Postgraduates' time management disposition and mental health: mediating role of life satisfaction and moderating role of core self-evaluations.

BACKGROUND: The current study aimed to investigate the relationship between postgraduates' time management disposition and mental health. As such, it constructed a moderated mediation model to examine the mediating role of life satisfaction on the relationship between graduate students' time management disposition and mental health and examine whether this role was moderated by core self-evaluations. METHODS: 455 postgraduates were surveyed by the Adolescence Time Management Disposition Inventory, the Adolescent Students' Life Satisfaction Scale, the revised version of the Chinese Core Self-Evaluation Scale, and the revised version of the Chinese General Health Questionnaire. RESULTS: Time management disposition, life satisfaction, core self-evaluation, and mental health were significantly correlated. Time management disposition indirectly affected mental health through the mediating effect of life satisfaction. Core self-evaluation moderated the second half of the mediating effect of time management disposition on mental health via life satisfaction. CONCLUSION: The findings reveal the mechanism between time management disposition and mental health, which will help school educators to guide postgraduates in developing good time management disposition and improving life satisfaction and core self-evaluation, and thus improve their mental health.

Targeting homologous recombination deficiency in uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma (uLMS) is a rare and aggressive gynaecological malignancy, with individuals with advanced uLMS having a five-year survival of < 10%. Mutations in the homologous recombination (HR) DNA repair pathway have been observed in ~ 10% of uLMS cases, with reports of some individuals benefiting from poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy, which targets this DNA repair defect. In this report, we screened individuals with uLMS, accrued nationally, for mutations in the HR repair pathway and explored new approaches to therapeutic targeting. METHODS: A cohort of 58 individuals with uLMS were screened for HR Deficiency (HRD) using whole genome sequencing (WGS), whole exome sequencing (WES) or NGS panel testing. Individuals identified to have HRD uLMS were offered PARPi therapy and clinical outcome details collected. Patient-derived xenografts (PDX) were generated for therapeutic targeting. RESULTS: All 13 uLMS samples analysed by WGS had a dominant COSMIC mutational signature 3; 11 of these had high genome-wide loss of heterozygosity (LOH) (> 0.2) but only two samples had a CHORD score > 50%, one of which had a homozygous pathogenic alteration in an HR gene (deletion in BRCA2). A further three samples harboured homozygous HRD alterations (all deletions in BRCA2), detected by WES or panel sequencing, with 5/58 (9%) individuals having HRD uLMS. All five individuals gained access to PARPi therapy. Two of three individuals with mature clinical follow up achieved a complete response or durable partial response (PR) with the subsequent addition of platinum to PARPi upon minor progression during initial PR on PARPi. Corresponding PDX responses were most rapid, complete and sustained with the PARP1-specific PARPi, AZD5305, compared with either olaparib alone or olaparib plus cisplatin, even in a paired sample of a BRCA2-deleted PDX, derived following PARPi therapy in the patient, which had developed PARPi-resistance mutations in PRKDC, encoding DNA-PKcs. CONCLUSIONS: Our work demonstrates the value of identifying HRD for therapeutic targeting by PARPi and platinum in individuals with the aggressive rare malignancy, uLMS and suggests that individuals with HRD uLMS should be included in trials of PARP1-specific PARPi.

Primary myelofibrosis: spectrum of imaging features and disease-related complications.

Primary myelofibrosis is a chronic clonal stem cell disorder that results in a build-up of marrow fibrosis and dysfunction, hypermetabolic states, and myeloid metaplasia. The clinical and radiological consequences can be quite diverse and range from the manifestations of osteosclerosis and extramedullary haematopoiesis to thrombohaemorrhagic complications from haemostatic dysfunction. In addition, there is the challenge of identifying less well-recognised sites of extramedullary haematopoiesis and their site-specific complications. The intent of this article is to illustrate the spectrum of primary myelofibrosis as declared though multimodality imaging, with examples of both common and rarer disease manifestations.

Transition-Metal-Free N-Arylation of Amines by Triarylsulfonium Triflates.

A simple and efficient method for transition-metal-free N-arylation of various amines by triarylsulfonium triflates is described. Both aliphatic and aromatic amines were smoothly converted at 80 °C in the presence of tBuOK or KOH to give the corresponding mono N-arylated products in good to high yields. The molar ratios of the reactants and the choice of bases had a big effect on the reaction. When a large excess of [Ph3 S][OTf] and tBuOK were employed for primary amines under the standard conditions, the bis(N-phenyl) products were predominantly formed. This method was also applicable to the synthesis of bioactive N-phenyl amino acid derivatives. The control experiments, the deuterium labelling study, and the presence of regioisomers of N-arylated products when using 4-substituted triarylsulfonium triflates suggested that the reaction might proceed through an aryne intermediate. The present protocol demonstrated that triarylsulfonium salts are versatile arylation reagents in the construction of CAr -N bonds.

Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial.

OBJECTIVE: To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. MATERIALS AND METHODS: This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan-Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. RESULTS: Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). CONCLUSION: The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.

Natural hosts infected with Babesia in Fujian Province, China / 中国人兽共患病学报

We explored the status of Babesia infection in natural hosts in Fujian Province.Rodents in Fujian Province were captured by the night trapping method during 2014-2016.Heart blood samples were collected.At the same time blood samples of ox,goats and dogs were also collected,from which the fragments of 18S rRNA gene of Babesia were amplified by polymerase chain reaction (PCR).Data on infection rate were analyzed with Chi-square or Fisher exact test to indicate statistical significance.Results showed that 5 917 cages were laid and 381 rodents were captured,density of rodent was 6.44％.The o verall Babesia infection rate in rodents was 7.61％,while infection rate in domesticated rodents was 1.68％,and the infection rate in wide rodents was 12.87％.The infection rate was higher in wild rodents than that in domesticated rodents,and the statistical analysis result revealed a significant difference.The infection rates in region of Central Fujian and Eastern Fujian was high,and no infection was found in Southern Fujian region.The statistical analysis result revealed a significant difference in infection rate among different regions.The infection rate of goats and dogs were determined to be 1.79 ％ and 0.55 ％,and no infection was found in ox.The infection rate was higher in rodents than that in other host animals,and the statistical analysis result revealed a significant difference.It is suggested that the rodents,especially the wide rodents are the main natural hosts of Babesia.

Natural hosts infected with Babesia in Fujian Province, China / 中国人兽共患病学报

We explored the status of Babesia infection in natural hosts in Fujian Province.Rodents in Fujian Province were captured by the night trapping method during 2014-2016.Heart blood samples were collected.At the same time blood samples of ox,goats and dogs were also collected,from which the fragments of 18S rRNA gene of Babesia were amplified by polymerase chain reaction (PCR).Data on infection rate were analyzed with Chi-square or Fisher exact test to indicate statistical significance.Results showed that 5 917 cages were laid and 381 rodents were captured,density of rodent was 6.44％.The o verall Babesia infection rate in rodents was 7.61％,while infection rate in domesticated rodents was 1.68％,and the infection rate in wide rodents was 12.87％.The infection rate was higher in wild rodents than that in domesticated rodents,and the statistical analysis result revealed a significant difference.The infection rates in region of Central Fujian and Eastern Fujian was high,and no infection was found in Southern Fujian region.The statistical analysis result revealed a significant difference in infection rate among different regions.The infection rate of goats and dogs were determined to be 1.79 ％ and 0.55 ％,and no infection was found in ox.The infection rate was higher in rodents than that in other host animals,and the statistical analysis result revealed a significant difference.It is suggested that the rodents,especially the wide rodents are the main natural hosts of Babesia.

A Fully Transparent Resistive Memory for Harsh Environments.

A fully transparent resistive memory (TRRAM) based on Hafnium oxide (HfO2) with excellent transparency, resistive switching capability, and environmental stability is demonstrated. The retention time measured at 85 °C is over 3 × 10(4) sec, and no significant degradation is observed in 130 cycling test. Compared with ZnO TRRAM, HfO2 TRRAM shows reliable performance under harsh conditions, such as high oxygen partial pressure, high moisture (relative humidity = 90% at 85 °C), corrosive agent exposure, and proton irradiation. Moreover, HfO2 TRRAM fabricated in cross-bar array structures manifests the feasibility of future high density memory applications. These findings not only pave the way for future TRRAM design, but also demonstrate the promising applicability of HfO2 TRRAM for harsh environments.

Wnt3a signal pathways activate MyoD expression by targeting cis-elements inside and outside its distal enhancer.

Wnt proteins are secreted cytokines and several Wnts are expressed in the developing somites and surrounding tissues. Without proper Wnt stimulation, the organization of the dermomyotome and myotome can become defective. These Wnt signals received by somitic cells can lead to activation of Pax3/Pax7 and myogenic regulatory factors (MRFs), especially Myf5 and MyoD. However, it is currently unknown whether Wnts activate Myf5 and MyoD through direct targeting of their cis-regulatory elements or via indirect pathways. To clarify this issue, in the present study, we tested the regulation of MyoD cis-regulatory elements by Wnt3a secreted from human embryonic kidney (HEK)-293T cells. We found that Wnt3a activated the MyoD proximal 6.0k promoter (P6P) only marginally, but highly enhanced the activity of the composite P6P plus distal enhancer (DE) reporter through canonical and non-canonical pathways. Further screening of the intervening fragments between the DE and the P6P identified a strong Wnt-response element (WRE) in the upstream -8 to -9k region (L fragment) that acted independently of the DE, but was dependent on the P6P. Deletion of a Pax3/Pax7-targeted site in the L fragment significantly reduced its response to Wnt3a, implying that Wnt3a activates the L fragment partially through Pax3/Pax7 action. Binding of ß-catenin and Pax7 to their target sites in the DE and the L fragment respectively was also demonstrated by ChIP. These observations demonstrated the first time that Wnt3a can directly activate MyoD expression through targeting cis-elements in the DE and the L fragment.

All-printed paper memory.

We report the memory device on paper by means of an all-printing approach. Using a sequence of inkjet and screen-printing techniques, a simple metal­insulator­metal device structure is fabricated on paper as a resistive random access memory with a potential to reach gigabyte capacities on an A4 paper. The printed-paper-based memory devices (PPMDs) exhibit reproducible switching endurance, reliable retention, tunable memory window, and the capability to operate under extreme bending conditions. In addition, the PBMD can be labeled on electronics or living objects for multifunctional, wearable, on-skin, and biocompatible applications. The disposability and the high-security data storage of the paper-based memory are also demonstrated to show the ease of data handling, which are not achievable for regular silicon-based electronic devices. We envision that the PPMDs manufactured by this cost-effective and time-efficient all-printing approach would be a key electronic component to fully activate a paper-based circuit and can be directly implemented in medical biosensors, multifunctional devices, and self-powered systems.

Resistive memory for harsh electronics: immunity to surface effect and high corrosion resistance via surface modification.

The tolerance/resistance of the electronic devices to extremely harsh environments is of supreme interest. Surface effects and chemical corrosion adversely affect stability and operation uniformity of metal oxide resistive memories. To achieve the surrounding-independent behavior, the surface modification is introduced into the ZnO memristors via incorporating fluorine to replace the oxygen sites. F-Zn bonds is formed to prevent oxygen chemisorption and ZnO dissolution upon corrosive atmospheric exposure, which effectively improves switching characteristics against harmful surroundings. In addition, the fluorine doping stabilizes the cycling endurance and narrows the distribution of switching parameters. The outcomes provide valuable insights for future nonvolatile memory developments in harsh electronics.

Valproic acid enhances Oct4 promoter activity through PI3K/Akt/mTOR pathway activated nuclear receptors.

Valproic acid (VPA) has been shown to increase the reprogramming efficiency of induced pluripotent stem cells (iPSC) from somatic cells, but the mechanism by which VPA enhances iPSC induction has not been defined. Here we demonstrated that VPA directly activated Oct4 promoter activity through activation of the PI3K/Akt/mTOR signaling pathway that targeted the proximal hormone response element (HRE, -41∼-22) in this promoter. The activating effect of VPA is highly specific as similar compounds or constitutional isomers failed to instigate Oct4 promoter activity. We further demonstrated that the upstream 2 half-sites in this HRE were essential to the activating effect of VPA and they were targeted by a subset of nuclear receptors, such as COUP-TFII and TR2. These findings show the first time that NRs are implicated in the VPA stimulated expression of stem cell-specific factors and should invite more investigation on the cooperation between VPA and NRs on iPSC induction.

Valproic acid enhances Oct4 promoter activity in myogenic cells.

Induced pluripotent stem (iPS) cells are reprogrammed from somatic cells through ectopic expression of stem cell-specific transcription factors, including Oct4, Nanog, Sox2, Lin28, Klf4, and c-Myc. Although iPS cells are similar to embryonic stem (ES) cells in their pluripotency, their inherited defects, such as insertion mutagenesis, employment of oncogenes, and low efficiency, associated with the reprogramming procedure have hindered their clinical application. A study has shown that valproic acid (VPA) treatment can significantly enhance the reprogramming efficiency and avoid the usage of oncogenes. To understand how VPA can enhance pluripotency, we stably transfected an Oct4 promoter driven luciferase reporter (Oct4-1.9k-Luc) into P19 embryonic carcinoma (EC) cells and C2C12 myoblasts and examined their response to VPA. We found that VPA could both activate Oct4 promoter and rescue its inhibition by retinoic acid (RA). In C2C12 myoblasts, VPA treatment also enhanced endogenous Oct4 expression but repressed that of MyoD. Furthermore, both RARalpha over-expression and mutation of a proximal hormone response element (HRE) blocked the activation effect of VPA on Oct4 promoter, implying that VPA may exert its activation effect through factors targeting this HRE. Taken together, these observations identify a molecular mechanism by which VPA directly regulate Oct4 expression to ensure the acquirement and maintenance of pluripotency.

Simultaneous overexpression of Oct4 and Nanog abrogates terminal myogenesis.

Oct4 and Nanog are two embryonic stem (ES) cell-specific transcription factors that play critical roles in the maintenance of ES cell pluripotency. In this study, we investigated the effects of Oct4 and Nanog expression on the differentiation state of myogenic cells, which is sustained by a strong positive feedback loop. Oct4 and Nanog, either independently or simultaneously, were overexpressed in C2C12 myoblasts, and the expression of myogenic lineage-specific genes and terminal differentiation was observed by RT-PCR. Overexpression of Oct4 in C2C12 cultures repressed, while exogenous Nanog did not significantly alter C2C12 terminal differentiation. The expression of Pax7 was reduced in all Oct4-overexpressing myoblasts, and we identified a major Oct4-binding site in the Pax7 promoter. Simultaneous expression of Oct4 and Nanog in myoblasts inhibited the formation of myotubes, concomitant with a reduction in the endogenous levels of hallmark myogenic markers. Furthermore, overexpression of Oct4 and Nanog induced the expression of their endogenous counterparts along with the expression of Sox2. Using mammalian two-hybrid assays, we confirmed that Oct4 functions as a transcriptional repressor whereas Nanog functions as a transcriptional activator during muscle terminal differentiation. Importantly, in nonobese diabetic (NOD) severe combined immunodeficiency (SCID) mice, the pluripotency of C2C12 cells was conferred by overexpression of Oct4 and Nanog. These results suggest that Oct4 in cooperation with Nanog strongly suppresses the myogenic differentiation program and promotes pluripotency in myoblasts.

Copper(II) complexes of salicylaldehyde hydrazones: synthesis, structure, and DNA interaction.

Three hydrazone ligands, H2L1-H2L3, made from salicylaldehyde and ibuprofen- or naproxen-derived hydrazides, were prepared and transformed into the corresponding copper(II) complexes [Cu(II)L1] x H2O, [Cu(II)L2], and [(Cu(II))2(L3)2] x H2O x DMF (Scheme). The X-ray crystal structure of the last-mentioned complex was solved (Fig. 1), showing a square-planar complexation geometry, and the single units were found to form a one-dimensional chain structure (Fig. 2). The interactions of these complexes with CT-DNA were studied by different techniques, indicating that they all bind to DNA by classical and/or non-classical intercalation modes.

Comparison of visual function following implantation of Acrysof Natural intraocular lenses with conventional intraocular lenses.

BACKGROUND: Recently an intraocular lens (IOL) has been introduced which blocks blue light. As blocking blue light may be to the patient's detriment, this study was designed to evaluate visual function following implantation of a blue-blocking (Acrysof Natural) IOL. METHODS: Patients were recruited for this non-randomized controlled interventional study, from those attending a private rural ophthalmology clinic for cataract surgery (n = 93). Only those who had previously had a conventional IOL implanted into one eye were offered an Acrysof Natural IOL for the second eye. Postoperatively patients underwent refracted Snellen visual acuity, contrast sensitivity using a CSV-1000E instrument and colour vision testing using a Farnsworth D-15 test, with a subset (n = 20) undergoing a Farnsworth-Munsell 100-Hue test. Results were then compared between eyes. Finally, a subset (n = 63) completed a survey designed to assess the subjective impact of the Acrysof Natural IOL. RESULTS: There were no statistically significant differences between eyes implanted with conventional IOLs compared with Acrysof Natural IOLs for visual acuity (t = 0.57; P = 0.57), contrast sensitivity (t = 0.43; P = 0.67 for 3 cycles per degree [cpd], t = 0.56; P = 0.58 for 6 cpd, t = 0.09; P = 0.93 for 12 cpd and t = 0.16; P = 0.87 for 18 cpd) or colour vision with the Farnsworth D-15 (Chi(2) = 0.38; P = 0.55) or the Farnsworth-Munsell 100-Hue test t = 0.34; P = 0.74). Most subjects reported that they could not tell a difference between the two IOLs subjectively or that any difference experienced was not significant. CONCLUSION: Our sample did not show any significant differences between eyes implanted with conventional IOLs and the Acrysof Natural IOL. We would suggest that the Acrysof Natural IOL may be used without any significant difference in visual function.