High-Performance Tin Oxide Thin-Film Transistors Realized by Codoping and Their Application in Logic Circuits.

Tin oxide is a promising channel material, offering the advantages of being low-cost and environmentally friendly and having a wide band gap. However, despite the high electron mobility of SnO2 in bulk, the corresponding thin-film transistors (TFTs) generally exhibit moderate performance, hindering their widespread application. Herein, we proposed a codoping strategy to improve both the electrical property and the stability of SnO2 TFTs. A comparative analysis between doped and undoped SnO2 was conducted. It is observed that taking advantage of the difference in ionic radii between two dopants (indium and gallium) and the tin ions in the host lattice can effectively reduce impurity-induced strain. Additionally, we investigated the effect of codoping content on SnO2 TFTs. The optimal codoped SnO2 (TIGO) TFTs demonstrate high performance, featuring a field-effect mobility of 15.9 cm2/V·s, a threshold voltage of 0.2 V, a subthreshold swing of 0.5 V/decade, and an on-to-off current ratio of 2.2 × 107. Furthermore, the devices show high stability under both positive and negative bias stress conditions with a small threshold voltage shift of 1.8 and -1.2 V, respectively. Utilizing the TIGO TFTs, we successfully constructed a resistor-loaded unipolar inverter with a high gain of 10.76. This study highlights the potential of codoped SnO2 TFTs for advanced applications in electronic devices.

Abnormal Fractional Amplitude of Low-Frequency Fluctuation as a Potential Imaging Biomarker for First-Episode Major Depressive Disorder: A Resting-State fMRI Study and Support Vector Machine Analysis.

Objective: Major depressive disorder (MDD) is a psychiatric disorder with serious negative health outcomes; however, there is no reliable method of diagnosis. This study explored the clinical diagnostic value of the fractional amplitude of low-frequency fluctuation (fALFF) based on the support vector machine (SVM) method for the diagnosis of MDD. Methods: A total of 198 first-episode MDD patients and 234 healthy controls were involved in this study, and all participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning. Imaging data were analyzed with the fALFF and SVM methods. Results: Compared with the healthy controls, the first-episode MDD patients showed higher fALFF in the left mid cingulum, right precuneus, and left superior frontal gyrus (SFG). The increased fALFF in these three brain regions was positively correlated with the executive control reaction time (ECRT), and the increased fALFF in the left mid cingulum and left SFG was positively correlated with the 17-item Hamilton Rating Scale for Depression (HRSD-17) scores. The SVM results showed that increased fALFF in the left mid cingulum, right precuneus, and left SFG exhibited high diagnostic accuracy of 72.92% (315/432), 71.76% (310/432), and 73.84% (319/432), respectively. The highest diagnostic accuracy of 76.39% (330/432) was demonstrated for the combination of increased fALFF in the right precuneus and left SFG, along with a sensitivity of 84.34% (167/198), and a specificity of 70.51% (165/234). Conclusion: Increased fALFF in the left mid cingulum, right precuneus, and left SFG may serve as a neuroimaging marker for first-episode MDD. The use of the increased fALFF in the right precuneus and left SFG in combination showed the best diagnostic value.

SIRT5 Represses Neurotrophic Pathways and Aß Production in Alzheimer's Disease by Targeting Autophagy.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in elderly individuals and characterized by impaired cognition and accumulation of ß-amyloid (Aß). Activating autophagy to clear Aß is a plausible approach for AD treatment. The levels of Aß and autophagy signaling factors in APP695/PS1-dE9 transgenic (APP/PS1) mice were detected by immuno histological analysis, real-time PCR, and the western blotting assay. The progression of AD was determined by Aß levels, activated neurons (MAP2+), and microglia (Iba-1+). The learning ability was measured using a Morris water maze. Reactive oxygen species (ROS) production, malondialdehyde (MDA) levels, and mitochondrial superoxide dismutase (SOD) activity were checked to determine oxidative stress. AD mice exhibited impaired autophagy and a decreased level of SIRT5. SIRT5 overexpression promoted autophagy, manifested by elevated Becn1 and ratio of LC3b-II/I, as well as suppressed oxidative stress. The SIRT5-ameliorated neuron damage was correlated with suppressed activation of microglia and astrocytes. Elevated SIRT5 expression decreased the inflammation in AD brains and neurons. Inhibition of autophagy abolished the protective role of SIRT5 in neurons during AD. Our findings suggested that SIRT5 overexpression could ameliorate the progression of AD both in vitro and in vivo through activating autophagy. We presented ectopic expression of SIRT5 as a promising therapeutic approach for AD.

MALAT1 Regulated mTOR-Mediated Tau Hyperphosphorylation by Acting as a ceRNA of miR144 in Hippocampus Cells Exposed to High Glucose.

AIM: High glucose (HG)-induced activation of mTOR promotes tau phosphorylation and leads to diabetes-associated dementia. This study aimed to explore the role of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in HG-induced neuronal cell injury. METHODS: Hippocampus cells were isolated from C57BL/6J mice. After 6 days of culture, the cells were incubated with 5.5 mM glucose in normal medium or 75 mM glucose for 4 days. Cells were transfected with miR-144 mimic, miR-144 inhibitor, siRNA for MALAT1 or corresponding controls. Gene expression was detected by PCR and Western blot analysis. RESULTS: HG increased the levels of MALAT1 and p-tau in hippocampal cells. Knockdown of MALAT1 partially reversed the effects of HG on mTOR activity and p-tau protein levels. MALAT1 functioned as competing endogenous RNA (ceRNA) for miR-144, and pre-treatment with MALAT1 siRNA decreased mTOR activity and p-tau protein level in HG-treated hippocampal cells, which was significantly attenuated by miR-144 mimics. Moreover, miR-144 negatively regulated the expression of mTOR and knockdown of MALAT1 suppressed mTOR, while overexpression of mTOR abrogated protective effects of MALAT1 knockdown in HG-treated hippocampal cells. CONCLUSION: MALAT1 knockdown prevented HG-induced mTOR activation and inhibited tau phosphorylation. MALAT1 may be a therapy target for diabetes associated dementia.

Association of LDL-C/HDL-C Ratio With Stroke Outcomes Within 1 Year After Onset: A Hospital-Based Follow-Up Study.

Stroke remains a leading cause of death and disability. The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C ratio) ratio has been confirmed to be a predictor of stroke. However, few studies have assessed the prognostic impact of the LDL-C/HDL-C ratio for stroke patients. We aimed to investigate the relationship between the LDL-C/HDL-C ratio and the prognosis following stroke in Chinese patients. A total of 3,410 patients who had experienced their first ischemic stroke was recruited to this study within 72 h of stroke onset. The patients were followed for at least 12 months. A multivariate regression analysis was used to assess the association between the LDL-C/HDL-C ratio and prognosis following stroke. We considered the LDL-C/HDL-C ratio as a continuous variable and stratified patients according to the LDL-C/HDL-C ratio quartile. A higher LDL-C/HDL-C ratio was associated with lower rates of death, recurrence, and moderate disability (defined as a modified Rankin scale score >2) at 3 months. Using group 1 as the reference group, the relative risk (RRs) at 3 months for death were 0.45 (95% confidence interval [CI]: 0.27, 0.77) for group 2, 0.58 (95% CI: 0.34, 0.98) for group 3, and 0.97 (95% CI: 0.60, 1.56) for group 4; for recurrence, the RRs were 0.75 (95% CI: 0.56, 0.99) for group 2, 0.65 (95% CI: 0.48, 0.89) for group 3, and 0.55 (95% CI: 0.39, 0.78) for group 4; and for moderate disability, the RRs were 0.74 (95% CI: 0.55, 0.99) for group 2, 0.65 (95% CI: 0.47, 0.89) for group 3, and 0.55 (95% CI: 0.39, 0.77) for group 4. At 12 months, patients in group 2 were the most protected against ischemic stroke death (RR: 0.57; 95% CI: 0.34, 0.95). However, there were no associations between the LDL-C/HDL-C ratio and stroke recurrence or moderate disability. A higher LDL-C/HDL-C ratio was found to protect against death, recurrence, and moderate disability at 3 months. However, there was no significant association between the LDL-C/HDL-C ratio and stroke recurrence or moderate disability at 12 months. These results nonetheless suggest that a higher LDL-C/HDL-C ratio was associated with short-term stroke prognosis.

Maresin1 Decreased Microglial Chemotaxis and Ameliorated Inflammation Induced by Amyloid-ß42 in Neuron-Microglia Co-Culture Models.

Inflammation resolution is regulated by specialized pro-resolving lipid mediators (SPMs) and the levels of SPMs are found decreased in Alzheimer's disease (AD) brain. We have previously found that one of the SPMs, Maresin1 (MaR1), improved neuronal survival and increase microglial phagocytosis of amyloid-ß 1-42 (Aß42); however, the mechanisms underlying the protective mechanism remain further investigation. We aim to investigate the effects of MaR1 on microglial chemotaxis and activation in this study. Both indirect and direct primary neuron and microglia co-culture system was used in this study. Our results showed MaR1 downregulated the increased microglial chemotaxis induced by Aß42. The microglial inactivation marker CD200R was downregulated by Aß42 and upregulated by MaR1. Pro-inflammatory cytokines secretion such as tumor necrosis factor (TNF)-α were increased by Aß42 and these changes were revised by MaR1 treatment. In addition, the levels of chemokine monocyte chemoattractant protein (MCP)-1 were increased while the levels of anti-inflammatory factor IL-10 secretion were decreased by Aß42, and these changes were abolished by MaR1 treatment. Moreover, by proteomics analysis, we identified cell signaling pathways affected by MaR1 were not only limited to inflammation-related pathways such as P38, but also in pathways involved in cell survival, autophagy, axon formation, and apoptosis, including PI3K/AKT, mTOR, ERK, caspase3, Cdc42, and p75NTR. In conclusion, MaR1 promoted inflammation resolution by inhibiting chemotaxis and regulating activation of microglia. MaR1 played a neuroprotective role by affecting cell signaling pathways involving inflammation, cell survival, autophagy, axon formation, and apoptosis inhibition.

Maresin 1 Improves Cognitive Decline and Ameliorates Inflammation in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative disease. Accumulating evidences suggest an active role of inflammation in the pathogenesis of AD. Inflammation resolution is an active process that terminates inflammation and facilitates the restoration of inflamed tissue to homeostasis. Resolution of inflammation has been shown to be conducted by a group of specialized pro-resolving lipid mediators (SPMs) including lipoxins, resolvins, protectins, and maresins (MaRs). Recent studies have demonstrated that failure of inflammation resolution can lead to chronic inflammation and, hence, contribute to AD progression. We have previously shown that MaR1 can improve neuronal survival and increase microglial phagocytosis of Aß. However, the effects of MaR1 on animal models of AD have not been reported. In this study, we aim to investigate the effects of MaR1 on behavioral deficits and pathological changes in a mouse model of AD. Mice received bilateral injections of Aß42 protein into the hippocampus, followed by administration of MaR1 by intra-cerebroventricular injection. The behavioral changes in the mice were analyzed using Morris water maze. Immunohistochemistry, Fluoro-Jade B (FJB) staining, cytometric beads array (CBA), and western blot analysis were used to demonstrate molecular changes in the mice hippocampus and cortex. Our results showed that MaR1 treatment significantly improved the cognitive decline, attenuated microglia and astrocyte activation. In addition, we found that MaR1 decreased the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1 production induced by Aß42 and increased the anti-inflammatory cytokines IL-2, IL-10 secretion with or without Aß42 stimulation. Moreover, western blot results showed that MaR1 up-regulated the levels of proteins related to survival pathway including PI3K/AKT, ERK and down-regulated the levels of proteins associated with inflammation, autophagy, and apoptosis pathways such as p38, mTOR and caspase 3. To conclude, MaR1 improved the cognitive decline, ameliorated pro-inflammatory glia cells activation via improving survival, enhancing autophagy, inhibiting inflammation and apoptosis pathways. In conclusion, this study shows that inflammation resolution may be a potential therapeutic target for AD.

Antitumor Effects of Berberine on Gliomas via Inactivation of Caspase-1-Mediated IL-1ß and IL-18 Release.

Gliomas arise in the glial cells of the brain or spine and are the most prevalent and devastating type of brain tumors. Studies of tumor immunology have established the importance of the tumor micro-environment as a driver of oncogenesis. Inflammatory mediators such as IL-1ß and IL-18 released by monocytes regulate transcriptional networks that are required for malignant cell growth. Berberine is a natural botanical alkaloid that is widely found in the Berberis species. Although it has been widely used as an anti-diarrheal treatment in North America for several decades, our study is the first to investigate berberine as an anti-tumor agent in glioma cells. In this study, we demonstrate that berberine significantly inhibits inflammatory cytokine Caspase-1 activation via ERK1/2 signaling and subsequent production of IL-1ß and IL-18 by glioma cells. Moreover, we found that berberine treatment led to decreased motility and subsequently cell death in U251 and U87 cells. In addition, our study is the first to indicate that berberine can reverse the process of epithelial-mesenchymal transition, a marker of tumor invasion. Taken together, our work supports berberine as a putative anti-tumor agent targeting glioma cells.

Roles of Specialized Pro-Resolving Lipid Mediators in Cerebral Ischemia Reperfusion Injury.

Ischemic stroke contributes to ~80% of all stroke cases. Recanalization with thrombolysis or endovascular thrombectomy are currently critical therapeutic strategies for rebuilding the blood supply following ischemic stroke. However, recanalization is often accompanied by cerebral ischemia reperfusion injury that is mediated by oxidative stress and inflammation. Resolution of inflammation belongs to the end stage of inflammation where inflammation is terminated and the repair of damaged tissue is started. Resolution of inflammation is mediated by a group of newly discovered lipid mediators called specialized pro-resolving lipid mediators (SPMs). Accumulating evidence suggests that SPMs decrease leukocyte infiltration, enhance efferocytosis, reduce local neuronal injury, and decrease both oxidative stress and the production of inflammatory cytokines in various in vitro and in vivo models of ischemic stroke. In this review, we summarize the mechanisms of reperfusion injury and the various roles of SPMs in stroke therapy.

Onjisaponin B (OB) is Neuroprotective During Cognitive Loss Through Immune-mediated and SIRT1 Pathways.

BACKGROUND: The purpose of the present study was to investigate the effects of Onjisaponin B (OB) in lipopolysaccharide (LPS)-induced cognitive deficits. METHODS: The rats were divided into four groups: sham group, LPS group (the model group), LPS + OB (1 mg/kg) group and LPS + OB (2 mg/kg) group. OB was treated three days before surgery and thereafter continuously for 7 days. Three days later, rats were intracerebroventricularly injected with LPS. The levels of inflammatory cytokines and the capability of free radical scavenging in serum and hippocampus were determined after the LPS challenge. PC12 cells were divided into control group, LPS group (the model group), LPS + OB (10 µM) group, LPS + OB (20 µM) group, LPS + OB (40 µM) group, LPS + OB (2 mg/kg) + nicotinamide group. The cell viability was measured by MTT assay. The protein expressions of Sirt1, p-AMPK, AMPK, Nrf-2, HO-1, Bcl-2, Bax, caspase-9, caspase-3, p-IκBα, IκBα, p-NF-κBp65 and NF-κBp65 were detected by western blot analysis. RESULTS: As a result, OB administration effectively relived the cognitive impairment, reduced the contents of IL-1ß, IL-6, TNF-α, MDA and restored SOD activities of SOD in serum and hippocampus of LPS-induced rats. Furthermore, OB treatment improved cell viability, ameliorated the alterations of IL-1ß, IL-6, TNF-α, MDA and SOD in the supernatant of LPS-induced PC12 cells. Of note, the expressions of Sirt1, Nrf-2, HO-1, Bcl-2 and p-AMPK were downregulated, while Bax, caspase-9, caspase-3 and the phosphorylations of IκBα and NF-κBp65 in the LPS-stimulated hippocampus and PC12 cells were increased attributed to the LPS stimulation. Nevertheless, the conditions were significantly attenuated by OB treatment. In the LPS-induced PC12 cell, nicotinamide, a SIRT1 inhibitor, abrogated the beneficial effects of OB, as indicated by the antioxidant, anti-inflammatory and anti-apoptosis signaling. CONCLUSION: Based on the above evidence, our results demonstrated that OB was a potential therapeutic candidate for LPS-induced cognitive deficits.

Circulating Memory T Follicular Helper Cells in Patients with Neuromyelitis Optica/Neuromyelitis Optica Spectrum Disorders.

OBJECTIVE: This study aimed to examine the potential role of memory T follicular helper (Tfh) cells in patients with neuromyelitis optica/neuromyelitis optica spectrum disorders (NMO/NMOSD). METHODS: The percentages of different subsets of circulating memory Tfh cells in 25 NMO/NMOSD patients before and after treatment as well as in 17 healthy controls were examined by flow cytometry. The levels of IL-21 and AQP4 Ab in plasma and CSF were measured by ELISA. RESULTS: The percentages and numbers of circulating memory Tfh cells, ICOS(+), CCR7(-), CCR7(-)ICOS(+), CCR7(+), CCR7(+)ICOS(+) memory Tfh cells, and the levels of IL-21 in plasma and CSF were significantly increased in NMO/NMOSD patients. The percentages of CCR7(-) and CCR7(-)ICOS(+) memory Tfh cells were positively correlated with ARR, plasma IL-21, and AQP4 Ab levels. The percentages of CCR7(+) and CCR7(+)ICOS(+) memory Tfh cells were positively correlated with CSF white blood cell counts, proteins, and IL-21 levels. Treatment with corticosteroids significantly reduced the numbers of CCR7(-)ICOS(+) and CCR7(+)ICOS(+) memory Tfh cells as well as plasma IL-21 levels in patients with partial remission. CONCLUSIONS: Our findings indicate that circulating memory Tfh cells may participate in the relapse and development of NMO/NMOSD and may serve as a new therapeutic target.

Value of higher-resolution MRI in assessing middle cerebral atherosclerosis and predicting capsular warning syndrome.

PURPOSE: To investigate the correlation between middle cerebral atherosclerosis and capsular warning syndrome (CWS) and assess the value of higher-resolution magnetic resonance imaging (MRI) in prognostication. MATERIALS AND METHODS: In all, 97 transient ischemic attack (TIA) patients who underwent an MRI from February 2010 to December 2013 were included in the retrospective study and divided into either a CWS or middle cerebral artery (MCA) TIA group according to their eventual clinical diagnosis. 3T MRI included fast-spin echo T2 -weighted imaging, double-inverse recovery T1 -weighted imaging, and T1 contrast-enhanced scan sequences. Baseline characteristics, MRI results in terms of MCA plaque formation, plaque characteristics such as enhancement, and development of infarction were compared between the two groups to study the distribution and characteristics of cerebral atherosclerotic plaques. Multivariate analysis identified factors associated with infarction 1 week after plaque identification. RESULTS: Based on the MR images, 76% of both groups of patients had middle cerebral atherosclerosis. Compared to TIA patients, the median age of CWS patients was younger (58 [range 42-73] vs. 67 [36-84] years, P = 0.003), and CWS patients had a lower rate of stroke history (10.9% vs. 41.2%, P = 0.001). Infarction was more common in CWS patients than in TIA patients (52.2% vs. 20.5%, P = 0.003) and a superior plaque was correlated with infarction occurrence (odds ratio 5.674, 95% confidence interval 1.112-28.958). CONCLUSION: Patients with CWS have large arterial plaques, including MCA plaques. There was a correlation between CWS and the MCA plaque location. J. Magn. Reson. Imaging 2016;44:1277-1283.

Intraepidermal nerve fiber density of healthy human.

OBJECTIVES: To analyze intraepidermal nerve fiber density (IEFND) by skin biopsy, evaluate the effect of age, anatomical sites, and ethnic origin on IEFND and develop a reference range of IENFD at the distal leg of healthy human. METHODS: Seventy skin biopsy specimens from surgical procedures involving 70 patients were analyzed. Specimens were fixed routinely in formalin and thereafter embedded in paraffin. Nerve fibers of 10-µm-thick sections were observed using immunoperoxidase staining with panaxonal antibody protein gene product 9·5 (PGP 9·5). The morphology of intraepidermal nerve fibers (IENFs) and the IENFD was determined using light microscope. The statistical analysis was performed with SPSS 16·0 software. RESULTS: No significant correlation was observed between IENFD and age (Pwrist  =  0·830, Pdistal leg  =  0·478). The significant correlation was observed between IENFD and anatomic site (P  =  0·001), the IENFD of upper arm and proximal thigh were significantly higher than that of wrist and distal leg. The reference range for IENFD of distal leg in normal Chinese humans was 40·55 fibers/mm(2). The IEFND of Chinese healthy human was significantly lower than that of Finnish (62·87 ± 15·25 vs 114·617 ± 32·322 fibers/mm(2), P < 0·05). DISCUSSION: Skin biopsy may be a useful tool in sensory neuropathies. IENFD is independent of age, but varies in different parts of the body. The proximal sites have a higher IENFD, but no significant difference is found between the wrist and distal leg.

Poplar plantation has the potential to alter the water balance in semiarid Inner Mongolia.

Poplar plantation is the most dominant broadleaf forest type in northern China. Since the mid-1990s plantation was intensified to combat desertification along China's northwestern border, i.e., within Inner Mongolia (IM). This evoked much concern regarding the ecological and environmental effects on areas that naturally grow grass or shrub vegetation. To highlight potential consequences of large-scale poplar plantations on the water budget within semiarid IM, we compared the growing season water balance (evapotranspiration (ET) and precipitation (PPT)) of a 3-yr old poplar plantation (Kp(3)) and a natural shrubland (Ks) in the Kubuqi Desert in western IM, and a 6-yr old poplar plantation (Bp(6)) growing under sub-humid climate near Beijing. The results showed that, despite 33% lower PPT at Kp(3), ET was 2% higher at Kp(3) (228 mm) as compared with Ks (223 mm) in May-September 2006. The difference derived mainly from higher ET at the plantation during drier periods of the growing season, which also indicated that the poplars must have partly transpired groundwater. Estimated growing season ET at Bp(6) was about 550 mm and more than 100% higher than at Kp(3). It is estimated that increases in leaf area index and net radiation at Kp(3) provide future potential for the poplars in Kubuqi to exceed the present ET and ET of the natural shrubland by 100-200%. These increases in ET are only possible through the permanent use of groundwater either directly by the trees or through increased irrigation. This may significantly change the water balance in the area (e.g., high ET at the cost of a reduction in the water table), which renders large-scale plantations a questionable tool in sustainable arid-land management.