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Deep rooting is an important trait in rice drought resistance. Genetic resources of deep-rooting varieties are valuable in breeding of water-saving and drought-resistant rice. In the present study, 234 BC2F7 backcross introgression lines were derived from a cross of Dongye 80 (an accession of Dongxiang wild rice as the donor parent) and R974 (an indica restorer line as the recurrent parent). A genetic linkage map containing 1 977 bin markers was constructed by ddRADSeq for QTL analysis. Thirty-one QTLs for four root traits (the number of deep roots, the number of shallow roots, the total number of deep roots and the ratio of deep roots) were assessed on six rice chromosomes in two environments (2020 Shanghai and 2021 Hainan). Two of the QTLs, qDR5.1 and qTR5.2, were located on chromosome 5 in a 70-kb interval. They were detected in both environments. qDR5.1 explained 13.35% of the phenotypic variance in 2020 Shanghai and 12.01% of the phenotypic variance in 2021 Hainan. qTR5.2 accounted for 10.88% and 10.93% of the phenotypic variance, respectively. One QTL (qRDR2.2) for the ratio of deep roots was detected on chromosome 2 in a 210-kb interval and accounted for 6.72% of the phenotypic variance in 2020. The positive effects of these three QTLs were all from Dongxiang wild rice. Furthermore, nine and four putative candidate genes were identified in qRDR2.2 and qDR5.1/qTR5.2, respectively. These findings added to our knowledge of the genetic control of root traits in rice. In addition, this study will facilitate the future isolation of candidate genes of the deep-rooting trait and the utilization of Dongxiang wild rice in the improvement of rice drought resistance.

During the transition from embryonic to adult life, the sites of hematopoiesis undergo dynamic shifts across various tissues. In adults, while bone marrow becomes the primary site for definitive hematopoiesis, the establishment of the bone marrow niche for accommodating hematopoietic stem cells (HSCs) remains incompletely understood. Here, we reveal that perinatal bone marrow mesenchymal stem cells (BMSCs) exhibit highly activated insulin-like growth factor 1 receptor (IGF1R) signaling compared to adult BMSCs. Deletion of Igf1r in perinatal BMSCs hinders the transition of HSCs from the fetal liver to the bone marrow in perinatal mice and disrupts hematopoiesis in adult individuals. Conversely, the deletion of Igf1r in adult BMSCs, adipocytes, osteoblasts, or endothelial cells does not affect HSCs in the bone marrow. Mechanistically, IGF1R signaling activates the transcription factor nuclear factor of activated T cells c1 (NFATc1) in perinatal BMSCs, which upregulates CXCL12 and other niche factors for HSC retention. Overall, IGF1R signaling in perinatal BMSCs regulates the development of the bone marrow niche for hematopoiesis., (Copyright © 2024 American Society of Hematology.)

Crocins are bioactive natural products that rarely exist in plants. High costs and resource shortage severely limit its development and application. Synthetic biology studies on crocins are of considerable global interest. However, the lack of high-efficiency genetic tools and complex cascade biocatalytic systems have substantially hindered progress in crocin biosynthesis-related research. Based on mutagenesis, a high-efficiency GjCCD4a mutant (N212m) was constructed with a catalytic efficiency that was 25.08-fold higher than that of the wild-type. Solubilized GjCCD4a was expressed via fusion with an MBP tag. Moreover, N212m and ten other genes were introduced into Escherichia coli for the de novo biosynthesis of five crocins. The engineered E57 strain produced crocins III and V with a total yield of 11.50 mg/L, and the E579 strain produced crocins I-V with a total output of 8.43 mg/L at shake-flask level. This study identified a marvelous genetic element (N212m) for crocin biosynthesis and achieved its de novo biosynthesis in E. coli using glucose. This study provides a reference for the large-scale production of five crocins using E. coli cell factories., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The construction of simple, stable, low-cost and reproducible enzyme-free electrochemical biosensors can effectively avoid the problem of signal attenuation caused by enzyme inactivation. Hererin, we prepared a novel nanoenzymes PdPtCu mesoporous nanocubes (MNCs) to construct a label-free sandwich electrochemical immunosensor for the highly sensitivity detection of HIV-p24. PdPtCu MNCs have excellent peroxidase activity against hydrogen peroxide (H 2 O 2 ) due to their synergistic ternary composition, large surface area and ability to penetrate mesoporous channels. Moreover, highly conductive and biocompatible gold nanoparticles@graphene oxide (AuNPs@GO) was introduced as a substrate to modify a glassy carbon electrode (GCE). Owing to the excellent electrochemical performance of the PdPtCu MNCs and AuNPs@GO, the developed immunosensors exhibited a good linear response from 0.04 pg/mL to 100 ng/mL with a low detection limit of 20 fg/mL. In addition, the established method exhibited excellent practical performance in human serum. This novel strategy provides a promising platform for ultrasensitive detection of the HIV-p24 in the field of clinical diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diagnostic features in near-infrared reflectance spectroscopy (NIRS) are the foundation of knowledge-based approach of petroleum hydrocarbon determination. However, a significant challenge arises when analyzing samples with low levels of petroleum hydrocarbon pollution, as they often lack distinctive diagnostic features in their sample NIRS spectra, limiting the effectiveness of this approach. To address this issue, we have developed a technical workflow for diagnostic spectrum construction and parameterization based on spectral subtraction. This method was applied on a set of NIRS spectra from soil samples that were contaminated with petroleum hydrocarbons (ranged between 178 and 1716 mg/kg of total petroleum hydrocarbon). Then two diagnostic features for low-level petroleum hydrocarbon pollution were found: (1) An overall downward concave emerged on diagnostic spectrum within both 2290-2370 nm and 1700-1780 nm for all low pollution levels even below 200 mg/kg; (2) An indicative pattern of asymmetric "W-shaped" double absorption valley occurred for those exceeding 1000 mg/kg, and its valleys located near 2310 nm, 2348 nm or 1727 nm, 1762 nm stably. These two features on diagnostic spectrum could be parameterized to detect, and the detection limit was at least about 10-50 times lower than that based on sample spectrum. These findings update our understanding on the detectability of spectral response from low petroleum hydrocarbon pollution, and widely extend the application of knowledge-based NIRS approach in either field detection or remote sensing identification for environmental management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Coral reefs worldwide have faced extensive damage due to natural catastrophes and anthropogenic disturbances.The decline can cause their widespread collapse and an inability to recover from natural disturbances, highlighting the urgent need for their protection. This study conducted an extensive ecological condition assessment of seven coral reef regions in China's offshore. Our findings revealed the presence of 204 species of scleractinian corals belonging to 16 families. Massive corals were the predominant reef-building corals in all regions. The degradation of coral reef ecosystems was apparent in the present compared to historical reef conditions. The ecosystem suffered varying degrees of damage in surveyed regions according to a novel assessment approach, impling more effective measures should be taken to mitigate the local pressures. Our research establishes a baseline for understanding the status of coral reefs that can be used in future and provides a crucial foundation to designate protective zones for their conservation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yihua Lyu reports financial support was provided by National Key Research and Development Project. Yihua Lyu reports financial support was provided by Young Talent Program of MNS. Yihua Lyu reports financial support was provided by National Investigation on Coral Reefs Ecology. Zhenxiong Yang reports financial support was provided by Science and Techology Plan Projects of Guangdong Province., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ecological risk assessment of emerging contaminants (ECs) is an international research hotspot and is also the focus of China's "14th Five-Year Plan". The Greater Bay Area (GBA) is one of the four major bay areas in the world and the most dynamic region in China. However, there are few studies on the risk assessment of ECs in the GBA, and there needs to be a systematic and comprehensive assessment of the ecological risk of ECs. We selectively collected environmental concentration and toxicity data reported in the literature before 2022 for 50 representative ECs. We use risk quotient (RQ), semi-probability, Margin of Safety (MOS), and joint Probability curve (JPC) methods for multiple-level risk assessment. The RQ results showed that there were primary ecological risks in 20 ECs. Nine ECs were screened by the semi-probability, MOS, and JPC methods. The total risk probability of nonylphenol (NP) to the GBA was 12.11 %, and the risk to the aquatic ecological environment was the highest, followed by α-endosulfan (α-END) and erythromycin (ERY). At the same time, a comprehensive assessment method was adopted to screen the list of medium and high-risk priority pollutants in the GBA. According to the comprehensive evaluation results, although the risk is low, perfluorooctanoic acid (PFOA) still deserves widespread attention. The results showed that NP, α-END, ERY, and PFOA may be the most concerned ECs in the GBA. This research fills the gap on the ECs ecological risk assessment of the GBA and can provide a theoretical reference for managers in the follow-up of ECs regulatory governance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Accurate assignment of 19 F NMR has long been a challenge, and quantum chemical methods are possible solutions. Herein we reported a scaling method for the prediction of 19 F NMR chemical shift with freely available ORCA program package. Performance of 31 DFT functionals coupled with 11 basis sets were evaluated and influence of geometry optimization was also studied with five functionals coupled with three basis sets. The significance of geometry was further examined through the execution of relaxed surface scans of seven flexible compounds, and averaged shieldings of obtained conformers yielded notable improvement of the correlation between calculated isotropic shielidings and experimental chemical shifts. Utilization of the best scaling factor obtained successfully assigned of fluorine atoms in multifluorinated molecules with different conformations. The method reported here was computationally inexpensive, easily available with acceptable accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Histones are essential components of chromatin and play an important role in regulating gene transcription and participating in DNA replication. Here, we performed a comprehensive analysis of this gene family. In this study, we identified 37 CsHistones that were classified into five groups (H1, H2A, H2B, H3 and H4). The closely linked subfamilies exhibited more similarity in terms of motifs and intron/exon numbers. Segmental duplication (SD) is the main driving force of cucumber CsHistones expansion. Analysis of cis-regulatory elements in the promoter region of CsHistones showed that CsHistones can respond to a variety of stresses. RNA-Seq analysis indicated that the expression of most CsHistones was associated with different stresses, including downy mildew, powdery mildew, wilt, heat, cold, salt stress, and waterlogging. Expression analysis showed that several genes of H3 group were highly expressed in different reproductive organs. Notably, CsCENH3 (CsHistone30) has the characteristics of a variant histone, and we demonstrated that CsCENH3 was localized on the nucleus and its proteins were expressed in centromere region. These findings provide valuable information for the identification and potential functions of Histone genes and ideas for the cultivation of CENH3-mediated haploid induction lines in cucumber., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Early accurate mammography screening and diagnosis can reduce the mortality of breast cancer. Although CNN-based breast cancer computer-aided diagnosis (CAD) systems have achieved significant results in recent years, precise diagnosis of lesions in mammogram remains a challenge due to low signal-to-noise ratio (SNR) and physiological characteristics. Many researchers achieved excellent performance in detecting mammographic images by inputting region of interest (ROI) annotations while ROI annotations require a great quantity of manual labor, time and resources. We propose a two-stage method that combines images preprocessing and model optimization to address the aforementioned challenges. Firstly, we propose the breast database preprocess (BDP) method to preprocess INbreast then we get INbreast † . The only label we need is benign or malignant label of one mammogram, not manual labeling such as ROI annotations. Secondly, we apply focal loss to ECA-Net50 which is an improved model based on ResNet50 with efficient channel attention (ECA) module. Our method can adaptively extract the key features of mammograms, meanwhile solving the problem of hard-to-classify samples and unbalanced categories. The AUC value of our method on INbreast † is 0.960, accuracy is 0.929, Recall is 0.928. The precision of our method on INbreast † is 0.883 which improved by 0.254 compared to ResNet50. In addition, we use Grad-CAM to visualize the effect of our model. The visualized heatmaps extracted by our method can focus more on lesion regions. Both numerical and visualized experiments demonstrate that our method achieves satisfactory performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effect of Urinary albumin creatinine ratio (UACR) on diabetic retinopathy (DR) in People with Type 2 diabetes (T2D) and the cut-off value of UACR for predicting DR using receiver operating characteristic curve (ROC)., Methods: A prospective cohort study of 2490 people with T2D was conducted with follow-up ranging from 3 to 10 years, with a mean follow-up of 7 years. Dilated fundus examination and urine examination were performed annually. Medical history and clinical data were collected and analyzed. Linear mixed effect models with unstructured variance-covariance were carried out to longitudinally assess the influence of UACR and other factors on DR, and ROC curve was drawn to evaluate the value of UACR in early diagnosis of DR., Results: Linear Mixed-effect models revealed that UACR was positively correlated with the development of DR (β = 0.001, 95 %CI: 1.023-1.241, P < 0.001). The area under the ROC curve for UACR was 0.634 (95 %CI: 0.605-0.664, P < 0.001), cut-off value for early diagnosis of DR was 27.81 mg/g, the sensitivity was 0.586, and the specificity was 0.632., Conclusion: UACR can predict the occurrence of DR in people with T2D, so it can be considered as a preliminary indicator of DR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Exposure to inorganic or organic arsenic compounds continues to pose substantial public health concerns for hundreds of millions of people around the globe. Highly exposed individuals are susceptible to various illnesses, including impairments and cancers of the lung, liver, skin and bladder. Long-term exposure to low-dose arsenic has been identified to induce aerobic glycolysis, which contributes to cells aberrant proliferation. However, the mechanism underlying arsenic-induced aerobic glycolysis is still unclear. Here, mtDNA copy number is enhanced in arsenic-exposed populations and a positive correlation between serum HK2 and urinary total arsenic was observed in the individuals with high urine arsenic (≥ 0.032 mg/L). In a rat model of trivalent arsenic (iAs 3+ ) exposure, the levels of HK2, NDUFA9 and NDUFB8 were increased in the rats treated with iAs 3+ daily by gavage for 12 weeks than those in the control rats. Subsequently, in a low-dose arsenic exposure cell model we found that 0.2 μmol/L iAs 3+ induced aerobic glycolysis to promote L-02 cells proliferation and inhibit apoptosis, in which HK2 played an important role. Further studies showed accumulated ROS determined the metabolic reprogramming via activating AKT and then increasing HK2 expression. On the one hand, activated AKT induced aerobic glycolysis by increasing HK2 to promote L-02 cells viability and DNA synthesis; on the other hand, phosphorylated AKT induced HK2 mitochondrial outer-membrane location with VDAC1 to inhibit apoptosis. Taken together, our results indicated that ROS induced by low-dose arsenic exposure determined energy metabolic reprogramming and acted a critical regulator for AKT-dependent HK2 expression and aerobic glycolysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Long term low dose exposure of arsenic has been reported to lead various cells proliferation and malignant transformation. GLUT1, as the key transporter of glucose, has been reported to have association with rapid proliferation of various cells or tumor cells. In our study, we found that low dose exposure to arsenic trioxide (0.1μmol/L As 2 O 3 ) could induce an increase in glucose uptake and promote cell viability and DNA synthesis. And, 2-DG, a non-metabolized glucose analog, significantly decreased the glucose uptake and cell proliferation of 0.1μmol/L As 2 O 3 treated L-02 cells. However, 4 mmol/L 2-DG was co-utilized with equal dose glucose had no significant effect on the cell proliferation of 0.1μmol/L As 2 O 3 treated L-02 cells. Further studies showed that exposure to 0.1μmol/L As 2 O 3 could promote the expression of GLUT1 on plasma membrane. Inhibition of GLUT1 expression by 5μmol/L BAY-876 significantly decreased the abilities of glucose uptake and cell proliferation in As 2 O 3 -treated L-02 cells. Moreover, 0.1μmol/L As 2 O 3 induced the AKT activation indicated by increased the phospho-AKT (Ser473 and Thr308). Knockdown AKT by shRNA or inhibited AKT activation by LY294002 was followed by significantly decreased glucose uptake, GLUT1 plasma membrane expression and cell proliferation in As 2 O 3 -treated L-02 cells. All in all, these results demonstrated that arsenic trioxide-induced AKT activation contributed to the cells proliferation through upregulating expression of GLUT1 on plasma membrane that enhanced glucose uptake., (Copyright © 2022 Elsevier B.V. All rights reserved.)

As a new type of environmental pollutant, environmental antibiotic residues have attracted widespread attention, and the degradation and removal of antibiotics has become an engaging topic for scholars. In this paper, Novozym 51003 industrialized laccase and syringaldehyde were combined to degrade sulfonamides in aquaculture wastewater. Design Expert10 software was used for multiple regression analysis, and a response surface regression model was established to obtain the optimal degradation parameters. In the actual application, the degradation system could maintain a stable performance within 9 h, and timely supplement of the mediator could achieve a better continuous degradation effect. Low concentrations of heavy metals and organic matter would not significantly affect the degradation performance of the laccase-mediator system, making the degradation system suitable for a wide range of water quality. Enzymatic reaction kinetics demonstrated a strong affinity of sulfadiazine to the substrate. Ten degradation products were speculated using high-resolution mass spectrum based on the mass/charge ratios and the publication results. Four types of possible degradation pathways of sulfadiazine were deduced. This work provides a practical method for the degradation and removal of sulfonamide antibiotics in actual sewage., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bone marrow-derived mesenchymal stem cells (BMSCs) support bone formation and constitute the stromal niche in regulating hematopoietic stem cells (HSCs). Stromal niche dysfunction affects HSC engraftment during transplantation; however, the underlying mechanisms remain elusive. In the present study, we found that all-trans retinoic acid (ATRA) and inflammation stress upregulated retinoic acid-inducible gene I (RIG-I) in BMSCs. Excess RIG-I expression damaged the clonogenicity, bone-forming ability of BMSCs and particularly their stromal niche function that supports HSC expansion in vitro and engraftment in vivo. Mechanistically, RIG-I elevation promoted the degradation of NRF2, a checkpoint for antioxidant cellular response, by altering the RIG-I-Trim25-Keap1-NRF2 complex, leading to reactive oxygen species (ROS) accumulation and BMSC damage. Genetic inhibition of RIG-I sustained NRF2 protein levels and reduced ROS levels in ATRA-treated BMSCs, thus preserving their clonogenicity, bone-forming ability, and stromal niche function in supporting HSC engraftment in mice. More importantly, RIG-I inhibition recovered the ATRA-treated stromal niche function to enhance HSC engraftment and emergency myelopoiesis for innate immunity against the bacterium Listeria monocytogenes during transplantation. Overall, we identified a noncanonical role of RIG-I in the regulation of the stromal niche for HSC transplantation., (© 2022 by The American Society of Hematology.)

Background: The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram (EGM) substrates of Brugada syndrome (BrS) have not been elucidated., Objective: The purpose of this study was to determine the effect of ajmaline and high pacing rate on the BrS substrates., Methods: Thirty-two patients with BrS (mean age 40 ± 12 years) and frequent ventricular fibrillation episodes underwent right ventricular outflow tract substrate electroanatomical and electrocardiographic imaging (ECGI) mapping before and after ajmaline administration and during high-rate atrial pacing. In 4 patients, epicardial mapping was performed using open thoracotomy with targeted biopsies., Results: Ajmaline increased the activation time delay in the substrate (33%; P = .002), ST-segment elevation in the right precordial leads (74%; P < .0001), and the area of delayed activation (170%; P < .0001), coinciding with the increased substrate size (75%; P < .0001). High atrial pacing rate increased the abnormal EGM duration at the right ventricular outflow tract areas from 112 ± 48 to 143 ± 66 ms (P = .003) and produced intermittent conduction block and/or excitation failure at the substrate sites, especially after ajmaline administration. Biopsies from the 4 patients with thoracotomy showed epicardial fibrosis where EGMs were normal at baseline but became fractionated after ajmaline administration. In some areas, local activation was absent and unipolar EGMs had a monophasic morphology resembling the shape of the action potential., Conclusion: Sodium current reduction with ajmaline severely compromises impulse conduction at the BrS fibrotic substrates by producing fractionated EGMs, conduction block, or excitation failure, leading to the Brugada ECG pattern and favoring ventricular fibrillation genesis., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Long-term excessive exposure to fluoride from environmental sources can cause serious public health problems such as dental fluorosis and skeletal fluorosis. The aberrant activation of osteoblasts in the early stage is one of the critical steps during the pathogenesis of skeletal fluorosis and canonical Wnt signaling pathway participate in the progress. However, the specific mechanism that how canonical Wnt signaling pathway was mediated is not yet clear. In this study, we found that miR-21-5p induced the activation of canonical Wnt signaling pathway via targeting PTEN and DKK2 during fluoride induced osteoblasts activation and firstly demonstrated the forward loop between canonical Wnt signaling and miR-21-5p in the process. These findings suggested an important regulatory role of miR-21-5p on canonical Wnt signaling pathway during skeletal fluorosis and miR-21-5p might be a potential therapeutic target for skeletal fluorosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: Aerobic training (AT) and resistance training (RT) can reduce blood glucose and type 2 diabetes risk, and increase muscle mass for prediabetes patients. However, the impact of long-term AT and RT on cardiovascular disease (CVD) risk remains unclear. The purpose of this study was to investigate the impact of AT and RT on CVD risk reduction in prediabetes patients., Materials and Methods: 248 prediabetes patients were enrolled in this multi-center randomized controlled trial (RCT). Patients were randomly divided into 3 groups: RT (n = 82), aerobic training (AT (n = 83)), and control group (n = 83). Participants in RT and AT groups had moderate RT or AT 3 times a week (150 min/week) under supervision in 3 research centers for 24 months. Primary outcome was CVD risk measured by Framingham Risk Score (FRS) and The Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool. Secondary outcomes included in HOMA2-IR, HbA1c, blood pressure and serum lipid profile., Results: Both RT and AT groups experienced a significant reduction in HOMA2-IR, HbA1c, LDL-C, TC, SBP, and DBP at the end of 12 and 24 months. Compared to the control group, Both RT and AT groups had significant reduction of the Chinese 10-year ICVD risk (P < 0.05), but FRS CVD risk declined significantly only in the AT group (all P < 0.05). Although FRS CVD risk decreased more in the RT group than in the control group, the difference was not statistically significant. After adjusting for age, gender, statin use, BMI, and WHR, in COX's proportional hazard model, RT (HR = 0.419, P = 0.037) and AT (HR = 0.310, P = 0.026) were protective factors for CVD risk in prediabetes patients. 24-month RT and AT decreased respectively 58.1% and 69.0% of CVD risk (10-year ICVD risk assessment) in prediabetes patients., Conclusions: This study demonstrated that 24-month moderate AT reduces the Chinese 10-year ICVD risk and FRS CVD risk in prediabetes patients. RT groups had significant reduction of CVD risk (10-year ICVD risk assessment) in prediabetes patients., Trial Registration: Clinical trial registration number: NCT02561377., Date of Registration: 24/09/2015., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The kidney toxicity of fluoride exposure has been demonstrated in animal studies, and a few studies have reported kidney function injury in children with fluoride exposure. However, epidemiological information for the effects of long-term fluoride exposure on adult kidney function remains limited., Methods: We conducted a cross-sectional investigation in Wenshui County, Shanxi Province to examine the association between fluoride exposure and kidney function in adults, and a total of 1070 adults were included in our study. Urinary fluoride concentrations were measured using the national standardized ion selective electrode method. And markers of kidney function injury (urinary NAG, serum RBP, serum Urea, serum C3, serum UA and serum αl-MG) were measured using automatic biochemical analyzer. Multivariate linear regression analysis and binary logistic regression model were used to assess the relationship between urinary fluoride and markers of kidney function injury., Results: Urinary fluoride was positively correlated with urinary NAG and serum Urea, negatively correlated with serum C3. In multivariate linear regression models, every 1 mg/L increment of urinary fluoride was associated with 1.583 U/L increase in urinary NAG, 0.199 mmol/L increase in serum Urea, 0.037 g/L decrease in serum C3 after adjusting for potential confounding factors. In the binary logistic regression model, higher levels of urinary fluoride were associated with an increased risk of kidney function injury. Determination of kidney function based on urinary NAG, every 1 mg/L increment in the urinary fluoride concentrations was associated with significant increases of 22.8% in the risk of kidney function injury after adjusting for potential confounding factors. Sensitivity analysis for the association between urinary fluoride concentrations and markers of kidney function (urinary NAG, serum Urea, and serum C3) by adjusting for the covariates, it is consistent with the primary analysis., Conclusions: Our study suggests that long-term fluoride exposure is associated with kidney function in adults, and urinary NAG is a sensitive and robust marker of kidney dysfunction caused by fluoride exposure, which could be considered for the identification of early kidney injury in endemic fluorosis areas., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Herein, we developed a flexible and cost-effective manual droplet operation system (MDOS) for performing miniaturized cell assays as well as single cell analysis. The MDOS consists of a manual x-y-z translation stage for liquid transferring and switching, a high-precision syringe pump for liquid driving and metering, a tapered capillary probe for droplet manipulation, a droplet array chip for droplet loading and reaction, sample/reagent reservoirs for storage, and a microscope for droplet observation, with a total expense of only $4,000. By using the flexible combination of three elementary operations of the x-y-z stage's moving and the pump's aspirating and depositing, the MDOS can manually achieve multiple droplet handling operations in the nanoliter to picoliter range, including droplet generation, assembling, fusion, diluting, and splitting. On this basis, multiple cell-related operations could be performed, such as nanoliter-scale in-droplet cell culture, cell coculture, drug stimulation, cell washing, and cell staining, as well as formation of picoliter single-cell droplets. The feasibility and flexibility of the MDOS was demonstrated in multi-mode miniaturized cell assays, including cell-based drug test, first-pass effect assay, and single-cell enzyme assay. The MDOS with the features of low cost, easy to build and flexible to use, could provide a promising alternative for performing miniaturized assays in routine laboratories, in addition to conventional microfluidic chip-based systems and automated robot systems., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An increase in oxidative stress is an important pathological mechanism of heart injury induced by doxorubicin (DOX). Tranilast is an anti-allergy drug that has been shown to possess good antioxidant activity in previous studies. The overexpression and secretion of chymase by mast cells (MCs) increase the pathological overexpression of angiotensin II (Ang II), which plays a crucial role in myocardial hypertrophy and the deterioration of heart disease. The MC stabilizer tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid; tran) prevents mast cells from degranulating, which may reduce DOX-induced Ang II synthesis. Therefore, in the present study, we hypothesized that tranilast will protect rats from DOX-induced myocardial damage via its antioxidant activity, thereby inhibiting Ang II expression. Thirty male Wistar rats were divided into three groups (n = 10 in each group) that received DOX, a combination of DOX and tranilast or saline (the control group) to test this hypothesis. Tranilast suppressed chymase expression, reduced Ang II levels and prevented the myocardial hypertrophy and the deterioration of heart function induced by DOX. Based on the findings of the present study, the suppression of chymase-dependent Ang-II production and the direct effect of tranilast on the inhibition of apoptosis and fibrosis because of its antioxidant stress capacity may contribute to the protective effect of tranilast against DOX-induced myocardial hypertrophy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The change of serum soluble Klotho (sKlotho) content is related to a variety of osteoarthropathy. However, its association with the severity of skeletal fluorosis (SF) is not clear. Here, the association of tea fluoride exposure with serum sKlotho levels and the severity of SF were investigated and further verified in a rat model of fluorosis. A cross sectional case control study was conducted in residents over 50 years old from brick-tea drinking areas in Qinghai and Xinjiang Provinces, China. Concentrations of fluoride in brick tea water and urine were determined by ion selective electrode method, and the levels of serum sKlotho were determined by ELISA method. Linear regression and ordered logistic regression models were constructed to examine the relationship among fluoride exposure, serum sKlotho levels and the severity of SF. The kidney and small intestine of Wistar rats were isolated for detection of Klotho by immunohistochemistry (IHC), and femoral artery blood was sampled to measure the serum levels of sKlotho. An increase of 1 mg/day in tea fluoride intake (TFI) was associated with a 12.070 pg/mL (95% CI: 0.452-23.689) increase in serum sKlotho levels and a 1.163-fold (95% CI: 1.007-1.342) increase in the severity of SF after adjusting for age, gender, and ethnicity. Serum sKlotho levels were also positively associated with the severity of SF (P < 0.05). The mediation analysis showed that serum sKlotho levels mediated 17.76% of the increase in the severity of SF caused by an increase of 1 mg/day of TFI. Moreover, a significant increase of serum sKlotho levels in fluoride-exposed groups was also seen in the rat model. The present study suggests that serum sKlotho may be a potential mediator of SF in brick tea-type fluorosis endemic areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Biochar is a good adsorbent for water pollutants. However, the effects of biochar on aquatic organisms are not well understood. In this study, different amounts of biochar (CK, 0 mg/g; T1, 10 mg/g; T2, 30 mg/g) were added to sediment to study changes in water quality and its impact on three submerged macrophytes (Hydrilla verticillata, Vallisneria natans, and Ceratophyllum demersum) and the sediment microbial community. The results indicated that biochar treatments significantly increased the water pH and conductivity. Compared with the initial values, the total phosphorus (P) contents in the water of the CK, T1, and T2 treatments decreased by 78.5%, 95.0%, and 58.3%, respectively, while the total nitrogen contents increased by 26.26%, -5.81%, and 19.70%, respectively. Compared with those in CK, the relative growth rates of H. verticillata, V. natans, and C. demersum in T1 increased by 28.4%, 163.1%, and 61.3%, respectively, while those in T2 showed no significant difference except that the growth rates of H. verticillata decreased by 17.7%. The P contents of the three submerged macrophytes increased with the increase of biochar addition, except that there was no significant difference between T2 and CK for H. verticillata. Biochar treatments reduced the biomass of total microbial, bacterial, and fungal phospholipid fatty acids in the sediment for H. verticillata and V. natans, and they increased fungal: bacterial ratios in the low-dose biochar treatments for V. natans and C. demersum. This study demonstrates that the addition of biochar to sediment significantly increased the pH and conductivity, and decreased total P contents in the water. Low-dose biochar treatments were more beneficial for water quality improvements and the growth of submerged macrophytes than high-dose biochar., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier B.V.)

Inhibiting giant cells (GCs) development is an important characteristic of introgression line cucumber IL10-1 against Meloidogyne incognita proved by our previous study, but the systematic regulatory pathways were unknown. To reveal the regulation pathways more comprehensively, in the current study, we performed a joint analysis of RNA-Seq and lable-free quantitative proteomics between the IL10-1 (resistant) and the CC3 (susceptible cucumber) after inoculation with M. incognita. The results indicated that flavonoid biosynthesis pathway was specifically enriched in IL10-1. And protein species of Csa5P590220 and Csa5P589940 associated with flavonoid biosynthesis were highly translated in IL10-1 compared with these in CC3 at 3 days post inoculation (dpi), which would resulted in the excess of flavonoids in IL10-1 roots. In addition, phosphoproteomic analysis found that phosphorylated protein species involved in MAPK signaling cascade were enhanced in IL10-1, while they were inhibited in CC3 at 3 dpi. Accordingly, we speculate that the enhanced MAPK cascade signaling plays an important role in signal transduction for IL10-1 regulating the flavonoid biosynthesis. Knowledge from the study provide important regulatory pathways and protein species of introgression line cucumber against M. incognita, which will help in efforts to improve the recognition of the resistance mechanism of plants against nematode. SIGNIFICANCE: The current approach of joint analysis in transcription level, protein level and protein phosphorylation level more comprehensively revealed the different expression patterns at the molecular level of resistant and susceptible cucumber after inoculation with M. incognita. Based on the different expression patterns, we explore the pathway of resistance regulation of resistant cucumber IL10-1. Moreover, our results are helpful for the discovery of key genes and then apply them to M. incognita-resistance breeding., Competing Interests: Declaration of Competing Interest The authors declare that don't have conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

The human induced pluripotent stem cell (iPSC) line ZJUCHi002-A was established from renal epithelial cells present in urine (urinary cells) collected from an 8-year-old Charcot-Marie-Tooth disease type 2A (CMT2A) patient carrying point mutation in MFN2 (c.752C > T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. The pluripotency, capacity of differentiation into 3 germ layers, silence of reprogramming factors and normal karyotype were all confirmed in this study., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The human iPSC cell line ZJUCHi001-A was established from renal epithelial cells present in urine (urinary cells) harvested from a 2-year-old Charcot-Marie-Tooth disease type 1B (CMT1B) patient carrying point mutation in MPZ (c.292C>T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. The pluripotency, capacity of differentiation into 3 germ layers, silence of reprogramming factors and normal karyotype for this cell line were all confirmed in this study., (Copyright © 2019. Published by Elsevier B.V.)

Background: Atrial septal defect (ASD) is one of the most common cardiac malformations worldwide. Several genes have been identified so far, which can merely explain small proportion of all the cases, therefore, it is anticipated that there are additional genes causing ASD. The aims of this study were to identify the causal gene of ostium secundum atrial septal defect (ASDII) in a Chinese family., Methods: Whole exome sequencing was performed in three affected members and one control in the ASDII family. We screened mutations of LBX2 in 300 unrelated ASD patients and validated in 400 normal controls by Sanger sequencing. LBX2 knockout zebrafish was generated by CRISPR/Cas9 to detect whether lbx2 deficiency influenced cardiac development., Results: A rare missense mutation in LBX2 (c.A403G: p.K135E) was identified as the pathogenic cause of ASD. Subsequent mutation screening revealed two missense variants in 3 of 300 sporadic patients. We observed expanded size of atrium and ventricle in LBX2 knockout zebrafish through hematoxylin-eosin staining, more incompact distribution of cardiac myocytes was also discovered in homozygote compared with in wildtype. Furthermore, we performed in situ hybridization of crip2 gene to trace the cardiac neural crest cells in the embryo stage and found that the migration of neural crest cells was obviously delayed in the homozygotes., Conclusions: We identified LBX2 for the first time as a pathogenic gene of ASDII. LBX2 deficiency may cause abnormal development of heart through influencing the migration of neural crest cells and affect the process of cardiac septation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A reliable liquid chromatography/tandem mass (LC-MS/MS) method was developed for quantitation of 3', 4'-dimethoxy flavonol-3-β-d-glucopyranoside (DF3G) in rat plasma using pantoprazole as the internal standard. An Agilent C18 column (100 mm × 3 mm, 3.5 μm) was performed for chromatographic separation with the mobile phase composed of methanol-water (containing formic acid) at a flow rate of 0.4 mL/min. A triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source in positive ion mode was applied to quantitative analysis by multiple reacting monitoring (MRM). The MRM precursor-product ion transition of DF3G and Pantoprazole (IS) were m/z 461.1 → 299.2 and 383.9 → 200.2, respectively. Calibration curves were recovered in a concentration range of 1-500 ng/mL for plasma with a limit of lower quantification (LLOQ) of 1 ng/mL. The intra-day and inter-day precision were not >10%. The accuracy of DF3G ranged from -10% to 0.53% in quality control (QC) samples at three concentrations. DF3G was not degraded during the analysis and the storage period. All the data were validated in accordance with the FDA bioanalytical method validation guideline. The LC-MS/MS method was successfully employed in the pharmacokinetic study of the DF3G after oral administration and intravenous injection in rats., (Copyright © 2018. Published by Elsevier B.V.)

To understand the impact of the Fukushima nuclear accident (FNA), 137 Cs, 134 Cs, 90 Sr, and gross beta were analyzed in the northeast South China Sea (NSCS), the Luzon Strait (LS) and its adjacent areas. 137 Cs, 90 Sr, and gross beta values in the NSCS were similar to those prior to the FNA. 90 Sr and 137 Cs in the LS and its adjacent areas were consistent with those in the NSCS. The high 137 Cs-peak values occurred at depth of 150 m whereas the high 90 Sr-peak values occurred at depth of 0.5 m. The 137 Cs and gross beta mean values in Cruise I were higher than those in Cruise II whereas the 90 Sr mean value was just the reverse. 134 Cs in all seawater were below the minimum detectable activity. The past and present data since the 1970s suggested 137 Cs and 90 Sr in the study areas still originated from global fallout and the FNA influence were negligible., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A gold(I)-catalyzed glycosylation of Kdo with glycosyl ortho-hexynylbenzoate as donor is reported. The couplings of Kdo ortho-hexynylbenzoate with a set of alcohols promoted by PPh 3 AuOTf afford Kdo glycosides with good β-selectivities. This glycosylation method allows for the synthesis of β-Kdo monosaccharide with a C5 linker at the reducing end for subsequent conjugation to carrier proteins and arrays., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The available evidence of Photodynamic therapy (PDT) combined with stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC) is still insufficient. It also remains unclear whether PDT influences systemic inflammatory response., Aim: To explore the clinical efficacy and safety of the combination treatment and the systemic inflammatory response in patients with EHCC., Methods: Patients with unresectable EHCC underwent either the combined treatment using Hematoporphyrin PDT and stent placement (PDT+stent group, n=12) or stent-only (stent group, n=27). The primary end-point was overall survival. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Quality of life was assessed using the Karnofsky performance scale (KPS) every 3 months., Results: Average survival time (13.8 vs. 9.6 months), and 6-month (91.7% vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT+stent group were significantly increased compared with the stent group. KPS scores in the PDT+stent group were significantly improved. TNF-α and IL-6 levels were significantly increased in the PDT+stent group., Conclusion: Hematoporphyrin-PDT combined with stent placement is an effective and safe treatment for EHCC. The treatment might promote systemic inflammatory response., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To examine the effect of case management on glycemic control and behavioral outcomes in adults with Type 2 diabetes in China., Methods: Participants were randomly assigned to a 1-year case management (CM) group (n=60) or control group (n=60). Monthly case management visits included identifying individuals' diabetes-related problems, setting goals, planning self-care, and evaluating progress. During a 1-year follow-up, all participants attended visits every 3 months without intervention., Results: In the CM vs. the control group, HbA1c was reduced at 6 months compared to baseline (P=0.034), with trends at 12 and 24 months, and empowerment ability improved (P<0.05). Also in the CM vs. controls, total self-care behaviors, the frequency of exercise, blood glucose testing, and foot care were higher (P<0.001) at 12 months, and the percentage of individuals with HbA1c ≤7.0% was higher (P=0.035) at 24 months., Conclusion: The case management intervention in China was effective at 6 months and, based on trends in HbA1c at 12 and 24 months and results for behavioral outcomes, the intervention shows promise and warrants more research., Practice Implications: A case management approach can enhance behavior change and glycemic control in Chinese with diabetes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The uses of laccase in the degradation and removal of antibiotics have recently been reported because of the high efficiency and environmental friendliness of laccase. However, these removal studies mostly refer to a limited number of antibiotics. In this study, soil adsorption was introduced into the laccase-oxidation system to assist the simultaneous removal of 14 kinds of sulfonamide, tetracycline, and quinolone antibiotics, which differed in structures and chemical properties. The complementary effects of laccase-mediated oxidation and soil adsorption enabled the simultaneous removal. Removal characteristics were determined by a comprehensive consideration of the separate optimum conditions for laccase oxidation and soil adsorption removal experiments. With concentrations of laccase, syringaldehyde (SA), and soil of 0.5mg/mL, 0.5mmol/L, and 50g/L, respectively, and at pH 6 and 25°C, the removal rates of each antibiotic exceeded 70% in 15min and were close to 100% in 180min. Sulfonamide antibiotics (SAs) were removed mainly by laccase oxidation and quinolone antibiotics (QUs) mainly by soil adsorption. Tetracycline antibiotics (TCs) were removed by both treatments in the coupled system, but laccase oxidation dominated. Electrostatic adsorption was speculated to be one of the adsorption mechanisms in soil adsorption with QUs and TCs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Numerous studies have demonstrated that both smoking and diabetes are risk factors for mortality and caused-specific cardiovascular events. However, few studies systematically investigated to what extent the excess risk could be attributed to smoking among diabetic patients., Methods: Literature references were searched up to April 2011 in MEDLINE and EMBASE, supplemented by manual searches. Inclusion criteria were prospective cohort studies, assessment of the association between smoking and total mortality, cardiovascular death, incidence of coronary heart disease (CHD), stroke and myocardial infarction (MI) in diabetic patients., Results: Of 3758 studies in the literature searched, 46 were eligible with approximately 130,000 diabetic patients. The relative risk (RR) comparing smokers with nonsmokers was 1.48[95% confidential interval (CI): 1.34-1.64] for total mortality (27 studies), 1.36(1.22-1.52) for cardiovascular mortality (9 studies), 1.54(1.31-1.82) for CHD (13 studies), 1.44(1.28-1.61) for stroke (9 studies) and 1.52(1.25-1.83) for MI (7 studies). Furthermore, the excess risk was observed among former and current smokers with a greater risk in current smokers. Subgroup analysis showed that the increased risk appeared to be consistent regardless of several study characteristics with the RRs ranging from 1.31 to 1.94 for all-cause mortality, 1.37 to 2.28 for CHD, 1.21 to 1.87 for stroke, 1.13 to 1.74 for cardiovascular mortality and 1.15 to 2.01 for MI., Conclusion: Smoking amplified the risk of mortality as well as cardiovascular events and the effect size for CHD appeared to be higher than other events in diabetic patients. Moreover, a trend of decreasing risk was observed among smoking quitters., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: In patients with sinoatrial nodal (SAN) dysfunction, atrial pauses lasting several seconds may follow rapid atrial pacing or paroxysmal tachycardia (tachy-brady arrhythmias). Clinical studies suggest that adenosine may play an important role in SAN dysfunction, but the mechanism remains unclear., Objective: To define the mechanism of SAN dysfunction induced by the combination of adenosine and tachycardia., Methods: We studied the mechanism of SAN dysfunction produced by a combination of adenosine and rapid atrial pacing in isolated coronary-perfused canine atrial preparations by using high-resolution optical mapping (n = 9). Sinus cycle length and sinoatrial conduction time (SACT) were measured during adenosine (1-100 μM) and DPCPX (1 μM; A1 receptor antagonist; n = 7) perfusion. Sinoatrial node recovery time was measured after 1 minute of "slow" pacing (3.3 Hz) or tachypacing (7-9 Hz)., Results: Adenosine significantly increased sinus cycle length (477 ± 62 ms vs 778 ± 114 ms; P<.01) and SACT during sinus rhythm (41 ± 11 ms vs 86 ± 16 ms; P<.01) in a dose-dependent manner. Adenosine dramatically affected SACT of the first SAN beat after tachypacing (41 ± 5 ms vs 221 ± 98 ms; P<.01). Moreover, at high concentrations of adenosine (10-100 μM), termination of tachypacing or atrial flutter/fibrillation produced atrial pauses of 4.2 ± 3.4 seconds (n = 5) owing to conduction block between the SAN and the atria, despite a stable SAN intrinsic rate. Conduction block was preferentially related to depressed excitability in SAN conduction pathways. Adenosine-induced changes were reversible on washout or DPCPX treatment., Conclusions: These data directly demonstrate that adenosine contributes to post-tachycardia atrial pauses through SAN exit block rather than slowed pacemaker automaticity. Thus, these data suggest an important modulatory role of adenosine in tachy-brady syndrome., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: To establish a profile of the modifiable cardiovascular disease (CVD) risk factors in the office-working population of Nanjing, China., Background: With increasing modernization in China, CVD is now common among Chinese. Relevant information on the prevalence of CVD risk factors in China is, however, limited., Methods: We recruited 2648 office working people aged 23-79 years without history of CVD or diabetes from 7 work units of Nanjing during the years 2003 to 2005. Information from a self-reported questionnaire on lifestyle, physical examination, fasting blood for lipid profiles, and a 75-gram oral glucose tolerance test (OGTT) were obtained from each participant. We analyzed the following 7 CVD risk factors: smoking, inadequate physical activity, unhealthy dietary habit, obesity, hypertension, dyslipidemia, and hyperglycemia., Results: The whole study population had an average of 2.8 risk factors, while 95.6%, 79.4% and 55.6% of them had respectively ≥ 1, ≥ 2 and ≥ 3 of the 7 CVD risk factors. Men had a higher proportion of smoking, hypertension, dyslipidemia, hyperglycemia, but lower in light physical activity compared with women. Number of CVD risk factors increased with age. Although risk factors in men were more common than women, they increased alarmingly in postmenopausal women., Conclusions: CVD risk factors are common in office-working people in Nanjing, China. Effective interventions and treatment against risk factors should be adopted in the high risk population, which may greatly reduce the future burden of CVD in the Chinese population., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: In this review, we assess and summarize evidence and gaps in the literature regarding diabetes education in mainland China., Methods: Using China/Chinese, diabetes and education as key words, articles were obtained from the National Science and Technology Library (NSTL), Chongqing Weipu and Qinghua Tongfang databases. Articles included in this review were further selected based on pre-determined criteria, including studying duration, outcome measurements, and inclusion of control groups., Results: Based on the 34 articles, we found that studies often took place in inpatient and outpatient department. Popular methods used were class teaching, or one-on-one teaching, and knowledge and glycemic control were mostly selected as the outcome measurements. Beneficial effects of diabetes education on knowledge, and glycemic control were demonstrated in studies during a relatively short follow-up (3-6 months). Limitations to the studies selected were that the effects of interventions on behavior change, BMI, blood pressure, lipids, and medical costs were not clearly addressed, and long-term outcomes and adherence to diabetes education was unknown., Conclusions: Diabetes education had positive impact on glycemic control in mainland China in short duration., Practice Implications: Future studies should use more creative ways of education, and the long-term impact of diabetes education should be evaluated., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: We previously showed that the cardioversion threshold (CVT) for ventricular tachycardia (VT) is phase dependent when a single monophasic shock (1MP) is used., Objective: The purpose of this study was to extend these findings to a biphasic shock (1BP) and to compare the efficacy of phase-independent multiple monophasic (5MP) and biphasic shocks (5BP)., Methods: Panoramic optical mapping with blebbistatin (5 microM) was performed in postmyocardial infarction rabbit hearts (n = 8). Flecainide (1.64 +/- 0.68 microM) was administered to promote sustained arrhythmias. 5MP and 5BP were applied within one VT cycle length (CL). Results were compared to 1BP and antitachycardia pacing., Results: We observed monomorphic VT with CL = 149.6 +/- 18.0 ms. Similar to 1MP, CVTs of 1BP were found to be phase dependent, and the maximum versus minimum CVT was 8.6 +/- 1.7 V/cm versus 3.7 +/- 1.9 V/cm, respectively (P = .0013). Efficacy of 5MP was higher than that of 1BP and 5BP. CVT was 3.2 +/- 1.4 V/cm for 5MP versus 5.3 +/- 1.9 V/cm for 5BP (P = .00027). 5MP versus averaged 1BP CVT was 3.6 +/- 2.1 V/cm versus. 6.8 +/- 1.5 V/cm, respectively (P = .00024). Antitachycardia pacing was found to be completely ineffective in this model., Conclusion: Maintenance of shock-induced virtual electrode polarization by multiple monophasic shocks over a VT cycle is responsible for unpinning of reentry leading to self-termination. Elimination of virtual electrode polarization by shock polarity reversal during multiple biphasic shocks proved ineffective. A significant reduction in CVT can be achieved by applying multiple monophasic shocks within one VT CL or one single shock at the proper coupling interval.

Background: Sudden cardiac death due to arrhythmia in the settings of chronic myocardial infarction (MI) is an important clinical problem. Arrhythmic risk post-MI continues indefinitely even if heart failure and acute ischemia are not present due to the anatomic substrate of the scar and border zone (BZ) tissue., Objective: The purpose of this study was to determine mechanisms of arrhythmia initiation and termination in a rabbit model of chronic MI., Methods: Ligation of the lateral division of the left circumflex artery was performed 72 +/- 29 days before acute experiments (n = 11). Flecainide (2.13 +/- 0.64 microM) was administered to promote sustained arrhythmias, which were induced with burst pacing or a multiple shock protocol (four pulses, 140-200 ms coupling interval)., Results: Panoramic optical mapping with blebbistatin (5 microM) revealed monomorphic ventricular tachycardia (VT) maintained by a single mother rotor (cycle length [CL] = 174.7 +/- 38.4 ms) as the primary mechanism of arrhythmia. Mother rotors were anchored to the scar or BZ for 16 of the 19 rotor locations recorded. Cardioversion thresholds (CVTs) were determined at various phases throughout the VT CL from external shock electrodes. CVTs were found to be phase dependent, and the maximum versus minimum CVT was 7.8 +/- 1.9 vs. 4.1 +/- 1.6 V/cm, respectively (P = .005). Antitachycardia pacing was found to be effective in only 2.7% of cases in this model., Conclusions: These results indicate that scar and BZ tissue heterogeneity provide the substrate for VT by attracting and stabilizing rotors. Additionally, a significant reduction in CVT may be achieved by appropriately timed shocks in which the shock-induced virtual electrode polarization interacts with the rotor to destabilize VT.

Previous studies have suggested that murine T cells are tolerant to epitopes derived from germ line variable regions of immunoglobulin (Ig) heavy (VH) or light chains. This has lead to the prediction that germ line VH-region epitopes found in neoplastic B cells cannot be used to provoke an antitumor immune response. To test these assumptions and address the question of how such a vaccine may alter the normal B-cell response, an antibody-forming B-cell hybridoma (1H6) expressing a conserved germ line VH gene with specificity for dextran was generated and used as a tumor model. Using algorithms for predicting major histocompatibility complex (MHC) binding, potential MHC class I and II binding peptides were identified within the 1H6 VH region, synthesized, and tested for MHC binding and immunogenicity. We show that germ line VH peptides, when presented by dendritic cells, are immunogenic in vitro and provoke a tumor-specific protective immune response in vivo. We conclude that (1) it is possible to induce a T-cell response to germ line VH peptides; (2) such peptides can be used to generate a B-cell tumor-specific vaccine; and (3) a vaccine targeting VH peptides expressed by the dominant dextran-specific B-cell clonotype had no effect upon the magnitude of the normal B-cell response to dextran.

The fatty acid compositions of 22 species of marine macrophytes, belonging to the Ceramiales, Cryptonemiales, Nemalionales, Laminariales, Chordariales, Scytosiphonales, Desmarestiales, Dictyosiphonales, Fucales, Dictyotales and Ulvales and collected from the Bohai Sea, were determined by capillary gas chromatography. The contents of polyunsaturated fatty acids (FAs) in the Bohai Sea algae, in comparison with the same species from the Yellow Sea were found to be lower. Red algae had relatively high levels of the acids 16:0, 18:1(n-7), 18:1(n-9), 20:5(n-3) and 20:4(n-6), and those examined were rich in C(20) PUFAs, these chiefly being arachidonic and eicosapentaenoic acids. The major FAs encountered in the Phaeophyta were 14:0, 16:0, 18:1(n-9), 18:2(n-6), 18:3(n-3), 18:4(n-3), 20:4(n-6) and 20:5(n-3). C(18)PUFAs are of greater abundance in the brown algae than in the red algae examined. All three green algae from the Ulvales had similar fatty acid patterns with major components, 16:0, 16:4(n-3), 18:1(n-7), 18:2(n-6), 18:3(n-3), and 18:4(n-3). They contained 16:3(n-3) and more 16:4(n-3), were rich in C(18)PUFAs, chiefly 18:3(n-3) and 18:4(n-3) and had 18:1(n-7)/18:1(n-9) ratios higher than 1.

Using a "split-synthesis" solid phase synthetic approach, bead libraries can be generated such that each bead displays only one chemical entity. This "one-bead one-compound" combinatorial library can then be assayed for specific biological properties using either a solid-phase on-bead binding or functional assay, or a releasable solution phase assay. Positive compound-beads can then be isolated for structure determination. Various assay systems to screen such a "one-bead one-compound" library are described. We have used this combinatorial library method to discover peptides that bind to the cell surface immunoglobulins of murine lymphoma cells. Such peptides, when presented in an oligomeric form to a lymphoma cell are able to induce signal transduction. Additionally, we have also applied the "one-bead one-compound" combinatory library approach to elucidate peptide substrate motifs for protein tyrosine kinases. Multiple distinct peptide motifs were identified for p60(c-src) protein tyrosine kinase. Using the identified peptide substrates as templates, potent and highly specific pseudosubstrate-based peptide inhibitors were developed.