Controllable preparation of graphene glass fiber fabric towards mass production and its application in self-adaptive thermal management.

Direct synthesis of graphene on nonmetallic substrates via chemical vapor deposition (CVD) has become a frontier research realm targeting transfer-free applications of CVD graphene. However, the stable mass production of graphene with a favorable growth rate and quality remains a grand challenge. Herein, graphene glass fiber fabric (GGFF) was successfully developed through the controllable growth of graphene on non-catalytic glass fiber fabric, employing a synergistic binary-precursor CVD strategy to alleviate the dilemma between growth rate and quality. The binary precursors consisted of acetylene and acetone, where acetylene with high decomposition efficiency fed rapid graphene growth while oxygen-containing acetone was adopted for improving the layer uniformity and quality. Notably, the bifurcating introducing-confluent premixing (BI-CP) system was self-built for the controllable introduction of gas and liquid precursors, enabling the stable production of GGFF. GGFF features solar absorption and infrared emission properties, based on which the self-adaptive dual-mode thermal management film was developed. This film can automatically switch between heating and cooling modes by spontaneously perceiving the temperature, achieving excellent thermal management performances with heating and cooling power of ∼501.2 and ∼108.6 W m-2, respectively. These findings unlock a new strategy for the large-scale batch production of graphene materials and inspire advanced possibilities for further applications.

Arctigenin derivative A-1 ameliorates motor dysfunction and pathological manifestations in SOD1G93A transgenic mice via the AMPK/SIRT1/PGC-1α and AMPK/SIRT1/IL-1ß/NF-κB pathways.

AIM: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized muscle atrophy, paralysis, and even death. Mitochondrial damage and neuroinflammation play key roles in the pathogenesis of ALS. In the present study, the efficacy of A-1, a derivative of arctigenin with AMP-activated protein kinase (AMPK) and silent information regulator 1 (SIRT1) activation for ALS, was investigated. METHODS: A-1 at 33.3 mg/kg was administrated in SOD1G93A transgenic mice orally from the 13th week for a 6-week treatment period. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes, and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl, and immunohistochemistry staining. Protein expression was detected with proteomics analysis, Western blotting, and ELISA. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. RESULTS: A-1 administration in SOD1G93A mice enhanced mobility, decreased skeletal muscle atrophy and fibrosis, mitigated loss of spinal motor neurons, and reduced glial activation. Additionally, A-1 treatment improved mitochondrial function, evidenced by elevated ATP levels and increased expression of key mitochondrial-related proteins. The A-1 treatment group showed decreased levels of IL-1ß, pIκBα/IκBα, and pNF-κB/NF-κB. CONCLUSIONS: A-1 treatment reduced motor neuron loss, improved gastrocnemius atrophy, and delayed ALS progression through the AMPK/SIRT1/PGC-1α pathway, which promotes mitochondrial biogenesis. Furthermore, the AMPK/SIRT1/IL-1ß/NF-κB pathway exerted neuroprotective effects by reducing neuroinflammation. These findings suggest A-1 as a promising therapeutic approach for ALS.

Screening of co-expressed genes in hypopharyngeal carcinoma with esophageal carcinoma based on RNA sequencing and Clinical Research.

To explore the hub comorbidity genes and potential pathogenic mechanisms of hypopharyngeal carcinoma with esophageal carcinoma, and evaluate their diagnostic value for hypopharyngeal carcinoma with co-morbid esophageal carcinoma. We performed gene sequencing on tumor tissues from 6 patients with hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma (hereafter referred to as "group A") and 6 patients with pure hypopharyngeal squamous cell carcinoma (hereafter referred to as "group B"). We analyzed the mechanism of hub genes in the development and progression of hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma through bioinformatics, and constructed an ROC curve and Nomogram prediction model to analyze the value of hub genes in clinical diagnosis and treatment. 44,876 genes were sequenced in 6 patients with group A and 6 patients with group B. Among them, 76 genes showed significant statistical differences between the group A and the group B.47 genes were expressed lower in the group A than in the group B, and 29 genes were expressed higher. The top five hub genes were GABRG2, CACNA1A, CNTNAP2, NOS1, and SCN4B. GABRG2, CNTNAP2, and SCN4B in the hub genes have high diagnostic value in determining whether hypopharyngeal carcinoma patients have combined esophageal carcinoma (AUC: 0.944, 0.944, 0.972). These genes could possibly be used as potential molecular markers for assessing the risk of co-morbidity of hypopharyngeal carcinoma combined with esophageal carcinoma.

FT4-to-FT3 ratio is a novel prognostic marker in subacute combined spinal cord degeneration patients.

Objectives: The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD. Methods: This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC). Results: About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, P < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; P < 0.001). Conclusions: We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.

Explore the pharmacological basis of ShengJiYiSui decoction in the treatment of amyotrophic lateral sclerosis based on network pharmacology and molecular docking technology.

Neurodegenerative illnesses have long been handled clinically by traditional Chinese medicine. This study is the first time to explore the pharmacological basis of application in amyotrophic lateral sclerosis (ALS) through network pharmacology and molecular docking techniques. In the present investigation, the TCMSP database and HIT2 database were examined for 9 TCM constituents of Sheng Ji Yu Sui Decoction (SJYSD), and the desired sites for the components were searched in the Drugbank database. and the Sjysd-target network was constructed. Associated targets for Amyotrophic lateral sclerosis (ALS) were then retrieved and collected in the OMIM, TTD, Genecards and DisGeNET databases. Protein-protein interaction and enrichment analysis were performed for the common targets of drugs and diseases, and molecular anchoring for the chosen core targets and related molecules was carried out. The results showed that SJYSD had 100 active compounds corresponding to 598 targets. ALS has a total of 5,325 genes. SJYSD and ALS share 163 genes, and these targets involve PI3K-AKT signaling, p53 signaling and IL-17 signaling, etc. The core components of luteolin and quercetin were discovered and may be used to treat ALS by regulating PI3K-AKT signaling pathway by HSP90AB1 protein.

Effect of CADM1 on TPF-induced chemotherapy in laryngeal squamous cell carcinoma.

OBJECTIVES: To explore the relationship between CADM1 expression and sensitivity to TPF-induced chemotherapy in laryngeal squamous cell carcinoma (LSCC) patients, then investigate its potential mechanisms. METHODS: Differential CADM1 expression was examined in chemotherapy-sensitive and chemotherapy-insensitive LSCC patient samples after TPF-induced chemotherapy using microarray analysis. Receiver operating characteristic (ROC) curve analysis and bioinformatics approaches were used to investigate the diagnostic value of CADM1. Small interfering RNAs (siRNAs) were used to knock down CADM1 expression in an LSCC cell line. Differential CADM1 expression was compared by qRT-PCR assays in 35 LSCC patients treated with chemotherapy, including 20 chemotherapy-sensitive and 15 chemotherapy-insensitive patients. RESULTS: Public database and primary patient data both suggest that CADM1 mRNA is expressed at lower levels in chemotherapy-insensitive LSCC samples, suggesting its potential usefulness as a biomarker. Knockdown of CADM1 with siRNAs led to decreased sensitivity of LSCC cells to TPF chemotherapy. CONCLUSIONS: Upregulation of CADM1 expression can alter the sensitivity of LSCC tumors to TPF induction chemotherapy. CADM1 is a possible molecular marker and therapeutic target for induction chemotherapy in LSCC patients.

Alginate foam gel modified by graphene oxide for wound dressing.

Recently, hydrogel dressings have been rapidly developed for wound healing. However, it is still a huge challenge to endow hydrogel wound dressings with excellent hemostatic performance. Here, a new wound treatment material, foam gel wound dressing, is reported, which possesses rapid hemostasis and antibacterial properties. The foam gel dressing is composed of chitooligosaccharide modified graphene oxide (CG) nanocomposites and calcium alginate foam substrate. In this system, CG has a strong interaction with platelets, which is helpful for rapid hemostasis. So the wound dressing could stop bleeding quickly within 10 s. Meanwhile, CG also provides excellent antibacterial properties to dressings, which is conducive to wound healing. Full-thickness wound healing experiments showed that compared with blank control and CG-free foam gel dressings, CG-loaded foam gel dressings shows better healing properties, and the wounds covered with them are almost completely healed within 12 days. In addition, histological morphology analysis displays CG-loaded wound dressing could significantly accelerate wound healing by reducing the inflammatory response and promoting vascular remodeling. This unique strategy provides a simple and practical method for the clinical application of the next generation of wound dressings.

Biocompatible Carboxymethyl Chitosan/GO-Based Sponge to Improve the Efficiency of Hemostasis and Wound Healing.

Sponges with highly absorptive properties have been widely used in emergency hemostasis. Graphene oxide (GO) has been extensively investigated in biomedical applications and is a promising candidate for hemostatic sponges. However, GO has been demonstrated to have adverse effects on the human body. To overcome this problem, a hemostatic sponge based on modified GO and carboxymethyl chitosan (CMCS) is successfully prepared, which has excellent water absorption ability and mechanical strength. Importantly, hemostasis assays showed that the composite sponge exhibited high hemostatic efficiency, and the possible hemostatic mechanism is also discussed in this study. Moreover, the results of in vitro antibacterial tests reveal that the composite sponge also presents strong antimicrobial effects against Staphylococcus aureus and Escherichia coli. Significantly, the composited sponge used as hemostatic dressing can effectively promote cell proliferation, achieving a wound closure rate of 95% on day 12. Such a graphene-based sponge with multiple advantageous features would hold broad prospects in the hemostatic field.

Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions. Here we produced cytotoxic amyloid fibrils from full-length apo human SOD1 under reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofilament with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3-55) and C-terminal segment (residues 86-153) with an intrinsic disordered segment. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight ß-strands (to form a ß-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen ß-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states.

Experimental and Theoretical Studies of Ultrafine Pd-Based Biochar Catalyst for Dehydrogenation of Formic Acid and Application of In Situ Hydrogenation.

In this work, a novel "foaming" strategy uses sodium bicarbonate (NaHCO3) and ammonium oxalate ((NH4)2C2O4) as the foaming agent, turning biomass-derived carboxymethyl cellulose (CMC) into N-doped porous carbon. Highly active palladium nanoparticles (Pd NPs) immobilized on nitrogen-doped porous carbon (Pd@MC(2)-P) are produced through a phosphate-mediation approach. The phosphoric acid (H3PO4) becomes the key to the synthesis of highly dispersed ultrafine Pd NPs on active Pd-cluster-edge (the edge of the Pd-cluster-100 and Pd-cluster-111 surfaces). The Pd@MC(2)-P exhibits high activity for formic acid (FA) dehydrogenation with an initial TOFg of 971 h-1 at room temperature. The subsequent hydrogenation of phenol using FA as an in situ hydrogen source on Pd@MC(2)-P and the highly efficient hydrogenation of phenol to cyclohexanone reaches more than 90% selectivity and 80% conversion. Density functional theory (DFT) calculations reveal that the reduced H poisoning and more exposed (100) surface over Pd nanoparticles are the keys to the Pd nanoparticles' high activity.

Characteristics of Anti-Contactin1 Antibody-Associated Autoimmune Nodopathies With Concomitant Membranous Nephropathy.

Background: The concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN. Methods: We detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathy via double immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodies via enzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics. Results: A 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43-78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels. Conclusion: The age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.

Loganin substantially ameliorates molecular deficits, pathologies and cognitive impairment in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease threatening the health of the elderly, but the available therapeutic and preventive drugs remain suboptimal. Loganin, an iridoid glycoside extracted from Cornus officinalis, is reported to have anti-inflammatory and memory-enhancing properties. This study is aimed to explore the influence of loganin on cognitive function in 3xTg-AD mice and the underlying mechanism associated with its neuroprotection. According to the results of behavioral tests, we found that administration of loganin could significantly alleviate anxiety behavior and improve memory deficits of 3xTg-AD mice. Furthermore, immunohistochemical analysis displayed that there were decreased Aß deposition in the hippocampus and cortex of 3xTg-AD mice treated with loganin compared with the control mice. Importantly, the Aß-related pathological change was mainly involved in altering APP expression and processing. And loganin was also found to reduce the levels of phosphorylated tau (i.e. pTauS396 and pTauS262) in 3xTg-AD mice. By performing 2D-DIGE combined with MALDI-TOF-MS/MS, we revealed 28 differentially expressed proteins in the 3xTg-AD mice treated with loganin compared with the control mice. Notably, 10 proteins largely involved in energy metabolism, synaptic proteins, inflammatory response, and ATP binding were simultaneously detected in 3xTg-AD mice compared to WT mice. The abnormal changes of energy metabolism (PAGM1 and ENO1), synaptic proteins (SYN2 and Cplx2), inflammatory response (1433Z) were verified by western blot. Overall, our study suggested that loganin could be used as a feasible candidate drug to ameliorate molecular deficits, pathologies and cognitive impairment for prevention and treatment of AD.

Tetramethylpyrazine Improves Cognitive Impairment and Modifies the Hippocampal Proteome in Two Mouse Models of Alzheimer's Disease.

Alzheimer's disease (AD), one of the most common neurodegenerative diseases, has no effective treatment. We studied the potential effects of tetramethylpyrazine (TMP), an alkaloid in the rhizome of Ligusticum chuanxiong Hort. used in Traditional Chinese Medicine (chuanxiong) to treat ischemic stroke, on AD progression in two AD mouse models. Eight-month-old 3xTg-AD mice received TMP treatment (10 mg/kg/d) for 1 month, and 4-month-old APP/PS1-AD mice received TMP treatment (10 mg/kg/d) for 2 months. Behavioral tests, including step-down passive avoidance (SDA), new object recognition (NOR), Morris water maze (MWM), and Contextual fear conditioning test showed that TMP significantly improved the learning and memory of the two AD-transgenic mice. In addition, TMP reduced beta-amyloid (Aß) levels and tau phosphorylation (p-tau). Venny map pointed out that 116 proteins were commonly changed in 3xTg mice vs. wild type (WT) mice and TMP-treated mice vs. -untreated mice. The same 130 proteins were commonly changed in APP/PS1 mice vs. WT mice and TMP-treated mice vs. -untreated mice. The functions of the common proteins modified by TMP in the two models were mainly involved in mitochondrial, synaptic, cytoskeleton, ATP binding, and GTP binding. Mitochondrial omics analysis revealed 21 and 20 differentially expressed mitochondrial proteins modified by TMP in 3xTg-AD mice and APP/PS1 mice, respectively. These differential proteins were located in the mitochondrial inner membrane, mitochondrial outer membrane, mitochondrial gap, and mitochondrial matrix, and the function of some proteins is closely related to oxidative phosphorylation (OXPHOS). Western-blot analysis confirmed that TMP changed the expression of OXPHOS complex proteins (sdhb, ndufa10, uqcrfs1, cox5b, atp5a) in the hippocampus of the two AD mice. Taken together, we demonstrated that TMP treatment changed the hippocampal proteome, reduced AD pathology, and reduced cognitive impairment in the two AD models. The changes might be associated with modification of the mitochondrial protein profile by TMP. The results of the study suggest that TMP can improve the symptoms of AD.

Deep cerebral venous blood flow monitoring by transcranial doppler ultrasonography in the treatment of cerebral venous sinus thrombosis: A case report.

We report the case of a patient in whom we used deep cerebral venous blood flow monitoring by transcranial Doppler ultrasonography to monitor the effect of anticoagulation therapy on cerebral venous sinus thrombosis. The blood flow velocity of deep cerebral veins increased in the early stage of cerebral venous sinus thrombosis, then gradually decreased to the normal level as the disease improved. Moreover, the recovery of the blood flow velocity of deep cerebral veins occurred earlier than the morphological recovery demonstrated by magnetic resonance venography.

Application of Structural and Functional Connectome Mismatch for Classification and Individualized Therapy in Alzheimer Disease.

While machine learning approaches to analyzing Alzheimer disease connectome neuroimaging data have been studied, many have limited ability to provide insight in individual patterns of disease and lack the ability to provide actionable information about where in the brain a specific patient's disease is located. We studied a cohort of patients with Alzheimer disease who underwent resting state functional magnetic resonance imaging and diffusion tractography imaging. These images were processed, and a structural and functional connectivity matrix was generated using the HCP cortical and subcortical atlas. By generating a machine learning model, individual-level structural and functional anomalies detection and characterization were explored in this study. Our study found that structural disease burden in Alzheimer's patients is mainly focused in the subcortical structures and the Default mode network (DMN). Interestingly, functional anomalies were less consistent between individuals and less common in general in these patients. More intriguing was that some structural anomalies were noted in all patients in the study, namely a reduction in fibers involving parcellations in the right anterior cingulate. Alternately, the functional consequences of connectivity loss were cortical and variable. Integrated structural/functional connectomics might provide a useful tool for assessing AD progression, while few concerns have been made for analyzing the mismatch between these two. We performed a preliminary exploration into a set of Alzheimer disease data, intending to improve a personalized approach to understanding individual connectomes in an actionable manner. Specifically, we found that there were consistent patterns of white matter fiber loss, mainly focused around the DMN and deep subcortical structures, which were present in nearly all patients with clinical AD. Functional magnetic resonance imaging shows abnormal functional connectivity different within the patients, which may be used as the individual target for further therapeutic strategies making, like non-invasive stimulation technology.

Case Report: Overlapping Multiple Sclerosis With Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report and Review of Literature.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder mediated by NMDAR antibodies, typically manifesting as behavioral complaints, psychosis, seizures, movement disorders, hypoventilation, and autonomic dysfunction. In recent years, the predisposing factors and pathophysiological mechanisms of anti-NMDAR encephalitis have been tried to be clarified. It has been recognized that an overlap may be observed between anti-NMDAR encephalitis and inflammatory demyelinating disease. However, anti-NMDAR encephalitis is rarely associated with multiple sclerosis. Here, we describe a Chinese female patient diagnosed with relapsing remitting multiple sclerosis who developed anti-NMDAR encephalitis. Further, we discuss the previously reported literature.

Neuroprotective Effect of Optogenetics Varies With Distance From Channelrhodopsin-2 Expression in an Amyloid-ß-Injected Mouse Model of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the most common cause of dementia. Optogenetics uses a combination of genetic engineering and light to activate or inhibit specific neurons in the brain. Objective: The objective of the study was to examine the effect of activation of glutamatergic neurons in the hippocampus of mice injected with Aß1-42 on memory function and biomarkers of neuroinflammation and neuroprotection in the brain to elucidate the clinical utility of optogenetic neuromodulation in AD. Methods: AAV5-CaMKII-channelrhodopsin-2 (CHR2)-mCherry (Aß-CHR2 mice) or AAV5-CaMKII-mCherry (Aß-non-CHR2 mice) was injected into the dentate gyrus (DG) of the bilateral hippocampus of an Aß1-42-injected mouse model of AD. The novel object recognition test was used to investigate working memory (M1), short-term memory (M2), and long-term memory (M3) after Aß1-42 injection. Hippocampus tissues were collected for immunohistochemical analysis. Results: Compared to controls, M1 and M2 were significantly higher in Aß-CHR2 mice, but there was no significant difference in M3; NeuN and synapsin expression were significantly increased in the DG of Aß-CHR2 mice, but not in CA1, CA3, the subventricular zone (SVZ), or the entorhinal cortex (ENT); GluR2 and IL-10 expressions were significantly increased, and GFAP expression was significantly decreased, in CA1, CA3, the DG, and the SVZ of Aß-CHR2 mice, but not in the ENT. Conclusion: Activation of glutamatergic neurons by optogenetics in the bilateral DG of an Aß-injected mouse model of AD improved M1 and M2, but not M3. A single-target optogenetics strategy has spatial limitations; therefore, a multiple targeted optogenetics approach to AD therapy should be explored.

Effect of coagulation function on cerebral microbleeds in intracerebral hemorrhage.

OBJECTIVE: Our study aimed to confirm whether coagulation function of patients presenting with intracerebral hemorrhage (ICH) was associated with onset of cerebral microbleeds (CMBs). METHODS: A total of 174 patients with basal ganglia ICH were divided into CMBs and non-CMBs groups. Indicators of coagulation function and other clinical data that included fibrinogen (FBI), prothrombin time (PT), activated partial thromboplastin time (APTT), and the international normalized ratio (INR) were compared by univariate and multivariate analysis between the two groups. A receiver operating characteristic (ROC) curve was plotted to determine the predictive value of coagulation function indicators for CMBs. RESULTS: Univariate analysis showed that APTT levels was significantly higher in the CMBs group than the non-CMBs group (30.20 ± 5.18 vs. 27.95 ± 4.19; p = .004), while there was no significant difference between PT, INR, and FBI. The proportion of male patients in the CMBs group was significantly higher than the non-CMBs group (76.58% vs. 52.38%, p = .001). Multifactor logistic regression analysis demonstrated that APTT and male gender were independent risk factors for CMBs in patients with ICH (OR 1.100, 95% CI: 1.026-1.180, p = .008; OR 2.957, 95% CI: 1.500-5.826, p = .002; respectively). ROC curve analysis indicated that the area under the curve of APTT and male gender for CMBs in patients with ICH was 0.641 and 0.621, respectively (p = .002 and .008; respectively). CONCLUSION: APTT was an independent risk factor for CMBs in patients with ICH.

Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer's disease.

Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson's disease, epilepsy and neurological diseases, but rarely Alzheimer's disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-ß1-42 peptide (Aß1-42). Subsequently, the region was stimulated with a 473 nm laser (1-3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1ß, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer's disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer's disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.