Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

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.

Evidence for an intra-tumoral microbiome in pituitary neuroendocrine tumors with different clinical phenotypes.

PURPOSE: Bacteria have been observed in the tumor environment for decades and have been demonstrated to play important roles in the pathogenesis and development of several different tumors. So far there is a clear lack of specific studies relating to the presence of bacteria in pituitary neuroendocrine tumors (PitNETs). METHODS: In this study, we performed five region-based amplification and bacterial 16 S rRNA sequencing to identify the microbiome of PitNET tissues across four clinical phenotypes. Multiple filter procedures were performed to inhibit the risk of contamination with bacteria and bacterial DNA. Histological analysis was also conducted to validate the localization of bacteria in the intra-tumoral region. RESULTS: We identified common and diverse bacterial types across the four clinical phenotypes of PitNET. We also predicted the potential functions of these bacteria in tumor phenotypes and found that these functions were reported in certain previous mechanistic studies. Our data indicate that the pathogenesis and development of tumors may correlate with the behavior of intra-tumoral bacteria. Histological results, including lipopolysaccharide (LPS) staining and fluorescence in situ hybridization (FISH) for bacterial 16 S rRNA clearly demonstrated the localization of bacteria in the intra-tumoral region. Staining for Iba-1 suggested that the proportion of microglia was more abundant in FISH-positive regions than in FISH-negative regions. Furthermore, in FISH-positive regions, the microglia exhibited a longitudinally branched morphology that was different to the compact morphology observed in FISH-negative regions. CONCLUSION: In summary, we provide an evidence for the existence of intra-tumoral bacteria in PitNET.

Design of a two-layer structure to significantly improve the performance of zinc oxide resistive memory.

Resistive random access memory (RRAM) is considered to be one of the important candidates for the next generation of memory devices. Zinc oxide resistive memory has also been studied for many years, but there are still some controversial topics and problems. Herein, an unusual resistance state has been observed in devices following the measurement and analysis of ZnO resistive memories with different thicknesses, a middle resistance state was speculated to explain the instability of ZnO RRAM. According to this speculation, a two-layer structure ZnO RRAM has been designed to significantly increase the device performance with the introduction of an HfO2 layer and the enhancement has also been explained based on the results of first-principles calculations.

HfO2-passivated black phosphorus field effect transistor with long-termed stability and enhanced current on/off ratio.

Enhanced on/off ratio, obvious threshold voltage left shift, newly emerging bipolar field effect performance and most importantly, excellent stability in ambient condition have been reported for the HfO2-passivated black phosphorus field effect transistors . Both Raman spectra and x-ray photoelectron spectroscopy (XPS) show a thickness reduction effect after HfO2 passivation, XPS further demonstrates that the formation of P-Hf and P-O chemical bonds contributes to the thinning of layered black phosphorus (BP), in which P-Hf bonds also provide chemical protection for BP flakes from degradation. Atomic force microscopy measures the thickness of the passivation layer and also verifies the stability of the passivated BP flakes.

Surface charge transfer doping of monolayer molybdenum disulfide by black phosphorus quantum dots.

Monolayer molybdenum disulfide (MoS2), consisting of covalently bonded S-Mo-S sandwiched layers, has high carrier mobility and a direct bandgap of 1.8 eV, offering properties for electronic and optoelectronic devices with high performance. Usually, it is essential to modulate the carrier concentrations and conductivities of monolayer MoS2 for practical applications. In this paper, black phosphorus (BP) quantum dots (QDs) were synthesized by a liquid exfoliation method successfully, and have a diameter of ∼5 nm as confirmed with a transmission electron microscope (TEM). BP QDs were utilized to decorate monolayer MoS2 grown by chemical vapor deposition (CVD). The Raman and PL spectra of the BP QD/MoS2 hybrid structure clearly indicate that BP QDs are an effective n-type doping scheme for monolayer MoS2. Back-gated monolayer MoS2 transistors were fabricated and show an improved source-drain current after BP QD modifications. A high electron concentration of ∼5.39 × 1012 cm-2 in monolayer MoS2 was achieved, which is beneficial for designing FETs and photodetector devices with novel functions.

T-antigen as a biomarker of progression-free survival in patients with glioblastoma.

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.

Clinical Value of Glycan Changes in Cerebrospinal Fluid for Evaluation of Post-Neurosurgical Bacterial Meningitis with Hemorrhagic Stroke Patients.

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.

Salivary microbiome profiles for different clinical phenotypes of pituitary adenomas by single-molecular long-read sequencing.

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.

Diagnosis of post-neurosurgical bacterial meningitis in patients with aneurysmal subarachnoid hemorrhage based on the immunity-related proteomics signature of the cerebrospinal fluid.

Introduction: Post-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. Methods: A 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. Results: We 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. Conclusion: In 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.

Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy.

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.

Quantitatively analyzing effects of meteorology and PM2.5 sources on low visual distance.

Low visual distance (0 to 10 km), a common pollution phenomenon, is a severe threat to the productivity and life of human society in China. In this study, we used the Positive Matrix Factorization model coupled with the Generalized Additive Model (PMF-GAM) to quantitatively analyze the effect of the meteorology and source emissions on visual distance. The results show that the relative importance of predictor variables is humidity and SN (sulfate and secondary organic carbon (SOC) plus nitrate) (H&SN, 69.14%), vehicle exhaust (VE, 13.5%), crustal dust (CD, 7.28%), temperature (T, 4.71%), coal combustion (CC, 4.08%), wind speed (WS, 1.08%) and atmospheric pressure (AP, 0.21%). Furthermore, the visual distance is higher when the humidity is lower (<20%), and the humidity with SN shows clear synergy effects when the humidity is higher (>60%).

Improvement in the quality of black phosphorus by selecting a mineralizer.

The low-cost synthesis of high-quality black phosphorus (BP) has always been a challenge. Herein, we selected different mineralizers to synthesize high-crystallinity BP by the chemical vapor transport (CVT) method and demonstrated that the use of Pb instead of Sn can lead to higher purity BP. Residual Sn in Sn-BP was confirmed by X-ray photoelectron spectroscopy (XPS), but no mineralizer impurity was observed in Pb-BP. The performance of FET devices showed that the hole mobility of Pb-BP was significantly higher than that of Sn-BP. On the other hand, the Pb-BP devices exhibited good bipolarity with the highest hole mobility of 523 cm2 V-1 s-1 at room temperature and electron mobility of up to 28 cm2 V-1 s-1.

Metal-assisted exfoliation of few-layer black phosphorus with high yield.

We introduce a metal-assisted exfoliation method to produce few-layer black phosphorus with the lateral size larger than 50 µm and the area 100 times larger than those exfoliated using the normal "scotch-tape" technique. Using a field effect transistor it was found the hole mobility is 68.6 cm2 V-1 s-1 and the current on/off ratio can reach about 2 × 105.

Source profiles and contributions of biofuel combustion for PM2.5, PM10 and their compositions, in a city influenced by biofuel stoves.

Source and ambient samples were collected in a city in China that uses considerable biofuel, to assess influence of biofuel combustion and other sources on particulate matter (PM). Profiles and size distribution of biofuel combustion were investigated. Higher levels in source profiles, a significant increase in heavy-biomass ambient and stronger correlations of K+, Cl-, OC and EC suggest that they can be tracers of biofuel combustion. And char-EC/soot-EC (8.5 for PM2.5 and 15.8 for PM10 of source samples) can also be used to distinguish it. In source samples, water-soluble organic carbon (WSOC) were approximately 28.0%-68.8% (PM2.5) and 27.2%-43.8% (PM10) of OC. For size distribution, biofuel combustion mainly produces smaller particles. OC1, OC2, EC1 and EC2 abundances showed two peaks with one below 1 µm and one above 2 µm. An advanced three-way factory analysis model was applied to quantify source contributions to ambient PM2.5 and PM10. Higher contributions of coal combustion, vehicular emission, nitrate and biofuel combustion occurred during the heavy-biomass period, and higher contributions of sulfate and crustal dust were observed during the light-biomass period. Mass and percentage contributions of biofuel combustion were significantly higher in heavy-biomass period. The biofuel combustion attributed above 45% of K+ and Cl-, above 30% of EC and about 20% of OC. In addition, through analysis of source profiles and contributions, they were consistently evident that biofuel combustion and crustal dust contributed more to cation than to anion, while sulfate & SOC and nitrate showed stronger influence on anion than on cation.