An atypical two-component system, AtcR/AtcK, simultaneously regulates the biosynthesis of multiple secondary metabolites in Streptomyces bingchenggensis.

Streptomyces bingchenggensis is an industrial producer of milbemycins, which are important anthelmintic and insecticidal agents. Two-component systems (TCSs), which are typically situated in the same operon and are composed of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Here, an atypical TCS, AtcR/AtcK, in which the encoding genes (sbi_06838/sbi_06839) are organized in a head-to-head pair, was demonstrated to be indispensable for the biosynthesis of multiple secondary metabolites in S. bingchenggensis. With the null TCS mutants, the production of milbemycin and yellow compound was abolished but nanchangmycin was overproduced. Transcriptional analysis and electrophoretic mobility shift assays showed that AtcR regulated the biosynthesis of these three secondary metabolites by a MilR3-mediated cascade. First, AtcR was activated by phosphorylation from signal-triggered AtcK. Second, the activated AtcR promoted the transcription of milR3. Third, MilR3 specifically activated the transcription of downstream genes from milbemycin and yellow compound biosynthetic gene clusters (BGCs) and nanR4 from the nanchangmycin BGC. Finally, because NanR4 is a specific repressor in the nanchangmycin BGC, activation of MilR3 downstream genes led to the production of yellow compound and milbemycin but inhibited nanchangmycin production. By rewiring the regulatory cascade, two strains were obtained, the yield of nanchangmycin was improved by 45-fold to 6.08 g/L and the production of milbemycin was increased twofold to 1.34 g/L. This work has broadened our knowledge on atypical TCSs and provided practical strategies to engineer strains for the production of secondary metabolites in Streptomyces.IMPORTANCEStreptomyces bingchenggensis is an important industrial strain that produces milbemycins. Two-component systems (TCSs), which consist of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Coupled encoding genes of TCSs are typically situated in the same operon. Here, TCSs with encoding genes situated in separate head-to-head neighbor operons were labeled atypical TCSs. It was found that the atypical TCS AtcR/AtcK played an indispensable role in the biosynthesis of milbemycin, yellow compound, and nanchangmycin in S. bingchenggensis. This atypical TCS regulated the biosynthesis of specialized metabolites in a cascade mediated via a cluster-situated regulator, MilR3. Through rewiring the regulatory pathways, strains were successfully engineered to overproduce milbemycin and nanchangmycin. To the best of our knowledge, this is the first report on atypical TCS, in which the encoding genes of RR and HK were situated in separate head-to-head neighbor operons, involved in secondary metabolism. In addition, data mining showed that atypical TCSs were widely distributed in actinobacteria.

Monitoring trends in the absolute lymphocyte count and the neutrophil-to-lymphocyte ratio in patients with breast cancer receiving eribulin.

BACKGROUND: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes. METHODS: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival. RESULTS: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals. CONCLUSION: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.

Does the Timing of Eribulin Treatment for Advanced or Metastatic Breast Cancer Matter? Evidence from a Real-World Setting.

BACKGROUND: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients. METHODS: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed. RESULTS: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%). CONCLUSIONS: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.

The development of a Chinese Healthy Eating Index for School-age Children and its Application in children from China Health and Nutrition Survey.

This study aimed to develop a Chinese Healthy Eating Index for School-age Children (CHEI-SC), apply it in the 2011 China Health and Nutrition Survey (CHNS) to assess dietary quality, and compared it with our former developed index named CHEI. Data of 3-day 24-hour diet recalls and household food inventory survey from 1600 school-age children in CHNS-2011 were used to develop the CHEI-SC, using the methods of standard portion size, energy-density-based approach, and least restrictive approach. The CHEI-SC included 19 components with a total score (T-score) ranging from 0 to 100. The investigated children had a median score of 49.6. Children with a higher T-score were more likely to have higher social economic status (SES), higher level of urbanisation, fewer family size, and regularly attending school. The CHEI-SC was able to assess dietary quality of Chinese school-age children, was sensitive to demographics, and more comprehensive and accurate than the CHEI.

Association of Dietary Pattern during Pregnancy and Gestational Diabetes Mellitus: A Prospective Cohort Study in Northern China.

OBJECTIVE: To examine the association of maternal dietary patterns during pregnancy with gestational diabetes mellitus (GDM) in northern China. METHODS: The dietary intakes of pregnant women were recorded twice by 24-hour dietary recalls for three days prior to having been diagnosed with GDM, at 5-15 and 24-28 gestational weeks, respectively. GDM was diagnosed, and serum glycosylated hemoglobin (HbA1c) was measured at 24-28 weeks. Dietary patterns were assessed by factor analysis. The association of the dietary pattern with GDM and HbA1c was examined by multiple logistic models. RESULTS: Of 753 participants, 64 (8.5%) were diagnosed with GDM. Four dietary patterns were identified: Western pattern (dairy, baked/fried food and white meat), traditional pattern (light-colored vegetables, fine grain, red meat and tubers), mixed pattern (edible fungi, shrimp/shellfish and red meat) and prudent pattern (dark-colored vegetables and deep-sea fish). Compared with the prudent pattern, both the Western pattern and the traditional pattern were associated with an increased risk of GDM (aOR = 4.40, 95% CI: 1.58-12.22; aOR = 4.88, 95% CI: 1.79-13.32) and a high level of HbA1c (aOR = 12.37, 95% CI: 1.47-103.91; aOR = 26.23, 95% CI: 2.54-270.74). Compared to the lowest quartile (Q), Q3 of the Western pattern scores and Q3-Q4 of the traditional pattern scores were associated with a higher risk of GDM. CONCLUSION: The consumption of the Western pattern or the traditional pattern during pregnancy may increase the risk of GDM.

Room-Temperature Continuous-Wave Microcavity Lasers from Solution-Processed Smooth Quasi-2D Perovskite Films with Low Thresholds.

Continuous-wave (CW) lasing in quasi-two-dimensional (2D) perovskite-based distributed feedback cavities has been achieved at room temperature; however, CW microcavity lasers comprising distributed Bragg reflectors (DBRs) have rarely been prepared using solution-processed quasi-2D perovskite films because the roughness of perovskite films significantly increases intersurface scattering loss in the microcavity. Herein, high-quality spin-coated quasi-2D perovskite gain films were prepared using an antisolvent to reduce roughness. The highly reflective top DBR mirrors were deposited via room-temperature e-beam evaporation to protect the perovskite gain layer. Lasing emission of the prepared quasi-2D perovskite microcavity lasers under CW optical pumping was clearly observed at room temperature, featuring a low threshold of ∼1.4 W cm-2 and beam divergence of ∼3.5°. It was concluded that these lasers originated from weakly coupled excitons. These results elucidate the importance of controlling the roughness of quasi-2D films to achieve CW lasing, thus facilitating the design of electrically pumped perovskite microcavity lasers.

[Investigation on the levels of carbon-, nitrogen-, iodine-containing disinfection by-products in a water plant in Jiangsu province, China].

OBJECTIVE: This work aimed to investigate the carbon-, nitrogen-, iodine-containing disinfection by-products (DBPs) formation and pollution situation in different treatment processes and pipe water of a water plant in Jiangsu province China. METHODS: 12 water samples were collected from raw water, different time points after the addition of chlorine, finished water and pipe water in July, 2011. Trihalomethanes (THM(4)), haloacetic acids (HAA(6)), haloacetonitriles (HAN(s)), chloropicrin (CPs), haloketones (HK(s)), iodoform (IF) and iodoacetic acid (IAA) were detected by gas chromatography with electron capture detector (GC-ECD) after liquid-liquid extraction. Nitrosamines (NAms) were detected by gas chromatography with mass spectrometer (GC-MS) after solid-phase extraction. The concentration of DBPs was represented as the mean of duplicate samples. RESULTS: Most DBPs were found in water treatment processes except dibromochloromethane (0.61 µg/L), chloroform (1.64 µg/L) and N-nitrosodimethylamine (3.06 ng/L), which were detected in raw water. Pre-chlorination formed HAA(6) (5.01 µg/L), HKs (0.66 µg/L), HANs (0.57 µg/L) and NAms (98.09 ng/L). Chlorination and post-chlorination led to a dramatic increase in the levels of THM(4), HAA(6) (70.31 and 43.71 µg/L, respectively), while Nams didn't increase. In finished water, bromodichloromethane (34.12 µg/L) had the highest concentration among THM(4) (70.31 µg/L), and so was trichloroacetic acid (13.45 µg/L) among HAA(6) (43.71 µg/L). Levels of HANs, HKs, and CPs were 14.96, 2.32, 0.96 µg/L, respectively. Levels of N-nitrosodimethylamine and N-nitrosodipropylamine were 21.22, 69.43 ng/L, respectively. IAA, IF and other six NAms including N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, N-nitrosomorpholine, N-nitrosopiperidine and N-nitrosodibutylamine were not detected in all water samples. CONCLUSION: Levels of DBPs in this water plant are relative high.and measures should be taken to control DBPs.

Estimating Carbon Sequestration Potential of Forest and Its Influencing Factors at Fine Spatial-Scales: A Case Study of Lushan City in Southern China.

Accurate prediction of forest carbon sequestration potential requires a comprehensive understanding of tree growth relationships. However, the studies for estimating carbon sequestration potential concerning tree growth relationships at fine spatial-scales have been limited. In this paper, we assessed the current carbon stock and predicted sequestration potential of Lushan City, where a region has rich vegetation types in southern China, by introducing parameters of diameter at breast height (DBH) and tree height in the method of coupling biomass expansion factor (BEF) and tree growth equation. The partial least squares regression (PLSR) was used to explore the role of combined condition factors (e.g., site, stand, climate) on carbon sequestration potential. The results showed that (1) in 2019, the total carbon stock of trees in Lushan City was 9.22 × 105 t, and the overall spatial distribution exhibited a decreasing tendency from northwest to south-central, and the carbon density increased with elevation; (2) By 2070, the carbon density of forest in Lushan City will reach a relatively stable state, and the carbon stock will continue to rise to 2.15 × 106 t, which is 2.33 times of the current level, indicating that Lushan forest will continue to serve as a carbon sink for the next fifty years; (3) Excluding the effect of tree growth, regional forest carbon sequestration potential was significantly influenced on site characteristics, which achieved the highest Variable Importance in Projection (VIP) value (2.19) for slope direction. Our study provided a better understanding of the relationships between forest growth and carbon sequestration potential at fine spatial-scales. The results regarding the condition factors and how their combination characteristics affect the potential for carbon sequestration could provide crucial insights for Chinese carbon policy and global carbon neutrality goals.

Estimation of the bio-accessibility of methylmercury from aquatic foods using a PBTK model with an approximate Bayesian computation method in Chinese pregnant women.

BACKGROUND: Fish are the primary source of protein and docosahexaenoic acid (DHA) for pregnant women and children, but methylmercury (MeHg) pollution is the potential hazard of fish consumption. In risk assessments, the bio-accessibility of MeHg is usually assumed to be 100%, which could lead to overestimation of dietary exposure. METHOD: An existing PBTK model was adapted to estimate parameters of the bio-accessibility based on MeHg exposure data from a cohort of 397 Chinese pregnant women. The posterior distributions of parameters were determined by using the ABC - MCMC. RMSEP and Spearman's rank correlation coefficients (Rho) were calculated to determine the goodness of model fitting. The Monte Carlo analysis was performed for the parameter distributions to estimate the model variability. RESULT: The median of daily MeHg intake and maternal MeHg levels were 0.018 µg/kg bw and 3.01 µg/kg in the early and middle terms of pregnancy. The estimated bio-accessibility of freshwater fish, marine fish and others were 46.1, 17.3 and 58.2%, separately. The RMSEP improved from 11.18 to 2.54 and the Rho improved from 0.19 to 0.22 after bio-accessibility optimization. The model variability was estimated to be 2.6. CONCLUSION: The bio-accessibility estimated in this study was comparable to that determined in previous in vitro studies. The optimized model could improve the prediction performance on the MeHg body burden by dietary exposure.

Modes of Transport to School and Their Associations with Weight Status: A Cross-Sectional Survey of Students in Shanghai, China.

Background: Over the past two decades, both transport modes as well as overweight/obesity have changed dramatically among students in China, but their relationships are not clear. This study aimed to investigate modes of transport to school and their associations with the weight status of Chinese students. Methods: A cross-sectional study was conducted with non-resident students aged 6 to 17 years from all 16 districts across Shanghai, China in October and November 2019. Information about sociodemographic characteristics and the models of travel to school among students was investigated using an online, self-administered, structured questionnaire (or those assisted by their parents). Weight and height were measured by school health workers, and the Chinese standard age adjusted BMI (weight/height2) was used to classify students' weight status. Cumulative logistic regression modelling was used to examine the relationships. Results: The main mode of transport to school was an active mode (46.5%, defined as walking, bicycling, or public transport), followed by an inactive mode of transport (30.5%, defined as a car or bicycle as a passenger), and a combination of both modes (23%). About one-third of the students were overweight or obese and 5% were underweight. No statistically significant association between transport modes and weight status was found in this study. Conclusions: In Shanghai, close to one-third of children travel to school by an inactive mode of transport. The findings of this study did not support the notion that an active mode to school could be beneficial for preventing overweight/obesity in students in China.

Evaluation of the Validity and Reliability of the Chinese Healthy Eating Index.

The Chinese Healthy Eating Index (CHEI) is a measuring instrument of diet quality in accordance with the Dietary Guidelines for Chinese (DGC)-2016. The objective of the study was to evaluate the validity and reliability of the CHEI. Data from 12,473 adults from the China Health and Nutrition Survey (CHNS)-2011, including 3-day-24-h dietary recalls were used in this study. The CHEI was assessed by four exemplary menus developed by the DGC-2016, the general linear models, the independent t-test and the Mann-Whitney U-test, the Spearman's correlation analysis, the principal components analysis (PCA), the Cronbach's coefficient, and the Pearson correlation with nutrient intakes. A higher CHEI score was linked with lower exposure to known risk factors of Chinese diets. The CHEI scored nearly perfect for exemplary menus for adult men (99.8), adult women (99.7), and the healthy elderly (99.1), but not for young children (91.2). The CHEI was able to distinguish the difference in diet quality between smokers and non-smokers (P < 0.0001), people with higher and lower education levels (P < 0.0001), and people living in urban and rural areas (P < 0.0001). Low correlations with energy intake for the CHEI total and component scores (|r| < 0.34, P < 0.01) supported the index assessed diet quality independently of diet quantity. The PCA indicated that underlying multiple dimensions compose the CHEI, and Cronbach's coefficient α was 0.22. Components of dairy, fruits and cooking oils had the greatest impact on the total score. People with a higher CHEI score had not only a higher absolute intake of nutrients (P < 0.001), but also a more nutrient-dense diet (P < 0.001). Our findings support the validity and reliability of the CHEI when using the 3-day-24-h recalls.

Supercritical Fluid-Assisted Fabrication of Indocyanine Green-Encapsulated Silk Fibroin Nanoparticles for Dual-Triggered Cancer Therapy.

Despite the success and advantages over traditional chemotherapeutic strategies, photothermal therapy (PTT) suffers from certain limitations, such as poor stability, low therapeutic efficacy of PTT agents in vivo, and their affinity loss during the multistep synthesis process of delivery carriers, among others. To address these limitations, we designed a stable, biocompatible, and dual-triggered formulation of indocyanine green (ICG)-encapsulated silk fibroin (SF) (ICG-SF) nanoparticles using supercritical fluid (SCF) technology. We demonstrated that ICG encapsulation in SF through this environmental-friendly approach has offered excellent photothermal stability, the pH-responsive release of ICG from SF specifically in the tumor acidic environment, and its substantial activation with near-infrared (NIR) light at 808 nm significantly enhanced the PTT efficiency. In vitro and in vivo photothermal experiments have shown that these ICG-SF nanoparticles were capable of devastating tumor cells merely under light-induced hyperthermia. Together, these results have suggested that the biocompatible ICG-SF nanoparticles prepared by the SCF process resulted in high PTT efficiency and may have a great potential as a delivery system for sustained cancer therapy.

[COX-2 and mPGES-1 expression in carotid atherosclerotic plaques].

OBJECTIVE: To investigate the changes in the expressions of inducible cyclooxygenase type 2 (COX-2) and membrane associated prostaglandin E-1(mPGES-1) in human carotid atherosclerotic plaques and to explore possible mechanisms of inflammatory process involved in plaque stability. METHODS: The mRNA and protein levels of COX-2 and mPGES-1 were compared between minimally and grossly atherosclerotic arterial tissues. COX-2 and mPGES-1 gene expression were established by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) in 10 mesenchymal artery controls and 24 atherosclerotic specimens. Presence of COX-2 and mPGES-1 protein was assessed by Western blotting. RESULTS: Immunohistochemical staining showed that the COX-2 and mPGES-1 immunoreactive substances were present in the cytoplasm of smooth muscle cell. Compared with the control group, immunostaining positive cells increased in carotid atherosclerotic plaque group. COX-2 and mPGES-1 gene expression was significantly elevated in atherosclerotic plaques (P< 0.05, respectively). The increased mRNA and protein levels of COX-2 and mPGES-1 were correlated in atherosclerotic tissue (P< 0.05). The mRNA and protein levels of COX-2 and mPGES-1 related to degree of pathological damage in atherosclerotic tissue (P< 0.05). COX-2 and mPGES-1 were not found in the control group (mesenteric vascular walls). CONCLUSION: COX-2 and mPGES-1 expression in plaques is significantly higher than that in the control group. These findings suggests that COX-2 and mPGES-1 might play a role in pathogenesis of atheroscleros and modulation of inflammatory process involved in plaque stability, and COX-2 may have proinflammatory enzyme properties.

The Development of a Chinese Healthy Eating Index and Its Application in the General Population.

The objective of this study was to develop a Chinese Healthy Eating Index (CHEI) based on the updated Dietary Guidelines for Chinese (DGC-2016) and to apply it in the 2011 China Health and Nutrition Survey (CHNS-2011) to assess diet quality and its association with typical sociodemographic/economic factors. Data from 14,584 participants (≥2 years) from the CHNS-2011, including three 24-h dietary recalls and additional variables, were used to develop the CHEI. The standard portion size was applied to quantify food consumption. The CHEI was designed as a continuous scoring system, comprising 17 components; the maximum total score is 100. The mean, 1st and 99th percentiles of the CHEI score were 52.4, 27.6 and 78.3, respectively. Young and middle-aged adults scored better than the elderly. Diet insufficiency was chiefly manifested in fruits, dairy, whole grains and poultry; diet excess was mainly reflected in red meat, cooking oils and sodium. The CHEI was positively associated with education and urbanization levels; current smokers and unmarried people obtained relative low CHEI scores. Occupation and body mass index (BMI) were also related to the CHEI. Our findings indicate that the CHEI is capable of recognizing differences in diet quality among the Chinese, and it is sensitive to typical sociodemographic/economic factors.

Comparison of the Clinical Efficacy of Retroperitoneal Laparoscopic Partial Nephrectomy and Radical Nephrectomy for Treating Small Renal Cell Carcinoma: Case Report and Literature Review.

BACKGROUND: Renal cell carcinoma (RCC) is a common malignancy of the urinary system with high rates of morbidity and mortality. OBJECTIVES: This study aimed to investigate and analyze the clinical efficacy of retroperitoneal laparoscopic partial nephrectomy and laparoscopic radical nephrectomy for the treatment of small RCC. METHODS: In this retrospective study of 45 patients with small RCC, the patients were divided into two treatment groups: Group A (retroperitoneal laparoscopic partial nephrectomy, 25 cases) and Group B (retroperitoneal laparoscopic radical nephrectomy, 20 cases). RESULTS: There were no statistically significant differences in the operative time, amount of intraoperative blood loss, length of hospital stay, preoperative creatinine level, postoperative creatinine level after 24 hours, and survival rate after 1, 2, and 3 years between the two groups (P > 0.05). CONCLUSIONS: There were no significant differences in the survival rates and short-term postoperative complications between the laparoscopic partial nephrectomy group and the laparoscopic radical nephrectomy group for small RCC, but the former was slightly more effective.

The antihypertensive effect of ethyl acetate extract from red raspberry fruit in hypertensive rats.

OBJECTIVES: To evaluate the antihypertensive effect of Xinjiang red raspberry fruit ethyl acetate extract (EER) on spontaneously hypertensive rats (SHR) and its possible mechanism from antioxidant perspective. MATERIALS AND METHODS: The SHR rats were randomly divided into 3 groups, and treated with EER low dose (EERL, 100 mg/kg/d), high dose (EERH, 200 mg/kg/d), and water (SHR) through gastric gavage daily for 5 weeks. Another 8 age-matched male Wistar-Kyoto rats were used as normotensive group (WKY). The systolic blood pressure (SBP) was measured by noninvasive tail-cuff method once a week. At the end of the treatment, blood samples were collected and serum concentrations of nitric oxide (NO), superoxide dismutase (SOD), malondialchehyche (MDA), and plasma endothelin (ET) were determined. RESULTS: Treatment of SHR rats with EER lowered the blood pressure compared with that treated with water (SHR), and the high dose showed more significant reduction in blood pressure. Treatment of SHR rats with EER increased serum NO and SOD levels and lowered ET and MDA levels. As compared with control group, NO levels were increased significantly in EERL (P < 0.01), SOD was elevated more significantly in both EERL and EERH (P < 0.01); MDA was decreased significantly in EERH group (P < 0.05), whereas plasma ET decreased more significantly in the EERH group (P < 0.05). CONCLUSIONS: The red raspberry extracts demonstrated a dose-dependent antihypertensive effects in SHR and this may be related to increased NO activation and improved vascular endothelial dysfunction via antioxidation. These results confirmed that raspberries rich in polyphenols have potential cardiovascular protective effects.