Efficient postprocessing technique for fabricating surface nanoscale axial photonics microresonators with subangstrom precision by femtosecond laser

We demonstrated the subangstrom precise correction of surface nanoscale axial photonics (SNAP) micro-resonators by the femtosecond (fs) laser postprocessing technique for the first time. The internal stress can be induced by fs laser inscriptions in the fiber, causing nanoscale effective radius variation (ERV). However, the obtained ultraprecise fabrication usually undergoes multiple tries. Here, we propose a novel postprocessing technique based on the fs laser that significantly reduces the ERV errors and improves the fabrication precision without iterative corrections. The postexposure process is achieved at the original exposure locations using lower pulse energy than that in the initial fabrication process. The results show that the ERV is nearly proportional to the pulse energy of the postexposure process. The slope of the ERV versus the pulse energy is 0.07 Å/nJ. The maximum of the postprocessed ERV can reach 8.0 Å. The repeatability was experimentally verified by accomplishing the correction on three SNAP microresonators with the precision of 0.75 Å. The developed fabrication technique with fs laser enables SNAP microresonators with new breakthrough applications for optomechanics and filters

Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.

Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead to network hyperexcitability. Here, we introduce a human Na+-activated K+ (KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, find motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increases KNa currents in cortical excitatory and inhibitory neurons, there is an increase in the KNa current across subthreshold voltages only in inhibitory neurons, particularly in those with non-fast-spiking properties, resulting in inhibitory-neuron-specific impairments in excitability and action potential (AP) generation. We further observe evidence of synaptic rewiring, including increases in homotypic synaptic connectivity, accompanied by network hyperexcitability and hypersynchronicity. These findings support inhibitory-neuron-specific mechanisms in mediating the epileptogenic effects of KCNT1 channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention

Neurodevelopmental deficits and cell-type-specific transcriptomic perturbations in a mouse model of HNRNPU haploinsufficiency.

Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency. Heterozygous mutants demonstrated global developmental delay, impaired ultrasonic vocalizations, cognitive dysfunction and increased seizure susceptibility, thus modeling aspects of the human disease. Single-cell RNA-sequencing of hippocampal and neocortical cells revealed widespread, yet modest, dysregulation of gene expression across mutant neuronal subtypes. We observed an increased burden of differentially-expressed genes in mutant excitatory neurons of the subiculum-a region of the hippocampus implicated in temporal lobe epilepsy. Evaluation of transcriptomic signature reversal as a therapeutic strategy highlights the potential importance of generating cell-type-specific signatures. Overall, this work provides insight into HNRNPU-mediated disease mechanisms and provides a framework for using single-cell RNA-sequencing to study transcriptional regulators implicated in disease

Second-Harmonic Generation of the Vortex Beams with Integer and Fractional Topological Charges

The single-pass second-harmonic generation (SHG) of a vortex beam under low fundamental wave depletion is systematically studied. Vortex modes at 1064 nm with integer topological charges from ±1 to ±9 and fractional ones at ±0.75 are generated by modulating the fundamental Gaussian beam with different spiral phase plates. The frequency doubling of these fundamental vortex modes is realized via single-pass SHG through the KTP. A detailed theoretical model is set up in the single-pass SHG of the vortex beams. Theoretical analysis indicates that the higher the order of the vortex beams, the lower the SHG efficiency, when the beam waists and fundamental power are given. The experimentally measured SHG output characteristics verify those obtained via theoretical analysis. Conservation of the orbital angular momentum during the SHG process is also verified, regardless of the fractional or integer vortex beams. SH LG0,2l vortex beams with high mode purity are obtained. The beam waists of fundamental/SH in KTP measured using a 4f system demonstrate that the Rayleigh ranges of the fundamental wave and SH wave are the same. The paper comprehensively presents some basic laws in the single-pass SHG of a vortex beam. In addition, it also indicates that SHG is an effective method to improve the mode purity of vortex beam

Effects of elevated CO2 and temperature on yield and fruit quality of strawberry (Fragaria × ananassa Duch.) at two levels of nitrogen application.

We investigated if elevated CO(2) could alleviate the negative effect of high temperature on fruit yield of strawberry (Fragaria × ananassa Duch. cv. Toyonoka) at different levels of nitrogen and also tested the combined effects of CO(2), temperature and nitrogen on fruit quality of plants cultivated in controlled growth chambers. Results show that elevated CO(2) and high temperature caused a further 12% and 35% decrease in fruit yield at low and high nitrogen, respectively. The fewer inflorescences and smaller umbel size during flower induction caused the reduction of fruit yield at elevated CO(2) and high temperature. Interestingly, nitrogen application has no beneficial effect on fruit yield, and this may be because of decreased sucrose export to the shoot apical meristem at floral transition. Moreover, elevated CO(2) increased the levels of dry matter-content, fructose, glucose, total sugar and sweetness index per dry matter, but decreased fruit nitrogen content, total antioxidant capacity and all antioxidant compounds per dry matter in strawberry fruit. The reduction of fruit nitrogen content and antioxidant activity was mainly caused by the dilution effect of accumulated non-structural carbohydrates sourced from the increased net photosynthetic rate at elevated CO(2). Thus, the quality of strawberry fruit would increase because of the increased sweetness and the similar amount of fruit nitrogen content, antioxidant activity per fresh matter at elevated CO(2). Overall, we found that elevated CO(2) improved the production of strawberry (including yield and quality) at low temperature, but decreased it at high temperature. The dramatic fluctuation in strawberry yield between low and high temperature at elevated CO(2) implies that more attention should be paid to the process of flower induction under climate change, especially in fruits that require winter chilling for reproductive growth

Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites

Abstract Background Extramammary Paget disease (EMPD) is a rare malignant dermatosis with poorly defined outcomes. We investigated clinical characteristics of invasive EMPD at different anatomic sites and by subject demographics to determine prognostic factors for overall survival (OS). Methods All patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) program, 1973–2013, of the U.S. National Cancer Institute. Patients with invasive EMPD of skin, vulva/labia, vagina, scrotum/penis, or other sites were included. After excluding patients with unknown radiation status, data of 2001 patients were analyzed. Primary endpoint was EMPD mortality by anatomic sites. Independent variables included patients’ demographic data, concurrent malignancy (ie, non-EMPD related cancers), tumor size, distant metastasis, and surgery and/or radiation or not. Results Multivariate regression analysis showed that mortality was significantly higher in patients with vaginal EMPD than in patients with vulvar/labial EMPD (adjusted hazard ratio [aHR] = 3.26, p < 0.001). Patients with distant metastasis had higher mortality than those without (aHR = 3.36, p < 0.001). Patients who received surgery had significantly lower mortality than those who did not receive surgery (aHR = 0.77, p = 0.030), and those treated with radiation had significantly higher mortality than those who did not receive radiation (aHR = 1.60, p = 0.002). Older age was associated with significantly increased mortality (aHR = 1.09, p < 0.001), and mortality was significantly higher in males than in females (aHR = 1.42, p = 0.008). Conclusions In conclusion, among EMPD patients, mortality is higher in patients with vaginal EMPD than in those with vulvar/labial EMPD and higher in those who are older, those with concurrent malignancy or distant metastasis. Mortality is also higher in males than in females. Surgery is a protective factor and radiation is a risk factor for OS. Greater understanding of EMPD clinical characteristics, and considering EMPD in differential diagnosis of chronic genital and perianal dermatoses may provide support for early EMPD diagnosis and definitive surgical treatment

Highly Selective Red-Emitting Fluorescent Probe for Imaging Cancer Cells in Situ by Targeting Pim‑1 Kinase

Based on the fact that enzyme-targeting probes are highly sensitive and selective, a novel red-emitting probe (<b>NB-BF</b>) for Pim-1 kinase including three parts, fluorophore (<b>NB</b>), linker, and inhibitor (<b>BF</b>), has been designed for cancer optical imaging. In its free state, <b>NB-BF</b> is folded and the fluorescence quenched by PET between fluorophore and inhibitor both in PBS buffer and in normal cells. Significantly, it emitted strong red fluorescence in Pim-1 overexpressed cancer cells. The specificity of <b>NB-BF</b> for Pim-1 kinase was directly demonstrated by gene silencing analysis. Furthermore, it is the first time to know where Pim-1 kinase mainly distributes at mitochondria with Pearson’s correlation factor (<i>R</i>_r) of 0.965 and to provide a fluorescent tool to verify the function of the Pim-1 kinase. More importantly, <b>NB-BF</b> was applied in tissue imaging and preferentially labeled tumors in vivo