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Abstract Background Smad4 is a critical effector of TGF-β signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. Results In the hippocampus, Smad4 is SUMOylated by the E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial learning and memory in rats by downregulating TPM2, a gene associated with skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial learning and memory, while TPM2 mRNA and protein expression increased after spatial training. Among the TPM2 mutations associated with skeletal myopathies, the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial learning and memory in rats. Conclusions We have identified a novel role of Smad4 SUMOylation and TPM2 in learning and memory formation. These results suggest that patients with skeletal myopathies who carry the TPM2E122K mutation may also have deficits in learning and memory functions.

Purpose: To report the first case of Neodymium Yttrium Aluminum Garnet (Nd:YAG) laser use to recanalize a CyPass occluded with a clot in the early postoperative follow-up. Observations: A 66 year-old woman with primary open angle glaucoma and cataract received combined cataract surgery plus CyPass in the right eye. Surgery was uneventful, however, there was a small amount of hyphema related to bleeding around the site of Cypass insertion. Intraocular pressure (IOP) was between 6 and 7 mmHg in the first week on no glaucoma medications. At the second postoperative week, IOP jumped to 30 mmHg and a clot was observed obstructing the CyPass lumen. We disrupted the clot with a single shot from a Nd:YAG laser. Twenty minutes after the laser, the IOP was 8 mmHg. CyPass was recanalized without complications. IOP was 11 mmHg at 1 month postoperatively with timolol 0.5% twice a day. Conclusions and importance: It is important to perform gonioscopy to evaluate for CyPass obstruction in cases of IOP spike. Nd:YAG laser may be a useful approach to recanalize the CyPass in the early postoperative follow-up. Keywords: Glaucoma, Lasers solid-state, Cataract extraction

Purpose: To report two cases of neurotrophic keratitis (NK) after micropulse transscleral cyclophotocoagulation (MP-TCP). Observations: Two patients with predisposing factors for decreased corneal sensation developed NK 1 month after MP-TCP. Both patients did not heal with initial treatment with topical antibiotic and preservative free artificial tears. One patient required use of a bandage contact lens and the other patient required tarsorrhaphy. Both eyes experienced recurrence of NK. Conclusions and importance: NK can be triggered after MP-TCP in patients with underlying predisposing factors for decreased corneal sensation. This uncommon but vision-threatening complication should be discussed preoperatively with high-risk patients as a possible adverse event after MP-TCP and followed closely postoperatively. Keywords: Glaucoma, Lasers solid-state, Micropulse transscleral cyclophotocoagulation, Neurotrophic keratitis

Despite effective prevention programs targeting cardiovascular risk factors, coronary artery disease (CAD) remains the leading cause of death. Novel biomarkers are needed for improved risk stratification and primary prevention. To assess for independent associations between plasma metabolites and specific CAD plaque phenotypes we performed liquid chromatography mass-spectrometry on plasma from 1002 patients in the BioHEART-CT study. Four metabolites were examined as candidate biomarkers. Dimethylguanidino valerate (DMGV) was associated with presence and amount of CAD (OR) 1.41 (95% Confidence Interval [CI] 1.12–1.79, p = 0.004), calcified plaque, and obstructive CAD (p < 0.05 for both). The association with amount of plaque remained after adjustment for traditional risk factors, ß-coefficient 0.17 (95% CI 0.02–0.32, p = 0.026). Glutamate was associated with the presence of non-calcified plaque, OR 1.48 (95% CI 1.09–2.01, p = 0.011). Phenylalanine was associated with amount of CAD, ß-coefficient 0.33 (95% CI 0.04–0.62, p = 0.025), amount of calcified plaque, (ß-coefficient 0.88, 95% CI 0.23–1.53, p = 0.008), and obstructive CAD, OR 1.84 (95% CI 1.01–3.31, p = 0.046). Trimethylamine N-oxide was negatively associated non-calcified plaque OR 0.72 (95% CI 0.53–0.97, p = 0.029) and the association remained when adjusted for traditional risk factors. In targeted metabolomic analyses including 53 known metabolites and controlling for a 5% false discovery rate, DMGV was strongly associated with the presence of calcified plaque, OR 1.59 (95% CI 1.26–2.01, p = 0.006), obstructive CAD, OR 2.33 (95% CI 1.59–3.43, p = 0.0009), and amount of CAD, ß-coefficient 0.3 (95% CI 0.14–0.45, p = 0.014). In multivariate analyses the lipid and nucleotide metabolic pathways were both associated with the presence of CAD, after adjustment for traditional risk factors. We report novel associations between CAD plaque phenotypes and four metabolites previously associated with CAD. We also identified two metabolic pathways strongly associated with CAD, independent of traditional risk factors. These pathways warrant further investigation at both a biomarker and mechanistic level.

Post-translational modifications of methyl-CpG-binding protein 2 (MeCP2) are important for its function and dysfunction in Rett syndrome. Here, Tai et al. show a functional interaction between MeCP2 SUMOylation and phosphorylation in rodent behavior and synaptic plasticity.

PURPOSE:This prospective study used anterior segment optical coherence tomography (AS-OCT) to determine how phacoemulsification (phaco) changes iris parameters in eyes with glaucoma or glaucoma suspect status. METHODS:Using Visante AS-OCT (Carl Zeiss Meditec AG), the following pre- and post-phaco parameters were measured: IT750 = iris thickness at 750 μm from the scleral spur; IT2000 = iris thickness 2000 μm from the scleral spur; ITCM = the maximum iris thickness at the middle one third of the iris; ICURV = iris curvature; IAREA = iris area; and pupil size = pupil diameter (mm). Only high-quality images with an identifiable scleral spur were included, and only the nasal quadrant was analyzed. A single glaucoma specialist analyzed the parameters according to the Zhongshan Angle Assessment Program (ZAAP, Guangzhou, China). Multivariate analysis was performed using mixed effects regression correcting for age, gender, and ethnicity. RESULTS:89 subjects and 110 eyes were included in this study. The mean age of subjects was 74.83 {+/-} 8.69 years old. Most common diagnoses were POAG and glaucoma suspect (23% and 52%, respectively), and 16% of subjects had an LPI. In multivariate analysis of AS-OCT parameters, decreases in IT750, IT2000, ITCM, ICURV, and pupil size were statistically significant (p

Purpose:To discuss a case of ovarian fibromatosis/massive ovarian oedema, intra-abdominal fibromatosis, sclerosing peritonitis and Meig’s syndrome. To review the reported therapeutic options.

PurposeTo report two cases of neurotrophic keratitis (NK) after micropulse transscleral cyclophotocoagulation (MP-TCP).ObservationsTwo patients with predisposing factors for decreased corneal sensation developed NK 1 month after MP-TCP. Both patients did not heal with initial treatment with topical antibiotic and preservative free artificial tears. One patient required use of a bandage contact lens and the other patient required tarsorrhaphy. Both eyes experienced recurrence of NK.Conclusions and importanceNK can be triggered after MP-TCP in patients with underlying predisposing factors for decreased corneal sensation. This uncommon but vision-threatening complication should be discussed preoperatively with high-risk patients as a possible adverse event after MP-TCP and followed closely postoperatively.

A new design for a double-sided high-pressure diamond anvil cell laser heating set-up is described. The prototype is deployed at beamline 12.2.2 of the Advanced Light Source at Lawrence Berkeley National Lab. Our compact design features shortened mechanical lever arms, which results in more stable imaging optics, and thus more user friendly and more reliable temperature measurements based on pyrometry. A modification of the peak scaling method was implemented for pyrometry, including an iterative method to determine the absolute peak temperature, thus allowing for quasi-real time temperature mapping of the actual hotspot within a laser-heated diamond anvil cell without any assumptions on shape, size, and symmetry of the hotspot and without any assumptions to the relationship between fitted temperature and peak temperature. This is important since we show that the relationship between peak temperature and temperature obtained by fitting the Planck function against the thermal emission spectrum averaged over the entire hotspot is not constant but depends on variable fitting parameters (in particular, the size and position of the fitting window). The accuracy of the method is confirmed through measuring melting points of metal wires at ambient pressure. Having absolute temperature maps in real time allows for more differentiated analyses of laser heating experiments. We present such an example of the pressure variations within a heated hotspot of AgI at a loaded base pressure of 3.8 GPa.

ObjectiveTo assess the current opinion and practice patterns from cornea experts regarding the benefit of corneal cross-linking (CXL) for infectious keratitis (IK).Methods and analysisAn international survey was distributed to corneal specialists via an internet survey. The survey data collected were analysed with descriptive statistics.ResultsA survey was sent to 190 recipients, and 29 (15%) respondents completed the survey with an average of 7 years' experience using CXL. A majority of respondents (66%) used CXL to treat IK due to bacterial, fungal, protozoan or unknown aetiology. Main indications to use CXL as adjuvant therapy were worsening infiltrate diameter or depth despite therapy (74%), followed by antibiotic resistance (68%), corneal thinning (53%), poor compliance with medication (26%) and other reasons (21%). Most respondents felt CXL would be at least moderately helpful as an adjuvant therapy for bacterial (96%) or fungal (75%) keratitis; about half (46%) thought it would be helpful for acanthamoeba keratitis. As sole therapy, fewer respondents believed CXL would be at least moderately helpful to treat bacterial (75%), fungal (58%) and acanthamoeba (43%) keratitis.ConclusionThe survey offered insights into current expert practices and opinions of using CXL as therapy for IK. The results of this survey serve to guide in the design of future clinical studies.

Context: No consensus has yet been formed on project development in lake-water conservancy on aspects such as lake quality, ecological environment, rural economy, social culture, leisure living environment and leisure aspirations due to the current lack of comprehensive discussion. Aims: This study mainly uses the case of Sun Moon Lake in Taiwan to verify the impact of lake-tourism optimisation and water-conservancy projects on the rural economy, water quality, ecology and sustainable development of tourism for local young people in the area around the lake. Methods: We employed open-sampling questionnaires and semistructured interviews to collect data and conducted multivariate analysis. Key results: The study investigated the hypothesis that optimising water-conservancy projects for lake tourism creates a stable leisure and tourism environment in rural areas, enhances visibility, and increases emotional exchanges and the preservation of historic sites. However, problems such as excessive tourism waste and a lack of public facilities negatively affect local young consumers' willingness to engage in tourism activities. Conclusions: Improving problems in the villages, ecology and natural environment surrounding lakes that are being conserved can increase young local individuals' willingness to engage in and share experiences of tourism activities. Implications: If the local government can improve the issues of protected villages, ecology and the natural environment around the lake, it can increase the willingness of local young people to participate in and share their experiences in tourism activities. Lake tourism-optimisation water-conservancy projects are indeed conducive to creating a safe leisure and tourism environment, thereby enhancing human interaction, historical monument protection and local visibility. However, problems such as shortage of basic public facilities and excessive tourism waste will still affect people's perception of the local environment and willingness to consume. This article belongs to the collection Ecological Monitoring and Assessment of Freshwater Ecosystems: New Trends and Future Challenges. [ABSTRACT FROM AUTHOR]

Recent literature suggests that the layer of adipocytes embedded in the skin below the dermis is far from being an inert spacer material. Instead, this layer of dermal white adipose tissue (dWAT) is a regulated lipid layer that comprises a crucial environmental defense. Among all the classes of biological molecules, lipids have the lowest thermal conductance and highest insulation potential. This property can be exploited by mammals to reduce heat loss, suppress brown adipose tissue activation, reduce the activation of thermogenic programs, and increase metabolic efficiency. Furthermore, this layer responds to bacterial challenge to provide a physical barrier and antimicrobial disinfection, and its expansion supports the growth of hair follicles and regenerating skin. In sum, this dWAT layer is a key defensive player with remarkable potential for modifying systemic metabolism, immune function, and physiology. In this review, we discuss the key literature illustrating the properties of this recently recognized adipose depot.

The study provided a qualitative investigation into problematic mobile phone use among the youth athlete population. The study aimed to identify the factors which contributed to problematic use, the effects of problematic use, and suggestions on how to help youth athletes overcome problematic use. Four focus groups sessions were conducted with a total of 21 Singaporean youth athletes (aged 12–18 years old) from four different sports. The data was analysed using reflexive thematic analysis. The findings indicated various factors which contributed to problematic use, namely personal attributes, needs fulfilment, and external influences. Effects of problematic use included areas such as shrinkage of time, performance deficits, and undesirable behaviours. There were various suggestions on how to overcome problematic use, which included strengthening internal resources and tapping into sources of external help. Future research should seek to use the knowledge derived from this study to create interventions to help youth athletes deal with their problematic mobile phone use. [ABSTRACT FROM AUTHOR]

Jia-Yu Liu,1 Chia-Hung Yen,2,3 Ya-Fan Lin,4 Yin-Hsun Feng,5 Yi-Ping Fang1,6,7 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Chemistry, National Dong Hwa University, Hualien, Taiwan; 5Division of Hematology and Oncology, Department of Internal Medicine, ChiMei Medical Center, Tainan, Taiwan; 6Regeneration Medicine and Cell Therapy Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Yi-Ping Fang, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, San Ming District, Kaohsiung, 80708, Taiwan, Tel +886 7 3121101 ext. 2261, Email ypfang@kmu.edu.twBackground: Belinostat, a histone deacetylase inhibitor used for hematological cancer treatments, however, it caused thrombocytopenia, poor solubility, and rapid clearance. To mitigate these issues, human serum albumin (HSA) was utilized as the core material for its high protein binding affinity and self-binding capabilities. The study focused on developing belinostat-loaded HSA nanoparticles to improve solubility, extend circulation time, and reduce adverse effects.Methods: Belinostat-loaded HSA nanoparticles were synthesized using a desolvation method, optimized for size, charge, and entrapment efficiency, and characterized by molecular docking and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity was assessed in vitro against HuT-78 cells, and in vivo pharmacokinetics and toxicology studies were conducted to evaluate therapeutic efficacy and safety.Results: The prepared belinostat–HSA nanoparticles exhibited the size of 150 nm with a charge of ~− 50 mV and a high entrapment efficiency (90%). Molecular docking confirmed that belinostat and HSA had a strong binding affinity (− 9.5 kcal mol− 1), and the entrapment of belinostat within HSA nanoparticles was also confirmed via FTIR. Belinostat–HSA nanoparticles were cytotoxic against HuT-78 with the dose–response relation (1– 100 μM). The highly concentrated (100 μM) belinostat–HSA nanoparticles maintained the viability of the peripheral blood mononuclear cells with 50% survival, which did not survive when exposed to belinostat (100 μM). The belinostat–HSA nanoparticles proved suitable for intravenous administration without causing hemolysis, exhibited prolonged circulation times, and improved in vivo platelet counts significantly (p < 0.05).Conclusion: In conclusion, the belinostat-loaded HSA nanoparticles significantly enhance the solubility and half-life of belinostat, reduce its adverse hematological effects, and maintain sustained drug release. These attributes underscore the potential of belinostat-HSA nanoparticles as a viable intravenous option for the treatment of hematological malignancies. Keywords: belinostat, human serum albumin nanoparticles, peripheral T-cell lymphoma, thrombocytopenia, pharmacokinetics

Abstract A confined, non-relativistic, accelerating electron is shown to emit thermal radiation. Since laboratories face spatial constraints when dealing with rectilinear motion, focusing on a finite total travel distance combines the benefits of simple theoretical analysis with prospects for table-top experimentation. We demonstrate an accelerated moving charge along an asymptotically static worldline with fixed transit distance and non-relativistic maximum speed, emitting self-consistent analytic power, spectra, and energy. The classical radiation is Planck distributed with an associated acceleration temperature. This is the first fully parametrized, spectrum-solved, finite-distance worldline.