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Acyltransferase domains (ATs) of polyketide synthases (PKSs) are critical for loading of acyl groups on acyl carrier protein domains (A) via self - and trans -acylation reactions, to produce structurally diverse polyketides. However, the interaction specificity between ATs and unusual acyl units is rarely documented. In Streptomyces tsukubaensis YN06, we found that AT4 FkbB [an AT in the fourth module of tacrolimus (FK506) PKS] transferred both allylmalonyl (allmal) and emthylmalonyl (ethmal) units to ACPs, which was supposed responsible for the production of both FK506 and its analog FK520, respectively. Mutations of five residues in AT4 FkbB (Q119A, L185I-V186D-V187T, and F203L) caused decreased efficiency of allmal transfer, but a higher ratio of ethmal transfer, supposedly due to less nucleophilic attacks between Ser599 in the active site of AT4 FkbB and the carbonyl carbon in the allmal unit, as observed from molecular dynamics simulations. Furthermore, reverse mutations of these five residues in ethmal-specific ATs to the corresponding residues of AT4 FkbB increased its binding affinity to allmal-CoA. Among these residues, Val187 of AT4 FkbB mainly contributed to allmal recognition, and V187K mutant produced less FK520 than wild type. Our findings thus suggested that five critical residues within AT4 FkbB were important for AT functionality in polyketide extension and potentially for targeting biosynthesis by generating desirable products and eliminating undesirable analogs.

An important aspect of genetic counseling is the recognition of and adaptation to the socio-cultural uniqueness of the different populations that a genetics clinic serves. The Central Valley of California is home to a large population from Mexico, with a significant proportion of indigenous ancestry originating from the state of Oaxaca. We report on our experience with two families of this community-one extended family with an early lethal inborn error of metabolism and the other with a chronic disfiguring form of ichthyosis. We identified multiple important factors that needed to be considered, including the matching of language dialects, adaptation to different social interaction conventions, acknowledgement of traditional medicine beliefs, and effective transmission of genetic terms and concepts, all of which should be incorporated into the interactions with these families when aiming to provide comprehensive genetic counseling.

Aim: Little is known regarding the extent to which dying patients with chronic obstructive pulmonary disease (COPD) receive life-sustaining procedures and palliative care in US hospitals. We examined temporal trends and the impact of palliative care on the use of life-sustaining procedures in this population., Materials and Methods: A retrospective nationwide cohort analysis was performed using weighted National Inpatient Sample (NIS) data obtained from 2010 to 2014. Decedents ≥18 years of age at the time of death and with a principal diagnosis of COPD were included. We examined the receipt of life-sustaining procedures, defined as1 ventilation (intubation, mechanical ventilation, and noninvasive ventilation),2 vasopressor use (infusion and intravascular monitoring),3 nutrition (enteral and parenteral infusion of concentrated nutrition),4 dialysis, and5 cardiopulmonary resuscitation as well as palliative care consultation and do not resuscitate (DNR). We used compound annual growth rates (CAGRs) and the Rao-Scott correction of the χ2 statistic to determine the statistical significance of temporal trends of life-sustaining procedures, palliative care utilization, and DNR status., Results: Among 37 312 324 hospitalizations, 38 425 patients were examined. The CAGRs of life-sustaining procedures were 6.61% and -9.73% among patients who underwent multiple procedures and patients who did not undergo any procedure, respectively (both P < .001). The CAGRs of palliative consultation and DNR were 5.25% and 36.62%, respectively (both P < .001)., Conclusions: Among adults with COPD dying in US hospitals between 2010 and 2014, the utilization of life-sustaining procedures, palliative care, and DNR status increased.

The current study evaluated risk factors of early hospital readmission in geriatric patients with acute heart failure (HF) and analyzed 2,279 consecutively hospitalized older adults with decompensated HF from November 2013 to October 2014 across 15 U.S. hospitals. The eTracker-HF was designed to make risk factors known to treating clinicians in electronic health records. Multilevel multivariate logistic regression was applied to examine the association between risk factors and all-cause and HF 30-day readmission rates. All-cause and HF 30-day readmission rates were 22.3% and 9.8%, respectively. Old age, non-White ethnicity, delirium, physical impairment, ejection fraction <40%, advanced chronic kidney disease, and previous myocardial infarction were associated with all-cause and HF readmission. Home health care use was inversely associated with early readmission. In addition to demographic and cardiovascular risk factors, geriatric syndromes were associated with early readmission. Discharge to home health care may reduce early readmission in these patients. [Res Gerontol Nurs. 2018; 11(4):190-197.]., (Copyright 2018, SLACK Incorporated.)

Objectives: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component in its pathogenesis. Through genome-wide association studies (GWAS), we recently identified 10 novel loci associated with SLE and uncovered a number of suggestive loci requiring further validation. This study aimed to validate those loci in independent cohorts and evaluate the role of SLE genetics in drug repositioning., Methods: We conducted GWAS and replication studies involving 12 280 SLE cases and 18 828 controls, and performed fine-mapping analyses to identify likely causal variants within the newly identified loci. We further scanned drug target databases to evaluate the role of SLE genetics in drug repositioning., Results: We identified three novel loci that surpassed genome-wide significance, including ST3AGL4 (rs13238909, p meta =4.40E-08), MFHAS1 (rs2428, p meta =1.17E-08) and CSNK2A2 (rs2731783, p meta =1.08E-09). We also confirmed the association of CD226 locus with SLE (rs763361, p meta =2.45E-08). Fine-mapping and functional analyses indicated that the putative causal variants in CSNK2A2 locus reside in an enhancer and are associated with expression of CSNK2A2 in B-lymphocytes, suggesting a potential mechanism of association. In addition, we demonstrated that SLE risk genes were more likely to be interacting proteins with targets of approved SLE drugs (OR=2.41, p=1.50E-03) which supports the role of genetic studies to repurpose drugs approved for other diseases for the treatment of SLE., Conclusion: This study identified three novel loci associated with SLE and demonstrated the role of SLE GWAS findings in drug repositioning., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A copper(i)-catalyzed dearomative borylation of N -alkoxycarbonyl protected indole-3-carboxylates has been developed. The boron addition in this reaction occurred regioselectively at the 2-position of indoles followed by diastereoselective protonation, affording the corresponding stable cyclic chiral α-amino boronates (2-borylindolines) in moderate to good yields with excellent diastereo- and enantioselectivities. The product 2c could be used as a versatile precursor to undergo subsequent stereoselective transformations, delivering highly functionalized 2,3,3-trisubstituted chiral indolines.

Background: Quality of health care needs to be improved in rural China. The Chinese government, based on the 1999 Law on Physicians, started implementing the Rural Doctor Practice Regulation in 2004 to increase the percentage of certified physicians among village doctors. Special exam-targeted training for rural doctors therefore was launched as a national initiative. This study examined these rural doctors' perceptions of whether that training helps them pass the exam and whether it improves their skills., Methods: Three counties were selected from the 4 counties in Changzhou City in eastern China, and 844 village doctors were surveyed by a questionnaire in July 2012. Chi-square test and Fisher exact test were used to identify differences of attitudes about the exam and training between the rural doctors and certified (assistant) doctors. Longitudinal annual statistics (1980-2014) of village doctors were further analyzed., Results: Eight hundred and forty-four village doctors were asked to participate, and 837 (99.17%) responded. Only 14.93% of the respondents had received physician (assistant) certification. Only 49.45% of the village doctors thought that the areas tested by the certification exam were closely related to the healthcare needs of rural populations. The majority (86.19%) felt that the training program was "very helpful" or "helpful" for preparing for the exam. More than half the village doctors (61.46%) attended the "weekly school". The village doctors considered the most effective method of learning was "continuous training (40.36%)" . The majority of the rural doctors (89.91%) said they would be willing to participate in the training and 96.87% stated that they could afford to pay up to 2000 yuan for it., Conclusions: The majority of village doctors in Changzhou City perceived that neither the certification exam nor the training for it are closely related to the actual healthcare needs of rural residents. Policies and programs should focus on providing exam-preparation training for selected rural doctors, reducing training expenditures, and utilizing web-based methods. The training focused on rural practice should be provided to all village doctors, even certified physicians. The government should also adjust the local licensing requirements to attract and recruit new village doctors.

Myocardial fibrosis occurs in the late stages of many cardiovascular diseases, and appears to be stimulated by various microRNAs (miRNAs). We previously found that miR-33 may stimulate cardiac remodeling. Here, we examined the involvement of miR-33 in myocardial fibrosis. Proximal left coronary descending artery occlusion was performed in rat, and antagomiR-33a was injected. Primary cardiac fibroblasts were cultured and transfected with miR-33a mimics and inhibitors. miR-33a levels were increased in the rat after surgery, and collagen deposition and heart fibrosis were observed in vivo . Inhibition of miR-33a suppressed fibroblast proliferation, reduced the mRNA and protein levels of collagen-related markers in vitro and in vivo , and rescued the histological damage in vivo . A dual-luciferase reporter system showed that matrix metalloproteinase 16 (MMP16) gene was the direct target of MiR-33a. These results suggest that miR-33 promoted myocardial fibrosis by inhibiting MMP16 and stimulating p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MiR-33 may act as a novel therapeutic target for treating myocardial fibrosis., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Our understanding of the diversity and evolution of vertebrate RNA viruses is largely limited to those found in mammalian and avian hosts and associated with overt disease. Here, using a large-scale meta-transcriptomic approach, we discover 214 vertebrate-associated viruses in reptiles, amphibians, lungfish, ray-finned fish, cartilaginous fish and jawless fish. The newly discovered viruses appear in every family or genus of RNA virus associated with vertebrate infection, including those containing human pathogens such as influenza virus, the Arenaviridae and Filoviridae families, and have branching orders that broadly reflected the phylogenetic history of their hosts. We establish a long evolutionary history for most groups of vertebrate RNA virus, and support this by evaluating evolutionary timescales using dated orthologous endogenous virus elements. We also identify new vertebrate-specific RNA viruses and genome architectures, and re-evaluate the evolution of vector-borne RNA viruses. In summary, this study reveals diverse virus-host associations across the entire evolutionary history of the vertebrates.

Objective: To define clinical and laboratory characteristics of bilateral vestibulopathy(BVP) and to propose diagnostic criteria of this disorder based on clinical and laboratory vestibular function test findings. Method: Forty-two case series with a clinical suspicion of BVP were retrospectively analyzed, in an attempt to determine etiology. Presenting auditory-vestibular symptoms, bedside dynamic visual acuity tests and laboratory test were reviewed, including bithermal caloric test, rotatory chair tests, video head impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP). Result: Among these 42 patients, dizziness was seen in 42 cases(100%), oscillopsia was seen in 21 cases(50%), hearing loss was seen in 30(71.4%). Eight cases(19%) had tinnitus. Twenty-five cases showed vestibular loss in dynamic visual acuity test (69.4%). Definite diagnosis of complete BVP was made in 36 patients when the patients showed abnormal findings on caloric test, rotatory chair test and vHIT in addition to the symptoms. Whereas probable diagnosis of partial BVP was obtained in 6 patients with abnormal caloric test and rotatory chair test but no pathological vHIT. VEMP (ocular or cervical) could be recorded in 20 patients. Fourteen cases were caused by ototoxic drugs while no causes could be determined in 6 cases among these 42 cases. Conclusion: The diagnosis of BVP is a challenge. Vestibular laboratory test battery which reflect full frequency function of VOR has great value to confirming the diagnosis and differentiate complete BVP to partial BVP. Diagnosis standard shall be made combining clinical history, characteristic symptoms and the results of auditory-vestibular function testing. Ototoxic drugs contribute most considering etiology., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Low frequency sensorineural deafness is a common subtype of idiopathic sudden deafness. Certain patients suffered recurrent attacks without vertigo, much alike Meniere's disease. Few of them developed into definite Meniere's disease during long-term follow-up in many clinical studies. Although the pathophysiology of recurrent low frequency deafness is yet unknown, the desease is considered associated with early state of endolymphatic hydrops or migraine. Otologists shall be aware of its clinical course and careful explanation is necessary at time of initial informed consent., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objectives: To examine trends and socioeconomic disparities for preventable dental-related emergency department (ED) visits in Nevada., Methods: We pooled retrospective data containing 66 267 ED visits involving dental conditions from Nevada hospital ED databases from 2009 to 2015. The dependent variable was nontraumatic dental conditions identified by International Classification of Diseases, Ninth Revision, codes; 3 independent variables included treatment year, health insurance status, and race/ethnicity., Results: Odds of ED visits for nontraumatic dental conditions increased 16% annually from 2009 to 2015 (odds ratio [OR] = 1.16; 95% confidence interval [CI] = 1.13, 1.19). Medicaid (OR = 2.16; 95% CI = 1.96, 2.39) and uninsured patients (OR = 2.75; 95% CI = 2.52, 3.00) presenting with nontraumatic dental conditions were 1 to 2 times more likely than those with private dental insurance to seek ED treatment. Black patients were more likely than White patients to seek ED treatment (OR = 1.13; 95% CI = 1.02, 1.24)., Conclusions: Socioeconomic and demographic factors were significantly associated with ED visits for nontraumatic dental conditions, with a steady increase in trends and a widening of socioeconomic disparities in recent years.

Background: The association between socioeconomic status (SES) and smoking behaviors may differ across countries. This study aimed to estimate the association between socioeconomic status (income, occupation and education) and multiple measures of smoking behaviors among the Chinese elderly population., Methods: Using data from the China Health and Retirement Longitudinal Study in 2013, we examined the relationship between socioeconomic status and smoking behaviors through multivariate regression analysis. Sample selection models were applied to correct for sample selection bias. Smoking behaviors were measured by four indicators: smoking status, cigarette consumption, health risks related to smoking, and smoking dependence. Analyses were stratified by gender and urban-rural residence., Results: Among Chinese people aged 45 years or older, smokers accounted for 40% of the population in 2013, smoking 19 cigarettes per day. It was also found that 79% of smokers were at an increased health risk. Overall, although the influence of income on smoking behaviors was small and even insignificant, occupation and education levels were significantly associated with smoking behaviors. Managers or professionals were more likely to smoke, however there was no significant relationship with smoking dependence. Individuals with higher educational attainment were less likely to be associated with smoking behaviors. In addition, gender and urban-rural differences existed in the relationship between SES and smoking behaviors., Conclusions: Smoking disparities among diverse levels of socioeconomic status existed but varied greatly by SES indicators and population characteristics. Tobacco control policies in China should be increasingly focused on populations with low socioeconomic status in order to break the link between socioeconomic disadvantage and smoking behaviors. Further actions should mitigate inequalities in education, improve the social culture of cigarette use, and tailor interventions based on characteristics of the population.

Background: Sex is an important but understudied factor in the genetics of human diseases. Analyses using a combination of gene expression data, ENCODE data, and evolutionary data of sex-biased gene expression in human tissues can give insight into the regulatory and evolutionary forces acting on sex-biased genes., Methods: In this study, we analyzed the differentially expressed genes between males and females. On the X chromosome, we used a novel method and investigated the status of genes that escape X-chromosome inactivation (escape genes), taking into account the clonality of lymphoblastoid cell lines (LCLs). To investigate the regulation of sex-biased differentially expressed genes (sDEG), we conducted pathway and transcription factor enrichment analyses on the sDEGs, as well as analyses on the genomic distribution of sDEGs. Evolutionary analyses were also conducted on both sDEGs and escape genes., Results: Genome-wide, we characterized differential gene expression between sexes in 462 RNA-seq samples and identified 587 sex-biased genes, or 3.2% of the genes surveyed. On the X chromosome, sDEGs were distributed in evolutionary strata in a similar pattern as escape genes. We found a trend of negative correlation between the gene expression breadth and nonsynonymous over synonymous mutation (dN/dS) ratios, showing a possible pleiotropic constraint on evolution of genes. Genome-wide, nine transcription factors were found enriched in binding to the regions surrounding the transcription start sites of female-biased genes. Many pathways and protein domains were enriched in sex-biased genes, some of which hint at sex-biased physiological processes., Conclusions: These findings lend insight into the regulatory and evolutionary forces shaping sex-biased gene expression and their involvement in the physiological and pathological processes in human health and diseases.

ConcanavalinA (conA) is a protein extracted from the concanavalin, which has specific recognition through mannose components on bacterial cell surfaces. A magnetic nanocarrier with the structure of a dopamine functionalized magnetic nanoparticles was grafted with conA, and was used for immobilization of recombinant Escherichia coli harboring glycerol dehydrogenase with the specific recognition between glycoconjugates and glycoprotein. The effect of various factors on the immobilization including temperature, pH, cell concentration and immobilization time were investigated. The highest immobilization yield of 91% was obtained under the conditions: enzyme/support 1.28mg/mg, pH 8.0, immobilization time 2h and temperature 4°C. The obtained immobilized cell was characterized and exhibited higher thermal stability compared with the free cell. After ten cycles, the immobilized cell remained 62% initial activity. These results indicate that the cell immobilized onto conA-grafted nanoparticles by specific recognition of glycoconjugates and glycoprotein is a potential method for preparation of stable cell, and the immobilized cell showed perspective applications in the biocatalysis and biosensors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The development of bromodomain and extraterminal domain (BET) bromodomain inhibitors and their examination in clinical studies, particularly in oncology settings, has garnered substantial recent interest. An effort to generate novel BET bromodomain inhibitors with excellent potency and drug metabolism and pharmacokinetics (DMPK) properties was initiated based upon elaboration of a simple pyridone core. Efforts to develop a bidentate interaction with a critical asparagine residue resulted in the incorporation of a pyrrolopyridone core, which improved potency by 9-19-fold. Additional structure-activity relationship (SAR) efforts aimed both at increasing potency and improving pharmacokinetic properties led to the discovery of the clinical candidate 63 (ABBV-075/mivebresib), which demonstrates excellent potency in biochemical and cellular assays, advantageous exposures and half-life both in animal models and in humans, and in vivo efficacy in mouse models of cancer progression and inflammation.

The objective of this retrospective study was to compare open reduction and internal fixation (ORIF) with primary partial arthrodesis for the treatment of Lisfranc injuries accompanied by comminution of the second metatarsal base. Thirty-four patients were treated with ORIF or primary partial arthrodesis from 2007 to 2013. The patients were followed for an average of 28.5 months. Evaluation was performed with clinical examination, radiography, Visual Analogue Scale (VAS), the American Orthopedic Foot and Ankle Society (AOFAS) Midfoot Score, and the Short Form 36 (SF-36). Fifteen patients were treated with ORIF, and nineteen patients were treated with primary partial arthrodesis. Anatomical reduction was obtained in all patients. At two years postoperatively, the mean AOFAS Midfoot score was 84.33 points in the ORIF group and 85.05 points in the primary partial arthrodesis group (P> 0.05). Also, no significant differences were seen in the VAS for pain (1.20 vs 1.05 points), SF-36 physical component (79.60 vs 79.89 points) or SF-36 mental component (77.07 vs 79.21 points). With longer and conservative postoperative management, ORIF as well as primary partial arthrodesis for Lisfranc injuries accompanied by comminution of the second metatarsal base led to similar medium-term outcome.

Objective: Timely Schistosoma japonicum detection improves outcomes in schistosomiasis. Here, we established a double antibody sandwich ELISA to detect Schistosoma japonicum., Methods: Sj29 polyclonal and monoclonal antibodies were developed and identified. A Sj29 double antibody sandwich ELISA was evaluated., Results: Assay sensitivity for detecting Schistosoma japonicum circulating antigen Sj29 was 76.7% (23/30), 54.5% (18/33) and 50.0% (18/36) in patients with acute, chronic and advanced schistosomiasis. No false positives or cross-reactivity was observed in healthy controls or patients with clonorchiasis, paragonimiasis, or ancylostomiasis, respectively. By contrast, false positives (5.7%) and cross-reactivity (6.5%-10%) were detected using an AWA-ELISA. The circulating antigen positive rates decreased significantly faster than that of the antibody detection after 6 months treatment (22.2%, 4/18 and 88.9%, 16/18). Chi-Square Tests revealed that Sj29 sandwich ELISA had lower sensitivity than AWA indirect ELISA in the detection of S. japonicum infected patients (p<0.05). Although our assay detection specificity in patients infected with other parasites or healthy controls appeared higher, the difference between the assays was insignificant. However, our assay showed significantly better results in monitoring praziquantel therapeutic effects (p=0.001), with antigen-positive rates decreasing significantly faster than antibody detection rates after 6 months of treatment (22.2%, 4/18 versus 88.9%, 16/18)., Conclusions: Sj29 double antibody sandwich ELISA was established. The specificity of this method for detecting healthy sera was 100%. Meanwhile, Sj29 sandwich ELISA may have a potential diagnostic capability to distinguish current from past infections and assess drug treatment responses., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the effect of endoplasmic reticulum stress in trophocytes, in patients with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty-one pregnant women who were hospitalized in Women's Hospital, School of Medicine, Zhejiang University from January to December 2015 were recruited. Thirty-one women who were diagnosed as ICP were defined as the ICP group and 30 healthy pregnant women were defined as the control group. The localization and expression intensity of glucose regulated protein 78 (GRP-78) in placental tissues were detected by immunohistochemistry technique. Electronic microscope was used to observe ultra-microstructure change of the endoplasmic reticulum in trophocytes and cell line Swan71. Reverse transcription (RT)-PCR and western blot were used to investigate the expression of GRP-78 mRNA and protein in Swan 71 cell. Results: (1) GRP-78 protein was mainly expressed in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts. The protein expression of GRP-78 in placentas of the ICP group (13.2±2.4) was significantly higher than that in the control group (7.8±1.3, P< 0.01). (2) The volume of endoplasmie reticulum did not increase and the microvilli developed well, with no swelling and no expansion of endoplasmic reticulum in the control group.In the ICP group, microvilli injury, endoplasmic reticulum edema were found; the volume of endoplasmic reticulum increased, with dilation, vacuolation and significant degranulation. After treated with 100 μmol/L cholyglycine for 24 hours, universal dilatation of the endoplasmic reticulum were seen in the Swan71 cells. (3) In Swan71 cells, cholylglycine displayed a concentration-dependent up-regulation on the expression of GRP-78. The expressions of GRP-78 mRNA in 0, 25, 50, 100 μmol/L cholylglycine experimental group were 1.01±0.17, 2.17±0.16, 5.47±0.36, 5.65±0.82, respectively. The expression of GRP-78 protein in 0, 25, 50, 100 μmol/L cholylglycine experimental group were 1.01±0.04, 1.17±0.15, 1.33±0.13, 1.73±0.13, respectively. The expression of GRP-78 mRNA and protein in 100 and 50 μmol/L cholylglycine experimental group were significantly higher than 0 μmol/L (all P< 0.01). Conclusion: The obvious expansion of endoplasmic reticulum and the increased expression of GRP-78 in trophocytes indicated that endoplasmic reticulum stress of trophocytes may be involved in the pathogenesis of ICP.

Three isostructural halozincates, [HNH][ZnX 4 ]·H 2 O (HNH 2+ = protonated nicotinohydrazide, X = I (1), Br (2), Cl (3)), have been synthesized and exhibit halogen-dependent photoinduced electron transfer and chromic properties. Due to the different electron-donating nature of halogen atoms, only iodozincate hybrid 1 can easily undergo photoinduced electron transfer and eye-detectable photochromic behavior, revealing a unique matching rule between a moderate electron acceptor and halozincates.

Coiled-coil domains can direct the assembly of protein block copolymers into physically cross-linked, viscoelastic hydrogels. Here, we describe the use of fluorescence recovery after photobleaching (FRAP) to probe chain mobility in reversible hydrogels assembled from engineered proteins bearing terminal coiled-coil domains. We show that chain mobility can be related to the underlying dynamics of the coiled-coil domains by application of a three-state "hopping" model of chain migration. We further show that genetic programming allows the effective mobility of network chains to be varied 500-fold through modest changes in protein sequence. Destabilization of the coiled-coil domains by site-directed mutagenesis increases the effective diffusivity of probe chains. Conversely, probe mobility is reduced by expanding the hydrophobic surface area of the coiled-coil domains through introduction of the bulky leucine surrogate homoisoleucine. Predictions from the three-state model imply asymmetric sequential binding of the terminal domains. Brownian Dynamics simulations suggest that binding asymmetry is a general feature of reversible gels, arising from a loss in entropy as chains transition to a conformationally restricted bridged state.

Design space approach was applied in this study to optimize the lime milk precipitation process of Lonicera Japonica (Jinyinhua) aqueous extract. The evaluation indices for this process were total organic acid purity and amounts of 6 organic acids obtained from per unit mass of medicinal materials. Four critical process parameters (CPPs) including drop speed of lime milk, pH value after adding lime milk, settling time and settling temperature were identified by using the weighted standardized partial regression coefficient method. Quantitative models between process evaluation indices and CPPs were established by a stepwise regression analysis. A design space was calculated by a Monte-Carlo simulation method, and then verified. The verification test results showed that the operation within the design space can guarantee the stability of the lime milk precipitation process. The recommended normal operation space is as follows： drop speed of lime milk of 1.00-1.25 mL•min⁻¹, pH value of 11.5-11.7, settling time of 1.0-1.2 h, and settling temperature of 10-20 ℃.., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Registered nurses (RNs) play an important role in safe medication administration and patient safety. This study examined a total of 1276 medication error (ME) incident reports made by RNs in hospital inpatient settings in the southwestern region of the United States. The most common drug class associated with MEs was cardiovascular drugs (24.7%). Among this class, anticoagulants had the most errors (11.3%). The antimicrobials was the second most common drug class associated with errors (19.1%) and vancomycin was the most common antimicrobial that caused errors in this category (6.1%). MEs occurred more frequently in the medical-surgical and intensive care units than any other hospital units. Ten percent of MEs reached the patients with harm and 11% reached the patients with increased monitoring. Understanding the contributing factors related to MEs, addressing and eliminating risk of errors across hospital units, and providing education and resources for nurses may help reduce MEs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Tomatidine is isolated from the fruits of tomato plants and found to have anti-inflammatory effects in macrophages. In the present study, we investigated whether tomatidine suppresses airway hyperresponsiveness (AHR) and eosinophil infiltration in asthmatic mice. BALB/c mice were sensitized with ovalbumin and treated with tomatidine by intraperitoneal injection. Airway resistance was measured by intubation analysis as an indication of airway responsiveness, and histological studies were performed to evaluate eosinophil infiltration in lung tissue. Tomatidine reduced AHR and decreased eosinophil infiltration in the lungs of asthmatic mice. Tomatidine suppressed Th2 cytokine production in bronchoalveolar lavage fluid. Tomatidine also blocked the expression of inflammatory and Th2 cytokine genes in lung tissue. In vitro , tomatidine inhibited proinflammatory cytokines and CCL11 production in inflammatory BEAS-2B bronchial epithelial cells. These results indicate that tomatidine contributes to the amelioration of AHR and eosinophil infiltration by blocking the inflammatory response and Th2 cell activity in asthmatic mice.

Objective: The aim of this study is to evaluate the clinical and radiologic results of primary Total Knee Arthroplasty (TKA) for elderly complex tibial plateau fractures., Materials and Methods: Between November 2010 and February 2012, six cases of elderly complex tibial plateau fractures were treated with primary TKA using the standard medial parapatellar approach. All six patients were available at follow up with mean duration of 32.3 months (range 25-41 months). There were 3 women and 3 men with an average age of 69.5 years (58-78 years) at the time of the arthroplasty., Results: The mean Hospital for Special Surgery (HSS) knee score was 89.8 (range 85-94): 6/6 excellent. The mean knee flexion was 119.2° (105-130°). No significant postoperative complications were noted. None of these patients had significant postoperative knee pain required revision surgery, or had radiographic loosening of the components at the latest follow-up., Conclusions: TKA is a suitable solution for the treatment of elderly patients with complex tibial plateau fractures., Level of Evidence: Level IV, Therapeutic study., (Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: To compare plan robustness of volumetric modulated arc therapy (VMAT) with intensity modulated radiation therapy (IMRT) and to compare the effectiveness of 3 plan robustness quantification methods., Methods and Materials: The VMAT and IMRT plans were created for 9 head and neck cancer patients. For each plan, 6 new perturbed dose distributions were computed using ±3 mm setup deviations along each of the 3 orientations. Worst-case analysis (WCA), dose-volume histogram (DVH) band (DVHB), and root-mean-square dose-volume histogram (RVH) were used to quantify plan robustness. In WCA, a shaded area in the DVH plot bounded by the DVHs from the lowest and highest dose per voxel was displayed. In DVHB, we displayed the envelope of all DVHs in band graphs of all the 7 dose distributions. The RVH represents the relative volume on the vertical axis and the root-mean-square-dose on the horizontal axis. The width from the first 2 methods at different target DVH indices (such as D 95% and D 5% ) and the area under the RVH curve for the target were used to indicate plan robustness. Results were compared using Wilcoxon signed-rank test., Results: The DVHB showed that the width at D 95% of IMRT was larger than that of VMAT (unit Gy) (1.59 vs 1.18) and the width at D 5% of IMRT was comparable to that of VMAT (0.59 vs 0.54). The WCA showed similar results between IMRT and VMAT plans (D 95% : 3.28 vs 3.00; D 5% : 1.68 vs 1.95). The RVH showed the area under the RVH curve of IMRT was comparable to that of VMAT (1.13 vs 1.15). No statistical significance was found in plan robustness between IMRT and VMAT., Conclusions: The VMAT is comparable to IMRT in terms of plan robustness. For the 3 quantification methods, WCA and DVHB are DVH parameter-dependent, whereas RVH captures the overall effect of uncertainties., Competing Interests: Notification None., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

By using 1-methyl-4-(carbomethoxy)pyridinium (MCMP + ) as counterions, two iodoargentate hybrids, 1D [MCMP][AgI 2 ] (1) and 3D [MCMP][Ag 3 I 4 ] (2) have been synthesized and they exhibit rare electron transfer photochromism with a fast response rate, a wide response range and a long-lived charge-separated state in iodometallate systems. Noteworthily, the marked differences in the structure and photochromic performance of 1 and 2 are largely ascribed to the different aggregating behavior of electron-deficient MCMP + counterions (C-HO hydrogen bonded trimer in 1 and π-π/C-Hπ chain in 2).

By employing in situ methylnicotinohydrazide dication (MNH(2+)) as an electron acceptor, we have constructed an iodocuprate(I) hybrid {[MNH][Cu2I3]2}n (1), which exhibits charge transfer (CT) thermochromism due to the intense absorption of CT and electron transfer (ET) photochromism with high photocoloration contrast and fast response to UV irradiation due to the synergetic effect of valence change of copper ions.

Objectives: The Chinese government has greatly increased funding for disease control and prevention since the 2003 Severe Acute Respiration Syndrome crisis, but it is also concerned whether these increased resources have been used efficiently to improve public health services. We aimed to assess the efficiency of county-level Centers for Disease Control and Prevention (CDCs) of China and to identify strategies for optimising their performance., Methods: A total of 446 county-level CDCs were selected based on systematic sampling throughout China. The data envelopment analysis framework was used to calculate the efficiency score of sampled CDCs in 2010. The Charnes, Cooper and Rhodes (CCR) model was applied to calculate the overall and scale efficiency, and the Banker, Charnes and Cooper (BCC) model was used to assess technical efficiency. Models included three inputs and seven outputs. A projection analysis was conducted to identify the difference between projection value and actual value for inputs and outputs., Results: The average overall efficiency score of CDCs was 0.317, and the average technical efficiency score was 0.442 and 88.3% with decreasing returns to scale. Projection analysis indicated that all seven categories of outputs were underproduced. CDCs in the eastern region tended to perform better than CDCs in the middle and the western region., Conclusions: Most county-level CDCs in China were operated inefficiently. Emphasis should be put on increasing staff and general operating expenses through current governmental funding, upgrading healthcare providers' competencies and enhancing the standardisation of operational management, so that CDCs could utilise their resources more efficiently., (© 2016 John Wiley & Sons Ltd.)

Backgroud: This study aimed to measure the poverty head count ratio and poverty gap of rural Yanbian in order to examine whether China's New Rural Cooperative Medical Scheme has alleviated its medical impoverishment and to compare the results of this alternative approach with those of a World Bank approach., Methods: This cross-sectional study was based on a stratified random sample survey of 1,987 households and 6,135 individuals conducted in 2008 across eight counties in Yanbian Korean Autonomous Prefecture, Jilin province, China. A new approach was developed to define and identify medical impoverishment. The poverty head count ratio, relative poverty gap, and average poverty gap were used to measure medical impoverishment. Changes in medical impoverishment after the reimbursement under the New Rural Cooperative Medical Scheme were also examined., Results: The government-run New Rural Cooperative Medical Scheme reduced the number of medically impoverished households by 24.6 %, as well as the relative and average gaps by 37.3 % and 38.9 %, respectively., Conclusions: China's New Rural Cooperative Medical Scheme has certain positive but limited effects on alleviating medical impoverishment in rural Yanbian regardless of how medical impoverishment is defined and measured. More governmental and private-sector efforts should therefore be encouraged to further improve the system in terms of financing, operation, and reimbursement policy.

The Unified Classification System has expanded and updated the Vancouver Classification System and applied treatment principles to all periprosthetic fractures. This study assessed the reliability and validity of the Unified Classification System for femur fractures after hip arthroplasty. Thirty-eight radiographs were finally evaluated by 6 observers, 3 consultants and 3 trainees. Each observer read the radiographs on 2 separate occasions, independently, at least 2 weeks apart. Interobserver and intraobserver agreement and validity were analyzed, using weighted κ statistics. The mean κ value for interobserver agreement was found to be 0.849 (0.838-0.871) for consultants (almost perfect agreement) and 0.761 (0.707-0.836) for the trainees (substantial agreement). Intraobserver κ values ranged from 0.740 to 0.903, showing substantial to almost perfect agreement. Validity analysis of 23 type B cases revealed 79.710% agreement within B1, B2, and B3 subgroups with a mean κ value of 0.694 (0.670-0.741) (substantial agreement).

Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10(-8). We observed interesting trends for rs9346455 (P=6.49x10(-6)) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10(-5)) and rs1012650 (P=1.47 × 10(-5)), and rs1059778 (P=1.49x10(-5)) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10(-7). Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59.

To investigate the effect of myocardial viscoeslasticity on heart function, this paper presents a finite element model based on a hyper-viscoelastic model for the passive myocardium and Hill's three-element model for the active contraction. The hyper-viscoelastic model considers the myocardium microstructure, while the active model is phenomenologically based on the combination of Hill's equation for the steady tetanized contraction and the specific time-length-force property of the myocardial muscle. To validate the finite element model, the end-diastole strains and the end-systole strain predicted by the model are compared with the experimental values in the literature. It is found that the proposed model not only can estimate well the pumping function of the heart, but also predicts the transverse shear strains. The finite element model is also applied to analyze the influence of viscoelasticity on the residual stresses in the myocardium., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To examine the association between patient race/ethnicity, insurance status, and their interaction with patient safety indicators among hospitalized patients., Methods: Cross-sectional study was conducted. Data were extracted from the 2009 National Inpatient Sample. A total of 3,052,268 patient safety indicator-related discharges were identified. Dependent variables were 11 patient safety indicators (PSI) whereas independent variables included race/ethnicity and insurance status., Results: As compared with White patients, African American patients were more likely to experience pressure ulcer, post-operative hemorrhage or hematoma, and post-operative pulmonary embolism (PE) or deep vein thrombosis (DVE); Asian/Pacific Islander patients were more likely to experience pressure ulcer, post-operative PE or DVT, and two obstetric care PSIs; whereas Hispanic/Latino patients were more likely to experience post-operative physiometabolic derangement and accidental puncture/laceration. As compared with patients with private insurance, Medicaid patients were more likely to experience pressure ulcer, post-operative physiological metabolic derangement, post-operative PE or DVT, post-operative respiratory failure, post-operative wound dehiscence, and death among surgeries. However, both obstetric care PSIs showed that African Americans, Hispanics, and uninsured patients were less likely to incur them in comparison with their respective counterparts. Furthermore, strong interactive effects between African American and Medicaid on PSIs were detected., Conclusions: Although mixed findings in disparities in PSIs were observed in our study, Asian/Pacific Islander patients and Medicaid patients seem to be the most vulnerable. Further, interactive effects between African American and Medicaid indicate that poverty may be a key factor related to disparities in health care. Future research is merited to identify underlying factors that are related to PSIs among Asian/Pacific Islander patients. Strategies are needed to improve PSIs among Medicaid patients, especially during the current Medicaid program expansion due to the implementation of the Affordable Care Act.

Objective: Sudden cardiac arrest (SCA) in the young is a rare event but the effects can be devastating. We sought to identify variables that would lead to an improvement in time to defibrillation (TDFB), a previously noted factor significantly influencing survival from cardiac arrest., Design: During the 2013-2014 academic year, the Clark county school district performed quarterly drills to practice the coordinated automated external defibrillator (AED) response. Variables including school, AED carrier, and drill characteristics were measured to determine influence on TDFB. Schools were grouped by TDFB at a cutoff of three minutes. Characteristics were sought for schools with TDFB below three minutes. A mixed regression model taking into account repeated measures was created to determine which variables influenced TDFB., Results: Time to overhead announcement, distance of AED from drill site, and time to setup AED were the variables influencing TDFB with statistical significance (P <.01)., Conclusions: This study supports the notion of early recognition, announcement, and close proximity to an AED during a SCA to ensure an early TDFB. These results are consistent with basic life support and the chain of survival tenets of the American Heart Association., (© 2016 Wiley Periodicals, Inc.)

Cardiovascular diseases (CVDs) are among the top health problems of the Chinese population. Although mounting evidence suggests that early childhood health status has an enduring effect on late life chronic morbidity, no study so far has analyzed the issue in China. Using nationally representative data from the 2013 China Health and Retirement Longitudinal Study (CHARLS), a Probit model and Two-Stage Residual Inclusion estimation estimator were applied to analyze the relationship between childhood health status and adulthood cardiovascular disease in rural China. Good childhood health was associated with reduced risk of adult CVDs. Given the long-term effects of childhood health on adulthood health later on, health policy and programs to improve the health status and well-being of Chinese populations over the entire life cycle, especially in persons' early life, are expected to be effective and successful.

Objective: Gastric cancer (GC) is one of the most common malignant tumors worldwide, particularly, prevalent in China. Despite the decreasing incidence of GC in China, the 5-year survival rate is still not over 30% yet. Therefore, early diagnosis and therapeutic outcome evaluation of GC remains as the issue to be resolved in a clinical setting., Materials and Methods: Recent studies have found the presence of a certain amount of circulating DNA in the peripheral blood of patients with malignant tumor and shown that these free DNA bear tumor-specific genetic information. The circulating DNA detection includes quantitative and qualitative methods and analysis. Combined monitoring of changes in circulating DNA levels and aberrant alteration of relevant tumor genes is likely to provide comprehensive real-time information to patients., Results: Under normal conditions, oncogene presents in the form of proto-oncogene such as K-ras, which is in non-carcinogenic status under the influence of tumor suppressor gene. When tumor suppressor gene is damaged or mutated of oncogene itself is induced for instance P53, oncogene is then activated and induces tumorigenesis. However, compared to gene mutation detection, the detection of DNA methylation is relatively more well-developed and stable., Conclusions: This article reviews the current status of the research on circulating DNA in the diagnosis, assessment of response to therapy and prognostic evaluation in GC. In addition, the advantage, current issue and prospect of using circulating DNA as tumor marker are also analyzed.

Adhesion molecules expressed on cerebral endothelial cells (ECs) mediate leukocyte recruitment and play a significant role in cerebral inflammation. Increased levels of adhesion molecules on the EC surface induce leukocyte infiltration into inflammatory areas and are thus hallmarkers of inflammation. Honokiol, isolated from the Chinese medicinal herb Magnolia officinalis, has various pharmacological activities, including anti-inflammatory effects, yet the nature of honokiol targeting molecules remains to be revealed. Here, we investigated the inhibitory effect of honokiol on neutrophil adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression, which underlie its molecular target, and mechanisms for inactivating nuclear factor κ enhancer binding protein (NF-κB) in mouse cerebral ECs. Honokiol inhibited tumour necrosis factor-α (TNF-α)-induced neutrophil adhesion and VCAM-1 gene expression in cerebral ECs. The inflammatory transcription factor NF-κB was downregulated by honokiol. Honokiol significantly blocked TNF-α-induced NF-κB p65 nuclear translocation and degradation of the proteasome-dependent inhibitor of NF-κB α (IκBα). From docking model prediction, honokiol directly targeted the ubiquitin-ubiquitin interface of Lys48-linked polychains. Moreover, honokiol prevented the TNF-α-induced Lys48-linked polyubiquitination, including IκBα-polyubiquitin interaction. Honokiol has protective anti-inflammatory effects on TNF-α-induced neutrophil adhesion and VCAM-1 gene expression in cerebral ECs, at least in part by directly inhibiting ubiquitination-mediated IκBα degradation and then preventing NF-κB nuclear translocation.

A series of novel benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives were designed and synthesized. The biological activities of these derivatives were then evaluated as potential antitumour agents. These compounds were assayed for growth-inhibitory activity against HCT116, MCF-7 and HepG2 cell lines in vitro. The IC50 values of compounds A1 and A7 against the cancer cells were 0.06-3.64 μM and 0.04-9.80 μM, respectively. Their antiproliferative activities were significantly better than that of 5-Fluorouracil (IC50: 56.96-174.50 μM) and were close to that of Paclitaxel (IC50: 0.026-1.53 μM). The activity of these derivatives was over 100 times more effective than other reported structures of chalcone analogues (licochalcone A). A preliminary mechanistic study suggested that these compounds inhibit p53-MDM2 binding. Compounds A1, A7 and A9 effectively inhibited tumour growth in BALB/c mice with colon carcinoma HCT116 cells. The group administered 200 mg/kg of compound A7 showed a 74.6% tumour growth inhibition with no signs of toxicity at high doses that was similar to the inhibition achieved with the 12.5 mg/kg irinotecan positive control (70.2%). Therefore, this class of benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives represents a promising lead structure for the development of possible p53-MDM2 inhibitors as new antitumour agents., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: To explore the expression of miR-135b in endometrial carcinoma and the mechanism by which miR-135b promotes the proliferation of endometrial cancer cells., Methods: The expressions of miR-135b and FOXO1 were using RT-PCR detected in 22 fresh endometrial cancer tissues and paired adjacent tissues and also in endometrial cancer cell lines JEC, Ishikawa, HEC-1-B, and RL-952. The RL-952 and Ishikawa cell lines were transfected with miR-135b mimics or inhibitors, and the changes in their proliferative activity were detected with MTT assay; the expressions of FOXO1 mRNA and protein were detected by RT-PCR and Western blotting, respectively., Results: The expression of miRNA135b was significantly up-regulated and FOXO1 expression was down-regulated in endometrial carcinoma tissues as compared with the adjacent tissues (P<0.05). The mRNA expression of miR-135b was negatively correlated with the expression of FOXO1 in endometrial carcinoma. In RL-952 and Ishikawa cell lines, transfection with miR-135b mimics obviously promoted the cell proliferation (P<0.05). Up-regulation of miR-135b significantly decreased the expressions of FOXO1 protein and mRNA (P<0.05), and down- regulation of miR-135b increased FOXO1 expressions (P<0.05)., Conclusions: MiR-135b plays an important role in the occurrence and development of endometrial carcinoma partially by regulating its target gene FOXO1.

Objectives: Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility., Methods: The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction., Results: Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR&#95;int=1.16, P&#95;int&#95;all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P&#95;all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets., Conclusions: Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Investigating whether socioeconomic characteristics determine if hospice is received at home or in a medical facility is important to examine, considering most patients prefer to die at home. This study relied upon The State Inpatient Data of Nevada. A total of 19 206 discharges were analyzed from the data set between 2009 and 2013. The results indicate that increasingly patients are being discharged to home and overall socioeconomic characteristics appear to have less of an influence over whether hospice is received at home or in a medical facility. Further research on the perspectives of patients would provide insight into whether patients' preferences or socioeconomic characteristics are more influential on where hospice services are received., (© The Author(s) 2014.)

We present a patient with neonatal onset of hypertonia and seizures identified through whole exome sequencing to have compound heterozygous variants, c.294dupA (p.Leu99fs) and c.1925C>A (p.Ala642Glu), in the BRCA1-associated protein required for ATM activation-1 (BRAT1) gene. Variants in BRAT1 have been identified to cause lethal neonatal rigidity and multifocal seizure syndrome (OMIM# 614498), which consistently manifests a severe neurological phenotype that includes neonatal presentation of rigidity and hypertonia, microcephaly and arrested head growth, intractable seizures, absence of developmental progress, apneic episodes, and death usually by 6 months of age. Our patient initially had a similarly severe neurological picture but remains alive at 6 years of age, expanding the phenotype to include longer term survival and providing further insights into genotype-phenotype correlations and the natural history of this disease., (© 2015 Wiley Periodicals, Inc.)

Three dibenzo[a,e]pentalene derivatives containing two redox-active amine substituents have been prepared. The degree of amine-amine electronic coupling through the dibenzo[a,e]pentalene bridge greatly depends on the substitution positions. Three monoamine compounds have been prepared for comparison studies. The experimental data and analysis were corroborated by time-dependent density functional theory results of mixed-valent compounds.

Background: Studies on the relationship between unemployment rate and smoking have yielded mixed results. The issue in China has not been studied. This study aims to examine the influence of unemployment rate on smoking in China., Methods: Logit model and two-stage least squares (2SLS) estimation were used to estimate the effects. Estimations were done for 4585 individual over 45 using data from China Health and Retirement Longitudinal Study conducted in Zhejiang and Gansu provinces in 2008 and 2012., Results: A percent increase in the unemployment rate resulted in the increase in the likelihood of smoking by a combined 9.1 percent for those who smoked including a 2.9% increase for those who smoked 1-10 cigarettes per day; a 2.8% increase for those who smoked 11-20 cigarettes per day; and a 3.4% increase for those who smoked 20 cigarettes or more per day. The effects were stronger for those who were employed. Non-drinkers were more likely to engage in smoking with increased unemployment rate. 2SLS estimation revealed the same association., Conclusions: The unemployment rate was positively associated with smoking behavior. Smoking control and intervention strategies should focus on both the individual's characteristics and the physical environment in which unemployment rate tend to rise.

Hybrid drug delivery system containing both organic and inorganic nanocarriers is expected to achieve its complementary advantages for the aim of improving the performance of antineoplastic drugs in tumor therapy. Here we report the use of liposomes and gold nanoparticles to construct a liposome with a hybrid Cluster Bomb structure and discuss its unique multi-order drug release property for liver tumor treatment. A very simple method is used for the hybrid liposome preparation and involves mixing two solutions containing liposomes loaded with either non-covalent or covalent Paclitaxel (PTX, namely free PTX or PTX-conjugated GNPs, respectively) by different ratio of volume (25:75, 50:50, 25:75, v/v). Various mixed liposomes were tested to determine the optimal conditions for maximum drug delivery. The optimized liposome was then tested using xenograft Heps tumor-bearing mice and showed the best efficacy for chemotherapeutic inhibition of tumor at PTX liposome: PTX-conjugated GNP liposome of 25:75 ratio (v/v). This system allows for simple and easy preparation while providing a more accurate site- and time-release mode for tumor treatment using antitumor drugs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)