS-STING pathway attenuated lung and kidney fibrosis. Collectively, the findings identify an alternative innate immune pathway and its critical role in organ fibrosis, report an innate immunity-directed translation program and suggest the therapeutic potential for targeting the STING-PERK pathway in treating fibrotic diseases.

Circ-RHOJ.1 regulated myocardial cell proliferation and apoptosis via targeting the miR-124-3p/NRG-1 axis in myocardial ischemia/reperfusion injury.

Introduction: Myocardial ischemia/reperfusion (I/R) injury is a leading cause of cardiac dysfunction. Circular RNAs (circRNAs) are involved in the pathogenesis of myocardial I/R injury. However, the functions and underlying mechanisms are unclear. The present study determined the role of circ-RHOJ.1 in regulating myocardial cell proliferation and apoptosis after I/R injury. Material and methods: Myocardial cells isolated from Sprague-Dawley rats were identified with an immunofluorescence assay using cardiac troponin T antibody. Expression of circ-RHOJ.1, miR-124-3p and neuregulin-1 (NRG1) mRNA was assessed with real-time quantitative polymerase chain reaction. NRG1 protein expression was evaluated with western blot and immunofluorescence assays. Dual-luciferase reporter assay was performed to confirm interaction between miR-124-3p and circ-RHOJ.1, and miR-124-3p and NRG1. Effects of circ-RHOJ.1 overexpression or miR-124-3p inhibition on cell proliferation and apoptosis were evaluated using cell counting kit (CCK)-8 assay and flow cytometry. Cytokines levels were analyzed with an enzyme-linked immunosorbent assay. Results: Myocardial cells were successfully isolated and had down-regulated expression of circ-RHOJ.1 and NRG1, and up-regulated expression of miR-124-3p after I/R injury. circ-RHOJ.1 acted as a sponge for miR-124-3p, and NRG1 served as a target gene of miR-124-3p. circ-RHOJ.1 overexpression or miR-124-3p inhibition increased interleukin (IL)-10 levels and reduced IL-2, IL-6, and tumor necrosis factor-α levels in myocardial cells after I/R injury. Functional assay results illustrated that circ-RHOJ.1 overexpression or miR-124-3p inhibition enhanced proliferation and inhibited apoptosis of myocardial cells after I/R injury. Conclusions: Circ-RHOJ.1 served as a molecular marker of myocardial I/R injury via regulation of miR-124-3p and NRG1 expression.

Leaf trait association in relation to herbivore defense, drought resistance, and economics in a tropical invasive plant.

PREMISE: Exploring how functional traits vary and covary is important to understand plant responses to environmental change. However, we have limited understanding of the ways multiple functional traits vary and covary within invasive species. METHODS: We measured 12 leaf traits of an invasive plant Chromolaena odorata, associated with plant or leaf economics, herbivore defense, and drought resistance on 10 introduced populations from Asia and 12 native populations from South and Central America, selected across a broad range of climatic conditions, and grown in a common garden. RESULTS: Species' range and climatic conditions influenced leaf traits, but trait variation across climate space differed between the introduced and native ranges. Traits that confer defense against herbivores and drought resistance were associated with economic strategy, but the patterns differed by range. Plants from introduced populations that were at the fast-return end of the spectrum (high photosynthetic capacity) had high physical defense traits (high trichome density), whereas plants from native populations that were at the fast-return end of the spectrum had high drought escape traits (early leaf senescence and high percentage of withered shoots). CONCLUSIONS: Our results indicate that invasive plants can rapidly adapt to novel environmental conditions. Chromolaena odorata showed multiple different functional trait covariation patterns and clines in the native and introduced ranges. Our results emphasize that interaction between multiple traits or functions should be considered when investigating the adaptive evolution of invasive plants.

Rutin Promotes Pancreatic Cancer Cell Apoptosis by Upregulating miRNA-877-3p Expression.

(1) Background: pancreatic cancer is one of the most serious cancers due to its rapid and inevitable fatality, which has been proved very difficult to treat, compared with many other common cancers. Thus, developing an effective therapeutic strategy, especially searching for potential drugs, is the focus of current research. The exact mechanism of rutin in pancreatic cancer remains unknown. (2) Method: three pancreatic cancer cell lines were used to study the anti-pancreatic cancer effect of rutin. The potent anti-proliferative, anti-migration and pro-apoptotic properties of rutin were uncovered by cell viability, a wound-healing migration assay, and a cell apoptosis assay. High-throughput sequencing technology was used to detect the change of miRNAs expression. Immunoblotting analysis was used to detect the expression of apoptotic proteins. (3) Results: CCK-8 and EDU assays revealed that rutin significantly inhibited pancreatic cancer cells' proliferation (p < 0.05). A wound-healing assay showed that rutin significantly suppressed pancreatic cancer cells' migration (p < 0.05). A flow cytometric assay showed that rutin could promote pancreatic cancer cells' apoptosis. Intriguingly, rutin significantly upregulated miR-877-3p expression to repress the transcription of Bcl-2 and to induce pancreatic cancer cell apoptosis. Accordingly, rutin and miR-877-3p mimics could promote apoptotic protein expression. (4) Conclusions: our findings indicate that rutin plays an important role in anti-pancreatic cancer effects through a rutin-miR-877-3p-Bcl-2 axis and suggests a potential therapeutic strategy for pancreatic cancer.

Endothelial colony-forming cell-derived exosomal miR-21-5p regulates autophagic flux to promote vascular endothelial repair by inhibiting SIPL1A2 in atherosclerosis.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) represents an efficient therapeutic method for atherosclerosis but conveys a risk of causing restenosis. Endothelial colony-forming cell-derived exosomes (ECFC-exosomes) are important mediators during vascular repair. This study aimed to investigate the therapeutic effects of ECFC-exosomes in a rat model of atherosclerosis and to explore the molecular mechanisms underlying the ECFC-exosome-mediated effects on ox-LDL-induced endothelial injury. METHODS: The effect of ECFC-exosome-mediated autophagy on ox-LDL-induced human microvascular endothelial cell (HMEC) injury was examined by cell counting kit-8 assay, scratch wound assay, tube formation assay, western blot and the Ad-mCherry-GFP-LC3B system. RNA-sequencing assays, bioinformatic analysis and dual-luciferase reporter assays were performed to confirm the interaction between the miR-21-5p abundance of ECFC-exosomes and SIPA1L2 in HMECs. The role and underlying mechanism of ECFC-exosomes in endothelial repair were explored using a high-fat diet combined with balloon injury to establish an atherosclerotic rat model of vascular injury. Evans blue staining, haematoxylin and eosin staining and western blotting were used to evaluate vascular injury. RESULTS: ECFC-exosomes were incorporated into HMECs and promoted HMEC proliferation, migration and tube formation by repairing autophagic flux and enhancing autophagic activity. Subsequently, we demonstrated that miR-21-5p, which is abundant in ECFC-exosomes, binds to the 3' untranslated region of SIPA1L2 to inhibit its expression, and knockout of miR-21-5p in ECFC-exosomes reversed ECFC-exosome-decreased SIPA1L2 expression in ox-LDL-induced HMEC injury. Knockdown of SIPA1L2 repaired autophagic flux and enhanced autophagic activity to promote cell proliferation in ox-LDL-treated HMECs. ECFC-exosome treatment attenuated vascular endothelial injury, regulated lipid balance and activated autophagy in an atherogenic rat model of vascular injury, whereas these effects were eliminated with ECFC-exosomes with knockdown of miR-21-5p. CONCLUSIONS: Our study demonstrated that ECFC-exosomes protect against atherosclerosis- or PTCA-induced vascular injury by rescuing autophagic flux and inhibiting SIAP1L2 expression through delivery of miR-21-5p. Video Abstract.

Genetic investigation of haemoglobinopathies in a large cohort of asymptomatic individuals reveals a higher carrier rate for ß-thalassaemia in Sichuan Province (Southwestern China).

The incidence of haemoglobinopathy is high in China, especially south of the Yangtze River. However, the exact status of haemoglobinopathy in Sichuan is unknown. To carry out a detailed research of haemoglobinopathy in individuals living in Sichuan, 13,298 subjects without clinical symptoms who were living in Sichuan Province, with an age distribution of 5-73 years, were included in this study. Between March 2014 and July 2017, these subjects received examinations at the Medical Lab of Chengdu Women's & Children's Central Hospital. Mean corpuscular volume (MCV) < 82 fL or mean corpuscular haemoglobin (MCH) < 27 pg was used to indicate haemoglobinopathy carriers. Abnormal haemoglobin was screened by electrophoresis, and genes were sequenced to identify genotypes. Genotype diagnosis of alpha- and beta-thalassaemia was carried out by using PCR and shunt hybridization. There were 638 suspected haemoglobinopathy carriers (4.80%, 638/13,298). DNA sequencing identified 6 subjects with abnormal haemoglobin genotypes and 15 subjects with Hb E. The frequency of heterozygosity for thalassaemia was 4.12% (1.48% for α-thalassaemia and 2.61% for ß-thalassaemia) in Sichuan Province. The mutation spectrum of α-thalassaemia consisted of the five most common mutations: --SEA, -α3.7, -α4.2, αCS, and αQS. Seven types of ß-thalassaemia mutation were found in this study: CD41-42 (-TTCT) was the most frequent (28.47%), followed by 17 (A > T), -28 (A > G), and IVS-II-654 (C > T). The main abnormal haemoglobin genotype (HbE) and thalassaemia genotype (--SEA, CD41-42 (-TTCT)) were consistent with those in other regions of China, but the carrier rate of ß-thalassaemia in Sichuan was higher than that of α-thalassaemia.

MiR-1247-3p protects rat cardiomyocytes against hypoxia/reoxygenation-induced injury via targeting BCL2L11 and caspase-2.

Acute myocardial infarction (AMI) represents a severe coronary heart disease with relatively high rate of mortality and usually can lead to the damage of the myocardial tissues. Reperfusion of the ischemic myocardial tissues can minimize AMI-induced damage. As far as we know, the molecular mechanisms underlying ischemia/reperfusion (I/R)-induced injury remains elusive. This study was undertaken to explore the role of miR-1247-3p in regulating myocardial I/R injury. The hypoxia/reoxygenation (H/R)-treated H9c2 cells showed a decreased cell viability and mitochondrial membrane potential with an increase in the apoptosis; furthermore, miR-1247-3p was down-regulated in these cells. MiR-1247-3p overexpression attenuated H/R-induced H9c2 cell injury; while miR-1247-3p knockdown in H9c2 cells exhibited similar effects being observed in H/R-treated cells. The bioinformatics prediction revealed Bcl-2-like protein 11 (BCL2L11) and caspase-2 were two potential targets for miR-1247-3p, and functional assays confirmed that miR-1247-3p targeted both BCL2L11 and caspase-2 3' untranslated regions, which lead to the repressed expression of these genes. Silencing of BCL2L11 and caspase-2 both, respectively, counteracted the H9c2 cell injury caused by H/R treatment. Moreover, BCL2L11 and caspase-2 overexpression, respectively, impaired the protective effects of miR-1247-3p overexpression on H/R-treated H9c2 cells. The data in the present investigation revealed that miR-1247-3p restoration exhibited protective effects on H/R-induced cardiomyocyte injury through targeting BCL2L11 and caspase-2, implying that miR-1247-3p along with caspase-2/BCL2L11 signaling may provide novel sight for a better understating of I/R-induced myocardial damage. The role of miR-1247-3p might be further confirmed in animal models and clinical studies.

Rapid genomic and phenotypic change in response to climate warming in a widespread plant invader.

Predicting plant distributions under climate change is constrained by our limited understanding of potential rapid adaptive evolution. In an experimental evolution study with the invasive common ragweed (Ambrosia artemisiifolia L.) we subjected replicated populations of the same initial genetic composition to simulated climate warming. Pooled DNA sequencing of parental and offspring populations showed that warming populations experienced greater genetic divergence from their parents, than control populations. In a common environment, offspring from warming populations showed more convergent phenotypes in seven out of nine plant traits, with later flowering and larger biomass, than plants from control populations. For both traits, we also found a significantly higher ratio of phenotypic to genetic differentiation across generations for warming than for control populations, indicating stronger response to selection under warming conditions. As a measure for evolutionary rate, the phenotypic and sequence divergence between generations were assessed using the Haldane metric. Our approach combining comparisons between generations (allochronic) and between treatments (synchronic) in an experimental evolutionary field study, and linking population genomic data with phenotyping analyses provided a powerful test to detect rapid responses to selection. Our findings demonstrate that ragweed populations can rapidly evolve in response to climate change within a single generation. Short-term evolutionary responses to climate change may aggravate the impact of some plant invaders in the future and should be considered when making predictions about future distributions and impacts of plant invaders.

Isolation, identification, and whole genome sequence analysis of the alginate-degrading bacterium Cobetia sp. cqz5-12.

Alginate-degrading bacteria or alginate lyases can be used to oligomerize alginate. In this study, an alginate-degrading bacterium with high alginolytic activity was successfully screened by using Sargassum fusiforme sludge. When the strain was grown on a plate containing sodium alginate, the transparent ring diameter (D) was 2.2 cm and the ratio (D/d) of transparent ring diameter to colony diameter (d) was 8.8. After 36 h in culture at a temperature of 28 °C shaken at 150 r/min, the enzymatic activity of the fermentation supernatant reached 160 U/mL, and the enzymatic activity of the bacterial precipitate harvested was 2,645 U/mL. The strain was named Cobetia sp. cqz5-12. Its genome is circular in shape, 4,209,007 bp in size, with a 62.36% GC content. It contains 3,498 predicted coding genes, 72 tRNA genes, and 21 rRNA genes. The functional annotations for the coding genes demonstrated that there were 181 coding genes in the genome related to carbohydrate transport and metabolism and 699 coding genes with unknown functions. Three putative coding genes, alg2107, alg2108 and alg2112, related to alginate degradation were identified by analyzing the carbohydrate active enzyme (CAZy) database. Moreover, proteins Alg2107 and Alg2112 were successfully expressed and exhibited alginate lyase activity.