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We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study. [ABSTRACT FROM AUTHOR]

Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-fransretinoic acid (ATRA), early death because of hemorrhage remains unacceptably common, and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APLassociated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs). Results from a series of coagulation assays have shown that promyelocytic extracellular chromatin increases thrombin and plasmin generation, causes a shortening of plasma clotting time of APL cells, and increases fibrin formation. DNase I but not anti-tissue factor antibody could inhibit these effects. Immunofluorescence staining showed that promyelocytic extracellular chromatin and phosphatidylserine on APL cells provide platforms for fibrin deposition and render clots more resistant to fibrinolysis. Additionally, coincubation assays revealed that promyelocytic extracellular chromatin is cytotoxic to ECs, converting them to a procoagulant phenotype. This cytotoxity was blocked by DNase I by 20% or activated protein C by 31 %. Our current results thus delineate the pathogenic role of promyelocytic extracellular chromatin in APL coagulopathy. Furthermore, the remaining coagulation disturbance in high-risk APL patients after ATRA administration may be treatable by intrinsic pathway inhibition via accelerating extracellular chromatin degradation. [ABSTRACT FROM AUTHOR]

Background: Cardiac catheterization has opened an innovative treatment field for cardiac disease; this treatment is becoming the most popular approach for pediatric congenital heart disease (CHD) and has led to a significant growth in the number of children with cardiac catheterization. Unfortunately, based on evidence, it has been demonstrated that the majority of children with CHD are at an increased risk of "non-cardiac" problems. Effective exercise therapy could improve their functional status significantly. As studies identifying the efficacy of exercise therapy are rare in this field, the aims of this study are to (1) identify the efficacy of a home-based exercise program to improve the motor function of children with CHD with cardiac catheterization, (2) reduce parental anxiety and parenting burden, and (3) improve the quality of life for parents whose children are diagnosed with CHD with cardiac catheterization through the program.Methods/design: A total of 300 children who will perform a cardiac catheterization will be randomly assigned to two groups: a home-based intervention group and a control group. The home-based intervention group will carry out a home-based exercise program, and the control group will receive only home-based exercise education. Assessments will be undertaken before catheterization and at 1, 3, and 6 months after catheterization. Motor ability quotients will be assessed as the primary outcomes. The modified Ross score, cardiac function, speed of sound at the tibia, functional independence of the children, anxiety, quality of life, and caregiver burden of their parents or the main caregivers will be the secondary outcome measurements.Discussion: The proposed prospective randomized controlled trial will evaluate the efficiency of a home-based exercise program for children with CHD with cardiac catheterization. We anticipate that the home-based exercise program may represent a valuable and efficient intervention for children with CHD and their families.Trial Registration: http://www.chictr.org.cn/ on: ChiCTR-IOR-16007762 . Registered on 13 January 2016. [ABSTRACT FROM AUTHOR]

Background: School scoliosis screening has been carried out around the world. The screen program has never been performed on Chongming Island, the third largest island in China and characterized less population exchange with the rest of China. This study was designed to examine scoliotic parameters in children from Chongming Island and determine whether the parameters differed from those of the published data.Methods: A total of 6824 children (3477 boys and 3347 girls) aged from 6 to 17 were recruited. The screen included Adam's test and scoliometer measurements. Posteroanterior radiographic evaluation was performed if trunk rotation was 5° or more.Results: One hundred seventy two were confirmed with Cobb angle of 10° or more; the prevalence was 2.52 %, higher in girls (3.11 %) than in boys (1.96 %) (p < 0.05). There was a weak positive correlation between prevalence and age. Majority curves were minor (from 10 to 19°). The most common thoracic curve was right curve (60.3 % of all thoracic curves), while the most common thoracolumbar (75.5 %) and lumbar curves (64.7 %) were left curves.Conclusions: The prevalence of scoliosis on Chongming Island was 2.52 %. This study indicates that epidemiology of scoliosis has regional variation, and genetic differences may contribute such difference. [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the most common treatments used for hepatocellular carcinoma (HCC), which effectively improves outcome and reduces tumor recurrence. However, the drug resistance mechanisms involved in chemotherapy, which is the predominant challenge in HCC treatment, remain to be fully elucidated. Therefore, there is an urgent requirement for the identification of novel therapeutic strategies or drugs. MicroRNAs (miRs) have become an area of interest, and in the present study, the effects of miR-133a and miR-326 on HepG2 cells, and their function on B-cell lymphoma-extra large (Bcl-xl) in HepG2 cells were investigated. Using computational programs, Bcl-xl was predicted as the common target gene of miR-133a and miR-326. A dual-luciferase reporter assay was used to verify the target genes of miRs. The mRNA and protein levels of Bcl-xl were observed to be downregulated following transfection with miR-133a or miR-326 mimics. Combining miR-133a or miR-326 with 5-fluorouracil (5-FU) or cisplatin (DDP) resulted in increased cell death. The results of the present study indicated that miR-133a, miR-326 and Bcl-xl acted protectively against the apoptosis, induced by 5-FU or DDP, in HepG2 cells. This suggested the potential use of miRs either as ancillary anti-cancer drugs or as anti-cancer drugs themselves. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cutoff value of HbA1c for predicting diabetes and prediabetes in a Chinese high risk population aged over 45.Methods: A total of 619 people aged over 45 without diabetes were randomly recruited to complete Finnish Diabetes Risk Score (FINDRISC) questionnaire. 208 high-risk individuals (defined by Diabetes Risk Score >=9) had OGTT and HbA1c determined at the same time.Results: In a Chinese population aged over 45, the best cutoff value of HbA1c for detecting diabetes and prediabetes was 5.8% and 5.4% respectively. The area under the receiver operating characteristic (AUROC) curve of HbA1c for detecting diabetes was 0.85 (95% CI: 0.80-0.90) and prediabetes was 0.62 (95% CI: 0.54-0.70). The combined use of HbA1c and fasting blood glucose (FPG) had larger AUROC than HbA1c alone (0.88, 95%CI: 0.83-0.92 in detecting diabetes vs 0.75, 95% CI: 0.67-0.82 in prediabetes), and had a higher sensitivity in predicting diabetes and higher specificity and positive predictive value (PPV) in predicting prediabetes. However, the AUROC between HbA1c alone and combined use in predicting diabetes was not significantly different (p=0.173).Conclusions: FINDRISC is feasible tool to screen people who are at high risk of diabetes. The cutoff values of HbA1c to diagnose diabetes and prediabetes in a Chinese high risk population aged over 45 were 5.8% and 5.4%, respectively. The sensitivity and specificity of HbA1c for detecting diabetes and prediabetes was relatively low, so that the combined use of HbA1c and FPG may be more effective in prediction. [ABSTRACT FROM AUTHOR]

A series of novel teraryl oxazolidinonecompounds was designed, synthesized, and evaluated for their antimicrobialactivity and toxicities. The compounds with aromatic N-heterocyclicsubstituents at the 4-position of pyrazolyl ring showed better antibacterialactivity against the tested bacteria than other compounds with differentpatterns of substitution. Among all potent compounds, 10fexhibited promising safety profile in MTT assays and in hERG K+channel inhibition test. Furthermore, its phosphate was foundto be highly soluble in water (47.1 mg/mL), which is beneficial forthe subsequent in vivo test. In MRSA systemic infection mice models, 10fphosphateexerted significantly improved survival protection compared with linezolid.The compound also demonstrated high oral bioavailability (F= 99.1%). Moreover, from the results of in vivo toxicologyexperiments, 10fphosphate would be predicted to haveless bone marrow suppression. [ABSTRACT FROM AUTHOR]

Background: Delayed motor development is reported in patients with congenital heart disease (CHD). Exercise is widely used to facilitate motor development and improve motor ability. Exercise for adolescents and adults with CHD has been extensively studied. However, the evidence of exercise for infants with CHD is sparse. This study aims to identify the effect of passive movement and active exercise on motor development within very young CHD infants with cardiac catheterization.Methods/design: A prospective and randomized controlled trial will be conducted in very young CHD infants with cardiac catheterization. A total of 147 infants with CHD will be randomized by a 1:1:1 allocation ratio by computer to an exercise intervention group, a home-based intervention group and a control group. The exercise intervention group will receive passive movement and active exercise from experienced physiotherapists in pediatrics three times a week for 12 weeks. The home-based intervention group will receive passive movement and active exercise from their parents or caregivers at home three times a week for 12 weeks. The control group will receive follow up only. The follow-up duration is 20 months. The primary outcome measures are the motor quotient measured by the Peabody Developmental Motor Scales-II. The secondary outcome measures are the Ross score, ventricular function, bone quality, body length, weight, head circumference, upper arm circumference, and adverse events.Discussion: This study has several important features, including the randomization process, the long follow-up duration, the control group, and the large sample size. The aim of this study is to determine whether 12-week passive movement and active exercise promotes motor development and produces other beneficial effects for very young CHD infants with cardiac catheterization. Therefore, this study will contribute new knowledge regarding the rehabilitation program in very young CHD infants with cardiac catheterization.Trial Registration: Current Controlled Trials ChiCTR-IOR-15005909 (January 31, 2015). [ABSTRACT FROM AUTHOR]

In order to better distinguish true hybrids in litchi crossbreeding, Fi generations of two litchi hybridized combinations namely that 'Xuehuaizi' x 'Guiwei' and 'Xuehuaizi' x 'Jiaohesanyuehong' were used as materials to identify true hybrids, to construct mapping populations and to study the genetic diversities of the two populations with EST-SSR markers. The results showed that F1 generations of the two hybrid populations could be identified with an identification rate of 100% by the combination of four pair primers, respectively, and the 159 individual plants of the two populations were true hybrids. In addition, variations were exited in leaf morphology of the progenies of the two populations and bands of parents absented were occurred on genotype. The clustering analysis showed that 113 F1 plants from the hybridized combination of 'Xuehuaizi' x 'Guiwei' were clustered into six categories (similarity coefficient was 0.68), and 63. 72% (72 plants) of which clustered into one group with male parent. The genetic distances between 32 plants (28. 3%) and their parents were far which indicated that larger variation or recombinant appeared in these plants. Forty six hybrid progenies of the combination of 'Xuehuaizi' x 'Jiaohesanyuehong' were divided into two categories when the similarity coefficient was 0. 642 and most individual plants (60. 87%) showed closer genetic relationship with female parent and partial maternal genetic tendency. It is concluded that EST-SSR markers are suitable to identify true hybrids of litchi. The construction of the two F1 mapping populations has established basis for further genetic linkage mapping, meanwhile, has accumulated materials for cultivar improvement of litchi. [ABSTRACT FROM AUTHOR]

An increasing number of studies have suggested that phosphoinositide 3-kinase-γ (PI3Kγ) and PI3Kδ are involved in the pathogenesis of autoimmune and inflammatory diseases, such as asthma and atherosclerosis. However, the underlying mechanism of acute hepatitis remains unknown. The present study aimed to determine the effect of PI3Kδ/γ inhibition on hepatic injury in a murine model of hepatitis induced by concanavalin A (ConA). It was demonstrated that the pharmacological inhibition of PI3Kδ/γ by TG100-115 did not prevent liver damage following ConA challenge. Furthermore, the PI3Kδ/γ inhibition resulted in elevated transaminase activity in the serum, aggravated hepatic lesions characterized by hepatic necrosis, increased inflammatory cell infiltration and apoptosis of hepatocytes. Survival tests demonstrated that TG100-115 significantly increased the death rate of mice following ConA challenge. In addition, TG100-115 increased the serum levels of the proinflammatory cytokine IL-2 following ConA injection. These results may oppose the development of PI3Kδ/γ inhibitors as therapeutic agents, particularly for the treatment of human hepatitis. [ABSTRACT FROM AUTHOR]

Background: Kernel weight, controlled by quantitative trait loci (QTL), is an important component of grain yield in maize. Cytokinins (CKs) participate in determining grain morphology and final grain yield in crops. ZmIPT2, which is expressed mainly in the basal transfer cell layer, endosperm, and embryo during maize kernel development, encodes an isopentenyl transferase (IPT) that is involved in CK biosynthesis. Results: The coding region of ZmIPT2 was sequenced across a panel of 175 maize inbred lines that are currently used in Chinese maize breeding programs. Only 16 single nucleotide polymorphisms (SNPs) and seven haplotypes were detected among these inbred lines. Nucleotide diversity (Π) within the ZmIPT2 window and coding region were 0.347 and 0.0047, respectively, and they were significantly lower than the mean nucleotide diversity value of 0.372 for maize Chromosome 2 (P < 0.01). Association mapping revealed that a single nucleotide change from cytosine (C) to thymine (T) in the ZmIPT2 coding region, which converted a proline residue into a serine residue, was significantly associated with hundred kernel weight (HKW) in three environments (P <0.05), and explained 4.76% of the total phenotypic variation. In vitro characterization suggests that the dimethylallyl diphospate (DMAPP) IPT activity of ZmIPT2-T is higher than that of ZmIPT2-C, as the amounts of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) consumed by ZmIPT2-T were 5.48-, 2.70-, and 1.87-fold, respectively, greater than those consumed by ZmIPT2-C. The effects of artificial selection on the ZmIPT2 coding region were evaluated using Tajima's D tests across six subgroups of Chinese maize germplasm, with the most frequent favorable allele identified in subgroup PB (Partner B). Conclusions: These results showed that ZmIPT2, which is associated with kernel weight, was subjected to artificial selection during the maize breeding process. ZmIPT2-T had higher IPT activity than ZmIPT2-C, and this favorable allele for kernel weight could be used in molecular marker-assisted selection for improvement of grain yield components in Chinese maize breeding programs. [ABSTRACT FROM AUTHOR]

The EC numbers represent enzymes and enzyme genes (genomic information), but they are also utilized as identifiers of enzymatic reactions (chemical information). In the present work (ECAssigner), our newly proposed reaction difference fingerprints (RDF) are applied to assign EC numbers to enzymatic reactions. The fingerprints of reactant molecules minus the fingerprints of product molecules will generate reaction difference fingerprints, which are then used to calculate reaction Euclidean distance, a reaction similarity measurement, of two reactions. The EC number of the most similar training reaction will be assigned to an input reaction. For 5120 balanced enzymatic reactions, the RDF with a fingerprint length at 3 obtained at the sub-subclass, subclass, and main class level with cross-validation accuracies of 83.1%, 86.7%, and 92.6% respectively. Compared with three published methods, ECAssigner is the first fully automatic server for EC number assignment. The EC assignment system (ECAssigner) is freely available via: http://cadd.whu.edu.cn/ecassigner/. [ABSTRACT FROM AUTHOR]

Foxtail millet (Setaria italica) is one of the oldest domesticated cereal crops in Eurasia, but identifying foxtail millets, especially in charred grains, and differentiating it from its wild ancestor, green foxtail (Setaria viridis), in the archaeobotanical remains, is still problematic. Phytolithic analysis provides a meaningful method for identifying this important crop. In this paper, the silicon structure patterns in the glumes, lemmas, and paleas from inflorescence bracts in 16 modern plants of foxtail millet and green foxtail from China and Europe are examined using light microscopy with phase-contrast and a microscopic interferometer. Our research shows that the silicon structure of VIII from upper lemmas and paleas in foxtail millet and green foxtail can be correspondingly divided into two groups. The size of VIII type phytolith of foxtail millet is bigger than that from green foxtail. Discriminant function analysis reveals that 78.4% of data on foxtail millet and 76.9% of data on green foxtail are correctly classified. This means certain morphotypes of phytoliths are relatively reliable tools for distinguishing foxtail millet from green foxtail. Our results also revealed that the husk phytolith morphologies of foxtail millets from China and Eastern Europe are markedly different from those from Western Europe. Our research gives a meaningful method of separating foxtail millet and green foxtail. The implications of these findings for understanding the history of foxtail millet domestication and cultivation in ancient civilizations are significant. [ABSTRACT FROM AUTHOR]

In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 μg F1 and 10 μg rV270) and SV2 (200 μg F1 and 100 μg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×106 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague. [ABSTRACT FROM AUTHOR]

Zhang, J., Lu, H., Wu, N., Li, F., Yang, X., Wang, W., Ma, M. & Zhang, X. 2010: Phytolith evidence for rice cultivation and spread in Mid-Late Neolithic archaeological sites in central North China. Boreas, Vol. 39, pp. 592–602. 10.1111/j.1502-3885.2010.00145.x. ISSN 0300-9483. The history of rice ( Oryza sativa) cultivation in North China is ambiguous owing to a lack of evidence from rice remains with precise ages in archaeological sites. In this paper, we present rice phytolith evidence from six archaeological sites in the Guanzhong Basin, central North China, dating from c. 5500 to 2100 cal. a BP (calibrated/calendar ages) based on 19 AMS-dates. The phytoliths found in the three archaeological sites located on the second river terrace (Quanhu, Yangguanzhai and Anban) include three types of phytoliths from rice, namely bulliform, parallel-bilobe and double-peaked. These findings suggest that the earliest cultivated rice in central North China occurred not later than c. 5690 cal. a BP. After c. 5500 cal. a BP, the farming pattern in the Guanzhong Basin was characterized by dominant dry crops (e.g. millets) and locally cultivated rice. A likely spread route of rice from the lower reaches of the Huanghe (Yellow) River towards the Guanzhong Basin in central North China is speculated to have happened at c. 5690 cal. a BP. The findings of this study help us to understand the farming pattern in the area and how rice spread across the semi-arid regions of East Asia. [ABSTRACT FROM AUTHOR]

The origin of millet from Neolithic China has generally been accepted, but it remains unknown whether common millet (Panicum miiaceum) or foxtail millet (Setaria italica) was the first species domesticated. Nor do we know the timing of their domestication and their routes of dispersal. Here, we report the discovery of husk phytoliths and biomolecular components identifiable solely as common millet from newly excavated storage pits at the Neolithic Cishan site, China, dated to between Ca. 10,300 and Ca. 8,700 calibrated years before present (cal yr BP). After Ca. 8,700 cal yr BP, the grain crops began to contain a small quantity of foxtail millet. Our research reveals that the common millet was the earliest dry farming crop in East Asia, which is probably attributed to its excellent resistance to drought. [ABSTRACT FROM AUTHOR]

Large individual differences have been identified toward varied addictive effects as evidenced in self-administration, place conditioning, and psychomotor stimulation paradigms, which have been primarily attributed to the role of congenital factors. However, it remains unknown whether environmental factors, like extraneous social stress events, could distinctively modulate animals with differentiated biobehavioral traits, such as rats with higher motor activity (high responder, HR) developed in a novel environment and their counterparts, LR (low responder) rats. In the present study, the influence of social crowding procedure upon morphine psychomotor effect was investigated. Moreover, the roles social stress played, respectively, on HRs and LRs were explored based on previous observation that HRs not only responded more to drugs but also to stress. Our results revealed that social crowding procedure could sensitize morphine psychomotor effect as a whole, and this effect was only evident for HR but not LR rats. The individual differences toward morphine psychomotor effects was indiscernible in rats housed in normal social conditions and only turned out to be significant under stress conditions. Given the fact that the occurrence of human addictive behavior usually happens within social environment permeated with various stress factors, the genetic and environmental elements may collaboratively contribute to the ultimate susceptibility of drug-prone individuals. [Copyright &y& Elsevier]

The detection efficiency (DE) of superconducting nanowire single-photon detectors (SNSPDs) at 1550 nm has been significantly improved in the past decades as a result of evolution of the optical structure, the materials, and the fabrication process. We discuss the general optical design for a high-efficiency SNSPD based on dielectric optical films that can detect wavelengths from visible to near infrared regions. This structure shows close-to-unity absorption and good insensitivity to the fine wavelength and the incident angle. We demonstrate an SNSPD specifically fabricated for the detection of 1064 nm wavelength with a maximal system DE of 87.4% ± 3.7%. The DEs of the SNSPDs for visible and near infrared wavelengths are also summarized and compared with those of semiconducting detectors. [ABSTRACT FROM AUTHOR]

A letter to the editor about the association of cardiovascular risk factors with body mass index is presented.