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Objectives: Early in the outbreak, to predict the final size of the COVID-19 outbreak in Dalian, Liaoning province, China, the finding can be used to provide a scientific reference for timely adjustment of prevention and control strategies., Methods: Data from COVID-19 patients were collected from August 26 to September 14 2022. Early in the outbreak, a Susceptible-Exposed-Infectious-Quarantine-Recovered (SEIQR) dynamics model with an epidemic amplifier effect, based on the basic model, was developed to fit the data and predict the final size of the COVID-19 outbreak in Dalian, Liaoning province, China. The mean absolute relative error(MARE), root mean squared error(RMSE) and mean absolute error(MAE) were used to assess the predictive capacity of the model., Results: From 26 August to 14 September 2022, 1132 confirmed cases and infected asymptomatic cases of COVID-19 (558 males and 574 females) were reported in Dalian. There were two epidemic amplifiers in this outbreak, namely, T Market and H Hotel. The outbreak size predicted by the combined application of the SEIQR model with these two amplifiers is 1168.34 cases, and MARE, RMSE and MAE compared to the actual value from September 1 to 14 is 1.894%, 21.473 and 17.492 respectively According to the fitting results of the basic SEIQR model, if there was no epidemic amplifier in this outbreak, the final outbreak size was 349.96 cases, which means that the T Market and H Hotel increased 822 infections through amplification., Conclusions: Early in the outbreak, it was effective and reliable to use the SEIQR transmission dynamics model with the amplifier effect to predict the final size of the COVID-19 outbreak in Dalian, Liaoning province, China, and the result can provide a theoretical basis for the early closing of the COVID-19 epidemic amplifier sites. Furthermore, the epidemic amplifier effect added to the model can solve the homogeneous mixing hypothesis problem that does not match the actual spread of infectious diseases but commonly used by researchers in the construction process of the dynamic model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 An et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation in the disparities in initiating these medications., Methods: Using 2017-2018 claims data from a 15% random nationwide sample of Medicare Part D beneficiaries, we identified individuals diagnosed with type 2 diabetes (T2D), who had ≥1 GLD prescriptions, and did not use SGLT2i or GLP1a in the year prior to the index date,1/1/2018. Patients were followed up for a year. The cohort was spatiotemporally linked to Dartmouth hospital-referral regions (HRRs), with each patient assigned to 1 of 306 HRRs. We performed multivariable Poisson regression to estimate adjusted initiation rates, and multivariable logistic regression to assess racial disparities in each HRR., Results: Among 795,469 individuals with T2D included in the analyses, the mean (SD) age was 73 (10) y, 53.3% were women, 12.2% were non-Hispanic Black, and 7.2% initiated a newer GLD in the follow-up year. In the adjusted model including clinical factors, compared to non-Hispanic White patients, non-Hispanic Black (initiation rate ratio, IRR [95% CI]: 0.66 [0.64-0.68]), American Indian/Alaska Native (0.74 [0.66-0.82]), Hispanic (0.85 [0.82-0.87]), and Asian/Pacific islander (0.94 [0.89-0.98]) patients were less likely to initiate newer GLDs. Significant geographic variation was observed across HRRs, with an initiation rate spanning 2.7%-13.6%., Conclusions: This study uncovered substantial geographic variation and the racial disparities in initiating newer GLDs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study investigated the oncological and functional outcomes of robot-assisted radical prostatectomy (RaRP) in high-risk and very high-risk prostate cancer patients., Materials and Methods: One hundred localized prostate cancer patients receiving RaRP from August 2015 to December 2020 were retrospectively enrolled. According to NCCN risk classification, patients were classified into two groups, below high-risk group, and high-risk/very high-risk group, to analyze continence outcome within postoperative year one and biochemical recurrence-free survival., Results: The mean age of the cohort was 69.7 ± 7.4 years with a median follow-up of 26.4 (range 3.3-71.3) months. Among them, 53%, and 47% patients were below high-risk group, and high-risk/very high-risk group, respectively. The median biochemical recurrence-free survival of the entire cohort was 53.1 months. The high-risk/very high-risk group without adjuvant treatment had significantly worse biochemical recurrence-free survival than the high-risk/very high-risk group with adjuvant treatment (19.6 vs. 60.5 months, p = 0.029). Rates of postoperative stress urinary incontinence at 1 week, 1 month, and 12 months were 50.7%, 43.7%, and 8.5%, respectively. High-risk/very high-risk patients had significantly higher rates of stress urinary incontinence at postoperative week 1 (75.8% vs. 28.9%) and month 1 (63.6% vs. 26.3%) than the below high-risk group (both p < 0.01). Rates of stress urinary incontinence after RaRP did not differ between two groups from postoperative 3 months to 12 months. The factor of high-risk / very high-risk group was a predictor of immediate but not for long-term postoperative stress urinary incontinence., Conclusions: High-risk and very high-risk prostate cancer patients receiving a combination of RaRP and adjuvant treatment had comparable biochemical recurrence-free survival to below high-risk prostate cancer patients. The high-risk/very high-risk factor impeded early but not long-term postoperative recovery of continence. RaRP can be considered a safe and feasible option for high-risk and very high-risk prostate cancer patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Patients with hemoglobinopathies have been reported to have higher rates of pulmonary complications. Few studies have investigated the association between thalassemia and asthma in children., Methods: We used the data of one million individuals randomly selected from the Registry for Beneficiaries of the National Health Insurance Research Database. One thalassemic child was matched with four control children without thalassemia according to sex, birth year, birth season, prematurity, and previous enteroviral infection., Results: A total of 800 hundred thalassemic children and 3200 controls were included. Children with thalassemia had higher rates of developing asthma (41.81 vs 25.70 per 1000 person-years, P < 0.001) than the non-thalassemia controls with an adjusted hazard ratio of 1.37 (95% confidence interval [CI] = 1.19-1.58). Boys in the thalassemia cohort had a significantly higher adjusted incidence hazard ratio (IRR) of asthma than those in the non-thalassemia cohort (adjusted IRR = 1.45, 95% CI = 1.02-1.73). The risk of atopic and nonatopic asthma was higher in the thalassemia cohort than in the non-thalassemia cohort (IRR = 1.3, 1.61, respectively)., Conclusions: Children with thalassemia were more likely to develop asthma. More attention should be paid to the early diagnosis of asthma and prevention of asthma attacks., Competing Interests: The authors have declared that no competing interests exist.

Introduction: From late 2014 through 2015, Scott County, Indiana faced an HIV outbreak triggered by opioid abuse and transition to injection drug use. Investigating the origins, risk factors, and responses related to this outbreak is critical to inform future surveillance, interventions, and policymaking. In response, this retrospective infoveillance study identifies and characterizes user-generated messages related to opioid abuse, heroin injection drug use, and HIV status using natural language processing (NLP) among Twitter users in Indiana during the period of this HIV outbreak., Materials and Methods: Our study consisted of two phases: data collection and processing, and data analysis. We collected Indiana geolocated tweets from the public Twitter API using Amazon Web Services EC2 instances filtered for geocoded messages in the immediate pre and post period of the outbreak. In the data analysis phase we applied an unsupervised machine learning approach using NLP called the Biterm Topic Model (BTM) to identify tweets related to opioid, heroin/injection, and HIV behavior and then examined these messages for HIV risk-related topics that could be associated with the outbreak., Results: More than 10 million geocoded tweets occurring in Indiana during the immediate pre and post period of the outbreak were collected for analysis. Using BTM, we identified 1350 tweets thought to be relevant to the outbreak and then confirmed 358 tweets using human annotation. The most prevalent themes identified were tweets related to self-reported abuse of illicit and prescription drugs, opioid use disorder, self-reported HIV status, and public sentiment regarding the outbreak. Geospatial analysis found that these messages clustered in population dense areas outside of the outbreak, including Indianapolis and neighboring Clark County., Discussion: This infoveillance study characterized the social media conversations of communities in Indiana in the pre and post period of the 2015 HIV outbreak. Behavioral themes detected reflect discussion about risk factors related to HIV transmission stemming from opioid and heroin abuse for priority populations, and also help identify community attitudes that could have motivated or detracted the use of HIV prevention methods, along with helping identify factors that can impede access to prevention services., Conclusions: Infoveillance approaches, such as the analysis conducted in this study, represent a possibly strategy to detect "signal" of the emergence of risk factors associated with an outbreak though may be limited in their scope and generalizability. Our results, in conjunction with other forms of public health surveillance, can leverage the growing ubiquity of social media platforms to better detect opioid-related HIV risk knowledge, attitudes and behavior, as well as inform future prevention efforts., Competing Interests: The authors have declared that no competing interests exist.

Background: Keeping older workers in employment is critical for societies facing the challenge of an ageing population. This study examined the association between types of health conditions and differentials in the probability of employment by level of education among men and women between 60-69 years of age in Canada, Denmark, Sweden and England., Methods: Data were drawn from the Canadian Community Health Survey, Survey of Health, Ageing and Retirement in Europe and English Longitudinal Study of Ageing. We combined country data, applied logistic regression, adjusted for educational level, and stratified the analysis by sex to calculate the odds ratio (OR) of employment (>15 hours work per week) for persons with physical health conditions, mental health conditions (depression) and physical-mental health comorbidity., Results: The odds of employment among men and women with physical-mental health comorbidity were lower compared to those with no/other conditions (men: OR 0.32, 95% CI: 0.25-0.42, women: OR 0.38 95% CI: 0.30-0.48). Women with low education had lower odds of employment compared to their counterparts with high education (OR 0.66, 95% CI: 0.57-0.76). The odds of employment at older ages was lower in Canada, Denmark and England compared with Sweden (e.g. English men: OR 0.48 95% CI 0.40-0.58; English women OR 0.33 95% CI 0.27-0.41)., Conclusions: The odds of employment beyond age 60 is lower for groups with low education, particularly women, and those with physical-mental health co-morbidities. As such, policies to extend working lives should not be 'one size fits all' but instead consider subgroups, in particular, these groups that we have shown to be most vulnerable on the labour market., Competing Interests: The authors have declared that no competing interests exists.

Objectives: Comorbidity is prevalent in older working ages and might affect employment exits. This study aimed to 1) assess the associations between comorbidity and different employment exit routes, and 2) examine such associations by gender., Methods: We used data from employed adults aged 50-62 in the Stockholm Public Health Survey 2002 and 2006, linked to longitudinal administrative income records (N = 10,416). The morbidity measure combined Limiting Longstanding Illness and Common Mental Disorder-captured by the General Health Questionnaire-12 (≥4)-into a categorical variable: 1) No Limiting Longstanding Illness, no Common Mental Disorder, 2) Limiting Longstanding Illness only, 3) Common Mental Disorder only, and 4) comorbid Limiting Longstanding Illness+Common Mental Disorder. Employment status was followed up until 2010, treating early retirement, disability pension and unemployment as employment exits. Competing risk regression analysed the associations between morbidity and employment exit routes, stratifying by gender., Results: Compared to No Limiting Longstanding Illness, no Common Mental Disorder, comorbid Limiting Longstanding Illness+Common Mental Disorder was associated with early retirement in men (subdistribution hazard ratio = 1.73, 95% confidence intervals: 1.08-2.76), but not in women. For men and women, strong associations for disability pension were observed with Limiting Longstanding Illness only (subdistribution hazard ratio = 11.43, 95% confidence intervals: 9.40-13.89) and Limiting Longstanding Illness+Common Mental Disorder (subdistribution hazard ratio = 14.25, 95% confidence intervals: 10.91-18.61), and to a lesser extent Common Mental Disorder only (subdistribution hazard ratio = 2.00, 95% confidence intervals: 1.31-3.05). Women were more likely to exit through disability pension than men (subdistribution hazard ratio = 1.96, 95% confidence intervals: 1.60-2.39). Common Mental Disorder only was the only morbidity category associated with unemployment (subdistribution hazard ratio = 1.70, 95% confidence intervals: 1.36-2.15)., Conclusions: Strong associations were observed between specific morbidity categories with different employment exit routes, which differed by gender. Initiatives to extend working lives should consider older workers' varied health needs to prevent inequalities in older age., Competing Interests: The authors have declared that no competing interests exist.

The ability for safe and rapid pathogenic sample transportation and subsequent detection is an increasing challenge throughout the world. Herein, we describe and use bead-beating, vortex, sonication, 903 protein saver cards, and Lyse-It methods, aiming to inactivate Gram-positive and -negative bacteria with subsequent genome DNA (quantitative Polymerase Chain Reaction) qPCR detection. The basic concepts behind the four chosen technologies is their versatility, cost, and ease of use in developed and underdeveloped countries. The four methods target the testing of bacterial resilience, cellular extraction from general and complex media and subsequent DNA extraction for qPCR detection and amplification. These results demonstrate that conventional high temperature heating, 903 protein saver cards, and Lyse-It are all viable options for inactivating bacterial growth for safe shipping. Additionally, Lyse-It was found to be particularly useful as this technology can inactivate bacteria, extract cells from 903 protein saver cards, lyse bacterial cells, and additionally keep genomic DNA viable for qPCR detection., Competing Interests: This work is supported by the UMBC-UMB Cholera joint training grant and the National Institutes of Health UMBC Graduate Training Chemistry Biology Interface Fellowship (T32GM066706-15). We note that the University of Maryland, Baltimore County (UMBC) has filed and has had issued several patents related to microwave-based lysing and DNA fragmentation. Those patents are licensed to Lyse-It LLC, a Maryland-based biotechnology company to which Dr. Geddes currently owns stock. Patent #: US US9500590B2. “Assays for pathogen detection using microwaves for lysing and accelerating metal-enhanced fluorescence”, Chris D. Geddes. Patent #: US10294451B2 “Flow and static lysing systems and methods for ultra-rapid isolation and fragmentation of biological materials by microwave irradiation”, Chris D. Geddes. Lyse-It LLC was not involved in the study design of the material within this paper,nor do any of the author receive any salaries or consultancies from Lyse-It LLC.

Presently, climate change has increased the frequency of extreme meteorological events such as tropical cyclones. In the western Pacific basin, these cyclones are called typhoons, and in this area, around Taiwan Island, their frequency has almost doubled since 2000. When approaching landmasses, typhoons have devastating effects on coastal vegetation. The increased frequency of these events has challenged the survival of coastal plant species and their posttyphoon recovery. In this study, a population of coastal gynodioecious Ficus pedunculosa var. mearnsii (Mearns fig) was surveyed for two years to investigate its recovery after Typhoon Morakot, which occurred in August 2009. Similar to all the Ficus species, the Mearns fig has an obligate mutualistic association with pollinating fig wasp species, which requires syconia (the closed Ficus inflorescence) to complete its life cycle. Moreover, male gynodioecious fig species produces both pollen and pollen vectors, whereas the female counterpart produces only seeds. The recovery of the Mearns fig was observed to be rapid, with the production of both leaves and syconia. The syconium:leaf ratio was greater for male trees than for female trees, indicating the importance of syconium production for the wasp survival. Pollinating wasps live for approximately 1 day; therefore, receptive syconia are crucial. Every typhoon season, few typhoons pass by the coasts where the Mearns fig grows, destroying all the leaves and syconia. In this paper, we highlight the potential diminution of the fig population that can lead to the extinction of the mutualistic pair of species. The effects of climate change on coastal species warrant wider surveys.

Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostate-specific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-γ+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-γ+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future.

Background: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR)., Methods: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups., Results: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis., Conclusions: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.

Purpose: To examine the long-term risk of essential tremor (ET) in migraine., Methods: Using population-based administrative data from a subset of the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22,696 newly diagnosed migraineurs (mean age 44.5 years) and a matched migraine-free cohort of 90,784 individuals in the period 2000-2008. Multivariable Cox proportional hazards regression analysis was conducted for assessing the ET risk for the migraine cohort compared to the migraine-free cohort., Results: After adjusting for covariates, the migraine cohort had a 1.83-fold increased risk (95% CI 1.50-2.23) of subsequent ET in comparison to the migraine-free cohort (8.97 vs. 4.81 per 10,000 person-years). In the subgroup analysis, patients with migraine were associated with higher risks of ET, regardless of gender, age or the existence of comorbidities., Conclusion: Our findings demonstrated an association between migraine and ET, suggesting a possible shared pathophysiology underpinning both disorders.

Purpose: This study aimed to clarify the prognostic utility of high-sensitivity C-reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the Intensity-Modulated Radiotherapy (IMRT) era., Patients and Methods: In this observational study, 1,589 non-metastatic NPC patients treated with IMRT were recruited. Blood samples were collected before treatment for examination of hs-CRP levels. We evaluated the association of pretreatment hs-CRP levels with overall survival rate (OS), progression free survival rate (PFS), locoregional relapse free survival rate (LRFS) and distant metastasis free survival rate (DMFS)., Results: Baseline hs-CRP levels were correlated with sex, clinical stage, body mass index, smoking status, and EBV DNA level. Multivariate analysis showed that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238-2.398; p = 0.001), PFS (HR:1.621; 95%CI:1.273-2.064; p<0.001) and DMFS (HR:1.879; 95%CI:1.394-2.531; p<0.001). In subgroups such as advanced-stage group, low EBV DNA group and high EBV DNA group, elevated hs-CRP levels still predicted poor clinical outcomes. Furthermore, in patients with chronic HBV infection, decreased 4-year survival was observed in the cohort of high hs-CRP levels, with 87.4% vs. 94.9% (p = 0.023) for OS, 65.2% vs. 90.8% (p<0.001) for PFS, and 67.6% vs. 95.0% (p<0.001) for DMFS. A similar finding was observed for patients with cardiovascular disease, with 79.1% vs. 90.2% (p = 0.020) for PFS, and 71.4% vs. 97.6% (p = 0.002) for DMFS., Conclusion: Elevated serum hs-CRP levels were correlated with poor survival for NPC patients in the IMRT era, playing a complementary role to TNM stage and EBV DNA. In addition, elevated hs-CRP level was still an effective indicator for patients with chronic HBV infection and cardiovascular disease.

Homocysteine level can lead to adverse effects on the brain white matter through endothelial dysfunction, microstructural inflammation, and neurotoxin effects. Despite previously observed associations between elevated homocysteine and macroscopic structural brain changes, it is still unknown whether microstructural associations of homocysteine on brain tissue properties can be observed in healthy subjects with routine MRI. To this end, we investigated potential relationships between homocysteine levels and microstructural measures computed with diffusion tensor imaging (DTI) in a cohort of 338 healthy participants. Significant positive correlations were observed between homocysteine levels and diffusivity measures in the bilateral temporal WM, the brainstem, and the bilateral cerebellar peduncle. This is the first study demonstrating that DTI is sufficiently sensitive to relate microstructural WM properties to homocysteine levels in healthy subjects.

Five B-class MADS-box genes, including four APETALA3 (AP3)-like PeMADS2∼5 and one PISTILLATA (PI)-like PeMADS6, specify the spectacular flower morphology in orchids. The PI-like PeMADS6 ubiquitously expresses in all floral organs. The four AP3-like genes, resulted from two duplication events, express ubiquitously at floral primordia and early floral organ stages, but show distinct expression profiles at late floral organ primordia and floral bud stages. Here, we isolated the upstream sequences of PeMADS2∼6 and studied the regulatory mechanism for their distinct gene expression. Phylogenetic footprinting analysis of the 1.3-kb upstream sequences of AP3-like PeMADS2∼5 showed that their promoter regions have sufficiently diverged and contributed to their subfunctionalization. The amplified promoter sequences of PeMADS2∼6 could drive beta-glucuronidase (GUS) gene expression in all floral organs, similar to their expression at the floral primordia stage. The promoter sequence of PeMADS4, exclusively expressed in lip and column, showed a 1.6∼3-fold higher expression in lip/column than in sepal/petal. Furthermore, we noted a 4.9-fold increase in histone acetylation (H3K9K14ac) in the translation start region of PeMADS4 in lip as compared in petal. All these results suggest that the regulation via the upstream sequences and increased H3K9K14ac level may act synergistically to display distinct expression profiles of the AP3-like genes at late floral organ primordia stage for Phalaenopsis floral morphogenesis.

The BioBricks standard has made the construction of DNA modules easier, quicker and cheaper. So far, over 100 BioBricks assembly schemes have been developed and many of them, including the original standard of BBF RFC 10, are now widely used. However, because the restriction endonucleases employed by these standards usually recognize short DNA sequences that are widely spread among natural DNA sequences, and these recognition sites must be removed before the parts construction, there is much inconvenience in dealing with large-size DNA parts (e.g., more than couple kilobases in length) with the present standards. Here, we introduce a new standard, namely iBrick, which uses two homing endonucleases of I-SceI and PI-PspI. Because both enzymes recognize long DNA sequences (>18 bps), their sites are extremely rare in natural DNA sources, thus providing additional convenience, especially in handling large pieces of DNA fragments. Using the iBrick standard, the carotenoid biosynthetic cluster (>4 kb) was successfully assembled and the actinorhodin biosynthetic cluster (>20 kb) was easily cloned and heterologously expressed. In addition, a corresponding nomenclature system has been established for the iBrick standard.

Background: The karst regions in South China have an abundance of endemic plants that face high extinction risks. The Chinese Gesneriaceae endemic Paraisometrum mileense ( = Oreocharis mileensis), was presumed extinct for 100 years. After its re-discovery, the species has become one of five key plants selected by the Chinese forestry government to establish a new conservation category for plants with extremely small populations. For conservation purposes, we studied the phylogenetic and population genetic status of P. mileense at the three only known localities in Guangxi, Guizhou and Yunnan., Methodology/principal Findings: We collected 64 samples (52 species) of Oreocharis and 8 samples from three provinces of P. mileense and generated molecular phylogenies, and inferred that P. mileense represents a relatively isolated and derived taxonomic unit within Oreocharis. Phylogeographic results of 104 samples of 12 populations of P. mileense indicated that the populations in Yunnan have derived from those in Guangxi and Guizhou. Based on AFLP data, the populations were found to harbor low levels of genetic diversity (He = 0.118), with no apparent gradient across the species' range, a restricted gene flow and significant isolation-by-distance with limited genetic differentiation among the populations across the three provinces (FST = 0.207, P<0.001). The 10 populations in Yunnan were found to represent two distinct lineages residing at different altitudes and distances from villages., Conclusion/significance: The low levels of genetic diversity found in P. mileense are perhaps a consequence of severe bottlenecks in the recent past. The distribution of the genetic diversity suggests that all populations are significant for conservation. Current in situ and ex situ measures are discussed. Further conservation actions are apparently needed to fully safeguard this conservation flagship species. Our work provides a model of an integrated study for the numerous endemic species in the karst regions with extremely small populations.

Esophageal carcinoma is one of the world's deadliest cancers. Esophageal squamous cell carcinoma (ESCC) is more frequent than adenocarcenoma (AC) in China. Platinum-based chemotherapy with surgical resection is a common treatment approach for ESCC; however, the treatment response is uncertain. Evidence suggests polymorphisms in genes encoding excision repair cross-complementing group 1 (ERCC1), a protein involved in nuclear excision repair (NER), may help predict response to cisplatin and other platinum-based chemotherapeutics. Multiple ERCC1 single nucleotide polymorphisms (SNPs) have been associated with platinum chemotherapy response. Two common SNPs occur at the C8092A and C118T loci. Our study aimed to determine if 1) an association exists between ERCC1 tumor expression and patient survival, 2) whether adjuvant therapy influence on survival is related to histological ERCC1 presence in tumor cell nuclei, and 3) whether other clinicopathological characteristics in a cohort of patients following surgery for various stages of ESCC are associated with tumor ERCC1 expression. One hundred eight patients were included in the study, and tumor biopsy was collected for genotyping and immunohistochemical analysis of ERCC1. Sixty-seven patients (62%) received no adjuvant therapy, and the rest had either platinum-based chemotherapy (28.5%), radiotherapy (6.5%) or both treatments (2.8%). Log-rank analysis revealed no significant connection between tumor ERCC1 expression (P = 0.12) or adjuvant therapy (P = 0.56) on patient survival. Also, non-parametric Mann-Whitney analysis showed no significant link between tumor size or nodus tumor formation and ERCC1 presence in patients in the study. Interestingly, C8092A SNP showed significant association with patient survival (P = 0.01), with patients homozygous for the mutant allele showing the most significantly reduced survival (P = 0.04) compared to those homozygous for the dominant allele (CC). Our results provide novel insight into the genotypic variation of patients from Quanzhou, Fujian province China.

Hippocampal neurons play a critical role in learning and memory; however, the effects of environmental mechanical forces on neurite extension and associated underlying mechanisms are largely unexplored, possibly due to difficulties in maintaining central nervous system neurons. Neuron adhesion, neurite length, and mechanotransduction are mainly influenced by the extracellular matrix (ECM), which is often associated with structural scaffolding. In this study, we investigated the relationship between substrate stiffness and hippocampal neurite outgrowth by controlling the ratios of polydimethylsiloxane (PDMS) base to curing agent to create substrates of varying stiffness. Immunostaining results demonstrated that hippocampal neurons have longer neurite elongation in 35:1 PDMS substrate compared those grown on 15:1 PDMS, indicating that soft substrates provide a more optimal stiffness for hippocampal neurons. Additionally, we discovered that pPKCα expression was higher in the 15:1 and 35:1 PDMS groups than in the poly-L-lysine-coated glass group. However, when we used a fibronectin (FN) coating, we found that pFAKy397 and pFAKy925 expression were higher in glass group than in the 15:1 or 35: 1 PDMS groups, but pPKCα and pERK1/2 expression were higher in the 35:1 PDMS group than in the glass group. These results support the hypothesis that environmental stiffness influences hippocampal neurite outgrowth and underlying signaling pathways.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is thought to play modulatory roles in the development of atherosclerosis. Here we evaluated the effects of a specific lp-PLA2 inhibitor on atherosclerosis in ApoE-deficient mice and its associated mechanisms., Methodology/principal Findings: ApoE-deficient mice fed an atherogenic high-fat diet for 17 weeks were divided into two groups. One group was administered the specific lp-PLA2 inhibitor, darapladib (50 mg/kg/day; p.o.) daily for 6 weeks, while the control group was administered saline. We observed no differences in body weight and serum lipids levels between the two groups at the end of the dietary period. Notably, serum lp-PLA2 activity as well as hs-CRP (C-reactive protein) and IL-6 (Interleukin-6) levels were significantly reduced in the darapladib group, compared with the vehicle group, while the serum PAF (platelet-activating factor) levels were similar between the two groups. Furthermore, the plaque area through the arch to the abdominal aorta was reduced in the darapladib group. Another finding of interest was that the macrophage content was decreased while collagen content was increased in atherosclerotic lesions at the aortic sinus in the darapladib group, compared with the vehicle group. Finally, quantitative RT-PCR performed to determine the expression patterns of specific inflammatory genes at atherosclerotic aortas revealed lower expression of MCP-1, VCAM-1 and TNF-α in the darapladib group., Conclusions/significance: Inhibition of lp-PLA2 by darapladib leads to attenuation of in vivo inflammation and decreased plaque formation in ApoE-deficient mice, supporting an anti-atherogenic role during the progression of atherosclerosis.