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Abstract Objective Glioblastoma (GBM) is one of the most aggressive brain tumors and often leads to poor outcomes. Studies have indicated that glycan levels are significantly correlated with the pathogenesis and development of cancers. However, whether glycan levels can serve as diagnostic or prognostic biomarkers in GBM remains unclear. Methods We obtained glycomic profiles in tissue and serum samples from 55 individuals with GBM using a well‐established lectin biochip platform probing with 11 specific lectins. Results Our univariate analysis showed that 5 out of the 11 lectin‐probed glycans (LPGs) were significantly higher in GBM tissues than in peri‐tumoral tissues. After logistic regression analyses, only the Jacalin‐probed T‐antigen difference between the two groups remained significant (p = 0.037). Moreover, survival‐related analyses showed that the level of Jacalin‐probed T‐antigen was significantly associated with the progression‐free survival (p = 0.038) of patients. However, none of the LPG levels were correlated with the overall survival or the chemosensitivity to temozolomide therapy. The correlation coefficient analysis showed a moderate‐to‐strong correlation in the Jacalin‐probed T‐antigen levels between GBM tissues and serum samples, indicating its potential usefulness as a non‐invasive GBM progression biomarker. Interpretation Glycomics analyses can be helpful in the prediction of GBM recurrences and may provide information useful for GBM glycan‐based target therapies or vaccine development.

Abstract Background Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. Methods MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. Results Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. Conclusions This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

ABSTRACT Pituitary adenomas (PAs) are common benign brain tumors. Although associations between the gastrointestinal microbiome and PA have been reported previously, studies on the distributions of salivary microbial species in PA patients and among their different clinical phenotypes are currently lacking. In this study, saliva samples from 42 patients and 20 healthy individuals were selected for third-generation sequencing. The PA group included four clinical phenotypes: adrenocorticotropic hormone-secreting PA (n = 6), growth hormone-secreting PA (n = 9), prolactin-secreting PA (n = 18), and nonfunctioning PA (n = 9). All samples were sequenced, and the data were clustered and de-chimerized to obtain information regarding the abundance of operational taxonomic units. We found that the species distributions in the saliva of PA patients were more abundant than those of healthy individuals. A total of 82 genera were identified across all samples, of which 14 and 17 genera were more abundant in the saliva samples of patients with PA and healthy individuals, respectively. In the phenotypic functional prediction, the phenotypes of anaerobic and Gram-positive organisms were more commonly seen in patients with PA than in healthy individuals. The bioinformatics prediction indicated that multiple metabolic pathways were involved in the pathogenesis of PA. In conclusion, this study highlighted the associations of salivary microbiome profiles with PA, which may improve the existing understanding of the pathogenesis of PA and provide diagnostic and therapeutic targets for PA. IMPORTANCE The gut and salivary microbiomes have been widely reported to be significantly associated with a number of neurological disorders. The stability of the microbiome in the oral cavity makes it a potentially ideal sample that can be conveniently obtained for the investigation of microbiome-based pathogenesis in diseases. In the present study, we used a single-molecule long-read sequencing technique to study the distribution of the salivary microbiota in patients with pituitary adenoma (PA) and healthy individuals, as well as among four clinical phenotypes of PA. We found that the diversity of salivary microbes was more abundant in PA patients than in healthy individuals. We also observed some unique genera in different PA phenotypes. The bioinformatics-based functional predictions identified potential links between microbes and different clinical phenotypes of PA. This study improves the existing understanding of the pathogenesis of PA and may provide diagnostic and therapeutic targets for PA.

Abstract Background Melatonin (MEL), an endogenous hormone, has been widely investigated in neurological diseases. Microglia (MG), a resident immunocyte localizing in central nervous system is reported to play important functions in the animal model of temporal lobe epilepsy (TLE). Some evidence showed that MEL influenced activation of MG, but the detailed model of action that MEL plays in remains uncertain. Methods In this study, we established a model of TLE in mice by stereotactic injection of kainic acid (KA). We treated the mice with MEL. Lipopolysaccharide, ROCK2‐knockdown (ROCK‐KD) and ‐overexpression (ROCK‐OE) of lentivirus‐treated cells were used in cell experiments to simulate an in vitro inflammatory model. Results The results of electrophysiological tests showed that MEL reduced frequency and severity of seizure. The results of behavioral tests indicated MEL improved cognition, learning, and memory ability. Histological evidences demonstrated a significant reduction of neuronal death in the hippocampus. In vivo study showed that MEL changed the polarization status of MG from a proinflammatory M1 phenotype to an anti‐inflammatory M2 phenotype by inversely regulating the RhoA/ROCK signaling pathway. In cytological study, we found that MEL had a significant protective effect in LPS‐treated BV‐2 cells and ROCK‐KD cells, while the protective effect of MEL was significantly attenuated in ROCK‐OE cells. Conclusion MEL played an antiepileptic role in the KA‐induced TLE modeling mice both in behavioral and histological levels, and changed MG polarization status by regulating the RhoA/ROCK signaling pathway.

IntroductionPost-neurosurgical bacterial meningitis (PNBM) is a serious complication for patients who receive neurosurgical treatment, but the diagnosis is difficult given the complicated microenvironment orchestrated by sterile brain injury and pathogenic infection. In this study, we explored potential diagnostic biomarkers and immunological features using a proteomics platform.MethodsA total of 31 patients with aneurysmal subarachnoid hemorrhage (aSAH) who received neurosurgical treatment were recruited for this study. Among them, 15 were diagnosed with PNBM. The remaining 16 patients were categorized into the non-PNBM group. Proteomics analysis of the cerebrospinal fluid (CSF) was conducted on the Olink platform, which contained 92 immunity-related molecules.ResultsWe found that the expressions of 27 CSF proteins were significantly different between the PNBM and non-PNBM groups. Of those 27 proteins, 15 proteins were upregulated and 12 were downregulated in the CSF of the PNBM group. The receiver operating characteristic curve analysis indicated that three proteins (pleiotrophin, CD27, and angiopoietin 1) had high diagnostic accuracy for PNBM. Furthermore, we also performed bioinformatics analysis to explore potential pathways and the subcellular localization of the proteins.ConclusionIn summary, we found a cohort of immunity-related molecules that can serve as potential diagnostic biomarkers for PNBM in patients with aSAH. These molecules also provide an immunological profile of PNBM.

Post-neurosurgical bacterial meningitis (PNBM) is one of the severe complications in patients receiving neurosurgical procedures. Recent studies have found microbe-related glycans play important roles in adhesion, invasion, and toxicity toward innate immunological reactions. In this study, we aimed to investigate the glycomic profile and its potential diagnostic efficacy in post-neurosurgical bacterial meningitis (PNBM) patients with hemorrhagic stroke. A total of 136 cerebrospinal fluid (CSF) samples were recruited and divided into a PNBM group and a non-PNBM group based on the clinical diagnostic criteria. A lectin biochip-based method was established for the detection of glycans in CSF. The clinicopathological data and biochemical parameters in CSF from all patients were analyzed. Two models for multivariate analysis investigating glycan changes in the CSF were conducted, aiming at determining the specific expression and diagnostic efficacy of lectin-probing glycans (LPGs) for PNBM. In univariate analysis, we found that 8 out of 11 LPGs were significantly correlated with PNBM. Model 1 multivariate analysis revealed that PNA (p = 0.034), Jacalin (p = 0.034) and LTL (p = 0.001) were differentially expressed in the CSF of PNBM patients compared with those of non-PNBM patients. Model 2 multivariate analysis further disclosed that LTL (p = 0.021) and CSF glucose (p < 0.001) had independent diagnostic efficacies in PNBM, with areas under the curve (AUC) of 0.703 and 0.922, respectively. In summary, this study provided a new insight into the subject of CSF glycomics concerning bacterial infection in patients with hemorrhagic stroke.

Usually the bi-layer MoS2 grown directly by chemical vapor deposition or exfoliated by mechanical method has an indirect band gap, which leads to poor optical property. In this work, we design and build the sandwich structure by stacking a bi-layer MoS2 with Au nanoparticles embedded in the adjacent layers. This structure shows a 45-fold enhancement in photoluminescence (PL) compared with the direct grown bi-layer MoS2. More importantly, the as-built bi-layer MoS2 area shows much stronger in the PL intensity than that of the monolayer MoS2 area. This work presents the optimized PL enhancement of this homogeneous MoS2 structure by the surface plasmon resonance (SPR) effect of the Au nanoparticles and the effect of direct bandgap bi-layer MoS2 structures via tuning the interlayer distance between the adjacent MoS2 layers.

【Abstract】Bronchobiliary fistula (BBF) is a rare condition in which there is a nonnatural communication be-tween the biliary tract and the bronchial trees. It is usually aroused by the complications of hepatic hydatidosis, he-patic amebic, biliary obstruction, trauma, neoplasm and he-patic abscess formation. In this paper, we described a pa-tient suffering from BBF that is secondary to trauma or surgery. Especially, BBF was detected in the left lung. Finally, we managed this case successfully without an open surgery. Key words: Bronchial fistula; Biliary fistula; Cholangiopancreatography, endoscopic retrograde; Endoscopy, gastrointestinal

We have studied the decomposition of methanol-d4 on thin film Al2O3/NiAl(100) under near-ambient-pressure conditions, with varied surface-probe techniques and calculations based on density-functional theory. Methanol-d4 neither adsorbed nor reacted on Al2O3/NiAl(100) at 400 K under ultrahigh vacuum conditions, whereas they dehydrogenated, largely to methoxy-d3 (CD3O*, * denoting adsorbates) and formaldehyde-d2 (CD2O*), on the surface when the methanol-d4 partial pressure was increased to 10−3 mbar and above. The dehydrogenation was facilitated by hydroxyl (OH* or OD*) from the dissociation of little co-adsorbed water; a small fraction of CD2O* interacted further with OH* (OD*) to form, via intermediate CD2OOH* (CD2OOD*), formic acid (DCOOH* or DCOOD*). A few surface carbonates were also yielded, likely on the defect sites of Al2O3/NiAl(100). The results suggest that alumina not only supports metal clusters but also participates in reactions under realistic catalytic conditions. One may consider accordingly the multiple functions of alumina while designing ideal catalysts. [ABSTRACT FROM AUTHOR]

Sudoku is an intelligence game that has fascinated many people. In addition to offering entertainment, it also attracts players to solve more challenging Sudoku questions. Sudoku novices tend to fail to focus on understanding the operation rules because the grid, words, and numbers of Sudoku are too complicated. The main purpose of this study is to integrate the concept of illustrations of labyrinthine multipath into the interface design of rules teaching of Sudoku to complete the learning design of Sudoku games. The research subjects were a total of 73 elementary school third graders in Miaoli County in Taiwan. The study used a single group pre-test and formal test design to investigate the difference in students' learning effectiveness of Sudoku rules before and after they played Sudoku games. This study used a self-developed ARCS learning motivation scale to analyze the effect of Sudoku game on students' learning motivation, and conducted in-depth interviews with three students with low learning achievement to observe their learning process and how their learning interest was aroused. The results showed that the Sudoku learning design with illustrations of labyrinthine multipath could help students understand Sudoku rules and enhance their learning interest in Sudoku.

The decomposition of methanol-d4 (CD3OD) on Rh nanoclusters grown by the deposition of Rh vapors onto an ordered thin film of Al2O3/NiAl(100) was studied, with various surface-probe techniques and largely under near-ambient-pressure (NAP) conditions. The results showed a superior reactivity of small Rh clusters (diameter < 1.5 nm) exposed to CD3OD at 5 × 10−3–0.1 mbar at 400 K; the gaseous production of CO and D2 from decomposed methanol-d4 per Rh surface site on the small Rh clusters with diameters of ∼1.1 nm was nearly 8 times that on large ones with diameters of ∼3.5 nm. The promotion of reactivity with decreased cluster size under NAP conditions was evidently greater than that under ultrahigh vacuum conditions. Moreover, the concentration of atomic carbon (C*; where * denotes adsorbate)—a key catalyst poisoner—yielded from the dissociation of CO* from dehydrogenated methanol-d4 was significantly smaller on small clusters (diameter < 1.5 nm). The NAP size effect on methanol-d4 decomposition involved the surface hydroxyl (OH*) from the little co-adsorbed water (H2O*) that was dissociated at a probability dependent on the cluster size. H2O* was more likely dissociated into OH* on small Rh clusters, by virtue of their more reactive d-band structure, and the OH* then effectively promoted the O–D cleavage of methanol-d4, as the rate-determining step, and thus the reaction probability; on the other hand, the OH* limited CO* dissociation on small Rh clusters via both adsorbate and lateral effects. These results suggest that the superior properties of small Rh clusters in both reactivity and anti-poisoning would persist and be highly applicable under "real-world" catalysis conditions. [ABSTRACT FROM AUTHOR]

Pt and Rh nanoclusters, grown on deposition of Pt and Rh vapors onto graphene/Pt(111), show separate reactivity toward the decomposition of methanol-d4. The Pt (Rh) clusters had a mean diameter 2.0–3.5 nm (2.1–4.0 nm) and height 0.45–0.94 nm (0.41–0.9 nm) evolving with the coverage; they were structurally ordered, having an fcc phase and growing in (111) orientation, and had lattice constants similar to their bulk values. Methanol-d4 on the Pt clusters did not decompose but desorbed mostly, disparate from that on Pt(111) surface; the disparity arose as the adsorption energies of methanol-d4 on most surface sites of the Pt clusters became smaller than their single crystal counterpart. This size effect, nevertheless, did not apply on the Rh clusters, despite their similar atomic stacking; the Rh clusters showed a reactivity similar to that of the Rh(111) surface because the adsorption energies of methanol-d4 on both Rh clusters and Rh(111) are comparable. The distinct size dependence was rationalized through their electronic structures and charge distribution of Fukui function mapping. Our results suggest that reactive transition metals do not necessarily become more reactive while they are scaled down to nanoscale; their reactivity evolves with their size in a manner largely dependent on their electronic nature. [ABSTRACT FROM AUTHOR]

To study the chemical constituents of Ludwigia octovalvis, the 80% ethanol extract from L. octovalvis was isolated by silica gel, Sephadex LH-20, Flash C18 and semi-preparative liquid chromatography, and the structures of obtained compounds were identified by physicochemical properties and spectral data. The cytotoxic activity of the isolates were evaluated by MTS method. The results were as follows: (1) Twenty compounds were isolated from L. octovalvis, and their structures were identified as (-)-lyoniresinol (1), 8,8′-bisdihydrosiringenin (2), 5-methoxy-(-)-isolariciresinol (3), (-)-isolariciresinol (4), 3,4′-di-O-methylellagic acid (5), 3,3′,4′-tri-O-methylellagic acid (6), 1,3,6-tri-O-galloyl-β-glucospyranose (7), corilagin (8), methyl gallate (9), ethyl gallate (10), terminaliate A (11), syringic acid (12), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (13), luteolin (14), kaempferol (15), 5,8-dihydroxy-7-methoxyflavone (16), nobiletin (17), tangeretin (18), α-tocopherolquinone (19), 5-O-(E)-p-coumaroyl quinic acid ethyl ester (20). Compounds 1-5, 7, 8, 11, 13, 16-20 were isolated from Ludwigia for the first time. Compounds 6, 9, 10, 12, 15 were isolated from this plant for the first time. (2) Compound 19 showed inhibitory activity against the leukemia HL-60 with the IC50 value of 10.31 μmol·L-1. Compounds 6-8, 19 showed inhibitory activity against the lung cancer cells A549 with the IC50 values of 25.82, 42.05, 36.94, 17.54 μmol·L-1, respectively. Compounds 6, 7, 11, 14, 19 showed inhibitory activity against the liver cancer SMMC-7721 with the IC50 values of 24.24, 26.35, 26.51, 33.34, 20.44 μmol·L-1, respectively. Compounds 6, 19 showed inhibitory activity against the breast cancer MDA-MB-231 with the IC50 values of 34.91, 21.13 μmol·L-1, respectively. Compounds 6, 7, 19 showed inhibitory activity against the colon cancer SW480 with the IC50 values of 36.03, 39.97, 5.52 μmol·L-1, respectively. The results of this study enrich the chemical constituents of L. octovalvis and provide a basis for the development of anti-tumor activity.

Resistance random access memory (RRAM) is considered a promising candidate for the next generation of non-volatile memory. In this work, we fabricate metal (Ag, Ti, or Pt)/ZnO/Pt RRAM cells and then systematically investigate the effects of different top electrodes and their performance. With the formation and rupture of Ag-bridge and the shapeless oxygen vacancy filaments under a series of positive and negative bias, the set and reset processes have been successfully conducted in the Ag/ZnO/Pt device with very low work voltage, high on-off ratio, and good endurance. When applying the voltage bias to the Ti/ZnO/Pt device, the interfacial oxygen ions’ migration causes the redox reaction of the conducting filament’s oxygen vacancies, leading to the formation and rupture of the conducting filaments but in a relatively poor endurance. At the same time, for the Pt/ZnO/Pt device, once the filaments in the functional layer consisting of oxygen vacancies are formed, it is difficult to disrupt, resulting in the permanent low resistance state after a forming-like process. The results demonstrated that the devices with a metallic conductive bridge mechanism show much better switching behaviors than those with an oxygen ion/vacancy filament mechanism. [ABSTRACT FROM AUTHOR]

Glucose is essential to the physiological processes of vertebrates. Mammalian physiological stability requires a relatively stable blood glucose level (~5 mM), whereas other vertebrates have greater flexibility in regulating blood glucose (0.5–25 mM). GCGR family receptors play an important role in vertebrate glucose regulation. Here, we examine the evolution of the GCGR family ligand-receptor systems in different species. Comparatively, we discover that the conserved sequences among GCG family ligands lead to the non-specific activation of ligands across species. In particular, we observe that glucagon-like peptide 1 receptor (GLP1R), glucagon-like peptide 2 receptor (GLP2R), and glucagon-like receptor (GCGLR, also called GCRPR) are arbitrarily activated by other members of the ligand family in birds. Moreover, we reveal that Gallus gallus GLP2 (gGLP2) effectively activates mammalian GLP1R and improves glucose tolerance in diabetic mice. Our study has important implications for understanding blood glucose stabilization in vertebrates and demonstrates that gGLP2 may be a potential drug for treating type 2 diabetes.