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Dinoflagellates, which are responsible for more than 80% of harmful algal blooms in coastal waters, are competitive in low-phosphate environments. However, the specific acclimated phosphorus strategies to adapt to phosphorus deficiency in dinoflagellates, particularly through intracellular phosphorus metabolism, remain largely unknown. Comprehensive physiological, biochemical, and transcriptomic analyses were conducted to investigate intracellular phosphorus modulation in a model dinoflagellate, Prorocentrum shikokuense, with a specific focus on membrane lipid remodeling and autophagy in response to phosphorus deficiency. Under phosphorus deficiency, P. shikokuense exhibited a preference to spare phospholipids with nonphospholipids. The major phospholipid classes of phosphatidylcholine and phosphatidylethanolamine decreased in content, whereas the betaine lipid class of diacylglyceryl carboxyhydroxymethylcholine increased in content. Furthermore, under phosphorus deficiency, P. shikokuense induced autophagy as a mechanism to conserve and recycle cellular phosphorus resources. The present study highlights the effective modulation of intracellular phosphorus in P. shikokuense through membrane phospholipid remodeling and autophagy and contributes to a comprehensive understanding of the acclimation strategies to low-phosphorus conditions in dinoflagellates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Extensive application of organophosphorus pesticides such as phenthoate results in its abundance in ecosystems, particularly in waterbodies, thereby providing the impetus to assess its role in aquatic organisms. However, the impact of phenthoate on marine algal physiological and proteomic response is yet to be explored despite its biological significance. In this study, we thus ought to investigate the impact of phenthoate in the marine dinoflagellate Prorocentrum lima, which is known for synthesizing okadaic acid (OA), the toxin responsible for diarrhetic shellfish poisoning (DSP). Our results showed that P. lima effectively absorbed phenthoate in seawater, with a reduction efficiency of 90.31% after 48 h. Surprisingly, the provision of phenthoate (100 and 1000 µg/L) substantially reduced the OA content of P. lima by 35.08% and 60.28% after 48 h, respectively. Meanwhile, phenthoate treatment significantly reduced the oxidative stress in P. lima. Proteomic analysis revealed that the expression level of seven crucial proteins involved in endocytosis was upregulated, suggesting that P. lima could absorb phenthoate via the endocytic signaling pathway. Importantly, phenthoate treatment resulted in the downregulation of proteins such as polyketide synthase (PKS)- 2, Cytochrome P450 (CYP450)- 1, and CYP450-2, involved in OA synthesis, thereby decreasing the OA biosynthesis by P. lima. Our results demonstrated the potential role of P. lima in the removal of phenthoate in water and exemplified the crucial proteins and their possible molecular mechanisms underpinning the phenthoate remediation by P. lima and also the regulatory role of phenthoate in restricting the OA metabolism. Collectively, these findings uncovered the synergistic mechanisms of phenthoate and P. lima in remediating phenthoate and reducing the toxic impact of P. lima., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Introduction of the mRNA vaccination for coronavirus disease 2019 (COVID-19) has been associated with an increase in cases of peri/myocarditis. In our retrospective cross-sectional study, we aim to (I) describe paediatric chest pain attendance, and (II) study resource utilisation in the Emergency Department (ED) of KK Women's and Children's Hospital (KKH), stratified by pre-pandemic, during the pandemic pre- and post-COVID vaccination introduction in adolescents., Methods: We reviewed records of adolescents aged 12 to 18 years old who presented to our ED with the triage complaint of chest pain between 1 January 2019 to 31 January 2022, and determined the attendance rates, aetiologies and resource utilisation during the above time periods., Results: There were 2,418 ED attendances for chest pain in our study population. Among 887 inpatient admissions for chest pain, 1.8% were attributed to a cardiac cause. Comparing the pre-pandemic period to the period after the mRNA COVID-19 vaccination was introduced, ED chest pain rates increased from a median of 0.5% of ED attendances [interquartile range (IQR), 0.3-0.5%] to 0.9% (IQR, 0.7-2.0%) (P<0.001), while admission rates increased from a median of 26.2% of ED attendances (IQR, 24.1-29.1%) to 40.9% (IQR, 37.6-56.6%) (P<0.001). Cardiac enzyme orders among ED visits for chest pain increased from a pre-pandemic median of 0% (IQR, 0.0-2.6%) to a post-vaccination median of 26.1% (IQR, 17.2-56.2%) (P<0.001) and were due to concerns for vaccine-related myocarditis. Seven cases of probable vaccine-related myocarditis presented with chest pain to our ED., Conclusions: Paediatric chest pain is largely non-cardiac in origin. ED chest pain attendance rates and resource utilisation increased after the introduction of mRNA COVID-19 vaccination in adolescents., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-230/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Polyphosphate (polyP) has long been recognized as a crucial intracellular reservoir for phosphorus in microorganisms. However, the dynamics of polyP and its regulatory mechanism in eukaryotic phytoplankton in response to variations in external phosphorus conditions remain poorly understood. A comprehensive investigation was conducted to examine the intracellular polyP-associated metabolic response of the dinoflagellate Karenia mikimotoi, a harmful algal bloom species, through integrated physiological, biochemical, and transcriptional analyses under varying external phosphorus conditions. Comparable growth curves and Fv/Fm between phosphorus-replete conditions and phosphorus-depleted conditions suggested that K. mikimotoi has a strong capability to mobilize the intracellular phosphorus pool for growth under phosphorus deficiency. Intracellular phosphate (IPi) and polyP contributed approximately 6-23 % and 1-3 %, respectively, to the overall particulate phosphorus (PP) content under different phosphorus conditions. The significant decrease in PP and increase in polyP:PP suggested that cellular phosphorus components other than polyP are preferred for utilization under phosphorus deficiency. Genes involved in polyP synthesis and hydrolysis were upregulated to maintain phosphorus homeostasis in K. mikimotoi. These findings provide novel insights into the specific cellular strategies for phosphorus storage and the transcriptional response in intracellular polyP metabolism in K. mikimotoi. Additionally, these results also indicate that polyP may not play a crucial role in cellular phosphorus storage in phytoplankton, at least in dinoflagellates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Interprofessional communication is needed to enhance the early recognition and management of patients with sepsis. Preparing medical and nursing students using virtual reality simulation has been shown to be an effective learning approach for sepsis team training. However, its scalability is constrained by unequal cohort sizes between medical and nursing students. An artificial intelligence (AI) medical team member can be implemented in a virtual reality simulation to engage nursing students in sepsis team training., Objective: This study aimed to evaluate the effectiveness of an AI-powered doctor versus a human-controlled doctor in training nursing students for sepsis care and interprofessional communication., Methods: A randomized controlled trial study was conducted with 64 nursing students who were randomly assigned to undertake sepsis team training with an AI-powered doctor (AI-powered group) or with medical students using virtual reality simulation (human-controlled group). Participants from both groups were tested on their sepsis and communication performance through simulation-based assessments (posttest). Participants' sepsis knowledge and self-efficacy in interprofessional communication were also evaluated before and after the study interventions., Results: A total of 32 nursing students from each group completed the simulation-based assessment, sepsis and communication knowledge test, and self-efficacy questionnaire. Compared with the baseline scores, both the AI-powered and human-controlled groups demonstrated significant improvements in communication knowledge (P=.001) and self-efficacy in interprofessional communication (P<.001) in posttest scores. For sepsis care knowledge, a significant improvement in sepsis care knowledge from the baseline was observed in the AI-powered group (P<.001) but not in the human-controlled group (P=.16). Although no significant differences were found in sepsis care performance between the groups (AI-powered group: mean 13.63, SD 4.23, vs human-controlled group: mean 12.75, SD 3.85, P=.39), the AI-powered group (mean 9.06, SD 1.78) had statistically significantly higher sepsis posttest knowledge scores (P=.009) than the human-controlled group (mean 7.75, SD 2.08). No significant differences were found in interprofessional communication performance between the 2 groups (AI-powered group: mean 29.34, SD 8.37, vs human-controlled group: mean 27.06, SD 5.69, P=.21). However, the human-controlled group (mean 69.6, SD 14.4) reported a significantly higher level of self-efficacy in interprofessional communication (P=.008) than the AI-powered group (mean 60.1, SD 13.3)., Conclusions: Our study suggested that AI-powered doctors are not inferior to human-controlled virtual reality simulations with respect to sepsis care and interprofessional communication performance, which supports the viability of implementing AI-powered doctors to achieve scalability in sepsis team training. Our findings also suggested that future innovations should focus on the sociability of AI-powered doctors to enhance users' interprofessional communication training. Perhaps in the nearer term, future studies should examine how to best blend AI-powered training with human-controlled virtual reality simulation to optimize clinical performance in sepsis care and interprofessional communication., Trial Registration: ClinicalTrials.gov NCT05953441; https://clinicaltrials.gov/study/NCT05953441., (©Sok Ying Liaw, Jian Zhi Tan, Khairul Dzakirin Bin Rusli, Rabindra Ratan, Wentao Zhou, Siriwan Lim, Tang Ching Lau, Betsy Seah, Wei Ling Chua. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.07.2023.)

Aim: To evaluate the effectiveness of an online program on nurse preceptors' knowledge and self-efficacy in their roles to support students' clinical education, and to examine their online experience., Background: Professional development of nurse preceptors is paramount to fostering work readiness of future graduate nurses on entering the workforce. The support from academic institutions in developing preceptors' roles in clinical teaching and assessment is pivotal., Design: This study employed a mixed-methods design., Method: A total of 59 nurse preceptors from six healthcare institutions participated in an online preceptor program by collaborating with academic educators in facilitating student clinical learning and assessment through telesimulation following web-based instruction. Pre-test and post-tests were administered to evaluate the preceptors' knowledge and self-efficacy in their roles. Survey questionnaires and focus group discussions were conducted to evaluate their online experience. SQUIRE 2.0 guidelines were applied., Results: The preceptors demonstrated significant improvements (p < .001) in knowledge and levels of self-efficacy in their preceptor roles immediately and 1 month after the program. The following four themes emerged from their learning experiences: 'interactive learning approach', 'academic-practice collaboration', 'better understanding of clinical assessment tool' and 'application of teaching strategies'. The preceptors reported positively on their motivation to learn using the web-based instruction and on their telesimulation experience., Conclusion: The study findings demonstrated effectiveness and feasibility of an online preceptor program to enhance preceptors' roles in supporting nursing students' transition to clinical practice, using a mix of web-based technologies to provide preceptors with self-directed and experiential learning approaches., Relevance to Clinical Practice: This study contributed to the development of an innovative online preceptor program that provided opportunity for academic-clinical collaboration and has broad applicability. The telesimulation created robust remote simulation experiences for preceptors, allowing them to collaborate with academic educators in facilitating students' clinical practice amid the COVID-19 pandemic., (© 2022 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Background: Virtual reality simulations are shown to be an effective approach for interprofessional nurse-physician communication training. However, its scalability is constrained by unequal medical-nursing cohort size, rendering a great challenge for all nursing students to form an interprofessional team with medical students. With the evolution of artificial intelligence (AI), an AI medical team player can be integrated into virtual reality simulations for more nursing students to engage in interprofessional team training., Objectives: To describe the development of a novel AI-enabled virtual reality simulation (AI-enabled VRS) and to evaluate nursing students' competencies and experiences in communicating with an AI medical doctor., Methods: A mixed-methods design using a one-group pretest-posttest design and focus group discussions were employed in the evaluation phase. Nursing students from a university were recruited to undertake the 2-hour AI-enabled VRS. Pre-test and post-tests were administered to evaluate the participants' communication knowledge and self-efficacy. Survey questionnaires were administered to examine their experiences with the virtual reality environment and the AI doctor. Five focus group discussions were conducted to gain deeper insight into their learning experiences., Results: The participants demonstrated significant improvements in communication knowledge and interprofessional communication self-efficacy after the learning. They reported positively on the acceptability, feasibility and usability of the AI-enabled VRS. The subscale of "human-like" feature of the AI medical doctor was rated the lowest. Three themes surrounding participants' experiences of the virtual learning emerged: "relate to the real world", "artificial intelligence versus human intelligence" and "complement with face-to-face learning"., Conclusions: This study demonstrates initial evidence on the potential of AI-enabled VRS in fostering nursing students' learning on interprofessional communication skills. The findings have also provided insights on how to improve the AI-enabled VRS, in particular, the expressiveness of the AI pedagogical agent and facilitating more dialogue trainings with learner-agent conversations., Competing Interests: Conflict of interest No conflict of interest has been declared by the authors., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Collaboration between academic institutions and clinical practice plays an important role in supporting students' learning in clinical practice. A virtual telesimulation was incorporated to provide academic-practice collaboration between academic educators and nurse preceptors to support students' clinical education., Purpose: The purpose was to evaluate the experiences of nursing students and academic educators on the perceived impact of virtual telesimulation in clinical education., Methods: A descriptive qualitative study using focus group discussions was conducted., Results: Four themes emerged: "coming together to know one another" for rapport building, "learning from different perspectives" to foster clinical learning and practice, "application of learning strategy" to stimulate case-based discussion, and "reaching out to more preceptors" to optimize its impact in clinical practice., Conclusions: Academic-practice collaboration using virtual telesimulation enabled students and academic educators to build rapport with clinical preceptors and learn from other practices, which in turn enhanced students' clinical learning experiences., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Simulation-based education can equip healthcare providers with the ability to respond to and manage stressors associated with rapidly deteriorating patient situations. However, little is known about the benefits of using virtual reality (VR) for this purpose., Objective: To compare between desktop VR and face-to-face simulation in stress responses and performance outcomes of a team-based simulation training in managing clinical deterioration., Design: A randomised controlled study METHOD: The study was conducted on 120 medical and nursing students working in interprofessional teams. The teams were randomly assigned to participate in a 2-h simulation using either the desktop VR or face-to-face simulation with simulated patient (SP). Biophysiological stress response, psychological stress, and confidence levels were measured before and after the simulation. Performance outcomes were evaluated after the simulation using a deteriorating patient scenario., Results: The systolic blood pressure and psychological stress response were significantly increased among participants in VR and SP groups; however, no significant differences were found between the groups. There was also no significant difference in confidence and performance outcomes between participants in the VR and SP groups for both medical and  nursing students. Although the psychological stress response was negatively correlated (r = -0.43; p < 0.01) with confidence levels, there was no association between stress response and performance score., Conclusion: Despite being less immersive, the desktop VR was capable of inducing psychological and physiological stress responses by placing emotional, social, and cognitive demands on learners. Additionally, by ensuring close alignment between the simulation tasks and the clinical tasks (i.e. functional fidelity), the desktop VR may provide similar performance outcomes as conventional simulation training. This evidence is timely given the rise in the use of virtual learning platforms to facilitate training during the COVID-19 pandemic where face-to-face training may not be feasible., Trial Registration: The study was registered at ClinicalTrials.gov NCT04330924., (© 2022. The Author(s).)

The Fujian Tanka people are officially classified as a southern Han ethnic group, whereas they have customs similar to Daic and Austronesion people. Whether they originated in Han or Daic people, there is no consensus. Three hypotheses have been proposed to explain the origin of this group: (1) the Han Chinese origin, (2) the ancient Daic origin, (3) and the admixture between Daic and Han. This study addressed this issue by analyzing the paternal Y chromosome and maternal mtDNA variation of 62 Fujian Tanka and 25 neighboring Han in Fujian. The southern East Asian predominant haplogroups (e.g., Y-chromosome O1a1a-P203 and O1b1a1a-M95, and mtDNA F2a, M7c1, and F1a1) had relatively high frequencies in Tanka. The interpopulation comparison revealed that the Tanka have a closer affinity with Daic populations than with Han Chinese in paternal lineages but are closely clustered with southern Han populations such as Hakka and Chaoshanese in maternal lineages. Network and haplotype-sharing analyses also support the admixture hypothesis. The Fujian Tanka mainly originate from the ancient indigenous Daic people and have only limited gene flows from Han Chinese populations. Notably, the divergence time inferred by the Tanka-specific haplotypes indicates that the formation of Fujian Tanka was a least 1033.8-1050.6 years before present (the early Northern Song dynasty), indicating that they are an indigenous population, not late Daic migrants from southwestern China.

Background and Aims: Hosting several global biodiversity hotspots, the region of the Qinghai-Tibetan Plateau (QTP) is exceptionally species-rich and harbours a remarkable level of endemism. Yet, despite a growing number of studies, factors fostering divergence, speciation and ultimately diversity remain poorly understood for QTP alpine plants. This is particularly the case for the role of hybridization. Here, we explored the evolutionary history of three closely related Gentiana endemic species, and tested whether our results supported the mountain geo-biodiversity hypothesis (MGH)., Methods: We genotyped 69 populations across the QTP with one chloroplast marker and 12 nuclear microsatellite loci. We performed phylogeographical analysis, Bayesian clustering, approximate Bayesian computation and principal components analysis to explore their genetic relationship and evolutionary history. In addition, we modelled their distribution under different climates., Key Results: Each species was composed of two geographically distinct clades, corresponding to the south-eastern and north-western parts of their distribution. Thus Gentiana veitchiorum and G. lawrencei var. farreri, which diverged recently, appear to have shared at least refugia in the past, from which their range expanded later on. Indeed, climatic niche modelling showed that both species went through continuous expansion from the Last Interglacial Maximum to the present day. Moreover, we have evidence of hybridization in the northwest clade of G. lawrencei var. farreri, which probably occurred in the refugium located on the plateau platform. Furthermore, phylogenetic and population genetic analyses suggested that G. dolichocalyx should be a geographically limited distinct species with low genetic differentiation from G. lawrencei var. farreri., Conclusions: Climatic fluctuations in the region of the QTP have played an important role in shaping the current genetic structure of G. lawrencei var. farreri and G. veitchiorum. We argue that a species pump effect did occur prior to the Last Interglacial Maximum, thus lending support to the MGH. However, our results do depart from expectations as suggested in the MGH for more recent distribution range and hybridization dynamics., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Over the years, the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies, as they exhibit higher therapeutic efficacies and improved toxicological profiles. Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits, asperuloside, an iridoid glycoside, has been proven to provide promising effects as a therapeutic agent for several diseases. Although, this potent substance exists in several genera, it is primarily found in plants belonging to the genus Eucommia. Recent decades have seen a surge in the research on Asperuloside, making it one of the most studied natural products in the field of medicine and pharmacology. In this review, we have attempted to study the various reported mechanisms of asperuloside that form the basis of its wide spectrum of pharmacological activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The mechanisms of the pathogenesis of epilepsy remain unclear. Recent research shows that the inflammatory process occurring in the brain may be a common and critical mechanism of seizures. Chitinase-3-like protein 1 (CHI3L1 or YKL-40) is a newly discovered inflammatory factor. We aimed to evaluate the role of YKL-40 as a biomarker for epilepsy. 124 subjects were classified as control group (n = 23), new-diagnosis epilepsy group (NDE, n = 34), drug responsive epilepsy group (DPE, n = 37), and drug-resistant epilepsy group (DRE, n = 30) YKL-40 was measured by ELISA in serum and cerebrospinal fluid (CSF). The concentrations of serum and CSF YKL-40 and its diagnostic accuracy for epilepsy were analysed. Patients with DRE had higher concentrations of YKL-40 in serum and CSF, while patients with NDE and DPE had increased YKL-40 levels in CSF but not serum in comparison with control. Moreover, serum and CSF YKL-40 provide high diagnostic accuracy for DRE. YKL-40 may play a possible pathogenic role in epilepsy. YKL-40 may represent a potential biomarker of brain inflammation in patients with DRE., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Epstein Barr virus positive T/NK lymphoproliferative disorders (EBV-TNKLPD) comprise a spectrum of neoplasms ranging from cutaneous lymphoid proliferations to aggressive lymphomas. The spectrum includes extranodal NK/T-cell lymphoma (ENKTL), aggressive NK-cell leukemia, and a group of EBV-TNKLPDs affecting children which are poorly characterized in terms of their molecular biology. Gene and miRNA expression profiling has elucidated RNA abnormalities which impact on disease biology, classification, and treatment of EBV-TNKLPD. Pathways promoting proliferation, such as Janus associated kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) and nuclear factor kB, are upregulated in ENKTL while upregulation of survivin and deregulation of p53 inhibit apoptosis in both ENKTL and chronic active EBV infection (CAEBV). Importantly, immune evasion via the programmed cell death-1 and its ligand, PD-1/PD-L1 checkpoint pathway, has been demonstrated to play an important role in ENKTL. Other pathogenic mechanisms involve EBV genes, microRNA deregulation, and a variety of other oncogenic signaling pathways. The identification of EBV-positive Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) as a tumor with a distinct molecular signature and clinical characteristics highlights the important contribution of the knowledge derived from gene and miRNA expression profiling in disease classification. Novel therapeutic targets identified through the study of RNA abnormalities provide hope for patients with EBV-TNKLPD, which often has a poor prognosis. Immune checkpoint inhibition and JAK inhibition in particular have shown promise and are being evaluated in clinical trials. In this review, we provide an overview of the key transcriptomic aberrancies in EBV-TNKLPD and discuss their translational potential.

Alzheimer's disease (AD) is characterized by senile plaques (SP) composed of β-amyloid protein (Aβ) and neurofibrillary tangles (NFTs) composed of intracellular hyperphosphorylated tau. Recently, nuclear receptor subfamily 4 group A member 1 (NR4A1) was implicated in synaptic plasticity, long-term memory formation, suggesting that it may play a role in the pathophysiology of AD. Here, we showed that the expression of NR4A1 was significantly increased in the hippocampus of APP/PS1 transgenic mice. In addition, NR4A1 overexpression in HT22 cells up-regulated APP and BACE1 levels, down-regulated ADAM10 expression, and promoted amyloidogenesis as indicated by decreased α-CTF levels and elevated β-CTF levels. Furthermore, a raised level of phospho-tau (p-tau, S396) was accompanied by p-GSK3β (S9) expression reducing, but total tau, p-tau (S262 and T231), CDK5 and ERK remained unchanged in NR4A1-overexpressing cells. Collectively, our results suggest that NR4A1 promotes the amyloidogenic processing of APP by regulating ADAM10 and BACE1 expression in HT22 cells; as well as NR4A1 accelerates tau hyperphosphorylation by GSK3β signal. Therefore, NR4A1 may play an important role in the pathogenesis of AD.

Objectives: To identify the Y-chromosomal genetic types for the soldier's remains from Huaihai Campaign, and to offer a clue for search of their paternal relatives., Methods: DNA of the remains were extracted by the ancient DNA extraction method. Yfiler kit was used for the multiplex amplification of 17 Y-STR loci. The haplogroups of the samples were speculated. Detailed genotyping of the selected Y-SNP was performed based on the latest Y-chromosome phylogenetic tree. Haplotype-sharing analysis was done based on the data of Y-SNP and Y-STR, the closest modern individual information to the genetic relationship of remains was gained., Results: A total of 8 Y-STR haplotypes were observed on 17 Y-STR loci of 8 male individuals. Furthermore, 6 Y-SNP haplogroups were identified, which were O2a1-M95+, O1a1-P203+, O3*-M122+/M234-, D1-M15+, C3*-ST and R1a1-M17+., Conclusions: Identification of Y-chromosomal genetic types for the soldier's remains from Huaihai Campaign shows a reference value on inferring the geographical origins of old materials., 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 Forensic Medicine)

A series of new 1-(carbamoylmethyl)-2-aryl-3,1-benzoxazines were prepared in moderate to good yields by BF₃·OEt₂-catalyzed reactions of aromatic aldehydes with 2-( N -substituted carbamoylmethylamino)benzyl alcohols. The structures of the target compounds were confirmed by IR, ¹H-NMR, 13 C-NMR, and elemental analyses. The fungicidal activities of the target compounds against plant fungi were preliminarily evaluated, and some of them exhibited good activity., Competing Interests: The authors declare no conflict of interest. All authors read and approved the final manuscript.

The intracellular trafficking and proteolytic processing of the membrane-bound amyloid precursor protein (APP) are coordinated events leading to the generation of pathogenic amyloid-beta (Aβ) peptides. The membrane transport of newly synthesized APP from the Golgi to the endolysosomal system is not well defined, yet it is likely to be critical for regulating its processing by β-secretase (BACE1) and γ-secretase. Here, we show that the majority of newly synthesized APP is transported from the trans-Golgi network (TGN) directly to early endosomes and then subsequently to the late endosomes/lysosomes with very little transported to the cell surface. We show that Arl5b, a small G protein localized to the TGN, and AP4 are essential for the post-Golgi transport of APP to early endosomes. Arl5b is physically associated with AP4 and is required for the recruitment of AP4, but not AP1, to the TGN. Depletion of either Arl5b or AP4 results in the accumulation of APP, but not BACE1, in the Golgi, and an increase in APP processing and Aβ secretion. These findings demonstrate that APP is diverted from BACE1 at the TGN for direct transport to early endosomes and that the TGN represents a site for APP processing with the subsequent secretion of Aβ., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Stratifying patients according to 15-day readmission risk would be useful in identifying those who may benefit from targeted interventions during and/or following hospital discharge that are designed to reduce the likelihood of readmission., Methods: A prediction model was derived via a case-control analysis of patients discharged from a tertiary hospital in Singapore using multivariate logistic regression. The model was validated in two independent external cohorts separated temporally and geographically. Model discrimination was assessed using the C-statistic, while calibration was assessed using the Hosmer-Lemeshow χ 2 and the Brier score statistics., Results: A total of 1291 patients were included with 670, 101, and 520 patients in the derivation, temporal, and geographical validation cohorts, respectively. Age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.03, p=0.008), anemia (OR 2.08, 95% CI 1.15-8.05, p=0.015), malignancy (OR 3.37, 95% CI 1.16-9.80, p=0.026), peptic ulcer disease (OR 3.05, 95% CI 1.12-8.26, p=0.029), chronic obstructive pulmonary disease (OR 3.16, 95% CI 1.24-8.05, p=0.016), number of discharge medications (OR 1.06, 95% CI 1.01-1.12, p=0.026), discharge to nursing homes (OR 3.57, 95% CI 1.57-8.34, p=0.003), and premature discharge against medical advice (OR 5.05, 95% CI 1.20-21.23, p=0.027) were independent predictors of 15-day readmission risk. The model demonstrated reasonable discrimination on the temporal and geographical validation cohorts with a C-statistic of 0.65 and 0.64, respectively. Model miscalibration was observed in both validation cohorts., Conclusion: A 15-day readmission risk prediction model is proposed and externally validated. The model facilitates the targeting of interventions for patients who are at high risk of an early readmission., (© 2017 Pharmacotherapy Publications, Inc.)

Synthesis of carbon nitrides (CN x ) by refluxing under nitrogen exhibited mixed growth mechanisms of oriented attachment and Ostwald ripening, leading to the formation of coral reef-like microstructures from spherical agglomerates. Some phase transformation from β-phase to α-phase CN x occurred upon refluxing for 1.5 h, producing a biphasic CN x . The N content relative to C was determined from CHN elemental analysis, and the presence of C═N and terminal groups (i.e., COOH and NH 2 ) was consistent with the Fourier transform infrared, nuclear magnetic resonance, and X-ray photoelectron spectroscopic results. The sample refluxed for 2.0 h (CN x /2.0 h) had the highest surface area of 24.5 m 2 ·g -1 and displayed enhanced adsorption capacities for methylene blue (MB) molecules and heavy metal ions Pb 2+ (720 mg·g -1 ), Cd 2+ (480 mg·g -1 ), and As(V) (220 mg·g -1 ), which was attributed to the presence of COOH functional groups. CN x samples had a negative surface charge that electrostatically attracted the cationic heavy metal ions as well as MB molecules for subsequent photodecomposition under visible-light illumination. The photocatalytic activity of CN x /2.0 h toward phenol, a common pollutant in aqueous waste, was also demonstrated and a possible photocatalytic route was proposed.

Background: Congenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS)., Methods: Clinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out., Results: The patients revealed variability in clinical and electrophysiological features. However, weakness, scoliosis, and repetitive-compound muscle action potential were found in all affected members in the family. A heterozygous C>T missense mutation at nucleotide 865 in acetylcholine receptor epsilon-subunit (CHRNE) gene that causes a leucine-to-phenylalanine substitution at position 289 (L289F) was found., Conclusions: We reported a SCCMS family of Chinese origin. In the family, classical clinical phenotype with phenotypic variability among different members was found. Genetic testing could help diagnose this rare disease.

Objective: To investigate the effect of zinc ion on the expression of osteoblastic proteins., Methods: Mice osteoblasts MC3T3-E1 cells were subcultured. Inflammatory environment model was established by tumor necrosis factor α(TNF-α)at a concentration of 10 mg/L. According to different concentration of Zn(2+), the cells were divided into TNF-α group, control group, group A(TNF-α+10(-4) mol/L Zn(2+)), group B(TNF-α+10(-5) mol/L Zn(2+)), group C(TNF-α+10(-6) mol/L Zn(2+)). After 24, 48, and 72 h of culture, cell counting kit-8(CCK-8)assay was used to analyze the proliferation of the cells. ALP activity was examined. Bone morphogenetic protein-2(BMP-2), Runt-related transcription factor 2(RUNX2), Osterix and receptor activator of NF-κB ligand(RANKL)protein levels were determined by Western blotting after 72 h of culture., Results: The cells grew by adherence after 24 h. After 72 h, the cells grew dense, and the cells showed long spindle shape or irregular shape. The proliferation of osteoblasts in TNF-α group, group B and group C became lower than that in the control group(P<0.05), and was not significantly different between group A and the control group(P >0.05). ALP activity examination demonstrated that the groups cultured for 72 h revealed the highest ALP activity and the most prominent differentation compared with 24 h and 48 h groups. ALP activity was significantly decreased in TNF-α group, group B and group C compared with control group(P<0.05), but was not significantly different between group A and control group(P>0.05). The protein levels of BMP-2, RUNX2 and Osterix were significantly decreased in TNF-α group, group B and group C compared with control group(P<0.05), while showed no significant difference between group A and the control group. Protein level of RANKL was significantly increased in TNF-α group, grope B and group C compared with control group(P<0.05), while showed no significant difference between group A and control group., Conclusions: The concentration of 10(-4) mol/L Zn(2+) can significantly increase the expression of osteoblastic proteins such as ALP, BMP-2, RUNX2, Osterix and decrease the expression of RANKL in mice osteoblasts in TNF-α inflammatory environment.

Porous nitrogen-modified titania (N-titania) monoliths with tailored morphologies were prepared using phase separation and agarose gel templating techniques. The doping and templating process were simultaneously carried out in a one-pot step using alcohol amine-assisted sol-gel chemistry. The amount of polymer used in the monoliths that were prepared using phase separation was shown to affect both the physical and optical properties: higher poly(ethylene glycol) content increased the specific surface area, porosity, and visible light absorption of the final materials. For the agarose-templated monoliths, the infiltration conditions affected the monolith morphology. A porous monolith with high surface area and the least shrinkage was obtained when the N containing alkoxide precursor was infiltrated into the agarose scaffolds at 60 °C. The effect of the diverse porous morphologies on the photocatalytic activity of N-titania was studied for the decomposition of methylene blue (MB) under visible and UV light irradiation. The highest visible light activity was achieved by the agarose-templated N-titania monolith, in part due to higher N incorporation. This sample also showed better UV activity, partly because of the higher specific surface area (up to 112 m(2) g(-1)) compared to the phase separation-induced monoliths (up to 103 m(2) g(-1)). Overall, agarose-templated, porous N-titania monoliths provided better features for effectively removing the MB contaminant.

Flowerlike WSe2 and WS2 microspheres were synthesized by a facile and scalable one-pot solvothermal method. Their formation mechanism followed the reaction between dissolved W(CO)6 and dissolved S or melted Se without complete decomposition of W(CO)6 into tungsten. As novel efficient sorbents, WSe2 and WS2 demonstrated outstanding uptake capacities for Pb(2+) and Hg(2+).

Background: The prevalence of chronic diseases is increasing in Asia, therefore compliance to the medications is of utmost importance to slow disease progression and improve outcomes. Dosage administration aids (DAAs) serve as important tool to improve the compliance of patients. However, there is a dearth of data on the stability of chronic medications in DAAs. Furthermore, data presented by our Western counterparts may not be applicable to us because of our extreme humidity and temperature. In this study, we aim to summarize the data available in the literature on the stability of chronic medications in DAA., Methods: We performed a literature search using electronic databases and related keywords., Results: In total, 24,336 articles were retrieved and 21 articles were found to be relevant to our topic. This commentary stratified drugs according to their treatment categories and key stability conclusions, DAA and conditions used and recommendations were presented., Conclusion: Due to the lack of specific data, pharmacists have to exercise their professional judgment with the help from professional guidelines when using DAA in repackaging medication. Manufacturers and regulators can play a greater role in filling the gap needed to provide pharmacists with necessary information to fulfill their function.

Increased length of stay (LOS) in the hospital incurs substantial financial costs on the healthcare system. Multiple factors are associated with LOS. However, few studies have been done to associate the impact of Total Daily Doses (TDD) and LOS. Hence, the aim of this study is to examine the association between patients' LOS upon readmission and their TDD before readmission. A retrospective cross-sectional study of readmission cases occurring from 1st January to 31st March 2013 was conducted at a regional hospital. Demographics and clinical variables were collected using electronic medical databases. Univariable and multiple linear regressions were used. Confounders such as comorbidities and drug related problems (DRP) were controlled for in this study. There were 432 patients and 649 readmissions examined. The average TDD and LOS were 18.04 ± 8.16 and 7.63 days ± 7.08 respectively. In the univariable analysis, variables that were significantly associated with the LOS included age above 75 year-old, race, comorbidity, number of comorbidities, number of medications, TDD and thrombocytopenia as DRPs. In the multiple linear regression, there was a statistically significant association between TDD (β = 0.0733, p = 0.030) and LOS. Variables that were found significant were age above 75 year-old (β = 1.5477, p = 0.008), Malay (β = -1.5123, p = 0.033), other races (β = -2.6174, p = 0.007), depression (β = 2.1551, p = 0.031) and thrombocytopenia as a type of DRP (β = 7.5548, p = 0.027). When TDD was replaced with number of medications, number of medications (β = 0.1487, p = 0.021), age of 75 year-old (β = 1.5303, p = 0.009), Malay (β = -1.4687, p = 0.038), race of others (β = -2.6499, p = 0.007), depression (β = 2.1951, p = 0.028) and thrombocytopenia as a type of DRP (β = 7.5260, p = 0.028) were significant. In conclusion, a significant relationship between TDD and number of medications before readmission and the LOS upon readmission was established. This finding highlights the importance of optimizing patients' TDD in the attempt of reducing their LOS.

Objectives: Osteopontin (OPN) is a non-traditional pro-inflammatory cytokine and is involved in muscle regeneration and inflammation. The aim of this study was to investigate the expression of OPN in skeletal muscle and serum of patients with IIMs., Methods: 45 patients with IIMs (27 with PM and 18 with DM) were included in the study. Patients received initial prednisone therapy (1-1.5 mg/kg/day) without other immunosuppressive agents. Muscle biopsies were taken before start of treatment and serum samples were collected from each patient before and after corticosteroid treatment. The expression of OPN in skeletal muscle was using immunofluorescence staining and western blotting. Serum OPN levels were detected by enzyme-linked immunosorbent assays (ELISA)., Results: OPN expression was increased in muscle samples from IIM patients compared to control muscle. The serum level of OPN was significantly higher in IIM patients than in controls. Moreover, the serum concentrations in the DM subgroup were significantly higher compared to the PM groups. Serum OPN levels positively correlated with creatinine kinase (CK), C-reactive protein (CRP) in PM and DM patients, respectively. After corticosteroid treatment, serum OPN levels decreased significantly in steroid responders compared to baseline, but no significant decrease was observed in steroid non-responders., Conclusions: OPN is increased in patients with DM and PM, both in muscle and serum. OPN may play an important role in the pathogenesis of IIMs. Moreover, serum OPN may be a potential biomarker for this illness, and changes in serum OPN may provide an index of therapeutic efficacy.

Endoplasmic reticulum (ER) stress is suggested to play an important role in the pathogenesis of myositis recently. The aim of this study was to investigate the serum concentration of an ER stress-specific chaperone protein HSPA5 in patients with inflammatory myopathies. Forty-five patients (27 with polymyositis (PM) and 18 with dermatomyositis (DM)) were included in the study, and all received prednisone therapy. Serum samples were collected from each patient before and after prednisone treatment. Serum HSPA5 levels were detected by enzyme-linked immunosorbent assays. The serum level of HSPA5 was significantly higher in myositis patients than in controls. In addition, the concentrations in the DM subgroup were significantly higher than in the PM groups. Serum HSPA5 levels were positively correlated with creatine kinase (CK) and C-reactive protein (CRP) in PM patients. In patients with DM, the serum HSPA5 concentrations were also found significantly correlated with CK, but not with CRP. After prednisone treatment, serum HSPA5 levels significantly decreased compared to baseline in steroid responders, but no marked decrease was observed in steroid non-responders. Serum HSPA5 is increased in patients with DM and PM. Increased concentrations of HSPA5 in serum may reflect the enhanced ER stress in muscle tissue. Decrease in serum HSPA5 levels appears in patients with clinical remission; therefore, HSPA5 may be a potential biomarker for inflammatory myopathies.

Gap junction protein beta 1 (GJB1) gene mutations lead to X-linked Charcot-Marie-Tooth (CMTX) disease. We investigated a Chinese family with CMTX and identified a novel GJB1 point mutation. Clinical and electrophysiological features of the pedigree were examined, and sequence alterations of the coding region of GJB1 that encode connexin32 were determined by direct sequencing. Sequence alignment of the mutation site was performed using Clustal W. Mutation effects were analysed using PolyPhen-2, SIFT and Mutation Taster software. The three-dimensional structures of the mutant and wild-type proteins were predicted by modeling with SWISS MODEL online software. The affected family members displayed typical Charcot-Marie-Tooth phenotypes, but phenotypic heterogeneity was observed. Nerve conduction velocities of all affected patients were slow. Sequencing of GJB1 revealed a heterozygous T>G missense mutation at nucleotide 212 in the proband, the proband's mother and the proband's daughter. The affected male sibling of the proband displayed a hemizygous missense mutation with T>G transition at the identical position on the GJB1 gene. This mutation resulted in an amino acid change from isoleucine to serine that was predicted to lead to tertiary structural alterations that would disrupt the function of the GJB1 protein. A novel point mutation in GJB1 was detected, expanding the spectrum of GJB1 mutations known to be associated with CMTX., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The effects of dietary l-arginine (Arg) on immunosuppression following infectious bursal disease virus (IBDV) inoculation in broiler chickens were evaluated. The design of this study was a 5 × 2 factorial arrangement (n = 5) with five Arg concentrations (starter: 9.9, 13.9, 17.6, 21.3 and 25.3 g kg(-1) ; grower-finisher: 9.5, 13.5, 17.1, 20.1 and 23.6 g kg(-1) ) with or without IBDV inoculation (IBDV or saline inoculation at 14 days). Chickens were sampled at 2, 4 and 6 days post-inoculation (DPI) and 42 days of age., Results: The IBDV inoculation decreased (P = 0.05) CD3(+) , CD4(+) , and CD8(+) T cell counts at 2 days post-inoculation (DPI) and monocyte counts at 6 DPI; and reduced (P < 0.05) bursal interleukin-1β (IL-1β) mRNA expression at 2 DPI and serum IL-6 concentration at 4 DPI. Increasing Arg concentration increased (P < 0.05) CD4(+) and CD8(+) T cell counts at 2 DPI, linearly increased (P = 0.05) CD3(+) T cell counts in IBDV-inoculated groups and monocyte counts in control groups at 4 DPI; increased (P < 0.05) serum IL-6 concentration in IBDV-inoculated groups at 2 DPI; and increased (P < 0.05) serum anti-IBDV antibody titres at 42 days of age., Conclusion: Varying concentrations of Arg supplementation attenuated IBDV inoculation induced immunosuppression via modulating circulating T cell sub-populations., (© 2014 Society of Chemical Industry.)

Objective: To investigate whether number of doses per day and number of medications are significantly associated with the number of readmissions and to study the association of readmission frequency with other medical and socio-demographic variables., Methods: Retrospective cross-sectional study involving 432 patients who were readmitted within 15 days of previous hospital discharge between January 1, 2013 and March 31, 2013. Relevant medical records were collected from the national electronic databases of every public tertiary hospital in Singapore. Significant variables (p < 0.05) were identified using forward selection and modeled using generalized linear mixed models., Results: A total of 649 unplanned readmissions were reviewed. At a multivariable level, number of readmission was significantly associated with the number of medications (p = 0.002) and number of doses per day (p = 0.003) after adjusting for race, liver disease, schizophrenia and non-compliance., Conclusion: Complex medication regimen (i.e. multiple medications and multiple doses per day) is a statistically significant predictor of number of readmissions. Simplifying therapeutic regimens with alternatives such as longer-acting or fixed-dose combination drugs may facilitate better patient adherence and reduce costly readmissions.

EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3. Overexpression of EZH2 has been found in a wide range of cancers, including those of the prostate and breast. In this review, we address the current understanding of the oncogenic role of EZH2, including its PRC2-dependent transcriptional repression and PRC2-independent gene activation. We also discuss the connections between EZH2 and other silencing enzymes, such as DNA methyltransferase and histone deacetylase. We comprehensively address the architecture of the PRC2 complex and the crucial roles of each subunit. Finally, we summarize new progress in developing EZH2 inhibitors, which could be a new epigenetic therapy for cancers.

Background: Long noncoding RNAs (lncRNAs) constitute a major, but poorly characterized part of human transcriptome. Recent evidence indicates that many lncRNAs are involved in cancer and can be used as predictive and prognostic biomarkers. Significant fraction of lncRNAs is represented on widely used microarray platforms, however they have usually been ignored in cancer studies., Results: We developed a computational pipeline to annotate lncRNAs on popular Affymetrix U133 microarrays, creating a resource allowing measurement of expression of 1581 lncRNAs. This resource can be utilized to interrogate existing microarray datasets for various lncRNA studies. We found that these lncRNAs fall into three distinct classes according to their statistical distribution by length. Remarkably, these three classes of lncRNAs were co-localized with protein coding genes exhibiting distinct gene ontology groups. This annotation was applied to microarray analysis which identified a 159 lncRNA signature that discriminates between localized and metastatic stages of neuroblastoma. Analysis of an independent patient cohort revealed that this signature differentiates also relapsing from non-relapsing primary tumors. This is the first example of the signature developed via the analysis of expression of lncRNAs solely. One of these lncRNAs, termed HOXD-AS1, is encoded in HOXD cluster. HOXD-AS1 is evolutionary conserved among hominids and has all bona fide features of a gene. Studying retinoid acid (RA) response of SH-SY5Y cell line, a model of human metastatic neuroblastoma, we found that HOXD-AS1 is a subject to morphogenic regulation, is activated by PI3K/Akt pathway and itself is involved in control of RA-induced cell differentiation. Knock-down experiments revealed that HOXD-AS1 controls expression levels of clinically significant protein-coding genes involved in angiogenesis and inflammation, the hallmarks of metastatic cancer., Conclusions: Our findings greatly extend the number of noncoding RNAs functionally implicated in tumor development and patient treatment and highlight their role as potential prognostic biomarkers of neuroblastomas.

Background: Mammalian genomes are extensively transcribed producing thousands of long non-protein-coding RNAs (lncRNAs). The biological significance and function of the vast majority of lncRNAs remain unclear. Recent studies have implicated several lncRNAs as playing important roles in embryonic development and cancer progression. LncRNAs are characterized with different genomic architectures in relationship with their associated protein-coding genes. Our study aimed at bridging lncRNA architecture with dynamical patterns of their expression using differentiating human neuroblastoma cells model., Results: LncRNA expression was studied in a 120-hours timecourse of differentiation of human neuroblastoma SH-SY5Y cells into neurons upon treatment with retinoic acid (RA), the compound used for the treatment of neuroblastoma. A custom microarray chip was utilized to interrogate expression levels of 9,267 lncRNAs in the course of differentiation. We categorized lncRNAs into 19 architecture classes according to their position relatively to protein-coding genes. For each architecture class, dynamics of expression of lncRNAs was studied in association with their protein-coding partners. It allowed us to demonstrate positive correlation of lncRNAs with their associated protein-coding genes at bidirectional promoters and for sense-antisense transcript pairs. In contrast, lncRNAs located in the introns and downstream of the protein-coding genes were characterized with negative correlation modes. We further classified the lncRNAs by the temporal patterns of their expression dynamics. We found that intronic and bidirectional promoter architectures are associated with rapid RA-dependent induction or repression of the corresponding lncRNAs, followed by their constant expression. At the same time, lncRNAs expressed downstream of protein-coding genes are characterized by rapid induction, followed by transcriptional repression. Quantitative RT-PCR analysis confirmed the discovered functional modes for several selected lncRNAs associated with proteins involved in cancer and embryonic development., Conclusions: This is the first report detailing dynamical changes of multiple lncRNAs during RA-induced neuroblastoma differentiation. Integration of genomic and transcriptomic levels of information allowed us to demonstrate specific behavior of lncRNAs organized in different genomic architectures. This study also provides a list of lncRNAs with possible roles in neuroblastoma.

Introduction: The aim of this study was to evaluate the dynamic volumetric CT in the assessment of the paediatric airway., Methods: Ethics board approval was obtained for this retrospective review. Eight infants (median age 6 months, range 3 weeks to 1 year, 50% female) at a tertiary paediatric centre with complex clinical respiratory presentation underwent volumetric CT assessment of their airways. The entire lungs were examined over 1-2 respiratory cycles. In four patients, intravenous contrast was administered to assess for vascular airway compression. The patients were not intubated. CT findings were correlated with bronchography and bronchoscopy, where available., Results: Two patients had diffuse tracheobronchomalacia associated with chronic lung disease. One patient demonstrated focal severe cervical tracheomalacia. One patient had a double aortic arch causing fixed narrowing with superimposed malacia of the distal trachea. Four patients had normal airways; one with chronic lung disease, one demonstrating air trapping. CT findings were concordant with bronchography (one case) and bronchoscopy (four cases) in all but one (CT negative, bronchoscopy positive) but did not alter patient management., Conclusion: The assessment of the paediatric airway, and in particular for tracheobronchomalacia, is difficult. Assessment with bronchography, bronchoscopy, helical CT and MR have issues with reliability, intubation, intratracheal/bronchial contrast administration and ionising radiation. Volumetric CT assesses the entire central airway in children at much lower radiation dose compared with previous dynamic CT imaging. This non-invasive, rapid assessment obviates the need for patient cooperation and enables evaluation of extratracheal intrathoracic structures. Volumetric CT enables four-dimensional assessment for paediatric tracheobronchomalacia without intubation or patient cooperation and at low radiation dose., (© 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.)

We have mapped a Jagged/Serrate-binding site to specific residues within the 12th EGF domain of human and Drosophila Notch. Two critical residues, involved in a hydrophobic interaction, provide a ligand-binding platform and are adjacent to a Fringe-sensitive residue that modulates Notch activity. Our data suggest that small variations within the binding site fine-tune ligand specificity, which may explain the observed sequence heterogeneity in mammalian Notch paralogues, and should allow the development of paralogue-specific ligand-blocking antibodies. As a proof of principle, we have generated a Notch-1-specific monoclonal antibody that blocks binding, thus paving the way for antibody tools for research and therapeutic applications.

Introduction: Pure mucinous breast carcinomas (PMBC) are commonly lobulated, therefore appear relatively benign compared with the imaging features of invasive ductal carcinoma. The aim of this study was to determine mammographic and sonographic patterns of PMBC, in particular features that may result in misdiagnosis., Methods: Retrospective review of available mammography and sonography in 90 patients diagnosed with PMBC within the Monash BreastScreen service, 1993-2011 inclusive., Results: PMBC commonly have indistinct or lobulated mammographic and sonographic margins. Mammographic calcifications are absent in the majority (82%). On ultrasound, these neoplasms are commonly isoechoic (51%) with normal posterior acoustic appearances (80%). However, most (77%) of these lesions have suspicious or definite imaging features of malignancy., Conclusion: PMBC are commonly lobulated with homogeneous, isoechoic and normal posterior acoustic sonographic appearances but rarely have benign imaging features., (© 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.)

Objective: To investigate the protective effects of sodium tanshinone B (STB) on brain damage following focal ischemia-reperfusion (I/R) injury through interfering with N-methyl-D-aspartic acid receptor (NMDAR) and excitatory and inhibitory amino acids, and evaluate the potential mechanisms of the neuroprotective activity of STB., Methods: Transient forebrain ischemia was induced by middle cerebral artery occlusion (MCAO). The rats were randomized into a sham operated group, a model group (I/R) and three STB different dose groups. Rats were pretreated with STB at the doses of 4, 8, 16 mg/kg (STB(1), STB(2), STB(3)) for 3 days before MCAO. The expression of NMDAR1 was detected by immunohistochemistry and Western blotting. The concentrations of glutamate and γ-aminobutyric acid (GABA) were analyzed using high performance liquid chromatography., Results: STB treatment reduced neurological defect scores, cerebral infarction volume and brain water content. The levels of NMDAR1 were significantly higher in the l/R and STB(1) groups than that of the sham and the STB(3) groups (P<0.01). Optical density of NMDAR1 was significantly increased in cornu ammonis (CA)1 region of the l/R group (P<0.05). STB treatment reduced NMDAR1 optical density in the CA1 region (P<0.01). The levels of glutamate were significantly lower in the hippocampus in the STB(3) group than that of the l/R, STB(1) and STB(2) groups (P<0.01)., Conclusion: Preconditioning with STB appears to be a simple and promising strategy to reduce or even prevent cerebral l/R injury and has potential for future clinical application.

Tracheobronchomalacia is characterised by excessive airway collapsibility due to weakness of airway walls and supporting cartilage. The standard definition requires reduction in cross-sectional area of at least 50% on expiration. However, there is a paucity of information regarding the normal range of central airway collapse among children of varying ages, ethnicities and genders, with and without coexisting pulmonary disease. Consequently, the threshold for pathological collapse is considered somewhat arbitrary. Available methods for assessing the airway dynamically--bronchoscopy, radiography, cine fluoroscopy, bronchography, CT and MR--have issues with reliability, the need for intubation, radiation dose and contrast administration. In addition, there are varying means of eliciting the diagnosis. Forced expiratory manoeuvres have been employed but can exaggerate normal physiological changes. Furthermore, radiographic evidence of tracheal compression does not necessarily translate into physiological or functional significance. Given that the criteria used to make the diagnosis of tracheobronchomalacia are poorly validated, further studies with larger patient samples are required to define the threshold for pathological airway collapse.

Unlabelled: OBJECTIVE To observe the changing laws of the protein expression of N-methyl D-aspartate receptor (NMDAR) in rat hippocampal subfields following focal ischemia/reperfusion injury, and to study the effects of sodium tanshinone B (STB) on it, thus exploring the possible mechanism of STB for treating cerebral ischemia., Methods: The rat model of focal cerebral ischemia/reperfusion injury was established using middle cerebral artery occlusion (MCAO) by reversibly inserting a nylon thread. The Wistar rats were randomly divided into the sham-operation group, the I/R model group, and the low, middle, and high dose STB groups. The neural functional disturbance was scored referring to the 5-grade Zea Longa EL standard. The protein expression of NMDAR1 in the ischemic side was detected using immunohistochemical assay., Results: There was statistical difference in the scores of the neural functional disturbance in the middle and high dose STB groups when compared with the model group (P < 0.01). Results of the immunohistochemical assay showed the expression of NMDAR1 in CA1 region was obviously higher in the I/R model group, the low and middle dose STB groups than in the sham-operation group (P < 0.01). The expression of NMDAR1 in CA1 region was obviously lower in the high dose STB group than in the I/R model group (P < 0.01), the low (P < 0.01) and middle dose STB groups (P < 0.05). The expression of NMDAR1 in CA3 region was obviously higher in the low dose STB group and the I/R model group than in the sham-operation group, the middle and high dose STB groups (P < 0.01). The expression of NMDAR1 in CA3 region was obviously higher in the high and middle dose STB groups than in the sham-operation group (P < 0.05)., Conclusions: STB could promote the recovery of neural functions in cerebral ischemia/reperfusion injury rats. STB fought against cerebral ischemia/reperfusion injury by lowering excitable neurotransmitter glumatic acid and reducing the protein expression of NMDAR1.

It is a major question in archaeology and anthropology whether human populations started to grow primarily after the advent of agriculture, i.e., the Neolithic time, especially in East Asia, which was one of the centers of ancient agricultural civilization. To answer this question requires an accurate estimation of the time of lineage expansion as well as that of population expansion in a population sample without ascertainment bias. In this study, we analyzed all available mtDNA genomes of East Asians ascertained by random sampling, a total of 367 complete mtDNA sequences generated by the 1000 Genome Project, including 249 Chinese (CHB, CHD, and CHS) and 118 Japanese (JPT). We found that major mtDNA lineages underwent expansions, all of which, except for two JPT-specific lineages, including D4, D4b2b, D4a, D4j, D5a2a, A, N9a, F1a1'4, F2, B4, B4a, G2a1 and M7b1'2'4, occurred before 10 kya, i.e., before the Neolithic time (symbolized by Dadiwan Culture at 7.9 kya) in East Asia. Consistent to this observation, the further analysis showed that the population expansion in East Asia started at 13 kya and lasted until 4 kya. The results suggest that the population growth in East Asia constituted a need for the introduction of agriculture and might be one of the driving forces that led to the further development of agriculture.

Objective: To investigate the effects of Salvianolic acid B preconditioned endothelial progenitor cells (EPCs) on the Nkx2.5 and GATA-4 gene expressions at the early stage of cell differentiation of bone mesenchymal stem cells (BMSc) transplanted into infarcted myocardium, in order to find out the best synergism for co-transplantation of the two kinds of cells., Methods: BMSc and EPCs of rats were isolated and cultured, and rats were modeled into acute myocardial infarction (AMI) by left coronary artery ligation. Then the EPCs preconditioned with different concentrations of Salvianolic acid B and BMSc or DMEM medium were implanted into heart ischemia area. Expressions of Nkx2.5 and GATA-4 mRNA expressions in myocardium were detected by Real-time RT-PCR 4 weeks later., Results: Compared with those in the non-implanted model rats' myocardium, the gene expression of Nkx2.5 and GATA-4 mRNA were significantly higher in all the transplantation receptive groups, comparisons between the implanted groups showed that the highest value of expressions (2. 654 +/- 0.606 of Nkx2.5 and 1.573 +/- 0.372 of GATA-4) displayed in the group contained more EPCs, for 8-fold to BMSc in volume., Conclusion: BMSc can differentiate into cardiac muscle like cells, and condition of their differentiation is related with the degree of the internal environment improved.

The ability to extract mitochondrial and nuclear DNA from ancient remains has enabled the study of ancient DNA, a legitimate field for over 20 years now. Recently, Y chromosome genotyping has begun to be applied to ancient DNA. The Y chromosome haplogroup in East Asia has since caught the attention of molecular anthropologists, as it is one of the most ethnic-related genetic markers of the region. In this paper, the Y chromosome haplogroup of DNA from ancient East Asians was examined, in order to genetically link them to modern populations. Fifty-six human remains were sampled from five archaeological sites, primarily along the Yangtze River. Strict criteria were followed to eliminate potential contamination. Five SNPs from the Y chromosome were successfully amplified from most of the samples, with at least 62.5% of the samples belonging to the O haplogroup, similar to the frequency for modern East Asian populations. A high frequency of O1 was found in Liangzhu Culture sites around the mouth of the Yangtze River, linking this culture to modern Austronesian and Daic populations. A rare haplogroup, O3d, was found at the Daxi site in the middle reaches of the Yangtze River, indicating that the Daxi people might be the ancestors of modern Hmong-Mien populations, which show only small traces of O3d today. Noticeable genetic segregation was observed among the prehistoric cultures, demonstrating the genetic foundation of the multiple origins of the Chinese Civilization.