7-Dehydrocholesterol: A sterol shield against an iron sword.

Li et al. and Freitas et al. recently identified 7-dehydrocholesterol (7-DHC), a sterol produced through the cholesterol biosynthetic pathway, as a lipid-soluble antioxidant that protects cells from ferroptosis, a cell death pathway triggered by iron-catalyzed phospholipid peroxidation.1,2.

Dural arteriovenous fistula with spinal dural arteriovenous fistula: a case report and review of the literature.

BACKGROUND: This paper analyzed the cases of dural arteriovenous fistula (DAVF) with spinal dural arteriovenous fistula (SDAVF) in the diagnosis and treatment process. CASE PRESENTATION: One case involving dural arteriovenous fistula (DAVF) with spinal dural arteriovenous fistula (SDAVF) from the 306th Hospital of PLA was retrospectively analyzed. The patient consulted the doctor due to lower limb sensory and motor disorders while exhibiting symptoms of urinary dysfunction. A computed tomographic angiography (CTA) and cerebral angiography confirmed the diagnosis of dural arteriovenous fistula (DAVF), necessitating surgical treatment. The patient was referred to our hospital for an magnetic resonance imaging (MRI) and a spinal angiography to obtain a confirmed diagnosis for spinal arteriovenous fistula, after which they underwent surgical fistula resection. The invasive intracranial dural arteriovenous fistula (DAVF) resection proceeded smoothly but did not ease the patient's symptoms. However, postoperative symptoms were partially relieved by the lumbar open spinal dural arteriovenous fistula adminstration. CONCLUSIONS: Since not enough is understood about these two diseases, the rate of misdiagnosis is significantly increased. Early diagnosis and treatment of spinal dural arteriovenous fistula (SDAVF) can play a positive role during the recovery from neural function damage.

Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases.

Ferroptosis, a regulated cell death pathway driven by accumulation of phospholipid peroxides, has been challenging to identify in physiological conditions owing to the lack of a specific marker. Here, we identify hyperoxidized peroxiredoxin 3 (PRDX3) as a marker for ferroptosis both in vitro and in vivo. During ferroptosis, mitochondrial lipid peroxides trigger PRDX3 hyperoxidation, a posttranslational modification that converts a Cys thiol to sulfinic or sulfonic acid. Once hyperoxidized, PRDX3 translocates from mitochondria to plasma membranes, where it inhibits cystine uptake, thereby causing ferroptosis. Applying hyperoxidized PRDX3 as a marker, we determined that ferroptosis is responsible for death of hepatocytes in mouse models of both alcoholic and nonalcoholic fatty liver diseases, the most prevalent chronic liver disorders. Our study highlights the importance of ferroptosis in pathophysiological conditions and opens the possibility to treat these liver diseases with drugs that inhibit ferroptosis.

A protein-lipid complex that detoxifies free fatty acids.

Fatty acids (FAs) are well known to serve as substrates for reactions that provide cells with membranes and energy. In contrast to these metabolic reactions, the physiological importance of FAs themselves known as free FAs (FFAs) in cells remains obscure. Since accumulation of FFAs in cells is toxic, cells must develop mechanisms to detoxify FFAs. One such mechanism is to sequester free polyunsaturated FAs (PUFAs) into a droplet-like structure assembled by Fas-Associated Factor 1 (FAF1), a cytosolic protein. This sequestration limits access of PUFAs to Fe2+ , thereby preventing Fe2+ -catalyzed PUFA peroxidation. Consequently, assembly of the FAF1-FFA complex is critical to protect cells from ferroptosis, a cell death pathway triggered by PUFA peroxidation. The observations that free PUFAs in cytosol are not randomly diffused but rather sequestered into a membraneless complex should open new directions to explore signaling pathways by which FFAs regulate cellular physiology.

Transcriptome analysis of gene expression in the tomato leaf premature senescence mutant.

Premature senescence of leaves can critically influence tomato yield and quality. In this study, the leaf premature senescence mutant MT318 was a spontaneous mutant and was controlled by a single recessive nuclear gene. The maximum photochemical efficiency (Fv/Fm), superoxide dismutase (SOD), and chlorophyll content in the leaves of mutant MT318 gradually decreased, while malondialdehyde (MDA) content significantly increased. Under the level 2 category, Gene Ontology (GO) enrichment analysis indicated that 45 terms were enriched, comprising 22 in biological process, 12 in cellular component, and 11 in molecular function. Genes are mainly involved in the metabolic processes (696 differentially expressed genes, DEGs), cellular processes (573 DEGs), single-organism processes (503 DEGs), and catalytic activity (675 DEGs). Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the 4 pathways with the largest number of genes were biosynthesis of secondary metabolites, plant-pathogen interaction, plant hormone signal transduction, and MAPK signaling pathway-plant. The 'plant hormone signal transduction' pathway was the most significantly enriched at the T2 stage. Pearson correlation analysis showed that the auxin regulatory pathway and SA signal transduction pathway may play important roles. These results not only lay the foundation for the further cloning and functional analysis of the MT318 premature senescence gene but also provide a reference for the study of tomato leaf senescence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01223-2.

FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids.

Iron-dependent peroxidation of polyunsaturated fatty acids (PUFAs) leads to ferroptosis. While detoxification reactions removing lipid peroxides in phospholipids such as that catalyzed by glutathione peroxidase 4 (GPX4) protect cells from ferroptosis, the mechanism through which cells prevent PUFA peroxidation was not completely understood. We previously identified Fas-associated factor 1 (FAF1) as a protein directly interacting with free PUFAs through its UAS domain. Here we report that this interaction is crucial to protect cells from ferroptosis. In the absence of FAF1, cultured cells became sensitive to ferroptosis upon exposure to physiological levels of PUFAs, and mice developed hepatic injury upon consuming a diet enriched in PUFA. Mechanistically, we demonstrate that FAF1 assembles a globular structure that sequesters free PUFAs into a hydrophobic core, a reaction that prevents PUFA peroxidation by limiting its access to iron. Our study suggests that peroxidation of free PUFAs contributes to ferroptosis, and FAF1 acts upstream of GPX4 to prevents initiation of ferroptosis by limiting peroxidation of free PUFAs.

Improvement in cognitive dysfunction following blast induced traumatic brain injury by thymosin α1 in rats: Involvement of inhibition of tau phosphorylation at the Thr205 epitope.

Cognitive impairment is a significant sequela of traumatic brain injury (TBI) especially blast induced traumatic brain injury (bTBI), which is characterized by rapid impairments of learning and memory ability. Although several neuroprotective agents have been postulated as promising drugs for bTBI in animal studies, very few ideal therapeutic options exist to improve cognitive impairment following bTBI. Thymosin α1(Tα1), a 28-amino-acid protein that possesses immunomodulatory functions, has exhibited beneficial effects in the treatment of infectious diseases, immunodeficiency diseases and cancers. However, it remains unclear whether Tα1 has a therapeutic role in bTBI. Thus, we hypothesized that Tα1 administration could reverse the outcomes of bTBI. The blast induced TBI (bTBI) rat model was established with the compressed gas driven blast injury model system. A consecutive Tα1 therapy (in 1 ml saline, twice a day) at a dose of 200 µg/kg or normal saline (NS) (1 ml, twice a day) for 3 days or 2 weeks was performed. Utilizing our newly designed bTBI model, we investigated the beneficial effects of Tα1 therapy on rats exposed to bTBI including: cognitive functions, general histology, regulatory T (Treg) cells, edema, inflammation reactions and the expression and phosphorylation level of tau via Morris Water Maze test (MWM test), HE staining, flow cytometry, brain water content (BWC) calculation, IL-6 assay and Western blotting, respectively. Tα1 treatment seemed to reduce the 24-hour mortality, albeit with no statistical significance. Moreover, Tα1 treatment markedly improved cognitive dysfunction by decreasing the escape latency in the acquisition phase, and increasing the crossing numbers in the probe phase of MWM test. More interestingly, Tα1 significantly inhibited tau phosphorylation at the Thr205 epitope, but not at the Ser404 and Ser262 epitopes. Tα1 increased the percentage of Treg cells and inhibited plasma IL-6 production on 3d post bTBI. Moreover, Tα1 suppressed brain edema as demonstrated by decrease of BWC. However, there was a lack of obvious change in histopathology in the brain upon Tα1 treatment. This is the first study showing that Tα1 improves neurological deficits after bTBI in rats, which is potentially related to the inhibition of tau phosphorylation at the Thr205 epitope, increased Treg cells and decreased inflammatory reactions and brain edema.

A novel model of blast induced traumatic brain injury caused by compressed gas produced sustained cognitive deficits in rats: involvement of phosphorylation of tau at the Thr205 epitope.

Improvised explosive devices (IEDs) represent the leading causes for casualties among civilians and soldiers in the present war (including counter-terrorism). Traumatic brain injury (TBI) caused by IEDs results in different degrees of impairment of cognition and behavior, but the exact brain pathophysiological mechanism following exposure to blast has not been clearly investigated. Here, we sought to establish a rat model of closed-head blast injury using compressed gas to deliver a single blast only to the brain without systemic injuries. The cognitive functions of these bTBI models were assessed by Morris Water Maze test (MWM test). The HE staining, flow cytometry, ELISA and Western Blotting were used to measure the effects of shock wave on general histology, regulatory T (Treg) cells percentage, inflammatory reactions, the expression and phosphorylation level of tau, respectively. In addition, the brain water content and 24 -h mortality were also assessed. As the distance from the blast source increased, the input pressure did not change, the overpressure decreased, and the mortality decreased. Receiver operating characteristic (ROC) curves for predicting 24 -h mortality using peak overpressure fits with the following areas under ROC curves: 0.833. In 2 weeks after blast injury, cognitive tests revealed significantly decreased performance at 20 cm distance from the blast (about 136.44 kPa) as demonstrated by increased escape latency in the acquisition phase, and decreased crossing numbers in the probe phase of MWM test. Interestingly, a single blast exposure (at 20 cm) lead to significantly increased tau phosphorylation at the Thr205 epitope but not at the Ser404 and Ser262 epitopes at 12 h, 24 h, 3d, and 7d after blast injury. Blast decreased the percentage of CD4+T cells, CD8+T cells, Treg cells and lymphocytes at different time points after blast injury, and blast increased the percentage of neutrophils at 12 h after blast injury and significantly increased IL-6 production at 12 h, 24 h and 3d after blast injury. In addition, blast lead to an increase of brain edema at 24 h and 3d after blast injury. However, no obvious alterations in brain gross pathology were found acutely in the blast-exposed rats. In conclusion, we established a rat model of simple craniocerebral blast injury characterized by impairment of cognitive function, Thr205 phosphorylation of tau, decreased Treg cells and increased inflammatory reactions and brain edema. We expect this model may help clarify the underlying mechanism after blast injury and possibly serve as a useful animal model in the development of novel therapeutic and diagnostic approaches.

Neurosurgery medical robot Remebot for the treatment of 17 patients with hypertensive intracerebral hemorrhage.

OBJECTIVE: To verify the minimally invasive surgical approach and therapeutic effects of using the medical neurosurgery robot Remebot to treat hypertensive intracerebral hemorrhage (HICH). METHODS: Clinical data for 17 HICH patients were analyzed retrospectively. Hematoma evacuation and tube drainage using Remebot frameless stereotaxic techniques were performed for all patients, and urokinase was injected into the hematomas after the operations. RESULTS: Robot-assisted stereotactic techniques can accurately guide hematoma punctures, and no deaths occurred among these patients. The average positioning error was 1.28 ± 0.49 mm. The average drainage duration was 3.4 days. The 3-month postoperative follow-up revealed improved neurological functions and quality of life for all patients. CONCLUSIONS: The medical neurosurgery robot Remebot is minimally invasive, has high positional accuracy, and facilitates surgical planning according to the shape of the hematoma. Therefore, robot-assisted surgery using Remebot represents a safe and effective treatment method for hematoma evacuation and tube drainage in HICH patients.

Establishment of a novel rat model of blast-related diffuse axonal injury.

Although studies concerning blast-related traumatic brain injury (bTBI) have demonstrated the significance of diffuse axonal injury (DAI), no standard models for this type of injury have been widely accepted. The present study investigated a mechanism of inducing DAI through real blast injury, which was achieved by performing instantaneous high-speed swinging of the rat head, thus establishing a stable animal model of blast DAI. Adult Sprague-Dawley rats weighing 150±10 g were randomly divided into experimental (n=16), control (n=10) and sham control (n=6) groups. The frontal, parietal and occipital cortex of the rats in the experimental group were exposed, whereas those of the control group were unexposed; the sham control group rats were anesthetized and attached to the craniocerebral blast device without experiencing a blast. The rats were subjected to craniocerebral blast injury through a blast equivalent to 400 mg of trinitrotoluene using an electric detonator. Biomechanical parameters, and physical and behavioural changes of the sagittal head swing were measured using a high-speed camera. Magnetic resonance imaging (MRI) scans were conducted at 2, 12, 24 and 48 h after craniocerebral injury, only the experimental group indicated brain stem injury. The rats were sacrificed immediately following the MRI at 48 h for pathological examination of the brain stem using haematoxylin and eosin staining. The results indicated that 14 rats (87.5%) in the experimental group exhibited blast DAI, while no DAI was observed in the control and sham control groups, and the difference between the groups was significant (P<0.05). The present results indicated that this experimental design may serve to provide a stable model of blast DAI in rats.

Surgical management of 142 cases of split cord malformations associated with osseous divide.

OBJECTIVES: To investigate the key surgical points in treating split cord malformations associated with osseous divide and scoliosis (SCM-OD-S). MATERIALS AND METHODS: The surgical options and methods of a total of 142 SCM-OD-S cases were retrospectively analyzed, and the surgical precautions and imaging diagnosis were also discussed. RESULTS: The 142 patients were performed osseous divide resection plus dural sac molding, which achieved good results and no serious complication such as spinal cord and nerve injury occurred; certain symptoms such as urination-defecation disorders, muscle strength subsidence, Pes Cavus, and toe movement disorder in partial patients achieved various degrees of relief, and it also created good conditions for next-step treatment against scoliosis. CONCLUSIONS: The diagnosis of SCM-OD mainly depended on imaging inspection, routine magnetic resonance imaging (MRI) combined with computed tomography (CT) 3D reconstruction, which can comprehensively evaluate the types and features of diastematomyelia as well as other concomitant diseases. SCM alone needed no treatment, but surgery will be the only means of treating SCM-OD. Intraoperatively removing osseous divide step-by-step, as well as carefully freeing the spinal cord and remodeling the dural sac, can lay good foundations for relieving tethered cord, improving neurological symptoms, and further scoliosis orthomorphia, thus particularly exhibiting importance for the growth and development of adolescents.

Stereotactic bilateral transfrontal minimal radiofrequency thermocoagulation of the amygdalohippocampal complex for bilateral medial temporal lobe epilepsy: a retrospective study of 12 patients.

Some patients with temporal lobe epilepsy have bilateral discharges and a few have bilateral medial temporal sclerosis. Stereotactic bilateral radiofrequency thermocoagulation (RFTC) of the amygdalohippocampal complex can terminate seizures or reduce seizure severity in patients with bilateral medial temporal lobe epilepsy (BMTLE). To explore the safety and efficacy of bilateral transfrontal minimal RFTC of the amygdalohippocampal complex for the treatment of BMTLE. A total of 12 BMTLE patients were treated with bilateral transfrontal minimal RFTC of the amygdalohippocampal complex under limited coagulations. The volumes of coagulated lesions were less than 0.6 cm3 Clinical outcomes were evaluated using Engel's classification, the Liverpool Seizure Severity Scale (LSSS) 2.0, Wechsler Adult Intelligence Scale-Revised (WAIS-R), and Wechsler Memory Scale-Revised (WMS-R). Quality of life (QOL) was evaluated using the 36-item Short Form Health Survey (SF-36). Of the 12 patients, five (42%) were assessed as Engel Class I during 12-62 months of follow-up. LSSS scores declined sharply compared with the baseline of patients not in the seizure-free category. Functions of memory and intelligence declined transiently without statistical significance (p>0.05) immediately after surgery, but improved significantly (p<0.05) six months later. The qualities of life improved except vitality. Bilateral transfrontal minimal RFTC of the amygdalohippocampal complex may terminate seizures or reduce seizure severity in patients with BMTLE. Under limited coagulations, neuropsychological function was not affected but improved along with seizure control.

Functional conservation of MIKC*-Type MADS box genes in Arabidopsis and rice pollen maturation.

There are two groups of MADS intervening keratin-like and C-terminal (MIKC)-type MADS box genes, MIKC(C) type and MIKC* type. In seed plants, the MIKC(C) type shows considerable diversity, but the MIKC* type has only two subgroups, P- and S-clade, which show conserved expression in the gametophyte. To examine the functional conservation of MIKC*-type genes, we characterized all three rice (Oryza sativa) MIKC*-type genes. All three genes are specifically expressed late in pollen development. The single knockdown or knockout lines, respectively, of the S-clade MADS62 and MADS63 did not show a mutant phenotype, but lines in which both S-clade genes were affected showed severe defects in pollen maturation and germination, as did knockdown lines of MADS68, the only P-clade gene in rice. The rice MIKC*-type proteins form strong heterodimeric complexes solely with partners from the other subclade; these complexes specifically bind to N10-type C-A-rich-G-boxes in vitro and regulate downstream gene expression by binding to N10-type promoter motifs. The rice MIKC* genes have a much lower degree of functional redundancy than the Arabidopsis thaliana MIKC* genes. Nevertheless, our data indicate that the function of heterodimeric MIKC*-type protein complexes in pollen development has been conserved since the divergence of monocots and eudicots, roughly 150 million years ago.

Analysis of floral transcription factors from Lycoris longituba.

Transcription factors (TFs) are proteins that bind to specific promoter regions of their target genes and regulate gene transcription. Many of these factors have been found to influence flowering. Lycoris longituba exhibits a great deal of diversity in flower color and flower form, making it a suitable model for the study of floral development. We have identified 338 putative TFs from more than thirty thousand ESTs sequenced from the floral tissue of L. longituba, and validated them using real-time RT-PCR. Fifty-one of the TFs were recognized as being potentially flower-specific, and the expression patterns of some of them during six flowering phases have been elucidated. Homolog annotation and phylogenetic analysis revealed that some TFs that belong to several TF families, such as MADS, MYB-related, NAC, and ABI3-VP1, were suggested to play important roles in the flowering process. Our dataset may be used to identify priority target TF genes for further study.

Characteristics of osseous septum of split cord malformation in patients presenting with scoliosis: a retrospective study of 48 cases.

BACKGROUND/AIMS: The coexistence of scoliosis and split cord malformation (SCM) is often encountered. The characteristics of the osseous septum of SCM are still unknown to us. Here we try to delineate the configuration and nature of the osseous septa. The correlation between scoliosis and SCM is also discussed. METHODS: 48 patients hospitalized for scoliosis were studied. SCM was subsequently identified in all of the patients. These patients underwent operations and were retrospectively evaluated. RESULTS: The figuration, component, location and nature of osseous septa are described. 47 of the 48 SCMs (98%) were type I. Only 1 case was type II. 43 patients (90%) had 1 osseous septum. The other 5 patients (10%) had 2 osseous septa at different levels. 41 septa (78%) were mainly made of cortical bone, another 6 septa (11%) were mainly made of cancellous bone, while the other 6 (11%) were bone together with soft tissues. The prominent central blood vessels were found in 19 cases (36%). 10 osseous septa (19%) were derived from neural arches. 15 osseous septa (28%) were from both vertebral bodies and neural arches. CONCLUSION: We assumed that SCM might contribute to the progress of scoliosis. It is recommended that removal of the spur be carried out before corrective surgery on the spine.

Bone marrow stromal cells can be delivered to the site of traumatic brain injury via intrathecal transplantation in rabbits.

Recent studies suggest that bone marrow stromal cells (BMSCs) are promising grafts for treatment of traumatic brain injury (TBI). Neural precursor cells (NPCs) have been detected in the site of cervical cord injury following intrathecal injection by lumbar puncture. So, this study is designed to determine whether BMSCs (after intrathecal administration by lumbar puncture) could also migrate to the TBI site. The cells were cultured in vitro and transfected with adenovirus green fluorescent protein (Ad-GFP), and then transplanted intrathecally or intravenously into an autologous rabbit model of TBI. The labeled, grafted cells were identified in the injured cerebral tissue using fluorescence microscopy. Results showed that the intrathecal protocol was more efficient than the intravenous one. And motor dysfunction was improved after autologous transplantation of BMSCs. This study suggests another attractive minimally invasive option for treating TBI.

[Characteristic of medical support and health care for Shenzhou-5 and Shenzhou-6 astronauts at main landing site].

OBJECTIVE: To investigate the characteristics of medical support and health care for the Shenzhou-5 and Shenzhou-6 astronauts at the main landing site, with special emphasis on the technical requirements for two astronauts during flight, in order to provide reference data for medical support in the battle field and disasters. METHODS: The data associated with accidental injuries of astronauts during the space flight collected from foreign nations and domestically were reviewed retrospectively. Based on the experience in medical support for Shenzhou-5 and Shenzhou-6 astronauts and the special environments of field operations, a scheme for first-aid and emergent treatment were drafted for a system of organization, prophylactic measurements, equipment and their effective implementation pending the test in the real situation. RESULTS: Two sets of high-quality intensive care unit (ICU) equipment were set up in helicopters, and an ambulance was equipped with the instruments and facilities that could be used in the first-aid and surgical operation in case accident and injuries should happen. The three sets of highly mobile ICU mentioned above could cover a vast area of both grassland and desert at the landing site to ensure that the astronauts could be rescued should accident occur, reaction to emergency would be most rapid and technique and equipment would be best. This scheme of first-aid for emergency which might occur in astronauts would seem to be a scientific, reasonable and practical system and would also meet the need in battle field. CONCLUSION: The first-aid scheme for astronauts at the main landing site, and its equipment, first aid strategies as well as it execution might provide an advanced system for medical aid and emergency treatment in the battlefield, disasters, and other special occasions.

[Establishment of a mobile intensive care unit].

OBJECTIVE: To discuss the experience of establishment of a mobile intensive care unit (ICU) for emergency treatment following astronaut flight, disaster, and regional war. METHODS: The data from both foreign and our countries as well as our own clinical experience of first-aid were reviewed, and a mobile ICU was established, including the equipment, supply of drugs, training, and organization. RESULTS: The mobile ICU was set up at the site of landing of the first Chinese astronaut, and proved to be efficient. The new model could be expected to be prompt in first-aid for casualties in disasters and warfare. CONCLUSION: The first-aid on spot of casualties might reduce the rates of invalidity and mortality during disasters and regional war.

[Measure on medical care and rescue for the first Chinese astronaut during manned space flight].

OBJECTIVE: To discuss the experience of medical care and rescue for the first Chinese astronaut during manned space flight. METHODS: Review the experiences of foreign nations in respect to accidental injuries of astronaut during manned space flight, the possible reasons were analyzed, and accordingly a reasonable and effective prophylactic measures and health care were formulated. RESULTS: An effective mobile intensive care unit (ICU) was established on desert or prairie where the capsule would land, so as to ensure the safety of the first Chinese astronaut, and to provide intensive care as well as successful emergency treatment in case of accidental injuries. CONCLUSION: Reasonable and effective prophylactic measures and health care appear to be an important aspect of the successful manned space flight.