Trends in blood pressure changes and hypertension prevalence in Australian adults before and during the COVID-19 pandemic.

Efforts to limit the impact of the coronavirus disease (COVID-19) pandemic led to the implementation of public health measures and reallocation of health resources. To investigate trends in blood pressure (BP), hypertension and BMI in the Australian population during the COVID-19 pandemic, data from publicly accessible health stations were analyzed. Average BP and BMI measured by the SiSU Health Station network in Australia in over 1.6 million health screenings were compared between the years 2018 and 2021. Additionally, paired trajectories for BP and BMI development before and during the COVID-19 pandemic were calculated. Comparisons between pre-COVID years and post-COVID years of 2018 versus 2020, 2019 versus 2020, 2018 versus 2021, and 2019 versus 2021 showed increases in average adjusted systolic BP of 2.0, 1.7, 2.6, and 2.3 mmHg, respectively. Paired analysis of longitudinal data showed an overall increase in the trajectory of systolic BP of 3.2 mmHg between pre- and post-COVID years. The prevalence of hypertension in users of the health stations increased by approximately 25% in the years 2020-2021. Similar trends were seen for BMI. Data from public Australian health stations indicated a strong trend toward higher BP during the COVID-19 pandemic. At the population level, BP increments have been shown to markedly increase cardiovascular disease risk. Anti-pandemic measures need to be carefully evaluated in terms of secondary public health effects and health support systems extended to effectively target cardiovascular risk.

A prognostic model for interventional thrombectomy in patients with acute ischemic stroke based on a BP neural network, random forest model and decision tree model.

OBJECTIVE: To investigate the predictive effect of a Back propagation (BP) neural network model, a random forest (RF) model and a decision tree model on the prognosis of interventional thrombolectomy for acute ischemic stroke (AIS) patients. METHODS: A total of 255 patients with AIS admitted to the Department of Neurology, Beiliu People's Hospital of Guangxi from March 2018 to February 2022 were retrospectively included, all of whom received interventional thromposectomy. Patients' prognosis was determined by the modified Rankin Scale (mRs) at 3 months after surgery, including the good prognosis group (mRs≤2 points) and the poor prognosis group (mRs 3-6 points). Clinical data of the two groups were collected to explore and screen the factors affecting poor clinical prognosis. Based on the selected influencing factors, the BP neural network, RF model, and decision tree models were established respectively, and their predictive performances were verified. RESULTS: All the three models predicted the same verification set data. The prediction accuracy, sensitivity and specificity of the BP neural network model were 0.961, 0.983 and 0.875, respectively. The prediction accuracy, sensitivity and specificity of the RF model were 0.948, 0.952 and 0.933, respectively. The prediction accuracy, sensitivity and specificity of the decision tree model were 0.882, 0.953 and 0.667, respectively. CONCLUSION: The three prediction models have shown good diagnostic efficacy and stability in the preliminary study of the prognosis of AIS mediated thrombectomy, which has important guiding significance for clinical prognosis assessment and selection of appropriate surgical population. The prediction model can be selected according to the actual situation of patients to provide more efficient guidance for clinicians.

Focusing on testosterone levels in male: A half-longitudinal study of polycyclic aromatic hydrocarbon exposure and diastolic blood pressure in coke oven workers.

Polycyclic aromatic hydrocarbons (PAHs) can interfere with testosterone levels, and low levels of testosterone are associated with increased cardiovascular events. To explore the role of testosterone in PAHs exposure and cardiovascular health, we used data from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) and a longitudinal database of 332 male coke oven workers from China. The urine PAHs, tobacco metabolites and plasma testosterone levels of coke oven workers were measured. There were inverse associations between serum (plasma) testosterone concentrations and the risk of dysarteriotony and dyslipidemia among the NHANES participants and coke oven workers. The results of the cross-lagged panel analysis among workers showed that the decrease in testosterone preceded the increase in diastolic blood pressure (DBP), and the absolute value of the path coefficient from baseline testosterone to follow-up DBP (ß2 = -8.162, P = 0.077) was significantly larger than the absolute value of the path coefficient from baseline DBP to follow-up testosterone (ß1 = -0.001, P = 0.781). Results from the half-longitudinal mediation analysis showed that baseline hydroxyfluorene predicted significant decreases in plasma testosterone from baseline to follow-up (path a: 0.71, 95% CI: 1.26, -0.16), whereas plasma testosterone at baseline also predicted significant increments in DBP from baseline to follow-up (path b: 9.22, 95% CI: 17.24, -1.19). The indirect effect of PAHs on DBP via plasma testosterone level was marginally significant (test for indirect effects a*b (P = 0.08)). In conclusion, testosterone level is a longitudinal precursor to increased DBP and plays an essential role in the association between PAHs exposure and damage to the cardiovascular system. Coke oven workers with low plasma testosterone levels are more likely to experience adverse changes in blood pressure and lipid levels after exposure to PAHs.

Galectin-1 Regulates RNA Expression and Alternative Splicing of Angiogenic Genes in HUVECs.

BACKGROUND: Angiogenesis is essential for tissue development, and therefore its dysregulation can cause various diseases, including cerebrovascular disease. Galectin-1, encoded by the lectin galactoside-binding soluble-1 gene (LGALS1), has critical roles in the regulation of angiogenesis, but the underlying mechanisms need further clarification. METHODS: LGALS1 was silenced in human umbilical vein endothelial cells (HUVECs) and whole transcriptome sequencing (RNA-seq) was then performed to investigate potential targets for galectin-1. Galectin-1-interacting RNA data was also integrated to explore how galectin-1 might regulate gene expression and alternative splicing (AS). RESULTS: A total of 1451 differentially expressed genes (DEGs) were found to be regulated by silencing LGALS1 (siLGALS1), comprising 604 up- and 847 down-regulated DEGs. Down-regulated DEGs were primarily enriched in angiogenesis and inflammatory response pathways, and included CCL2, GJA5, CALCRL, ACKR3, HEY1, AQP1, CD34, ECM1, RAMP2, and SELP. These were validated by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) experiments. siLGALS1 was also used to analyze dysregulated AS profiles, such as the promotion of exon skipping (ES) and intron retention, and inhibition of cassette exon events. Interestingly, regulated AS genes (RASGs) were found to be enriched in focal adhesion and in the angiogenesis-associated vascular endothelial growth factor (VEGF) signaling pathway. Furthermore, based on our previously published RNA interactome data for galectin-1, hundreds of RASGs were found to be bound by galectin-1, including those enriched in the angiogenesis pathway. CONCLUSIONS: Our results demonstrate that galectin-1 can regulate angiogenesis-related genes at transcriptional and post-transcriptional levels, probably by binding to the transcripts. These findings expand our understanding of the functions of galectin-1 and the molecular mechanisms that underlie angiogenesis. They also indicate that galectin-1 could serve as a therapeutic target for future anti-angiogenic treatments.

Effect of Club cell secretory proteins on the association of tobacco smoke and PAH co-exposure with lung function decline: A longitudinal observation of Chinese coke oven workers.

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAH) and tobacco smoke is associated with epithelial damage and reduced lung function. Club cell secretory protein (CC16) is a known biomarker for lung epithelial cells. However, the potential relationships between PAH and tobacco smoke exposure, CC16 levels, and reduced lung function remain unclear. OBJECTIVES: This longitudinal study aimed to explore the potential role of CC16 in the association of tobacco smoke and PAH co-exposure with lung function. METHODS: We enrolled 313 workers from a coking plant in China in 2014 and followed them up in 2019. The concentrations of PAH and nicotine metabolites in urine were determined using high-performance liquid chromatography (HPLC) with a fluorescence detector and HPLC-tandem mass spectrometry, respectively. The plasma CC16 concentration was determined using an enzyme-linked immunosorbent assay. RESULTS: An analysis of the generalized estimating equation showed that each 1-unit increase in log-transformation of the last tertile of trans-3'-hydroxycotinine (3HC) was associated with a 3.30 ng/ml decrease in CC16. Restricted cubic spline analysis revealed a significant nonlinear dose-effect association between cotinine (COT) and CC16 (Pnonlinear = 0.018). In the low- CC16 subgroup, we found a significant association between total nicotine metabolites and forced vital capacity (FVC%) (ß: 1.45, 95% CI: 2.87, -0.03), and the associations of nicotine (NIC), COT, and 3HC with FVC% were all of marginal significance. High levels of total hydroxyl polycyclic aromatic hydrocarbons (ΣOH-PAH) and NIC in the urine had an interactive effect on the decline of CC16 (P < 0.05). Cross-lagged panel analysis indicated that the decrease in CC16 preceded the decrease in FVC%. CC16 mediated the association between elevated nicotine metabolites and decreased FVC% in the low- CC16 subgroup. CONCLUSIONS: CC16 plays an essential role in the association of PAH and tobacco smoke exposure with reduced lung function. Coke oven workers with low plasma CC16 levels are more likely to experience decreased lung function after tobacco smoke exposure.

Different observation period of exercise training in amyotrophic lateral sclerosis patients: A meta-analysis.

Objective: The purpose of this meta-analysis was to evaluate the effect of more intensive exercise training on the functional ability of patients with amyotrophic lateral sclerosis. Methods: Randomized controlled trials on exercise training in amyotrophic lateral sclerosis patients were retrieved from PubMed, Embase, Web of Science, Cochrane Library and other databases, and meta-analysis was conducted using a fixed effect model or random effect model. Sensitivity analysis was used as a means to study heterogeneity. Results: A total of 8 randomized controlled trials involving 330 patients with amyotrophic lateral sclerosis were included in this study. The results showed that there was statistical significance in the influence of more intensive exercise training on amyotrophic lateral sclerosis Functional Rating Scale in the short term (0-4 months) and the medium term (5-8 months) (P < 0.05). There was no significant difference in the effect of the amyotrophic lateral sclerosis Functional Rating Scale-Revised in the short term (0-4 months) or long term (9-12 months) (P ≥ 0.05). In the medium term (5-8 months), there was statistical significance (P < 0.05). There was no significant difference in Forced vital capacity (FVC%) in the short term (0-4 months) (P > 0.05). Conclusion: More intensive exercise training may slow the decline in functional score of amyotrophic lateral sclerosis patients, and more studies should be carried out in the future to verify the effect of more intensive exercise training in patients with amyotrophic lateral sclerosis.

Facile preparation of Fe3O4@Pt nanoparticles as peroxidase mimics for sensitive glucose detection by a paper-based colorimetric assay.

A simple strategy to rapidly detect glucose was developed by utilizing core (Fe3O4)-shell (Pt) magnetic nanoparticles (Fe3O4@Pt NPs) as a nanoenzyme and a paper-based colorimetric sensor. In the presence of H2O2, Fe3O4@Pt NPs catalyze the redox reaction of 3,3',5,5'-tetramethylbenzidine (TMB) and generate a colour change from colourless to blue. On this basis, a colorimetric glucose sensing method assisted by glucose oxidase (GOx) was developed. Under the optimal conditions, the detection limits of the proposed assay for H2O2 and glucose were 0.36 µM and 1.27 µM, respectively. Furthermore, the fabricated colorimetric method was successfully applied to analyze glucose concentrations by using a paper device as a measuring platform without a spectrometer. In addition, this method exhibited satisfactory recovery for glucose detection in human serum samples and urine samples, which satisfied the requirements for normal detection of real samples. This study provides a good candidate for health monitoring of glucose and also expands the applications of nanoenzymes and paper-based colorimetric assays in point-of-care testing.

RCT protocol for driving performance in people with Parkinson's using autonomous in-vehicle technologies.

Introduction: Driving is an essential facilitator of independence, community participation, and quality of life. Drivers with Parkinson's Disease (PD) make more driving errors and fail on-road evaluations more than healthy controls. In-vehicle technologies may mitigate PD-related driving impairments and associated driving errors. Establishing a rigorous study protocol will increase the internal validity and the transparency of the scientific work. Methods: We present a protocol to assess the efficacy of autonomous in-vehicle technologies (Level 1) on the driving performance of drivers with PD via a randomized crossover design with random allocation. Drivers with a PD diagnosis based on established clinical criteria (N = 105), referred by neurologists, are exposed to two driving conditions (technology activated or not) on a standardized road course as they drove a 2019 Toyota Camry. The researchers collected demographic, clinical, on-road data observational and kinematic, and video data to understand several primary outcome variables, i.e., number of speeding, lane maintenance, signaling, and total driving errors. Discussion: The protocol may enhance participant adherence, decrease attrition, provide early and accurate identification of eligible participants, ensure data integrity, and improve the study flow. One limitation is that the protocol may change due to unforeseen circumstances and assumptions upon implementation. A strength is that the protocol ensures the study team executes the planned research in a systematic and consistent way.Following, adapting, and refining the protocol will enhance the scientific investigation to quantify the nuances of driving among those with PD in the era of automated in-vehicle technologies. Trial registration: ClinicalTrials.gov NCT04660500.

Antibiofilm Effects of Epigallocatechin Gallate Against Proteus mirabilis Wild-Type and Ampicillin-Induced Strains.

Proteus mirabilis is an opportunistic pathogen associated with nosocomial infections and foodborne diseases. The resistance and biofilm formation of P. mirabilis have been a great concern. In this study a multidrug-resistant P. mirabilis strain 012 was exposed to a lethal dose of ampicillin (10 mg/mL, 2.5-fold minimal bactericidal concentration) for 24 h at 37°C. After resuscitation and isolation, five variant isolates were selected and subjected to ampicillin induction by repeatedly streaking on ampicillin-containing plates (10 mg/mL) for at least three times. In biofilm formation assays by using crystal violet staining, we found that the variant strains had enhanced biofilm-forming abilities. (-)-epigallocatechin-3-gallate (EGCG) at a minimum inhibitory concentration (MIC) (256 µg/mL) significantly reduced the biofilm formation of all variant strains and the wild-type strain (p < 0.01). Sub-MIC of EGCG (128 µg/mL) suppressed the biofilms of wild-type and two variants. However, it stimulated the biofilms of the other three variants. The antibiofilm effects of EGCG against the wild-type strain were further confirmed by confocal laser scanning microscopy. Scanning electron microscopy revealed that EGCG induced variants to form more fibrous structures. Our results revealed that a lethal dose of antibiotic exposure increased antibiotic resistance and biofilm formation of P. mirabilis. EGCG may be used as a promising antibiofilm agent to prevent the P. mirabilis biofilm formation in the food industry. However, the sub-MIC of EGCG is not effective and will not be applied.

Ratiometric fluorescent probe for the on-site monitoring of coexisted Hg2+ and F- in sequence.

The monitoring of mercury and fluoride ions (Hg2+ and F-) has aroused wide concerns owing to the high toxicity of Hg2+ and the duplicitous nature of F- to human health. As far as we known, more than 100 million people in poverty-stricken areas are still at high risk of being over-exposed to Hg2+ and F- via drinking water. Simple and cost-effective luminescent methods are highly promising for on-site water monitoring in rural areas. However, the development of multipurpose luminescent probes that are accurate and sensitive remains challenging. Herein, a new strategy for rationally designing a multipurpose ratiometric probe is present. The obtained probe is consisted of two emission units with energy transfer between them, which exhibit high coordination affinities to the two coexisted toxic targets (Hg2+ and F-), respectively. Thus, two distinct routes for efficiently modulating the energy transfer in the probe are present to trigger the responses to the two targets in sequence. By detecting the shift of the emission color with a smartphone, an on-site water monitoring method is successfully established with the detection limits as low as 2.7 nM for Hg2+ and 1.9 µM for F-. The present study can expend the toolbox for water monitoring in rural regions.

One-Step Microwave-Assisted Synthesis of PtNiCo/rGO Electrocatalysts with High Electrochemical Performance for Direct Methanol Fuel Cells.

Platinum (Pt) is widely used as an activator in direct methanol fuel cells (DMFCs). However, the development of Pt catalyst is hindered due to its high cost and CO poisoning. A multi-metallic catalyst is a promising catalyst for fuel cells. We develop a simple and rapid method to synthesize PtNiCo/rGO nanocomposites (NCs). The PtNiCo/rGO NCs catalyst was obtained by microwave-assisted synthesis of graphene oxide (GO) with Pt, Ni, and Co precursors in ethylene glycol (EG) solution after heating for 20 min. The Pt-Ni-Co nanoparticles showed a narrow particle size distribution and were uniformly dispersed on the reduced graphene oxide without agglomeration. Compared with PtNiCo catalyst, PtNiCo/rGO NCs have superior electrocatalytic properties, including a large electrochemical active surface area (ECSA), the high catalytic activity of methanol, excellent anti-toxic properties, and high electrochemical stability. The ECSA can be up to 87.41 m2/g at a scan rate of 50 mV/s. They also have the lowest oxidation potential of CO. These excellent electrochemical performances are attributed to the uniform dispersion of PtNiCo nanoparticles, good conductivity, stability, and large specific surface area of the rGO carrier. The synthesized PtNiCo/rGO nanoparticles have an average size of 17.03 ± 1.93 nm. We also investigated the effect of catalyst material size on electrocatalytic performance, and the results indicate that PtNiCo/rGO NC catalysts can replace anode catalyst materials in fuel cell applications in the future.

Galectin-1-RNA interaction map reveals potential regulatory roles in angiogenesis.

Hyperactive angiogenesis contributes to the immunosuppressive microenvironment important for immunotherapy. Galectin-1, encoded by LGALS1, can trigger the vascular signaling programs and mediate the anti-angiogenic treatment response. However, the mechanism through which galectin-1 regulates angiogenesis is poorly understood. It has been suggested that galectin-1 may associate with mRNAs in cells. This study applied the iRIP-seq methodology to study the potential role of galectin-1 as an RNA-binding protein. We found that galectin-1 interacts with a large number of mRNAs, with a preference for binding near stop codons and a preference for UGCA/UGGA and GAGCAG as binding motifs. Galectin-1 binds to the mRNAs of angiogenesis-associated genes including VEGFA, EGR1, and LAMA5, suggesting that galectin-1 may regulate angiogenesis via its mRNA-binding activity. We further show that shLGALS1 inhibits capillary tube formation in an in vitro angiogenesis assay and alters the expression levels of several galectin-1-bound angiogenesis-associated mRNAs. These results uncover a previously unrecognized mRNA-binding activity of galectin-1.

Severe Guillain-Barré syndrome associated with chronic hepatitis B: A case report and literature review.

RATIONALE: Guillain-Barré syndrome (GBS) is a postinfectious autoimmune peripheral neuropathy characterized by acute paralysis of the limbs. Clinically, extrahepatic manifestations of neurologic involvement in chronic hepatitis B (CHB) are uncommon. Little attention has been paid to the relationship between GBS and CHB viral infection. PATIENT CONCERNS: We presented a severe case of a 34-year-old man with general fatigue, anorexia, jaundice, numbness, and even muscle atrophy in the limbs, and respiratory failure during an acute exacerbation of CHB. DIAGNOSES: Serological liver enzymes test confirmed an acute exacerbation of CHB. Nerve conduction studies revealed the features of acute motor and sensory axonal neuropathy combined with acute inflammatory demyelinating polyneuropathy, and cerebrospinal fluid analysis showed albuminocytologic dissociation. Clinical manifestations and the test results were consistent with a diagnosis of severe CHB-related GBS. INTERVENTIONS: He was treated with mechanical ventilation, 2 courses of intravenous immunoglobulin, antichronic hepatitis B drugs therapy supplemented by hepatoprotection, acupuncture and rehabilitation. OUTCOMES: After 29 days of hospitalization, his neurological condition improved. At a 6-month follow-up visit, he was able to walk with the support of another person. LESSONS: The acute exacerbation of CHB may be a potential predisposing factor for the onset of GBS. This case is a reminder to clinicians that during the acute exacerbation of CHB, patients with neurological symptoms in the limbs should be considered for potential CHB-related GBS.

Clinical characteristics of a group of deaths with COVID-19 pneumonia in Wuhan, China: a retrospective case series.

BACKGROUND: With the widespread outbreak of novel coronavirus diseases 2019(COVID-19), more and more death cases were reported, however, limited data are available for the patients who died. We aimed to explore the clinical characteristics of deaths with COVID-19 pneumonia. METHODS: We abstracted and analyzed epidemiological, demographic, clinical, and laboratory data from 83 death cases with COVID-19 pneumonia in East Hospital of Wuhan University Renmin Hospital, between January 26, 2020, and February 28, 2020. RESULTS: Of the 83 deaths, none was the medical staff. The mean age was 71.8 years (SD 13.2; range, 34-97 years) and 53(63.9%) were male. The median from onset to admission was 10 days (IQR 7-14: range, 2-43 days), to death was 17 days (IQR 14-21: range, 6-54 days). Most deaths (66[80%]) had underlying comorbid diseases, the most of which was hypertension [47(57%)]. The main initial symptoms of these 83 deaths were shortness of breath(98.8%), fever(94%), and myalgia or fatigue(90.4%). Laboratory analyses showed the lymphocytopenia in 69(83%) deaths, hypoalbuminemia in 77(93%) deaths, the elevation of lactate dehydrogenase in 79(95%) deaths, procalcitonin in 69(83%) deaths and C-reactive protein in 79(95%) deaths. All 83 patients received antiviral treatment, 81(97.6%) deaths received antibiotic therapy, 54(65.1%) deaths received glucocorticoid therapy, and 20(24.1%) patients received invasive mechanical ventilation. CONCLUSION: Most of the deaths with COVID-19 pneumonia were elderly patients with underlying comorbid diseases, especially those over 70 years of age. The time of death after the onset of the disease was mostly 15-21 days. More care should be given to the elderly in further prevention and control strategies of COVID-19.

Isolation of Trametes hirsuta La-7 with high laccase-productivity and its application in metabolism of 17ß-estradiol.

Estrogens, which are extensive in the eco-environments, are a category of high-toxic emerging contaminants that induce metabolic disorders and even carcinogenic risks in wildlife and humans. Here we investigate whether fungus-secreted laccase can be used as a green catalyst to eliminate a representative estrogen, 17ß-estradiol (E2). A white-rot fungus Trametes hirsuta La-7 with high laccase-productivity, was isolated from pig manure-contaminated soil. Extracellular laccase activity expressed by strain La-7 was 65.4 U·mL-1 for a 3 d inoculation under the optimal fermentation parameters. The concentrated-crude laccase from Trametes hirsuta La-7 (CC-ThLac) was capable of effectively metabolizing E2 at pH 4-6, and the apparent pseudo first-order reaction rate constant and half-life values were respectively 0.027-0.055 min-1 and 25.86-12.67 min (R2 > 0.98). The mass measurement of high-resolution mass spectrometry in combination with 13C-isotope labeling identified that the main by-products of E2 metabolism were dimers, trimers, and tetramers, which are consistent with radical-driven C-C and/or C-O-C covalent coupling pathway, involving the initial enzymatic production of phenoxy radical intermediates and then the successive oxidative-oligomerization of radical intermediates. The formation of oligomers dramatically reduced the estrogenic activity of E2. Additionally, CC-ThLac also exhibited high-efficiency metabolism capability toward E2 in the natural water and pig manure, with more than 94.4% and 91.0% of E2 having been metabolized, respectively. These findings provide a broad prospect for the clean biotechnological applications of Trametes hirsuta La-7 in estrogen-contaminated ecosystems.

Low-Temperature Solution-Processed Zinc Tin Oxide Film as a Cathode Interlayer for Organic Solar Cells.

In this study, Sn-doped ZnO (ZTO) is prepared by a sol-gel method and is employed as an electron transport material for organic solar cells (OSCs). After Sn modification, the fabricated ZTO films exhibited better charge transport properties and smoother surface morphology, especially for those processed at a low temperature of 120 °C. By incorporation of the high-temperature (200 °C) processed ZTO films, inverted OSCs showed the highest power conversion efficiency (PCE) of 9.32%, which is higher than those based on the same temperature processed ZnO films. For the devices based on the low-temperature processed ZTO, a high PCE over 9.0% with long-term stability was achieved, which is much better than those based on the same temperature processed ZnO (8.46% PCE). Here, the ZTO films can be fabricated without high-temperature annealing, demonstrating their great potential as electron transport layers for efficient flexible OSCs.

Interfacial Materials for Organic Solar Cells: Recent Advances and Perspectives.

Organic solar cells (OSCs) have shown great promise as low-cost photovoltaic devices for solar energy conversion over the past decade. Interfacial engineering provides a powerful strategy to enhance efficiency and stability of OSCs. With the rapid advances of interface layer materials and active layer materials, power conversion efficiencies (PCEs) of both single-junction and tandem OSCs have exceeded a landmark value of 10%. This review summarizes the latest advances in interfacial layers for single-junction and tandem OSCs. Electron or hole transporting materials, including metal oxides, polymers/small-molecules, metals and metal salts/complexes, carbon-based materials, organic-inorganic hybrids/composites, and other emerging materials, are systemically presented as cathode and anode interface layers for high performance OSCs. Meanwhile, incorporating these electron-transporting and hole-transporting layer materials as building blocks, a variety of interconnecting layers for conventional or inverted tandem OSCs are comprehensively discussed, along with their functions to bridge the difference between adjacent subcells. By analyzing the structure-property relationships of various interfacial materials, the important design rules for such materials towards high efficiency and stable OSCs are highlighted. Finally, we present a brief summary as well as some perspectives to help researchers understand the current challenges and opportunities in this emerging area of research.

Tanshinone IIA protects PC12 cells from ß-amyloid(25-35)-induced apoptosis via PI3K/Akt signaling pathway.

For the aging populations of any nation, Dementia is becoming a primary problem and Alzheimer's dementia (AD) is the most common type. However, until now, there is no effective treatment for AD. Tanshinone IIA (Tan IIA) has been reported for neuroprotective potential to against amyloid ß peptides (Aß)-induced cytotoxicity in the rat pheochromocytoma cell line PC-12, which is widely used as AD research model, but the mechanism still remains unclear. To investigate the effect of Tan IIA and the possible molecular mechanism in the apoptosis of PC12 cells, we induced apoptosis in PC12 cells with ß-amyloid(25-35), and treated cells with Tan IIA. After 24 h treatment, we found that Tan IIA increased the cell viability and reduced the number of apoptotic cells induced by Aß(25-35). However, neuroprotection of Tan IIA was abolished by PI3K inhibitor LY294002. Meanwhile, Treatment with lithium chloride, a phosphorylation inhibitor of GSK3ß, which is a downstream target of PI3K/Akt, can block Aß(25-35)-induced cell apoptosis in a Tan IIA-like manner. Our findings suggest that Tan IIA is an effective neuroprotective agent and a viable candidate in AD therapy and PI3K/Akt activation and GSK3ß phosphorylation are involved in the neuroprotection of Tan IIA.

The neuroprotective effects of cyclin-dependent kinase-5 inhibition in mice with Niemann-Pick disease type C.

In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 (cdk-5) inhibition in mice with Niemann-Pick disease type C (NPC) (npc(-/-)), recombinant adeno-associated virus (rAAV) carrying the small interfering RNA (siRNA) specific for cdk-5 gene was injected into 3-day-old npc(-/-) mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc(-/-) mice and non-surgery age-matched npc(-/-) mice were employed as controls (n=6-10/group). From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc(-/-) mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc(-/-) mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc(-/-) mice, and significantly attenuated the hyperphosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuroprotective effect on neurons in NPC mice.

Packaging and functional identification of recombinant adeno-associated virus encoding cdc2-siRNA.

Cyclin dependent kinases (cdks) play an important role in the pathogenesis of multiple neurodegenerative diseases. To explore the possibility of cdks-related gene therapy for neurodegenerative diseases, we packed recombinant adeno-associated virus (rAAV) encoding cdc2-siRNA. The expressing plasmid pAAV-MCS-EGFP-U6-cdc2-siRNA was constructed by using molecular biological techniques. The rAAV encoding cdc2-siRNA (rAAV-EGFP-U6-cdc2-siRNA) was packed by calcium phosphate mediated co-transfection of the plasmid pAAV-MCS-EGFP-U6-cdc2-siRNA, p-RC and p-Helper into AAV-293 cells. DNA sequencing proved the successful construction of U6-cdc2-siRNA in pAAV-MCS-EGFP. Seventy-two h after packaging, the expression of EGFP could be detected in AAV-293 cells. Western blotting revealed that cdc2 gene expression in AAV-293 cells was down-regulated markedly after transfection with rAAV-EGFP-U6-cdc2-siRNA, which evidenced the satisfactory silencing effect of this virus. It was concluded that the packaging of rAAV encoding cdc2-siRNA was successful. rAAV encoding cdc2-siRNA could silence cdc2 gene effectively, which might offer a novel means for the treatment of neurodegenerative diseases.