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Background: Adropin is a peptide encoded by the energy homeostasis-associated gene ( Enho ) that is highly expressed in the brain. Aging and stroke are associated with reduced adropin levels in the brain and plasma. We showed that treatment with synthetic adropin provides long-lasting neuroprotection in permanent ischemic stroke. However, it is unknown whether the protective effects of adropin are observed in aged animals following cerebral ischemia/reperfusion. We hypothesized that adropin provides neuroprotection in aged mice subjected to transient middle cerebral artery occlusion. Methods: Aged (18–24 months old) male mice were subjected to 30 minutes of middle cerebral artery occlusion followed by 48 hours or 14 days of reperfusion. Sensorimotor (weight grip test and open field) and cognitive tests (Y-maze and novel object recognition) were performed at defined time points. Infarct volume was quantified by 2,3,5-triphenyltetrazolium chloride staining at 48 hours or Cresyl violet staining at 14 days post–middle cerebral artery occlusion. Blood-brain barrier damage, tight junction proteins, and MMP-9 (matrix metalloproteinase-9) were assessed 48 hours after middle cerebral artery occlusion by ELISA and Western blots. Results: Genetic deletion of Enho significantly increased infarct volume and worsened neurological function, whereas overexpression of adropin dramatically reduced stroke volume compared to wild-type controls. Postischemic treatment with synthetic adropin peptide given at the onset of reperfusion markedly reduced infarct volume, brain edema, and significantly improved locomotor function and muscular strength at 48 hours. Delayed adropin treatment (4 hours after the stroke onset) reduced body weight loss, infarct volume, and muscular strength dysfunction, and improved long-term cognitive function. Postischemic adropin treatment significantly reduced blood-brain barrier damage. This effect was associated with reduced MMP-9 and preservation of tight junction proteins by adropin treatment. Conclusions: These data unveil a promising neuroprotective role of adropin in the aged brain after transient ischemic stroke via reducing neurovascular damage. These findings suggest that poststroke adropin therapy is a potential strategy to minimize brain injury and improve functional recovery in ischemic stroke patients.

Poststroke infections are common complications of stroke and are highly associated with poor outcomes for patients. Stroke induces profound immunodepression coupled with alterations to autonomic signaling, which together render the body more susceptible to infection from without (nosocomial/community-acquired infection) and from within (commensal bacterial infection). Critical to the hypothesis of commensal infection is the phenomenon of poststroke gut permeability and gut dysbiosis. Few studies have provided adequate explanations for the mechanisms underlying the molecular alterations that produce a more permeable gut and perturbed gut microbiota after stroke. A dysregulation in the production of matrix MMP-7 (metalloproteinase-7) may play a critical role in the progression of gut permeability after stroke. By cleaving junctional and extracellular matrix proteins, MMP-7 is capable of compromising gut barrier integrity. Because of MMP-7’s unique abundance in the small intestine and its capacity to be induced in states of bacterial invasion and inflammation, along with its unique degradative capability, MMP-7 may be crucially important to the progression of gut permeability after ischemic stroke.

Background: Stroke is associated with profound immunodepression and aberrations of autonomic signaling which render the body more susceptible to infection from without and from within. Dramatic alterations of sensitive signaling networks within the gut after stroke along with systemic inflammation may promote pathways that evoke a leaky gut. The enzyme matrix metalloproteinase 7 (MMP-7) has been shown to play a prominent role in evoking gut permeability in models of systemic inflammation. We found that stoke elicits a profound increase in MMP-7 across the small intestine rapidly after injury. Hypothesis: We hypothesize that this increase in MMP-7 in the gut after stroke contributes to post-stroke gut permeability and that mice deficient in MMP-7 are protected from this effect. Methods: Young (2-5-month-old) Mmp7 knockout ( Mmp7 -/- ) and wild type (WT) control littermates were subjected to 45min-tMCAO. At 3h post-tMCAO, mice were injected intraocularly with 200mg/kg FITC-inulin at 3h post-tMCAO and euthanized 1h later. Aged (24-month-old) Mmp7 -/- mice and WT control littermates were subjected to pMCAO, injected intraocularly with 200mg/kg FITC-inulin at 47h, and euthanized 1h later. Intestinal tissue was collected, homogenized, and used to detect FITC-inulin as well as for Western blotting and RT-qPCR. Results: We demonstrate that MMP-7 levels rapidly increase throughout the small intestine after stroke at 6h and 24h post-stroke. This increase in MMP-7 is accompanied by a concurrent decrease in tight junction proteins and increase in intestinal permeability at 3h post-transient middle cerebral artery occlusion (tMCAO) and 48h post-permanent (p)MCAO. Interestingly, MMP-7 deficient mice are protected from gut permeability after stroke. Conclusion: Our data identify a novel causative agent in the phenomenon of gut permeability observed after stroke and prompt further study of the role of MMP’s in promoting gut permeability after stroke.

There is increasing interest in the production of value-added chemicals by oxidizing glucose with the aid of photocatalysis in an aqueous medium. Herein, a new SnO2-OVs/CoPz composite was prepared ...

To realize the high-efficiency acquisition of environmental mechanical energy, traditional triboelectric nanogenerators (TENGs) based on contact-separation consist of two separate triboelectric layers. Their large contact-separation gap increases the overall volume of the device, making it difficult to realize miniaturization and flexibility. This work, therefore, presents a fully enclosed all-in-one-shaped flexible TENG (FEAST) with an air cavity using rubber mixing and high-temperature vulcanization. The air pressure inside the enclosed air cavity facilitates effective contact-separation of the FEAST. The homogeneous integration between the triboelectric layer and the electrode layer enhances structural firmness without using extra spacer materials. The developed FEAST presents excellent mechanical durability even after 10000 cycles. By increasing the active contact area between the triboelectric materials, a maximum peak-peak output voltage, current, and power density of 130 V, 1.1 µA, and 277 mW/m2, respectively, were obtained with an effective stress area of 1 cm2. Moreover, the fully enclosed structure ensures that the output performance is not affected by the external environment. The FEAST was fixed onto the sole of a shoe to demonstrate its applicability in harvesting mechanical energy from human motions. Overall, the developed method provides a simple approach for optimizing the structure of TENGs and is compatible with large-scale manufacturing.

g-C3N4/CoPz (cobalt tetra(2,3-bis(butylthio)maleonitrile)porphyrazine) composite was found to be highly photocatalytic active in oxidation of glucose to gluconic acid and glucaric acid using H2O2 as the oxidant under mild conditions. Under the optimal conditions, the total selectivity of gluconic acid and glucaric acid reached 79.4% with 52.1% of glucose conversion under xenon lamp irradiation within 20 min. The surface modification of g-C3N4 by CoPz displayed a significantly enhanced photocatalytic activity and improved selectivity to gluconic acid and glucaric acid in glucose oxidation in comparison to pure g-C3N4, this was attributed to the synergistic effect between g-C3N4 and CoPz. The influence of the CoPz content, H2O2 addition, glucose concentration and catalyst amount on the glucose oxidation were further evaluated and discussed. g-C3N4/CoPz composite exhibited more efficient separation of the photogenerated carriers in comparison to the individual components, which was responsible for its enhanced photocatalytic activity. The CoPz modification can enhance the adsorption of glucose and reduce the adsorption of organic acids on the surface of catalyst, more importantly, the presence of CoPz can reduce the formation of strong and nonselective hydroxyl radical (·OH), thus obtaining high selectivity of gluconic acid and glucaric acid. In addition, recyclability experiments revealed that the g-C3N4/CoPz composite photocatalyst was stable after five cycles with no apparent loss in activity or selectivity.

Selective oxidation of glucose into gluconic acid and glucaric acid with molecular oxygen under mild conditions in only water as the solvent remains a challenge. To achieve highly selective oxidation of glucose to gluconic acid and glucaric acid, a new TiO2/HPW/CoPz composite photocatalyst was prepared through modifying TiO2 with HPW (phosphotungstic acid) and CoPz (cobalt tetra(2-hydroxymethyl-1,4-dithiin)porphyrazine), which was well characterized by Raman spectroscopy, X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), inductively coupled plasma-mass spectrometry (ICP-MS) and scanning electron microscopy energy-dispersive spectrometry (SEM-EDS). Remarkably, it was found that this composite photocatalyst can efficiently catalyze oxidation of glucose to gluconic acid and glucaric acid with atmospheric oxygen at high selectivity in water under simulated sunlight irradiation. For example, the total selectivity for both acids can reach up to 80.4% with 22.2% glucose conversion under the optimized conditions. The excellent photocatalytic performance of the TiO2/HPW/CoPz composite was attributed to the synergistic effect between the components. To elucidate the roles of HPW and CoPz in the photocatalytic process, a series of experiments including surface photocurrent, electrochemical impedance, electron spin resonance (ESR) spectroscopy, zeta potential and adsorption behavior measurements were performed. It has been demonstrated that the presence of HPW can effectively reduce the adsorption capacity of gluconic acid and glucaric acid on the surface of the catalyst and suppress their further oxidation, resulting in a high selectivity to both acids. Meanwhile the presence of CoPz can improve the separation efficiency of photogenerated charges and accelerate the production of active species, facilitating the conversion of glucose without sacrificing the acid selectivity.

Background: Receptor-interacting serine-threonine protein kinase 2 (Ripk2) is involved in the signaling pathways of members of the NOD family of cytosolic pattern recognition receptors. Ripk2 has been implicated in the caspase-1 pathway of hypoxia and ischemia-induced neuronal cell death, as well as the pathology of neuroinflammatory diseases like multiple sclerosis. Ischemic stroke is characterized by brain injury resulting from initial hypoxia/ischemia-induced cell death and secondary neuroinflammation. Hypothesis: Since Ripk2 is implicated in both pathways, we hypothesized that the genetic deletion of Ripk2 will improve outcomes for animals after experimental stroke. Methods: We utilized Ripk2 knockout ( Ripk2 -/- ) mice (3-4 months old) and subjected them to 45min of transient middle cerebral artery occlusion (tMCAO) along with wild-type (WT) control littermates. Infarct size was measured at 24h by TTC staining. RNA was isolated from the ipsilateral and contralateral cortices for RT-qPCR. Weight grip test, vertical grid test, and open field behavioral tests were conducted before and up to 21 days after tMCAO with novel object recognition and Y-maze tests occurring at day 28. Results: After 24h, Ripk2 -/- mice had significantly smaller infarct sizes than wild-type (WT) mice. Ripk2 -/- mice also had much lower expression of proinflammatory cytokines ( Tnfα, Il1β, and Il6 ) and chemokines ( Ccl2 and Cxcl1 ) in the ipsilateral cortex relative to WT, implicating a diminished proinflammatory response to ischemia/reperfusion injury in Ripk2 -/- animals. Ripk2 -/- mice displayed significantly better neurological deficit scores compared to WT at 24h, 48h, 7d, 14d, and 21d post-tMCAO. Ripk2 -/- mice also performed much better than WT at acute time points in a battery of behavioral tests, such as the weight grip test, vertical grid test, and open field test. Neurological assessment via novel object recognition and Y-maze tests showed no difference between genotypes at 28d. Conclusions: Our findings support the hypothesis that Ripk2 plays a detrimental role in the pathology of ischemic stroke. Understanding Ripk2’s role in stroke pathology may reveal a novel therapeutic target for the treatment of ischemic stroke.

Background: Adropin is a peptide encoded by the energy homeostasis associated gene ( Enho ) highly expressed in the brain. Our unpublished data revealed robust effects of adropin on reducing neurovascular damage and behavioral impairments in young mice following stroke. However, it is unknown whether these protective effects of adropin are observed in aged animals after stroke. Hypothesis: Considering that aging is the most critical risk factor for stroke, we hypothesized that adropin provides neuroprotection in aged mice subjected to ischemic stroke. Methods: Aged (18-24 months old) male adropin knockout ( Enho -/- ), adropin overexpressing transgenics (AdrTg), and their corresponding control littermates were subjected to permanent middle cerebral artery occlusion (pMCAO). Adhesive removal, nesting behavior, and novel object recognition test were conducted before and up to 14 days after MCAO. Infarct volume was quantified by MRI at 14 days post-MCAO. In a separate experiment, we utilized aged male Enho -/- and AdrTg mice subjected to 30 min of transient MCAO (tMCAO). To investigate the potential therapeutic benefit of adropin in stroke, aged wild-type mice were randomly selected to receive a bolus injection of vehicle or synthetic adropin (900 nmol/kg; i.v.) at the onset of ischemia. Neurobehavioral tests were performed before and at 48h after stroke, and infarct size was measured by TTC staining at 48h. Results: Adropin deficiency consistently increased infarct volume and exacerbated neurological impairments in permanent and transient MCAO mice compared to Enho -/- . In contrast, transgenic overexpression of adropin significantly improved neurological function compared to WT mice. Also, AdrTg mice displayed better recovery of recognition memory function, whereas Enho -/- mice exhibited worse stroke outcomes compared to wild-type littermates following pMCAO. Similarly, treatment with synthetic adropin peptide resulted in a smaller stroke volume and better motor function recovery than vehicle-treated mice following tMCAO. Conclusions: These findings consistently show that transgenic overexpression of adropin or post-ischemic treatment with adropin peptide is neuroprotective in aged mice subjected to ischemic stroke.

Introduction: Accumulating evidence indicates that b romodomain and e xtra- t erminal domain (BET) proteins play a pivotal role in the transcriptional regulation of the inflammatory response, and consequently, BET inhibition has emerged as a promising novel therapeutic strategy to reduce inflammation linked to many diseases, including ischemic brain injury. dBET1 is the first BET-targeted proteolysis-targeting chimera (PROTAC) that induces a rapid and efficient deletion of BET proteins in vivo . Hypothesis: In this study, we hypothesized that dBET1 protects against brain damage and neurological deficits in a transient cerebral ischemia mouse model through the regulation of the inflammatory process. Methods: Adult C57BL/6 WT mice were subjected to transient cerebral ischemia surgery (tMCAO) and were administered intraperitoneally with dBET1 (30 mg/kg) or vehicle at 4 and 24 hours after the stroke onset. Infarct volume, neurological deficits, blood-brain barrier integrity, and several inflammatory mediators were examined 48h after tMCAO. Results: The expression level of the BET protein, BRD4, in the cerebral cortex was remarkably lower in the dBET1-treated animals compared to the controls. dBET1 significantly reduced infarct volume (56.2±7.9%, P≤0.01, n=13-14) and improved the neurological performance in the open field test, vertical grid test, and neurological deficit scoring (P≤0.05, n=19-20). In dBET1-treated mice, in both ischemic striatum and cerebral cortex, the inflammation-associated reactive gliosis in astrocytes and microglia was significantly attenuated (P≤0.05, n=6), along with a reduction in stroke-mediated blood-brain barrier damage and neutrophil infiltration. Mechanistically, dBET1 produced a dramatic decrease in the expression levels of pro-inflammatory mediators, while it enhanced levels of anti-inflammatory mediators (P≤0.05, n=6). Conclusion: Overall, this study provides direct in vivo evidence that BET protein degradation with dBET1 suppresses neuroinflammation and leads to anatomical and functional protection against ischemic brain damage. Blocking BET proteins is a promising new strategy to reduce neuroinflammation and eventually improve functional outcomes in stroke.

Introduction Complement C5a is an important component of the innate immune system. An increasing number of reports have revealed the relevance of C5a in tumor progression; however, its exact role in metastatic renal cell carcinoma (mRCC) remains unknown. Methods We evaluated C5a expression in tumor tissue microarrays of 231 mRCC patients and analyzed the relationship between C5a levels and clinical outcomes, and the expression of epithelial-mesenchymal transition (EMT)-related proteins, programmed cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). In-vitro functional experiments using exogenous C5a stimulation and C5a silencing in renal cell carcinoma cells were used to validate the tissue findings. Results High C5a expression was associated with poor therapeutic responses, poor overall and progression-free survival, and high expression of EMT-related proteins and PD-1/PD-L1 in mRCC patients. Exogenous C5a promoted proliferation, migration, and invasion of renal cell carcinoma cells, and induced the expression of EMT-related proteins and PD-1/PD-L1. Conversely, C5a silencing inhibited migration and invasion of renal cell carcinoma cells and decreased the expression of EMT-related proteins and PD-1/PD-L1. Conclusions Our findings indicate that elevated C5a expression is associated with poor outcomes in patients with mRCC, and this effect may be partly attributed to the ability of C5a to promote EMT and PD-1/PD-L1 expression. C5a may be a potential novel target for the treatment of mRCC.

Adropin is a highly-conserved peptide that has been shown to preserve endothelial barrier function. Blood-brain barrier (BBB) disruption is a key pathological event in cerebral ischemia. However, the effects of adropin on ischemic stroke outcomes remain unexplored. Hypothesizing that adropin exerts neuroprotective effects by maintaining BBB integrity, we investigated the role of adropin in stroke pathology utilizing loss- and gain-of-function genetic approaches combined with pharmacological treatment with synthetic adropin peptide. Long-term anatomical and functional outcomes were evaluated using histology, MRI, and a battery of sensorimotor and cognitive tests in mice subjected to ischemic stroke. Brain ischemia decreased endogenous adropin levels in the brain and plasma. Adropin treatment or transgenic adropin overexpression robustly reduced brain injury and improved long-term sensorimotor and cognitive function in young and aged mice subjected to ischemic stroke. In contrast, genetic deletion of adropin exacerbated ischemic brain injury, irrespective of sex. Mechanistically, adropin treatment reduced BBB damage, degradation of tight junction proteins, matrix metalloproteinase-9 activity, oxidative stress, and infiltration of neutrophils into the ischemic brain. Adropin significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS), Akt, and ERK1/2. While adropin therapy was remarkably protective in wild-type mice, it failed to reduce brain injury in eNOS-deficient animals, suggesting that eNOS is required for the protective effects of adropin in stroke. These data provide the first causal evidence that adropin exerts neurovascular protection in stroke through an eNOS-dependent mechanism. We identify adropin as a novel neuroprotective peptide with the potential to improve stroke outcomes., Graphical abstract Image 1, Highlights • Ischemic stroke decreases endogenous adropin levels in the brain and plasma. • Adropin treatment improves stroke outcomes in young and aged mice. • Adropin genetic deletion exacerbates stroke injury. • Stroke-induced blood-brain barrier disruption is prevented by adropin. • Mechanistically, adropin reduces stroke damage through an eNOS-dependent pathway.

AIMS/HYPOTHESIS: Normal cellular prion protein (PrP(C)) is a conserved mammalian glycoprotein found on the outer plasma membrane leaflet through a glycophosphatidylinositol anchor. Although PrP(C) is expressed by a wide range of tissues throughout the body, the complete repertoire of its functions has not been fully determined. The misfolded pathogenic isoform PrP(Sc) (the scrapie form of PrP) is a causative agent of neurodegenerative prion diseases. The aim of this study is to evaluate PrP(C) localisation, expression and trafficking in pancreases from organ donors with and without type 1 diabetes and to infer PrP(C) function through studies on interacting protein partners. METHODS: In order to evaluate localisation and trafficking of PrP(C) in the human pancreas, 12 non-diabetic, 12 type 1 diabetic and 12 autoantibody-positive organ donor tissue samples were analysed using immunofluorescence analysis. Furthermore, total RNA was isolated from 29 non-diabetic, 29 type 1 diabetic and 24 autoantibody-positive donors to estimate PrP(C) expression in the human pancreas. Additionally, we performed PrP(C)-specific immunoblot analysis on total pancreatic protein from non-diabetic and type 1 diabetic organ donors to test whether changes in PrP(C) mRNA levels leads to a concomitant increase in PrP(C) protein levels in human pancreases. RESULTS: In non-diabetic and type 1 diabetic pancreases (the latter displaying both insulin-positive [INS(+)] and -negative [INS(−)] islets), we found PrP(C) in islets co-registering with beta cells in all INS(+) islets and, strikingly, unexpected activation of PrP(C) in alpha cells within diabetic INS(−) islets. We found PrP(C) localised to the plasma membrane and endoplasmic reticulum (ER) but not the Golgi, defining two cellular pools and an unconventional protein trafficking mechanism bypassing the Golgi. We demonstrate PrP(C) co-registration with established protein partners, neural cell adhesion molecule 1 (NCAM1) and stress-inducible phosphoprotein 1 (STI1; encoded by STIP1) on the plasma membrane and ER, respectively, linking PrP(C) function with cyto-protection, signalling, differentiation and morphogenesis. We demonstrate that both PRNP (encoding PrP(C)) and STIP1 gene expression are dramatically altered in type 1 diabetic and autoantibody-positive pancreases. CONCLUSIONS/INTERPRETATION: As the first study to address PrP(C) expression in non-diabetic and type 1 diabetic human pancreas, we provide new insights for PrP(C) in the pathogenesis of type 1 diabetes. We evaluated the cell-type specific expression of PrP(C) in the human pancreas and discovered possible connections with potential interacting proteins that we speculate might address mechanisms relevant to the role of PrP(C) in the human pancreas.

At concentrations found in humans after ingestion of one to two cups of green tea, epicatechin-3-gallate (ECG) modulates Na/K-ATPase conformation and activity. Akin to ouabain, an archetypal Na/K-ATPase ligand of the cardiotonic steroid (CTS) family, ECG also activates protein kinase C epsilon type (PKCe) translocation and increases the force of contraction of the rat heart. This study evaluated whether, like ouabain, ECG also modulates Na/K-ATPase/Src receptor function and triggers pre- and postconditioning against ischemia/reperfusion (I/R) injury. In vitro, ECG activated the purified Na/K-ATPase/Src complex. In Langendorff-perfused rat hearts, submicromolar concentrations of ECG administered either before or after ischemia reduced infarct size by more than 40%, decreased lactate dehydrogenase release, and improved the recovery of cardiac function. ECG protection was blocked by PKCe inhibition and attenuated by mitochondrial KATP channel inhibition. In a unique mammalian cell system with depleted Na/K-ATPase α1 expression, ECG-induced PKCe activation persisted but protection against I/R was blunted. Taken together, these results reveal a Na/K-ATPase- and PKCe-dependent mechanism of protection by ECG that is also distinct from the mechanism of action of ouabain. These ECG properties likely contribute to the positive impact of green tea consumption on cardiovaascular health and warrant further investigation into the role of cardiac Na/K-ATPase signaling in the cardioprotective effect of green tea consumption. SIGNIFICANCE STATEMENT: Consumption of green tea, the richest dietary source of ECG, is associated with a reduced risk of cardiac mortality. Antioxidant effects of ECG and other tea polyphenols are well known, but reported for concentrations well above dietary levels. Therefore, the mechanism underlying the cardioprotective effect of green tea remains incompletely understood. This study provides experimental evidence that ECG concentrations commonly detected in humans after consumption of a cup of tea trigger the Na/K-ATPase/Src receptor in a cell-free system, activate a CTS-like signaling pathway, and provide PKCe-dependent protection against ischemia/reperfusion injury in rat hearts. Mechanistic studies in mammalian cells with targeted Na/K-ATPase depletion revealed that although Na/K-ATPase does not mediate ECG-induced PKCe activation, it is required for ECG-induced protection against ischemia/reperfusion injury.

A new iron tetra(2,3-bis(butylthio)maleonitrile)porphyrazine (FePz(SBu)8) has been synthesized, then it was loaded on H-ZSM-5 zeolite to obtain a supported biomimetic photocatalyst H-ZSM-5/FePz(SBu)8. Using H2O2 as oxidant, the photocatalytic selective oxidation of glucose in water under visible light (λ ≥ 420 nm) irradiation was carried out in presence of H-ZSM-5/FePz(SBu)8. Under such conditions, the glucose can be efficiently converted into value-added chemicals such as glucaric acid, gluconic acid, arabinose, glycerol and formic acid. More importantly, in comparison with pure FePz(SBu)8 and pure H-ZSM-5 zeolite, the H-ZSM-5/FePz(SBu)8 exhibited a higher photocatalytic activity for glucose oxidation and the formation of glucaric acid was observed only when H-ZSM-5/FePz(SBu)8 was used, deriving from the synergistic effect between FePz(SBu)8 and H-ZSM-5 zeolite. Some reaction parameters of glucose oxidation catalyzed by the H-ZSM-5/FePz(SBu)8 were discussed, such as loading amount of FePz(SBu)8, H2O2:glucose ratio, glucose concentration, and so on. It was demonstrated that the Soret-band of FePz(SBu)8 contributed more to the visible light photocatalytic activity than the Q-band during the photocatalytic process. The stability of H-ZSM-5/FePz(SBu)8 during the photocatalytic process was further evaluated by the reusability test. In addition, the generation of reactive oxygen species was determined by electron spin resonance (ESR) technology and scavenger experiments. A possible reaction pathway of glucose oxidation was also discussed.

As a typical visible-light-responsive organic semiconductor photocatalyst, graphitic carbon nitride (gCN) only exhibits moderate photoreactivity beacuse of its low specific area, limited light harvesting ability and quick recombination of photo-generated carriers. Herein, we report the fabrication of gCN nanosheets (gCN-NSs) with large BET surface area, excellent visible-light-absorptive property and efficient separation of carriers by direct polymerization of amidinourea, the product from the hydrolysis of dicyandiamine (DCDA). When compared with that of bulk gCN (S0) synthesized by direct polymerization of DCDA, the visible photocatalytic hydrogen evoluation rate of gCN-NSs (S2 sample) obtained by condensation of amidinourea improved 4.9 times, which is also 2.4 times higher than that of gCN-NSs (Su sample) which is prepared by polymerization of urea. The enhanced visible photocatalytic activity gCN-NSs (S2) toward hydrogen production can be ascribed to the combined effects of enlarged BET surface that provides more active sites for adsorption and photocatalytic reaction, compacted π-π layer stacking which facilitates the efficient separation of photo-generated carriers, negatively shifted CB potential and improved hydrophilic property that favor the electron transfer at the interfaces between gCN and water. In addition, the product yield of gCN-NSs (S2 sample) from the polymerization of amidinourea is 11.9%, which is 10.8 times higher than Su sample that prepared from urea (only 1.1%).

As part of the neurovascular unit, the blood-brain barrier (BBB) is a unique, dynamic regulatory boundary that limits and regulates the exchange of molecules, ions, and cells between the blood and the central nervous system. Disruption of the BBB plays an important role in the development of neurological dysfunction in ischemic stroke. Blood-borne substances and cells have restricted access to the brain due to the presence of tight junctions between the endothelial cells of the BBB. Following stroke, there is loss of BBB tight junction integrity, leading to increased paracellular permeability, which results in vasogenic edema, hemorrhagic transformation, and increased mortality. Thus, understanding principal mediators and molecular mechanisms involved in BBB disruption is critical for the development of novel therapeutics to treat ischemic stroke. This review discusses the current knowledge of how neuroinflammation contributes to BBB damage in ischemic stroke. Specifically, we provide an updated overview of the role of cytokines, chemokines, oxidative and nitrosative stress, adhesion molecules, matrix metalloproteinases, and vascular endothelial growth factor as well as the role of different cell types in the regulation of BBB permeability in ischemic stroke.

A new composite photocatalyst, ZnO/CoPzS8, was obtained by immobilizing cobalt tetra(2,3-bis(butylthio)maleonitrile)porphyrazine (CoPzS8) onto the surface of home-prepared ZnO. The ZnO/CoPzS8 composite was well characterized by X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. It turned out that CoPzS8 was successfully loaded onto the ZnO surface and there existed an interaction between ZnO and CoPzS8. By using the ZnO/CoPzS8 composite photocatalyst, the photocatalytic oxidation of glucose to value-added chemicals in pure water was conducted under simulated sunlight irradiation without adding any acid or base. The ZnO/CoPzS8 composite exhibited a higher photocatalytic activity in comparison to pure ZnO and pure CoPzS8 owing to the synergistic effect between ZnO and CoPzS8. Gluconic acid, arabinose, glycerol and formic acid were all observed as oxidation products when pure ZnO or ZnO/CoPzS8 composite was used. More importantly, glucaric acid was also obtained in the ZnO/CoPzS8 photocatalytic system, indicating that the presence of CoPzS8 changed the glucose reaction pathway. In addition, the active species generated in the photocatalytic process were further identified by electron spin resonance (ESR) technology and scavenger experiments. A possible photocatalytic conversion pathway of glucose has been proposed according to the experimental results.

The selective conversion of glucose into value-added chemicals in the presence of only water is a challenging topic. In this work, selective photocatalytic oxidation of glucose in water was studied using iron thioporphyrazine modified SnO2 (SnO2/FePz(SBu)8) as the catalyst and atmospheric air as the oxidant under simulated sunlight irradiation. It was found that value-added organic acids including glucaric acid, gluconic acid and formic acid could be obtained from the oxidation of glucose under such conditions. The effects of the FePz(SBu)8 content, glucose concentration and additional addition on the conversion of glucose and the selectivity of the organic acids were further explored. Under the optimized conditions, the total selectivity for the organic acids on the SnO2/FePz(SBu)8 photocatalyst reached up to 52.2% at 34.2% glucose conversion. More importantly, it has been demonstrated that the presence of FePz(SBu)8 on the surface of SnO2 can keep the selectivity of the organic acids unchanged under conditions of increasing the glucose conversion. To illustrate the synergistic effect for the enhanced photocatalytic activity between FePz(SBu)8 and SnO2, surface photocurrent, electron spin resonance (ESR) spectra and adsorption behavior experiments were carried out on pure SnO2 and SnO2/FePz(SBu)8. It was found that the introduction of FePz(SBu)8 could enhance the separation of photogenerated charge, promote the generation of active species for photocatalysis and improve the adsorption capacity of glucose, which are beneficial to the enhancement of photocatalytic activity. Additionally, a possible pathway of glucose oxidation was proposed through both detailed analysis of the oxidation intermediate of glucose and comparative experiments with different organic acids as the substrates, indicating that the formation of organic acids were fulfilled by two parallel and subsequent reactions at the beginning of the reaction.

The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevance to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged 75y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18- month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines of cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential novel therapy against neurological aging.

Adropin is most abundant in neural tissues yet its neurological functions are unclear. Data from post-mortem human brain tissue samples indicates adropin expression occurs predominantly in astrocytes, peaks during critical post-natal periods of brain development, and then declines with aging. Previous experiments indicate adropin regulates mitochondrial metabolism. Gene clusters correlating with adropin are age- and dementia-specific, possibly indicating survivor bias. In people aged 75y) with dementia, adropin expression correlates with genes linked to mitochondrial metabolism and neurodegenerative conditions. In the ‘old-old’ (>75y) without dementia, adropin correlates with genes involved in morphogenesis, growth of neuronal processes (dendrites, axons) and synapse function. Accordingly, adropin elicits neurotrophic responses in primary cultured neurons. Adropin expression also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in people without dementia, indicating a link to cellular stressors. How variation in brain adropin expression affects neurological aging was investigated using C57BL/6J mice. In mice, adropin is more widely expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia. Preventing the decline in expression observed with aging of mice using transgenesis improved cognitive function and resilience, while also reducing mRNA markers of inflammation in 18-month old mice. Treating 18-month old mice with adropin peptide also improved cognitive performance. These results link adropin expression to cellular energy metabolism and stress responses in the brain and indicates a possible relationship with aging-related cognitive decline.