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Background: Conjunctival prolapse (CP) is an uncommon but challenging condition following maximal levator resection (MLR) and other extensive periorbital procedures. MLR extending beyond the Whitnall's ligament is frequently performed to address severe blepharoptosis with poor levator function (LF). Patients with CP may encounter symptoms such as ocular discomfort, tearing, vision impairment, persistent conjunctival chemosis, lagophthalmos, or exposure keratopathy. Typically, surgical intervention becomes necessary if conservative measures prove to be ineffective; nevertheless, there is no consensus regarding the optimal treatment approach., Objectives: This study aimed to propose a simple sutureless direct excision method and explore the surgical advancements in CP correction through a systematic review., Methods: Patients with recurrent CP after MLR who underwent sutureless direct excision of the conjunctiva using loupe magnifiers at a tertiary hospital were included in this study. The clinical evolution and surgical results were recorded. PubMed, MEDLINE, EMBASE, and Web of Science databases were queried following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol., Results: The comprehensive analysis of 1858 articles identified 88 patients from 24 studies, highlighting that blepharoptosis surgery is predominantly associated with CP (36.6%). Surgically treated CP showed a higher resolution rate compared to those managed conservatively (54.8% vs. 45.2%; p = 0.034). No relapse was observed in patients treated with sutureless direct excision of CP in long-term follow-up., Conclusion: We proposed a simple sutureless direct excision technique that offers a straightforward and efficient approach in treating CP, which is particularly suitable for cases requiring excision lengths >16 mm during MLR. Furthermore, stitch removal can be obviated after surgery., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Accurate assessment of wound areas is crucial in making therapeutic decisions, as the prognosis and changes in the size of the wound over time play a significant role. An ideal assessment method should possess qualities such as speed, affordability, accuracy, user-friendliness for both patients and healthcare professionals, and suitability for daily clinical practice. This study aims to introduce a handheld 3-dimensional (3D) scanner and evaluate its accuracy in measuring wound areas. Engineers from the Industrial Technology Research Institute in Taiwan developed a handheld 3D scanner with the intention of extending its application to the medical field. A project was conducted to validate the accuracy of this 3D scanner. We utilized a smartphone (Asus ZenFone 2 with a 13-million-pixel rear camera), a digital single-lens reflex digital camera (Nikon, D5000, Tokyo, Japan), and the 3D scanner to repeatedly measure square papers of known size that were affixed to the curved surface of life-size facial mask or medical teaching breast models. The "Image J" software was employed for 2-dimensional image measurements, while the "3D Edit" software was used to assess the "area of interest" on 3D objects. By using square papers with predetermined dimensions, the measurement-associated error rate (ER) could be calculated for each image. Three repeated measurements were performed using the "Image J" software for each square paper. The ERs of the 3D scan images were all below 3%, with an average ER of 1.64% in this study. The close-up mode of the smartphone exhibited the highest ER. It was observed that as the area increased, the ER also increased in the digital single-lens reflex camera group. The extension distortion effect caused by the wide-angle lens on the smartphone may increase the ER. However, the definition of a healthy skin edge may vary, and different algorithms for calculating the measurement area are employed in various 3D measurement software. Therefore, further validation of their accuracy for medical purposes is necessary. Effective communication with software engineers and discussions on meeting clinical requirements are crucial steps in enhancing the functionality of the 3D scanner., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Home health care (HHC) and nursing home care (NHC) are mainstays of long-term service in the aged population. Therefore, we aimed to investigate the factors associated with 1-year medical utilization and mortality in HHC and NHC recipients in Northern Taiwan., Design: This study employed a prospective cohort design., Setting and Participants: We enrolled 815 HHC and NHC participants who started receiving medical care services from the National Taiwan University Hospital, Beihu Branch between January 2015 and December 2017., Methods: Multivariate Poisson regression modeling was used to quantify the relationship between care model (HHC vs NHC) and medical utilization. Cox proportional-hazards modeling was used to estimate hazard ratios and factors associated with mortality., Results: Compared with NHC recipients, HHC recipients had higher 1-year utilization of emergency department services [incidence rate ratio (IRR) 2.04, 95% CI 1.16-3.59] and hospital admissions (IRR 1.49, 95% CI 1.14-1.93), as well as longer total hospital length of stay (LOS) (IRR 1.61, 95% CI 1.52-1.71) and LOS per hospital admission (IRR 1.31, 95% CI 1.22-1.41). Living at home or in a nursing home did not affect the 1-year mortality., Conclusions and Implications: Compared with NHC recipients, HHC recipients had a higher number of emergency department services and hospital admissions, as well as longer hospital LOS. Policies should be developed to reduce emergency department and hospitalization utilization in HHC recipients., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Interactions between physical forces and membrane proteins underpin many forms of environmental sensation and acclimation. Microbes survive osmotic stresses with the help of mechanically gated ion channels and osmolyte transporters. Plant mechanosensitive ion channels have been shown to function in defense signaling. Here, we engineered genetically encoded osmolality sensors (OzTracs) by fusing fluorescent protein spectral variants to the mechanosensitive ion channels MscL from E. coli or MSL10 from A. thaliana . When expressed in yeast cells, the OzTrac sensors reported osmolality changes as a proportional change in the emission ratio of the two fluorescent protein domains. Live-cell imaging revealed an accumulation of fluorescent sensors in internal aggregates, presumably derived from the endomembrane system. Thus, OzTrac sensors serve as osmolality-dependent reporters through an indirect mechanism, such as effects on molecular crowding or fluorophore solvation.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy caused by monoallelic loss-of-function variants in the SCN1A gene. SCN1A encodes for the alpha subunit of the voltage-gated type I sodium channel (Na V 1.1), the primary voltage-gated sodium channel responsible for generation of action potentials in GABAergic inhibitory interneurons. In these studies, we tested the efficacy of an adeno-associated virus serotype 9 (AAV9) SCN1A gene regulation therapy, AAV9-RE GABA -eTF SCN1A , designed to target transgene expression to GABAergic inhibitory neurons and reduce off-target expression within excitatory cells, in the Scn1a +/- mouse model of DS. Biodistribution and preliminary safety were evaluated in nonhuman primates (NHPs). AAV9-RE GABA -eTF SCN1A was engineered to upregulate SCN1A expression levels within GABAergic inhibitory interneurons to correct the underlying haploinsufficiency and circuit dysfunction. A single bilateral intracerebroventricular (ICV) injection of AAV9-RE GABA -eTF SCN1A in Scn1a +/- postnatal day 1 mice led to increased SCN1A mRNA transcripts, specifically within GABAergic inhibitory interneurons, and Na V 1.1 protein levels in the brain. This was associated with a significant decrease in the occurrence of spontaneous and hyperthermia-induced seizures, and prolonged survival for over a year. In NHPs, delivery of AAV9-RE GABA -eTF SCN1A by unilateral ICV injection led to widespread vector biodistribution and transgene expression throughout the brain, including key structures involved in epilepsy and cognitive behaviors, such as hippocampus and cortex. AAV9-RE GABA -eTF SCN1A was well tolerated, with no adverse events during administration, no detectable changes in clinical observations, no adverse findings in histopathology, and no dorsal root ganglion-related toxicity. Our results support the clinical development of AAV9-RE GABA -eTF SCN1A (ETX101) as an effective and targeted disease-modifying approach to SCN1A + DS.

Aim: Neutrophil infiltration and increased oxidative stress are involved in the pathogenesis and severity of psoriasis. Although the therapy of psoriasis remains elusive, targeting treatment to reduce oxidative stress is considered a potential option. Our study demonstrates the anti-inflammatory effects of a natural furocoumarin, imperatorin, on activated human neutrophils and psoriasiform dermatitis in mice. Results: Imperatorin inhibited superoxide anion generation, neutrophil adhesion, and migration in N -formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-stimulated human neutrophils. Further studies showed that imperatorin induced a decrease in cAMP-specific phosphodiesterase (PDE) activity, and increased intracellular cAMP levels and protein kinase A (PKA) activity in human neutrophils. The enzyme activities of PDE4 subtypes, but not PDE3 and PDE7, were inhibited by imperatorin. Furthermore, imperatorin inhibited the phosphorylation of protein kinase B (Akt), extracellular regulated kinase (ERK), and c-Jun N -terminal kinase (JNK), as well as Ca 2+ mobilization in fMLF-stimulated neutrophils. These suppressive effects of imperatorin on cell responses and signaling were reversed by PKA inhibitor, suggesting that cAMP/PKA is involved in the anti-inflammatory effects of imperatorin. In vivo studies of imiquimod- and interleukin-23-induced mouse psoriasiform dermatitis demonstrated that imperatorin alleviated skin desquamation, epidermal thickening, keratinocyte hyperproliferation, and neutrophil infiltration. Innovation and Conclusion: Our results demonstrate that imperatorin inhibits human neutrophil respiratory burst, adhesion, and migration through the elevation of cAMP/PKA to inhibit Akt, ERK, JNK, and Ca 2+ mobilization. Imperatorin is a natural inhibitor of PDE4A/B/C and may serve as a lead for developing new therapeutics to treat neutrophilic psoriasis. Antioxid. Redox Signal. 35, 885-903.

Background and Objectives: Prior research has successfully identified linguistic and behavioral patterns associated with schizophrenia spectrum disorders (SSD) from user generated social media activity. Few studies, however, have explored the potential for image analysis to inform psychiatric care for individuals with SSD. Given the popularity of image-based platforms, such as Instagram, investigating user generated image data could further strengthen associations between social media activity and behavioral health. Methods: We collected 11,947 Instagram posts across 68 participants (mean age = 23.6; 59% male) with schizophrenia spectrum disorders (SSD; n = 34) and healthy volunteers (HV; n = 34). We extracted image features including color composition, aspect ratio, and number of faces depicted. Additionally, we considered social connections and behavioral features. We explored differences in usage patterns between SSD and HV participants. Results: Individuals with SSD posted images with lower saturation ( p = 0.033) and lower colorfulness ( p = 0.005) compared to HVs, as well as images showing fewer faces on average ( SSD = 1.5, HV = 2.4, p < 0.001). Further, individuals with SSD demonstrated a lower ratio of followers to following compared to HV participants ( p = 0.025). Conclusion: Differences in uploaded images and user activity on Instagram were identified in individuals with SSD. These differences highlight potential digital biomarkers of SSD from Instagram data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hänsel, Lin, Sobolev, Muscat, Yum-Chan, De Choudhury, Kane and Birnbaum.)

Activation of autophagy plays a critical role in DNA repair, especially for the process of homologous recombination. Despite upregulation of autophagy promotes both the survival and the death of cells, the pathways that govern the pro-cell death effects of autophagy are still incompletely understood. YM155 is originally developed as an expression suppressant of BIRC5 (an anti-apoptotic molecule) and it has reached Phase I/II clinical trials for the treatment of variety types of cancer. However, the target-specificity of YM155 has recently been challenged as several studies reported that YM155 exhibits direct DNA damaging effects. Recently, we discovered that BIRC5 is an autophagy negative-modulator. Using function-comparative analysis, we found in the current study that YM155 and BIRC5 siRNA both induced early "autophagy-dependent ROS production-mediated" DNA damage/strand breaks and concurrently downregulated the expression of RAD54L, RAD51, and MRE11, which are molecules known for their important roles in homologous recombination, in human cancer (MCF7, MDA-MB-231, and SK-BR-3) and mouse embryonic fibroblast (MEF) cells. Similar to the effects of YM155 and BIRC5 siRNA, downregulation of RAD54L and RAD51 by siRNA induced autophagy and DNA damage/strand breaks in cells, suggesting YM155/BIRC5 siRNA might also induce autophagy partly through RAD54L and RAD51 downregulations. We further observed that prolonged YM155 and BIRC5 siRNA treatment induced autophagic vesicle formation proximal to the nucleus and triggered DNA leakage. In conclusion, our findings reveal a novel mechanism of action of YM155 (i.e. induces autophagy-dependent ROS production-mediated DNA damage) in cancer cells and show the functional complexity of BIRC5 and autophagy involving the modulation of genome stability, highlighting that upregulation of autophagy is not always beneficial to the DNA repair process. Our findings can aid the development of a variety of BIRC5-directly/indirectly targeted anticancer therapies that are currently under pre-clinical and clinical investigations., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Lifelong learning is embedded in the culture of medicine, but there are limited tools currently available for many clinicians, including hospitalists, to help improve their own practice. Although there are requirements for continuing medical education, resources for learning new clinical guidelines, and developing fields aimed at facilitating peer-to-peer feedback, there is a gap in the availability of tools that enable clinicians to learn based on their own patients and clinical decisions., Objective: The aim of this study was to explore the technologies or modifications to existing systems that could be used to benefit hospitalist physicians in pursuing self-assessment and improvement by understanding physicians' current practices and their reactions to proposed possibilities., Methods: Semistructured interviews were conducted in two separate stages with analysis performed after each stage. In the first stage, interviews (N=12) were conducted to understand the ways in which hospitalist physicians are currently gathering feedback and assessing their practice. A thematic analysis of these interviews informed the prototype used to elicit responses in the second stage., Results: Clinicians actively look for feedback that they can apply to their practice, with the majority of the feedback obtained through self-assessment. The following three themes surrounding this aspect were identified in the first round of semistructured interviews: collaboration, self-reliance, and uncertainty, each with three related subthemes. Using a wireframe, the second round of interviews led to identifying the features that are currently challenging to use or could be made available with technology., Conclusions: Based on each theme and subtheme, we provide targeted recommendations for use by relevant stakeholders such as institutions, clinicians, and technologists. Most hospitalist self-assessments occur on a rolling basis, specifically using data in electronic medical records as their primary source. Specific objective data points or subjective patient relationships lead clinicians to review their patient cases and to assess their own performance. However, current systems are not built for these analyses or for clinicians to perform self-assessment, making this a burdensome and incomplete process. Building a platform that focuses on providing and curating the information used for self-assessment could help physicians make more accurately informed changes to their own clinical practice and decision-making., (©Andrew Lukas Yin, Pargol Gheissari, Inna Wanyin Lin, Michael Sobolev, John P Pollak, Curtis Cole, Deborah Estrin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 03.11.2020.)

Rationale: Lymphadenectomy for tongue cancer in the neck region is often accompanied by local impaired mobility, gland damage, difficult in swallowing, and postoperative complication and seriously affects patients life quality. We reported a case of subcutaneous adhesions and scar hyperplasia in the neck region after lymphadenectomy for tongue lesions accompanied by impaired neck mobility and difficult in swallowing was treated using Fu's subcutaneous needling (FSN) treatment., Patient Concerns: A 55-year-old male with tongue cancer received surgical intervention with lymphadenectomy 8 years ago was revealed a 15 cm-long curved surgical incision in the neck region and surrounded by numerous scar tissues., Diagnosis: Post-operation subcutaneous adhesions and scar hyperplasia in the neck region after lymphadenectomy was diagnosed., Interventions: FSN treatment was performed 2 to 3 times per week for 1 month to sway the affected tightened muscle and dissociate the superficial fascia beneath the scar resulted in a considerable improvement in neck movement., Outcomes: The Vancouver Scar Scale (VSS) was as follows: color (M) - 1; vascular distribution (V) - 0, thickness (H) - 2, and flexibility (P) - 4, with a total of 7 points before FSN treatment. The VSS after 1 month of FSN treatment was as follows: M1, V0, H2, and P2, with a total of 5 points. Neck mobility in different directions, i.e., stretching to the back of the neck and laterally bending the neck to the left and/or right side, was improved (P < .05)., Lessons: At present, treatment of chronic scar hyperplasia has certain side effects and limitations. FSN is safe and convenient, with minimal destruction of the superficial fascia, having evident effects of dissociating tissue adhesion under scars and compensating for deficiencies in scar hyperplasia treatment. It can provide new ideas for future treatments.

The dose adjustment of anti-diabetic drugs during traveling abroad remains an important issue for the diabetic patients. However, there are few studies exploring the changes in blood sugar in patients with type 2 diabetes mellitus (T2DM) when traveling abroad. The study aimed to investigate the hypoglycemic episodes, sugar control, and associated factors during travel among patients with T2DM.A questionnaire was administrated to T2DM patients visiting the family medicine clinic in a medical center from September 2016 to April 2017. The Chi-square test was used to examine the differences in risk factors of hypoglycemia between hypoglycemic group and non-hypoglycemic group. Multivariate logistic regression models were used to examine the risk factors for the hypoglycemia.A total of 65 males and 74 females completed the questionnaire. The mean age was 59.3 ± 12.1 year olds, the mean BMI was 28.1 ± 5.9 kg/m, and the mean HbA1C was 7.4 ± 1.1%. There was 8.6% of diabetic patients reporting hypoglycemic episodes during travel. The hypoglycemic episodes were significantly related to the numbers of crossing time zones after adjusting for possible confounders. Only 21.6% of subjects told physicians their travel plan whereas two third of the physicians did not provide pre-travel consultation.The hypoglycemic episodes sometimes occurred and were related to the numbers of crossing time zones in diabetic travelers. The proportion of pre-travel consultation was low in patients with T2DM. Besides, most of the physicians did not offer pre-travel education when patients mentioned their traveling plan. The willing and ability of physicians to offer the pre-travel diabetic education deserved further investigation.

Various surgical techniques for canalicular laceration reconstruction have been described in previous study. But there are still two difficult points which may take time in the operation even with the assistance of magnification. We present a simple and effective way to achieve the bicanalicular nasal intubation for the single canalicular laceration. From Jan 2005 to Dec 2015, 20 patients (21 eyes) with upper or lower canalicular laceration were treated with the Crawford lacrimal intubation set by this stitch guide method. We used the eye pigtail probe and the steel probe of the intubation set to dispose a 4-0 Nylon suture as a guide to pull down the silicone tube to the nostril. The functional and anatomic success rates in the 20 eyes are 90% (18/20) and 85% (17/20) respectively. The average time for bicanalicular nasal intubation by this method is 6.87 ± 1.83 min. The result of stitch guide technique to achieve bicanalicular nasal intubation in single canalicular laceration reconstruction is almost the same as the traditional method. Our anatomic and functional success rates are 85% and 90% respectively which are comparable to the previous studies. But this new method takes less time to complete the intubation with little variation. The magnification with microscopy could be omitted and no new instrument is needed. The stitch guide technique for bicanalicular nasal intubation with Crawford intubation system is a reliable and easy way to perform in single canalicular laceration reconstruction., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

A new polyprenylated polycyclic acylphloroglucinol, garcimultiflorone K (1), has been isolated from the stems of Garcinia multiflora, together with two known compounds, garcimultiflorone A (2) and garcimultiflorone B (3). The structure of new compound 1 was determined through spectroscopic methods including 1D and 2D NMR and MS analyses. The anti-angiogenic and anti-cancer effects of compounds 1-3 were evaluated in human endothelial progenitor cells (EPCs) and cancer cells. Of these, garcimultiflorone K (1) displayed the most potent anti-angiogenic property by suppressing cell growth and tube formation of EPCs. Compound 1 also exhibited growth-inhibitory activities against human hepatocellular carcinoma cell line SK-Hep-1 and hormone refractory prostate cancer cell line PC-3 with GI 50 values of 4.3 ± 1.6 and 6.6 ± 0.4 μM, respectively., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Rationale: Although numerous reconstruction protocols have been reported for lower leg trauma, those for distal leg trauma remain few. We present the case of a woman with an implant exposure wound, who was successfully treated through fat grafting, without major flap surgery., Patient Concerns: An 83-year-old woman with an exposed implant in lower extremity received reconstruction surgery once and the surgery failed. She refused additional major surgery and negative pressure wound therapy., Diagnoses: The diagnosis of a tibia and fibula shaft open fracture (type IIIA) complicated with an exposed implant was made., Interventions: The procedure was performed by deploying purified and emulsified fat with a Micro-Autologous Fat Transplantation gun. The required lipoaspirate amount was grossly estimated using a standard formula: 0.5 cc of a lipoaspirate per square centimeter of wound. We prepared the lipoaspirate simply through centrifugation followed by physical emulsification. The endpoint of fat grafting was when lipoaspirate began to flow out of the wound. The initial dressing after the procedure included the topical usage of biomycin ointment with AQUACEL Foam (ConvaTec Inc., NC, USA) coverage, which was later changed to INTRASITE gel (Smith & Nephew, London, UK) with a gauze dressing for 4 weeks. After 4 weeks, dressing components were changed to Mepilex (Mölnlycke Health Care, Gothenburg, Sweden) alone., Outcomes: The wound healed completely without requiring major flap surgery by 18 weeks after surgery., Lessons: Fat grafting is one kind of cell therapy and potentially has regenerative effects during wound healing. Fat grafting is critical in the healing processes of complicated wounds and might be considered a step in reconstruction surgery.

Bisphenol A (BPA) is a well-known endocrine disrupting chemical (EDC) that is used to manufacture plastic consumer products. It is well known that exposure to BPA can induce defects in gonad development and negatively influences reproductive function in both males and females. In this study, we assessed the effects of BPA on hormone production in Leydig cells, which secrete hormones in the testes and support male fertility. We examined two steroidogenic enzymes, CYP11A1 and CYP19 that involved in sex hormone synthesis in mouse MA-10 Leydig cells. We found that BPA activated CYP gene in both mRNA and protein levels then resulted in alteration of the normal sex hormone ratio. Furthermore, we found that BPA induced c-Jun phosphorylation and contributed to CYP gene expression. Similar results were observed in an animal study. In conclusion, BPA disrupts the hormone environment in testis via steroidogenic gene activation through the JNK/c-Jun signaling pathway., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Sporamin is a tuberous storage protein with trypsin inhibitory activity in sweet potato (Ipomoea batatas Lam.), which accounts for 85% of the soluble protein in tubers. It is constitutively expressed in tuberous roots but is expressed in leaves only after wounding. Thus far, its wound-inducible signal transduction mechanisms remain unclear. In the present work, a 53-bp DNA region, sporamin wound-response cis-element (SWRE), was identified in the sporamin promoter and was determined to be responsible for the wounding response. Using yeast one-hybrid screening, a NAC domain protein, IbNAC1, that specifically bound to the 5'-TACAATATC-3' sequence in SWRE was isolated from a cDNA library from wounded leaves. IbNAC1 was constitutively expressed in root tissues and was induced earlier than sporamin following the wounding of leaves. Transgenic sweet potato plants overexpressing IbNAC1 had greatly increased sporamin expression, increased trypsin inhibitory activity, and elevated resistance against Spodoptera litura. We further demonstrated that IbNAC1 has multiple biological functions in the jasmonic acid (JA) response, including the inhibition of root formation, accumulation of anthocyanin, regulation of aging processes, reduction of abiotic tolerance, and overproduction of reactive oxygen species (ROS). Thus, IbNAC1 is a core transcription factor that reprograms the transcriptional response to wounding via the JA-mediated pathway in sweet potato., (© 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.)

Certain commonly used compounds that interfere with the functions of the endocrine system are classified as endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA) is an EDC that is widely used in food containers. BPA levels in human sera are commonly observed to be approximately 1-100 nM. Compared with the effects of BPA on the gonads, its effects on the adrenal gland are poorly understood. To investigate the influence of BPA on steroidogenesis, we examined the activity of the steroidogenic gene Cyp11a1 and its regulatory pathways in mouse Y1 adrenal cortex cells. Treatment with BPA at < 100 µM did not cause cell death. However, increased promoter activity and protein expression of Cyp11a1 were induced by low doses of BPA (10-1000 nM). Moreover, BPA induced c-Jun phosphorylation, and a specific inhibitor of c-Jun N-terminal kinase (JNK) significantly suppressed BPA-induced steroidogenesis. Thus, treatment of adrenal cells with low doses of BPA activated Cyp11a1 and increased corticosterone production through the JNK/c-Jun signaling pathway. Identical results were observed in rats after BPA injection. The abnormal induction of hormone synthesis by BPA in the adrenal gland might be linked to human metabolic defects and neuropsychiatric disorders., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Developing plant embryos depend on nutrition from maternal tissues via the seed coat and endosperm, but the mechanisms that supply nutrients to plant embryos have remained elusive. Sucrose, the major transport form of carbohydrate in plants, is delivered via the phloem to the maternal seed coat and then secreted from the seed coat to feed the embryo. Here, we show that seed filling in Arabidopsis thaliana requires the three sucrose transporters SWEET11, 12, and 15. SWEET11, 12, and 15 exhibit specific spatiotemporal expression patterns in developing seeds, but only a sweet11;12;15 triple mutant showed severe seed defects, which include retarded embryo development, reduced seed weight, and reduced starch and lipid content, causing a "wrinkled" seed phenotype. In sweet11;12;15 triple mutants, starch accumulated in the seed coat but not the embryo, implicating SWEET-mediated sucrose efflux in the transfer of sugars from seed coat to embryo. This cascade of sequentially expressed SWEETs provides the feeding pathway for the plant embryo, an important feature for yield potential., (© 2015 American Society of Plant Biologists. All rights reserved.)

Meristic variation is often limited in serially homologous systems with high internal differentiation and high developmental modularity. The mammalian neck, an extreme example, has a fixed (at seven) count of diversely specialized segments. Imposition of the mammalian cervical constraint has been tentatively linked to the origin of the diaphragm, which is muscularized by cells that migrate from cervical somites during development. With six cervical vertebrae, the genus Trichechus (manatee) has apparently broken this constraint, although the mechanism of constraint escape is unknown. Hypotheses for the developmental origin of Trichechus cervical morphology include cervical rib 7 repatterning, a primaxial/abaxial patterning shift, and local homeosis at the cervical/thoracic boundary. We tested predictions of these hypotheses by documenting vertebral morphology, axial ossification patterns, regionalization of the postcranial skeleton, and the relationship of thoracic ribs to sternal subunits in a large data set of fetal and adult Trichechus and Dugong specimens. These observations forced rejection of all three hypotheses. We propose alternatively that a global slowing of the rate of somitogenesis reduced somite count and disrupted alignment of Hox-generated anatomical markers relative to somite (and vertebral) boundaries throughout the Trichechus column. This hypothesis is consistent with observations of the full range of traditional cervical morphologies in the six cervical vertebrae, conserved postcranial proportions, and column-wide reduction in count relative to its sister taxon, Dugong. It also suggests that the origin of the mammalian cervical constraint lies in patterning, not in count, and that Trichechus and the tree sloths have broken the constraint using different developmental mechanisms., (© 2014 Wiley Periodicals, Inc.)

The therapeutic applications of many anticancer or antimicrobial metal complexes often suffer from low solubility and low stability in physiological conditions or from drug resistance. To circumvent these problems, nanoparticle systems that allow controlled release and specific accumulation in the targeted disease tissue are of advantage for efficient treatment with minimal toxicity. The focus of this Research News is metal-based nanomaterials comprising anticancer gold(III)/platinum(II) complexes or antimicrobial silver, highlighting the controlled-release properties of self-assembled metal systems., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A functional voltage-gated K(+) (Kv) channel comprises four pore-forming α-subunits, and only members of the same Kv channel subfamily may co-assemble to form heterotetramers. The ether-à-go-go family of Kv channels (KCNH) encompasses three distinct subfamilies: Eag (Kv10), Erg (Kv11), and Elk (Kv12). Members of different ether-à-go-go subfamilies, such as Eag and Erg, fail to form heterotetramers. Although a short stretch of amino acid sequences in the distal C-terminal section has been implicated in subfamily-specific subunit assembly, it remains unclear whether this region serves as the sole and/or principal subfamily recognition domain for Eag and Erg. Here we aim to ascertain the structural basis underlying the subfamily specificity of ether-à-go-go channels by generating various chimeric constructs between rat Eag1 and human Erg subunits. Biochemical and electrophysiological characterizations of the subunit interaction properties of a series of different chimeric and truncation constructs over the C terminus suggested that the putative C-terminal recognition domain is dispensable for subfamily-specific assembly. Further chimeric analyses over the N terminus revealed that the N-terminal region may also harbor a subfamily recognition domain. Importantly, exchanging either the N-terminal or the C-terminal domain alone led to a virtual loss of the intersubfamily assembly boundary. By contrast, simultaneously swapping both recognition domains resulted in a reversal of subfamily specificity. Our observations are consistent with the notion that both the N-terminal and the C-terminal recognition domains are required to sustain the subfamily-specific assembly of rat Eag1 and human Erg., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Plants respond differently to mechanical wounding and herbivore attack, using distinct pathways for defense. The versatile sweet potato sporamin possesses multiple biological functions in response to stress. However, the regulation of sporamin gene expression that is activated upon mechanical damage or herbivore attack has not been well studied., Results: Biochemical analysis revealed that different patterns of Reactive oxygen species (ROS) and antioxidant mechanism exist between mechanical wounding (MW) and herbivore attack (HA) in the sweet potato leaf. Using LC-ESI-MS (Liquid chromatography electrospray ionization mass spectrometry analysis), only the endogenous JA (jasmonic acid) level was found to increase dramatically after MW in a time-dependent manner, whereas both endogenous JA and SA (salicylic acid) increase in parallel after HA. Through yeast one-hybrid screening, two transcription factors IbNAC1 (no apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), and cup-shaped cotyledon (CUC)) and IbWRKY1 were isolated, which interact with the sporamin promoter fragment of SWRE (sporamin wounding-responsive element) regulatory sequences. Exogenous application of MeJA (methyl jasmonate), SA and DIECA (diethyldithiocarbamic acid, JAs biosynthesis inhibitor) on sweet potato leaves was employed, and the results revealed that IbNAC1 mediated the expression of sporamin through a JA-dependent signaling pathway upon MW, whereas both IbNAC1 and IbWRKY1 coordinately regulated sporamin expression through JA- and SA-dependent pathways upon HA. Transcriptome analysis identified MYC2/4 and JAZ2/TIFY10A (jasmonate ZIM/tify-domain), the repressor and activator of JA and SA signaling among others, as the genes that play an intermediate role in the JA and SA pathways, and these results were further validated by qRT-PCR (quantitative real-time polymerase chain reaction)., Conclusion: This work has improved our understanding of the differential regulatory mechanism of sporamin expression. Our study illustrates that sweet potato sporamin expression is differentially induced upon abiotic MW and biotic HA that involves IbNAC1 and IbWRKY1 and is dependent on the JA and SA signaling pathways. Thus, we established a model to address the plant-wounding response upon physical and biotic damage.

Angiosperms developed floral nectaries that reward pollinating insects. Although nectar function and composition have been characterized, the mechanism of nectar secretion has remained unclear. Here we identify SWEET9 as a nectary-specific sugar transporter in three eudicot species: Arabidopsis thaliana, Brassica rapa (extrastaminal nectaries) and Nicotiana attenuata (gynoecial nectaries). We show that SWEET9 is essential for nectar production and can function as an efflux transporter. We also show that sucrose phosphate synthase genes, encoding key enzymes for sucrose biosynthesis, are highly expressed in nectaries and that their expression is also essential for nectar secretion. Together these data are consistent with a model in which sucrose is synthesized in the nectary parenchyma and subsequently secreted into the extracellular space via SWEET9, where sucrose is hydrolysed by an apoplasmic invertase to produce a mixture of sucrose, glucose and fructose. The recruitment of SWEET9 for sucrose export may have been a key innovation, and could have coincided with the evolution of core eudicots and contributed to the evolution of nectar secretion to reward pollinators.

A silver complex of N,N'-disubstituted cyclic thiourea inhibits inflammatory cytokine-stimulated NF-κB activity via IκB kinase inactivation.

Objective: To present the application of three-dimensional (3D) ultrasonography in the early prenatal diagnosis of fetal arthrogryposis., Case Report: A 26-year-old multipara had a fetus with anomalies of the limbs as shown by conventional ultrasonography at 18 weeks of gestation. A follow-up 3D ultrasonogram at the same gestational age was consistent with the diagnosis of arthrogryposis. Based on an abnormal chromosome 18p on the fetal karyotype, termination of the pregnancy was performed at 22 weeks' gestation. The outward appearance of the fetus coincided with the prenatal sonographic findings of arthrogryposis., Conclusion: As an advanced and sophisticated technology, 3D ultrasonography can serve as a useful technique for the early diagnosis of fetal anomalies, including arthrogryposis. The earlier the diagnosis is established, the earlier the appropriate management can be initiated, including counseling, additional work-up and timely termination of pregnancy, if indicated.

This study investigated the correlation between results of the pelvic organ prolapse quantification (POPQ) system at 3 days and at 2 months postpartum with obstetric parameters and lower urinary tract symptoms (LUTS) in 125 primiparae with vaginal delivery. The clinical characteristics, prevalence of pregnancy-related LUTS, and POPQ scores were evaluated. Regarding the relationship of obstetric parameters with POPQ scoring, the gh was found positively correlated with the body mass index and vaginal laceration at 2 months postpartum. The POPQ evaluation did not find the LUTS to be significantly related to the prolapse score. The mean scores of points C and D were significantly increased, and gh, pb, and tvl were significantly decreased between the initial and 2-month follow-up scores. Our results revealed that a decrease in vaginal size is the principal change during the first 2 months postpartum and that with the exception of gh, neither the obstetric parameters nor the LUTS were associated with the POPQ scoring system.