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Chemical gardens formed from two metal salts (MCl2 or MSO4) have been investigated to understand the effects of mixing on the growth of precipitate tubes.

We have developed a self-propelled object, which is composed of a plastic cup and a camphor disk, on water to reflect its three-dimensional shape in the nature of motion.

Differentiation of suprasellar xanthogranuloma (XG) from adult craniopharyngioma (CP) can be problematic in endoscopic extended transsphenoidal surgery.We reviewed the clinical data, preoperative imaging, intraoperative endoscopic findings, and intraoperative frozen section pathology in newly diagnosed adult CPs (19 patients) and XGs (6 patients).Intracystic signal intensity was often high on T1-weighted magnetic resonance images in the XGs but low in the CPs (P = 0.015). Capsular intensity was low on T2-weighted imaging in XGs but iso to high in CPs (P0.001). Capsular gadolinium enhancement was often seen in CPs and not in XGs (P0.001). CPs often had a solid component with contrast enhancement but none in XGs (P0.001). Intraoperative endoscopic observations frequently found a whitish solid component in the CPs but yellow to brown fibrous granulomatous lesions in XGs (P0.001). The tumor capsule was dark grayish and soft in CPs, whereas it was fibrously hard in XGs (P = 0.002). Yellowish hemosiderin deposits were seen in all XGs (P = 0.003). Intraoperative pathologic diagnosis of CP was all verified whereas no evidence of tumor was found in XGs (P0.001). Partial removal was performed in 4 patients with XGs. No recurrence was observed in these patients during the follow-up period (1.5-8 years).Careful interpretation of preoperative magnetic resonance imaging, intraoperative endoscopic findings, and intraoperative frozen section diagnosis may be important for the differential diagnosis between XG and CP. In endoscopic-extended transsphenoidal surgery, intentional partial removal can be effective for XG after careful diagnosis.

Background Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. Methods SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. Results High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. Conclusions High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood. In this study, we performed a clinicopathological and molecular analysis of 3 cases of meningeal SFT with ESGs. All cases presented with an extra-axial mass in the CPA, which is a rarer location for intracranial ESGs compared to the sellar region. Histologically, except for the presence of ESGs, there was no significant difference between current cases and ordinary SFTs. The ESGs demonstrated no cellular atypia, and although the spindle tumor cells were immunopositive for STAT6, the ESGs were negative in all cases, supporting that the ESGs are non-neoplastic components. In 1 case, ESGs were found only in the primary tumor and disappeared in recurrence/dissemination. Of note, molecular analysis identified NAB2 exon 4-STAT6 exon 2 in all cases. In conclusion, our results suggest that ESGs particularly in the CPA may be associated with SFTs and that meningeal SFTs with ESGs may be associated with the minor fusion variant of NAB2-STAT6 in the intracranial lesions.

Interfacial chemical dynamics on a droplet generate various self-propelled motions. For example, ballistic and random motions arise depending on the physicochemical conditions inside the droplet and its environment. In this study, we focus on the relationship between oxidant concentrations in an aqueous droplet and its mode of self-propelled motion in an oil phase including surfactant. We demonstrated that the chemical conditions inside self-propelled aqueous droplets were changed systematically, indicating that random motion appeared at higher concentrations of oxidants, which were H2SO4 and BrO3-, and ballistic motion at lower concentrations. In addition, spontaneous mode switching from ballistic to random motion was successfully demonstrated by adding malonic acid, wherein the initially observed reduced state of the aqueous solution suddenly changed to the oxidized state. Although we only observed one-time transition and have not yet succeeded to realize alternation between ballistic (reduced state) and random motion (oxidized state), such spontaneous transitions are fundamental steps in realizing artificial cells and understanding the fundamental mechanisms of life-like behavior, such as bacterial chemotaxis originating from periodical run-and-tumble motion.

The oral microbiome plays an important role in the human microbial community and in maintaining the health of an individual. Imbalances in the oral microbiome may contribute to oral and systemic diseases. The progression of periodontal disease is closely related to the growth of bacteria, such as Porphyromonas gingivalis, in the oral cavity. However, the pathogen growth mechanism specific to periodontal disease remains unknown. This study aimed to identify bacteria associated with periodontal health by focusing on hemolytic bacteria. Unstimulated saliva samples were collected from ten periodontitis patients and five healthy subjects to detect and identify the presence of hemolytic bacteria. The saliva of healthy subjects contained a higher proportion of G. haemolysans than saliva samples from patients with periodontitis. Growth inhibition assays indicated that the protein components contained in the culture supernatant of G. haemolysans directly suppressed the growth of P. gingivalis. This study shows that the presence of G. haemolysans in saliva is associated with periodontal health and that it inhibits the growth of P. gingivalis in vitro.

The route selection of self-propelled filter papers impregnated with camphor for two-branched water channels was investigated. The two-branched water channel was composed of a stem channel and two branch channels, and the branch channels were connected to the stem channel at a junction. When a single camphor paper reached the junction from the stem channel, it selected one of the two routes equivalently. Three or five camphor papers which were placed on a stem channel exhibited either alternate or random route selection depending on the characteristic length between the leading and following papers, Lc. That is, the alternate route selection of the camphor papers for the two-branched water channels was observed at Lc ≤ 25 mm. By contrast, the alternate route selection was broken at Lc > 25 mm. The physicochemical meaning of the threshold value, Lth ∼ 26 mm, between the alternate and random route selections was discussed based on the experimental results. In addition, the distribution length of camphor molecules developed from the leading camphor paper and the change in the spatial gradient of surface tension around the junction supports the value of Lth. These results suggest that autonomous phenomena using inanimate self-propelled objects are important to understand collective motion in living organisms.

Various spatiotemporal patterns were created on the surface or in the body of cation-exchange resin beads which were loaded with the catalyst of the Belousov-Zhabotinsky (BZ) reaction. Either global oscillations (GO) or traveling waves (TW) and the switching between them were observed in the previous papers, but it was not clear how chemicals contribute to the reaction inside/around the BZ bead. In this paper, we scanned the electrical potential, E, from +1 to -1 V (negative scan) and then turned from -1 to +1 V (positive scan) to control the switching between GO and TW. We found that the electrical switching potential from TW to GO, ETG, and from GO to TW, EGT, depended on the scanning direction of E and the diameter of the bead, d. The present study suggests that the electrode-induced increase of the inhibitor, Br-, and the activator, HBrO2, around the BZ bead plays an important role in determining ETG and EGT.

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

Spatio-temporal patterns, namely global oscillations (GO) and traveling waves (TW), were investigated in spherical microbeads loaded with a catalyst for the Belousov–Zhabotinsky (BZ) reaction onto the surface (2D-loaded) or the entire volume of the bead (3D-loaded). GO and TW selectively appeared in the 2D- and 3D-loaded beads, respectively, placed on a polyethylene terephthalate (PET) sheet in the catalyst-free BZ solution. We examined two types of coupling of the two beads: 2D–3D and 3D–3D couplings. In both cases, synchronization occurred when the minimum distance between the two beads, l, was shorter than the threshold. Herein, we reported not only temporal information, that is, phase difference, but also spatial information, that is, the directions of the TW propagating through the coupled BZ beads. In the synchronization for the 2D–3D coupling, TW in the 3D-loaded bead were initiated from the point near the 2D-loaded bead as a pacemaker and propagated in the opposite direction. By contrast, the directions of the TW in the 3D-loaded bead changed depending on l in the synchronization for the 3D–3D coupling. These experimental results can be quantitatively reproduced by numerical calculations based on the diffusion dynamics of an activator of the BZ reaction. Our results suggest that the features of spatio-temporal wave propagation are indicative of the configuration of the oscillators.

We report herein experimental observations of the reciprocating motion of a self-propelled droplet floating on the surface of an aqueous surfactant solution and a simple reaction model capable of reproducing the observed behavior of the droplet. The reciprocating motion was observed in a quasi-one-dimensional annular channel, so the reciprocation was not caused by reflections at boundaries. To understand the reciprocation, our model assumes a reaction between the surface active substance emitted from the droplet and surfactants dissolved in the aqueous solution. This reaction invokes an inversion of the surface tension gradient and thus the droplet's reciprocation. We show that the model can reproduce experimental results semi-quantitatively using numerical simulations with realistic parameters.

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant tumors of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (rarely) BRG1. Most AT/RT are identified as primary tumors; however, rare AT/RT or INI1-deficient RTs arising from other primary tumors have been reported. Here, we report 3 cases of hitherto unclassifiable low-grade tumors with loss of INI1 nuclear expression, for which we propose the designation of central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency (CNS LGDIT-INI1), 2 of which progressed to secondary RT. All 3 CNS LGDIT-INI1 exhibited a similar histology: diffusely distributed small tumor cells with round to oval or irregular nuclei and scant cytoplasm were admixed with degenerative neurons and large reactive astrocytes in an edematous, myxoid, or collagenous background. Mitotic figures were absent. Immunohistochemistry revealed that the tumor cells in all 3 CNS LGDIT-INI1 and 2 RT were negative for INI1. Genetically, total or partial homozygous deletions of the INI1 gene were detected in all CNS LGDIT-INI1 and RT excluding 1 CNS LGDIT-INI1 without sufficient DNA quality and quantity. Despite the loss of INI1 expression, these low-grade lesions were clearly distinguishable from AT/RT by their low proliferative activity, diffusely infiltrative growth pattern, and lack of rhabdoid cells and polyphenotypic immunoreactivity. In conclusion, CNS LGDIT-INI1 may represent a rare group of tumors that are clinically indolent but have a high propensity to progress to RT.

Improvement of the water-impermeable barrier function of skin is clinically important, because barrier abnormality is associated with various skin diseases, such as psoriasis or atopic dermatitis. We have shown that topical application of fatty acids, sex hormones, hexoses, polyols and polymers influences barrier homeostasis, but the effects are highly dependent on even small variations of molecular structure. Moreover, the effects appear within one hour after application and thus are likely to be non-genomic (physicochemical) phenomena. Secretion of lipids from lamellar bodies into the intercellular space between stratum granulosum and stratum corneum is a crucial step in epidermal water-impermeable barrier homeostasis, especially at the early stage of barrier recovery after damage, and phase transition of the lipid lamellar structure in the epidermis is an important part of this process. Therefore, we evaluated the effects of the above molecules on the physicochemical properties of phospholipid monolayers and liposomes as models of the lamellar body membrane and cell membrane. Molecules that influenced the barrier recovery process also altered the stability of liposomes and the air-water surface pressure of phospholipid monolayers. Studies using attenuated total reflection Fourier-transform infrared spectroscopy (ATR FT-IR), differential scanning calorimetry (DSC) and 13 C nuclear magnetic resonance (NMR) spectrometry suggested that molecules influencing barrier recovery interact specifically with phospholipids. The idea that molecules interacting with phospholipids may influence barrier homeostasis should open up new approaches to the treatment of a variety of skin diseases.

Although the microtubule-associated protein tau is well studied in human neurodegeneration, the role of tau in neoplastic brain diseases is not well understood. Recently, studies have shown tau mRNA expression is associated with improved survival in human infiltrating gliomas. However, the biologic basis of this association is largely unexplored. Using 2 independent publicly available mRNA databases, we show that high tau mRNA expression is associated with improved patient survival in infiltrating gliomas. Higher tau protein expression is also associated with improved patient prognosis in infiltrating gliomas by immunohistochemical staining of tissue microarrays. This prognostic association is in part due to higher tau mRNA and protein expression in IDH-mutant infiltrating astrocytomas. Expression of tau in an IDH-wildtype glioblastoma cell line selectively impairs cell migration in assays designed to mimic tumor invasion. These findings suggest that tau expression is not only associated with IDH mutation status but also may contribute to improved patient outcomes by impairing tumor invasion.

BCORL1 encodes a transcriptional corepressor homolog to BCOR. BCORL1 rearrangements have been previously described as rare events, and among them, CREBBP-BCORL1 has been reported only in 2 cases of ossifying fibromyxoid tumors. Herein, we present the first case of diffusely infiltrating glioma with CREBBP-BCORL1 involving a 17-year-old female patient. Histologically, the tumor was composed of a diffusely infiltrative proliferation of small tumor cells with moderate cellularity showing prominent microcystic formation. DNA methylation analysis revealed that the current case and a previously reported anaplastic ependymoma with EP300-BCORL1 were clustered together in close proximity to but distinct from methylation class high-grade neuroepithelial tumor with BCOR alteration. RNA sequencing demonstrated high mRNA expression of not only BCORL1 but BCOR, and the latter was compatible with diffuse nuclear expression of BCOR detected by immunohistochemistry. Our findings suggest that central nervous system tumors with CREBBP/EP300-BCORL1 may exhibit diverse morphologies but form a distinct DNA methylation group and that BCORL1 fusion genes may lead to upregulation of both BCOR and BCORL1.

Previous studies have unravelled glycolytic oscillations in cancer cells, such as HeLa cervical and DU145 prostate cancer cells, using a monolayer culture system. Here, we demonstrate glycolytic oscillations in HeLa cervical cancer cell spheroids. Experiments revealed that a small number of HeLa cells in spheroids exhibited heterogeneous oscillations with a higher frequency than those in monolayers. Model analyses and our previous experiments indicated that the higher frequencies of oscillations in spheroids were mostly due to the increase in glycolytic enzyme activity in the cells, and to the decrease in glucose concentration by diffusional transport of glucose from the surface to inside the spheroids, as well as the increase in cell density through spheroid formation. These results and our previous studies imply that more malignant cancer cells tend to exhibit glycolytic oscillations with higher frequencies than less malignant cells. Adjacent cells in spheroids oscillated within a 10% difference in frequency, but did not synchronize with each other. This suggests that weak cell-to-cell interactions might exist among HeLa cells connected with cadherins in the spheroid microenvironment; however, the interactions were not strong enough to induce synchronization of glycolytic oscillations.

Background and Aims: A considerable number of patients with ulcerative colitis (UC) who initially respond to golimumab (GLM), an anti-TNF-α antibody, gradually lose clinical response. Therapeutic drug monitoring has been proposed to optimize serum anti-TNF-α antibody concentrations before the loss of response; however, little is known about ideal serum GLM concentrations. We aimed to evaluate whether the serum GLM trough levels (TLs) early after the initiation of induction therapy affect the long-term outcomes in UC and to identify the early GLM TLs that should be targeted for better long-term outcomes. Methods: Thirty-one patients were prospectively evaluated. The primary outcome was clinical remission at 54 weeks, and we measured the serum GLM TLs at weeks 6, 10, and 14. Receiver operating characteristic (ROC) curves were constructed to identify optimal GLM TL thresholds early after induction therapy that were associated with clinical remission at week 54. Results: The GLM TL at week 14, but not at weeks 6 or 10, was significantly associated with clinical remission at week 54 (median [IQR] 1.6 [1.3–1.6] μg/mL vs. 0.9 [0.6–1.3] μg/mL; p = 0.04). The area under the ROC curve for GLM TLs at week 14 was 0.78. We identified a week-14 GLM TL of 1.1 μg/mL as the target threshold for achieving clinical remission at week 54. Conclusion: Our results demonstrate the value of early serum GLM TLs in predicting the long-term outcomes of GLM for patients with UC.

Background and Aims: The calcineurin inhibitor tacrolimus is reportedly effective for moderate/severe ulcerative colitis (UC); however, it is also reportedly associated with nephrotoxicity. We investigated the risk factors for tacrolimus-induced nephrotoxicity and whether renal impairment adversely affected the outcomes of tacrolimus treatment in patients with UC. Methods: We conducted a retrospective study of 93 patients with UC who were administered tacrolimus leading to high trough levels (10–15 ng/mL) for 2 weeks and low trough levels (5–10 ng/mL) for 3 months. Results: Acute kidney injury (AKI) occurred in 44 patients (47.3%) during tacrolimus treatment. Of these patients, 34 (36.6%) developed AKI during the high trough phase and 17 (18.3%) developed AKI when the trough value exceeded the original target value of 15 ng/mL. Multivariate logistic regression analysis revealed that the male sex was significantly associated with AKI (p = 0.002, AOR = 4.38, 95% CI [1.69–11.3]). Clinical remission rate after 4, 8, 12, and 24 weeks of tacrolimus treatment in patients with AKI was lower than that in patients without AKI. Six patients (6.5%) had chronic kidney disease (CKD) after tacrolimus treatment completion, and all patients with CKD developed AKI during treatment. The median duration of treatment with no improvement in AKI was significantly longer in patients with CKD than in those without CKD (p = 0.016). Conclusion: We revealed the risk factors for tacrolimus-induced nephrotoxicity. Renal impairment occurrence adversely affected the tacrolimus treatment outcome; therefore, it is important to carefully administer tacrolimus to prevent renal impairment.

Two novel amphiphiles, N-(3-nitrophenyl)stearamide (MANA) and N,N′-(4-nitro-1,3-phenylene)distearamide (OPANA), were synthesized by reacting nitroanilines with one or two equivalents of stearic acid. We investigated how the molecular structures of these compounds influenced the characteristics of a self-propelled camphor disk placed on a monolayer of the synthesized amphiphiles. Three types of motion were observed at different surface pressures (Π): continuous motion (Π &lt, 4 mN m−1), deceleration (4 mN ≤ Π ≤ 20 mN m−1), and no motion (Π &gt, 20 mN m−1). The speed of the motion of the camphor disks was inversely related to Π for both MANA and OPANA at the temperatures tested, when Π increased in the respective molecular layers under compression. The spectroscopic evidence from UV-Vis, NMR, and ESI-TOF-MS revealed that the dependence of the speed of the motion on Π originates from the intermolecular interactions that are present in the monolayers. This study suggests that it is possible to control the self-propelled motion by manipulating contributing factors at the molecular level.

Chemical traveling waves play an important role in biological functions, such as the propagation of action potential and signal transduction in the nervous system. Such chemical waves are also observed in inanimate systems and are used to clarify their fundamental properties. In this study, chemical waves were generated with equivalent spacing on an excitable medium of the Belousov–Zhabotinsky reaction. The homogeneous distribution of the waves was unstable and low- and high-density regions were observed. In order to understand the fundamental mechanism of the observations, numerical calculations were performed using a mathematical model, the modified Oregonator model, including photosensitive terms. However, the homogeneous distribution of the traveling waves was stable over time in the numerical results. These results indicate that further modification of the model is required to reproduce our experimental observations and to discover the fundamental mechanism for the destabilization of the homogeneous-distributed chemical traveling waves.

We report a histological and genetic study of concurrent oligodendroglioma and a microscopic pleomorphic xanthoastrocytoma (PXA)-like lesion in a 48-year-old male. He presented with generalized seizure, and magnetic resonance imaging revealed a nonenhanced left frontal lobe mass suggesting low-grade glioma. The patient underwent craniotomy and tumor resection. Histopathological examination of the surgical specimen showed an oligodendroglioma with a PXA-like element; the latter measured 0.9 mm and occupied a Virchow-Robin space of the superficial cortex. The whole tumor had no elevated mitotic activity, microvascular proliferation or necrosis. Each component was immunohistochemically isocitrate dehydrogenase (IDH1)-R132H positive, p53 negative and ATRX positive. Genetic analyses clarified identical IDH1 G395A mutation, promoter C228T mutation and 1p/19q codeletion in both elements. Careful integration of histology and telomerase reverse transcriptase (TERT) molecular parameters revealed that this case was an oligodendroglioma showing PXA-like features, rather than a collision tumor. This case provides further insights into the gliomagenesis.

Atypical teratoid/rhabdoid tumors (AT/RT) are rare, highly malignant neoplasms of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (extremely rarely) BRG1. The vast majority of AT/RT are recognized as primary tumors; however, rare AT/RT or INI1-deficient RT arising from other primary tumors have been reported. To better characterize secondary RT, we performed a histological and molecular analysis of four RT arising from pleomorphic xanthoastrocytoma (PXA), anaplastic PXA, low-grade astrocytoma, or ependymoma. Histologically, although conventional AT/RT are usually not largely composed of rhabdoid cells, three secondary RT were composed mainly of rhabdoid cells, two of which arising from (anaplastic) PXA exhibited marked nuclear pleomorphism reminiscent of that in the precursor lesions. Regarding INI1 alterations, although mutations including small indels are frequent in conventional AT/RT, only in one secondary RT had a mutation. Moreover, together with previously reported cases, biallelic INI1 inactivation in secondary RT was mostly due to biallelic focal and/or broad deletions. Although conventional AT/RT have stable chromosomal profiles, i.e., the frequency of copy number changes involving chromosomes other than chromosome 22 is remarkably low, our array comparative genomic hybridization analysis revealed numerous copy number changes in the secondary RT. In conclusion, secondary RT of the central nervous system are clinicopathologically and molecularly different from conventional pediatric AT/RT, and a nosological issue is whether these secondary RT should be called secondary "AT/RT" as most of the reported cases were.