Oxytocin-induced increases in cytokines and clinical effect on the core social features of autism: Analyses of RCT datasets.

Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) < 0.001), IL-9 (56.64, 20.46 to 92.82, PFDR < 0.001) and MIP-1b (18.27, 4.96 to 31.57, PFDR < 0.001) compared with placebo. Inverted U-shape dose-response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (PFDR < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = -0.05, -0.10 to 0.003, P = 0.067; IL-9: -0.01, -0.02 to -0.003, P = 0.005; MIP-1b: -0.02, -0.04 to -0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed. Trial registration: UMIN000015264, NCT03466671/UMIN000031412.

Is oral Streptococcus mutans with collagen-binding protein a risk factor for intracranial aneurysm rupture or formation?

OBJECTIVE: Streptococcus mutans (SM) with the collagen-binding protein Cnm is a unique member of the oral resident flora because it causes hemorrhagic vascular disorders. In the multicenter study, we examined the relationship between Cnm-positive SM (CP-SM) and intracranial aneurysm (IA) rupture, which remains unknown. METHODS: Between May 2013 and June 2018, we collected whole saliva samples from 431 patients with ruptured IAs (RIAs) and 470 patients with unruptured IAs (UIAs). Data were collected on age, sex, smoking and drinking habits, family history of subarachnoid hemorrhage, aneurysm size, number of teeth, and comorbidities of lifestyle disease. RESULTS: There was no difference in the positivity rate of patients with CP-SM between the patients with RIAs (17.2%) and those with UIAs (19.4%). The rate of positivity for CP-SM was significantly higher in all IAs <5 mm than in those ≥10 mm in diameter (P=0.0304). In the entire cohort, the rate of positivity for CP-SM was lower in larger aneurysms than in smaller aneurysms (P=0.0393). CONCLUSIONS: The rate of positivity for CP-SM was lower among patients with large UIAs. These findings are consistent with the hypothesis that CP-SM plays a role in the formation of vulnerable IAs that tend to rupture before becoming larger.

Dietary Iron Restriction Protects against Aneurysm Rupture in a Mouse Model of Intracranial Aneurysm.

INTRODUCTION: Iron accumulation in vessel walls induces oxidative stress and inflammation, which can cause cerebrovascular damage, vascular wall degeneration, and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture. METHODS: Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet (n = 23) or a normal diet (n = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination. RESULTS: The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; p < 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2'-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p < 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2'-deoxyguanosine in both normal diet and iron-restricted diet mouse aneurysms. CONCLUSIONS: These findings suggest that iron is involved in intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture.

Effects of volatile anesthetics on circadian rhythm in mice: a comparative study of sevoflurane, desflurane, and isoflurane.

PURPOSE: Volatile anesthetics affect the circadian rhythm of mammals, although the effects of different types of anesthetics are unclear. Here, we anesthetized mice using several volatile anesthetics at two different times during the day. Our objective was to compare the effects of these anesthetics on circadian rhythm. METHODS: Male adult C57BL/6 J mice were divided into eight groups (n = 8 each) based on the anesthetic (sevoflurane, desflurane, isoflurane, or no anesthesia) and anesthesia time (Zeitgeber time [ZT] 6-12 or ZT18-24). Mice were anesthetized for 6 h using a 0.5 minimum alveolar concentration (MAC) dose under constant dark conditions. The difference between the start of the active phase before and after anesthesia was measured as a phase shift. Clock genes were measured by polymerase chain reaction in suprachiasmatic nucleus (SCN) samples removed from mouse brain after anesthesia (n = 8-9 each). RESULTS: Phase shift after anesthesia at ZT6-12 using sevoflurane (- 0.49 h) was smaller compared with desflurane (- 1.1 h) and isoflurane (- 1.4 h) (p < 0.05). Clock mRNA (ZT6-12, p < 0.05) and Per2 mRNA (ZT18-24, p < 0.05) expression were different between the groups after anesthesia. CONCLUSION: 0.5 MAC sevoflurane anesthesia administered during the late inactive to early active phase has less impact on the phase shift of circadian rhythm than desflurane and isoflurane. This may be due to differences in the effects of volatile anesthetics on the expression of clock genes in the SCN, the master clock of the circadian rhythm.

Effect of a novel nasal oxytocin spray with enhanced bioavailability on autism: a randomized trial.

Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration-time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose-response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0-14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose-response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = -0.5; 95% CI: -1.1 to 0.1; per protocol set: P = 0.012, mean difference = -0.8; 95% CI: -1.3 to -0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose-response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial.

Numerical Analysis for Light Absorption Spectra of the Base of DNA-Wrapped Single-Walled Carbon Nanotubes.

This study numerically demonstrates the light absorption spectra of each base of DNA-wrapped single-walled carbon nanotubes (SWCNTs). Previous experimental and theoretical studies show that the optical properties of these composites are different from the bare SWCNTs. In this work, we investigated the bases of DNA that influence optical properties. To obtain stable molecular states for studying optical properties, molecular dynamics calculations were performed. Additionally, light absorption spectra in the ultraviolet-to-near-infrared region of one type of base-wrapped (e.g., adenine-, thymine-, cytosine-, or guanine-wrapped) SWCNTs were investigated by utilizing the semi-empirical molecular orbital theory using SCIGRESS commercial software. This method can significantly reduce the calculation time compared to the ab initio molecular orbital method, making the handling of composites of bases and SWCNTs possible. We found that the largest peaks appear at a wavelength of around 300 nm for all the composites. Furthermore, we found that the light absorption spectra above 570 nm are strongly influenced by adenine and cytosine. Thus, our computational results provide insight into the optical properties and the effects of base-SWCNTs that are difficult to investigate experimentally under the influence of solvents and various molecules.

Dasatinib suppresses atherosclerotic lesions by suppressing cholesterol uptake in a mouse model of hypercholesterolemia.

Although the use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia is known to cause vascular adverse events (VAEs), the frequency of VAEs during dasatinib administration is not high, and the same holds for atherosclerosis-related VAEs. However, its effect on atherosclerosis remains controversial. In this study, our primary objective was to investigate how dasatinib affects atherosclerosis. Ldlr-/-/Apobec1-/- mice, which are highly prone to develop atherosclerosis, were administered dasatinib. After 16 weeks, we evaluated their atherosclerotic lesions. We used bone-marrow-derived macrophages to investigate the uptake of oxidized low-density lipoprotein (LDL) complexed with DiI dye (DiI-oxLDL). RNA sequencing and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were performed to explore the potential effects of dasatinib on cholesterol metabolism. Dasatinib administration significantly reduced atherosclerotic lesions (P < 0.001 and P = 0.013) and DiI-oxLDL uptake (P < 0.001) unlike other TKIs. RNA sequencing and RT-qPCR suggested that Sort1, which encodes sortilin, a known regulator of LDL uptake, and Cd36 were potential targets of dasatinib. In conclusion, dasatinib induced elevated LDL-C levels, but oxLDL uptake in macrophages were suppressed, resulting in reducing atherosclerotic lesions. These results further our understanding of the differences in VAEs between dasatinib and other TKIs.

Efficacy and safety of propranolol cream in infantile hemangioma: A prospective pilot study.

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35-150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1-85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.

An Efficient Method of Observing Diatom Frustules via Digital Holographic Microscopy.

Herein, we propose a convenient method to enable pretreatment of target objects using digital holographic microscopy (DHM). As a test sample, we used diatom frustules (Nitzschia sp.) as the target objects. In the generally used sample preparation method, the frustule suspension is added dropwise onto a glass substrate or into a glass chamber. While our work confirms good observation of purified frustules using the typical sample preparation method, we also demonstrate a new procedure to observe unseparated structures of frustules prepared by baking them on a mica surface. The baked frustules on the mica surface were transferred to a glass chamber with 1% sodium dodecyl sulfate solution. In this manner, the unseparated structures of the diatom frustules were clearly observed. Furthermore, metal-coated frustules prepared by sputtering onto them on a mica surface were also clearly observed using the same procedure. Our method can be applied for the observation of any target object that is pretreated on a solid surface. We expect our proposed method to be a basis for establishing DHM techniques for microscopic observations of biomaterials.

Successful lactation in Plgrkt-deficient female mice caused by a 1-bp deletion of exon4.

Plasminogen (Pg) activation on the cell surface is important for various (patho)physiologic conditions, and Plg-RKT is a cell membrane protein that binds to Pg and promotes its activation. To evaluate the role of Plg-RKT in atherosclerosis, Plgrkt gene in Ldlr-/-/Apobec1-/- was modified using in vivo CRISPR/Cas9. Synthetic RNA for Plgrkt and Cas9 complex was electroporated into the fertilized eggs in the oviducts. Plgrkt deficient mice were established through a 1-bp deletion, and in this research communication we report their lactational ability. In contrast to Plgrkt-/- mice developed by a conventional method, these newly developed mice did not suffer lactation failure and could maintain their pups until weaning. The major obvious difference between these lines is the area of gene modification. The conventionally developed mouse possesses about 10 kb deletion of Plgrkt, which might relate to the lactation failure. Lactation failure is a lethal phenotype in mammals, and analyses of causative genes are especially important for dairy industries. Further genome-wide analyses with both Plgrkt-/- mice may help to establish causative genes for lactation failure.

Fibrin-mediated growth restriction of early-stage human trophoblasts is switched to growth promotion through fibrinolysis.

STUDY QUESTION: Does fibrin promote trophoblast growth in human and mouse blastocysts during early embryo implantation? SUMMARY ANSWER: Mouse blastocysts were unaffected by fibrin; however, human blastocysts were significantly suppressed by fibrin in trophoblast growth and then switched to growth promotion through increased fibrinolysis with urokinase-type plasminogen activator (uPA) activity. WHAT IS KNOWN ALREADY: Fibrin(ogen) plays an important role in various physiological processes and is also critical for maintaining feto-maternal attachment during pregnancy. The addition of fibrin to embryo transfer media has been used to increase implantation rates in human ART; however, its mechanism of action' in vitro has not yet been characterized. STUDY DESIGN, SIZE, DURATION: Vitrified mouse and human blastocysts were warmed and individually cultured in vitro for up to 120 and 168 h, respectively, on a fibrin substrate. Blastocysts were cultured at 37°C in 6% CO2, 5% O2 and 89% N2. Blastocyst development and related fibrinolytic factors were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: ICR strain mouse embryos were purchased from a commercial supplier. Human blastocysts were donated with informed consent from two fertility centers. Mouse and human blastocysts cultured on fibrin-coated plates were compared to those on non-coated and collagen-coated plates in vitro. Trophoblast growth and fibrin degradation were assessed based on the cell area and fibrin-free area, respectively. Fibrinolytic factors were detected in supernatants using plasminogen-casein zymography. The fibrinolytic activity of blastocysts was investigated using a selective uPA inhibitor, exogenous uPA, plasminogen activator inhibitor-1 (PAI-1) inhibitor and fibrin degradation products (FDPs). Fibrinolysis-related mRNA expression level was detected using quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Fibrin did not affect the developmental speed or morphology of mouse blastocysts, and a large fibrin-degrading region was observed in the attachment stage. In contrast, fibrin significantly suppressed the outgrowth of trophoblasts in human blastocysts, and trophoblasts grew after the appearance of small fibrin-degrading regions. uPA was identified as a fibrinolytic factor in the conditioned medium, and uPA activity was significantly weaker in human blastocysts than in mouse blastocysts. The inhibition of uPA significantly reduced the outgrowth of trophoblasts in mouse and human blastocysts. Human blastocysts expressed PLAU (uPA), PLAUR (uPA receptor), SERPINE1 (PAI-1) and SERPINB2 (PAI-2), whereas mouse blastocysts were limited to Plau, Plaur and Serpine1. In a subsequent experiment on human blastocysts, the addition of exogenous uPA and the PAI-1 inhibitor promoted trophoblast growth in the presence of fibrin, as did the addition of FDPs. LIMITATIONS, REASONS FOR CAUTION: This model excludes maternal factors and may not be fully reproduced in vivo. Donated human embryos are surplus embryos that may inherently exhibit reduced embryonic development. In addition, donated ART-derived embryos may exhibit weak uPA activity, because women with sufficient uPA-active embryos may not originally require ART. The present study used orthodox culture methods, and results may change with the application of recently developed protocols for culture blastocysts beyond the implantation stage. WIDER IMPLICATIONS OF THE FINDINGS: The present results suggest that the distinct features of trophoblast outgrowth in human blastocysts observed in the presence of fibrin are regulated by a phenotypic conversion induced by contact with fibrin and FDPs. Mouse embryos did not exhibit the human phenomenon, indicating that the present results may be limited to humans. STUDY FUNDING/COMPETING INTEREST(S): The present study was supported by the Department of Obstetrics and Gynecology at the Hamamatsu University School of Medicine and Kishokai Medical Corporation. None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Sinking of Four Species of Living Diatom Cells Directly Observed by a "Tumbled" Optical Microscope.

The study of the sinking phenomenon of diatom cells, which have a slightly larger specific gravity (~1.3) compared to that of water, is an important research topic for understanding photosynthetic efficiency. In this study, we successfully demonstrated the observation of the sinking behaviors of four different species of diatom using a homemade "tumbled" optical microscope. A homemade 1 mm3 microchamber was employed to decrease the effects of convection currents. In the microchamber, diatom cells were basically settled in a linear manner without floating, although some of the cells were rotated during their sinking. Sinking speeds of the four species of diatom cells, Nitzschia sp., Pheodactylum tricornutum, Navicula sp., and Odontella aurita, were 0.81 ± 5.56, 3.03 ± 10.17, 3.29 ± 7.39, and 11.22 ± 21.42 µm/s, respectively, based on the automatic tracking analysis of the centroids of each cell. Manual analysis of a vector between two longitudinal ends of the cells (two-point analysis) was effective for quantitatively characterizing the rotation phenomenon; therefore, angles and angular velocities of rotating cells were well determined as a function of time. The effects of the cell shapes on sinking velocity could be explained by simulation analysis using the modified Stokes' law proposed by Miklasz et al.

Optical Response Characteristics of Single-Walled Carbon Nanotube Chirality Exposed to Oxidants with Different Oxidizing Power.

Semiconductor single-walled carbon nanotubes (SWNTs) have unique characteristics owing to differences in the three-dimensional structure (chirality) expressed by the chiral index (n,m), and many studies on the redox characteristics of chirality have been reported. In this study, we investigated the relationship between the chirality of SWNTs and the oxidizing power of oxidants by measuring the near-infrared (NIR) absorption spectra of two double-stranded DNA-SWNT complexes with the addition of three oxidants with different oxidizing powers. A dispersion was prepared by mixing 0.5 mg of SWNT powder with 1 mg/mL of DNA solution. Different concentrations of hydrogen peroxide (H2O2), potassium hexachloroidylate (IV) (K2IrCl6), or potassium permanganate (KMnO4) were added to the dispersion to induce oxidation. Thereafter, a catechin solution was added to observe if the absorbance of the oxidized dispersion was restored by the reducing action of the catechin. We found that the difference in the oxidizing power had a significant effect on the detection sensitivity of the chiralities of the SWNTs. Furthermore, we revealed a detectable range of oxidants with different oxidizing powers for each chirality.

Dispersion of Carbon Nanotubes with "Green" Detergents.

Solubilization of carbon nanotubes (CNTs) is a fundamental technique for the use of CNTs and their conjugates as nanodevices and nanobiodevices. In this work, we demonstrate the preparation of CNT suspensions with "green" detergents made from coconuts and bamboo as fundamental research in CNT nanotechnology. Single-walled CNTs (SWNTs) with a few carboxylic acid groups (3-5%) and pristine multi-walled CNTs (MWNTs) were mixed in each detergent solution and sonicated with a bath-type sonicator. The prepared suspensions were characterized using absorbance spectroscopy, scanning electron microscopy, and Raman spectroscopy. Among the eight combinations of CNTs and detergents (two types of CNTs and four detergents, including sodium dodecyl sulfate (SDS) as the standard), SWNTs/MWNTs were well dispersed in all combinations except the combination of the MWNTs and the bamboo detergent. The stability of the suspensions prepared with coconut detergents was better than that prepared with SDS. Because the efficiency of the bamboo detergents against the MWNTs differed significantly from that against the SWNTs, the natural detergent might be useful for separating CNTs. Our results revealed that the use of the "green" detergents had the advantage of dispersing CNTs as well as SDS.

An efficient method to quantitatively detect competitive adsorption of DNA on single-walled carbon nanotube surfaces.

In this study, we quantitatively detected adsorption and desorption of DNA molecules that competed with sodium cholate (SC) molecules on single-walled carbon nanotubes (SWNTs) by fluorescence spectroscopy. In previous studies, competitive adsorption and/or replacement were studied based on techniques such as near-infrared (NIR) absorbance and photoluminescence (PL) spectroscopy of SWNTs. In those studies, adsorption of organic molecules was detected as spectral changes in SWNTs, but not in organic molecules. In this study, we employed fluorescent-labeled DNA (Fc-DNA) to detect competitive adsorption through quenching of fluorescent dyes that were attached to DNA molecules. Through this approach, the adsorption behaviors of DNA molecules could be directly determined. Hence, we found that Fc-DNA molecules adsorbed on SWNT surfaces that were pre-wrapped with SC when the SC concentration was reduced. However, when SC concentrations recovered after three days of incubation, detachment of Fc-DNA molecules was observed. In addition, our method could be applied to evaluate the adsorption of fluorescent dyes on SWNT surfaces instead of DNA molecules. Hence, our method is effective in studying competitive adsorption of organic molecules on SWNT surfaces. The obtained information is complementary to that obtained from NIR spectroscopy of SWNTs.

Nanobody production can be simplified by direct secretion from Escherichia coli.

It is well known that camelids (camels and llamas) have fully functional antibodies with only a heavy chain consisting of a single variable domain and two constant domains. This single variable domain is called a "nanobody" and many nanobodies are synthesized in the cytosol of Escherichia coli, however, most of the nanobodies become inclusion bodies without tags to enhance their solubility. We generated a vector system to enable the secretary expression of nanobodies in Escherichia coli. In this system, several NBs were secreted into the culture supernatant. Since the vector contained 6xHis tag and AviTAG, biotinylation (even fluorescent-labeled) of AviTAG was achieved during cell culture, and purification of the supernatant was a step by immobilized metal ion adsorption chromatography. The procedure described in this study is believed to be as simple as regular plasmid minipreps. Therefore, many laboratories can use this method.

Decomposition of amyloid fibrils by NIR-active upconversion nanoparticles.

We demonstrate amyloid fibril (AF) decomposition induced by NIR-active upconversion nanoparticles complexed with photosensitisers. The process is triggered by upconversion, which initiates a photochemical reaction cascade that culminates in the generation of the highly reactive singlet-oxygen product 1O2 close to the amyloid superstructures, resulting in AF decomposition.

Dual Therapy with Vonoprazan and Amoxicillin Is as Effective as Triple Therapy with Vonoprazan, Amoxicillin and Clarithromycin for Eradication of Helicobacter pylori.

BACKGROUNDS/AIMS: Vonoprazan (VPZ) is the first clinically available potassium competitive acid blocker. This class of agents provides faster and more potent acid inhibition than proton pump inhibitors. Most strains of Helicobacter pylori are sensitive to amoxicillin. We hypothesized that dual therapy with VPZ and amoxicillin would provide the sufficient eradication rate for H. pylori infection. To evaluate this, we compared the eradication rate by the dual VPZ/amoxicillin therapy with that by the standard triple VPZ/amoxicillin/clarithromycin therapy. METHODS: Non-inferiority of the eradication rate of H. pylori by the dual therapy with VPZ 20 mg twice daily (bid) and amoxicillin 500 mg 3 times daily (tid) for 1 week to that by the triple therapy with VPZ 20 mg bid, amoxicillin 750 mg bid and clarithromycin 200 mg bid for 1 week was retrospectively studied. Propensity score matching was performed to improve comparability between 2 regimen groups. Successful eradication was diagnosed using the [13C]-urea breath test at 1-2 months after the end of eradication therapy. RESULTS: The intention-to-treat analysis demonstrated that the eradication rate by the dual therapy (92.9%; 95% CI 82.7-98.0%, 52/56) was not inferior to that of the triple therapy (91.9%; 95% CI 80.4-97.0%, 51/56; OR 1.275, 95% CI 0.324-5.017%, p = 0.728). There were no statistically significant differences in incidences of adverse events between 2 regimens. CONCLUSION: VPZ-based dual therapy (VPZ 20 mg bid and amoxicillin 500 mg tid for 1 week) provides an acceptable eradication rate of H. pylori infection without the need for second antimicrobial agents, such as clarithromycin.

A convenient method of attaching fluorescent dyes on single-walled carbon nanotubes pre-wrapped with DNA molecules.

We demonstrated the attachment of different kinds of dyes, Uranine, Rhodamime 800 (R800), and Indocyanine green (ICG), to single-walled carbon nanotubes pre-wrapped with single-stranded DNAs (ssDNA-SWCNTs). A new but simple method was employed, in which a dye solution was added to ssDNA-SWCNTs that had been prepared beforehand in the conventional way. Resulting conjugates of dyes, DNA, and SWCNTs were precisely evaluated by ultraviolet to near-infrared fluorescence/absorbance spectrometry and atomic force microscopy. In particular, simultaneous measurements of fluorescence and absorbance spectroscopy enabled us to find differences in the behaviors of the dyes on SWCNT surfaces. As a result, the fluorescence/absorbance spectra of dyes showed significant changes upon adsorption on SWCNTs. The fluorescence/absorbance peaks of Uranine, R800, and ICG were quenched by 41.3/2.8%, 72.3/48.9%, and 88.3/45.0%, respectively, in the presence of 11.5 µg/mL SWCNTs. We concluded firstly that by pre-wrapping SWCNTs with ssDNA, stable hybrids with these components were obtained even if the dyes used were relatively hydrophobic and secondly that Uranine retained light absorption on the surface of SWCNT while R800 and ICG did not.

A fundamental study of photoluminescence modulation from DNA-wrapped single-walled carbon nanotubes.

In this study, we investigated the interaction of base sequence-assigned single-stranded DNA (ssDNA) molecules with the surfaces of single-walled carbon nanotube (SWNT)-thymine (T30)/cytosine (C30) hybrids (T30/C30-SWNT), by measuring the modulation of near-infrared (NIR) photoluminescence (PL). Significant PL shifts were observed when T30/C30-SWNTs were reacted with 30-mers of adenine (A30)/guanine (G30). In contrast, when non-complementary ssDNA was used, no significant energy shift was observed in the PL modulation except when T30-SWNTs were reacted with G30. Furthermore, atomic force microscopy (AFM) measurements revealed that the average heights of the T30-SWNTs and C30-SWNTs, after reaction with A30 were 2 ± 0.6 and 1.1 ± 0.3 nm, respectively. This result was in good agreement with the results of PL measurements. Our data reveal that DNA hybridization could be detected by measuring PL from SWNTs, without the use of fluorescent molecules. This leads to the possibility of developing nanotube-based photoelectric conversion or optical switch devices driven by organic molecules.