Clot removAl with or without decompRessive craniectomy under ICP monitoring for supratentorial IntraCerebral Hemorrhage (CARICH): a randomized controlled trial.

BACKGROUND: Decompressive craniectomy, a surgery to remove part of the skull and open the dura mater, maybe an effective treatment for controlling intracranial hypertension. It remains great interest to elucidate whether decompressive craniectomy is beneficial to intracerebral hemorrhage patients who warrant clot removal to prevent intracranial hypertension. METHODS: The trial was a prospective, pragmatic, controlled trial involving adult patients with intracerebral hemorrhage who were undergoing removal of hematoma. Intracerebral hemorrhage patients were randomly assigned at a 1:1 ratioto undergo clot removal with or without decompressive craniectomy under the monitoring of intracranial pressure. The primary outcome was the proportion of unfavorable functional outcome (modified Rankin Scale 3-6) at 3 months. Secondary outcomes included the mortality at 3 months and the occurrence of re-operation. RESULTS: A total of 102 patients were assigned to the clot removal with decompressive craniectomy group and 102 to the clot removal group. Median hematoma volume was 54.0 mL (range 30-80 mL) and median preoperative Glasgow Coma Scale was 10 (range 5-15). At 3 months, 94 patients (92.2%) in clot removal with decompressive craniectomy group and 83 patients (81.4%) in the clot removal group had unfavorable functional outcome (P=0.023). Fourteen patients (13.7%) in the clot removal with decompressive craniectomy group died versus five patients (4.9%) in the clot removal group (P=0.030). The number of patients with re-operation was similar between the clot removal with decompressive craniectomy group and clot removal group (5.9% vs. 3.9%; P=0.517). Postoperative intracranial pressure values were not significantly different between two groups and the mean values were less than 20 mmHg. CONCLUSIONS: Clot removal without decompressive craniectomy decreased the rate of modified Rankin Scale score of 3-6 and mortality in patients with intracerebral hemorrhage, compared with clot removal with decompressive craniectomy.

Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury.

Intracerebral hemorrhage (ICH), as a type of life-threatening and highly disabled disease, has limited therapeutic approaches. Here, we show that exosomes derived from young healthy human plasma exhibiting typical exosomes features could facilitate functional recovery of ICH mice. When these exosomes are intraventricularly delivered into the brain after ICH, they mainly distribute around the hematoma and could be internalized by neuronal cells. Strikingly, exosomes administration markedly enhanced the behavioral recovery of ICH mice through reducing brain injury and cell ferroptosis. MiRNA sequencing revealed that microRNA-25-3p (miR-25-3p) was differentially expressed miRNA in the exosomes from young healthy human plasma, compared with exosomes from the old control. Importantly, miR-25-3p mimicked the treatment effect of exosomes on behavioral improvement, and mediated the neuroprotective effect of exosomes against ferroptosis in ICH. Furthermore, luciferase assay and western blotting data illustrated that P53 as assumed the role of a downstream effector of miR-25-3p, thereby regulating SLC7A11/GPX4 pathway to counteract ferroptosis. Taken together, these findings firstly reveal that exosomes from young healthy human plasma improve functional recovery through counteracting ferroptotic injury by regulating P53/SLC7A11/GPX4 axis after ICH. Given the easy availability of plasma exosomes, our study provides a potent therapeutic strategy for ICH patients with quick clinical translation in the near future.

Flotation separation of coal dust from foundry dust enhanced by pre-soaking assisted mechanical stirring.

Foundry dust is the main refractory solid waste in the foundry industry, and its resource utilization is a top priority for realizing green and cleaner production. The massive amount of coal dust in foundry dust is a potential impediment to the recycling of foundry dust, and the efficient separation of coal dust is crucial to solving the above problems. In this paper, the flotation separation of coal dust from foundry dust enhanced by pre-soaking assisted mechanical stirring was reported. The influence of pre-soaking, stirring speed, and stirring time on the flotation results of foundry dust was systematically studied, and the enhancement mechanism was analyzed based on the microstructure and hydrophobicity of foundry dust. Flotation kinetics experiments with different stirring time were conducted to clarify the flotation process of foundry dust. The results indicate that the pre-soaking of foundry dust is beneficial for the water-absorbing swelling of clay minerals coated on the surface of coal dust, and the subsequent mechanical stirring pretreatment promotes the monomer dissociation of foundry dust, which increases the contact angle of foundry dust and considerably improves the flotation results. The optimal stirring speed and stirring time were 2400 rpm and 30 min, respectively. The classical first-order model presented the highest degree of fitting with the flotation data among the five flotation kinetics models. Therefore, the pre-soaking assisted mechanical stirring is a promising method for promoting flotation separation and the complete recycling of foundry dust.

Amelioration of White Matter Injury Through Mitigating Ferroptosis Following Hepcidin Treatment After Spinal Cord Injury.

Spinal cord injury (SCI) usually introduces permanent or long-lasting neurological impairments. Maintaining the integrity of the limited number of white matter bundles (5-10%) preserves wholly or partially locomotor following SCI. Considering that the basic structure of white matter bundles is axon wrapped by oligodendrocytes, promoting oligodendrocytes survival might be a feasible strategy for reducing white matter injury (WMI) after SCI. Oligodendrocytes are rich in unsaturated fatty acid and susceptible to ferroptosis-induced damage. Hence, exploring method to reduce ferroptosis is supposed to expedite oligodendrocytes survival, thereafter mitigating WMI to facilitate functional recovery post-SCI. Here, the results indicated the administration of hepcidin reduced iron accumulation to promote oligodendrocytes survival and to decrease spinal cord atrophy, therefore facilitating functional recovery. Then, the WMI was evidently decreased owing to attenuating ferroptosis. Subsequently, the results revealed that the expression of divalent metal transporter 1 (DMT1) and transferrin receptor (TfR) was expressed in CC1+ cells. The expression level of DMT1 and TfR was significantly increased, while this phenomenon was obviously neutralized with the administration of hepcidin in the epicenter of spinal cord after SCI. Afterward, the application of hepcidin downregulated reactive oxygen species (ROS) overload, which was evidently increased with the treatment of 20 µM FeCl3, therefore increasing cell viability and reducing lactate dehydrogenase (LDH) activity through downregulating the expression of DMT1 and TfR to inhibit ferroptosis in oligodendrocyte progenitor cells (OPCs). The present study provides evidence that the application of hepcidin facilitates oligodendrocytes survival to alleviate WMI via reducing the expression of DMT1 and TfR.

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.

Coumarin 1,4-enedione for selective detection of hydrazine in aqueous solution and fluorescence imaging in living cells.

Hydrazine is a widely used but highly toxic chemical reagent, and the development of a fluorescent probe for hydrazine detection is very meaningful. In this study, a novel coumarin-derived fluorescent probe containing a 1,4-enedione moiety for hydrazine detection was developed. The recognition of hydrazine with the probe brings about obvious fluorescence enhancement over other environmentally relevant ions and amine-containing species. The limit of detection for hydrazine is 2.7×10-8 M in aqueous solution. The fluorescence enhancement was ascribed to the cyclization reaction of the 1,4-enedione moiety of the probe and hydrazine which form a six-membered pyridazine ring and intramolecular charge transfer (ICT) mechanism. The mass spectrometry (MS), nuclear magnetic resonance (NMR) analysis and theoretical calculations confirmed the recognition produced. The probe can be used to determine trace hydrazine in real water samples. More importantly, the probe also showed good potential in detecting hydrazine by imaging of living HeLa cells.

MiR-279-3p regulates deltamethrin resistance through CYP325BB1 in Culex pipiens pallens.

BACKGROUND: The overuse of insecticides to control insect vectors has promoted extensive insecticide resistance in mosquitoes. In this study, the functions of microRNA (miR)-279-3p and its target CYP325BB1 in the regulation of deltamethrin resistance in Culex pipiens pallens was investigated. METHODS: Quantitative real-time reverse transcription PCR was used to detect the expression levels of miR-279-3p and CYP325BB1. Then, the dual-luciferase reporter assay system, RNA interference, CDC bottle bioassay and Cell Counting Kit-8 (CCK-8) assay were used to explore the roles of these molecules in deltamethrin resistance both in vivo and in vitro. RESULTS: The expression patterns of miR-279-3p and CYP325BB1 were compared between deltamethrin-sensitive (DS-strain) and deltamethrin-resistant (DR-strain) mosquitoes. Luciferase activity was downregulated by miR-279-3p, the effect of which was ablated by a mutation of the putative binding site for CYP325BB1. In DR-strain mosquitoes, the expression of miR-279-3p was increased by microinjection and oral feeding of miR-279-3p agomir (mimic). CYP325BB1 mRNA levels were downregulated, which resulted in a higher mortality of the mosquitoes in miR-279-3p mimic-treated groups. In the DS-strain mosquitoes, microinjection of a miR-279-3p inhibitor decreased miR-279-3p expression, whereas the expression of CYP325BB1 was increased; the mortality of these mosquitoes decreased significantly. In addition, overexpression of pIB/V5-His-CYP325BB1 changed the sensitivity of C6/36 cells to deltamethrin in vitro. Also in DR-strain mosquitoes, downregulation of CYP325BB1 expression by microinjection of si-CYP325BB1 increased mosquito mortality in vivo. CONCLUSIONS: These findings provide empirical evidence of the involvement of miRNAs in the regulation of insecticide resistance and indicate that miR-279-3p suppresses the expression of CYP325BB1, which in turn decreases deltamethrin resistance, resulting in increased mosquito mortality. Taken together, the results provide important information for use in the development of future mosquito control strategies.

Combination of the Distance From Tumor Edge to Subventricular Zone and IDH Mutation Predicts Prognosis of Patients With Glioma.

Both subventricular zone (SVZ) contact and isocitrate dehydrogenase 1 (IDH1) mutation have been reported to be related to the outcome of glioma, respectively. However, far too little attention has been paid to the role of tumor edge-SVZ distance in the outcome of glioma. We aim to assess the value of tumor-SVZ distance, as well as combined tumor-SVZ distance and IDH status, in predicting the outcome of gliomas (WHO grade II-IV). Here, the MR images and clinical data from 146 patients were included in the current study. The relationship between survival and the tumor-SVZ distance as well as survival and combination of tumor-SVZ distance and IDH status were determined via univariate and multivariate analyses. In univariate analysis of tumor-SVZ distance, the patients were divided into three types (SVZ involvement, tumor-SVZ distance from 0 to 10 mm, and tumor-SVZ distance >10 mm). The results showed that the OS (p = 0.02) and PFS (p = 0.002) for the patients had a positive correlation with the tumor-SVZ distance. In addition, simple linear correlation found a significant relationship between the two parameters (OS and PFS) and tumor-SVZ distance in patients with non-SVZ-contacting glioma. Combination analysis of the tumor-SVZ distance and IDH status showed that IDH1 mutation and SVZ non-involvement enable favorable outcomes, whereas IDH1 wild type with SVZ involvement indicates a significantly worse prognosis in all patients. Moreover, in patients with non-SVZ-contacting glioma, IDH1 mutation concurrent with tumor-SVZ distance >10 mm has better OS and PFS. IDH1 wild type and tumor-SVZ distance from 0 to 10 mm suggest poorer OS and PFS. Multivariate analysis showed WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, gross total resection, and chemotherapy serve as independent predictors of OS. WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, and chemotherapy serve as independent predictors of PFS of patients with glioma. In conclusion, tumor-SVZ distance and IDH1 mutation status are the determinants affecting patient outcome.

A novel ESIPT fluorescent probe derived from 3-hydroxyphthalimide for hydrazine detection in aqueous solution and living cells.

Hydrazine is a highly toxic and flammable liquid that can damage human liver, kidney, and central nervous system. Therefore, it is valuable to seek a quick and sensitive method for hydrazine detection in environmental and biological science. Herein, a new fluorescent probe derived from 3-hydroxyphthalimide was synthesized. This probe can rapidly and selectively detect hydrazine with a low detection limit of 4.3 × 10-7 M. The recognition principle is based on hydrazine-induced acetyl deprotection and excited-state intramolecular proton transfer (ESIPT) process. Moreover, test paper and fluorescence image experiments showed that this probe had potential to monitor hydrazine in the environment and living cells.

[Clinical application of self-made minimally invasive hood-assisted transforaminal lumbar interbody fusion via modified bilateral Wiltse approach in the treatment of lumbar degenerative diseases].

OBJECTIVE: To explore the advantages of self made minimally invasive hook assisted transforaminal lumbar interbody fusion (TLIF) via modified bilateral Wiltse approach in the treatment of lumbar degenerative diseases. METHODS: The clinical data of 140 patients underwent lumbar spine fusion surgery from October 2016 to October 2017 were retrospectively analyzed. Among them, 72 cases were treated by self-made minimally invasive hook-assisted TLIF via modified bilateral Wiltse approach (group A), there were 37 males and 35 females, aged (48±16) years old;68 cases were treated by TLIF via traditional posterior median approach (group B ), there were 38 males and 30 females, aged (45±15) years old. The surgical incision size, operation time, intraoperative blood loss volume, postoperative drainage volume, postoperative wound healing, and intervertebral fusion rate at the final follow-up were recorded between two groups. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to assess the clinical efficacy. RESULTS: All the patients were followed up for 3 to 13 (8±5) months. The wound in group A healed well after operation, and 1 case in group B occurred wound necrosis after operation, and healed after debridement and suture. There were no significant differences in operation time and postoperative fusion rate between two surgical methods (P>0.05). Group A had obvious advantages in surgical incision size, intraoperative blood loss volume and postoperative drainage volume (P<0.05), and the postoperative VAS score of low back pain and ODI were better than group B (P<0.05). CONCLUSION: The self made minimally invasive hook assistedTLIF via modified bilateral Wiltse approach has the characteristics of minimally invasive, less intraoperative blood loss, less postoperative drainage, fewer complications, and more stable fusion in the treatment of lumbar degenerative desease.

MiR-4448 is involved in deltamethrin resistance by targeting CYP4H31 in Culex pipiens pallens.

BACKGROUND: Culex pipiens (Cx. pipiens) complex, which acts as a vector of viruses and is widespread and abundant worldwide, including West Nile virus, Japanese encephalitis virus, and Sindbis virus, can cause serious vector-borne diseases affecting human health. Unfortunately, mosquitoes have developed deltamethrin resistance because of its long-term overuse, representing a major challenge to mosquito control. Understanding the molecular regulatory mechanisms of resistance is vital to control mosquitoes. MicroRNAs (miRNAs) are short non-coding RNAs that have been demonstrated to be important regulators of gene expression across a wide variety of organisms, which might function in mosquito deltamethrin resistance. In the present study, we aimed to investigate the regulatory functions of miR-4448 and CYP4H31 in the formation of insecticidal resistance in mosquito Culex pipiens pallens. METHODS: We used quantitative real-time reverse transcription PCR to measure miR-4448 and CYP4H31 (encoding a cytochrome P450) expression levels. The regulatory functions of miR-4448 and CYP4H31 were assessed using dual-luciferase reporter assays. Then, oral feeding, RNA interference, and the American Centers for Disease Control and Prevention bottle bioassay were used to determine miR-4448's association with deltamethrin resistance by targeting CYP4H31 in vivo. Cell Counting Kit-8 (CCK-8) was also used to detect the viability of pIB/V5-His-CYP4H31-transfected C6/36 cells after deltamethrin treatment in vitro. RESULTS: MiR-4448 was downregulated in the deltamethrin-resistant strain (DR strain), whereas CYP4H31 was downregulated in deltamethrin-susceptible strain. CYP4H31 expression was downregulated by miR-4448 recognizing and binding to its 3' untranslated region. Functional verification experiments showed that miR-4448 overexpression resulted in lower expression of CYP4H31. The mortality of miR-4448 mimic-injected DR strain mosquitoes was higher than that of the controls. CCK-8 assays showed that CYP4H31 decreased cellular resistance to deltamethrin in vitro and the mortality of the DR strain increased when CYP4H31 was knocked down in vivo. CONCLUSIONS: In mosquitoes, miR-4448 participates in deltamethrin resistance by targeting CYP4H31. The results of the present study increase our understanding of deltamethrin resistance mechanisms.

Comprehensive utilization of foundry dust: Coal powder and clay minerals separation by ultrasonic-assisted flotation.

Clay sand casting generates a large amount of foundry dust (FD), and the presence of coal powder in the FD makes it difficult to recycle and utilize. The landfill of the FD creates a serious environmental pollution and wastes a valuable resource. To improve the above situation, the FD was analyzed and characterized by X-ray fluorescence spectrometer (XRF), X-ray diffraction (XRD) and electron probe microanalyzer (EPMA). An ultrasonic-assisted flotation process was developed for the comprehensive utilization of the FD, and the effects of ultrasonic time on the flotation performance and flotation kinetics were investigated. In addition, the two-stage flotation of the FD was conducted. Obtained results showed that the FD mainly consisted of coal powder and clay minerals, and the coal powder was covered by clay minerals. The separation efficiency of the coal powder and clay minerals can be significantly enhanced by ultrasonic pretreatment, and the optimal ultrasonic time was 30 min. The flotation kinetics analysis results indicated that the first-order model with rectangular distribution was more reasonable for the data fitting of the ultrasonic-assisted flotation. Furthermore, the concentrate and tailings obtained by the two-stage flotation had achieved an acceptable result, favoring the comprehensive utilization of the FD.

[Vesselplasty for the treatment of spinal metastases complicated by posterior wall destruction of vertebral body].

OBJECTIVE: To evaluate the early clinical efficacy and safety of vesselplasty for the treatment of spinal metastases complicated by posterior wall destruction of vertebral body. METHODS: The clinical data of 19 patients(21 segments) with spinal metastases complicated by posterior wall destruction of vertebral body treated from January 2016 to January 2017 were retrospectively analyzed. There were 15 males and 4 females, aged 40 to 85 years old with a mean of (66.00±10.25) years . All patients had severe low back pain before the operation, which were diagnosed by CT as damage-type metastatic tumor of the vertebral posterior wall. All patients were treated by vesselplasty technique. Nineteen vertebrae received percutaneous unilateral pedicle puncture and two vertebrae received percutaneous bilateral pedicle puncture. VAS, ODI were recorded before operation, 1 d and 3 d after operation respectively. X-ray and CT scan were used to observe bone cement leakage and complications. RESULTS: All the operations were successful and postoperative pain was significantly relieved. Postoperative VAS score and ODI of the two groups were significantly improved (P<0.05). A small amount of bone cement leakage occurred in one vertebral body, which was a vertebral venous plexus leakage, but no clinical symptoms after operation. CONCLUSION: Vesselplasty for the treatment of spinal metastases complicated by posterior wall destruction of vertebral body can significantly reduce the symptoms of thoracolumbar back pain, improve the quality of life, reduce the incidence of bone cement leakage, and has high clinical efficacy and safety.

LncRNA THRIL aggravates sepsis-induced acute lung injury by regulating miR-424/ROCK2 axis.

Here, we aimed to investigate the role of long noncoding RNA (lncRNA) THRIL in septic-induced acute lung injury. C57BL/6 mice were injected with Adenoviruses (Ad)-shTHRIL or negative control (NC) before caecal ligation and puncture (CLP) operation. MPVECs were transfected with Ad-shTHRIL or NC, followed by lipopolysaccharide (LPS) treatment. MiR-424 and Rho-associated kinase 2 (ROCK2) were predicted and verified as direct targets of THRIL and miR-424, respectively, by using dual-luciferase reporter assay. ROCK2 overexpression vector and shTHRIL were co-transfected into mouse pulmonary microvascular endothelial cells for 24 h before LPS treatment. Our results showed that THRIL was highly expressed in the lung of sepsis mice. CLP triggered severe lung injury and apoptosis in mice, which was abolished by THRIL knockdown. Moreover, CLP treatment visibly increased protein concentration, the number of total cell of neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). Besides, elevated protein levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were observed in both lung and BALF. However, inhibition of THRIL reduced the number of inflammatory cells and the production of pro-inflammatory cytokines in sepsis mouse model. The effect of THRIL on inflammatory response and apoptosis in the lung was confirmed in sepsis cell model. Moreover, mechanistic studies have shown that THRIL up-regulated ROCK2 level through sponging miR-424. Furthermore, ROCK2 overexpression reversed the inhibitory effects of THRIL knockdown on LPS-induced inflammatory response and apoptosis. Overall, in vivo and in vitro results suggested that THRIL accelerates sepsis-induced lung injury by sponging miR-424 and further restoring ROCK2.

Traumatic prolapse of the globe into the anterior cranial fossa: a case report.

BACKGROUND: Orbital fracture associated with traumatic intracranial prolapse of the eyeball is rare. In all previously reported cases, vision was severely impaired with no light perception. Herein, we report a case of traumatic prolapse of the globe into the anterior cranial fossa, in which the patient's vision was preserved by early repositioning. CASE PRESENTATION: The present case report focused on a man hit by a steel pipe, leading to prolapse of the globe of the right eye into the anterior cranial fossa through fractures in the superior orbit roof, accompanied by cerebral contusion. The eyeball was immediately repositioned into the orbital cavity, along which the wound tract was debrided and the skull base was repaired. The patient underwent a follow-up period of 12 months, during which the visual acuity increased to 12/20 without any intracranial infections. However, the patient's ptosis persisted and was associated with complete loss of supraduction. CONCLUSIONS: In this case, early diagnosis and proper globe repositioning with reconstruction of the orbital roof could allow recovery of vision, as well as prevention of intracranial infection.

Attenuation of White Matter Damage Following Deferoxamine Treatment in Rats After Spinal Cord Injury.

BACKGROUND: With little information available on axonal and myelin damage surrounding the contusion, the study of spinal cord injury (SCI) so far has focused on neuronal death. In this study, we investigated the role of iron overload in long-term oligodendroglia death and progressive white matter damage to rats after SCI using the iron chelator, deferoxamine (DFX). METHODS: Female Sprague-Dawley rats received either a contusion at T10 or sham-surgery. The rats were treated with DFX or vehicle. All rats were evaluated in behavioral assessments and then euthanized at different time points. Spinal cords were analyzed by diaminobenzidine-enhanced Perls' staining, non-heme iron measurements, Western blotting, immunohistochemistry, and transmission electron microscopy. RESULTS: Iron accumulation after SCI resulted in the upregulation of transferrin receptor and divalent metal transporter 1, which exacerbated the intracellular iron overload. DFX treatment reduced iron overload-induced delayed oligodendrocyte death (e.g., 21 days: 47.12 ± 10.5 vs. 20.02 ± 9.4 x 103/mm2 in the vehicle-treated group, n = 4, P < 0.05). After SCI, the markers of axonal damage and demyelination were increased in white matter in the vehicle-treated group compared with the DFX-treated group (P < 0.05). CONCLUSIONS: Iron overload plays an important role in progressive white matter damage after SCI. DFX may be an effective treatment for white matter damage after SCI.

Deferoxamine therapy reduces brain hemin accumulation after intracerebral hemorrhage in piglets.

Hemopexin (Hpx) is critical for hemin scavenging after the erythrocyte lysis that occurs following intracerebral hemorrhage (ICH). Low-density lipoprotein receptor-related protein-1 (LRP1, also called CD91) is an important receptor through which the hemin-Hpx complex can undergo endocytosis. This study investigated changes in the hemin-Hpx-CD91 axis in both hematoma and perihematomal tissue in a large animal ICH model. The effect of deferoxamine (DFX) on hemin-Hpx-CD91 was also examined. The study consisted of two parts. First, piglets had an injection of autologous blood into the right frontal lobe of brain and were euthanized from day 1 to day 7. Hematoma and perihematomal tissue of brains were used for hemin assay, immunohistochemistry, and immunofluorescence. Second, piglets with ICH were treated with deferoxamine or vehicle, and were euthanized for hemin measurement and Hpx and CD91 immunohistochemistry. We found that there was an increase of hemin levels within the hematoma and perihematomal brain tissue after ICH. Hpx and CD91-positive cells were present in the clot and perihematomal tissue from day 1. Hpx and CD91 positive cells were Iba1 positive. After DFX therapy, hemin dropped markedly in the hematoma and perihematomal brain tissue. Furthermore, DFX treatment decreased the number of Hpx and CD91 positive cells in and around the hematoma. In conclusion, hemin accumulation occurs in and around the hematoma. Increases in Hpx and CD91 may be important in scavenging that hemin. DFX treatment decreased hemin release from the hematoma and reduced the expression of Hpx and CD91.

Oxiracetam or fastigial nucleus stimulation reduces cognitive injury at high altitude.

BACKGROUND: Cognitive impairment is common in people travelling to high altitude. Oxiracetam and electrical stimulation of cerebellar fastigial nucleus may have beneficial impacts. This study was to investigate the effects of preconditioning with Oxiracetam or fastigial nucleus stimulation (FNS) on cognitive decline following the ascension to high altitude. METHODS: The study was conducted on 60 male military voluntary members who were divided into control group, Oxiracetam group, and fastigial nucleus stimulation group. Transcranial doppler sonography, auditory evoked potential, electroencephalogram (EEG), and cognitive assessments were performed. RESULTS: People could still suffer cognitive dysfunction at 4,000 m high altitude despite that they have lived at 1,800 m altitude for several years. The 4,000 m altitude environment also prolonged P300 and N200 latencies. Both Oxiracetam and FNS improved cognitive function, reduced the prolonged latencies of Event Related Potentials (P300 and N200), decreased the average velocity of brain arteries, and enhanced EEG power spectral entropy at 4,000 m altitude. CONCLUSIONS: Neurophysiological evidences suggest the underlying mechanism of cognitive impairments. Both Oxiracetam and FNS can reduce cognitive decline post arrival at high altitude. They could be a potential pretreatment method for cognitive dysfunction resulted from high altitude.

New Colorimetric and Fluorometric Fluoride Ion Probe Based on Anthra[1,9-cd]pyrazol-6(2H)-one.

New colorimetric and fluorometric fluoride ion probe, anthra[1,9-cd]pyrazol- 6(2H)-one (1), was synthesized by one-step condensation. The probe 1 shows F--selective color change from colorless to pink and appearance of red fluorescence. The fluorescence quantum yield of free probe 1 in DMSO was calculated to be 0.03. After addition of 15 equiv. of F-, its fluorescence quantum yield can be increased to 0.37. The analytical detection limit for F- was 2.8 × 10- 7 M. 1H NMR analysis and DFT calculation show that the F--induced colorimetric and fluorometric responses of 1 are driven by deprotonation process. Graphical Abstract.

Copper chromogenic reaction based colorimetric immunoassay for rapid and sensitive detection of a tumor biomarker.

A new colorimetric immunoassay method was developed for the rapid and sensitive detection of a tumor biomarker of carcinoembryonic antigen (CEA) by combination of a magnetic bead (MB)-based sandwich immunoassay and a copper chromogenic reaction. The magnetic immunoassay platform was constructed through the covalent immobilization of the capture antibody on the surface of carboxylated magnetic beads. After immuno-recognition of CEA, signal antibody-functionalized copper oxide nanoparticle (CuO NP) probes were applied for sandwich immunoreaction to form an immunocomplex. The CuO NP labels quantitatively captured onto the immunocomplex were then dissolved in acid solution to release high-content copper ions. Based on the coordination of these ions with the newly synthesized chromogenic agent of 1,2-diphenyl-2-(2-(pyridin-2-yl)hydrazono)ethanone, a red complex was produced for the colorimetric signal readout, resulting in the successful construction of a sensitive immunoassay method for CEA detection. Under the optimum conditions, this method showed a wide linear range over three orders of magnitude and a low detection limit of 26 pg/mL. Besides, this method showed excellent performance with low cost, rapid and convenient operation as well as satisfactory reproducibility, stability and accuracy, thus providing great potentials for practical applications.