Pulse pattern manipulation of dichromatic soliton complexes by a twistable tapered-fiber filter.

Soliton complexes highlight the particle-like dynamics of dissipative pulses. However, simple and reliable manipulation of bound solitons remains challenging, particularly for all-polarization-maintaining (PM) configurations that are free from random polarization perturbations. Here, we report controllable pulse patterns of robustly coexisting dichromatic soliton complexes in an all-PM fiber laser based on a twistable tapered-fiber filter. According to the twist angle, dichromatic pulses are switched between different patterns, and components at each wavelength can be independently manipulated, extending encodings from the time to the frequency domain. To the best of our knowledge, it is the first experimental demonstration of dual-wavelength soliton complexes that different pulse patterns coexist at separated wavebands.

Pump-power-controlled L-band wavelength-tunable mode-locked fiber laser utilizing nonlinear polarization evolution in all-polarization-maintaining fibers.

We present for the first time, to the best of our knowledge, the pump-power-controlled, all-polarization-maintaining (all-PM), all-fiber configured, wavelength-tunable mode-locked fiber laser in the L-band (1565 to 1625 nm). A tuning range over 20 nm (1568.2  to 1588.9 nm) is attained simply by varying the pump power between 45 and 115 mW. Our work represents the first demonstration of wavelength tuning in all-PM configured nonlinear polarization evolution (NPE) lasers. The non-mechanical and electrically controllable tuning method offers ease of use and cost efficiency within an advanced all-PM, all-fiber design, indicating promising adaptability to diverse wavelength bands.

Inhibition of BMP signaling pathway induced senescence and calcification in anaplastic meningioma.

PURPOSE: Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor prognosis. The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target. METHODS: The effects of bone morphogenetic protein (BMP) signal inhibitor (K02288) and upstream regulator Gremlin2 (GREM2) on meningioma's growth and senescence were examined. In brief, we examined as follows: 1) Proliferation assay by inhibiting BMP signaling. 2) Comprehensive analysis of forced expression GREM2.3) Correlation between GREM2 mRNA expression and proliferation marker in 87 of our clinical samples. 4) Enrichment analysis between GREM2 high/low expressed groups using RNA-seq data (42 cases) from the public database GREIN. 5) Changes in metabolites and senescence markers associated with BMP signal suppression. RESULTS: Inhibitors of BMP receptor (BMPR1A) and forced expression of GREM2 shifted tryptophan metabolism from kynurenine/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD + /NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. Reanalyzed RNA-seq data of clinical samples obtained from GREIN showed that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results. CONCLUSIONS: The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.

Fast wavelength-swept polarization maintaining all-fiber mode-locked laser based on a piezo-stretched fiber Lyot filter.

We demonstrate for the first time a strain-controlled all polarization-maintaining (PM) fiber Lyot filter based on a piezoelectric lead zirconate titanate (PZT) fiber stretcher. This filter is implemented in an all-PM mode-locked fiber laser to serve as a novel wavelength-tuning mechanism for fast wavelength sweeping. The center wavelength of the output laser can be tuned across a range from 1540 nm to 1567 nm linearly. And the strain sensitivity achieved in the proposed all-PM fiber Lyot filter is 0.052nm/µÎµ, which is 43 times higher than that achievable by other strain-controlled filters such as a fiber Bragg grating filter (0.0012nm/µÎµ). Wavelength-swept rates up to 500 Hz and wavelength tuning speeds up to 13,000 nm/s are demonstrated, which is hundreds of times faster than what is attainable with conventional sub-picosecond mode-locked lasers based on mechanical tuning methods. This highly repeatable and swift wavelength-tunable all-PM fiber mode-locked laser is a promising source for applications requiring fast wavelength tunability, such as coherent Raman microscopy.

Ranging disambiguation of LiDAR using chirped amplitude-modulated phase-shift method.

Ranging ambiguity is the major challenge in most LiDAR techniques with amplitude modulation, which limits the performance of range detection due to the tradeoff between the ranging precision and the unambiguous range. Here we propose a novel disambiguation method using a laser with chirped amplitude modulation (sweeping modulation frequency), which can in theory infinitely expand the unambiguous range and completely solve the ranging ambiguation problem. The usage of the earlier proposed Chirped Amplitude-Modulated Phase-Shift (CAMPS) technique enables us to detect the phase-shift of chirped signals with high precision. Incorporating this technique with the proposed disambiguation method, the absolute distance well beyond the conventional unambiguous range can easily be found with merely <1% frequency sweep range. When certain conditions are met, the Non-Mechanical Spectrally Scanned LiDAR (NMSL) system employing the CAMPS method and the Dispersion-Tuned Swept Laser (DTSL) can also realize disambiguation in non-mechanical line-scanning measurement.

All-polarization-maintaining, efficiently wavelength-tunable, Er-doped mode-locked fiber laser with a compact reflective Lyot filter.

Wavelength tunable mode-locked fiber lasers have highly potential applications in precision spectroscopy, nonlinear microscopy and photonic sensing. Here, we present a compact and thermal-sensitive reflective Lyot filter and utilize it for all-polarization-maintaining efficiently wavelength-tunable Er-doped carbon-nanotube-mode-locked laser for the first time, to the best of our knowledge. The output wavelength of the laser can be tuned from 1544.46 nm to 1572.71 nm, with a wide tuning range of 28.25 nm, and a remarkable tuning efficiency of 0.589 nm/°C, when the angle-spliced fiber is only 8.2 cm and the free spectral range of the filter is 31.32 nm. Dual-wavelength mode-locking is also achieved at boundary temperatures when increasing the pump power. Due to its compact size and reflection configuration, the proposed reflective Lyot filter is promising for realizing highly efficient wavelength tuning and multiwavelength generation in all-polarization-maintaining fiber lasers where reflective filters are needed.

L-band mode-locked fiber laser using all polarization-maintaining nonlinear polarization rotation.

For the first time, to the best of our knowledge, in the soliton regime, we demonstrate an L-band fiber laser mode-locked by all polarization-maintaining (all-PM) nonlinear polarization rotation (NPR). A numerical study suggests that lengthening the NPR section boosts modulation depth and lowers saturation power of the artificial saturable absorber (SA). With the longest NPR section to date (21 m), the laser emits 1.25-ps soliton pulses at 1584.2 nm and a 3.9-MHz repetition rate. Our laser provides a promising L-band seed source, exhibiting improved repeatability and stability compared with non-PM L-band pulse fiber lasers.

Flat visible spectrum by a genetic algorithm optimized photonic crystal fiber in the GHz comb spacing.

Coherent and flat supercontinuum (SC) sources are demanded for applications of metrology, spectroscopy, and bio-imaging. However, the process of SC generation is usually very complicated. We demonstrated a convenient and efficient method based on a genetic algorithm (GA). According to an objective spectrum, this algorithm could reverse-design the geometry of a fiber or waveguide without knowing the specific non-linear processes involved. Using this method, we designed a dispersion-managed photonic crystal fiber (PCF) for SC generation at 1 GHz comb spacing. With an input pulse of ∼150 fs, 450 pJ at 1050 nm, a 3 dB fluctuation spectrum ranging from 510 nm to 850 nm is obtained, which is absolutely fit to the calibration of an astronomical spectrograph.

Control of Dissolution and Supersaturation/Precipitation of Poorly Water-Soluble Drugs from Cocrystals Based on Solubility Products: A Case Study with a Ketoconazole Cocrystal.

This study demonstrates in vitro and in vivo control of cocrystal dissolution with drug supersaturation/precipitation based on the solubility product of a cocrystal. As a cocrystal model, KTZ-4ABA (ketoconazole, KTZ, a poorly water-soluble drug cocrystal, with 4-aminobenzoic acid, 4ABA, a coformer) was used. The presence of 4ABA in the dissolution media dramatically reduced the dissolution rate of KTZ-4ABA and regulated the supersaturation/precipitation of KTZ, supported by the solubility product of KTZ-4ABA. In the in vitro dissolution study, the combined solid form of KTZ-4ABA and a ten-fold amount of 4ABA significantly lowered the degree of KTZ supersaturation without precipitation and further cocrystal dissolution. To confirm cocrystal dissolution control in the gastrointestinal tract with the same composition as the in vitro study, an in vivo oral administration study with rats was conducted. When KTZ was coadministered to rats in the cocrystal form, an excess of 4ABA coadministered with KTZ-4ABA in the solid form reduced the maximum plasma KTZ concentration (Cmax), prolonged the time to reach the Cmax, but did not influence the area under the plasma concentration-time curve. These results demonstrate that both in vitro and in vivo cocrystal dissolution can be regulated by adding an appropriate amount of coformer based on the solubility product, which can be one of the promising strategies for the oral use of cocrystal formulations.

Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

Extraction of a metallic susceptor after accidental ingestion of the heated tobaccostick TEREA™: a case report.

BACKGROUND: Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. CASE PRESENTATION: A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. CONCLUSIONS: Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting.

Novel Strategy Involving High-Dose Chemotherapy with Stem Cell Rescue Followed by Intrathecal Topotecan Maintenance Therapy without Whole-Brain Irradiation for Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive central nervous system tumor that typically affects children under three years old and has poor survival with a high risk for neurologic deficits. The primary purpose of this study was to successfully treat the disease and delay or avoid whole-brain radiotherapy for children with AT/RT. A retrospective analysis was performed for six children diagnosed with AT/RT and treated with multimodal treatment at a single institute between 2014 and 2020. Furthermore, germline SMARCB1 aberrations and MGMT methylation status of the tumors were analyzed. One patient who did not receive a modified IRS-III regimen replaced with ifosphamide, carboplatin, and etoposide (ICE) in induction chemotherapy was excluded from this analysis. Five patients who received ICE therapy were under three years old. After a surgical approach, they received intensive chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) followed by intrathecal topotecan maintenance therapy. Three patients underwent single HDCT/autoPBSCT, and the other two received sequential treatment. Two patients with germline SMARCB1 aberrations and metastases died of progressive AT/RT or therapy-related malignancy, while 3 with localized tumors without germline SMARCB1 aberrations remained alive. One survivor received local radiotherapy only, while the other two did not undergo radiotherapy. All three surviving patients were able to avoid whole-brain radiotherapy. Our results suggest that AT/RT patients with localized tumors without germline SMARCB1 aberrations can be rescued with multimodal therapy, including induction therapy containing ICE followed by HDCT/autoPBSCT and intrathecal topotecan maintenance therapy without radiotherapy. Further large-scale studies are necessary to confirm this hypothesis.

Marine Plasmalogens: A Gift from the Sea with Benefits for Age-Associated Diseases.

Aging increases oxidative and inflammatory stress caused by a reduction in metabolism and clearance, thus leading to the development of age-associated diseases. The quality of our daily diet and exercise is important for the prevention of these diseases. Marine resources contain various valuable nutrients, and unique glycerophospholipid plasmalogens are found abundantly in some marine invertebrates, including ascidians. One of the major classes, the ethanolamine class (PlsEtn), exists in a high ratio to phospholipids in the brain and blood, while decreased levels have been reported in patients with age-associated diseases, including Alzheimer's disease. Animal studies have shown that the administration of marine PlsEtn prepared from marine invertebrates improved PlsEtn levels in the body and alleviated inflammation. Animal and human studies have reported that marine PlsEtn ameliorates cognitive impairment. In this review, we highlight the biological significance, relationships with age-associated diseases, food functions, and healthcare materials of plasmalogens based on recent knowledge and discuss the contribution of marine plasmalogens to health maintenance in aging.

[Stage â £ Gastric Cancer with Long Term Survival by Conversion Surgery-A Case Report].

A 78-year-old man presenting with a chief complaint of discomfort was found to have advanced gastric cancer invading pancreatic body, and with the metastasis of paraaortic lymph node(No. 16). After 3 courses of the S-1 plus oxaliplatin regimen, CT scan showed the disappearance of invasion to pancreatic body, and the No. 16 lymph node. Then total gastrectomy(D2+No. 19+No. 16a1+No. 16a2), Roux-en-Y reconstruction and cholecystectomy were undergoing. Histological assessment for treatment response showed Grade 1a, and we finally diagnosed gastric cancer: MU, Post, type 2, 30×20 mm, tub1>por1, ypT3, ypN1, ycM0, ypStage ⅡB. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 19. S-1 as adjuvant chemotherapy was performed for 12 months, and no recurrence was recognized for 5 years and 9 months after operation.

[A Case Report of Organ Preservation by Total Neoadjuvant Therapy and Local Excision for Lower Rectal Cancer].

In our department, total neoadjuvant therapy(TNT), which is a combination of preoperative chemotherapy and preoperative chemoradiotherapy(nCRT), has been introduced for the purpose of local and systemic disease control for lower rectal cancer. For patients in whom a clinical complete response(cCR)was obtained by TNT, we avoid the surgery and preserve organs, and follow-up strictly under the informed consent(watch and wait). In addition, for patients with remarkably reduced primary lesions(near cCR)without lymphadenopathy after TNT, the option of omitting total mesorectal excision (TME)and performing organ preservation by local excision can be introduced. Here, we report a case in which near cCR was obtained by TNT and organ preservation was performed by local excision. A 67-year-old man with lower rectal cancer(AV 5 cm, 15 mm, type 2, cT2N0M0, cStage Ⅰ)was referred to our department with a desire to preserve the anus. TNT with nCRT→CAPOX was performed, and near cCR was obtained. After that, full thickness local excision of the residual disease was performed by transanal minimally invasive surgery(TAMIS). The final pathological diagnosis was Rb, 0.7 mm, por2, ypT1a, ypPM0, ypDM0, ypRM0. No recurrence is recognized for 3 years and 10 months after the operation.

Broadband similariton generation in a mode-locked Yb-doped fiber laser.

We experimentally demonstrated a broadband similariton generated from a mode-locked Yb-doped fiber laser with dispersion compensation. The broadest spectrum was obtained by pushing the net dispersion to its limitation and fully exploiting the gain bandwidth. The spectrum was 115 nm broad in 10 dB bandwidth and 36 nm broad in 3 dB bandwidth. The output was 105 mW optical power at 545 mW pump power. Simulation combined with experiment was performed to investigate and confirm the mode-locking regime of the laser. Experimental observations agreed well with the numerical simulation. We believe our study provides a practical route for designing broadband mode-locked fiber lasers.

Polarization-maintaining all-fiber tunable mode-locked laser based on a thermally controlled Lyot filter.

We propose and demonstrate for the first time, to the best of our knowledge, a thermally controlled all polarization-maintaining (PM) fiber Lyot filter. This filter is implemented in an all-PM mode-locked fiber laser to achieve wavelength tunability. When operating in the single-wavelength tunable mode, the center wavelength can be tuned across a range from 1546 nm to 1571 nm. Furthermore, the laser can also operate in a dual-wavelength mode with center wavelengths at 1545 nm and 1571 nm. The temperature sensitivity achieved in our all-PM fiber Lyot filter is 0.602 nm/°C, which is over 46 times higher than other fiber-based filters such as a fiber Bragg grating filter (0.013 nm/°C). This highly stable and versatile wavelength-tunable all-PM fiber mode-locked laser is a promising source for various applications requiring wavelength tunability and/or dual-wavelength output, such as coherent Raman microscopy and dual-comb spectroscopy.

Optical single-sideband modulation for a coherent Doppler lidar.

The first, to the best of our knowledge, implementation of optical single-sideband modulation (OSSBM) in coherent Doppler lidar (CDL) is demonstrated for use with short pulse widths. It is shown that by providing more bandwidth through a higher intermediate frequency (IF), the OSSBM CDL addresses cross talk between the IF and baseband spectra, reducing spectral distortion. Ultimately, a 4-ns pulse width with a 1-GHz IF is achieved and the effectiveness of the OSSBM CDL is confirmed through velocimetry experiments. This represents a several fold improvement over current fiber-based CDL implementations.

Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol-rRNA axis.

BACKGROUND: Glioma-initiating cells (GICs) are the source of glioma cells that can self-renew, have pluripotency, and are treatment-resistant, so are the starting point for relapse and eventual death despite multimodality therapy. L-[methyl-11C] methionine PET has observed high accumulation at the time of recurrence, it is important to understand the mechanism of tumor cell activation caused by the reorganization of methionine metabolism.  METHODS: We cultured cells in methionine-deprived culture medium for comprehensive analysis. Based on the obtained results, the possible target molecules were chemically inhibited and the respective markers were analyzed. RESULTS: Methionine depletion markedly decreased proliferation and increased cell death of GICs. Decreased S-adenosyl-methionine, which is synthesized intracellularly by catalyzed by methionine adenosyltransferase using methionine, triggered the following: (i) global DNA demethylation, (ii) hyper-methylation of signaling pathways regulating pluripotency of stem cells, (iii) decreased expression of the core-genes and pluripotent markers of stem cells including FOXM1, SOX2, SOX4, PROM1, and OLIG2, (iv) decreased cholesterol synthesis and increased excretion mainly through decreased SREBF2, and (v) down-regulation of the large subunit of ribosomal protein configured 28S and ACA43, small nucleolar RNA guiding the pseudouridylation of 28S rRNA, which is essential for translation. In addition, inhibition of cholesterol synthesis with statin resulted in a phenotype similar to that of methionine depletion and decreases in stem cell markers and small nucleolar RNA ACA43. Moreover, suppression of FOXM1 decreased stem cell markers such as SOX4 and PROM1. The gene expression profile for cholesterol production was obtained from the Ivy Glioblastoma Atlas Project database and compared between tumor cells with relatively low methionine levels in areas of pseudopalisading arrangement around necrosis and tumor cells in the infiltrating region, showing that cells in the infiltrating region have higher capacity to produce cholesterol. CONCLUSIONS: Methionine metabolism is closely related with self-renewal, pluripotency, and cell death in GICs through modification of cholesterol biosynthesis, especially in the SREBF2-FOXM1 and ACA43 axis with modification of rRNA.

Importance of Gastric Secretion and the Rapid Gastric Emptying of Ingested Water along the Lesser Curvature ("Magenstraße") in Predicting the In Vivo Performance of Liquid Oral Dosage Forms in the Fed State Using a Modeling and Simulation.

The objective of the present study was to develop an in silico model of the stomach for predicting oral drug absorption in fed humans. We focused on a model capable of simulating dynamic fluid volume changes and included a simulated Magenstraße "stomach road," a route along the lesser curvature that often carries fluids rapidly to assess the gastric emptying of drugs. Two types of model liquid drug formulations, liquid-filled soft gelatin capsules (enzalutamide, cyclosporine, and nifedipine) and oral solutions (levofloxacin and fenfluramine), were used. An in silico model was assembled, and simulations were performed using Stella Professional software. The secretion rate of the gastric juice induced by food ingestion was assessed along with the gastric emptying of the ingested water via the Magenstraße in the fed state. The model for the fed state successfully described the in vivo performance of the model drug formulations. These results clearly indicate the importance of including gastric secretion and the kinetics of Magenstraße when predicting the in vivo performance of dosage forms using an in silico modeling and simulation of fed humans. This simulation model should be further optimized to allow for the different physiological mechanisms following the ingestion of different types of meals, as well as modifications for interindividual and intraindividual variabilities in gastrointestinal physiology in the fed state in the future.