Saxagliptin reduces the injury of Alzheimer's disease cell model by down-regulating the expression of miR-483-5p.

This study aimed to investigate the effect of saxagliptin on the injury of Alzheimer's disease (AD) cell model and its possible mechanism. SK-N-SH cells were cultured in vitro and divided into CON group, AD group, AD+L-SAX group, AD+M-SAX group, AD+H-SAX group, AD+anti-miR-NC group, AD+anti-miR-483-5p group, AD+SAX+miR-NC group and AD+SAX+miR-483-5p group. Then the levels of MDA, SOD and GSH-Px in each group were detected by ELISA method; cell apoptosis was detected by flow cytometry; the protein expression levels of Bax and Bcl-2 were detected by Western Blot; the expression level of miR-483-5p was detected by RT-qPCR. Compared with the control group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p increased in the AD group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein decreased (P<0.05). Compared with the AD group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p decreased in the AD+L-SAX group, AD+M-SAX group and AD+H-SAX group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein increased (P<0.05). Compared with AD+anti-miR-NC group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p decreased in the AD+anti-miR-483-5p group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein increased (P<0.05). Compared with AD+SAX+miR-NC group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p increased in the AD+SAX+miR-483-5p group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein decreased (P<0.05). Saxagliptin may reduce the injury of Alzheimer's disease cell model by down-regulating the expression of miR-483-5p.

High-sensitivity-cardiac troponin for accelerated diagnosis of acute myocardial infarction: A systematic review and meta-analysis.

OBJECTIVES: Cardiovascular disease is the leading cause of mortality and morbidity. Serial troponin tests have been endorsed as essential diagnostic steps to rule out/-in acute myocardial infarction (AMI), and hs-cTn assays have shown promise in enhancing the accuracy and efficiency of AMI diagnosis in the emergency department (ED). METHODS: A systematic review and meta-analysis of diagnostic test accuracy studies were conducted to compare the diagnostic performance of various accelerated diagnostic algorithms of hs-cTn assays for patients with symptoms of AMI. Random-effects bivariate meta-analysis was conducted to estimate the summary sensitivity, specificity, likelihood ratios, and area under receiver operating characteristic curve. RESULTS: In the systematic review consisting of 56 studies and 67,945 patients, both hs-cTnT and hs-cTnI-based 0-, 1-, 2- and 0-1 h algorithms showed a pooled sensitivity >90%. The hs-cTnI-based algorithm showed a pooled specificity >80%. The hs-cTnT-based algorithms had a specificity of 68% for the 0-h algorithm and of around 80% for the 1-, 2-, and 0-1 h algorithms. The heterogeneities of all diagnostic algorithms were mild (I2 < 50%). CONCLUSION: Both hs-cTnI- and hs-cTnT-based accelerated diagnostic algorithms have high sensitivities but moderate specificities for early diagnosis of AMI. Overall, hs-cTnI-based algorithms have slightly higher specificities in early diagnosis of AMI. For patients presenting ED with typical symptoms, the use of hs-cTnT or hs-cTnI assays at the 99th percentile may help identify patients with low risk for AMI and promote early discharge from the ED.

Pickering Emulsion-Derived Liquid-Solid Hybrid Catalyst for Bridging Homogeneous and Heterogeneous Catalysis.

We describe a novel method to prepare a liquid-solid hybrid catalyst via interfacial growth of a porous silica crust around Pickering emulsion droplets, which allowed us to overcome the current limitations of both homogeneous and heterogeneous catalysts. The inner micron-scaled liquid (for example, ionic liquids) pool of the resultant catalyst can host free homogeneous molecular catalysts or enzymes to create a true homogeneous catalysis environment. The porous silica crust of the hybrid catalyst has excellent stability, which makes it amenable to packing directly in fixed-bed reactors for continuous flow catalysis. As a proof of concept, the enzymatic kinetic resolution of racemic alcohols, CrIII(salen) complex-catalyzed asymmetric ring opening of epoxides and Pd-catalyzed Tsuji-Trost allylic substitution reactions were used to verify the generality and versatility of our strategy for bridging homogeneous and heterogeneous catalysis. The hybrid catalyst-based continuous flow system exhibited a 1.6∼16-fold enhancement in activity relative to homogeneous counterparts even over 1500 h, and the afforded enantioselectivities were completely equal to those obtained in the homogeneous counterpart systems. Interestingly, the catalytic efficiency can be tuned through rational engineering of the porous crust and the dimensions of the liquid pool, resulting in features of an innovatively designed catalyst. This contribution provides a new method to design efficient catalysts that can bridge the conceptual and technical gaps between homogeneous and heterogeneous catalysis.

Green, fast, and large-scale synthesis of highly fluorescent Au nanoclusters for Cu2+ detection and temperature sensing.

Gold nanoclusters have attracted widespread attention because of their unique optical and physical properties. However, traditional synthesis methods are complicated and require additional reducing agents, while the yield is often very low. Such resource and time-consuming synthesis processes limit their further application. Herein, a rapid sonochemical route is used to synthesize fluorescent Au nanoclusters in large quantities using glutathione (GSH) both as a capping and reducing agent. These Au nanoclusters are synthesized quickly (∼40 min) due to the presence of ultrasonic waves, and show orange red photoluminescence (Em = 598 nm), small size (∼2 nm) and good dispersion in aqueous solution. Moreover, GSH, as a protecting agent on the surface of resultant Au nanoclusters, has many functional groups including carboxyl and amino groups because of which the nanoclusters show high photo-, storage-, metal- and pH-stability. A stable Au nanoclusters-based nano-sensor is designed for highly sensitive and selective label-free detection of Cu2+ with a low limit of detection of 7 ppb (based on S/N = 3). The fluorescent probe can be used in versatile nanothermometry devices, because their photoluminescence intensity correlates strongly with temperature and varies considerably over a wide temperature range (20-80 °C). Therefore, the novel fluorescent sensing probe has great application prospects in Cu2+ detection and temperature sensing.

NIR-driven multifunctional PEC biosensor based on aptamer-modified PDA/MnO2 photoelectrode for bacterial detection and inactivation.

Sensitive detection and effective inactivation of bacteria are essential in preventing foodborne bacterial infection that poses a significant threat to human health. Herein, a near-infrared (NIR)-driven multifunctional photoelectrochemical (PEC) biosensor was constructed for detection and inactivation of S. aureus. Based on the covalent bonding between amine and carboxyl groups, carboxyl-functionalized SA31 aptamer was immobilized on the PDA/MnO2 photoelectrode. In the presence of S. aureus, SA31 aptamer can specifically capture S. aureus, causing the decrease of photocurrent signal owing to steric hindrance effect. Leveraging photocurrent-off signal, there existed a satisfied linear relationship between the photocurrent variation and the logarithm of S. aureus concentration, achieving a wide linear range from 10 to 107 CFU/mL with a low detection limit of 2.0 CFU/mL. Notably, PDA/MnO2 with peroxidase-like activity facilitated the catalytic oxidation of S. aureus with assistance of hydrogen peroxide (H2O2) to cause the inactivation of S. aureus. Desorption of inactivated S. aureus from the photoelectrode led to a recovery of photocurrent signal, enabling a "signal on" switch. Simultaneously, the excellent photothermal performance of the PDA/MnO2 converted light energy into heat energy under the irradiation of NIR light (808 nm, 1.5 W/cm2), triggering the synergistic antibacterial effect against S. aureus (97.36%). This work provides a novel strategy for fabricating the detection and inactivation of bacteria in practical applications.

How the black hole illusion environment affects operational performance at different flight phases in aviation.

The black hole illusion (BHI) is a subtype of spatial disorientation that can result in fatal consequences in aviation. Research on the BHI has generally focused on altitude deviation, and few studies have examined the effect across different flight phases. In a simulation-based experiment, 18 participants performed 12 simulated approach and landing tasks in normal and BHI environments. Flight performance was analyzed with 14 flight parameters and was compared across five points and three phases, which were referenced from a National Transportation Safety Board report and other previous studies. Results showed that multiple flight parameters were significantly impaired and that their influences varied from the initial approach to the final touchdown. In the BHI environment, participants tended to descend aggressively during the approach phase and flew a lower but similar glidepath during the last approach phase. They might have realized the abnormal situation induced by the BHI but usually were unable to recover from the dangerous maneuver in time. Additionally, the result of glide path error, one of the most commonly used variables in previous BHI research, was only significant during the last approach phase. Flight stability was also impaired in the BHI environment. This is the first study to systematically analyze the BHI effects on multiple flight parameters at different flight phases. The use of this experimental paradigm could facilitate future research to evaluate and prevent the BHI in a more comprehensive way.

Tenon excision with fibrin glue-assisted reattachment of conjunctiva flap (T.E.F.A.R.C) for the treatment of conjunctivochalasis.

To observe the surgical outcome of "Tenon Excision with Fibrin Glue-Assisted Reattachment of Conjunctiva Flap" (T.E.F.A.R.C.) for the treatment of symptomatic conjunctivochalasis (CCH). This is a retrospective case series of CCH patients undergoing T.E.F.A.R.C. from January 2017 to December 2020 were reviewed. Seven patients (14 eyes) with symptomatic CCH received T.E.F.A.R.C. in both eyes. The symptoms before and after the procedures were compared and surgical complication was evaluated. The mean follow-up time was 13.7 ± 2.14 months. After the operation, resolution of the symptoms was reported in 12 eyes (86%). The grade of CCH decreased from 3 to 0 in all 14 eyes, and the restoration of inferior conjunctival surface and fornix within 1 day was also observed in all eyes. Most patients had localized injection and mild chemosis after the operation, which mostly recovered within 3 weeks. No complication or recurrence of CCH was reported after 1 year of follow-up. In conclusion, T.E.F.A.R.C. is a simple and effective treatment option for CCH with less surgical complication. Future larger studies are needed to confirm its clinical applicability.

Personalized multidisciplinary approach of orbital apex foreign body: A case report and literature review.

Foreign bodies in the intraconal space are unusual, and lodgment at the orbital apex was even more unusual. High-velocity object injuries, such as gunshots or industrial accidents, are the common causes of intraorbital foreign bodies. It is difficult for surgeons to retrieve foreign bodies from the orbital apex as it is a deep, narrow space with critical surrounding structures. The use of an image-guided navigation system improves the accuracy of transnasal endoscopic surgery and causes less damage. We present a case in which a bullet became lodged in the orbital apex and was successfully removed using transnasal endoscopic surgery with the collaboration of otolaryngologists and ophthalmologists. To summarize, orbital apex foreign bodies are harmful, and prompt removal with a personalized multidisciplinary approach is critical.

Podocalyxin EBP50 ezrin molecular complex enhances the metastatic potential of renal cell carcinoma through recruiting Rac1 guanine nucleotide exchange factor ARHGEF7.

Podocalyxin was initially identified in glomerular podocytes to critically maintain the structural and functional integrity of the glomerular ultrafiltrative apparatus. Lately, it has emerged as a malignant marker in tumors arising from a variety of tissue origins. By immunohistochemistry, we identified that 9.6% of renal cell carcinoma patients overexpress this protein. This subset of patients had significantly shorter disease-specific and overall survivals, and, importantly, we established podocalyxin overexpression as an independent prognostic factor for latent distant metastasis with multivariate analysis. Podocalyxin down-regulation by small interfering RNA led to defective migration in model renal tubular cells, which was corrected by re-expression of podocalyxin. The activity of the small GTPase Rac1, a well-characterized modulator of cell migration, was diminished by podocalyxin knock-down. Conversely, podocalyxin overexpression in human embryonic kidney cells up-regulated Rac1 activity, which depended on a complex formed by podocalyxin, ERM-binding phosphoprotein 50, ezrin, and ARHGEF7, a Rac1 activator. Therefore, podocalyxin can serve as a biomarker to identify renal cell carcinoma patients with higher metastatic potential for more aggressive intervention at earlier clinical stages.

Biological and biocompatible characteristics of fullerenols nanomaterials for tissue engineering.

Fullerenes, as hydrophobic molecules, are limited in biomedical function due to their very low solubility. But taking C60(OH)ₓ as an example, the properties of fullerenols were analyzed. It was found that fullerenols had good stability, water solubility, good biocompatibility and low cytotoxicity by adding a hydroxyl group to carbon atoms. In the biomedical field, it has been found that fullerene C60 can be used as a powerful free radical scavenger, with antioxidant activity, with antibacterial and inhibitory effects on cancer cells. Fullerenols inherit the good properties of fullerenes, and are better used in cancer treatment, including loading drug therapy and directly as an anticancer drug. In addition, fullerenols are also used in the repair of myocardial injury, the treatment of myocardial infarction and neuroprotection. With the development of tissue engineering technology, the preparation of nerve scaffolds which can improve ischemia, hypoxia and oxidative stress after nerve injury has become a research hotspot. The electron absorption and reduction characteristics of fullerenols in biomedical research bring new ideas for the treatment of oxidative stress in the repair of peripheral nerve defects. It seems that the research on fullerenols loaded neural scaffold has great prospects.

Peripapillary Choroid Thickness as a Predisposing Factor for Nonarteritic Anterior Ischemic Optic Neuropathy: A Semiautomated OCT Study.

Purpose: The purpose of this study was to investigate the correlations between peripapillary choroidal thickness (PCT) and nonarteritic ischemic optic neuropathy (NAION) by using semiautomated optic coherence tomography (OCT). Methods: A total of 35 NAION eyes, 29 unaffected fellow eyes, and 40 eyes from an age-matched control group were recruited. Enhanced-depth imaging OCT was performed after the resolution of disc edema. PCT was measured using a customized semiautomated MATLAB program. Regression models adjusted for multiple variables were used to inspect the correlation between mean PCT and NAION. Results: The mean PCT in NAION eyes, unaffected fellow eyes, and the control group was 197.09 ± 38.09, 196.52 ± 38.47, and 153.53 ± 29.92 µm, respectively. The mean PCT was significantly thicker both in NAION-affected eyes and fellow eyes compared with the control group (P < 0.001). No significant difference existed between NAION-affected eyes and unaffected fellow eyes. The PCT of the superior quadrant was significantly thicker than that of the inferior quadrant in all three groups. In the multivariate logistic regression, PCT was the only predisposing factor for NAION. However, the value of the PCT was not correlated with final visual outcomes. Conclusions: With a semiautomated program to alleviate the missing measurements, our study demonstrated significantly thicker PCT in both NAION-affected and unaffected eyes of patients, which indicated that peripapillary pachychoroid is a predisposing factor for NAION but may not be a prognostic factor for visual outcomes. Translational Relevance: Accurate measurement of PCT by using semiautomated OCT illustrates the correlation between choroidal vasculature and NAION.

The CAG repeat in SCA12 functions as a cis element to up-regulate PPP2R2B expression.

PPP2R2B, a protein widely expressed in neurons, regulates the protein phosphatase 2A (PP2A) activity for dephosphorylation of tau and other substrates. CAG repeat expansion at the 5'-end of the PPP2R2B gene causes autosomal dominant spinocerebellar ataxia type 12. In the present study, we investigated the roles of CAG repeats and flanking cis elements and the associated proteins in controlling PPP2R2B expression. Deletion/site-directed mutagenesis, in silico searches and cDNA overexpression revealed that CREB1 and SP1 bind to the conserved sequence upstream the CAG repeats to up-regulate PPP2R2B expression, whereas TFAP4 binds to the conserved sequence downstream the CAG repeats to down-regulate PPP2R2B expression. The binding of CREB1, SP1, and TFAP4 to the PPP2R2B promoter was further confirmed by DNA pull-down and ChIP-PCR assays. CAG repeats itself also function as a cis element to up-regulate PPP2R2B expression as AT repeat length has no effect on PPP2R2B expression. Together, our data provide evidence that CREB1, SP1, and TFAP4 play roles in modulating PPP2R2B expression, thus offering a mechanism of regulating PP2A activity as the treatment of neurodegenerative diseases associated with abnormal PP2A activity.

PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.

PPP2R2B, a protein widely expressed in neurons throughout the brain, regulates the protein phosphatase 2A (PP2A) activity for the microtubule-associated protein tau and other substrates. Altered PP2A activity has been implicated in spinocerebellar ataxia 12, Alzheimer's disease (AD), and other tauopathies. Through a case-control study and a reporter assay, we investigated the association of PPP2R2B CAG repeat polymorphism with Taiwanese AD, essential tremor (ET), Parkinson's disease (PD), and schizophrenia and clarified the functional implication of this polymorphism. The distribution of the alleles was not significantly different between patients and controls, with 68.6-76.1% alleles at lengths of 10, 13, and 16 triplets. No expanded alleles were detected in either group. However, the frequency of the individuals carrying the short 5-, 6-, and 7-triplet alleles was notably higher in patients with AD (5/180 [2.8%], Fisher's exact test, P = 0.003; including 2 homozygotes) and ET (4/132 [3.0%], Fisher's exact test, P < 0.001) than in the controls (1/625 [0.2%]). The PPP2R2B transcriptional activity was significantly lower in the luciferase reporter constructs containing the (CAG)(5-7) allele than in those containing the common 10-, 13-, and 16-triplet alleles in both neuroblastoma and embryonic kidney cells. Therefore, our preliminary results suggest that the PPP2R2B gene CAG repeat polymorphism may be functional and may, in part, play a role in conferring susceptibility to AD and ET in Taiwan.

Effects of Dark Septate Endophytes on the Performance of Hedysarum scoparium Under Water Deficit Stress.

Hedysarum scoparium, a species characterized by rapid growth and high drought resistance, has been used widely for vegetative restoration of arid regions in Northwest China that are prone to desertification. Desert soil is typically deficient in available water and the alleviation of drought stress to host plants by endophytes could be an efficient strategy to increase the success of desert restoration. With the objective to seek more beneficial symbionts that can be used in the revegetation strategies, we addressed the question whether H. scoparium can benefit from inoculation by dark septate endophytes (DSEs) isolated from other desert plants. We investigated the influences of four non-host DSE strains (Phialophora sp., Knufia sp., Leptosphaeria sp., and Embellisia chlamydospora) isolated from other desert plants on the performance of H. scoparium under different soil water conditions. Differences in plant performance, such as plant growth, antioxidant enzyme activities, carbon, nitrogen, and phosphorous concentration under all the treatments, were examined. Four DSE strains could colonize the roots of H. scoparium successfully, and they established a positive symbiosis with the host plants depending on DSE species and water availability. The greatest benefits of DSE inoculation occurred in water stress treatment. Specifically, Phialophora sp. and Leptosphaeria sp. improved the root biomass, total biomass, nutrient concentration, and antioxidant enzyme activities of host plants under water deficit conditions. These data contribute to the understanding of the ecological function of DSE fungi in drylands.

Glycosylated liposomes loading carbon dots for targeted recognition to HepG2 cells.

It is important to obtain the targeted nanocarriers during cancer treatment. Herein, mannosylated liposomes encapsulating carbon dots (CDs) are provided for targeted recognition of liver cancer HepG2 cells, which is based on the specific interaction between D-mannose and glycoprotein on the surface of HepG2 cells. CDs were prepared by hydrothermal method. Then, they were encapsulated into liposomes by hydrophobic force. The encapsulation of CDs into liposomes increases their stability and fluorescence intensity. Furthermore, D-mannose can also be inserted into liposomes by the aldehyde amine reaction between aldehyde groups of mannose molecules and amino groups of liposomes. The obtained D-mannose-CDs-liposomes (Man-CDs-liposomes) exhibit selectively tracking and efficiently labelling for cancer cells. The work highlights the potential application of CDs for bioimaging and diagnostic.

ß-Sitosterol-2-hydroxypropyl-ß-cyclodextrin inclusion complex: Characterization and inhibitory effect on adipogenesis in 3T3-L1 pre-adipocytes.

ß-Sitosterol (Sit) has been used as a functional food additive. Among its many beneficial effects, this phytosterol plays a role in controlling obesity by inhibiting the adipogenesis process of pre-adipocytes. However, the highly lipophilic character of Sit limits its bioavailability. In the present study, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was used to form a complex with Sit, namely the Sit-HP-ß-CD inclusion complex, and the inhibitory effect of this complex on adipogenesis in the 3T3-L1 pre-adipocyte cell line was investigated. The results of DSC, TLC, 1H NMR spectroscopy, and 2D ROESY showed that the Sit-HP-ß-CD inclusion complex was successfully synthesized. In addition, the inhibitory effect of the Sit-HP-ß-CD inclusion complex on adipogenesis was evaluated using the Oil Red O staining method and western blot analysis after a 14-day adipogenesis induction in 3T3-L1 pre-adipocytes. The results showed that the Sit-HP-ß-CD inclusion complex had a higher efficiency than Sit in reducing intracellular lipid accumulation and the expression levels of PPARγ and FAS in 3T3-L1 cells, suggesting that the inhibitory effect on adipogenesis was improved by the formation of the Sit and HP-ß-CD complex.

Expanded trinucleotide repeats in the TBP/SCA17 gene mapped to chromosome 6q27 are associated with schizophrenia.

Schizophrenia has a complex and non-Mendelian mode of inheritance. Recently, trinucleotide repeat (TNR)-containing genes have been considered as the candidate genes predisposing to schizophrenia. The purpose of this study was to determine whether a genetic association could be observed between schizophrenia and the TNR polymorphisms within the KLHL1AS/SCA8, PPP2R2B/SCA12, and TBP/SCA17 genes. We studied 100 unrelated schizophrenia patients and 124 controls without evident neurodegenerative or psychiatric disorders. The overall allele frequency distributions of the KLHL1AS/SCA8 and PPP2R2B/SCA12 genes were not significantly different between the schizophrenic patients and the control subjects (P>0.05). The allele frequency distribution in the schizophrenic patients was significantly different from that in the controls at the TBP/SCA17 gene (P=0.0149), with an increased frequency of 36 repeats in the patients and two patients carrying 45 TNR expansions were identified. TBP/SCA17 is the TATA box binding protein gene mapped to chromosome 6q27. The study suggests that TNR expansions of the TBP/SCA17 gene may contribute to the genetic risk of schizophrenia in rare cases.