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Rutin, a flavonoid found in fruits and vegetables, is a potential anticancer compound with strong anticancer activity. Therefore, electrochemical sensor was developed for the detection of rutin. In this study, CoWO4 nanosheets were synthesized via a hydrothermal method, and porous carbon (PC) was prepared via high-temperature pyrolysis. Successful preparation of the materials was confirmed, and characterization was performed by transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin. The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability. PC has a high surface-to-volume ratio and superior conductivity. Moreover, the hydrophobicity of PC allows large amounts of rutin to be adsorbed, there by increasing the concentration of rutin at the electrode surface. Owing to the synergistic effect of the 3D CoWO4 nanosheets and PC, the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity. The sensor showed a good linear range (5–5000 ng/mL) with a detection limit of 0.45 ng/mL. The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

A one-pot, base-mediated approach to Acanthus ilicifolius Linn alkaloid 2-benzoxazolinone derivatives is developed. Starting from trichloroacetic acid, o-aminophenol, substituted benzaldehydes and alkyl isocyanides, the desired 2-benzoxazolinone derivatives are obtained in good yields via a tandem Ugi condensation and intramolecular haloform cyclization at room temperature in the presence of Et3N.

Purpose To report the anatomic and functional outcomes of autologous retinal transplantation (ART). Design Multicenter, retrospective, interventional, consecutive case series. Participants One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. Methods All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. Main Outcome Measures Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. Results One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P Conclusions In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

The detection of tumor-related exosomes is of great significance. In this work, a fluorescence aptasensor was designed for the determination of tumor-related exosomes based on the capture of magnetic nanoparticles (MNPs) and specific recognition of an aptamer. MNPs were used as substrates to capture the exosomes by modifying the CD63 antibody on the MNP surface. Probe 1 consists of PDL-1 aptamer sequence and a section of other sequences. PDL-1 expression was observed on the surface of exosomes; the aptamer of PDL-1 could combine with PDL-1 with high affinity. Thus, the immunoassay-type compounds of “MNPs–exosomes–probe 1” were formed. The other section of probe 1 triggered the HCR with probe 2 and probe 3 and formed the super-long dsDNA. The addition of GelRed resulted in the generation of an amplified fluorescence signal. The proposed design demonstrated a good linearity with the exosome concentration ranging from 300 to 107 particles per mL and with a low detection limit of 100 particles per mL. This aptasensor also exhibited high specificity for tumor-related exosomes, and was successfully applied in biological samples.

An electrochemical aptasensor with high sensitivity, specificity, and good intra-day reproducibility is reported to meet the detection needs of vascular endothelial growth factor (VEGF). The toehold-mediated strand displacement recycling amplification and VEGF aptamer are integrated in the biosensor. The probe A is hybridized with the VEGF aptamer to form the probe A–aptamer complex. When VEGF is introduced, the aptamer specifically binds with VEGF, and probe A can be liberated. Then, the free probe A captures the toehold region of the Hp1, leading the exposure of the toehold region on the other end of Hp1. Similarly, Hp2 and Hp3 are also immobilized on the surface of the electrode; thus, the methylene blue labelled on Hp2 and Hp3 causes the current response. With the signal transduction mechanism, the expression level of VEGF can be detected quantitatively. With a series of optimizations of sensor parameters, high sensitivity and specificity of the VEGF detection sensor can be achieved with a detection limit as low as 10 pg mL−1. This significant performance has good intra-day reproducibility, and it can be applied to human biological samples such as serum, urine, and saliva to detect the VEGF content.

Heavy metal pollutants pose a serious threat to the environment and the health of organisms. This study explored the basic characteristics of poly (acrylic acid)/acrylamide (PAAAM) hydrogel, and evaluated its application in heavy metal ions removal from simulated and real electroplating wastewater. The results showed that PAAAM displayed the highest swelling ratio and adsorption capacity of 5% AM. The swelling ratio of 5%-AM-PAAAM reached 30000% in pH 4.0–7.0. The adsorption of Cu2+ and Ni2+ reached equilibrium in 60 min, with the maximum adsorption capacities of 159.45 and 107.68 mg/g, respectively. The adsorption kinetics fitted the pseudo-second-order model and the adsorption isotherm followed the Langmuir model, exhibiting an exothermic adsorption process. In competitive removal process, 5%-AM-PAAAM showed selective adsorption to Cu2+ than Ni2+ in aquatic solution. The adsorption mechanism was related to the O-H groups in acrylic acid based on X-ray photoelectron spectroscopy (XPS) detection. In summary, 5%-AM-PAAAM was a specific adsorbent for Cu2+ in aquatic solution with high Cu2+ concentration.

Seven new cucurbitane-type triterpenoids, kuguaovins A–G (1–7), and five known ones were isolated from the rattans of wild Momordica charantia. Their structures were established by spectroscopic da...

Background To evaluate the feasibility of a surgical technique using a sub-perfluoro-n-octane (PFO) injection of ocular viscoelastic device (OVD) to stabilize inverted internal limiting membrane (ILM) flap for the treatment of macular hole retinal detachment (MHRD). Methods This study was a retrospective, consecutive, interventional case series. Patients who underwent MHRD surgery with sub-PFO injection of OVD to stabilize inverted ILM flap onto the macular hole (MH) were reviewed. The color fundus and optical coherence tomography (OCT) images were collected and evaluated. The best-corrected visual acuity (BCVA) before and after surgery were compared as the functional outcome. Results The study included 8 eyes of 8 consecutive patients (mean age: 61.8 ± 7.1 years; mean follow-up period: 9.0 ± 2.5 months). All eyes (100%) achieved successful MH closure; 7 eyes (87.5%) demonstrated complete retinal reattachment, and 1 eye (12.5%) had minimal residual subretinal fluid parafoveally. Of the 8 patients, 7 patients (87.5%) had achieved improvement in BCVA after the primary surgery, whereas 1 eye remained stable. The average BCVA before and after the surgery at the last visit improved from 20/843 (1.63 ± 0.48 logMAR) to 20/200 (1.00 ± 0.39 logMAR) (P = 0.016). Anatomically, near-normal foveal contour was noted in five (62.5%) eyes at the final follow-up. Conclusions The use of sub-PFO injection of OVD in MHRD surgery could stabilize inverted ILM flaps, achieve good anatomical results and improve postoperative BCVA.

Oxacillin resistance mediated bymecAinStaphylococcus lugdunensisis emerging in some geographic areas. We evaluated cefoxitin disk diffusion (DD) and a new oxacillin agar (supplemented with 2 μg/ml oxacillin and 2% sodium chloride) screen for the detection ofmecA-mediated resistance inS. lugdunensis. A total of 300 consecutive, non-duplicated clinicalS. lugdunensisisolates from diverse sources in Hong Kong in 2019 were tested. The categorical agreement and errors obtained between cefoxitin DD test, oxacillin agar screen andmecAPCR were analyzed. Isolates with discordant results were further tested by MIC, penicillin binding protein 2a (PBP2a) assays, population analysis and molecular typing. PCR showed that 62 isolates weremecA-positive and 238 isolates weremecA-negative. For cefoxitin DD results interpreted usingS. aureus/S. lugdunensisbreakpoints, the categorical agreement (CA) for two brands of Muller-Hinton agars, MH-II (Becton Dickinson) and MH-E (bioMérieux) were both 96.0%; MEs were both 0%; and VMEs were 19.4 and 12.9%, respectively. The new oxacillin agar reliably differentiatedmecA-positive andmecA-negative isolates (100% CA) without any ME or VME results. The 8 isolates with false susceptibility in the cefoxitin DD testing had cefoxitin and oxacillin MICs in the susceptible range. The isolates showed heterogeneous oxacillin resistance with resistant subpopulations at low frequencies. All had positive PBP2a results and were typed as sequence type 27/SCCmecV. The findings highlight the inability of cefoxitin DD and MIC tests for reliable detection of somemecA-positiveS. lugdunensisisolates.

BACKGROUND Preclinical and clinical studies have shown that the extract of Cynanchum paniculatum (bunge) kitag and the fukeqianjin formulation have beneficial effects in pelvic inflammatory disease (PID). This study aimed to compare the effects of Cynanchum paniculatum and fukeqianjin with a new decoction, xiaoyuningkun, consisting of Melia toosendan, Angelica biserrata, and Cynanchum paniculatum, in a mouse model of PID. MATERIAL AND METHODS The mouse model of PID included injection of the upper genital tract with hydrochloric acid (HCl) and lipopolysaccharide (LPS). The control group underwent sham treatment with 0.9% physiological saline. Cynanchum paniculatum, fukeqianjin, and xiaoyuningkun decoction were administered orally for 15 days. Acetic acid-induced writhing and thermal nociception hot plate tests evaluated the analgesic effects of treatment. Mouse uterus and Fallopian tubes were examined histologically to evaluate the degree of inflammation. Immunohistochemistry was used to measure the protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF). Enzyme-linked immunosorbent assay (ELISA) measured serum levels of inflammatory cytokines. RESULTS Treatment with xiaoyuningkun decoction significantly reduced the pain threshold in the mouse model of PID and the degree of inflammation in the uterus and Fallopian tubes compared with Cynanchum paniculatum and fukeqianjin. Cynanchum paniculatum decoction significantly reduced the serum levels of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-alpha), ICAM-1, and VEGF, and the expression of ICAM-1 and VEGF in the mouse uterus and Fallopian tubes. CONCLUSIONS The new xiaoyuningkun decoction had analgesic and anti-inflammatory effects in the mouse model of PID, possibly by inhibiting ICAM-1, VEGF, and inflammatory cytokines.

A simple and versatile route for the synthesis of mesoporous carbon nanotube (CNT)-supported platinum/tungsten carbide (Pt/WC) nanoparticles (NPs) was set up via vapor deposition process. Amorphous...

This work reports the synthesis of new and efficient composite photocatalysts (Bi12SiO20/g-C3N4) via the controlled hydrothermal method. The Bi12SiO20/g-C3N4 composites were characterized by XRD, SEM-EDS, HRTEM, FT-IR, XPS, DRS, BET, PL, and EPR. In comparison to pure Bi12SiO20 and g-C3N4, the Bi12SiO20/g-C3N4 materials showed significantly higher photocatalytic activity for degradation of crystal violet (CV) under visible-light irradiation (99% in 48 h). The 5 wt% Bi12SiO20/g-C3N4 composite revealed the highest rate constant of CV degradation (0.078 h−1); 15 and 2 times larger than the constants obtained with individual Bi12SiO20 and g-C3N4, respectively. Further investigation of the photocatalytic activity of the 5 wt% Bi12SiO20/g-C3N4 materials were performed on other organic pollutants. 98% degradation of 2-hydroxybenzoic acid (2-HBA) and 99.5% degradation of rhodamine-B (RhB) were achieved upon exposure to visible-light irradiation for 72 h with 5 wt% Bi12SiO20/g-C3N4. Bi12SiO20/GO (graphene oxide) composites were also synthesized to compare the photocatalytic activities of different Bi heterojunctions. It was found that Bi12SiO20/g-C3N4 photocatalysts had enhanced photocatalytic activity in degradation of CV and 2-HBA and were considerably more stable in recycling experiments in comparison to Bi12SiO20/GO photocatalysts. Lastly, the plausible photocatalytic mechanism for the Bi12SiO20/g-C3N4 composite material was proposed and the principal active species involved in the photodegradation of CV were investigated using scavenger and ESR experiments. The Bi12SiO20/g-C3N4 composite demonstrates good photocatalytic activity, stability and reusability, demonstrating its prospective use in photodegradation applications under visible-light irradiation.

Perimenopausal syndrome (PMS) has a high incidence rate and affects the physical and mental health of middle-aged and elderly women. The blockage of PMS is significant in improving the health of perimenopausal women. Currently, for PMS prevention and treatment, traditional Chinese medicine (TCM) has become an ideal choice because of its safety and effectiveness. This study aimed to explore the anti-PMS effects of Ziyin Bushen Decoction (DKTP) and the underlying mechanism. Thirty female Wistar rats were divided into 5 groups (n = 6): control group, low-dose DKTP group, medium-dose DKTP group, high-dose DKTP group, and nilestriol group. The estradiol (E2) level in rat peripheral blood was analyzed using an E2 Radioimmunoassay Kit, and uterine morphologic changes were examined by hematoxylin-eosin staining. Learning and memory ability of rats was assessed by Morris water maze (MWM) and novel object recognition (NOR) task. E2 synthesis, metabolism, and transport associated estrogen receptor-alpha (ERα), GnRHR, CYP17, CYP11A1, CYP19, 17βHSD, STS, and SHGB were assessed to explore the E2-promoting mechanism of DKTP during PMS treatment. The loss of learning and memory, the decreased estrous and uterine coefficient, and the presence of histopathological changes suggests a successful establishment of rat PMS model. Following DKTP or nilestriol treatment, the above results were reversed. E2 level in serum, uterine, and ovarian tissues was upregulated upon different concentrations of DKTP treatment, indicating that DKTP promotes the E2 level in a dose-dependent manner. DKTP also increased the expression of ERα, CYP17, CYP11A1, CYP19, 17βHSD, STS, and SHGB while decreased the GnRHR expression in uterine and ovarian tissues, revealing that these key molecules involved in estrogen synthesis, metabolism, and transport in PMS rats. We confirmed the anti-PMS effect of DKTP through enhancing E2 production. Exploring a novel drug based on improving E2 synthesis, metabolism, and transport may represent a novel strategy for PMS prevention and treatment.

Vascular endothelial growth factor (VEGF) is the principal growth factor responsible for the retinal neovascularization in the pathogenesis of retinopathy of prematurity (ROP). Current therapies for ROP include laser ablation and intravitreal anti-VEGF injection. However, these treatments either destroy the peripheral retina or associate with problems of persistent peripheral avascular retina or later recurrence of ROP. In the present study we investigated a new therapeutic approach by exploring the potential role of a specific microRNA, miR-126, in regulating VEGFA expression and retinal neovascularization in a rat oxygen-induced retinopathy (OIR) model. We demonstrated that miR-126 mimic and plasmid effectively suppresses VEGFA mRNA expression in both human and rat retinal pigment epithelium cell lines, quantified with qRT-PCR. Animal experiments on rat OIR model revealed that intravitreal injection of miR-126 plasmid efficiently downregulated VEGFA expression in the intraocular fluid and retinal tissues measured by ELISA, and significantly suppressed retinal neovascularization, which was confirmed by calculating sizes of neovascularization areas on fluorescence microscopic images of flat mounted retina stained with Alexa Fluor 594-conjugated isolectin B4 to visualize blood vessels. Together, these results showed that intravitreal injection of miR-126 plasmid could inhibit retinal neovascularization by down-regulating VEGFA expression, suggesting a potential therapeutic effect for ROP.

We have demonstrated world-record thermophotovoltaic (TPV) conversion efficiency in two materials systems operating at two different thermal emitter temperatures. A GaAs-based PV device under a 2330 °C thermal emitter produced an efficiency of (31 ± 2)%, and an In 0.53 Ga 0.47 As -based PV device under a 1300 °C thermal emitter produced an efficiency of (30 ± 2)%. The electrical output power densities of the cells were 2.45 W/cm2 and 0.658 W/cm2, respectively. Critical to these high efficiencies were the cells' high reflectance of photon energies below the absorber band gap. Unlike solar PV, for which sub-band gap (SBG) light is lost, a TPV cell can reflect SBG light back to the thermal emitter where it can be recycled. The demonstrations were made on a custom-built measurement platform in which a ~ 100 cm2 graphite thermal emitter was heated under vacuum. The TPV efficiencies were evaluated by comparing the measured electrical output power of the cell with the total power absorbed by the cell. The measured TPV efficiencies as a function of thermal emitter temperature were corroborated by our full system modeling. As far as the authors are aware, these are the highest TPV conversion efficiencies ever measured, and device improvements should yield > 40% efficiency in the near future.

The formation of N-(2'-(diphenylphosphoryl)-[1,1′-biphenyl]-2-yl)-2,3,4,5,6-pentafluorobenzamide (3_eaaa) has been achieved through the palladium-catalyzed and Ag(I)-assisted C H functionalization of N-([1,1′-biphenyl]-2-yl)-2,3,4,5,6-pentafluorobenzamide (1_eaa) via phosphination and in the presence of diphenylphosphine oxide (2_a). The reaction was accompanied with small amount of carbazole derivative, (9H-carbazol-9-yl)(perfluorophenyl)methanone (4_eaa). Crystal structures of 3_eaaa and 4_eaa were both determined by X-ray crystal diffraction methods. Indeed, phosphination took place at the ortho-position of inter-annular ring of 1_eaa. Substituents with various electron-withdrawing/donating capacities on the amido-fragment of 1 were found to greatly affect the ratio distribution of products 3 and 4. By contrast, substituents on various locations of the biphenyl in 1 do not influence much on the outcome of the products distribution. A reaction mechanism is proposed to account for these experimental observations. Computational studies employing Density Functional Theory methods (DFT) on this proposed mechanism found that the electron density property of the palladium metal center in the intermediate II is critical to the formation of either 3 or 4. A relatively electron-poor palladium metal center favors the pathway of forming 3. On the contrary, the pathway of producing 4 will be prevailed while the palladium metal center is having fair amount of electron-density in the proposed intermediate II.

The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24‐GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24‐GCB cells in a dose‐dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24‐GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24‐GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24‐GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.

Summary Background Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ribavirin for treating patients with COVID-19. Methods This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. Findings Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study. Interpretation Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. Funding The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

The syntheses, structures and thermal properties of six coordination polymers based on semi-rigid N,N′-bis(3-pyridinyl)terephthalamide (L1), flexible N,N′-di(3-pyridyl)adipoamide (L2) and N,N′-di(3-pyridyl)suberoamide (L3) and auxiliary dicarboxylate ligands, [M(L1)(AIPA)·2H2O]n, (M = Ni, 1; Co, 2; H2AIPA = 5-acetamido isophthalic acid), [Ni(L2)(AIPA)(H2O)2]n, 3, [Co(L2)0.5(AIPA)(H2O)]n, 4, [Co(L3)(2,4-PDC)(H2O)]n (2,4-H2PDC = 2,4-pyridinedicarboxylic acid), 5, and [Co(L3)(5-Br-IPA)(H2O)]n (5-Br H2IPA = 5-bromoisophthalic acid), 6, are reported, which have been structurally characterized by X-ray crystallography. Complexes 1 and 2 are isomorphous, forming 3D nets with the new (4⋅6⋅8)(4⋅64⋅85) topology, which can be further simplified as self-catenated networks with the (424⋅64)-8T2 topology, while 3 is a 1D looped chain and 4 and 6 show 2D layers with the (42⋅63⋅8)(42⋅6)-3,4L83 and (44⋅62)-sql topologies, respectively. Moreover, complex 5 shows quadruple-strained helices formed by cobalt ions and L3 ligands, which are supported by 2,4-PDC2- anions to construct the rare single-walled metal-organic nanotubes that are supported by extensive N H --O and O H --O hydrogen bonds. The roles of ligand flexibility and the identity of the metal ion in the formation of 1–6 as well as their thermal properties are discussed.

To perform preclinical studies to determine the efficacy and safety of anthocyanins as stains for the internal limiting membrane (ILM) of the eye.Cyanidin (Cya), delphinidin (Del), luteolinidin (Lut), peonidin (Peo) and pelargonidin (Pel) were evaluated. These natural dyes were used to stain the lens capsule and ILM of pig eyes. The effects of these dyes on retinal cell viability was determined using a water-soluble tetrazolium salt assay, and oxidative stress was measured in vitro. Histopathology, in situ TUNEL labelling, transmission electronic microscopy (TEM), and electroretinography (ERG) were performed on rats following the intravitreal and subretinal injection of the neuroprotective dyes.All anthocyanins stained the lens capsule and ILM of the pigs at a concentration of 1 mg/ml. Del, Lut and Peo were non-toxic and produced survival rates in the ARPE19 and RGC5 cells that were similar to those in control cells. We treated eyes with HThis preclinical study, Del, Lut, and Peo show potential as staining agents and warrant further investigation as vital dyes.

Purpose To investigate the clinical features in carriers of X-linked retinitis pigmentosa, X-linked ocular albinism, and choroideremia (CHM) using multimodal imaging and to assess their diagnostic value in these three mosaic retinopathies. Methods We prospectively examined 14 carriers of 3 X-linked recessive disorders (X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM). Details of abnormalities of retinal morphology were evaluated using fundus photography, fundus autofluorescence (FAF) imaging, and spectral domain optical coherence tomography. Results In six X-linked retinitis pigmentosa carriers, fundus appearance varied from unremarkable to the presence of tapetal-like reflex and pigmentary changes. On FAF imaging, all carriers exhibited a bright radial reflex against a dark background. By spectral domain optical coherence tomography, loss of the ellipsoid zone in the macula was observed in 3 carriers (50%). Regarding the retinal laminar architecture, 4 carriers (66.7%) showed thinning of the outer nuclear layer and a dentate appearance of the outer plexiform layer. All five X-linked ocular albinism carriers showed a characteristic mud-splatter patterned fundus, dark radial streaks against a bright background on FAF imaging, and a normal-appearing retinal structure by spectral domain optical coherence tomography imaging. Two of the 3 CHM carriers (66.7%) showed a diffuse moth-eaten appearance of the fundus, and all 3 showed irregular hyper-FAF and hypo-FAF spots throughout the affected area. In the CHM carriers, the structural changes observed by spectral domain optical coherence tomography imaging were variable. Conclusion Our findings in an Asian cohort suggest that FAF imaging is a practical diagnostic test for differentiating X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM carriers. Wide-field FAF is an easy and helpful adjunct to testing for the correct diagnosis and identification of lyonization in carriers of these three mosaic retinopathies.

Nitrile rubber O-rings seals for packaging barrel was stored in China tropical marine atmosphere environments for 10 years, and then the sealing function of nitrile rubber O-ring was failed. By comparing the molecular structure, cross-link density, thermal decomposition, content of elements and chemical functional groups of the original nitrile rubber seals, the surface and interior of nitrile rubber seals storage for 10 years, a long-term natural failure mechanism was studied. The results showed that: the surface content of dibutyl phthalate and dibutyl sebacate, the surface carbonyl peak height and the surface content of oxygen element were higher than that in internal; the surface cross-link density was lower than that in internal but still higher than in original sample; and surface carbon- to-oxygen ratio were lower than that in internal and original sample. After aging for 10 years, the weight loss of plasticizer decreased, and the main chain content increased. It can be inferred that nitrile rubber mainly undergoes oxygen-absorbing cross-linking reaction to form carboxylic acids and esters, which is accompanied by the migration and enrichment of two plasticizers to the surface, causing reductions in elasticity and elasticity. The residual permanent compression set was lower than the design critical value, and the sealing function for the packaging barrel was lost, and a leak occurred.

In this study, the partially sulfidized Ni-Co/reduced graphene oxide (NCS/NC/RGO) hybrid was developed as a supercapacitor electrode material. Because Ni-Co sulfide (NCS) possessed good pseudocapacitor property and non-sulfidized Ni-Co (NC) alloy had high conductivity, we attempted to optimize the electrochemical performance of NCS/NC/RGO hybrid by controlling the sulfidation of NC/RGO hybrid. RGO was incorporated as a substrate to help the dispersion of NCS/NC nanoparticles and contribute some capacitance. It was demonstrated that an appropriate sulfidation of NC/RGO hybrid could lead to the highest capacitance effectively. Moreover, the optimal NCS/NC/RGO hybrid also exhibited good stability. The result revealed that the strategy to optimize the capacitor performance of NCS/NC/RGO hybrid via the controlled sulfidation of NC/RGO hybrid was indeed effective.

Porous cobalt sulfide (CoSx)/reduced graphene oxide (rGO) hybrid films has been fabricated as a flexible freestanding supercapacitor electrode via the co-assembly and sulfidation of 2D metal organic framework (MOF) nanoflakes and graphene oxide (GO). Firstly, zeolitic imidazolate-67 (ZIF-67) nanocubes were added into the aqueous solution of GO to yield a mixed dispersion of ZIF-67 and GO (ZIF-GO). It was found that the morphology of ZIF-67 changed from nanocubes to 2D nanoflakes owing to the concentration change, which favored the formation of hybrid film. Secondly, the sandwich-like GO/ZIF-GO/GO hybrid film was fabricated by the successive vacuum membrane filtration of GO, ZIF-GO, and GO solutions. Finally, the hybrid film was sulfidized via a hydrothermal process using thioacetamide as the sulfur source. This process also led to the reduction of GO to rGO. The resulting rGO/CoSx-rGO/rGO hybrid film was shown to have good electrochemical performance because it combined the good pseudocapacitor property of cobalt sulfide as well as the good conductivity and electric double layer capacitor property of rGO. In addition, an all-solid-state asymmetric supercapacitor (aSC) was assembled using rGO/CoSx-rGO/rGO hybrid film and active carbon as the positive and negative electrodes, respectively. It exhibited an energy density of 10.56 Wh kg−1 and a power density of 2250 W kg−1. Also, it retained 92.8% of initial capacitance after 10,000 cycles. The good electrochemical performance revealed that the resulting aSC has great potential in the practical application of supercapacitors.

Cimicifuga simplex is a medicinal herb which has a wide range of biological activities. We isolated seven 9,19-cycloartenol glycosides from the roots of C. simplex, and among the glycosides, G3 exhibited the strongest inhibitory effect on immune responses, including suppressing the differentiation of CD4+ T cells and directly suppressing the cytokine-induced JAK/STAT signaling pathways. In the IL-23-induced mouse ear model of skin disease, G3 repressed disease development by inhibiting the expression of pro-inflammatory mediators in murine ear skin. Moreover, G3 affected the maturation of DCs in vitro, thereby inducing T cell differentiation, resulting in an increased Treg phenotype and decreased Th17 phenotype. This study provides new evidence that G3 might ameliorate chronic inflammatory skin diseases by suppressing pathogenic CD4+ T cell differentiation and the IL-17+RORγt+/IL-10+FoxP3+ ratio. These findings suggest that G3 might mediate the therapeutic effects observed in psoriasis patients following treatment with C. simplex.

Surgical management of macular hole retinal detachment (MHRD) in a myopic eye is a challenging task. Either pars plana vitrectomy or macular buckling alone cannot address all of the pathogenic factors involved in MHRD. Recently, improvements in surgical techniques and new surgical methods have enhanced macular hole closure rates and retinal reattachment rates, but the functional results still remain poor. Although to date there is no general consensus, and controversy remains on the most appropriate surgical treatment, vitrectomy with various additional internal limiting membrane peeling techniques have generally been considered the preferred surgical approach in recent years.

Voriconazole (VCZ) is a widely used triazole drug for the treatment of serious incidence of invasive fungal infections (IFIs), and its most commonly reported clinical side effect is hepatotoxicity. The mechanism of VCZ-induced hepatotoxicity is unclear, and no specific marker can be used for prediction and diagnosis. This study aims to apply the targeted metabolomics approach to identify specific VCZ-induced metabolites related to hepatotoxicity via liquid chromatography-triple quadrupole mass spectrometry (LC-QqQ-MS) in a C57BL/6 mouse model. Mice treated with three repeated doses of 40 mg/kg VCZ by tail vein injection to induce hepatotoxicity (VCZ-induced hepatotoxicity group, n = 8) were compared with mice without treatment (control group, n = 10). Both liver tissue and plasma were collected and analyzed to propose underlying mechanisms associated with VCZ-induced hepatotoxicity. The results indicated that the metabolites associated with oxidative stress were altered, and alterations in the metabolites involved in glutathione biosynthesis were noticed. The ratio of glutamine to glutamate showed a significant reduction in the VCZ-induced hepatotoxicity group compared to the control group, suggesting that glutamine might be transformed into glutamate for glutathione biosynthesis. Accordingly, we proposed that VCZ-induced hepatotoxicity is associated with oxidative stress to cause cell dysfunction, leading to alterations in energy metabolism, the urea cycle, and nucleoside metabolism. To the best of our knowledge, this is the first study to apply metabolomics for investigating the mechanism of VCZ-induced hepatotoxicity.

An electrochemical aptasensing method is described for the determination of the biomarker CA125. It combines aptamer recognition and target-triggered strand displacement amplification. Flower like gold nanostructures were electrodeposited on a screen-printed carbon electrode to increase the sensor surface, to assemble more toehold-containing hairpin probe 1 (Hp1), and to improve the accessibility for DNA strands. Under the optimal conditions, this assay has a linear response in the 0.05 to 50 ng•mL−1 CA125 concentration range, with a low detection limit of 5.0 pg•mL−1. This method is specific and stable. It was successfully applied to the detection of CA125 in spiked biological samples, with recoveries between 82.5% and 104.1%.

The crystal habit of metallic tin (Sn) on a nickel foam electrode (Sn/Ni) was manipulated by cationic surfactants in order to assess the selective conversion of NO3−. The Sn electroplating additive included benzethonium chloride (BZT), cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), and hexyltrimethylammonium bromide (C6TAB). Characterization showed that FSn(200) (= Sn(200)/[Sn(200) + Sn(101)]), which indicated that the preference of the Sn(200) facet was modified by the surfactants. FSn(200) was in the following order: BZT > CPC > CTAC > C6TAB-Sn/Ni. As FSn(200) increased, a positive correlation between selectivity of N2 (SN2) and FSn(200) existed. The highest amount of SN2 (as high as 65 %) was obtained at FSn(200) = 0.95. The consecutive kinetics was derived to define the formation rate of the nitrogen compound in the constant current mode. NO3- and NO2- adsorption determined the effectiveness of nitrate reduction on the Sn(200) surface, which efficiently mediated H species formation.

Nonstoichiometric silicon carbide (SiC) bus/ring waveguide resonator based all-optical data-format follower and inverter is demonstrated to perform ultrafast dual-functional wavelength and data-format conversion. The buried Si quantum dots (Si-QDs) with strong quantum confinement effect effectively result in a significant change on the nonlinear refractive index of 3.14 × 10–13 cm2/W, which induces a red-shift of 0.07 nm on the resonant wavelength comb of the nonstoichiometric SiC ring waveguide resonator. By injecting the 12 Gbit/s optical pulsed return-to-zero on–off keying (PRZ-OOK) data stream into the ring waveguide at a notched wavelength of 1551.08 nm, the induced red-shift on resonant wavelengths allows versatile all-optical data processing functions, including data wavelength conversion and data format following/inversion, on the data patterns transferred to the probe. The eye-opening diagram analysis at 12 Gbit/s reveals that the data transferred to the probe can provide a signal-to-noise ratio ...

This study investigated the effects of growth factors and internal limiting membrane components on Müller cell migration. We studied the effects of epidermal growth factor (EGF), fibroblast growth factor (FGF), somatomedin (IGF-1), platelet derived growth factor (PDGF), and stromal cell-derived factor-1 alpha (SDF-1α) as well as collagen IV, laminin, and fibronectin on the proliferative and migratory activities of rat Müller cells in vitro. A water soluble tetrazolium-1 assay was used to quantify the viability of Müller cells in respective cultures, and analysis was performed using an enzyme-linked immunosorbent assay reader. All the factors examined had significant proliferative effects on cultured Müller cells (p .05). A two-well Ibidi silicone culture insert was used to assess Müller cell migration. Müller cells cultured in EGF, FGF, IGF-1, collagen IV, and laminin but not in SDF, PDGF, or fibronectin effectively increased the cell migratory activity (p .001). In addition, combined EGF and collagen IV, combined FGF and collagen IV, and combined IGF-1 and laminin exhibited more significant (p .001) effects on Müller cell migration compared with culture a single factor. In summary, this study revealed the combinatorial effects of various growth factors and individual internal limiting membrane constituents. This may assist Müller cell migration together with the macular hole healing process.

Introduction Gastric carcinoma (GC), hepatocellular carcinoma (HCC) and pancreatic carcinoma (PC) are gastrointestinal cancers (GIC) with high mortality, which seriously threaten health of the global population. The Chinese herbal medicine Astragalus membranaceus (AM) is widely used in anti-cancer treatment, including GIC. However, the potential pharmacological mechanism remains unclear. This study aimed to investigate the underlying mechanism of AM in the treatment of GIC based on network pharmacology. Methods The database TCMSP was employed to identify the effective chemical components and potential targets of AM. GeneCards and DisGeNET databases were employed to screen associated genes of GIC. The active compounds and targets of AM in treating GIC were identified through network pharmacologic analysis. GO and KEGG enrichment analyses and survival analysis were performed to predict the anti-cancer mechanism and hub genes of AM in treating GIC. Results A total of 17 active compounds and 110 targets involving AM for treating GIC were identified. Quercetin, kaempferol, formononetin, isorhamnetin, 7-O-methylisomucronulatol and calycosin are main active compounds of AM for treating GIC. AKT1, CCND1, CASP3, EGF, FOS, IL6, IL10, JUN, MAPK1, MAPK8, MMP2, MMP9, MYC, PTEN, PTGS2 (COX-2), TNF and VEGFA are the hub genes for AM for treating GIC. AM mainly plays an anti-GIC role by regulating PI3K-Akt signaling pathway, MAPK pathway and TNF pathway. Conclusions The potential molecular mechanism of AM in treating GIC were unveiled based on network pharmacology analysis at the first time, which may provide a new strategy for the development of more effective anti-cancer drugs.

Voriconazole is one of the most frequently used antifungal drugs for the initial treatment of invasive aspergillosis, but liver-related adverse events occur frequently and usually lead to drug discontinuation. Moreover, the mechanism of voriconazole-induced hepatotoxicity remains unsettled. A holistic understanding of its mechanism is critical to prevent liver-related adverse events. Metabolomics has been demonstrated to be a helpful strategy for investigating drug-induced toxicity. This study aimed to utilize human plasma samples to investigate the mechanism of voriconazole-induced hepatotoxicity through a metabolomics approach. Patients that were administered voriconazole were classified into a voriconazole-induced hepatotoxicity group and control group (n = 65, 18% hepatotoxicity). Plasma samples were analyzed by targeted metabolomics using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. The obtained peak areas for each metabolite were utilized for correlation analysis, fold change evaluation, and univariate statistical tests to identify metabolites associated with voriconazole-induced hepatotoxicity. This study showed a significantly lower glutamine-to-glutamate ratio (p = .04) and a higher β-N-acetylglucosamine (p = .003) in the voriconazole-induced hepatotoxicity group, implying the presence of oxidative stress. Other significant metabolites also indicated several adaptive responses to oxidative stress in patients with voriconazole-induced toxicity, including cell repair, energy production, and alteration to bile acid hemostasis. Furthermore, a metabolite panel consisting of α-ketoglutarate, glycocholate, and β-N-acetylglucosamine demonstrated better performance for detecting voriconazole-induced hepatotoxicity than conventional liver function tests. These metabolomics findings reveal that voriconazole-induced hepatotoxicity is associated with oxidative stress.

Surfactants, namely, cetyltrimethylammonium chloride, polydiallyldimethylammonium chloride, and benzethonium chloride were used to control the crystal growth of metallic Cu nanoparticles supported on stainless steel mesh electrodes as to improve the selective electrochemical conversion of NO3− to non-toxic N2. Results showed that the Cu(200)/Cu(111) ratio controlled the selectivity of N2, NO2−, and NH4+. The Kd value increased from 10% to 30% when the Cu(200)/Cu(111) intensity ratio was decreased 60% to 30%, meaning increase Cu(111) increased N2 production. Furthermore, the presence of a second metal, namely, Pd increased the N2 selectivity. The best N2 yield (XN2 = 22%), occurring on monometallic Cu, synthesized with BZT at 1-time CMC was further increased to XN2 = 65% over bimetallic Pd0.27Cu0.73/SS. The selectivity of nitrite (SNO2-) and ammonium (SNH4+) on Cu/SS were 33.1 and 43.5%, respectively, which were decreased to 0.30 and 34.0%, respectively, on bimetallic Pd0.27Cu0.73/SS.

Three-dimensional (3D) nickel phosphide/reduced graphene oxide (rGO)/nickel oxide composite on nickel foam (Ni2P/rGO/NiO/NF) is fabricated as a supercapacitor (SC) electrode material via the two-step electrochemical deposition of graphene oxide (GO) and nickel phosphide on the nickel foam. Typically, rGO/NiO/NF is fabricated at first by the electrochemical treatment of nickel foam at 10 V in 0.1 M sulfuric acid with GO for 10 min. The result reveals that NiO nanosheets are vertically grown on the surface of nickel foam and rGO is deposited on the surface of NiO/NF, leading to the enhancement of capacity. Secondly, nickel phosphide is electrochemically deposited on the surface of rGO/NiO/NF in the sodium hypophosphite-based aqueous solution at 10 mA cm-2 to yield the Ni2P/rGO/NiO/NF. The deposition of Ni2P leads to a much higher capacity. The optimal areal and mass specific capacities are obtained as 3.59 C cm-2 and 742 C g-1 at the electrochemical deposition time of 30 and 10 min, respectively. The high capacity reveals that the proposed two-step electrochemical fabrication process is facile and effective. In addition, the Ni2P/rGO/NiO/NF electrode-based all-solid-state asymmetric SC was fabricated and could successfully turn on a light-emitting diode light. This revealed its feasibility in practical application and confirmed that the resulting 3D Ni2P/rGO/NiO/NF has a great potential as the SC electrode material.

Gemcitabine (GCB), which functions via the inhibition of DNA synthesis, is commonly used in the treatment of bladder cancer; however, its response rate is not satisfactory due to the development of drug resistance. The potential for phytochemicals to reverse drug resistance in bladder cancer tumor cells was evaluated. A human bladder cancer cell line, T24, was cultured, and GCB-resistant cells (T24-GCB) were also established. The acquired resistance of T24-GCB to GCB was measured using an MTT assay. The gene expression of ATP-binding cassette (ABC) transporter protein family members was analyzed using reverse transcription-quantitative PCR analysis, and western blotting was performed to verify ABC family protein, cytoplasmic thymidine kinase (TK) and poly (ADP-ribose) polymerase (PARP) expression on whole cell lysates. Subsequently, resveratrol and curcumin were used to evaluate their modulation potential in decreasing the drug resistance of T24-GCB cells to GCB using MTT and migration assays. T24-GCB cells have increased drug resistance ability, with an 18.75-fold higher ID(50) value compared with native T24 cells (105 vs. 5.6 nM). T24-GCB cells also exhibit increased cross resistance to mitomycin C and paclitaxel. The mRNA expression of ABCC2 in T24-GCB cells increased compared with that in native T24 cells. Via western blot analysis, it was determined that the expression of ABCC2 protein was also increased in T24-GCB cells. Conversely, the expression of ABCB1, ABCG2, deoxycytidine kinase (DCK), TK1 and TK2 decreased. Following curcumin and resveratrol treatment alone or combined with GCB, additive cytotoxic enhancement was observed, and the migratory abilities of T24-GCB cells were significantly decreased. Western blot analysis revealed that ABCC2 protein expression increased, and DCK, TK1 and TK2 expression decreased following co-treatment of T24-GCB cells with GCB + curcumin or resveratrol compared with GCB alone. Of note, there was a marked increase in cleaved-PARP expression in T24-GCB cells treated with a combination of GCB + curcumin or resveratrol. Both curcumin and resveratrol could reverse the drug resistance of T24-GCB cells in an additive pattern though PARP enhancement without changes in ABCC2 and DCK, TK1 and TK2 expression.

Vascular endothelial growth factor (VEGF) is an important mediator of the pathological neovascularization and vascular permeability of the eye. The increasing use of intravitreal therapies targeting VEGF has revolutionized the treatment of pediatric vitreoretinal diseases. In retinopathy of prematurity (ROP), the role of VEGF in pathogenesis has been well recognized and the use of anti-VEGF treatment in phase 2 ROP has demonstrated promising results, particularly in severe cases of posterior disease. This has made VEGF an established target in the treatment of pediatric retinal diseases known to have abnormal vascular activity. However, questions remain about late systemic and neurodevelopmental effects after anti-VEGF therapy for children because intravitreal injection of anti-VEGF may result in systemic circulation of anti-VEGF agent and a corresponding suppression of systemic VEGF. We do not currently know whether the short-term suppression of systemic VEGF affects long-term neurodevelopmental outcomes because VEGF is a vital supporting factor during neurodevelopment. This review article focuses on the evidence for the use of anti-VEGF treatment in certain pediatric ocular diseases, including ROP, Coats disease, and retinoblastoma. More extensive and prospective studies are warranted to further elucidate the role of anti-VEGF therapy in these diseases and illustrate how we can optimally use these agents in pediatric patients.

The spatially ordered and vertically oriented TiO2 nanotube (TNT) arrays were prepared by a two-step anodization process. The TNT arrays (TNAs) were annealed at 450 °C for 30 min, yielding discrete, hollow nanotube structures with anatase phase. CuInS2 (CIS) and In2S3 (InS) chalcogenide nanoparticles were deposited on the top surface, walls, and bottom of the TNAs by repeated drop-casting in ambient atmosphere. Suitable photosensitizer coverage was achieved with CIS5 and InS3CIS5, when exposed to visible light, efficiently generated photoelectrons that traveled uniformly into TNAs. The TNA/CIS10 nanostructures were oversaturated with CIS nanoparticles, resulting in more defects and an overly thick absorption layer promoting premature electron–hole pair recombination. Electrochemical impedance spectroscopy (EIS) analysis indicated that the mass transfer in polysulfide electrolyte occurred sufficiently quickly for the Nernst diffusion impedance (Zd) to be neglected. The equivalent circuit of the TNA nanostructures in polysulfide electrolyte exposed to light was modeled by two serial RQ circuits. The impedance in lower frequency regions contributed to the mechanism of the interface charge transfer when exposed to light. When a positive bias was applied, the photosensitized electrons could travel from the CIS photoabsorption layer through the TNAs, and into Ti electrode more efficiently. The relaxation behavior of open circuit potential exhibited by the TNA/InS3CIS5 nanostructures showing that the enhanced lifetime of photo-induced electrons was a function of the InS3 buffer layer. The novelty of facile drop-casting chalcogenide photosensitive composition containing an excess of sulfur avoided the use of toxic H2S gas and other toxic solvents. The charge transfer mechanisms were established on the basis of the behaviors of suitable photosensitive layers and function of buffer layer.

Nobiletin, a bioactive polymethoxylated flavone (5,6,7,8,3(') ,4(') -hexamethoxyflavone), is abundant in citrus fruit peel. Although nobiletin exhibits antitumor activity against various cancer cells, the effect of nobiletin on glioma cells remains unclear. The aim of this study was to determine the effects of nobiletin on the human U87 and Hs683 glioma cell lines. Treating glioma cells with nobiletin (20-100 µm) reduced cell viability and arrested the cell cycle in the G0/G1 phase, as detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide (PI) staining, respectively; however, nobiletin did not induce cell apoptosis according to PI-annexin V double staining. Data from western blotting showed that nobiletin significantly attenuated the expression of cyclin D1, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and E2 promoter-binding factor 1 (E2F1) and the phosphorylation of Akt/protein kinase B and mitogen-activated protein kinases, including p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Our data also showed that nobiletin inhibited glioma cell migration, as detected by both functional wound healing and transwell migration assays. Altogether, the present results suggest that nobiletin inhibits mitogen-activated protein kinase and Akt/protein kinase B pathways and downregulates positive regulators of the cell cycle, leading to subsequent suppression of glioma cell proliferation and migration. Our findings evidence that nobiletin may have potential for treating glioblastoma multiforme.

The influence of renal dysfunction on the clinical presentation and outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of renal dysfunction on the outcomes of patients with acute first-ever ischemic stroke.Nine-hundred thirty-four patients with acute first-ever ischemic stroke were enrolled and followed for 3 years. Renal function was assessed using the equation of the Modification Diet for Renal Disease for estimated glomerular filtration rate (eGFR). Serum creatinine levels were obtained within 3 days of acute stroke onset. Reduced eGFR was defined as eGFR60ml/min/1.73m(2). Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded.Total 264 patients (28.3%) had a reduced eGFR. The prevalence of older age, hypertension, and atrial fibrillation was significantly higher in patients with a reduced eGFR. Total anterior circulation syndrome occurred more frequently among patients with a reduced eGFR (P=0.010). Multivariate Cox regression revealed that a reduced eGFR is a significant predictor of 3-year mortality (HR=1.67, 95% CI=1.06-2.62, P=0.026).Reduced eGFR during the acute stroke stage is associated with increased risk of 3-year mortality. Furthermore, risk of acute complications and poor functional outcomes following discharge was significantly higher in patients with a reduced eGFR.

Multipotent adult neural precursor cells (NPCs) have tremendous intrinsic potential to repair the damaged spinal cord. However, evidence shows that the regenerative capabilities of endogenous and transplanted NPCs are limited in the microenvironment of spinal cord injury (SCI). We previously demonstrated that injury-induced upregulation of matrix chondroitin sulfate proteoglycans (CSPGs) restricts the survival, migration, integration, and differentiation of NPCs following SCI. CSPGs are long-lasting components of the astroglial scar that are formed around the lesion. Our recent in vivo studies demonstrated that removing CSPGs from the SCI environment enhances the potential of transplanted and endogenous adult NPCs for spinal cord repair; however, the mechanisms by which CSPGs regulate NPCs remain unclear. In this study, using in vitro models recapitulating the extracellular matrix of SCI, we investigated the direct role of CSPGs in modulating the properties of adult spinal cord NPCs. We show that CSPGs significantly decrease NPCs growth, attachment, survival, proliferation, and oligodendrocytes differentiation. Moreover, using genetic models, we show that CSPGs regulate NPCs by signaling on receptor protein tyrosine phosphate sigma (RPTPσ) and leukocyte common antigen-related phosphatase (LAR). Intracellularly, CSPGs inhibitory effects are mediated through Rho/ROCK pathway and inhibition of Akt and Erk1/2 phosphorylation. Downregulation of RPTPσ and LAR and blockade of ROCK in NPCs attenuates the inhibitory effects of CSPGS. Our work provide novel evidence uncovering how upregulation of CSPGs challenges the response of NPCs in their post-SCI niche and identifies new therapeutic targets for enhancing NPC-based therapies for SCI repair. Stem Cells 2015;33:2550–2563

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9,19-cyclolanostane triterpenoid glycosides, which are distributed widely in Cimicifuga plants, but not in other members of the Ranunculaceae family, and are considered to be characteristics of the Cimicifuga genus. This type of triterpenoid glycoside possesses several important biological activities. More than 120 cycloartane triterpene glycosides have been isolated from Cimicifuga simplex Wormsk. The aim of this review article is to summarize all the major findings based on the available scientific literatures on C. simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid glycosides. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.

Aims To interpret how the thickness of the peripapillary retinal nerve fiber layer (RNFL) changes with increasing age, axial length, or anterior chamber depth as measured by spectral domain optical coherence tomography (OCT) in the normal elderly population in Taiwan. Methods A total of 82 volunteers (143 eyes) were enrolled. Generalized estimating equations were used to evaluate the correlation. Results The RNFL was significantly thinner in the superonasal (p = 0.004), inferotemporal (p = 0.046), and temporolower (p = 0.009) segments with age. The same trend was also observed in the superotemporal (p = 0.330) segment, although it was not statistically significant. The global RNFL thickness decreased by 4.97 μm per decade (β = -0.497; p = 0.021), and thinning was significant in the superonasal (-9.90 μm per decade, p < 0.001) and temporolower (-6.78 μm per decade, p < 0.001) segments; the same trend showed borderline significance in the superotemporal (-6.96 μm per decade, p = 0.073) and inferotemporal (-7.23 μm per decade, p = 0.059) segments. In eyes with longer axial length, the RNFLs significantly decreased in the non-temporal segments. Global RNFL thickness decreased by 3.086 μm for each additional millimeter of axial length (β = -3.086; p < 0.001). Conclusions Changes in RNFL thickness were correlated with age in the superonasal, superotemporal, inferotemporal, and temporolower segments, and were correlated with axial length in the non-temporal segments. Anterior chamber depth was not correlated with RNFL thickness.

The toxicity of gadolinium-based contrast agents (GBCAs) has drawn a lot of attention. Nephrogenic systemic fibrosis (NSF), a lethal disease related to the use of GBCAs, is still not understood. Recently, gadolinium retention is found in brain tissues after repeated use of GBCAs in magnetic resonance imaging (MRI). However, most of the works investigating the toxicity of GBCAs are focusing on its high-concentration (0.5–10 mM) part, which is not reflective of the physiological conditions in human beings. Macrophages play a regulatory role in immune responses and are responsible for the fibrosis process. Their role in gadolinium retention and the pathogenesis of NSF, however, has seldom been investigated. This study aimed to evaluate the immune response generated by macrophages (RAW 264.7) exposing to low levels of GBCAs. The incubation concentration of GBCAs, including Omniscan®, Primovist®, Magnevist®, and Gadovist®, is proportional to the level of gadolinium uptake when detected via inductively coupled plasma mass spectrometry (ICP-MS) and imaged by MRI, whereas Primovist® treatment groups have highest gadolinium uptake among all of the tested concentrations. Low-concentration (2.5 μmol/L) Gd chloride or GBCAs exposure promoted the reactive production of oxygen species (ROS), nitrate/nitrite, prostaglandin E2 (PGE2), and suppressed the potential of mitochondrial membrane. There was higher ROS, nitrate/nitrite, and PGE2 production in the Primovist®, Omniscan®, and Magnevist® groups compared to the Gadovist® group. In face of lipopolysaccharide (LPS) stimulation, Primovist®, Omniscan®, and Magnevist® groups exhibited elevated nitrite/nitrate and suppressed IL-1β secretion and IL-6 and IL-10 secretion. Moreover, upon LPS stimulation, there is decreased TNF-α secretion 4 hours after Primovist® or Omiscan® exposure but the TNF-α secretion increased at 24 hours. Our data suggest that there is upregulated inflammation even in the presence of low levels of GBCAs, even similar to the physiological condition in murine macrophage. Further investigation of GBCAs on the human macrophage or in vivo animal study may clarify the role of macrophage on the pathogenesis of NSF and other GBCAs-related disease.

Spontaneous hemothorax due to anticoagulant use is extremely rare in clinical practice. Dabigatran is a novel anticoagulant to prevent stroke or thromboembolic episodes in patients with nonvalvular atrial fibrillation. We report on an 83-year-old man who received dabigatran therapy (110 mg twice daily) for 7 months and developed massive spontaneous hemothorax and acute renal failure. The patient was admitted to the hospital with complaint of a dull ache in the chest and dyspnea. Chest computed tomography scan revealed massive pleural effusion in the left hemithorax with atelectasis. Acute renal failure was observed 4 days later after admission. Almost 2500 mL of blood was repeatedly drained by ultrasound-guided thoracocentesis, followed by a dramatic decrease in serum red blood cell count, hemoglobin and hematocrit. After excluding other possible causes, diagnostic withdrawal was performed for dabigatran, and plasma transfusion was conducted to supply the lost blood volume. A causal relationship was established, because the patient’s renal function gradually improved and no further pleural effusion developed after dabigatran was discontinued. This is a rare case report of massive spontaneous hemothorax caused by dabigatran. Therefore, practitioners should be aware of hemothorax as a potential complication of dabigatran therapy.

Nonlinear wavelength generations by using the optical waveguides are more compact, low cost, and efficient than using the traditional solid state systems [1], and the generated broadband light sources can be utilized in optical coherence tomography, frequency metrology, optical communications, and many other. In this work, the high quality of tantalum pentoxide (Ta 2 O 5 ) micro-ring resonator has been fabricated to realize the low power parametric frequency conversion in the communication region. Figure 1 shows the illustration and scanning electron microscope (SEM) image of Ta 2 O 5 based micro-ring resonator. The width/height of the ring waveguides is set as 1.5μm/0.7μm for the anomalous dispersion, which is a key element to minimize the phase mismatch in the parametric frequency conversion process. By fitting the transmission spectrum of the Ta2O5 ring resonator, the load quality factor is ∼50000 and the loss coefficient is ∼0.5cm−1. The unload quality factor is estimated to be ∼180000, which is the best record of Ta 2 O 5 based micro-ring resonator [2].

Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted in the expression and secretion of antibodies which bind to Meth. The viral vector was then examined in adult ICR mice. Systemic administration of AAV-MethAb resulted in long-term expression of MethAb in the serum for up to 29 weeks. Serum collected from the animals receiving AAV-MethAb retained a high specificity for (+)-Meth. Animals were challenged with Meth five weeks after viral injection. Meth levels in the brain and serum were reduced while Meth-induced locomotor activity was significantly attenuated. In conclusion, AAV-MethAb administration effectively depletes Meth from brain and serum while reducing the behavioral response to Meth, and thus is a potential therapeutic approach for Meth abuse.

Transition metal oxides with a perovskite crystal structure exhibit a variety of physical properties associated with the lattice. Among these materials, strontium ruthenate (SrRuO3) displays unusually strong coupling of charge, spin and lattice degrees of freedom that can give rise to the photostriction, that is, changes in the dimensions of material due to the absorption of light. In this study, we observe a photon-induced strain as high as 1.12% in single domain SrRuO3, which we attribute to a nonequilibrium of phonons that are a result of the strong interaction between the crystalline lattice and electrons excited by light. In addition, these light-induced changes in the SrRuO3 lattice affect its electrical resistance. The observation of both photostriction and photoresistance in SrRuO3 suggests the possibility of utilizing the mechanical and optical functionalities of the material for next-generation optoelectronics, such as remote switches, light-controlled elastic micromotors, microactuators and other optomechanical systems., Light-induced deformation known as photostriction could be used for green energy devices but in most materials the effect is too small to be of practical use. Here, Wei et al. study the photostriction of strontium ruthenate and find photon-induced strain efficiencies of more than one percent.

Porous iron oxide (Fe2O3) nanowhiskers with diameter of about 50–150 nm, and lengthen about 6–10 μm were successfully synthesized by a self-assembly method. The pores structure was characterized by scanning electron microscopy, transmission electron microscopy. The pore size distribution calculated from desorption branch by using the density functional theory method revealed that the Fe2O3 whiskers was composed of pores with diameter of bout 6, 8, 10.5, 13.5 nm respectively. On the basis of all the observations, we propose that the porous Fe2O3 nanowhiskers formation was directed by the in-situ oxidation of self-assembly ferric fluoride whiskers. The integrated thin carbon layer was considered to be critical to keep the integrity of the porous Fe2O3 nanowhiskers