Association of Circulating Carbohydrate Antigen 19-9 Level with Type 2 Diabetic Kidney Disease in Chinese Adults: A Cross-Sectional Study.

Objective: Very few and conflicting data are available regarding the correlation between circulating carbohydrate antigen 19-9 (CA19-9) levels and diabetic kidney disease (DKD) and its components including albuminuria and a low estimated glomerular filtration rate (eGFR). This study aimed to examine the association of circulating CA19-9 and DKD in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: A total of 402 hospitalized T2DM patients between September 2017 and December 2021 were included in this cross-sectional study. There were 224 and 178 subjects in non-DKD and DKD groups, respectively. Serum CA19-9 was measured by chemiluminescence method, and its potential relationship with DKD was evaluated by multivariate logistic regression and correlation analyses, and receiver operating characteristic (ROC) curve analysis. Results: T2DM patients with DKD had significantly higher serum CA19-9 levels than those without, and serum CA19-9 levels were positively related to urinary albumin-to-creatinine ratio and negatively to eGFR (P<0.01). Multivariate regression analysis revealed that serum CA 19-9 was an independent factor of DKD [odds ratio (OR), 1.018; 95% confidence interval (CI), 1.002-1.035; P<0.05]. Moreover, an increased progressively risk of DKD with an increase in serum CA19-9 quartiles was observed (P for trend <0.001), and T2DM patients in the highest serum CA19-9 quartile were associated with an increased likelihood of DKD when compared to those in the lowest quartile (OR: 2.936, 95% CI 1.129-7.633, P<0.05). Last, the analysis of ROC curves suggested that serum CA 19-9 at a cut of 25.09 U/mL resulted in the highest Youden index with sensitivity 43.8% and 75.4% specificity to predict the presence of DKD. Conclusion: These results showed that high circulating CA19-9 was related to DKD and may serve as a useful biomarker of DKD in hospitalized Chinese T2DM patients.

Increased Systemic Immune-Inflammation Index Was Associated with Type 2 Diabetic Peripheral Neuropathy: A Cross-Sectional Study in the Chinese Population.

Background: Systemic immune-inflammation index (SII), a novel inflammatory marker, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications, however, the relation between SII and diabetic peripheral neuropathy (DPN) has been never reported. We aimed to explore whether SII is associated with DPN in Chinese population. Methods: A cross-sectional study was conducted among 1460 hospitalized patients with T2DM. SII was calculated as the platelet count × neutrophil count/lymphocyte count, and its possible association with DPN was investigated by correlation and multivariate logistic regression analysis, and subgroup analyses. Results: Patients with higher SII quartiles had higher vibration perception threshold and prevalence of DPN (all P<0.01), and SII was independently positively associated with the prevalence of DPN (P<0.01). Multivariate logistic regression analysis showed that the risk of prevalence of DPN increased progressively across SII quartiles (P for trend <0.01), and participants in the highest quartile of SII was at a significantly increased risk of prevalent DPN compared to those in the lowest quartile after adjustment for potential confounding factors (odds rate: 1.211, 95% confidence intervals 1.045-1.404, P<0.05). Stratified analysis revealed positive associations of SII quartiles with risk of prevalent DPN only in men, people less than 65 years old, with body mass index <24 kg/m2, duration of diabetes >5 years, hypertension, dyslipidaemia, poor glycaemic control, and estimated glomerular filtration rate <90 mL/min/1.73 m2 (P for trend <0.01 or P for trend <0.05). The receiver operating characteristic curve analysis revealed that the optimal cut-off point of SII for predicting DPN was 617.67 in patients with T2DM, with a sensitivity of 45.3% and a specificity of 73%. Conclusion: The present study showed that higher SII is independently associated with increased risk of DPN, and SII might serve as a new risk biomarker for DPN in Chinese population.

Therapeutic potential and pharmacological significance of extracellular vesicles derived from traditional medicinal plants.

Medicinal plants are the primary sources for the discovery of novel medicines and the basis of ethnopharmacological research. While existing studies mainly focus on the chemical compounds, there is little research about the functions of other contents in medicinal plants. Extracellular vesicles (EVs) are functionally active, nanoscale, membrane-bound vesicles secreted by almost all eukaryotic cells. Intriguingly, plant-derived extracellular vesicles (PDEVs) also have been implicated to play an important role in therapeutic application. PDEVs were reported to have physical and chemical properties similar to mammalian EVs, which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. Besides these properties, PDEVs also exhibit unique advantages, especially intrinsic bioactivity, high stability, and easy absorption. PDEVs were found to be transferred into recipient cells and significantly affect their biological process involved in many diseases, such as inflammation and tumors. PDEVs also could offer unique morphological and compositional characteristics as natural nanocarriers by innately shuttling bioactive lipids, RNA, proteins, and other pharmacologically active substances. In addition, PDEVs could effectively encapsulate hydrophobic and hydrophilic chemicals, remain stable, and cross stringent biological barriers. Thus, this study focuses on the pharmacological action and mechanisms of PDEVs in therapeutic applications. We also systemically deal with facets of PDEVs, ranging from their isolation to composition, biological functions, and biotherapeutic roles. Efforts are also made to elucidate recent advances in re-engineering PDEVs applied as stable, effective, and non-immunogenic therapeutic applications to meet the ever-stringent demands. Considering its unique advantages, these studies not only provide relevant scientific evidence on therapeutic applications but could also replenish and inherit precious cultural heritage.

Cognitive control subprocess deficits and compensatory modulation mechanisms in patients with frontal lobe injury revealed by EEG markers: a basic study to guide brain stimulation.

Background: Frontal lobe injury (FLI) is related to cognitive control impairments, but the influences of FLI on the internal subprocesses of cognitive control remain unclear. Aims: We sought to identify specific biomarkers for long-term dysfunction or compensatory modulation in different cognitive control subprocesses. Methods: A retrospective case-control study was conducted. Event-related potentials (ERP), oscillations and functional connectivity were used to analyse electroencephalography (EEG) data from 12 patients with unilateral frontal lobe injury (UFLI), 12 patients with bilateral frontal lobe injury (BFLI) and 26 healthy controls (HCs) during a Go/NoGo task, which included several subprocesses: perceptual processing, anticipatory preparation, conflict monitoring and response decision. Results: Compared with the HC group, N2 (the second negative peak in the averaged ERP waveform) latency, and frontal and parietal oscillations were decreased only in the BFLI group, whereas P3 (the third positive peak in the averaged ERP waveform) amplitudes and sensorimotor oscillations were decreased in both patient groups. The functional connectivity of the four subprocesses was as follows: alpha connections of posterior networks in the BFLI group were lower than in the HC and UFLI groups, and these alpha connections were negatively correlated with neuropsychological tests. Theta connections of the dorsal frontoparietal network in the bilateral hemispheres of the BFLI group were lower than in the HC and UFLI groups, and these connections in the uninjured hemisphere of the UFLI group were higher than in the HC group, which were negatively correlated with behavioural performances. Delta and theta connections of the midfrontal-related networks in the BFLI group were lower than in the HC group. Theta across-network connections in the HC group were higher than in the BFLI group but lower than in the UFLI group. Conclusions: The enhancement of low-frequency connections reflects compensatory mechanisms. In contrast, alpha connections are the opposite, therefore revealing more abnormal neural activity and less compensatory connectivity as the severity of injury increases. The nodes of the above networks may serve as stimulating targets for early treatment to restore corresponding functions. EEG biomarkers can measure neuromodulation effects in heterogeneous patients.

Aspartate aminotransferase/alanine aminotransferase ratio was associated with type 2 diabetic peripheral neuropathy in a Chinese population: A cross-sectional study.

Objective: Despite previous research that focused on aspartate aminotransferase/alanine aminotransferase ratio (AAR) as predictors of type 2 diabetes mellitus (T2DM) and cardiovascular disease, there has been limited research evaluating the association between AAR and diabetic microvascular complications. This study aimed to investigate the association of AAR with diabetic peripheral neuropathy (DPN). Methods: A total of 1562 hospitalized patients with T2DM were divided into four groups according to AAR quartiles. The relationship between AAR and DPN and related parameters was explored by the Spearman correlation coefficients, multivariable logistic regression analysis, and receiver operating characteristic (ROC) curves. Results: Patients with higher AAR quartiles had higher levels of vibration perception threshold (VPT) and presence of DPN, and AAR was positively associated with VPT and presence of DPN independent of sex, age, body mass index, and diabetic duration (P<0.01 or P<0.05). Moreover, AAR remained significantly associated with a higher odds ratio (OR) of DPN (OR 2.413, 95% confidence interval [CI] 1.081-5.386, P<0.05) after multivariate adjustment. Additionally, the risk of presence of DPN increased progressively as AAR quartiles increased (all P for trend <0.01) in both male and female subjects, and the highest quartile of AAR of male and female subjects was respectively associated with 107.3% (95% CI: 1.386-3.101; P<0.01) and 136.8% (95% CI: 1.550-3.618; P<0.01) increased odds of DPN compared with the lower quartiles. Last, the analysis of receiver operating characteristic curves revealed that the best cutoff values for AAR to predict the presence of DPN were 0.906 (sensitivity: 70.3%; specificity: 49.2%; and area under the curve [AUC]: 0.618) and 1.402 (sensitivity: 38%; specificity: 81.9%; and AUC: 0.600) in male and female subjects, respectively. Conclusions: These findings suggest that the high AAR may be associated with the presence of DPN in Chinese patients with T2DM, and may be used as an additional indicator of risk of DPN.

Structural Engineering Enabled Bimetallic (Ti1- y Nby )2 AlC Solid Solution Structure for Efficient Electromagnetic Wave Absorption in Gigahertz.

Microstructures play a critical role to influence the polarization behavior of dielectric materials, which determines the electromagnetic response ability in gigahertz. However, the relationship between them, especially in the solid-solution structures is still absent. Herein, a series of (Ti1- y Nby )2 AlC MAX phase solid solutions with nano-laminated structures have been employed to illuminate the aforementioned problem. The relationship has been investigated by the lattice distortion constructed via tuning the composition from Ti to Nb in the M-site atomic layer. Experimental characterizations indicated that the dielectric response behaviors between declined conduction loss and boosted polarization loss can be well balanced by niobium atom manipulative solid-solution engineering, which is conducive to impedance matching and electromagnetic absorption performance. Theoretical calculation further proved that the origin of electric dipoles is ascribed to the charge density differences resulting from the altered microscopic atomic distribution. As a result, the Ti1.2 Nb0.8 AlC exhibits the mostly optimized microwave absorption property, in which a minimum reflection loss of -42 dB and an effective absorption bandwidth of 4.3 GHz under an ultra-thin thickness of 1.4 mm can be obtained. This work provides insight into the structural engineering in modifying electromagnetic response performance at gigahertz and which can be expanded to other solid-solution materials.

Ruxolitinib, a promising therapeutic candidate for traumatic brain injury through maintaining the homeostasis of cathepsin B.

Traumatic brain injury (TBI) is one of the main causes of death and disability in the world. Owing to the heterogeneity and complexity of TBI pathogenesis, there is still no specific drug. Our previous studies have proved the neuroprotective effect of Ruxolitinib (Ruxo) on TBI, but further are needed to explore the potent mechanisms and potential translational application. Compelling evidence indicates that Cathepsin B (CTSB) plays an important role in TBI. However, the relationships between Ruxo and CTSB upon TBI remain non-elucidated. In this study, we established a mouse model of moderate TBI to clarify it. The neurological deficit in the behavioral test was alleviated when Ruxo administrated at 6 h post-TBI. Additionally, Ruxo significantly reduced the lesion volume. As for the pathological process of acute phase, Ruxo remarkably reduced the expression of proteins associated with cell demise, neuroinflammation, and neurodegeneration. Then the expression and location of CTSB were detected respectively. We found that the expression of CTSB exhibits a transient decrease and then persistent increase following TBI. The distribution of CTSB, mainly located at NeuN-positive neurons was unchanged. Importantly, the dysregulation of CTSB expression was reversed with the treatment of Ruxo. The timepoint was chosen when CTSB decreased, to further analyze its change in the extracted organelles; and Ruxo maintained the homeostasis of it in sub-cellular. In summary, our results demonstrate that Ruxo plays neuroprotection through maintaining the homeostasis of CTSB, and will be a promising therapeutic candidate for TBI in clinic.

Recent Advances in Biomaterials-Based Therapies for Alleviation and Regeneration of Traumatic Brain Injury.

Traumatic brain injury (TBI), a major public health problem accompanied with numerous complications, usually leads to serve disability and huge financial burden. The adverse and unfavorable pathological environment triggers a series of secondary injuries, resulting in serious loss of nerve function and huge obstacle of endogenous nerve regeneration. With the advances in adaptive tissue regeneration biomaterials, regulation of detrimental microenvironment to reduce the secondary injury and to promote the neurogenesis becomes possible. The adaptive biomaterials could respond and regulate biochemical, cellular, and physiological events in the secondary injury, including excitotoxicity, oxidative stress, and neuroinflammation, to rebuild circumstances suitable for regeneration. In this review, the development of pathology after TBI is discussed, followed by the introduction of adaptive biomaterials based on various pathological characteristics. The adaptive biomaterials carried with neurotrophic factors and stem cells for TBI treatment are then summarized. Finally, the current drawbacks and future perspective of biomaterials for TBI treatment are suggested.

Association of systemic immune-inflammation index with diabetic kidney disease in patients with type 2 diabetes: a cross-sectional study in Chinese population.

Objective: Systemic immune-inflammation index (SII), a novel inflammatory marker, has been reported to be associated with diabetic kidney disease (DKD) in the U.S., however, such a close relationship with DKD in other countries, including China, has not been never determined. We aimed to explore the association between SII and DKD in Chinese population. Methods: A total of 1922 hospitalized patients with type 2 diabetes mellitus (T2DM) included in this cross-sectional study were divided into three groups based on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR): non-DKD group, DKD stages 1-2 Alb group, and DKD-non-Alb+DKD stage 3 Alb group. The possible association of SII with DKD was investigated by correlation and multivariate logistic regression analysis, and receiver-operating characteristic (ROC) curves analysis. Results: Moving from the non-DKD group to the DKD-non-Alb+DKD stage 3 Alb group, SII level was gradually increased (P for trend <0.01). Partial correlation analysis revealed that SII was positively associated with urinary ACR and prevalence of DKD, and negatively with eGFR (all P<0.01). Multivariate logistic regression analysis showed that SII remained independently significantly associated with the presence of DKD after adjustment for all confounding factors [(odds ratio (OR), 2.735; 95% confidence interval (CI), 1.840-4.063; P < 0.01)]. Moreover, compared with subjects in the lowest quartile of SII (Q1), the fully adjusted OR for presence of DKD was 1.060 (95% CI 0.773-1.455) in Q2, 1.167 (95% CI 0.995-1.368) in Q3, 1.266 (95% CI 1.129-1.420) in the highest quartile (Q4) (P for trend <0.01). Similar results were observed in presence of DKD stages 1-2 Alb or presence of DKD-non- Alb+DKD stage 3 Alb among SII quartiles. Last, the analysis of ROC curves revealed that the best cutoff values for SII to predict DKD, Alb DKD stages 1- 2, and DKD-non-Alb+ DKD stage 3 Alb were 609.85 (sensitivity: 48.3%; specificity: 72.8%), 601.71 (sensitivity: 43.9%; specificity: 72.3%), and 589.27 (sensitivity: 61.1%; specificity: 71.1%), respectively. Conclusion: Higher SII is independently associated with an increased risk of the presence and severity of DKD, and SII might be a promising biomarker for DKD and its distinct phenotypes in Chinese population.

Boosting the lithium-ion storage performance of perovskite SrxVO3-δ via Sr cation and O anion deficient engineering.

Perovskite SrVO3 has been investigated as a promising lithium storage anode where the V cation plays the role of the redox center, combining excellent cycle stability and safe operating potential versus Li metal plating, with limited capacity. Here, we demonstrate the possibility to boost the lithium storage properties, by reducing the non-redox active Sr cation content and fine-tuning the O anion vacancies while maintaining a non-stoichiometric SrxVO3-δ perovskite structure. Theoretical investigations suggest that Sr vacancy can work as favorable Li+ storage sites and preferential transport channels for guest Li+ ions, contributing to the increased specific capacity and rate performance. In contrast, inducing O anion vacancy in SrxVO3-δ can improve rate performance while compromising the specific capacity. Our experimental results confirm the enhancement of specific capacities by fine adjusting the Sr and O vacancies, with a maximum capacity of 444 mAh g-1 achieved with Sr0.63VO3-δ, which is a 37% increase versus stoichiometric SrVO3. Although rich defects have been induced, SrxVO3-δ electrodes maintain a stable perovskite structure during cycling versus a LiFePO4 cathode, and the full-cell could achieve more than 6000 discharge/charge cycles with 80% capacity retention. This result highlights the possibility to use the cation defective-based engineering approach to design high-capacity perovskite oxide anode materials.

Surface-fill H2S-releasing silk fibroin hydrogel for brain repair through the repression of neuronal pyroptosis.

Traumatic brain injury (TBI) remains the major cause of disability and mortality worldwide due to the persistent neuroinflammation and neuronal death induced by TBI. Among them, pyroptosis, a specific type of programmed cell death (PCD) triggered by inflammatory signals, plays a significant part in the pathological process after TBI. Inhibition of neuroinflammation and pyroptosis is considered a possible strategy for the treatment of TBI. In our previous study, exogenous hydrogen sulfide(H2S) exerted a neuroprotective effect after TBI. Here, we developed a surface-fill H2S-releasing silk fibroin (SF) hydrogel (H2S@SF hydrogel) to achieve small-dose local administration and avoid volatile and toxic side effects. We used a controlled cortical impact (CCI) to establish a mild TBI model in mice to examine the effect of H2S@SF hydrogel on TBI-induced pyroptosis. We found that H2S@SF hydrogel inhibited the expression of H2S synthase in neurons after TBI and significantly inhibited TBI-induced neuronal pyroptosis. In addition, immunofluorescence staining results showed that the necroptosis protein receptor-interacting serine/threonine-protein kinase 1 (RIPK1) partially colocalized with the pyroptosis protein Gasdermin D (GSDMD) in the same cells. H2S@SF hydrogel can also inhibit the expression of the necroptosis protein. Moreover, H2S@SF hydrogel also alleviates brain edema and the degree of neurodegeneration in the acute phase of TBI. The neuroprotective effect of H2S@SF hydrogel was further confirmed by wire-grip test, open field test, Morris water maze, beam balance test, radial arm maze, tail suspension, and forced swimming test. Lastly, we also measured spared tissue volume, reactive astrocytes and activated microglia to demonstrate H2S@SF hydrogel impacts on long-term prognosis in TBI. Our study provides a new theoretical basis for the treatment of H2S after TBI and the clinical application of H2S@SF hydrogel. STATEMENT OF SIGNIFICANCE: Silk fibroin (SF) hydrogel controls the release of hydrogen sulfide (H2S) to inhibit neuronal pyroptosis and neuroinflammation in injured brain tissue. In this study, we synthesized a surface-fill H2S-releasing silk fibroin hydrogel, which could slowly release H2S to reshape the homeostasis of endogenous H2S in injured neurons and inhibit neuronal pyroptosis in a mouse model of traumatic brain injury. Meanwhile, H2S@SF hydrogel could alleviate brain edema and the degree of neurodegeneration, improve motor dysfunction, anxious behavior and memory impairment caused by TBI, reduce tissue loss and ameliorate neuroinflammation. Our study provides a new theoretical basis for the treatment of H2S after TBI and the clinical application of H2S@SF hydrogel.

Corrigendum: Doppler evaluation of hepatic hemodynamics after living donor liver transplantation in infants.

[This corrects the article DOI: 10.3389/fbioe.2022.903385.].

Doppler evaluation of hepatic hemodynamics after living donor liver transplantation in infants.

Objective: The aim of this study was to explore the hemodynamic changes of hepatic artery and portal vein detected by Doppler ultrasound (DU) in infants who underwent living donor liver transplantation (LDLT). Methods: The data of 41 infant patients (22 Males, 19 Females, median age of 5 months) were collected in the Children's Hospital affiliated to the Chongqing Medical University from May 2018 to December 2019. The patients underwent left lateral segment LDLT (LLS -LDLT) because of biliary atresia (BA). Hemodynamic parameters, including the peak systolic velocity (PSV), resistivity index (RI) of the hepatic artery (HA), portal vein velocity (PVV), and portal vein flow (PVF) were recorded from Doppler ultrasound on the day before the operation, and on the 1st, the 7th, the 14th and the 30th day after LDLT procedures. The changes of PSVHA, RIHA, PVV and PVF before and on the 1st day after transplantation were analyzed by paired t-test. The comparison of the data between different postoperative time points were assessed by ANOVA. Results: Compared with the parameters measured before LDLT, PSVHA, and RIHA decreased, and PVV and PVF increased significantly (p < 0.001) on the 1st day after LLS-LDLT. As for PSV, there was no significant difference between the 7th day and the 1st day after transplantation (POD7 VS POD1, p = 0.167) while there was a substantial difference between the 14th, 30th and 1st day after LT (POD14 vs. POD1, p = 0.003) (POD30 vs. POD1, p < 0.001). And there was a significant difference between the 14th, 30th, and 7th days after LT (POD14 vs. POD7, p = 0.014) (POD30 vs. POD7, p < 0.001). There was no significant difference between 30th and 14th after transplantation (POD30 vs. POD14, p = 0.092). As for RIHA and PVV, the decrease was slow within the first month after the operation, and there was no significant difference at different times. Conclusion: We have identified major hepatic flow changes that occurred in 41 infants who underwent LLS -LDLT due to BA. The data could be used for future studies of LDLT in infants including hemodynamic modeling, liver regeneration and clinical management.

Implantation of injectable SF hydrogel with sustained hydrogen sulfide delivery reduces neuronal pyroptosis and enhances functional recovery after severe intracerebral hemorrhage.

Hydrogen sulfide (H2S), an important endogenous signaling molecule, plays an important neuroprotective role in the central nervous system. However, there is no ideal delivery material or method involving the sustained and controlled release of H2S for clinical application in brain diseases. Silk fibroin (SF)-based hydrogels have become a potentially promising strategy for local, controlled, sustained drug release in the treatment of various disorders. Here, we show a silk fibroin (SF)-based hydrogel with sustained H2S delivery (H2S@SF hydrogel) is effective in treating brain injury through stereotactic orthotopic injection in a severe intracerebral hemorrhage (ICH) mouse model. In this study, we observed H2S@SF hydrogel sustained H2S release in vitro and in vivo. The physicochemical properties of H2S@SF hydrogel were studied using FE-SEM, Raman spectroscopy and Rheological analysis. Treatment with H2S@SF hydrogel attenuated brain edema, reduced hemorrhage volume and improved the recovery of neurological deficits after severe ICH following stereotactic orthotopic injection. Double immunofluorescent staining also revealed that H2S@SF hydrogel may reduce cell pyroptosis in the striatum, cortex and hippocampus. However, when using endogenous H2S production inhibitor AOAA, H2S@SF hydrogel could not suppress ICH-induced cell pyroptosis. Hence, the therapeutic effect of the H2S@SF hydrogel may be partly the result of the slow-release of H2S and/or the effect of the SF hydrogel on the production of endogenous H2S. Altogether, the results exhibit promising attributes of injectable silk fibroin hydrogel and the utility of H2S-loaded injectable SF hydrogel as an alternative biomaterial toward brain injury treatment for clinical application.

Silk Fibroin Hydrogels Could Be Therapeutic Biomaterials for Neurological Diseases.

Silk fibroin, a natural macromolecular protein without physiological activity, has been widely used in different fields, such as the regeneration of bones, cartilage, nerves, and other tissues. Due to irrevocable neuronal injury, the treatment and prognosis of neurological diseases need to be investigated. Despite attempts to propel neuroprotective therapeutic approaches, numerous attempts to translate effective therapies for brain disease have been largely unsuccessful. As a good candidate for biomedical applications, hydrogels based on silk fibroin effectively amplify their advantages. The ability of nerve tissue regeneration, inflammation regulation, the slow release of drugs, antioxidative stress, regulation of cell death, and hemostasis could lead to a new approach to treating neurological disorders. In this review, we introduced the preparation of SF hydrogels and then delineated the probable mechanism of silk fibroin in the treatment of neurological diseases. Finally, we showed the application of silk fibroin in neurological diseases.

Spatiotemporal Dynamics of Covert Attention With Different Degrees of Central Visual Field Defects: An ERP and sLORETA Study.

Purpose: The present study aimed to investigate the spatiotemporal dynamics of covert attention by simulating different degrees of central visual field defects in healthy subjects. Methods: An electroencephalogram (EEG) was recorded while 40 normal-sighted subjects performed a target discrimination task. Target stimuli simulated different defect degrees of the central visual field by artificially central scotomas (5, 10, 20, and 30 degrees of visual angle) masked on the center of black-and-white checkerboards. Event-related potentials (ERPs) and standardized low-resolution brain electromagnetic tomography (sLORETA) based on ERPs were analyzed. Results: ERP results indicated that during early perceptual processes, compared with 5-degree and 10-degree defects, N1 amplitudes of 20-degree and 30-degree defects decreased, whereas P2 amplitudes significantly reduced in 30-degree defects. During later discrimination and decision processing, N2 amplitudes gradually increased from 5-degree to 30-degree defects, whereas P3 amplitudes gradually decreased. Source localization indicated that 5-degree and 10-degree defects had stronger activations than 20-degree and 30-degree defects from the occipital cortex to the ventral stream and dorsal streams. Especially, 30-degree defects primarily recruited additional activations in the ventrolateral prefrontal cortex and ventral stream and later caused the disconnection of dorsolateral prefrontal-posterior parietal cortices in the dorsal stream. Conclusions: Different degrees of central visual field defects differed in distinct spatiotemporal characteristics at multiple stages of covert attention, from top-down forward feedback and attentional allocation to executive controls through ventral and dorsal processing streams, suggesting that the combination of ERP and source localization can reveal the spatiotemporal control capacity of the cortex on central visual field defects.

Interleukin-13 Affects the Recovery Processes in a Mouse Model of Hemorrhagic Stroke with Bilateral Tibial Fracture.

As one form of stroke, intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease, which has high morbidity and mortality and lacks effective medical treatment. Increased infiltration of inflammatory cytokines coupled with pyroptotic cell death is involved in the pathophysiological process of ICH. However, little is known about whether concomitant fracture patients have the same progression of inflammation and pyroptosis. Hence, we respectively established the mouse ICH model and ICH with bilateral tibial fracture model (MI) to explore the potential cross-talk between the above two injuries. We found that MI obviously reversed the expressions of pyroptosis-associated proteins, which were remarkably up-regulated at the acute phase after ICH. Similar results were observed in neuronal expressions via double immunostaining. Furthermore, brain edema was also significantly alleviated in mice who suffered MI, when compared with ICH alone. To better clarify the potential mechanisms that mediated this cross-talk, recombinant mouse interleukin-13 (IL-13) was used to investigate its effect on pyroptosis in the mouse MI model, in which a lower level of IL-13 was observed. Remarkably, IL-13 administration re-awakened cell death, which was mirrored by the re-upregulation of pyroptosis-associated proteins and PI-positive cell counts. The results of hemorrhage volume and behavioral tests further confirmed its critical role in regulating neurological functions. Besides, the IL-13-treated MI group showed poor outcomes of fracture healing. To sum up, our research indicates that controlling the IL-13 content in the acute phase would be a promising target in influencing the outcomes of brain injury and fracture, and meanwhile, provides new evidence in repairing compound injuries in clinics.

Autophagy inhibition facilitates wound closure partially dependent on the YAP/IL-33 signaling in a mouse model of skin wound healing.

Autophagy is a self-phagocytic and highly evolutionarily conserved intracellular lysosomal catabolic system, which plays a vital role in a variety of trauma models, including skin wound healing (SWH). However, the roles and potential mechanisms of autophagy in SWH are still controversial. We firstly investigated the role of autophagy in SWH-induced wound closure rate, inflammatory response, and histopathology, utilizing an inhibitor of autophagy 3-methyladenine (3-MA) and its agonist rapamycin (RAP). As expected, we found 3-MA treatment remarkably increased the wound closure rate, combated inflammation response, and mitigated histopathological changes, while RAP delivery aggravated SWH-induced pathological damage. To further exploit the underlying mechanism of autophagy regulating inflammation, the specific inhibitors of yes-associated protein (YAP), Verteporfin, and Anti-IL-33 were applied. Herein, treating with 3-MA markedly suppressed the expression of tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6, promoted that of IL-10, IL-33, and ST2, while RAP administration reverted SWH-induced the up-regulation of these inflammatory cytokines mentioned above. Importantly, Verteporfin administration not only down-regulated the expression levels of YAP, TNF-α, and IL-6 but also up-regulated that of IL-33 and IL-10. Unexpectedly, 3-MA or RAP retreatment did not have any impact on the changes in IL-33 among these inflammatory indicators. Furthermore, elevated expression of IL-33 promoted wound closure and alleviated the pathological damage, whereas, its antagonist Anti-IL-33 treatment overtly reversed the above-mentioned effects of IL-33. Moreover, 3-MA in combination with anti-IL-33 treatment reversed the role of 3-MA alone in mitigated pathological changes, but they failed to revert the effect of anti-IL-33 alone on worsening pathological damage. In sum, emerging data support the novel contribution of the YAP/IL-33 pathway in autophagy inhibition against SWH-induced pathological damage, and highlight that the autophagy/YAP/IL-33 signal axis is expected to become a new therapeutic target for SWH.

Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Various forms of cells death are involved in the pathological process of TBI, without exception to ferroptosis, which is mainly triggered by iron-dependent lipid peroxidation. Although there have been studies on ferroptosis and TBI, the effect of ruxolitinib (Ruxo), one type of FDA approved drugs for treating myelofibrosis, on the process of ferroptosis post-TBI is remained non-elucidated. Therefore, using a controlled cortical impact device to establish the mouse TBI model, we examined the effect of Ruxo on TBI-induced ferroptosis, in which the inhibitor of ferroptosis, Ferrostatin-1 (Fer-1) was used as a positive control. Moreover, we also respectively explored the effects of these two interventions on neurological deficits caused by TBI. We firstly examined the expression patterns of ferroptosis-related markers at protein level at different time points after TBI. And based on the expression changes of these markers, we chose 12 h post-TBI to prove the effect of Ruxo on ferroptosis. Importantly, we found the intensely inhibitory effect of Ruxo on ferroptosis, which is in parallel with the results obtained after Fer-1-treatment. In addition, these two treatments both alleviated the content of brain water and degree of neurodegeneration in the acute phase of TBI. Finally, we further confirmed the neuroprotective effect of Ruxo or Fer-1 via the wire-grip test, Morris water maze and open field test, respectively. Thereafter, the lesion volume and iron deposition were also measured to certificate their effects on the long-term outcomes of TBI. Our results ultimately demonstrate that inhibiting ferroptosis exerts neuroprotection, and this is another neuroprotective mechanism of Ruxo on TBI.

Ocular Dominance and Functional Asymmetry in Visual Attention Networks.

Purpose: The dorsal attention network (DAN) and the ventral attention network (VAN) are known to support visual attention, but the influences of ocular dominance on the attention networks are unclear. We aimed to explore how visual cortical asymmetry of the attention networks correlate with neurophysiological oscillation and connectivity markers of attentional processes. Methods: An oddball task with concentric circle stimuli of three different sizes (i.e., spot size of 5°, 20°, or 30° of visual angle) was used to vary task difficulty. Event-related oscillations and interareal communication were tested with an electroencephalogram-based visual evoked components as a function of ocular dominance in 30 healthy subjects. Results: Accuracy rates were higher in the dominant eyes compared with the nondominant eyes. Compared with the nondominant eyes, the dominant eyes had higher theta, low-alpha, and low-beta powers and lower high-alpha powers within the nodes of VAN and DAN. Furthermore, visual information processed by the dominant and nondominant eye had different fates, that is, the dominant eyes mainly relied on theta and low-alpha connectivity within both the VAN and the DAN, whereas the nondominant eyes mainly relied on theta connectivity within the VAN and high-alpha connectivity within the DAN. The difference in accuracy rate between the two eyes was correlated with the low-alpha oscillations in the anterior DAN area and low-alpha connectivity of the left DAN. Conclusions: The ocular dominance processing and interareal communication reveal a cortical asymmetry underlying attention, and this reflects a two-way modulatory mechanism within attention networks in the human brain.