The role of nonequilibrium LO phonons, Pauli exclusion, and intervalley pathways on the relaxation of hot carriers in InGaAs/InGaAsP multi-quantum-wells.

Under continuous-wave laser excitation in a lattice-matched In0.53Ga0.47As/In0.8Ga0.2As0.44P0.56 multi-quantum-well (MQW) structure, the carrier temperature extracted from photoluminescence rises faster for 405 nm compared with 980 nm excitation, as the injected carrier density increases. Ensemble Monte Carlo simulation of the carrier dynamics in the MQW system shows that this carrier temperature rise is dominated by nonequilibrium LO phonon effects, with the Pauli exclusion having a significant effect at high carrier densities. Further, we find a significant fraction of carriers reside in the satellite L-valleys for 405 nm excitation due to strong intervalley transfer, leading to a cooler steady-state electron temperature in the central valley compared with the case when intervalley transfer is excluded from the model. Good agreement between experiment and simulation has been shown, and detailed analysis has been presented. This study expands our knowledge of the dynamics of the hot carrier population in semiconductors, which can be applied to further limit energy loss in solar cells.

Tetrahydrofolate Alleviates the Inhibitory Effect of Oxidative Stress on Neural Stem Cell Proliferation through PTEN/Akt/mTOR Pathway.

Neural stem cell (NSC) proliferation is the initial step for NSC participating in neurorehabilitation after central nervous system (CNS) injury. During this process, oxidative stress is always involved in restricting the regenerative ability of NSC. Tetrahydrofolate (THF) is susceptible to oxidative stress and exhibits a high antioxidant activity. While its effect on NSC proliferation under oxidative stress condition remains obscure. Here, NSC were isolated from embryonic mice and identified using immunofluorescent staining. Meanwhile, the results showed that THF (5 µM and 10 µM) attenuated oxidative stress induced by 50 µM hydrogen peroxide (H2O2) in NSC using mitochondrial hydroxyl radical detection and Western blotting assays. Afterward, administration of THF markedly alleviated the inhibitory effect of oxidative stress on NSC proliferation, which was evidenced by Cell Counting Kit-8 (CCK8), neurosphere formation, and immunofluorescence of Ki67 assays. Thereafter, the results revealed that PTEN/Akt/mTOR signaling pathway played a pivotal role in counteracting oxidative stress to rescue the inhibitory effect of oxidative stress on NSC proliferation using Western blotting assays and gene knockdown techniques. Collectively, these results demonstrate that THF mitigates the inhibitory effect of oxidative stress on NSC proliferation via PTEN/Akt/mTOR signaling pathway, which provides evidence for administrating THF to potentiate the neuro-reparative capacity of NSC in the treatment of CNS diseases with the presence of oxidative stress.

Ferrostatin-1 Alleviates White Matter Injury Via Decreasing Ferroptosis Following Spinal Cord Injury.

Spinal cord injury (SCI), a devastating neurological impairment, usually imposes a long-term psychological stress and high socioeconomic burden for the sufferers and their family. Recent researchers have paid arousing attention to white matter injury and the underlying mechanism following SCI. Ferroptosis has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improving functional recovery after traumatic brain injury (TBI) and SCI. However, the role of ferroptosis in white matter injury and the therapeutic effect of ferrostatin-1 on SCI are still unknown. Here, our results indicated that ferroptosis played a pivotal role in the secondary white matter injury, and ferrostatin-1 could reduce iron and reactive oxygen species (ROS) accumulation and downregulate the ferroptosis-related genes and its products of IREB2 and PTGS2 to further inhibit ferroptosis in oligodendrocyte, finally reducing white matter injury and promoting functional recovery following SCI in rats. Meanwhile, the results demonstrated that ferrostatin-1 held the potential of inhibiting the activation of reactive astrocyte and microglia. Mechanically, the present study deciphers the potential mechanism of white matter damage, which enlarges the therapeutic effects of ferrostatin-1 on SCI and even in other central nervous system (CNS) diseases existing ferroptosis.

Usage of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker in Hypertension Intracerebral Hemorrhage.

BACKGROUND: Inflammation plays an essential role in secondary brain injury after intracerebral hemorrhage (ICH). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been suggested to suppress neuroinflammation after central nervous system (CNS) damage in animal models. However, the role of ACEIs and ARBs in ICH patients with hypertension remains unresolved in clinic. The aim of the present study is to evaluate the effect of ACEIs/ARBs on ICH patients with hypertension using a retrospective, single-center data analysis. METHODS: ICH patients diagnosed by computerized tomographic (CT) at Southwest Hospital, Third Military Medical University were included in the present research from January 2015 to December 2019. According to the medical history for the usage of antihypertensive drugs, patients were assigned into either ACEIs/ARBs group or non-ACEIs/ARBs group. Demographics, clinical baseline, radiological documents and treatments were collected and these data were statistically analyzed between the two groups. RESULTS: A total of 635 ICH patients with hypertension were included and allocated into 2 groups according to the usage of antihypertensive drugs: 281 in the ACEIs/ARBs group and 354 in the non-ACEIs/ARBs group. The results presented that the 3-months mortality and prevalence of ICH-associated pneumonia were lower in ACEIs/ARBs group than that in non-ACEIs/ARBs group (5.0% vs 11.9%, p=0.002; 58.4% vs 66.7%, p=0.031). While, there was no significant difference in favorable outcome (40.2% vs 33.9%, p=0.101) between the two groups. Furthermore, patients in ACEIs/ARBs group exhibited significantly less perihematomal edema volume on days 3 (23.5 ± 14.4 versus 28.7 ± 20.1 mL, p=0.045) and 7 (21.0 ± 13.7 versus 25.7 ± 17.6 mL, p=0.044), compared to that in non- ACEIs/ARBs group. CONCLUSION: The usage of ACEIs/ARBs helps decrease mortality, perihematomal edema volume, and prevalence of ICH-associated pneumonia in ICH patients with hypertension.

Long-term Outcomes and Risk Factors Related to Hydrocephalus After Intracerebral Hemorrhage.

Hydrocephalus after intracerebral hemorrhage (ICH) is a common and treatable complication. However, the long-term outcomes and factors for predicting hydrocephalus have seldom been studied. The goal of this study was to determine the long-term outcomes and analyze the risk factors of hydrocephalus after ICH. A consecutive series of 1342 patients with ICH were reviewed from 2010 to 2016 to identify significant risk factors for hydrocephalus. Patients with a first-ever ICH without any prior diagnosis of hydrocephalus after ICH were followed up for survival status and cause of death. Risk factors for hydrocephalus were evaluated by using logistic regression analysis. Out of a total of 1342 ICH patients, 120 patients (8.9%) had hydrocephalus. The risk factors for hydrocephalus (≤ 3 days) were infratentorial hemorrhage (p = 0.000), extension to ventricles (p = 0.000), greater ICH volume (p = 0.09), and hematoma expansion (p = 0.01). Extension to ventricles (p = 0.022) was the only independent risk factor for hydrocephalus (4-13 days), while extension to ventricles (p = 0.028), decompressive craniotomy (p = 0.032), and intracranial infection (p = 0.001) were independent predictors of hydrocephalus (≥ 14 days). Patients were followed up for a median of 5.2 years (IQR 3.3-7.3 years). Estimated all-cause mortality was significantly higher in the ICH patients with hydrocephalus than that without hydrocephalus (HR 3.22, 95% CI 2.42-4.28; p = 0.000). Fifty-nine (49.2%) died and 40 (33.3%) had a favorable outcome in patients with hydrocephalus. Of all deaths, 30.5% were from ICH and 64.4% from infection. Hydrocephalus is a frequent complication of ICH and most commonly occurs at the onset of ICH. Patients with hydrocephalus show relatively higher mortality. ClinicalTrials.gov Identifier: NCT02135783 (May 7, 2014).

Development and validation of a nomogram for predicting hematoma expansion in intracerebral hemorrhage.

BACKGROUND AND OBJECTIVE: To develop and validate a clinical nomogram for individualized predicting hematoma expansion (HE) in patients with Intracerebral Hemorrhage (ICH). METHODS: A total of 1025 patients with ICH were retrospectively enrolled in the development cohort between 2010 and 2016. We identified and integrated significant factors for HE to build a nomogram. The model was subjected to validation with a separate cohort of 397 patients from the 2017-2019. The predictive accuracy and discriminative ability were measured by concordance index (C-index). The primary outcome was HE, defined as hematoma growth more than 6 mL or 33% increase in the volume. RESULTS: A total of 1025 patients were included for univariable analysis. HE occurred in 180 patients (17.6%). The time to initial CT (≤6h vs. >6 h; p = 0.001), NIHSS score (0-4 vs. 5-14 vs. ≥15; p = 0.031), CTA spot sign (yes vs. no vs. absent; p = 0.018), hypodensities (p = 0.000), blend sign (p = 0.005), and INR (<1.2 vs. ≥1.2; p = 0.009) were identified and entered into the nomogram. The calibration curves for probability of HE showed optimal agreement between nomogram prediction and actual observation. The C-index was 0.751. The validation cohort consisted of 397 patients and HE occurred in 78 patients (19.6%). The C-index was 0.743. CONCLUSIONS: We developed and validated a nomogram that can individually predict HE for ICH in Chinese populations. This practical prognostic nomogram may help clinicians make decision of clinical practice and design of clinical studies.

Comparison of epidemiological and clinical features between two chronological cohorts of patients with intracerebral hemorrhage.

To investigate the differences in the epidemiological and clinical characteristics of patients with intracerebral hemorrhage (ICH) treated at our institution over the last few decades. Two chronological cohorts with ten-year-interval were established and epidemiological and clinical data were retrospectively collected from patients with ICH, and data were analyzed using SPSS 13.0. The time windows for the two cohorts were from January 1, 2010 to December 31, 2014 (2010-2014 cohort) and January 1, 2000 to December 31, 2004 (2000-2004 cohort). 1598 patients with ICH were enrolled: 360 patients in the 2000-2004 cohort and 1238 patients in the 2010-2014 cohort. ICH often occurred in patients aged from 45 to 75 years, without a sex bias, accounting for 69.6% of patients. Hypertension (60.7%) was still the main risk factors. Meanwhile, the risk factors of smoking (28.9%) and drinking (23.3%) were often present in male patients but not female patients (p ≤ 0.001). The incidence of pulmonary infection, the main complication during hospitalization, was 40.8% in the 2000-2004 cohort and 61.8% in the 2010-2014 cohort (p ≤ 0.001). Moreover, the incidence of gastrointestinal hemorrhage was 12.5% in the 2000-2004 cohort and 6.0% in the 2010-2014 cohort (p ≤ 0.001). The epidemiological and clinical features have changed over the past 10 years. The mortality was reduced but still high, as evidenced by the increased hospitalization rate of patients with ICH. Current preventions and therapeutic strategies for ICH are effective, but more strategies must be developed to improve the outcome of ICH and decrease the incidence of pulmonary infection.

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/ß-Catenin Pathway After Ischemic Stroke.

Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide. Post-stroke pneumonia is a common complication in patients with ischemic stroke and always associated with 1-year mortality. Though ambroxol therapy often serves as a supplementary treatment for post-stroke pneumonia in ischemic stroke patients, its effect on functional recovery and potential mechanism after ischemic stroke remain elusive. In the present study, the results indicated that administration of 70 mg/kg and 100 mg/kg enhanced functional recovery by virtue of decreasing infarct volume. The potential mechanism, to some extent, was due to promoting NSCs differentiation into neurons and interfering NSCs differentiation into astrocytes through increasing GCase expression to activate Wnt/ß-catenin signaling pathway in penumbra after ischemic stroke, which advanced basic knowledge of ambroxol in regulating NSCs differentiation and provided a feasible therapy for ischemic stroke treatment, even in other brain disorders in clinic.

Effects of Atorvastatin on Surgical Treatments of Chronic Subdural Hematoma.

OBJECTIVE: To investigate the effects of atorvastatin on the surgical treatment of patients with chronic subdural hematoma (CSDH). METHODS: Our retrospective study included 245 consecutive adult patients undergoing burr-hole craniotomy for CSDH. Data included baseline characteristics and recurrence, postoperative complications, and mortality. Univariate and multivariate regression models analyzed the association between administration of atorvastatin perioperatively and recurrence rates. RESULTS: Multivariate analysis showed perioperative atorvastatin administration (odds ratio [OR] 0.336; P = 0.039), diabetes mellitus (OR 3.949, P = 0.010), and GCS of 15 preoperatively (OR 0.197; P = 0.020) to be significantly related to recurrence risk. Postoperative complications and mortality did not significantly differ between patients with and those without atorvastatin therapy. CONCLUSIONS: Our findings demonstrate that the administration of atorvastatin perioperatively is associated with a lower risk of CSDH recurrence rate. The use of atorvastatin perioperatively was not associated with higher rates of morbidity or mortality.

TRPV4 Blockade Preserves the Blood-Brain Barrier by Inhibiting Stress Fiber Formation in a Rat Model of Intracerebral Hemorrhage.

Blood-brain barrier (BBB) disruption and subsequent brain edema play important roles in the secondary neuronal death and neurological dysfunction that are observed following intracerebral hemorrhage (ICH). In previous studies, transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable mechanosensitive channel, was shown to induce cytotoxicity in many types of cells and to play a role in orchestrating barrier functions. In the present study, we explored the role of TRPV4 in ICH-induced brain injury, specifically investigating its effect on BBB disruption. Autologous arterial blood was injected into the basal ganglia of rats to mimic ICH. Adult male Sprague Dawley rats were randomly assigned to sham and experimental groups for studies on the time course of TRPV4 expression after ICH. The selective TRPV4 antagonist HC-067047 and TRPV4 siRNA were administered to evaluate the effects of TRPV4 inhibition. GSK1016790A, a TRPV4 agonist, was administered to naive rats to verify the involvement of TRPV4-induced BBB disruption. A PKC inhibitor, dihydrochloride (H7), and a selective RhoA inhibitor, C3 transferase, were administered to clarify the involvement of the PKCα/RhoA/MLC2 pathway following ICH. Post-ICH assessments including functional tests, brain edema measurements, Evans blue extravasation, western blotting and immunohistochemical assays were performed. TRPV4 inhibition remarkably ameliorated neurological symptoms, brain edema, and neuronal death, as well as BBB disruption, 24-72 h following ICH. Meanwhile, TRPV4 blockade preserved the expression of adherens and tight junction proteins, as well as BBB integrity, by inhibiting stress fiber formation, which might be correlated with the regulation of components of the PKCα/RhoA/MLC2 pathway. Furthermore, adherens and tight junction protein degradation induced by GSK1016790A treatment in naive rats was also related to PKCα/RhoA/MLC2-pathway-mediated stress fiber formation. Based on these findings, therapeutic interventions targeting TRPV4 may represent a novel approach to ameliorate secondary brain injury following ICH.

Electromagnetic Fields for the Regulation of Neural Stem Cells.

Localized magnetic fields (MFs) could easily penetrate the scalp, skull, and meninges, thus inducing an electrical current in both the central and peripheral nervous systems, which is primarily used in transcranial magnetic stimulation (TMS) for inducing specific effects on different regions or cells that play roles in various brain activities. Studies of repetitive transcranial magnetic stimulation (rTMS) have led to novel attractive therapeutic approaches. Neural stem cells (NSCs) in adult human brain are able to self-renew and possess multidifferential ability to maintain homeostasis and repair damage after acute central nervous system. In the present review, we summarized the electrical activity of NSCs and the fundamental mechanism of electromagnetic fields and their effects on regulating NSC proliferation, differentiation, migration, and maturation. Although it was authorized for the rTMS use in resistant depression patients by US FDA, there are still unveiling mechanism and limitations for rTMS in clinical applications of acute central nervous system injury, especially on NSC regulation as a rehabilitation strategy. More in-depth studies should be performed to provide detailed parameters and mechanisms of rTMS in further studies, making it a powerful tool to treat people who are surviving with acute central nervous system injuries.

Reduced Subthreshold Characteristics and Flicker Noise of an AlGaAs/InGaAs PHEMT Using Liquid Phase Deposited TiO2 as a Gate Dielectric.

This study presents the fabrication and improved properties of an AlGaAs/InGaAs metal-oxide-semiconductor pseudomorphic high-electron-mobility transistor (MOS-PHEMT) using liquid phase deposited titanium dioxide (LPD-TiO2) as a gate dielectric. Sulfur pretreatment and postoxidation rapid thermal annealing (RTA) were consecutively employed before and after the gate dielectric was deposited to fill dangling bonds and therefore release interface trapped charges. Compared with a benchmark PHEMT, the AlGaAs/InGaAs MOS-PHEMT using LPD-TiO2 exhibited larger gate bias operation, higher breakdown voltage, suppressed subthreshold characteristics, and reduced flicker noise. As a result, the device with proposed process and using LPD-TiO2 as a gate dielectric is promising for high-speed applications that demand little noise at low frequencies.

Hypoxia Induces autophagic cell death through hypoxia-inducible factor 1α in microglia.

As phagocytic cells of central nervous system, excessive activation or cell death of microglia is involved in a lot of nervous system injury and degenerative disease, such as stroke, epilepsy, Parkinson's disease, Alzheimer's disease. Accumulating evidence indicates that hypoxia upregulates HIF-1α expression leading to cell death of microglia. However, the exact mechanism of cell death induced by hypoxia in microglia is not clear. In the current study, we showed that hypoxia induced cell death and autophagy in microglia. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (BECN1 and ATG5) decreased the cell death induced by hypoxia in microglia cells. Moreover, the suppression of HIF-1α using either pharmacologic inhibitors (3-MA, Baf A1) or RNA interference decreased the microglia death and autophagy in vitro. Taken together, these data indicate that hypoxia contributes to autophagic cell death of microglia through HIF-1α, and provide novel therapeutic interventions for cerebral hypoxic diseases associated with microglia activation.

Curcumin inhibits microglia inflammation and confers neuroprotection in intracerebral hemorrhage.

Much evidence demonstrates that microglia mediated neuroinflammation is an important contributor to the inflammatory injury in intracerebral hemorrhage (ICH). Therefore, the compounds that can inhibit neuroinflammation are greatly needed. In the current study, we examined whether curcumin, present in a Chinese medicinal plant, could prevent ICH induced microglia activation and confer protection against neurotoxicity. The cytokines of microglia were measured by ELISA, p38MAPK/PKC and NF-κB were measured by Western blot and EMSA. Microglial toxicity was assessed using MTT and FACS assays. And neurological function was evaluated by animal behavioristics. We found that curcumin prevented ICH-induced inflammatory molecules through NF-κB activation via the p38MAPK/PKC pathway in vitro. In addition, curcumin protected hippocampal HT22 cells from indirect toxicity mediated by ICH-treated microglia cells. Further, curcumin also attenuated ICH-induced neurological deficit and cerebral water content in vivo. Together, our findings suggest that curcumin could suppress ICH induced inflammatory injury and represent a novel herbal sources for ICH therapeutical strategy.

Cerebral paragonimiasis: a retrospective analysis of 89 cases.

PURPOSE: We reviewed the clinical and follow-up data of 89 cases with cerebral paragonimiasis and summarized the disease characteristics, diagnostic strategies and treatment experience, with an expectation of establishing standard diagnosis and treatment for cerebral paragonimiasis. METHODS: A total of 89 cases (age: 2-64 years) of cerebral paragonimiasis admitted and treated in our hospital in the past 10 years were included in this study. The clinical symptoms were manifested by headache, epilepsy, paralysis, etc. In order to confirm the diagnosis, we performed imaging examinations (e.g., CT and MRI) and laboratory tests (ELISA and eosinophil counting). Seventy-two patients received oral administration of praziquantel only, 16 cases received surgical resection of the lesions and 33 cases received appropriate anti-epileptic therapies. The diagnostic, treatment and follow-up data were statistically analyzed. RESULTS: Follow-up was performed for 73 cases for a period of 6-48 months and the original symptoms were markedly improved without recurrence. 15 patients were lost to follow-up after discharge. One patient died of epilepticus insult, high fever and convulsions. Although 4 patients still had seizures within 6 months of treatment, seizure frequency was significantly reduced. Histopathological evaluation demonstrated inflammatory changes with esoinophilic infiltration in all 16 patients who underwent surgical resection. CONCLUSIONS: Young patients (age: <18 years) are more likely to have cerebral hemorrhage. SWI imaging contributes to the diagnosis of hemorrhagic lesions. Cerebral paragonimiasis can cause epilepsy, especially grand mal seizures.