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.

Differences and allometric relationships among assimilative branch traits of four shrubs in Central Asia.

Shrubs play a major role in maintaining ecosystem stability in the arid deserts of Central Asia. During the long-term adaptation to extreme arid environments, shrubs have developed special assimilative branches that replace leaves for photosynthesis. In this study, four dominant shrubs with assimilative branches, namely Haloxylon ammodendron, Haloxylon persicum, Calligonum mongolicum, and Ephedra przewalskii, were selected as the research objects, and the dry mass, total length, node number, and basal diameter of their assimilative branches and the average length of the first three nodes were carefully measured, and the allometric relationships among five traits of four species were systematically compared. The results indicated that: (1) Four desert shrubs have different assimilative branches traits. Compared with H. persicum and H. ammodendron, C. mongolicum and E. przewalskii have longer internodes and fewer nodes. The dry mass of H. ammodendron and the basal diameter of H. persicum were the smallest; (2) Significant allometric scaling relationships were found between dry mass, total length, basal diameter, and each trait of assimilative branches, all of which were significantly less than 1; (3) The scaling exponents of the allometric relationship between four traits and the dry mass of assimilative branches of H. persicum were greater or significantly greater than those of H. ammodendron. The scaling exponents of the relationships between the basal diameter, dry mass, and total length of E. przewalskii were higher than those of the other three shrubs. Therefore, although different species have adapted to drought and high temperatures by convergence, there was great variability in morphological characteristics of assimilative branches, as well as in the scaling exponents of relationships among traits. The results of this study will provide valuable insights into the ecological functions of assimilative branches and survival strategies of these shrubs to cope with aridity and drought in desert environments.

Microwave assisted extraction, characterization of a polysaccharide from Salvia miltiorrhiza Bunge and its antioxidant effects via ferroptosis-mediated activation of the Nrf2/HO-1 pathway.

A microwave-assisted extraction procedure for the crude Salvia miltiorrhiza polysaccharides (SMPs) obtained from Salvia miltiorrhiza Bunge was optimized. Four independent variables were studied: microwave power, extraction time, solvent-to-solid ratio, and concentration of ethanol, with optimal settings of 1200 W, 12 min, 38, and 86 %, respectively. The SMPs were successively purified by DEAE Sepharose Fast Flow and Sephadex G-100 chromatography to produce a novel polysaccharide termed SMP1. The SMP1 was composed of glucose, galactose, and fructose in a molar ratio of 1:1.67:1.12 with an average molecular weight of 6087 Da. Pharmacological studies showed that SMP1 protected from OGD/R-induced ferroptosis and lipid peroxidation by activating Nrf2/HO-1 pathway in PC12 cells. Our research systematically indicated that polysaccharide could inhibit ferroptosis to alleviate oxidative stress injury, which laid the foundation for the future clinical application of Salvia miltiorrhiza polysaccharide.

Hydroxysafflor yellow A and anhydrosafflor yellow B alleviate ferroptosis and parthanatos in PC12 cells injured by OGD/R.

Ferroptosis and parthanatos are two types of programmed cell death associated with cerebral ischemia. There is a sizeable interest in seeking chemical components for the regulation of ferroptosis and parthanatos. Hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) mitigated cell death caused by oxidative stress due to antioxidant capacity, yet the mechanism is still uncertain. Thus, we investigated whether HSYA and AHSYB prevent death through these two pathways with the aim to elucidate their potential protective mechanisms of cerebral ischemia. In this study, oxidative stress model was established by treating PC12 cells with oxygen glucose deprivation and reperfusion (OGD/R). Cellular functions and signaling pathways were analyzed in PC12 cells using cell counting kit-8 (CCK-8), flow cytometry, ELISA, iron assay kit, transmission electron microscopy (TEM), immunofluorescence, and western blot analysis. And the research proved HSYA and AHSYB protected cells from oxidative stress. The phenomenon is associated with ferroptosis and parthanatos. HSYA and AHSYB upregulated cystine/glutamate antiporter system xc- (system xc-) and glutathione peroxidase 4 (GPX4), returned the levels of GSH/GSSG ratio, reactive oxygen species (ROS) and iron ion, as well as alleviated lipid peroxidation. By reason of reducing ROS, HSYA and AHSYB restrained poly(ADP-ribose) polymerase-1 (PARP-1) overactivation, reduced the production of excess poly(ADP-ribose) (PAR) polymer and apoptosis inducing factor (AIF) nuclear translocation. The results suggested that HSYA and AHSYB limited ferroptosis and parthanatos to alleviate oxidative stress in PC12 cells. These findings may have implications for improving understanding of how drugs reduce oxidative stress and develop new strategies for treating degenerative diseases such as cerebral ischemia.

Protective effects of polysaccharides on cerebral ischemia: A mini-review of the mechanisms.

Cerebral ischemia, a common cerebrovascular disease, is one of the great threats to human health. Nowadays, many drugs used in the treatment of cerebral ischemia such as clot busting drugs, antiplatelet drugs, and neuroprotective drugs have limits. It is urgent finding new effective treatments for the patients. Researches have confirmed that many kinds of polysaccharides from natural resources possess therapeutic effects on cerebral ischemia, but are still lack of a comprehensively understanding. In this paper, based on the pathophysiology of cerebral ischemic injury, we summarize the latest discoveries and advancements of 29 kinds of polysaccharides, focusing on their ameliorating effects on cerebral ischemia and the underlying mechanisms. Several mechanisms are involved, mainly including antioxidant activities, anti-inflammatory activities, regulating neuron apoptosis, as well as resisting nitrosative stress injury. Besides, polysaccharides show protective effects through certain signaling pathways including PI3K/Akt, MAPK, and NF-κB, PARP-1/AIF, JNK3/c-Jun/Fas-L, and Nrf2/HO-1 signaling pathways. The main goal of this mini-review is to emphasize the important roles of polysaccharides in attenuating cerebral ischemic injury through the elucidation of mechanisms.

Characteristics of Visual Evoked Potential in Different Parts of Visual Impairment. / 不同部位损伤致视力障碍的视觉诱发电位特征.

OBJECTIVES: To study the quantitative and qualitative differences of visual evoked potential (VEP) in monocular visual impairment after different parts of visual pathway injury. METHODS: A total of 91 subjects with monocular visual impairment caused by trauma were selected and divided into intraocular refractive media-injury group (eyeball injury group for short), optic nerve injury group, central nervous system injury and intracranial combined injury group according to the injury cause and anatomical segment. Pattern Reversal visual evoked potential (PR-VEP) P100 peak time and amplitude, Flash visual evoked potential (F-VEP) P2 peak time and amplitude were recorded respectively. SPSS 26.0 software was used to analyze the differences of quantitative (peak time and amplitude) and qualitative indexes (spatial frequency sweep-VEP acuity threshold, and abnormal waveform category and frequency) of the four groups. RESULTS: Compared with healthy eyes, the PR-VEP P100 waveforms of the intraocular eyeball injury group and the F-VEP P2 waveforms of the optic nerve group showed significant differences in prolonged peak time and decreased amplitude in injured eyes (P<0.05). The PR-VEP amplitudes of healthy eyes were lower than those of injured eyes at multiple spatial frequencies in central nervous system injury group and intracranial combined injury group (P<0.05).The amplitude of PR-VEP in patients with visual impairment involving central injury was lower than that in patients with eye injury at multiple spatial frequencies. The frequency of VEP P waveforms reaching the threshold of the intraocular injury group and the optic nerve injury group were siginificantly different from the intracranial combined injury group, respectively(P<0.008 3), and the frequency of abnormal reduction of VEP amplitude of threshold were significantly different from the central nervous system injury group, respectively(P<0.008 3). CONCLUSIONS: VEP can distinguish central injury from peripheral injury, eyeball injury from nerve injury in peripheral injury, but cannot distinguish simple intracranial injury from complex injury, which provides basic data and basis for further research on the location of visual impairment injury.

A cationic tetrahedral Zn(ii) cluster based on a new salicylamide imine multidentate ligand: synthesis, structure and fluorescence sensing study.

A monocationic ZnII tetrahedral cluster, [Zn4L3(µ3-OH)]·NO3·1.25H2O (Zn4L3) based on a new salicylamide imine ligand H2L, H2L = 1-(2-hydroxy-3-methoxy-benzamido)-3-(2-hydroxy-3-methoxy-benzylideneamino)-propane, has been prepared. Single crystal X-ray analysis reveals that three deprotonated ligands L2- chelate three Zn(ii) centres with their salicylamide moiety in such a way that the three salicylimine groups attached to the other side of the three chelates are converged to bind another Zn(ii) centre to provide a tetrahedral cluster with two phenyl groups of the same ligand L2- being close enough to present a strong intramolecular ππ stacking effect. Fluorescence studies indicate that Zn4L3 is stable in water and exhibits highly sensitive and selective recognition of phosphates against other common anions including CO32-, HCO3-, NO3-, F-, Cl-, Br-, I-, HSO4-, SO42-, OAc-, BF4-, ClO4- and CF3SO3- in HEPES buffer solution (pH = 7.4) + DMSO (V : V = 1 : 9). The excellent sensing capability of Zn4L3 for phosphate against other common anions with a low detection limit of 0.15 µM renders it a candidate probe for phosphate detection. Furthermore, the observed fluorescence quenching responses of Zn4L3 towards phosphates were highly reversible. The possible sensing mechanisms for phosphate detection by Zn4L3 was investigated by means of 1H NMR, UV-Vis spectra and high-resolution ESI-MS spectra and the results indicate that phosphates could exclusively decompose Zn4L3 to release H2L in HEPES buffer solution (pH = 7.4) + DMSO (V : V = 1 : 9).

An analysis on treatment effect of blue light phototherapy combined with Bifico in treating neonatal hemolytic jaundice.

This study aimed to discuss and evaluate the clinical effect of blue light phototherapy combined with bifico in treating neonatal hemolytic jaundice. One hundred and twenty cases with neonatal hemolytic jaundice were randomly divided into treatment group and control group, 60 cases in each group. Neonatal patients in the control group were treated with traditional treatment, including administration of enzyme inducer phenobarbital and blue light phototherapy for 8 consecutive hours every day. Neonatal patients in the treatment group received bifico orally based on traditional treatment. Clinical effects of the two groups were observed after one course of treatment (7 days as one course). During the first course, serum bilirubin level in the treatment group treated with blue light phototherapy combined with bifico declined more rapidly (P<0.01) and more significantly (P<0.01) than that in the control group, and the mean time for eliminating jaundice was significantly reduced (P<0.05). The total effective rate was 91.67% in the treatment group, while that was 85.00% in the control group, which suggested that the treatment effect of the treatment group was better than that of the control group and the difference between the two groups was statistically significant (P<0.05). Compared with traditional treatment, the treatment effect of blue light phototherapy combined with bifico in treating neonatal hemolytic jaundice is significantly improved and the speed of eliminating jaundice is also higher. Thus, it is worthy to be applied in clinical practice.

Coordination-Driven Self-Assembled ZnII6-LnIII3 Metallocycles Based on a Salicylamide Imine Ligand: Synthesis, Structure, and Selective Luminescence Enhancement Induced by OAc.

Five heterometallic ZnII6-LnIII3 macrocycles based on a salicylamide imine multidentate unsymmetrical ligand H2L [1-(2-hydroxy-3-methoxy-benzamido)-2-(2-hydroxy-3-methoxy-benzylideneamino)-ethane] have been prepared via a coordination-driven self-assembly strategy. Single-crystal X-ray diffraction analysis reveals that the five metallocycles are isomorphic with a formula of [Zn6Ln3L6(OH)2(NO3)4(H2O)]·3NO3· nCH3CN (ZnLn-1, where Ln = Pr, Nd, Eu, Tb, or Yb; for ZnPr-1, n = 4; for ZnNd-1, ZnEu-1, and ZnTb-1, n = 2; for ZnYb-1, n = 3), where six octadentate ligands L2- and two in situ-formed µ2-OH- ions bridged the alternating ZnII-LnIII-ZnII subunits into a macrocycle. Along with the structural novelty, ZnNd-1 shows distinctive enhanced emission in the visible and near-infrared range upon addition of OAc-. On the basis of ultraviolet-visible spectroscopy, 1H nuclear magnetic resonance, single-crystal X-ray diffraction, and high-resolution electrospray ionization mass spectrometry, we deduced that this emission enhancement could be attributed to the synergistic effect of TICT and the absent nonradiative transition of µ2-OH- induced distinctively by OAc- bridging. Our results demonstrate that the NdIII-containing heterometallic macrocycle can act as a host for anion exchanging and provide a nice example of heterometallic macrocycles with interesting properties and potential applications.

Automatic Conflict Monitoring by Event-Related Potentials Could be used to Estimate Visual Acuity Levels.

Numerous studies have explored the physical attribute features or face perceptions in conflict processing, while complicate gradient conflicts were rarely discussed. The aim of the study was to discuss the relationship between the event-related potential (ERP) component features and different visual acuity levels by using the modified S1-S2 task under non-attention status. Three visual acuity levels were applied, each with four orientations of "E" optotype stimuli randomly presented in the center of the visual field while participants were required to concentrate on listening to stories. The results showed that the amplitudes of P1 and P3 as well as difference P3 were larger in supra-threshold condition. In threshold condition, larger amplitudes for both N2 and difference N2 exhibited in frontal and central areas. In sub-threshold condition, there was no endogenous component elicited by mismatch stimuli except smaller anterior N1. Meanwhile, the specific distributions of N1 and N2 were presented and compared with previous face processing. The findings showed that visual conflict processing took place not only at an early stage but also at the late period, which might be as the consequences of interaction between conflict strength and involuntary attention. We concluded that automatic conflict detecting of visual icons by the serial ERP components could distinguish different visual acuity levels. The involvement of endogenous components could reveal the specific mechanism of more precise and fine conflict identification of complex physical attributes under non-attention status, furthermore could be used as valid markers to estimate the magnitude of visual acuity objectively.

IL-33 Exerts Neuroprotective Effect in Mice Intracerebral Hemorrhage Model Through Suppressing Inflammation/Apoptotic/Autophagic Pathway.

Interleukin-33 (IL-33) is a recently identified member of the IL-1 family that exerts biologic functions by binding to a heterodimer composed of IL-1 receptor-related protein ST2L and IL-1RAcP. However, the role of IL-33 and whether IL-33 accounts for inflammation, apoptotic, and autophagic neuropathology after intracerebral hemorrhage (ICH) are not clear. Here, we established a mouse ICH model in this study, to determine the role of IL-33 and explore the underlying mechanism. Male mice were subjected to an infusion of type IV collagenase/saline into the left striatum to induce ICH/sham model. IL-33, soluble ST2 (sST2), or saline were also administered by a single intracerebroventricular (i.c.v.) injection, respectively. The results showed that the expression level of IL-33 markedly decreased within 6 h and reached the valleys at 6 and 72 h after ICH vs. sham group. In parallel, ST2L (a transmembrane form receptor of IL-33) significantly increased within 6 h and reached the peaks at 6 h and 24 h after ICH vs. sham group. In addition, administration of IL-33 alleviated cerebral water contents, reduced the number of PI- and TUNEL-positive cells, and improved neurological function after ICH. Moreover, IL-33 treatment apparently suppressed the expression of pro-inflammation cytokines IL-1ß and TNF-α, evidently increased Bcl-2 but decreased cleaved-caspase-3, and obviously decreased the levels of autophagy-associated proteins LC3-II and Beclin-1 but maintained P62 at high level after ICH. On the contrary, treatment with sST2, a decoy receptor of IL-33, exacerbated ICH-induced brain damage and neurological dysfunction by promoting apoptosis, and enhancing autophagic activity. In conclusion, IL-33 provides neuroprotection through suppressing inflammation, apoptotic, and autophagic activation in collagenase-induced ICH model.

[Research Progress of Event-related Potential in Mild Cognitive Impairment].

Mild cognitive impairment caused by craniocerebral trauma is the key points and difficulties in judicial authentication. This article has comparative analysis of each mode of event-related potential (classical Oddball, Eriksen flanker task and so on), which can provide a more objective method for such craniocerebral trauma cases in clinical forensic judicial authentication.

The automatic processing of visual information at different visual acuity levels: An ERP study.

This study investigated the subjective visual acuity by recording ERPs elicited by task-irrelevant visual changes. Optotypes stimuli were presented in the center of the visual field at three threshold levels (supra-threshold, threshold and sub-threshold) while participants were listening to stories. The results showed that neither vMMN nor P3a component was elicited by optotypes stimuli on the sub-threshold condition, whereas, vMMN was elicited under supra-threshold and threshold conditions, with no significant differences between those vMMN amplitudes of two conditions. The P3a amplitude was larger for supra-threshold condition than that for threshold condition. These data demonstrated that the emergence of vMMN could only reflect the automatic detection of orientation-changes in the supra-threshold and threshold conditions compared to the sub-threshold condition, whereas the P3a amplitude could reflect the difference in processing of supra-threshold and threshold stimuli.

Poloxamer-188 can attenuate blood-brain barrier damage to exert neuroprotective effect in mice intracerebral hemorrhage model.

Blood-brain barrier (BBB) disruption and brain edema formation play important roles in the secondary neuronal death and neurological dysfunction induced by intracerebral hemorrhage (ICH). Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to be capable of sealing damaged cell membranes and decrease neuronal cell death. In this study, we explored whether P188 had a protective effect against ICH and its underlying mechanisms. Male ICR mice were subjected to infusion of type IV collagenase (to induce ICH) of saline (for shams) into the left striatum. The results showed that P188-12 mg post-treatment by tail intravenous injection significantly ameliorated the neurological symptoms and brain edema, attenuated BBB permeability, and decreased cell insults and injury volume at 24 and 72 h after ICH. Furthermore, P188 maintained the protein levels of tight junction (TJ) proteins including claudin-5, occludin, and zonula occludens-1, and reversed the increases of nuclear factor-kappaB (NF-κB), matrix metalloproteinase (MMP)-2, and MMP-9 protein expression at 72 h post ICH. Immunofluorescence showed P188 treatment rearranged the structure of TJ proteins in a continuous and linear pattern. Therefore, the present study concludes that P188 can protect against ICH, and the protective effect was associated with preventing BBB disruption through NF-κB-MMPs-mediated TJ proteins degradation.

Anti-necroptosis chemical necrostatin-1 can also suppress apoptotic and autophagic pathway to exert neuroprotective effect in mice intracerebral hemorrhage model.

Necroptosis was recently discovered as one form of programmed cell death (PCD) and could be specifically inhibited by necrostatin-1. The aim of this study was to examine the effect of necrostatin-1 on brain injury and investigate the role of necrostatin-1 on the other two types PCD (apoptosis and autophagic cell death) in a mouse intracerebral hemorrhage (ICH) model. Male ICR mice received an infusion of type IV collagenase to induce ICH or saline as control into the left striatum. In the presence of vehicle, 3-MA, zVAD, and necrostatin-1 were pretreated with a single intracerebroventricular (i.c.v.) injection in the ipsilateral ventricle 15 min before ICH, respectively. Compared with vehicle groups, necrostatin-1 treatment significantly reduced injury volume and propidium iodide-positive cells at 24 and 72 h after ICH. Immunoblotting analysis showed that necrostatin-1 treatment suppressed autophagic-associated proteins (LC3-II, Beclin-1) and maintained p62 at normal level at 24 and 72 h after ICH. In addition, necrostatin-1 treatment enhanced the protein level of Bcl-2 and decreased the protein level of cleaved caspase-3 and the Beclin-1/Bcl-2 ratio at 24 and 72 h after ICH. Moreover, both 3-MA and necrostatin-1 treatment could suppress cleaved caspase-3 and LC3-II production, whereas zVAD treatment could inhibit caspase-3 cleavage but increased LC3-II protein levels at 72 h after ICH. Taken together, the data demonstrated for the first time that the specific inhibitor necrostatin-1 suppressed apoptosis and autophagy to exert these neuroprotective effects after ICH and that there existed a cross-talk among necroptosis, apoptosis, and autophagy after ICH.