Abnormalities of structural covariance of insular subregions in drug-naïve OCD patients.

The insula plays a significant role in the neural mechanisms of obsessive-compulsive disorder. Previous studies have identified functional and structural abnormalities in insula in obsessive-compulsive disorder patients. The predictive coding model in the context of interoception can explain the psychological and neuropathological manifestations observed in obsessive-compulsive disorder. The model is based on the degree of laminar differentiation of cerebral cortex. The interindividual differences in a local measure of brain structure often covary with interindividual differences in other brain regions. We investigated the anatomical network involving the insula in a drug-naïve obsessive-compulsive disorder sample. We recruited 58 obsessive-compulsive disorder patients and 84 matched health controls. The cortical thickness covariance maps between groups were compared at each vertex. We also evaluated the modulation of Yale-Brown Obsessive-Compulsive Scale scores and obsessive-compulsive disorder duration on thickness covariance. Our findings indicated that the thickness covariance seeded from granular and dysgranular insula are different compared with controls. The duration and severity of obsessive-compulsive disorder can modulate the thickness covariance of granular and dysgranular insula with posterior cingulate cortex and rostral anterior cingulate cortex. Our results revealed aberrant insular structural characteristics and cortical thickness covariance in obsessive-compulsive disorder patients, contributing to a better understanding of the involvement of insula in the pathological mechanisms underlying obsessive-compulsive disorder.

Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice.

Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

Effect of long-term care insurance policy on depression in non-disabled people: evidence from China.

BACKGROUND: Policy effect might be multidimensional and spill over to non-recipients. It is unclear how the implementation of Long-Term Care Insurance (LTCI) policy affects depression in non-disabled people and how this effect differs in different non-disabled groups. METHODS: Using time-varying differences-in-differences method and nationally representative health survey data in wave 2011, wave 2013, wave 2015 and wave 2018 from the China Health and Retirement Longitudinal Study, we assessed the effect of LTCI policy on depression in non-disabled people aged 45 years and older, and discussed the heterogeneity of effect across different population characteristics: retirement, financial support and social participation status. RESULTS: We found LTCI policy statistically significant reduced depression by 0.76 units in non-disabled people compared to non-pilot cities. Depression in non-disabled people who unretired, with financial support and without social participation was reduced by 0.8267, 0.7079 and 1.2161 units, respectively. CONCLUSIONS: Depression in non-disabled people was statistically significant reduced because of LTCI policy in China, and non-disabled people who unretired, with financial support and without social participation benefited more from LTCI policy. Our findings highlight the depression-reducing effect of LTCI policy in non-recipients and suggest that non-disabled people who unretired, with financial support and without social participation should be concerned during LTCI policy progress.

Health spillover studies of long-term care insurance in China: evidence from spousal caregivers from disabled families.

BACKGROUND: To alleviate the shortage of caregivers associated with disabled persons, China has implemented a pilot policy for long-term care insurance. This policy has the characteristics of "familialization" and "de-familialization" policy orientation, and it is indeed essential to clarify whether the policy has a positive spillover effect on the health of family caregivers, which is of great value to the pilot from local practice to national institutional arrangement. METHODS: Based on the China Health and Retirement Longitudinal Study microdata and time-varying DID method, our study used the implementation of the pilot policy as a "quasi-natural experiment" to assess the health spillover effects of the pilot policy on family spousal caregivers. RESULTS: This policy significantly improved the health of spousal caregivers, increasing self-rated health and life satisfaction, and reducing depression; Compared with female, urban and central-western spousal caregivers, male, rural and eastern spousal caregivers were "beneficiaries" in more dimensional health. CONCLUSIONS: Our research indicated that spousal caregivers of disabled people, particularly male, rural and eastern spousal caregivers, experienced positive health spillovers after implementing long-term care insurance. These results suggest that the imbalance between supply and demand of nursing staff could be solved in terms of de-familialization and familialization, spousal caregivers should be promoted to equally enjoy the policy benefits on gender, urban-rural and regions.

Composite film with adjustable number of layers for slow release of humic acid and soil remediation.

In this study, to improve the soil amendment performance of film materials, composite films with the adjustable number of layers and controlled slow-release time were prepared using sodium alginate (SA), chitosan (CS) and activated charcoal (AC) as raw materials. The prepared multilayer films exhibited a wide pH response range and excellent slow-release time. The cumulative release of humic acid (HA) increased from 19.87 ± 0.98% to 66.72 ± 1.06% with increasing the pH from 4.0 to 10.0 after 700 h of slow-release. In addition, after 50 d of remediation in red soil, plantation soil, and saline soil, the NH4+-N, Olsen-P, Olsen-K, and organic matter contents in the three soils were increased by 2.91-28.62 mg/kg, 46.97-70.43 mg/kg, 55.89-77.01 mg/kg, and 12.47-22.52 g/kg, respectively, and were able to provide sustained crop growth promotion effect. This study demonstrates the promising application of multilayer film in soil remediation and agricultural production.

Role of vaccine in fighting the variants of COVID-19.

In this paper, we investigate the effectiveness of COVID-19 vaccination in controlling the infectivity and mortality of the SARS-CoV-2. Two major variants Delta and Omicron are investigated respectively. The main method used in the research is the multifractal detrended fluctuation analysis (MF-DFA). We use Δ α as the evaluation of control effectiveness. In the transmission stages of Delta and Omicron, we observe whether Δ α shows a downward trend by gradually expanding the length of time series. Vaccine effectiveness is evaluated using a time series of newly diagnosed patients and newly reported deaths. Data samples are taken from 9 different countries. According to the obtained results, the vaccine controls infectivity and mortality of the virus in the Delta transmission stage, but infectivity control is less effective than mortality. In the Omicron transmission stage, the immune effect of the vaccine is not obvious, which may be related to the high infectivity of Omicron. However, the vaccine is still effective in controlling mortality. We also find that the immune effect of vaccine on Omicron was lower than that of Delta. Finally, we observe that the immune effect of the vaccine in 'Poland' was abnormal. By analyzing the vaccination curve, we conclude that in 'Poland', when the growth rate of vaccination rate slowed down, the immune effect of the vaccine was very poor in terms of pathogenicity and lethality. Therefore, we suggest that all countries should continue to strengthen the vaccination rate. A higher or faster growth rate of vaccination rate will help control the infectivity and mortality rate, especially in the effectiveness of controlling mortality. Our research can be used to evaluate the effectiveness of vaccines for epidemic prevention and control, the formulation of epidemic prevention measures and vaccination policies for different countries with respect to their current pandemic situation accordingly.

Factors associated with disease relapse rate in the Neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study. METHODS: Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded. RESULTS: 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants. CONCLUSION: It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors.

A novel ratiometric fluorescence probe for the detection of copper (II) and silver(I) based on assembling dye-doped silica core-shell nanoparticles with gold nanoclusters.

A creatively designed and constructed a multifunctional ratiometric fluorescence probe is reported by assembling glutathione (GSH)-protected gold nanoclusters (AuNCs) with fluorescein-doped mesoporous silica nanoparticle (FS) for the detection of Cu2+ and Ag+ ions, which could eliminate most interferences by self-calibration. Under the excitation at 450 nm, the fluorescence connected with AuNCs can rapidly respond by quenching or enhancement, respectively, for Cu2+ and Ag+ ions, while the fluorescein isothiocyante (FITC) fluorescence served as reference with negligible change. The fluorescence intensity ratio showed good linear relationships with Cu2+ and Ag+ concentrations in the range 0.5-10 µM and 0.1-8 µM, respectively. The detection limits were as low as 140 nM and 60 nM for Cu2+ and Ag+ ions, respectively. The color change induced by fluorescent intensity ratio variation could also be employed for visual discrimination. The AuNC-embedded FS (FS-Au) nanoprobe was successfully used for Cu2+ and Ag+ ion determination in drinking water and intracellular Cu2+ imaging, which exhibits promising prospects in cost-effective and rapid determination of both Cu2+ and Ag+ with good sensitivity and selectivity.

The Modified Exenatide Microspheres: PLGA-PEG-PLGA Gel and Zinc-Exenatide Complex Synergistically Reduce Burst Release and Shorten Platform Stage.

The existing exenatide microspheres have the problem of burst release in the early stage, and minimal release in the middle stage which makes it difficult to achieve effective blood drug concentration (platform period). In this study, the modified exenatide microspheres were constructed to address the aforementioned issues. Poly(D,L-lactic-co-glycolic acid) (PLGA) and triblock copolymer with sol-gel conversion characteristics (PLGA-PEG-PLGA gel) were introduced as carriers to prepare microspheres. The hot gel characteristics and hydrophilicity of PLGA-PEG-PLGA gel were utilized to decline the burst release and shorten the platform period. Simultaneously, zinc acetate and exenatide were combined to generate an insoluble complex to further reduce the burst release. Herein, we prepared three types of exenatide microspheres using the solvent evaporation method and investigated their characterization as well as in vitro and in vivo release. According to the experimental findings, the modified exenatide microspheres, i.e., PLGA-PEG-PLGA gel and PLGA co-loaded zinc-exenatide insoluble complex microspheres (Zn-EXT-Gel-MS), had smooth and rounded surfaces, with a particle size of 24.7 µm, and the encapsulation rate reached 89.43%. And it was released for 40 days in vitro, behaving better than the other two microspheres in terms of release behavior. When this product was administered subcutaneously to rats, it produced a comparatively constant plasma exenatide concentration that lasted for 24 days and superior bioavailability than the exenatide microspheres (EXT-MS). The creation of modified exenatide microspheres may serve as a heuristic method for other long-acting medications. Schematic diagram of the synthesis process and release curves of three types of exenatide microspheres in vitro and in vivo.

Degradation of FA reduces Aß neurotoxicity and Alzheimer-related phenotypes.

Dysregulation of formaldehyde (FA) has been implicated in the development of Alzheimer's Disease (AD). Elevated FA levels in Alzheimer's patients and animal models are associated with impaired cognitive functions. However, the exact role of FA in AD remains unknown. We now identified that oxidative demethylation at serine8/26 of amyloid-beta protein (Aß) induced FA generation and FA cross-linked with the lysine28 residue in the ß-turn of Aß monomer to form Aß dimers, and then accelerated Aß oligomerization and fibrillogenesis in vitro. However, Aß42 mutation in serine8/26, lysine28 abolished Aß self-aggregation. Furthermore, Aß inhibited the activity of formaldehyde dehydrogenase (FDH), the enzyme for FA degradation, resulting in FA accumulation. In turn, excess of FA stimulated Aß aggregation both in vitro and in vivo by increasing the formation of Aß oligomers and fibrils. We found that degradation of FA by formaldehyde scavenger-NaHSO3 or coenzyme Q10 reduced Aß aggregation and ameliorated the neurotoxicity, and improved the cognitive performance in APP/PS1 mice. Our study provides evidence that endogenous FA is essential for Aß self-aggregation and scavenging FA could be an effective strategy for treating AD.

Neuroleptic malignant-like syndrome associated multiple system atrophy: report on three cases.

BACKGROUND: Multiple system atrophy (MSA) associated with neuroleptic malignant-like syndrome (NMLS) is rare and few cases have been described in the literature. CASE PRESENTATION: In the present study, three patients with MSA associated with NMLS were analyzed from January 2012 to January 2020 to characterize their clinical presentations. Data collected from the patients for analysis included general patient history, the fluctuation and severity of disease symptoms, the indicated therapies and disease progression at follow-up. All patients had histories of sudden withdrawal or reduction of levodopa prior to the onset of symptoms. Clinical presentations were characterized by hyperthermia, autonomic dysfunction, worsening of extrapyramidal symptoms, and elevated serum creatine kinase (CK) levels. During hospitalization, one patient rapidly progressed and died, while the other two patients were successfully treated. CONCLUSIONS: Early diagnosis and treatment are very important for patient outcomes in NMLS. Notably, the correct dose and time of administration of dopaminergic medication may be key in treating NMLS.

Construction and Evaluation of Hyaluronic Acid-Coated Flurbiprofen-Layered Double Hydroxide Ocular Drug Delivery System.

In this study, flurbiprofen (FB) was selected as the model drug, and hyaluronic acid-coated flurbiprofen-layered double hydroxide ophthalmic drug delivery system (HA-FB-LDH) was designed and prepared. In this system, the model drug flurbiprofen was intercalated in layered double hydroxide and coated with hyaluronic acid (HA), so as to prolong the corneal residence time and increase the corneal permeability of the drug. Layered double hydroxide (LDH) was prepared by alcohol-water coprecipitation method. Through single factor investigation, the optimum preparation conditions were obtained as follows: The Mg/Al ratio was 2:1, the reaction pH was 11.0, the hydrothermal reaction time was 24 h, and the hydrothermal reaction temperature was 100°C. Under these conditions, the particle size of LDH was 116.4 ± 0.8 nm, the potential was 42.2 ± 1.2 mV, and a relatively regular crystal structure could be had. Then FB was intercalated into the LDH layer to prepare flurbiprofen-layered double hydroxide (FB-LDH). In the end, HA-FB-LDH was prepared by the stirring-ultrasonic method, in which through prescription screening, the molecular weight of HA was 200-400 kDa and the concentration of HA solution was 1.25 mg·mL -1, the final particle size of HA-FB-LDH was 185.8 ± 3.3 nm, and potential of - 31.4 ± 0.7 mV. The successful loading of FB and the coating of HA were verified by XRD, FTIR, TGA, TEM, and other characterization methods. The results of in vitro stability experiment indicated that the coating of HA could significantly enhance the stability of LDH in the presence of electrolytes. The in vitro release results suggested that the cumulative release amounts of FB-LDH and HA-FB-LDH within 12 h were 92.99 ± 0.37% and 74.82 ± 0.29% respectively, showing a certain sustained release effect. At the same time, the release mechanism of FB-LDH was preliminarily explored by in vitro release experiment, which proved that the release mechanism of FB-LDH was mainly ion exchange. The results of in vivo ocular irritation experiments demonstrated that the ophthalmic preparation studied in this paper was safe and non-irritating. The results of tear pharmacokinetics in rabbits showed that the area under the curve(AUC), the average residence time (MRT), and the highest concentration (Cmax) in tears in the HA-FB-LDH group were 4.43, 4.48, and 2.27 times higher than those in eye drops group separately. Furthermore, the AUC of the HA-FB-LDH group was 1.48 times higher than that of the FB-LDH group. The above results suggested that HA-FB-LDH could improve the precorneal residence time. The results of aqueous humor pharmacokinetics in rabbits indicated that the AUC, MRT, and maximum concentration (Cmax) in aqueous humor in the HA-FB-LDH group were 6.88, 2.15, and 4.08 times of those in the eye drop group respectively. Additionally, the AUC and MRT of the HA-FB-LDH group were 1.55 and 1.63 times those of the FB-LDH group separately. These mentioned findings verified that HA-FB-LDH could enhance the corneal permeability of the drug. The fluorescent substance-fluoresce isothiocyanate (FITC) was substituted for FB intercalation in LDH for in vitro tissue imaging study of rabbits, whose results stated clearly that FITC-LDH and HA-FITC-LDH could both prolong the precorneal residence time of drugs, and HA-FITC-LDH could increase the corneal permeability of the drug to a certain extent. To sum up, HA-FB-LDH, which can overcome the shortcomings of low bioavailability of traditional eye drops to a certain degree, is a safe and effective ophthalmic drug delivery system.

The association between perceived hospital ethical climate and self-evaluated care quality for COVID-19 patients: the mediating role of ethical sensitivity among Chinese anti-pandemic nurses.

BACKGROUND: The COVID-19 pandemic called for a new ethical climate in the designated hospitals and imposed challenges on care quality for anti-pandemic nurses. Less was known about whether hospital ethical climate and nurses' ethical sensitivity were associated with care quality. This study examined the association between the perceived hospital ethical climate and self-evaluated quality of care for COVID-19 patients among anti-pandemic nurses, and explored the mediating role of ethical sensitivity in this relationship. METHODS: A cross-sectional study was conducted through an online survey. A total of 399 anti-pandemic nurses from ten designated hospitals in three provinces of China were recruited to fill out an online survey. Multiple linear regression analysis and a bootstrap test were used to examine the relationships between ethical climate, ethical sensitivity and care quality. RESULTS: Nurses reported mean scores of 4.43 ± 0.577 (out of 5) for hospital ethical climate, 45.00 ± 7.085 (out of 54) for ethical sensitivity, and 5.35 ± 0.661 (out of 6) for self-evaluated care quality. After controlling for covariates, perceived hospital ethical climate was positively associated with self-evaluated care quality (direct effect = 0.710, 95% confidence interval [CI] 0.628, 0.792), and was partly mediated by ethical sensitivity (indirect effect = 0.078, 95% confidence interval [CI] 0.002, 0.145). CONCLUSIONS: Chinese nurses who cared for COVID-19 patients perceived high levels of hospital ethical climate, ethical sensitivity, and self-evaluated care quality. Positive perceptions of hospital ethical climate were both directly associated with a higher level of self-evaluated care quality and indirectly associated, through the mediation effect of ethical sensitivity among anti-pandemic nurses.

Emergency stress management among nurses: A lesson from the COVID-19 outbreak in China-a cross-sectional study.

AIMS AND OBJECTIVES: To assess the level of stress response, self-efficacy and perceived social support status of working nurses during the outbreak of the COVID-19 and investigate potential factors affecting their stress. BACKGROUND: The stress level of clinical nurses directly affects their physical and mental health and work efficiency. DESIGN: This study was a cross-sectional investigation, which was performed following the STROBE checklist. The current study was conducted in February 2020 by selecting clinical nurses from the Zigong First People's Hospital for investigation. METHODS: At the peak of the COVID-19 outbreak in China, we assessed clinical nurses with the Stanford Acute Stress Reaction Questionnaire, the General Self-Efficacy Scale and the Perceived Social Support Scale. Specifically, the nurses were divided into three groups: (a) nurses supporting Wuhan; (b) nurses in the department of treating the COVID-19 patients in our hospital (epidemic department); and (c) nurses in the general department without the COVID-19 patients in our hospital (non-epidemic department). RESULTS: A total of 1092 clinical nurses were surveyed with 94 nurses in Wuhan, 130 nurses treating COVID-19 patients in our hospital and 868 nurses working without direct contact with diagnosed COVID-19 patients. The mean stress score of all surveyed nurses was 33.15 (SD: 25.551). There was a statistically significant difference in stress response scores between different departments. Noticeably, the nurses who went to support in Wuhan showed a weaker stress response than the nurses who stayed in our hospital (mean: 19.98 (Wuhan) vs. 32.70 (epidemic department in our hospital) vs. 34.64 (non-epidemic department in our hospital)). In addition, stress was negatively correlated with general self-efficacy and perceived social support. CONCLUSION: The present study suggested that the stress status of second-line nurse without direct contact with diagnosed COVID-19 patients was more severe than that of first-line nurses who had direct contact with COVID-19 patients. RELEVANCE TO CLINICAL PRACTICE: Our study indicated the importance of psychological status of second-line medical staff during the global pandemic.

Asymmetric Coordination Toward a Photoinduced Single-Chain Magnet Showing High Coercivity Values.

The production of photo-switchable molecular nanomagnets with substantial coercivity, which is indispensable for information storage and process applications, is challenging. Introducing photo-responsive spin-crossover units provides a feasible means of controlling the magnetic anisotropy, interactions, and overall nanomagnet properties. Herein, we report a cyanide-bridged chain 1⋅12H2 O ({[(Pz Tp)FeIII (CN)3 ]2 FeII (Pmat)2 }n ⋅12 H2 O) generated by linking the FeII -based spin-crossover unit with the [(Pz Tp)Fe(CN)3 ]- (Pz Tp: tetrakis(pyrazolyl)borate) building block in the presence of asymmetric ditopic ligand Pmat ((4-pyridine-4-yl)methyleneamino-1,2,4-triazole). Structural characterization revealed that the introduction of this asymmetric ligand led to a distorted coordination environment of FeII ions, which were equatorially coordinated by four cyanide N atoms, and apically coordinated by one pyridine N atom and one triazole N atom. Upon 808-nm light irradiation, 1⋅12H2 O underwent photoinduced spin-crossover and exhibited single-chain magnet behavior with a coercive field of up to 1.3 T. This represents a 3d-based photoinduced single-chain magnet exhibiting pronounced hysteresis.

Synthesis and Performance of a Novel High-Efficiency Coal Dust Suppressant Based on Self-Healing Gel.

During transportation and storage, coal produces a lot of dust, which pollutes the environment and threatens the occupational health of workers. Although many dust suppressants have been developed for dust prevention at work, the implementation of current dust suppressants does not meet the requirements due to various factors such as the hydrophobic nature of coal dust and a harsh external environment. In this study, hydroxyethyl cellulose, acrylamide, and stearyl methyl acrylate were used for micelle polymerization to prepare an environmental protection dust suppressant for preventing dust during coal storage and transportation. The microstructure of the reactants and the products was analyzed by Fourier transform infrared as well as scanning electron microscopy. The strength and self-healing tensile properties of binder coal were taken as indicators to determine the best synthesis dosage and conditions. The dust suppressant particles are applied to the dust accumulation area, contact each other after water absorption, and swell to complete the healing, to achieve the purpose of dust control. The evaluation of the relevant properties of the dust suppressant reveals that the dust suppressant has a good covering effect, an excellent dust suppressant performance, and a significant dust suppression action.

The miR-141/neuropilin-1 axis is associated with the clinicopathology and contributes to the growth and metastasis of pancreatic cancer.

BACKGROUND: Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor interacting with multiple signaling pathways that underpin the biological behavior and fate of cancer cells. However, in pancreatic cancer, the mechanisms underlying the function of NRP-1 in cell proliferation and metastasis and the involvement of regulatory upstream miRNAs remain unclear. METHODS: Potential miRNAs were mined by using multiple bioinformatics prediction tools and validated by luciferase assays. The expression of NRP-1 and miRNA-141 (miR-141) in pancreatic tissues and cells was examined by immunohistochemistry, immunoblotting and/or real-time RT-PCR. Stable transfected cells depleted of NRP-1 were generated, and regulatory effects of miR-141 were investigated by transfecting cells with miR-141 mimics and anti-miR-141. Assays of cell viability, proliferation, cell cycle distribution, transwell migration and cell scratch were employed. Xenograft tumor models were established to assess the effects of NRP-1 depletion on tumorigenesis and liver metastasis, and therapeutic effects of miR-141 on tumor growth. The role of miR-141/NRP-1 axis in regulating epithelial-mesenchymal transition (EMT) by co-interacting the TGF-ß pathway was examined. RESULTS: In this study, of 12 candidate miRNAs identified, miR-141 showed the strongest ability to regulate NRP-1. In pancreatic cancer tissues and cells, the expression level of NRP-1 was negatively correlated with that of miR-141. NRP-1 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues, and its expression levels were positively correlated with tumor grade, lymph metastasis and AJCC staging. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest at the G0/G1 phase through upregulating p27 and downregulating cyclin E and cyclin-dependent kinase 2, and reduced cell migration by inhibiting EMT through upregulating E-cadherin and downregulating Snail and N-cadherin. Through downregulating NRP-1, miR-141 mimics showed a similar effect as NRP-1 depletion on cell proliferation and migration. NRP-1 depletion suppressed tumor growth and liver metastasis and miR-141 mimics inhibited the growth of established tumors in mice. NRP-1 depletion and/or miR-141 mimics inhibited the activation of the TGF-ß pathway stimulated by TGF-ß ligand. CONCLUSIONS: The present results indicate that NRP-1 is negatively regulated by miR-141 and the miR-141/NRP-1 axis may serve as potentially valuable biomarkers and therapeutic targets for pancreatic cancer.

Subjective cognitive decline: preclinical manifestation of Alzheimer's disease.

Subjective cognitive decline (SCD), characterized by a very early and subtle cognitive decline prior to the appearance of objective cognitive impairment, is considered to be the preclinical manifestation of Alzheimer's disease (AD). Given the lack of significant abnormalities in standardized neuropsychological assessments for individuals with SCD, biochemical and neuroimaging biomarkers may be important indicators of the preclinical stage of AD. The application of various biomarkers derived from the cerebrospinal fluid and neuroimaging thus has the potential to make AD-related pathology detectable in vivo. In this review, we discuss the conceptual evolution of SCD as an entity and further elucidate characteristic cerebrospinal fluid and neuroimaging biomarkers of SCD.

Qizhufang (ZSF) Ameliorates Hepatic Iron Overload via Signal Transducer and Activator of Transcription 3 (STAT3) Pathway.

BACKGROUND Iron overload is a prominent characteristic of liver injury, but there is no effective treatment at present. Qizhufang (ZSF) is a Chinese herbal formula showed anti-HBV activities, improved liver function, and anti-fibrosis effect. ZSF showed a series of liver-protection functions, but whether ZSF can relieve hepatic iron overload is still unclear. MATERIAL AND METHODS Ferric ammonium citrate (FAC) was used to construct iron-overloaded LO2 cells. The cell apoptosis and proliferation were measured by flow cytometry and CCK-8 assay, respectively. ROS level was analyzed by fluorescence probe. RNA and protein expressions were assessed by real-time PCR and Western blot. RESULTS FAC upregulated apoptosis rate, ROS level, and expression of hepcidin and p-STAT3, but suppressed proliferation and expression of DMT1, FPN1, and CP in LO2 cells. However, Qizhufang (ZSF) reversed the effect of FAC. We also found that hepcidin overexpression suppressed the expressions of DMT1, FPN1, and CP, which were reversed by ZSF. Additionally, STAT3 inhibitor AG490 suppressed hepcidin expression. Moreover, exogenous IL-6 reversed the effect of ZSF on apoptosis rate, ROS level, and the expression of hepcidin, DMT1, FNP1, CP, and p-STAT3. CONCLUSIONS Qizhufang (ZSF) can ameliorate iron overload-induced injury by suppressing hepcidin via the STAT3 pathway in LO2 cells.

Amplified electrochemical immunoassay for 5-methylcytosine using a nanocomposite prepared from graphene oxide, magnetite nanoparticles and ß-cyclodextrin.

A nanocomposite was prepared from ß-cyclodextrin (ß-CD) functionalized graphene oxide and magnetic nanoparticles (GO/Fe3O4/ß-CD). In parallel, a polyamidoamine dendrimer conjugated to avidinylated alkaline phosphatase (PAMAM-avidin-ALP) was prepared and exploited as a signal amplification unit in a voltammetric immunoassay for 5-methylcytosine (5mC) in genomic DNA. The GO/Fe3O4/ß-CD as a substrate material exhibited good solubility, electrical conductivity and large surface. This is beneficial for the further modification of antibodies (Ab) by host-guest interaction and amide bonds. By taking advantage of three-dimensional structure to capture avidin-ALP by amide linkages, PAMAM was used as a catalytic signal amplification element in this assay. Under the optimized condition and at a typical working potential of 0.94 V, the response to 5mC is linear in the 0.01-50 nM concentration range with a detection limit of 3.2 pM (at S/N = 3). The method is stable, selective and reproducible. It was applied to the determination of 5mC in genomic DNA of human tissue. Graphical abstract An electrochemical immunoassay was constructed for 5-methylcytosine detection based on nanocomposite of graphene oxide, magnetite nanoparticles and ß-cyclodextrin, and enzymatic signal amplification.