Human disturbances dominated the unprecedentedly high frequency of Yellow River flood over the last millennium.

A warming climate may increase flood hazard through boosting the global hydrological cycle. However, human impact through modifications to the river and its catchment is not well quantified. Here, we show a 12,000-year-long record of Yellow River flood events by synthesizing sedimentary and documentary data of levee overtops and breaches. Our result reveals that flood events in the Yellow River basin became almost an order of magnitude more frequent during the last millennium than the middle Holocene and 81 ± 6% of the increased flood frequency can be ascribed to anthropogenic disturbances. Our findings not only shed light on the long-term dynamics of flood hazards in this world's most sediment-laden river but also inform policy of sustainable management of large rivers under anthropogenic stress elsewhere.

Possible obliquity-forced warmth in southern Asia during the last glacial stage.

Orbital-scale global climatic changes during the late Quaternary are dominated by high-latitude influenced ~100,000-year global ice-age cycles and monsoon influenced ~23,000-year low-latitude hydroclimate variations. However, the shortage of highly-resolved land temperature records remains a limiting factor for achieving a comprehensive understanding of long-term low-latitude terrestrial climatic changes. Here, we report paired mean annual air temperature (MAAT) and monsoon intensity proxy records over the past 88,000 years from Lake Tengchongqinghai in southwestern China. While summer monsoon intensity follows the ~23,000-year precession beat found also in previous studies, we identify previously unrecognized warm periods at 88,000-71,000 and 45,000-22,000 years ago, with 2-3 °C amplitudes that are close to our recorded full glacial-interglacial range. Using advanced transient climate simulations and comparing with forcing factors, we find that these warm periods in our MAAT record probably depends on local annual mean insolation, which is controlled by Earth's ~41,000-year obliquity cycles and is anti-phased to annual mean insolation at high latitudes. The coincidence of our identified warm periods and intervals of high-frequent dated archaeological evidence highlights the importance of temperature on anatomically modern humans in Asia during the last glacial stage.

The onset of sleep disturbances and their associations with anxiety after acute high-altitude exposure at 3700 m.

Sleep disturbances and psychiatric repercussions pose great challenges at high altitude; however, few studies have investigated sleep disturbance and anxiety profiles and their associations after acute exposure in consecutive patients. Thus, we aimed to study the profiles of sleep disturbances in consecutive patients after high-altitude exposure and the association of such disturbances with anxiety. A total of 668 participants were recruited at sea level and 3700 m. The trials were performed at sea level (1 week prior to a 2-h flight to a high-altitude destination) and at 3700 m (24, 72, and 168 h). Sleep disturbances were assessed by self-reported sleep patterns and scores on the Athens Insomnia Scale (AIS). State anxiety was assessed using the Self-Rating Anxiety Scale (SAS). In our study, the incidence of sleep disturbances increased significantly after acute high-altitude exposure (65.3%, 434/668) and then gradually decreased after 72 h (50%, 141/282) and 168 h (44%, 124/282). The sleep assessments AIS [2.0 (4.0) vs. 4.0 (5.0)] and ESS [4.0 (4.0) vs. 5.0 (5.0)] increased significantly (p < 0.05). Also, the SAS increased significantly from 26.25 (3.75) to 28.75 (7.5). The SAS was significantly high in sleep disturbance group [31.25 (7.5) vs. 27.5 (5), p < 0.001] than in the non-sleep- disturbance group. The baseline SAS and AIS scores were significantly higher in participants with sleep disturbances than in those without (p < 0.01). Age, baseline insomnia, sleepiness, fatigue, and higher SAS were predictors of sleep disturbances in univariate regression (all p values < 0.05). However, only an older age (p = 0.045) and a higher baseline SAS (p = 0.018) remained independent predictors of sleep disturbances. Our findings indicated that acute high-altitude exposure triggers the onset of sleep disturbances, which are closely associated with anxiety. Furthermore, baseline state anxiety and age are independent predictors of sleep disturbances at high altitude.

C-doped ZnO decorated with Au nanoparticles constructed from the metal-organic framework ZIF-8 for photodegradation of organic dyes.

Recently, engineering metal-organic frameworks (MOFs) into metal oxides by solid state thermal decomposition has attracted wide attention for photocatalytic applications. Here, a series of C-doped ZnO materials decorated with Au nanoparticles (Au/C-ZnO) were constructed via controlled pyrolysis of ZIF-8 adsorbing different amounts of HAuCl4·4H2O. In this pyrolysis process, ZIF-8 was transformed into C-doped ZnO according to the EDX and XPS analysis. Meanwhile, HAuCl4·4H2O was transformed into Au nanoparticles that were uniformly dispersed on the surface of C-ZnO as seen in TEM images. The photocatalytic activity of as-prepared catalysts was evaluated by the degradation of methyl orange under UV-vis light irradiation. It was found that the photocatalytic activity of Au/C-ZnO was better than C-ZnO and pure ZnO. Furthermore, Au/C-ZnO exhibited high photocatalytic stability. After three consecutive cycles, there was no noticeable deactivation in the reaction. This unusual photocatalytic activity was attributed to the synergistic effect of C-doping and Au NPs.

Constructing ZIF-8 derived C-ZnS/ZnMoO4@MoS2 and C-ZnS/MoS2 nanocomposites using a simple one-pot strategy to enhance photocatalytic degradation activity.

Efficient C-ZnS/ZnMoO4@MoS2 and C-ZnS/MoS2 nanocomposite photocatalysts, using ZIF-8 derived C-ZnO as a precursor were successfully synthesized using a simple one-pot procedure. This is the first application that involves transforming ZIF-8 into C-ZnMoO4 for photocatalysis. The C-ZnS/ZnMoO4@MoS2 and C-ZnS/MoS2 heterostructures were characterized by X-ray diffraction, UV-vis, X-ray photoelectron spectroscopy, electrochemical impedance spectroscopy, photocurrent measurements, scanning electron microscopy and transmission electron microscopy. The ZM2 sample of C-ZnS/ZnMoO4@MoS2 exhibited enhanced photocatalytic activity of about 2.9 times as high as that of ZIF-8 derived C-ZnO in the reduction of tetracycline hydrochloride, and also showed obvious photocatalytic activity 1.81 and 3.33 times as high as that of a ZM3 sample of C-ZnS/MoS2 and ZIF-8 derived C-ZnO in the degradation of RhB, respectively. The improved photodegradation activity is a result of the heterogenous structure and the tighter contact between C-ZnS and C-ZnMoO4 compared with the physical contact of general heterogenous photocatalysts. The C-ZnS/ZnMoO4@MoS2 heterostructure photocatalyst is expected to be a new type of nanomaterial for the degradation of pollutants from wastewater.

Underestimated ecosystem carbon turnover time and sequestration under the steady state assumption: A perspective from long-term data assimilation.

It is critical to accurately estimate carbon (C) turnover time as it dominates the uncertainty in ecosystem C sinks and their response to future climate change. In the absence of direct observations of ecosystem C losses, C turnover times are commonly estimated under the steady state assumption (SSA), which has been applied across a large range of temporal and spatial scales including many at which the validity of the assumption is likely to be violated. However, the errors associated with improperly applying SSA to estimate C turnover time and its covariance with climate as well as ecosystem C sequestrations have yet to be fully quantified. Here, we developed a novel model-data fusion framework and systematically analyzed the SSA-induced biases using time-series data collected from 10 permanent forest plots in the eastern China monsoon region. The results showed that (a) the SSA significantly underestimated mean turnover times (MTTs) by 29%, thereby leading to a 4.83-fold underestimation of the net ecosystem productivity (NEP) in these forest ecosystems, a major C sink globally; (b) the SSA-induced bias in MTT and NEP correlates negatively with forest age, which provides a significant caveat for applying the SSA to young-aged ecosystems; and (c) the sensitivity of MTT to temperature and precipitation was 22% and 42% lower, respectively, under the SSA. Thus, under the expected climate change, spatiotemporal changes in MTT are likely to be underestimated, thereby resulting in large errors in the variability of predicted global NEP. With the development of observation technology and the accumulation of spatiotemporal data, we suggest estimating MTTs at the disequilibrium state via long-term data assimilation, thereby effectively reducing the uncertainty in ecosystem C sequestration estimations and providing a better understanding of regional or global C cycle dynamics and C-climate feedback.

MiR-27b directly targets Rab3D to inhibit the malignant phenotype in colorectal cancer.

MiRNAs, as oncogenes or as anti-oncogenes, play critically regulated roles in the initiation and progression of colorectal cancer at posttranscriptional level. However, the underlying functions of miR-27b in colorectal cancer remain largely unexplored. Here, we demonstrated miR-27b is significantly down-regulated in colorectal cancer tissues, and decreased miR-27b expression was closely associated with shorter overall survival of patients with colorectal cancer. By gain- and loss-of-function studies, we showed miR-27b remarkably suppressed cell proliferation and invasion of colorectal cancer. Furthermore, luciferase reporter assay identified Rab3D was the direct functional target of miR-27b. And Rab3D partly reversed the suppression of cell proliferation and invasion caused by miR-27b mimics. Finally, the animal experiment showed miR-27b plays a crucial role on colorectal cancer progression by targeting Rab3D. Taken together, our study implied miR-27b inhibits cell growth and invasion by targeting Rab3D, and miR-27b is a potential biomarker for prognosis and therapeutic target in colorectal cancer.

Acute Mountain Sickness Is Associated With a High Ratio of Endogenous Testosterone to Estradiol After High-Altitude Exposure at 3,700 m in Young Chinese Men.

Background: A large proportion of populations suffer from acute mountain sickness (AMS) after exposure at high altitude. AMS is closely related with age and gender implying that the sex hormones may play critical roles in AMS. Our observational study aimed to identify the association between the endogenous testosterone (T), estradiol (E2) and AMS. Methods: A total of 113 subjects were recruited in 2012. The participants were evaluated at 500 m and after acute (1 day) and short-term (7 days) high-altitude exposure at 3,700 m. The subjects also completed a case report form questionnaire and underwent blood pressure measurements and an echocardiography examination. The red blood cell (RBC) count, Hb concentration ([Hb]), hematocrit (HCT), E2, T, and erythropoietin (EPO) were measured. Results: Upon acute high-altitude exposure, E2 and EPO were significantly lower in AMS+ group, and T/E2 and stroke volume were higher. On the 1st day, AMS score correlated positively with the T/E2 ratio while it negatively correlated with E2. After 7 days at 3,700 m, the AMS+ subjects had higher erythropoietic parameters: EPO, T, and T/E2 were significantly higher in the AMS+ group. [Hb], RBC count, HCT, EPO, T and T/E2 were also correlated with AMS score. EPO, HCT, and the RBC count were also correlated with T/E2. Regression analyses indicated that T/E2 significantly correlated to AMS score and T/E2 on the 1st day was an independent predictor for AMS on the 7th day. Conclusion: AMS was correlated with T/E2 ratio and EPO. After short-term exposure, higher T/E2 may contribute to AMS together with EPO via erythropoiesis. Furthermore, T/E2 level at high altitude in the early stage was an independent predictor for AMS in the latter stage.

Physiological and psychological factors associated with onset of high-altitude headache in Chinese men upon acute high-altitude exposure at 3700 m.

Aim We aimed to identify clinical characteristics and risk factors associated with onset of high-altitude headache (HAH) after acute exposure at 3700 m. Method In two hours, 163 individuals ascended by plane to 3700 m. Demographic information, physiological and psychological measurements, cognitive function, physical work capacity tests and profile of mood states within one week prior to the departure and within 24 hours after arrival were examined. Results HAH patients featured significantly higher vertebral artery diastolic velocity (Vd), heart rate (HR) and pulmonary artery diameter. HAH was also associated with a more negative mood state, including scores for tension anxiety, depression, hostility, fatigue and confusion, as well as lower vigor (all p values <0.05). Furthermore, negative emotions were positively related to HAH severity. HAH slightly decreased cognitive functioning. HR, Vd, lack of vigor, confusion and self-reported anxiety (all p values <0.05) were independent risk factors for HAH. We have identified three independent baseline predictors for HAH including internal diameter of the left ventricle (LVD), Athens Insomnia Scale (AIS) and confusion score. Conclusions Higher HR, Vd, confusion and self-reported anxiety and insufficient vigor were independent risk factors for HAH. Furthermore, higher baseline LVD, AIS and confusion score are independent predictors of HAH.

A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness.

OBJECTIVE: The current study aimed to identify the predictive values of psychological factors that are evaluated by the Symptoms Checklist-90 (SCL-90) for acute mountain sickness (AMS). METHODS: The subjects (n=285, non-acclimatized young Chinese men), who were recruited in July 2013, completed a case report questionnaire. In addition, their vital signs (heart rate [HR], blood pressure and pulse oxygen saturation) were measured, and their psychological factors were examined using the SCL-90 at sea level. AMS was diagnosed using the Lake Louise self-assessment scoring system in the morning of the second day after their arrival at 3450m. RESULTS: Of the nine factors of the SCL-90, the AMS patients (AMS score≥3) were characterized by significantly higher scores for baseline somatization [14.0 (5.0) vs. 13.0 (3.0), p<0.001], obsession-compulsion, depression, anxiety and hostility compared with the non-AMS group (all p values<0.05). Spearman's correlation analyses revealed associations between AMS scores and somatization (r=0.316, p<0.001), depression, anxiety, obsession-compulsion, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideation and psychoticism scores (all p values<0.001). Although all nine factors were associated with AMS in a univariate regression (all p<0.05), a further adjusted logistic regression analysis indicated that only baseline somatization score (odds ratio=1.129, p=0.001) was an independent predictor of AMS. Furthermore, some non-AMS often-occurred symptoms (paresthesia, shortness of breath, reduced activity and tinnitus) were also found to be associated with the baseline SCL-90 scores. CONCLUSION: AMS is correlated with the baseline somatization score at sea level, which was measured using the SCL-90. A higher baseline somatization score is also an independent predictor of AMS.

Principal Component Analysis and Risk Factors for Acute Mountain Sickness upon Acute Exposure at 3700 m.

OBJECTIVE: We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors. METHODS: The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO2), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses. RESULTS: The AMS patients had a higher diastolic vertebral artery velocity (Vd; p = 0.018), a higher HR (p = 0.006) and a lower SpO2. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher Vd (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS. CONCLUSIONS: Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and Vd, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS.

Lack of association of CYP11B2-344C/T polymorphism with essential hypertension: a meta-analysis.

OBJECTIVE: A meta-analysis was carried out to evaluate the correlation between CYP11B2-344C/T polymorphism and essential hypertension susceptibility. METHODS: By retrieving relevant databases and collecting domestic and international literatures about the correlation between CYP11B2-344C/T polymorphism and essential hypertension, the quality of literature were evaluated according to NEWCASTLE-OTTAWA case-control study quality rating scale (NOS). RevMan 5.0 was used to select the best genetic model, analysis the heterogeneity, calculate combined OR and the 95% CI. RESULTS: 8532 subjects were included in this study. Compared with the control group, the OR (95% CI) values of dominant model, recessive model, and additive model were 1.01 (95% CI: 0.81~1.25), 1.03 (95% CI: 0.83~1.19) and 1.10 (95% CI: 0.93-1.29). CONCLUSION: There is no evidence to confirm that CYP11B2 (-344C/T) polymorphism is associated with susceptibility of essential hypertension.

Hemodynamic characteristics of high-altitude headache following acute high altitude exposure at 3700 m in young Chinese men.

BACKGROUND: This study aimed to identify the systemic and cerebral hemodynamic characteristics and their roles in high-altitude headache (HAH) among young Chinese men following acute exposure. METHODS: The subjects (n = 385) were recruited in June and July of 2012. They completed case report form questionnaires, as well as heart rate (HR), blood pressure, echocardiogram and transcranial Doppler examinations at 3700 m following a two-hour plane flight. A subgroup of 129 participants was examined at two altitudes (500 and 3700 m). RESULTS: HAH was characterized by increased HR and cardiac output (CO) and lower saturation pulse oxygen (SpO(2)) (all p < 0.05). The change in tricuspid regurgitation was also different between the HAH positive (HAH+) and HAH negative (HAH-) subjects. Furthermore, the HAH+ subjects exhibited faster mean (V(m)), systolic (V(s)) and diastolic (V(d)) velocities in the basilar artery (BA; all p < 0.05) and a faster V(d) ( 25.96 ± 4.97 cm/s vs. 24.76 ± 4.76 cm/s, p = 0.045) in the left vertebral artery (VA). The bilateral VA asymmetry was also significantly different between the two groups. The pulsatility index (PI) and resistance index (RI) of left VA were lower in the HAH subjects (p < 0.05) and were negatively correlated with HAH (p < 0.05). Baseline CO and Vm in left VA (or right MCA in different regressions) were independent predictors for HAH, whereas CO/HR and ΔV(d) (V(d) difference between bilateral VAs) were independent risk factors for HAH at 3700 m. CONCLUSIONS: HAH was characterized, in part, by increased systemic hemodynamics and posterior cerebral circulation, which was reflected by the BA and left VA velocities, and lower arterial resistance and compliance. Furthermore, baseline CO and V(m) in left VA or right MCA at sea level were independent predictors for HAH, whilst bilateral VA asymmetry may contribute to the development of HAH at high altitude.

Cerebral hemodynamic characteristics of acute mountain sickness upon acute high-altitude exposure at 3,700 m in young Chinese men.

PURPOSE: We aimed at identifying the cerebral hemodynamic characteristics of acute mountain sickness (AMS). METHODS: Transcranial Doppler (TCD) sonography examinations were performed between 18 and 24 h after arrival at 3,700 m via plane from 500 m (n = 454). A subgroup of 151 subjects received TCD examinations at both altitudes. RESULTS: The velocities of the middle cerebral artery, vertebral artery (VA) and basilar artery (BA) increased while the pulsatility indexes (PIs) and resistance indexes (RIs) decreased significantly (all p < 0.05). Velocities of BA were higher in AMS (AMS+) individuals when compared with non-AMS (AMS-) subjects (systolic velocity: 66 ± 12 vs. 69 ± 15 cm/s, diastolic velocity: 29 ± 7 vs. 31 ± 8 cm/s and mean velocity, 42 ± 9 vs. 44 ± 10 cm/s). AMS was characterized by higher diastolic velocity [V d_VA (26 ± 4 vs. 25 ± 4, p = 0.013)] with lower PI and RI (both p = 0.004) in VA. Furthermore, the asymmetry index (AI) of VAs was significantly lower in the AMS + group [-5.7 % (21.0 %) vs. -2.5 % (17.8 %), p = 0.016]. The AMS score was closely correlated with the hemodynamic parameters of BA and the V d_VA, PI, RI and AI of VA. CONCLUSION: AMS is associated with alterations in cerebral hemodynamics in the posterior circulation rather than the anterior one, and is characterized by higher blood velocity with lower resistance. In addition, the asymmetry of VAs may be involved in AMS.

The luminescent properties and toxicity controllability investigation of novel ZnO quantum dots with Schiff base complexes modification.

The Schiff base complexes modified ZnO quantum dots (ZnO-SBC QDs) are successfully synthesized via the reflux and chemical co-precipitation route. For control experiments, we also synthesized the ZnO QDs and amino-modified ZnO QDs (ZnO-NH2 QDs). The structures and morphologies of the samples were characterized via X-ray powder diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), FTIR spectroscopy (IR), Fluorescence Spectrometer (FL) and so on. The XRD pattern shows that the three types of QDs possess hexagonal wurtzite structures. The TEM investigation reveals that the as-prepared products have hexagonal morphologies. The plane fringe with 0.26 nm crystalline plane spacing of three types of quantum dots is assigned to the ZnO {002} planes via HR-TEM, which match with the lattice parameter of the hexagonal wurtzite structure of ZnO and also coincide with the data obtained by XRD. By analyzing the fluorescence emission and excitation spectra of ZnO QDs, ZnO-NH2 QDs, ZnO-SBC QDs and Schiff base complexes, we find that the ZnO-SBC QDs still have a perfect fluorescence emission which makes it interesting candidates for luminescence applications such as biochemical sensors and fluorescent labels to mark the cells and DNA. This novel ZnO-SBC QDs under UV irradiation is capable of generating reactive oxygen species by UV irradiation and may be used for the photodynamic therapy. The surface modification with Schiff base complexes makes it difficult to release Zn2+, therefore the toxicity is much more controllable.

CCN1 promotes the differentiation of endothelial progenitor cells and reendothelialization in the early phase after vascular injury.

Endothelial progenitor cells (EPCs) contribute to the process of reendothelialization and prevent neointimal formation after vascular injury. The present study was designed to investigate whether the cysteine-rich 61 (CYR61, CCN1), an important matricellular component of local vascular microenvironment, has effect on EPCs differentiation and reendothelialization in response to vascular injury in rat. Following balloon injury, CCN1 was rapidly induced and dynamically changed at vascular lesions. Overexpression of CCN1 by adenovirus (Ad-CCN1) accelerated reendothelialization and inhibited neointimal formation in the early phase (day 14) after vascular injury (p < 0.05), while no effect was shown on day 21. Ad-CCN1 treatment increased the adhering EPCs on the surface of injured vessels on day 7, and the ratio of GFP- and vWF-positive area to the total luminal length on day 14 was 2.3-fold higher in the Ad-CCN1-EPC-transplanted group than in controls. Consistent with these findings, CCN1-stimulated EPC differentiation in vitro and 20 genes were found differentially expressed during CCN1-induced EPC differentiation, including Id1, Vegf-b, Vegf-c, Kdr, Igf-1, Ereg, Tgf, Mdk, Ptn, Timp2, etc. Among them, negative transcriptional regulator Id1 was associated with CCN1 effect on EPC differentiation. Our data suggest that CCN1, from the microenvironment of injured vessels, enhances reendothelialization via a direct action on EPC differentiation, revealing a possible new mechanism underlying the process of vascular repair.

Freshwater outburst from Lake Superior as a trigger for the cold event 9300 years ago.

Paleoclimate proxy records reveal a pervasive cooling event with a Northern Hemispheric extent approximately 9300 years ago. Coeval changes in the oceanic circulation of the North Atlantic imply freshwater forcing. However, the source, magnitude, and routing of meltwater have remained unknown. Located in central North America, Lake Superior is a key site for regulating the outflow of glacial meltwater to the oceans. Here, we show evidence for an approximately 45-meter rapid lake-level fall in this basin, centered on 9300 calibrated years before the present, due to the failure of a glacial drift dam on the southeast corner of the lake. We ascribe the widespread climate anomaly approximately 9300 years ago to this freshwater outburst delivered to the North Atlantic Ocean through the Lake Huron-North Bay-Ottawa River-St. Lawrence River valleys.

Inhibitor of DNA binding-1 promotes the migration and proliferation of endothelial progenitor cells in vitro.

Migration and proliferation of endothelial progenitor cells (EPCs) are the key mechanisms in re-endothelialization after vascular injury. Inhibitor of DNA binding-1 (Id1) function has been linked to the proliferation, migration, and senescence of cells, and studies have shed light on the relationship between Id1 and the biological functions of EPCs. On the basis of the available data concerning Id1 and the behavior of EPCs, we hypothesized that Id1 was an important regulator in modulating the migration and proliferation of EPCs. Culture of spleen-derived EPCs was done as previously described. Id1 was presented at low levels in EPCs. Id1 was localized predominantly in the cytoplasm, and was rapidly upregulated by stimulation with serum and vascular endothelial growth factor. The migration and proliferation of EPCs were extensively improved by overexpression of adenovirus-mediated exogenous Id1 and inhibited by silencing of endogenous Id1 in EPCs. These results suggest that Id1 has a direct role in regulation of the migration and proliferation in EPCs.

[Autologous mesenchymal stem cell implantation promotes myocardial expressions of growth factors and improves cardiac function in failing rat hearts].

OBJECTIVE: To explore the underlying mechanism of mesenchymal stem cells (MSCs) transfer induced cardiac function improvement in failing hearts. METHODS: Congestive heart failure (CHF) was induced in rats by cauterization of the heart wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 days after cauterization. RESULTS: Ten weeks later, cardiomyocyte nucleus mitotic index, capillary density and expression of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) were significantly increased in the border zone and significantly reduced in the remote myocardium in CHF rats (all P<0.05 vs. sham). Besides cardiac function improvement and left ventricular remodeling attenuation evidenced by hemodynamic and echocardiographic examinations, expressions of IGF-1, HGF and VEGF in the remote myocardium and in the border zone were also significantly upregulated (P<0.05 or P<0.01 vs. CHF), and cardiomyocyte nucleus mitotic index as well as capillary density were significantly increased in CHF rats with MSCs (P<0.05 or P<0.01 vs. CHF). Moreover, collagen area was significantly reduced and myocardial area was significantly increased in the border zone in these rats too. CONCLUSION: Autologous MSC implantation upregulated expressions of growth factors enhanced cardioangiogenesis which might be the underlying mechanisms for improved cardiac function and attenuated left ventricular remodeling induced by MSCs transplantation in failing rat myocardium.

[Effect of carvedilol and perindopril on Ca(2+) pump activity and Ca(2+)-release channel density in myocardial sarcoplasmic reticulum in rats with chronic heart failure following myocardial infarction].

OBJECTIVE: To study the effects of carvedilol combined with perindopril on Ca(2+) pump activity and the density of Ca(2+)-release channel ryanodine receptor (RyR2) in the myocardial sarcoplasmic reticulum (SR) in rats with chronic heart failure caused by myocardial infarction. METHODS: Rat models of chronic heart failure established by left coronary artery ligation were divided into different groups and treated with carvedilol (6 mg.kg(-1).d(-1)), perindopril (4 mg.kg(-1).d(-1)), terazosin (2 mg.kg(-1).d(-1)), or the combination of carvedilol (6 mg.kg(-1).d(-1)) and perindopril (4 mg.kg(-1).d(-1)) for 9 weeks. Another 12 rats with sham operation served as the sham-operated group. The hemodynamic parameters, activity of SR Ca(2+) pump, and RyR2 density were determined. RESULTS: Compared with shame-operated group, the rats with chronic heart failure showed significantly increased left ventricular end-diastolic pressure (LVEDP) (P<0.01) and decreased +dP/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Both monotherapies with carvedilol and perindopril attenuated the increment of LVEDP, and significantly increased +dp/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Combined treatment even further enhanced the therapeutic effects, whereas terazosin produced no obvious effect. The activity of SR Ca(2+) pump was strongly correlated to +dp/dtmax and -dp/dtmax (r=0.596 and 0.684, respectively, P<0.01). CONCLUSION: Prolonged treatment with beta-blocker carvedilol in combination with ACE inhibitor perindopril may improve the hemodynamic parameters, enhance Ca(2+) pump activity and increase the density of RyR2 of myocardial SR more effectively than either monotherapy in preventing and treating chronic heart failure following myocardial infarction.