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Background: Postoperative cognitive dysfunction (POCD) is a common neurological complication of anesthesia and surgery in aging individuals. Neuroinflammation has been identified as a hallmark of POCD. However, safe and effective treatments of POCD are still lacking. Itaconate is an immunoregulatory metabolite derived from the tricarboxylic acid cycle that exerts anti-inflammatory effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we investigated the effects and underlying mechanism of 4-octyl itaconate (OI), a cell-permeable itaconate derivative, on POCD in aged mice. Methods: A POCD animal model was established by performing aseptic laparotomy in 18-month-old male C57BL/6 mice under isoflurane anesthesia while maintaining spontaneous ventilation. OI was intraperitoneally injected into the mice after surgery. Primary microglia and neurons were isolated and treated to lipopolysaccharide (LPS), isoflurane, and OI. Cognitive function, neuroinflammatory responses, as well as levels of gut microbiota and their metabolites were evaluated. To determine the mechanisms underlying the therapeutic effects of OI in POCD, ML385, an antagonist of Nrf2, was administered intraperitoneally. Cognitive function, neuroinflammatory responses, endogenous neurogenesis, neuronal apoptosis, and Nrf2/extracellular signal-related kinases (ERK) signaling pathway were evaluated. Results: Our findings revealed that OI treatment significantly alleviated anesthesia/surgery-induced cognitive impairment, concomitant with reduced levels of the neuroinflammatory cytokines IL-1β and IL-6, as well as suppressed activation of microglia and astrocytes in the hippocampus. Similarly, OI treatment inhibited the expression of IL-1β and IL-6 in LPS and isoflurane-induced primary microglia in vitro. Intraperitoneal administration of OI led to alterations in the gut microbiota and promoted the production of microbiota-derived metabolites associated with neurogenesis. We further confirmed that OI promoted endogenous neurogenesis and inhibited neuronal apoptosis in the hippocampal dentate gyrus of aged mice. Mechanistically, we observed a decrease in Nrf2 expression in hippocampal neurons both in vitro and in vivo, which was reversed by OI treatment. We found that Nrf2 was required for OI treatment to inhibit neuroinflammation in POCD. The enhanced POCD recovery and promotion of neurogenesis triggered by OI exposure were, at least partially, mediated by the activation of the Nrf2/ERK signaling pathway. Conclusions: Our findings demonstrate that OI can attenuate anesthesia/surgery-induced cognitive impairment by stabilizing the gut microbiota and activating Nrf2 signaling to restrict neuroinflammation and promote neurogenesis. Boosting endogenous itaconate or supplementation with exogenous itaconate derivatives may represent novel strategies for the treatment of POCD. [ABSTRACT FROM AUTHOR]

Photocatalytic conversion of low‐concentration CO2 is considered as a promising way to simultaneously mitigate the environmental and energy issues. However, the weak CO2 adsorption and tough CO2 activation process seriously compromise the CO production, due to the chemical inertness of CO2 molecule and the formed fragile metal‐C/O bond. Herein, we designed and fabricated oxygen vacancy contained Co3O4 hollow nanoparticles on ordered macroporous N‐doped carbon framework (Vo−HCo3O4/OMNC) towards photoreduction of low‐concentration CO2. In situ spectra and ab initio molecular dynamics simulations reveal that the constructed oxygen vacancy is able to break the local structural symmetry of Co−O−Co sites. The formation of asymmetric active site switches the CO2 configuration from a single‐site linear model to a multiple‐sites bending one with a highly stable configuration, enhancing the binding and structural polarization of CO2 molecules. As a result, Vo−HCo3O4/OMNC shows unprecedent activity in the photocatalytic conversion of low‐concentration CO2 (10 % CO2/Ar) under laboratory light source or even natural sunlight, affording a syngas yield of 337.8 or 95.2 mmol g−1 h−1, respectively, with an apparent quantum yield up to 4.2 %. [ABSTRACT FROM AUTHOR]

Photocatalytic conversion of low‐concentration CO2 is considered as a promising way to simultaneously mitigate the environmental and energy issues. However, the weak CO2 adsorption and tough CO2 activation process seriously compromise the CO production, due to the chemical inertness of CO2 molecule and the formed fragile metal‐C/O bond. Herein, we designed and fabricated oxygen vacancy contained Co3O4 hollow nanoparticles on ordered macroporous N‐doped carbon framework (Vo−HCo3O4/OMNC) towards photoreduction of low‐concentration CO2. In situ spectra and ab initio molecular dynamics simulations reveal that the constructed oxygen vacancy is able to break the local structural symmetry of Co−O−Co sites. The formation of asymmetric active site switches the CO2 configuration from a single‐site linear model to a multiple‐sites bending one with a highly stable configuration, enhancing the binding and structural polarization of CO2 molecules. As a result, Vo−HCo3O4/OMNC shows unprecedent activity in the photocatalytic conversion of low‐concentration CO2 (10 % CO2/Ar) under laboratory light source or even natural sunlight, affording a syngas yield of 337.8 or 95.2 mmol g−1 h−1, respectively, with an apparent quantum yield up to 4.2 %. [ABSTRACT FROM AUTHOR]

Photocatalytic conversion of low‐concentration CO2 is considered as a promising way to simultaneously mitigate the environmental and energy issues. However, the weak CO2 adsorption and tough CO2 activation process seriously compromise the CO production, due to the chemical inertness of CO2 molecule and the formed fragile metal‐C/O bond. Herein, we designed and fabricated oxygen vacancy contained Co3O4 hollow nanoparticles on ordered macroporous N‐doped carbon framework (Vo−HCo3O4/OMNC) towards photoreduction of low‐concentration CO2. In situ spectra and ab initio molecular dynamics simulations reveal that the constructed oxygen vacancy is able to break the local structural symmetry of Co−O−Co sites. The formation of asymmetric active site switches the CO2 configuration from a single‐site linear model to a multiple‐sites bending one with a highly stable configuration, enhancing the binding and structural polarization of CO2 molecules. As a result, Vo−HCo3O4/OMNC shows unprecedent activity in the photocatalytic conversion of low‐concentration CO2 (10 % CO2/Ar) under laboratory light source or even natural sunlight, affording a syngas yield of 337.8 or 95.2 mmol g−1 h−1, respectively, with an apparent quantum yield up to 4.2 %. [ABSTRACT FROM AUTHOR]

Photocatalytic conversion of low‐concentration CO2 is considered as a promising way to simultaneously mitigate the environmental and energy issues. However, the weak CO2 adsorption and tough CO2 activation process seriously compromise the CO production, due to the chemical inertness of CO2 molecule and the formed fragile metal‐C/O bond. Herein, we designed and fabricated oxygen vacancy contained Co3O4 hollow nanoparticles on ordered macroporous N‐doped carbon framework (Vo−HCo3O4/OMNC) towards photoreduction of low‐concentration CO2. In situ spectra and ab initio molecular dynamics simulations reveal that the constructed oxygen vacancy is able to break the local structural symmetry of Co−O−Co sites. The formation of asymmetric active site switches the CO2 configuration from a single‐site linear model to a multiple‐sites bending one with a highly stable configuration, enhancing the binding and structural polarization of CO2 molecules. As a result, Vo−HCo3O4/OMNC shows unprecedent activity in the photocatalytic conversion of low‐concentration CO2 (10 % CO2/Ar) under laboratory light source or even natural sunlight, affording a syngas yield of 337.8 or 95.2 mmol g−1 h−1, respectively, with an apparent quantum yield up to 4.2 %. [ABSTRACT FROM AUTHOR]

Photocatalytic conversion of CO2 into syngas is a promising way to address the energy and environmental challenges. Here we report the integration of Ni−Co dual sites on Ni doped Co3O4 ultrathin nanosheets assembled double‐hollow nanotube (Ni−Co3O4 NSDHN) for efficient photoreduction of low‐concentration CO2. Quasi in situ spectra and density functional theory calculations demonstrate that the declining of d‐band center of Ni−Co dual sites enables the electrons accumulation in the dxz/dyz‐2π* and dz2‐5σ orbitals. As a result, the binding strength of *CO is weakened and the *H adsorption site is modulated from metal sites to an oxygen site. Remarkably, Ni−Co3O4 NSDHN exhibits superior diluted CO2 photoconversion activity and controllable selectivity under the irradiation of visible light or even natural sunlight. A syngas evolution rate of 170.0 mmol g−1 h−1 with an apparent quantum yield of 3.7 % and continuously adjustable CO/H2 ratios from 1 : 10 to 10 : 1 are achieved. [ABSTRACT FROM AUTHOR]

Aims: Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified., Method: A model of middle cerebral artery occlusion (MCAO), a rat ischemia-reperfusion (I/R) injury model, and an in vitro oxygen-glucose deprivation/re-oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging-wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno-associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms., Results: tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury-induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO-mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury-induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury., Conclusion: tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2-PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Photocatalytic conversion of CO 2 into syngas is a promising way to address the energy and environmental challenges. Here we report the integration of Ni-Co dual sites on Ni doped Co 3 O 4 ultrathin nanosheets assembled double-hollow nanotube (Ni-Co 3 O 4 NSDHN) for efficient photoreduction of low-concentration CO 2 . Quasi in situ spectra and density functional theory calculations demonstrate that the declining of d-band center of Ni-Co dual sites enables the electrons accumulation in the d xz /d yz -2π* and d z2 -5σ orbitals. As a result, the binding strength of *CO is weakened and the *H adsorption site is modulated from metal sites to an oxygen site. Remarkably, Ni-Co 3 O 4 NSDHN exhibits superior diluted CO 2 photoconversion activity and controllable selectivity under the irradiation of visible light or even natural sunlight. A syngas evolution rate of 170.0 mmol g -1  h -1 with an apparent quantum yield of 3.7 % and continuously adjustable CO/H 2 ratios from 1 : 10 to 10 : 1 are achieved., (© 2022 Wiley-VCH GmbH.)