Self-Powered Colorful Dynamic Electrowetting Display Systems Based on Triboelectricity.

Electrowetting displays (EWDs) based on microfluidics are highly sought after in the fields of electronic devices, smart homes, and information communication. However, the power supply of the EWD systems for visually engaging multi-color displays remains a big challenge. Herein, self-powered colorful dynamic display systems are developed by integrating the triboelectric nanogenerator (TENG) with the EWD device. The TENG is designed with a nanotube-patterned surface and can generate open-circuit voltages ranging from 30 to 295 V by controlling the contact area. The wetting property of the micro-droplet exhibits a response to the applied voltage, enabling the triboelectricity-triggered electrowetting-on-dielectric. Driven by the voltage of 160 V, the monochromatic EWD exhibits bright color switching from magenta to transparent with a pixel aperture ratio of 78%, and the recovery process can be rapidly completed. Furthermore, the self-powered colorful dynamic EWD system can be achieved. By selectively applying the voltage to the pixels in the three monochromatic layers that constitute the colorful EWD, the wetting properties of the fluids can be controlled, allowing for colorful dynamic display. This work contributes to the advancement of color display technology for portable and wearable electronic ink displays, indoor and outdoor sports equipment, and information communication.

A study evaluating liquid-based endometrial cytology test and transvaginal ultrasonography as a screening tool for endometrial cancer in 570 postmenopausal women.

OBJECTIVE: To evaluate the combination of transvaginal ultrasonography (TVS) and endometrial cytology test (ECT) as a potential diagnostic strategy for endometrial cancer and endometrial precancerous lesions in postmenopausal patients. METHODS: 570 postmenopausal patients admitted in our hospital due to abnormal bleeding or other symptoms and/or with endometrium thickness over 5 mm on ultrasound. The endometrial thickness was evaluated by TVS. Following obtainment with written consent, all patients underwent ECT, hysteroscopy and then dilatation and curettage (D&C). Cytological sampling was conducted by scratching the uterus cavity using SAP-1 and the samples were prepared as liquid-based smear using SurePath technology. The samples were stained using Papanicolaou method. The correlation between cytological diagnosis and TVS results with the D&C histological diagnosis was analyzed. The WHO classification was used for diagnosis. RESULTS: Sensitivity of ECT, TVS, ECT or TVS positive, ECT and TVS positive to diagnose atypical hyperplasia or worse were estimated at 80.7%, 86.8%, 97.4%, 70.2%, specificity at 94.7%, 20.4%, 17.5%, 88.4%, positive predictive value at 58.2%, 21.1%, 22.8%, 60.2%, negative predictive value at 94.4%, 86.1%, 96.4%, 92.2%, and accuracy at 84.6%, 33.7%, 33.5%, 84.7%, respectively. CONCLUSIONS: Transvaginal ultrasonography and Endometrial cytology test may be regarded as a effective first-line method in endometrial pathology detection in postmenopausal women.

[Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism].

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 µg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). CONCLUSION: The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.

Genetic parameter estimates for three antioxidant factors in cultured Takifugu rubripes.

Genetic parameters of three antioxidant factors, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), were evaluated in liver samples from 840 Takifugu rubripes individuals from 28 full-sib families. Heritability values of SOD, CAT, and GPX were 0.17, 0.18, and 0.14, respectively, and the full-sib family effect values for these antioxidant factors were 0.46, 0.47, and 0.49, respectively. The ranges of phenotypic and genetic correlations among the three immune factors were 0.748-0.848 and 0.726-0.806, respectively. Considering the low heritability and high full-sib family effect of the three antioxidant indexes, the use of both genome-wide selection and clustered regularly interspaced short palindromic repeats (CRISPR) is promising for genetically improving the three antioxidant indexes in cultured fish. In addition, given positive phenotypic and genetic correlations among the three antioxidant enzymes SOD, CAT and GPX, the antioxidant competence of Takifugu rubripes can be improved by genetically improving these three antioxidant traits via multi-trait integrated breeding technology or indirect selection.

Successful Spermatogonial Stem Cells Transplantation within Pleuronectiformes: First Breakthrough at inter-family Level in Marine Fish.

As a promising biotechnology, fish germ cell transplantation shows potentials in conservation germplasm resource, propagation of elite species, and generation of transgenic individuals. In this study, we successfully transplanted the Japanese flounder (P. olivaceus), summer flounder (P. dentatus), and turbot (S. maximus) spermatogonia into triploid Japanese flounder larvae, and achieved high transplantation efficiency of 100%, 75-95% and 33-50% by fluorescence tracking and molecular analysis, respectively. Eventually, donor-derived spermatozoa produced offspring by artificial insemination. We only found male and intersex chimeras in inter-family transplantations, while male and female chimeras in both intra-species and intra-genus transplantations. Moreover, the intersex chimeras could mature and produce turbot functional spermatozoa. We firstly realized inter-family transplantation in marine fish species. These results demonstrated successful spermatogonial stem cells transplantation within Pleuronectiformes, suggesting the germ cells migration, incorporation and maturation within order were conserved across a wide range of teleost species.

Transcriptome analysis reveals that high temperatures alter modes of lipid metabolism in juvenile turbot (Scophthalmus maximus) liver.

With the increase in farming density and the continuously high summer temperatures against the background of global warming, high temperature stress has become a major challenge in fish farming. In this study, we simulated the high temperature environments (20 °C, 24 °C, and 28 °C) that may occur during turbot culture. High-throughput sequencing was used to investigate the lipid metabolism response patterns in juvenile turbot liver under high temperature stress. A total of 2067 differentially expressed genes (DEGs) were identified. KEGG analysis revealed that the DEGs were mainly associated with glycerophospholipid metabolism, steroid biosynthesis, glycerolipid metabolism, fatty acid metabolic pathways, and the PPAR signaling pathway. A regulatory network was constructed to further elucidate the transcriptional regulation of lipid metabolism. We speculated that high temperature activates PPAR signaling pathway through interaction with ligands such as fatty acids. On the one hand, the HMGCS1 gene in this pathway can inhibit sterol synthesis by down-regulating the expression of key genes in steroid biosynthesis pathway (SQLE, EBP, and DHCR24). On the other hand, the expression of ACSL1 in this pathway is significantly increased under high temperature, which may play an important role in regulating fatty acid metabolism. Moreover, we collected blood and detected changes in serum lipid parameters; the variation patterns were also consistent with our results. These findings reveal that lipid metabolism has an important regulatory role in stress resistance when turbot is exposed to high temperatures.

Physicians Leading Physicians: A Physician Engagement Intervention Decreases Inappropriate Use of IICU Level of Care Accommodations.

Following the adoption of an acuity-adaptable unit model in an academic medical center, a $13M increase in cost of intermediate intensive care unit (IICU) accommodations was observed. The authors followed A3 methodology to determine the root cause of this increase and developed a 3-prong intervention centered on physician engagement, given that physicians have the ability to order a patient's level of care. This intervention consisted of: (1) identifying physician champions to promote appropriate IICU use, (2) visual changes to essential electronic medical record tools, and (3) data-driven feedback to physician champions. In the year following intervention deployment, average IICU length of stay decreased from 1.08 to 0.62 days and average IICU use decreased from 21.4% to 12.3%, corresponding to ~$5.7M cost savings with no significant change in balancing measures observed. Together, these results demonstrate that a multicomponent intervention aimed at engaging physicians reduced inappropriate IICU use with no increase in adverse events.

Heat stress-induced HSP90 expression is dependent on ERK and HSF1 activation in turbot (Scophthalmus maximus) kidney cells.

Mitogen-activated protein kinases (MAPKs) and heat shock proteins (HSPs) are ubiquitous proteins that are functional mediators in both normal and stressed states of the cell. In this study, we performed heat stress (37 °C) experiments on turbot kidney (TK) cells. Heat stress expression patterns of HSP90, as well as the expression and phosphorylation levels of extracellular-regulated signal kinases (ERKs) and the transcription factor HSF1 and c-Fos, were examined. The results show that heat stress activates ERK1/2 and HSF1, and induces HSP90 gene expression in TK cells. Inhibition of ERK activation attenuates heat stress-induced HSP90 gene expression. The double luciferase reporter gene experiment showed that HSF1 is an important transcription factor for heat-induced HSP90 gene expression. Likewise, c-Fos does not directly regulate the heat-induced expression of HSP90 in turbot kidney cells. To our knowledge, this is the first study to report a signaling pathway that regulates the heat shock response in turbot cells. Our results may facilitate an understanding of the underlying molecular mechanisms of the cellular stress response in marine fish.

Timing and Predictors of Subspecialty Career Choice Among Internal Medicine Residents: A Retrospective Cohort Study.

BACKGROUND: Internal medicine residents face numerous career options after residency training. Little is known about when residents make their final career choice. OBJECTIVE: We assessed the timing and predictive factors of final career choices among internal medicine residents at graduation, including demographics, pre-residency career preferences, and rotation scheduling. METHODS: We conducted a retrospective study of graduates of an academic internal medicine residency program from 2014 to 2017. Main measures included demographics, rotation schedules, and self-reported career choices for residents at 5 time points: recruitment day, immediately after Match Day, end of postgraduate year 1 (PGY-1), end of PGY-2, and at graduation. RESULTS: Of the 138 residents eligible for the study, 5 were excluded based on participation in a fast-track program for an Accreditation Council for Graduate Medical Education subspecialty fellowship. Among the remaining 133 residents, 48 (36%) pursued general internal medicine fields and 78 (59%) pursued fellowship training. Career choices from recruitment day, Match Day, and PGY-1 were only weakly predictive of the career choice. Many choices demonstrated low concordance throughout training, and general medicine fields (primary care, hospital medicine) were frequently not decided until after PGY-2. Early clinical exposure to subspecialty rotations did not predict final career choice. CONCLUSIONS: Early career choices before and during residency training may have low predictability toward final career choices upon graduation in internal medicine. These choices may continue to have low predictability beyond PGY-2 for many specialties. Early clinical exposure may not predict final career choice for subspecialties.

High temperature increases the gsdf expression in masculinization of genetically female Japanese flounder (Paralichthys olivaceus).

In teleosts, sex is plastic and is influenced by environmental factors. Elevated temperatures have masculinizing effects on the phenotypic sex of certain sensitive species. In this study, we reared genetic XX Japanese flounder at a high temperature (27.5 ±â€¯0.5 °C) and obtained a population of sex-reversal XX males (male ratio, 95.24%). We comparatively analyzed the dynamic characteristics of germ cells and gsdf (gonadal soma-derived factor) expression during sexual differentiation for the experimental (27.5 ±â€¯0.5 °C) and control (18 °C ±â€¯0.5 °C) groups. The results revealed that the germ cell proliferation inhibited and gsdf expression up-regulated in the experimental group, and the gsdf mRNA and proteins expressed in somatic cells that had direct contact with germline stem cells (with Nanos 2 protein expression) including spermatogonia and oogonia by ISH (in situ hybridization) and IHC (immunohistochemistry). In addition, we also overexpressed the gsdf in XX flounders, and the germ cell number of XX flounders bearing gsdf gene significantly decreased and sometimes disappeared completely, which was consistent with the results from high-temperature induction. Therefore, based on all the results, we speculated that the high expression of gsdf might inhibit germ cell proliferation during sex differentiation, and eventually cause sex reversal in the high-temperature induced masculinization of XX Japanese flounder.

Identification of type A spermatogonia in turbot (Scophthalmus maximus) using a new cell-surface marker of Lymphocyte antigen 75 (ly75/CD205).

Turbot (Schophthalmus maximus) is one of the most important economic marine flatfish species. However, due to rapid development of the industry, genetic resource recession has brought down the efficiency of aquaculture. Therefore, conservation of the genetic resource is increasingly demanded. Recent research proved that type A spermatogonia possesses the properties of spermatogonia stem cell, and it might provide an ideal solution. Therefore, it is necessary to develop an appropriate molecular marker on type A spermatogonia to further isolate and purify of type A spermatogonia in turbot. In this study, turbot lymphocyte antigen 75 (smly75) gene was identified and its localizations of expressions and the temporal transcription patterns were evaluated qualitatively and semiquantitatively. Investigation in testes of development of spermatogonia showed that smly75 mRNA, contrast with vasa and dnd mRNA, was exclusively localized in type A spermatogonia and not detected in type B spermatogonia, spermatocytes or gonadal somatic cells by in situ hybridization. Thus, the smly75 could be a new and convincing molecular marker on identification of type A spermatogonia. In addition, specifically to development pattern of type A spermatogonia, from 7- to 14- month testes, spermatogonia were dominated and the number of type A spermatogonia was increased, corresponding that smly75 expression was up-regulated gradually, while, in 16 month testes, accompanied by that several spermatogonia differentiated into primary spermatocytes, the smly75 expression down-regulated. Finally, broaden in the whole reproductive cycle, the smly75 transcription significantly variated with the differentiation of germ cells and in accordance with the number of type A spermatogonia. It is suggested that testes from 8 to 14 month old males could be used for further isolation and purification of type A-SG. These results will not only help to better understand type A spermatogonia, but also further facilitate type A spematogonia-mediated germ cell manipulation in turbot.

Progestin is important for testicular development of male turbot (Scophthalmus maximus) during the annual reproductive cycle through functionally distinct progestin receptors.

In teleost, sex steroid hormones are critical for reproduction. Progestin is known to promote spermiation. To further understand the functions of progestin via its receptors during the annual reproductive cycle in male turbot (Scophthalmus maximus), we observed testicular development, quantified several sex steroid hormones, detected the expression of progestin receptors, and measured various sperm parameters. Results showed that the turbot testicular structure was of the lobular type. During breeding season, a number of spermatocytes (stage III) developed into spermatids (stage IV), then differentiated into sperm during spermiogenesis (stage V), and finally regressed to spermatocytes (stage VI). Concomitant with testicular development, serum progesterone (P4) and 17α,20ß-dihydroxy-4-pregnen-3-one (DHP) exhibited higher levels from stage IV to V than other stages. Furthermore, males with higher motility sperm showed higher levels of P4 and DHP compared with fish with lower motility sperm. These results indicated that P4 and DHP might induce spermatogenesis due to seasonal changes. Concurrently, in testes, the nuclear progesterone receptor (pgr) was expressed throughout the reproductive cycle and its level peaked during spermiogenesis while expression of membrane progestin receptor alpha (mPRα) did not change significantly. However, in sperm, mPRα expression was higher than in testes and had a significant positive correlation with curvilinear velocities (VCL), sperm motility, and motility duration. In conclusion, progestin appears to exert a direct pgr-mediated effect on spermiogenesis and improve sperm motility characteristics depending on the abundance of mPRα protein in sperm during spermiation.

Atrial Fibrillation Associated Genetic Variants and Left Atrial Histology: Evaluation for Molecular Sub-Phenotypes.

INTRODUCTION: Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with atrial fibrillation (AF), but the mechanisms underlying these relationships have not yet been elucidated. Inflammation and fibrosis have been posited as important mechanisms responsible for AF. We sought to investigate the impact of SNP carrier status on inflammation and fibrosis in left atrial appendage tissue. METHODS AND RESULTS: Carrier status of 10 AF-associated SNPs was evaluated on DNA extracted from left atrial appendage tissue in 176 individuals (120 with AF). The presence of inflammation was evaluated through visual quantification of leukocyte infiltration following hematoxylin and eosin staining, while fibrosis was quantified using picrosirius red with fast green staining. Unadjusted and adjusted linear and logistic regression models were utilized to evaluate for an association between SNP carrier status and inflammation and fibrosis. On adjusted logistic regression analysis, the rs7164883 SNP (intronic within HCN4) was associated with a reduced odds of inflammation (odds ratio: 0.42; 95% CI: 0.22-0.81, P = 0.01), and was not associated with fibrosis on adjusted linear regression analysis (ß-coefficient: -0.31; 95% CI: -1.03-0.40, P = 0.40). None of the remaining SNPs exhibited significant associations with left atrial inflammation or fibrosis. CONCLUSIONS: Among 10 AF-associated SNPs, a single genetic variant was associated with reduced left atrial inflammation, while no histologic differences were observed in the remaining 9. The known AF-associated SNPs do not appear to predispose to the development of pro-inflammatory or pro-fibrotic AF sub-phenotypes.

Characteristics of unselected high-burden premature ventricular contraction patients.

BACKGROUND: High-burden premature ventricular contractions (PVCs) may be an important determinant of heart failure (HF) in patients presenting for PVC ablation. The prevalence and characteristics of high-burden PVC patients outside this setting remain unknown. We, therefore, sought to determine predictors of high-burden PVCs and, among high-burden PVC patients, predictors of HF. METHODS: We identified all patients undergoing a 24-48-hour Holter study showing at least 20% PVCs between 2005 and 2013 at the University of California, San Francisco. Three time-matched controls undergoing Holter monitoring were selected for each high-burden PVC patient. Medical records were reviewed and test characteristics of PVC counts from 12-lead electrocardiograms (ECG) as predictors of high-burden PVC Holters were analyzed. RESULTS: Among 5,091 participants, 66 (1.3%) exhibited at least 20% PVCs. After multivariate adjustment, high-burden PVC patients had a three-fold greater odds of HF (odds ratio [OR] 3.15; 95% confidence interval [CI] 1.28-6.50; P = 0.005) and 10-fold greater odds of having a first-degree family member with sudden death (OR 9.97; 95% CI 1.78-60.8; P = 0.011). The C-statistic for the number of PVCs on 12-lead electrocardiogram as a predictor of high-burden PVCs was 0.7949. Among high-burden PVC patients, HF was associated with a history of coronary artery bypass grafting (OR 11.76; 95% CI 1.30-106.49; P = 0.028). CONCLUSION: Among all undergoing Holter monitoring, 1.3% exhibited high-burden PVCs, a phenomenon associated with HF and a first-degree family history of sudden death. In an analysis restricted to high-burden PVC patients, a history of coronary artery bypass grafting was a predictor of HF.

Group II archaeal chaperonin recognition of partially folded human γD-crystallin mutants.

The features in partially folded intermediates that allow the group II chaperonins to distinguish partially folded from native states remain unclear. The archaeal group II chaperonin from Methanococcus Mauripaludis (Mm-Cpn) assists the in vitro refolding of the well-characterized ß-sheet lens protein human γD-crystallin (HγD-Crys). The domain interface and buried cores of this Greek key conformation include side chains, which might be exposed in partially folded intermediates. We sought to assess whether particular features buried in the native state, but absent from the native protein surface, might serve as recognition signals. The features tested were (a) paired aromatic side chains, (b) side chains in the interface between the duplicated domains of HγD-Crys, and (c) side chains in the buried core which result in congenital cataract when substituted. We tested the Mm-Cpn suppression of aggregation of these HγD-Crys mutants upon dilution out of denaturant. Mm-Cpn was capable of suppressing the off-pathway aggregation of the three classes of mutants indicating that the buried residues were not recognition signals. In fact, Mm-Cpn recognized the HγD-Crys mutants better than (wild-type) WT and refolded most mutant HγD-Crys to levels twice that of WT HγD-Crys. This presumably represents the increased population or longer lifetimes of the partially folded intermediates of the mutant proteins. The results suggest that Mm-Cpn does not recognize the features of HγD-Crys tested-paired aromatics, exposed domain interface, or destabilized core-but rather recognizes other features of the partially folded ß-sheet conformation that are absent or inaccessible in the native state of HγD-Crys.

A novel method for producing mono-biotinylated, biologically active neurotrophic factors: an essential reagent for single molecule study of axonal transport.

In this report, we describe a novel method for producing mature and biologically active mono-biotinylated nerve growth factors (mBtNGF) that can be used for single molecule studies of real-time movement of neurotrophins within axons of neurons. We inserted an AviTag sequence into the C-terminal of the full length mouse preproNGF cDNA and cloned the fusion construct into a pcDNA3.1 mammalian expression vector. We also subcloned the Escherichia coli biotin ligase, BirA, into a pcDNA3.1 vector. These two plasmids were then transiently co-expressed in HEK293FT cells. As a result, the AviTag located in the C-terminal of preproNGF was selectively ligated to a single biotin by BirA. The prepro sequence of NGF was subsequently cleaved within the cell. Mature mono-biotinylated NGF (mBtNGF) was secreted into cell culture media and was purified using Ni resin. We carried out activity assays and our results showed that mBtNGF retained biological activities that were comparable to normal NGF purified from mouse sub maxillary glands. We further verified the biotinylation efficiency of mBtNGF and the level of non-biotinylated NGF was virtually undetectable in the final preparation. Finally, by conjugating to quantum-dot streptavidin, mBtNGF was successfully used for single molecule study of axonal NGF trafficking in neurons.