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Developing efficient bifunctional catalysts for nonprecious metal-based oxygen reduction (ORR) and oxygen evolution (OER) is crucial to enhance the practical application of zinc-air batteries. The study harnessed electrostatic forces to anchor the nanoflower-like NiCo2O4 onto graphene oxide, mitigating the poor inherent conductivity in NiCo2O4 as a transition metal oxide and preventing excessive agglomeration of the nanoflower-like structures during catalysis. Consequently, the resulting composite, NiCo2O4-GO/C, exhibited notably superior ORR and OER catalytic performance compared to pure nanoflower-like NiCo2O4. Notably, it excelled in OER catalytic activity of the OER relative to the precious metal RuO2. As a bifunctional catalyst for ORR and OER, NiCo2O4-GO/C displayed a potential difference of 0.88 V between the ORR half-wave potential and the OER potential at 10 mA·cm-2, significantly lower than the 1.08 V observed for pure flower-like NiCo2O4 and comparable to the 0.88 V exhibited by precious metal catalysts Pt/C + RuO2. The NiCo2O4-GO/C-based zinc-air battery demonstrated a discharge capacity of 817.3 mA h·g-1, surpassing that of precious metal-based zinc-air batteries. Moreover, charge-discharge cycling tests indicated the superior stability of the NiCo2O4-GO/C-based zinc-air battery compared to its precious metal-based counterparts.

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In order to limit the anode corrosion and improve the battery activity, magnesium-air batteries with organic/inorganic double solutions (0.5 M Mg(ClO4)2-N,N-dimethylformamide (DMF)/0.6 M NaCl-H2O, 0.5 M Mg(ClO4)2-acetonitrile (AN)/0.6 M NaCl-H2O) were prepared. The discharge performance, discharge morphology, and corrosion performance of magnesium anode were researched. Results obtained show that organic electrolytes separate the anode from the aqueous electrolyte, thus improving the anode utilization rate. Due to the NaCl electrolyte used in the air cathode side, batteries show higher discharge voltages. As an example, a better discharge performance has been observed in Mg(ClO4)2-DMF/NaCl-H2O double electrolytes at 1 mA cm-2 discharge. This is attributed to there being no obvious absorption of corrosion products on the anode surface. The results of the discharge morphology and electrochemical impedance spectroscopy agree well with the discharge performance. The magnesium anode discharge mechanism is different for different solutions.

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The importance of self-feedback autaptic transmission in modulating spike-time irregularity is still poorly understood. By using a biophysical model that incorporates autaptic coupling, we here show that self-innervation of neurons participates in the modulation of irregular neuronal firing, primarily by regulating the occurrence frequency of burst firing. In particular, we find that both excitatory and electrical autapses increase the occurrence of burst firing, thus reducing neuronal firing regularity. In contrast, inhibitory autapses suppress burst firing and therefore tend to improve the regularity of neuronal firing. Importantly, we show that these findings are independent of the firing properties of individual neurons, and as such can be observed for neurons operating in different modes. Our results provide an insightful mechanistic understanding of how different types of autapses shape irregular firing at the single-neuron level, and they highlight the functional importance of autaptic self-innervation in taming and modulating neurodynamics.

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The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2-4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies.

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Bone cells respond to various mechanical stimuli including fluid shear stress (FSS) in vitro. Induction of cyclooxygenase-2 (COX-2) is thought to be important for the anabolic effects of mechanical loading. Recently, extracellular-signal-regulated kinase 5 (ERK5) has been found to be involved in multiple cellular processes. However, the relationship between ERK5 and the induction of COX-2 is still unknown. Here, we investigated the potential involvement of ERK5 in the response of pre-osteoblastic MC3T3-E1 cells upon FSS. MC3T3-E1 cells were subjected to 12 dyn/cm(2) FSS. Then, we established a ERK5 small interfering RNA (siRNA) transfected cell line using the MC3T3-E1 cells. After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction and Western blotting, the expression of COX-2, cAMP response element-binding protein (CREB), and nuclear factor kappa B cells (NF-κB) were assayed for downstream effectors of activated ERK5 under FSS by Western blotting. Our results showed that FSS could stimulate COX-2 activity, and induce the phosphorylation of ERK5, CREB, and NF-κB. When the MC3T3-E1 cells were transfected using siRNA before exposure to FSS, COX-2 activity was suppressed, and the phosphorylation of CREB and NF-κB was significantly downregulated. In summary, we demonstrated that ERK5 pathway is essential in the induction of COX-2 gene.

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Patient-specific instrumentation (PSI) has recently been introduced to improve the alignment following total knee arthroplasty (TKA). However, controversy remains between PSI and conventional instrumentation. The aim of this study is to compare the accuracy of PSI with conventional instruments for total knee arthroplasty (TKA). A systematic literature search was performed in databases including PubMed, the Cochrane Library, EMBASE, and Web of Science. All of the available randomized, controlled trials (RCTs) or non-randomized, controlled trials (nRCTs) comparing PSI with conventional instruments for TKA were identified. A statistical analysis was performed of this meta-analysis. Eighteen studies with 2417 patients were included in the authors' final analysis. The results of the meta-analysis demonstrated that there were no statistical differences in outliers of the mechanical axis (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.61-1.11), the femoral component in the coronal (RR, 0.56; 95% CI, 0.32-1.05) and sagittal (RR, 0.83; 95% CI, 0.60-1.14) plane, the tibial component in the coronal (RR, 0.84; 95% CI, 0.52-1.35) and sagittal (RR, 1.04; 95% CI, 0.69-1.55) plane, and the femoral component rotation (RR, 1.02; 95% CI, 0.57, 1.83) between the 2 groups. In addition, subgroup analysis showed that the study design and imaging used for preoperative scanning did not affect the outcome of the alignment, but a different PSI system might. The authors' meta-analysis indicated that the accuracy of PSI was not superior to conventional instruments for patients undergoing TKA. Future RCTs should focus on functional outcomes and component survivorship with mid- to long-term follow-up.

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BACKGROUND: Renal dysfunction has been proposed for the risk factor for stroke and bleeding in atrial fibrillation (AF). The impact of changes in renal dysfunction over time and the relationship to stroke and bleeding risk in these patients remain unknown. We investigated sequential change in renal function (estimated glomerular filtration rate, eGFR) and the risk for clinical events (ischaemic stroke, death and major bleeding) over time in a cohort of 617 AF patients followed up for 2 years. METHODS: eGFR was estimated at baseline, 6 months and 12 months using three formulas (Modification of Diet in Renal Disease equation, MDRD, Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI, and Cockcroft-Gault equation). Changes in eGFR and the risk for clinical events were analysed by Cox models, receiver operating curves (ROC), and Kaplan-Meier survival curves. RESULTS: When patients with eGFR≤60 ml/min/1.73 m(2) were compared to patients with eGFR>60 ml/min/1.73 m(2), there was an increase over time in stroke or death, or death, with impaired renal function (all p<0.05). An absolute decrease in eGFR≥15 ml/min/1.73 m(2) on Cockcroft-Gault and CKD-EPI and ≥25 ml/min/1.73 m(2) on MDRD were associated with an increased risk for stroke or death, death, and ischaemic stroke at 6 months (all p<0.05), but not major bleeding. A relative reduction (decline of ≥25%) in eGFR was also an independent risk. ROC analysis showed that a relative reduction in eGFR ≥25% at 6 months and 12 months modestly predicted the occurrence of stroke or death in patients with AF (c-indexes: 0.57 to 0.61, p<0.05). CONCLUSION: In patients with AF, an absolute decrease in eGFR ≥15 ml/min/1.73 m(2) on Cockcroft-Gault and CKD-EPI, and ≥25 ml/min/1.73 m(2) on MDRD, or a relative reduction (≥25%) in eGFR, independently predicted the risk for the endpoints 'stroke or death', 'death' or (at 6 months) ischaemic stroke. Deteriorating renal function increases the risk of death in AF patients.

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BACKGROUND: Female patients with atrial fibrillation (AF) are at increased risk of stroke. It is unclear what contributes to the gender-related differences in stroke and mortality amongst AF patients. This is pertinent since oral anticoagulation use results in a significant reduction in stroke, as well as all-cause mortality. OBJECTIVE: We investigated gender-related risk factors for stroke and mortality in a cohort of Chinese patients with AF. METHODS: We studied 1034 AF patients (27% females, median age 75 years) who were followed-up for an average of 1.9 years for the principal primary endpoint of 'ischaemic stroke and death'. Gender-specific effect of risk factors for stroke and death was analyzed. RESULTS: Patients at high stroke risk (CHADS2 or CHADS2-VASc ≥ 2) and HAS-BLED ≥ 3 had higher rates of ischaemic stroke and death, but ischaemic stroke rates in females with HAS-BLED ≥ 3 did not differ between CHADS2 0-1 and ≥ 2 (~3 per 100 person-years). On multivariate analysis of non-anticoagulated patients (n=885), independent predictors of 'ischaemic stroke and death' in both males and females were age>75, prior stroke and renal dysfunction (all p<0.05). Independent predictors of 'ischaemic stroke' in females were prior stroke, vascular disease and renal dysfunction (all p<0.05). When females were compared to males, adjusted for baseline characteristics, independent predictors for 'ischaemic stroke and death' amongst females were prior stroke (hazard ratio, HR 2.40; 95% confidence interval, CI, 1.17-4.91, p=0.017) and renal dysfunction (HR 5.30; 95%CI 2.39-11.74, p<0.001). When females were compared to males, renal dysfunction remained a predictor for the secondary endpoints of ischaemic stroke (HR 4.37, p=0.05) and all-cause mortality (HR 4.15, p=0.003). CONCLUSIONS: Renal dysfunction may be a contributor to the greater risk of stroke and death in female Chinese patients with AF. This increased risk is largely driven by the impact on all-cause mortality.

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BACKGROUND: Risk stratification schemes assessing stroke and thromboembolism (stroke/TE) and bleeding relating to atrial fibrillation (AF) have largely been derived and validated in Western populations. We assessed risk factors that constitute scores for assessing stroke/TE (CHADS2, CHA2DS2-VASc) and bleeding (HAS-BLED), and the predictive value of these scores in a large cohort of Chinese patients with AF. METHODS AND RESULTS: We studied 1034 AF patients (27.1% female, median age 75; 85.6% non-anticoagulated) with mean follow-up of 1.9 years. On multivariate analysis, vascular disease was independently associated with stroke/TE in non-anticoagulated patients (p=0.04). In patients with a CHADS2 or CHA2DS2-VASc score=1, the rate of stroke/TE was 2.9% and 0.9% respectively, but in patients at "high risk" (scores ≥ 2), this rate was 4.6% and 4.5%, respectively. The c-statistics for predicting stroke/TE with CHADS2 and CHA2DS2-VASc were 0.58 (p=0.109) and 0.72 (p<0.001), respectively. Compared to CHADS2, the use of CHA2DS2-VASc would result in a Net Reclassification Improvement (NRI) of 16.6% (p=0.009) and an Integrated Discrimination Improvement (IDI) of 1.1% (p=0.002). Cumulative survival of the patients with a CHA2DS2-VASc score≥2 was decreased compared to those with a CHA2DS2-VASc score 0-1 (p<0.001), but the CHADS2 was not predictive of mortality. There was an increased risk of major bleeding with increasing HAS-BLED score (c-statistic 0.61, 95% CI: 0.51-0.71, p=0.042). CONCLUSIONS: Vascular disease was a strong independent predictor of stroke/TE in Chinese patients with AF. The CHA2DS2-VASc score performed better than CHADS2 in predicting stroke/TE in this Chinese AF population. Cumulative survival of the patients at high risk with the CHA2DS2-VASc score (but not using CHADS2) was significantly decreased.

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BACKGROUND: The risk of stroke associated with atrial fibrillation (AF) is higher in Far Eastern population than in Western population, and warfarin use suboptimal. There is uncertainty whether the novel oral anticoagulants (NOACs) would have a major impact on stroke prevention in Far Eastern populations with AF. OBJECTIVES: We investigated current antithrombotic therapy use on stroke and bleeding risk, determinants of warfarin use and performed a modeling analysis of the net clinical benefit of the NOACs (apixaban, dabigatran) in a large cohort of Chinese patients with AF. METHODS: We studied 1034 Chinese patients (27.1% female, median age 75 years, interquartile range [IQR]: 63-83) with AF who were followed-up for an average of 1.9 years (IQR: 1.43-2.64). Stroke/thromboembolism (TE), and major bleeding associated to antithrombotic treatment were investigated. A modeling analysis was performed for the net clinical benefit balancing major bleeding against stroke/TE for dabigatran 110 mg bid, dabigatran 150 mg bid and apixaban, using their respective recent clinical trial outcome data. RESULTS: Using a Cox proportional hazard model, the Hazard Ratio [HR (95% confidence interval, CI)] for stroke/TE compared to no-antithrombotic therapy (no ATT) was 1.27 (0.65-2.50) on aspirin, 1.40 (0.35-3.57) on clopidogrel, 1.52 (0.72-3.23) on dual antiplatelets and 1.65 (0.76-3.57) on warfarin. The risk for major bleeding was 0.35 (0.14-0.85) on aspirin, 0.74 (0.24-2.29) on clopidogrel, 0.35 (0.11-1.10) on dual antiplatelets, and 0.88 (0.36-2.17) on warfarin. Binary logistic regression analysis showed persistent/permanent AF (Odds Ratio, OR, 2.03 [95%CI 1.05-3.92], p=0.035) was associated with warfarin use, but age ≥75 years (0.26 [0.16-0.42], p<0.001), aspirin (0.18 [0.12-0.27], p<0.001) and clopidogrel (0.17 [0.08-0.33], p<0.001) were independent determinants of non-use of warfarin. On modeling net clinical benefit (per 100 person-years [95% CI]), apixaban use compared to antiplatelet agents or no ATT was 3.29 (2.15-4.30) using Singer's method and 2.08 (1.18-3.21) with Connolly's method amongst high-risk patients. The use of dabigatran 110 mg bid and 150 mg bid compared to antiplatelet agents could reduce an additional 18.1 stroke/TE and 24.3 stroke/TE events, respectively. Compared to warfarin, dabigatran 150 mg bid had the best net clinical benefit. CONCLUSIONS: There was suboptimal stroke prevention with no difference between antiplatelet and OAC treated patients, perhaps reflecting an inappropriate Target INR range. On modeling analyses, the use of the NOACs (apixaban and dabigatran) could provide better stroke prevention compared to antiplatelet (or warfarin) use in this Chinese AF population, with a positive net clinical benefit.

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Previous studies have indicated that central sensitization is a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation and astrocytes play an important role in the central sensitization. The current study investigated the role of amino acid transport system A in central sensitization and hyperalgesia induced by intraplantar injection of formalin in rats. Formalin (5%, 50µl) injected subcutaneously into the unilateral hindpaw pad induced typical biphase nociceptive behaviors, including licking/biting and flinching of the injected paw and an increase of glial fibrillary acid protein (GFAP, an activated astrocyte marker) expression in spinal dorsal horn, and these effects could be attenuated by intrathecal injection of the competitive inhibitor of amino acid system A transporter, methylaminoisobutyric acid (MeAIB, 0.1, 0.3, 0.5, and 0.7mmol), in a dose-dependent manner. Intrathecal injection of vehicle (PBS) had no effect on the formalin-induced nociceptive behaviors and increase of the GFAP. These findings suggest that amino acid transport system A is involved in inflammation-induced nociception, and inhibition of this transporter system results in inhibition of the central sensitization and hyperalgesia.

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