Powerful Q-switched Raman laser at 589 nm with a repetition rate between 200 and 500 kHz.

We demonstrate a highly powerful acousto-optically Q-switched Nd:YVO4 yellow laser at 589 nm by using a Np-cut KGW crystal and a phase-matching lithium triborate crystal to performance the intracavity stimulated Raman scattering and second-harmonic generation, respectively. We experimentally verify that the design of the separate cavity is superior to the conventional design of the shared cavity. By using the separate cavity, the optical-to-optical efficiency can be generally higher than 32% for the repetition rate within 200-500 kHz. The maximum output power at 589 nm can be up to 15.1 W at an incident pump power of 40 W and a repetition rate of 400 kHz.

High-power diode-pumped Nd:GdVO4/KGW Raman laser at 578 nm.

A diode-pumped neodymium-doped gadolinium vanadate (Nd:GdVO4) laser is developed as a compact efficient yellow light at 578 nm by means of intracavity stimulated Raman scattering (SRS) in a potassium gadolinium tungstate (KGW) crystal and the second-harmonic generation in a lithium triborate crystal. The SRS process with a shift of 768cm-1 is achieved by setting the polarization of the fundamental wave along the Ng axis of the KGW crystal. The self-Raman effect arising from the Nd:GdVO4 crystal is systematically explored by employing two kinds of coating specification for the output coupler. With a specific coating on the output coupler to suppress the self-Raman effect, the maximum output power at 578 nm can reach 3.1 W at a pump power of 32 W. Moreover, two different lengths for the Nd:GdVO4 crystal are individually used to verify the influence of the self-Raman effect on the lasing efficiency.

Efficient solid-state Raman yellow laser at 579.5 nm.

A highly efficient diode-pumped Nd:YVO4/KGW Raman yellow laser is developed to produce a 6.8 W yellow light at 579.5 nm accompanied by a 3.2 W Stokes wave at 1159 nm under an incident pump power of 30 W. The intracavity stimulated Raman scattering with the shift of 768cm-1 is generated by setting the polarization of the fundamental wave along the Ng direction of an Np-cut KGW crystal. The Nd:YVO4 gain medium is coated as a cavity mirror to reduce the cavity losses for the fundamental wave. More importantly, the KGW crystal is specially coated to prevent the Stokes wave from propagating through the gain medium to minimize the cavity losses for the Stokes wave.

Exploiting a monolithic passively Q-switched Nd:YAG laser to mimic a single neuron cell under periodic stimulation.

A monolithic passively Q-switched Nd:YAG laser under periodic pulse pumping is originally exploited to emulate the response of a single neuron cell stimulated by periodic pulse inputs. Experimental results reveal that the output characteristics of the monolithic passively Q-switched laser can analogously manifest not only the firing patterns but also the frequency-locked plateaus of the single neuron cell. Moreover, the sine circle map is innovatively used to generate the output pulse sequences that can exactly correspond to experimental firing patterns. The present exploration indicates that a monolithic passively Q-switched solid-state laser is highly feasible to be developed as a compact artificial neuron cell.

Combined Atomic Force Microscope and Volumetric Light Sheet System for Correlative Force and Fluorescence Mechanobiology Studies.

The central goals of mechanobiology are to understand how cells generate force and how they respond to environmental mechanical stimuli. A full picture of these processes requires high-resolution, volumetric imaging with time-correlated force measurements. Here we present an instrument that combines an open-top, single-objective light sheet fluorescence microscope with an atomic force microscope (AFM), providing simultaneous volumetric imaging with high spatiotemporal resolution and high dynamic range force capability (10 pN - 100 nN). With this system we have captured lysosome trafficking, vimentin nuclear caging, and actin dynamics on the order of one second per single-cell volume. To showcase the unique advantages of combining Line Bessel light sheet imaging with AFM, we measured the forces exerted by a macrophage during FcɣR-mediated phagocytosis while performing both sequential two-color, fixed plane and volumetric imaging of F-actin. This unique instrument allows for a myriad of novel studies investigating the coupling of cellular dynamics and mechanical forces.

Compact efficient high-power triple-color Nd:YVO4 yellow-lime-green self-Raman lasers.

A novel, to the best of our knowledge, approach is developed to realize a high-power compact efficient yellow-lime-green triple-color ${\rm Nd}:{{\rm YVO}_4}$Nd:YVO4 self-Raman laser. The 588 nm yellow laser, the 559 nm lime laser, and the 532 nm green laser are converted from the 1064 nm fundamental wave and the 1176 nm Stokes Raman field. The simultaneous three-color operation is accomplished with three stages to step-by-step generate the 588 nm, 559 nm, and 532 nm lasers by using three different lithium triborate (LBO) crystals. By tuning the temperature of each individual LBO crystal, the 588 nm, 559 nm, and 532 nm output powers can be nearly the same and concurrently up to 2.4 W at the incident pump power of 30 W, corresponding to a conversion efficiency of 24% for the total output power.

Pre-processing visualization of hyperspectral fluorescent data with Spectrally Encoded Enhanced Representations.

Hyperspectral fluorescence imaging is gaining popularity for it enables multiplexing of spatio-temporal dynamics across scales for molecules, cells and tissues with multiple fluorescent labels. This is made possible by adding the dimension of wavelength to the dataset. The resulting datasets are high in information density and often require lengthy analyses to separate the overlapping fluorescent spectra. Understanding and visualizing these large multi-dimensional datasets during acquisition and pre-processing can be challenging. Here we present Spectrally Encoded Enhanced Representations (SEER), an approach for improved and computationally efficient simultaneous color visualization of multiple spectral components of hyperspectral fluorescence images. Exploiting the mathematical properties of the phasor method, we transform the wavelength space into information-rich color maps for RGB display visualization. We present multiple biological fluorescent samples and highlight SEER's enhancement of specific and subtle spectral differences, providing a fast, intuitive and mathematical way to interpret hyperspectral images during collection, pre-processing and analysis.

Recent advances in hidradenitis suppurativa in pediatrics.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can cause significant physical, mental, and socioeconomic burden. There remains a paucity of literature on HS in the pediatric population. This systematic review highlights recent advances in pediatric HS in epidemiology, presentation, comorbidities, and management. PubMed, Embase, Google Scholar, and Clinicaltrials.gov databases were used to identify trials and articles published on HS in pediatric patients between January 2015 and October 2019. A total of 39 articles were included. Current evidence suggests that pediatric onset HS may be associated with genetic factors along with endocrine and metabolic abnormalities. Delayed diagnosis in children with HS contributes to poor outcomes. Overall, children and adults with HS share similar lesion types and involved areas. Pediatric HS is associated with a number of comorbid conditions including acne, obesity, inflammatory joint disease, Down syndrome, inflammatory bowel disease, and diabetes. There are currently no pediatric treatment guidelines. Adalimumab is approved for the treatment of moderate-to-severe HS in children 12 and older. Other targeted immunomodulators and hormonal modulators are under investigation. Although the number of studies concerning HS are increasing, further investigation is warranted to better characterize HS, facilitate early diagnosis, and determine the best management for children.

Tumour cell-derived WNT5B modulates in vitro lymphangiogenesis via induction of partial endothelial-mesenchymal transition of lymphatic endothelial cells.

Metastasis of the cervical lymph nodes frequently leads to poor survival of patients with oral squamous cell carcinoma (OSCC). The underlying mechanisms of lymph node metastasis are unclear. Wingless-type MMTV integration site family, member 5B (WNT5B), one component of the WNT signal pathway, was markedly up-regulated in OSCC sublines with high potential of lymphatic metastasis compared to that in OSCC cells with low nodal metastasis. Increased WNT5B mRNA was demonstrated in human OSCC tissues in comparison with adjacent non-tumorous tissues. Interestingly, the high level of WNT5B protein in serum was associated with lymph node metastasis in OSCC patients. Knockdown of WNT5B expression in OSCC sublines did not affect tumour growth but impaired lymph node metastasis and tumour lymphangiogenesis of orthotopic transplantation. Conditioned medium from WNT5B knockdown cells reduced the tube formation of lymphatic endothelial cells (LECs). In contrast, recombinant WNT5B enhanced the tube formation, permeability and migration of LECs. In LECs stained with phalloidin, the morphology of those treated with recombinant WNT5B changed from flat to spindle-like. Recombinant WNT5B also increased α-smooth muscle actin and inhibited the expression of vascular endothelial-cadherin but retained characteristics of endothelial cells. The results suggest that WNT5B functions in the partial endothelial-mesenchymal transition (EndoMT). Furthermore, WNT5B-induced tube formation was impaired in the LECs following the knockdown of EndoMT-related transcription factor, SNAIL or SLUG. The WNT5B-induced expression of Snail or Slug was abolished by IWR-1-endo and Rac1 inhibitors, which are involved in the WNT/ß-catenin and planar cell polarity pathways, respectively. Collectively, the data suggest that WNT5B induces tube formation by regulating the expression of Snail and Slug proteins through activation of canonical and non-canonical WNT signalling pathways.

Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome.

Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology.

Basic biology and therapeutic implications of lncRNA.

Long non-coding RNAs (lncRNA), a class of non-coding RNA molecules recently identified largely due to the efforts of FANTOM, and later GENCODE and ENCODE consortia, have been a subject of intense investigation in the past decade. Extensive efforts to get deeper understanding of lncRNA biology have yielded evidence of their diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation and epigenetic regulation. Here we will briefly review the recent studies in the field of lncRNA biology focusing mostly on mammalian species and discuss their therapeutic implications.

Genetic polymorphisms in the prostaglandin pathway genes and risk of head and neck cancer.

OBJECTIVE: Previous studies examining the association between genetic variations in prostaglandin pathway and risk of head and neck cancer (HNC) have only included polymorphisms in the PTGS2 (COX2) gene. This study investigated the association between genetic polymorphisms of six prostaglandin pathway genes (PGDS, PTGDS, PTGES, PTGIS, PTGS1 and PTGS2), and risk of HNC. METHODS: Interviews regarding the consumption of alcohol, betel quid, and cigarette were conducted with 222 HNC cases and 214 controls. Genotyping was performed for 48 tag and functional single-nucleotide polymorphisms (SNPs). RESULTS: Two tag SNPs of PTGIS showed a significant association with HNC risk [rs522962: log-additive odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.01-1.99 and dominant OR = 1.58, 95% CI: 1.02-2.47; rs6125671: log-additive OR = 1.49, 95% CI: 1.08-2.05 and dominant OR = 1.96, 95% CI: 1.16-3.32]. In addition, a region in PTGIS tagged by rs927068 and rs6019902 was significantly associated with risk of HNC (global P = 0.007). Finally, several SNPs interacted with betel quid and cigarette to influence the risk of HNC. CONCLUSIONS: Genetic variations in prostaglandin pathway genes are associated with risk of HNC and may modify the relationship between use of betel quid or cigarette and development of HNC.

Vitamin D receptor variability and physical activity are jointly associated with low handgrip strength and osteoporosis in community-dwelling elderly people in Taiwan: the Taichung Community Health Study for Elders (TCHS-E).

UNLABELLED: We studied 472 elders to assess joint association of vitamin D receptor (VDR) variability and physical activity on low handgrip strength (LHS) and osteoporosis (OST). Our findings showed that higher risks of OST were associated with physically inactive elders with some specific VDR variations, highlighting the importance of promotion program for physical activity. INTRODUCTION: The aim of this study was to determine the joint association between VDR variability and physical activity on LHS and OST in community-dwelling elders. METHODS: Bone mineral density of the lumbar spine (LS), the femoral neck (FN), and the total hip were measured by dual-energy X-ray absorptiometry. Four single-nucleotide polymorphisms (SNPs) (rs7975232, rs1544410, rs2239185, and rs3782905) of the VDR gene were examined in 472 participants. RESULTS: Physical inactivity and each of the four SNPs were jointly associated with a significantly greater risk of LHS in people than that associated with each of the VDR SNPs or low physical activity alone. Physically inactive men with the AG or AA genotype of rs2239185 had a significantly greater risk of overall, LS, and FN OST than those of physically active men with the GG genotype [odds ratio (OR) 3.57, 95 % confidence interval (CI) 1.10-11.65; OR 4.74, 95 % CI 1.43-15.70; and OR 5.06, 95 % CI 1.08-23.71, respectively]. Similarly, physically inactive women with the CG or CC genotype of rs3782905 and the AG or AA genotype of rs1544410 had a significantly greater risk of FN OST than physically active women with the GG genotype (OR 5.33, 95 % CI 1.23-23.06 and OR 5.36, 95 % CI 1.11-25.94, respectively). CONCLUSIONS: VDR polymorphisms and physical activity are jointly associated with LHS and OST in elders. Health care programs should promote physical activity among elders as a cost-effective way to prevent LHS and OST, especially in those who may be genetically predisposed.

Prognostic factors associated with mortality before and during anti-tuberculosis treatment.

OBJECTIVE: To identify factors associated with death before the start of anti-tuberculosis treatment, and early and late during treatment, among adult Taiwanese with culture-positive pulmonary tuberculosis (PTB). METHOD: All adult culture-positive PTB patients in Taipei, Taiwan, were included in a retrospective cohort study in 2005-2010. RESULTS: Of 4438 patients (mean age 64.6 years, 70.6% male), 76.8% were successfully treated, 5.4% died before start of treatment, 9.0% died within 8 weeks of treatment initiation and 8.8% died >8 weeks after treatment initiation. After controlling for potential confounders, age ≥ 65 years and male sex were associated with higher risks of death at all time periods investigated. High school education or higher reduced the risk of death before the start of and during treatment, while unemployment increased the risk of mortality during treatment. Cavity on chest X-ray and positivity for acid-fast bacilli were associated with lower risk of mortality before the start of treatment. CONCLUSION: To lower mortality among adult culture-positive PTB patients, it is imperative for clinicians to maintain high awareness of TB and provide more intensive care early, especially for men, the elderly and people with lower socio-economic status (e.g., the unemployed and less educated).

Glycated matrix up-regulates inflammatory signaling similarly to Porphyromonas gingivalis lipopolysaccharide.

BACKGROUND AND OBJECTIVE: Hyperglycemia and advanced glycation end-products (AGEs) have been hypothesized as the etiologic factors of diabetic periodontitis. The aim of this study was to clarify in greater detail the patterns of AGE-mediated periodontal inflammation under various physiological conditions. MATERIAL AND METHODS: The deposition of AGEs and expression of the receptor for AGEs (RAGE) were identified by immunohistochemistry in Sprague-Dawley rats with experimentally induced periodontitis or diabetes. Human periodontal ligament cells (PDLCs) and mesenchymal stem cells (MSCs) were cultured under simulated conditions of hyperglycemia, Porphyromonas gingivalis lipopolysaccharide (LPS) stimulation and matrix glycation. Cell viability and expression of toll-like receptors (TLRs), Rage, an inflammatory signaling initiator (nuclear factor kappa light chain enhancer of activator ß cells), an oxidative stressor (heme oxygenase-1) and collagen synthesis (type I and type IV) genes were evaluated. RESULTS: The deposition of AGEs and the expression of Rage were evident in the inflamed periodontal tissues in all rats and appeared to be enhanced in rats with diabetes. Matrix glycation augmented cytotoxicity, up-regulated RAGE and TLRs in both PDLCs and MSCs, and significantly activated downstream inflammatory signaling in MSCs. Oxidative stress was significantly increased under matrix glycation in both PDLCs and MSCs and was significantly increased at a high-glucose concentration in MSCs. A consistent decrease in expression of type I and type IV collagens was observed in MSCs, but a delayed reduction was noted in PDLCs. CONCLUSIONS: Matrix glycation modulated cell behavior to induce inflammation equivalent to that produced by incubation with P. gingivalis LPS. Periodontal inflammation also led to matrix glycation, thus demonstrating a definite interaction between diabetes and periodontitis.