Dumbbell shaped craniorbital cavernous hemangioma.

BACKGROUND: Cavernous hemangioma of the orbit is a benign tumor mostly located behind the eye globe, but it rarely spread into the brain, which is called cerebral cavernous malformation as well, the lesion in the brain is irregular and enlarged blood. Here we report one particular case of craniorbital cavernous hemangioma. CASE PRESENTATION: A 53-year-old woman presented with exophthalmos of the right eye and reduced vision. Computerized tomographical (CT) scan showed osteolytic honeycomb radial changes of the outer plate of the skull. A magnetic resonance imaging (MRI) scan was performed to obtain further details. T1-weighted (T1W) imaging showed slightly low signal mixed with small patchy high signal. T2-weighted (T2W) imaging showed uneven high signal. There was obvious enhancement in the middle and no enhancement in the peripheral bars. A surgically manage was performed using a left frontotemporal approach, the tumor excised fully, and the histopathology results revealed a cavernous hemangioma. The patient recovered well in the follow-up. Post-operative CT scan identified the lesion was successfully resected, MRI scan also showed full resection and enhanced signal from the presence of fat. CONCLUSIONS: Craniorbital cavernous hemangioma is uncommon, however within the cranium, they can lead to numerous complications particularly if affecting the visual apparatus. it could be diagnosed by imaging, which CT scan shows osteolytic honeycomb radial changes of the outer plate of the skull, T1W imaging shows slightly low signal mixed with small patchy high signal, T2W imaging shows uneven high signal, it is obvious enhancement in the middle and no enhancement in the peripheral bars. The surgically manage is the ideally treatment when there are some symptoms.

MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury.

Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite advances in treatment for SAH, the prognosis remains poor. We have previously demonstrated that glycine, a non-essential amino acid is involved in neuroprotection following intracerebral hemorrhage via the Phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway. However, whether it has a role in inducing neuroprotection in SAH is not known. The present study was designed to investigate the role of glycine in SAH. In this study, we show that glycine can reduce brain edema and protect neurons in SAH via a novel pathway. Following a hemorrhagic episode, there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), and this can be reversed with glycine treatment. We also found that administration of glycine can reduce neuronal cell death in SAH by activating the AKT pathway. Glycine was shown to upregulate miRNA-26b, which led to PTEN downregulation followed by AKT activation, resulting in inhibition of neuronal death. Inhibition of miRNA-26b, PTEN or AKT activation suppressed the neuroprotective effects of glycine. Glycine treatment also suppressed SAH-induced M1 microglial polarization and thereby inflammation. Taken together, we conclude that glycine has neuroprotective effects in SAH and is mediated by the miRNA-26b/PTEN/AKT signaling pathway, which may be a therapeutic target for treatment of SAH injury.

Aging Reduces an ERRalpha-Directed Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells.

Aging deteriorates osteogenic capacity of mesenchymal stem/stromal cells (MSCs), contributing to imbalanced bone remodeling and osteoporosis. Glutaminase (Gls) catabolizes glutamine into glutamate at the first step of mitochondrial glutamine (Gln)-dependent anaplerosis which is essential for MSCs upon osteogenic differentiation. Estrogen-related receptor α (ERRα) regulates genes required for mitochondrial function. Here, we found that ERRα and Gls are upregulated by osteogenic induction in human MSCs (hMSCs). In contrast, osteogenic differentiation capacity and glutamine consumption of MSCs, as well as ERRα, Gls and osteogenic marker genes are significantly reduced with age. We demonstrated that ERRα binds to response elements on Gls promoter and affects glutamine anaplerosis through transcriptional induction of Gls. Conversely, mTOR inhibitor rapamycin, ERRα inverse agonist compound 29 or Gls inhibitor BPTES leads to reduced Gln anaplerosis and deteriorated osteogenic differentiation of hMSCs. Importantly, overexpression of ERRα or Gls restored impairment by these inhibitors. Finally, we proved that compensated ERRα or Gls expression indeed potentiated Gln anaplerosis and osteogenic capability of elderly mice MSCs in vitro. Together, we establish that Gls is a novel ERRα target gene and ERRα/Gls signaling pathway plays an important role in osteogenic differentiation of MSCs, providing new sights into novel regenerative therapeutics development. Our findings suggest that restoring age-related mitochondrial Gln-dependent anaplerosis may be beneficial for degenerative bone disorders such as osteoporosis. Stem Cells 2017;35:411-424.

Curcumin Inhibits Monocyte Chemoattractant Protein-1 Expression in TNF-α induced Astrocytes Through AMPK Pathway.

Curcumin, a phenolic pigment, plays an inhibitory role in astrocytes activation, a key step for neuropathic pain (NP). The present study aimed to investigate the mechanism behind the therapeutic effect of Curcumin on NP in vitro. Specifically, we investigated the inhibitory effect of Curcumin on tumor necrosis factor-α (TNF-α)-induced astrocyte migration. We also studied the effects of Curcumin on monocyte chemoattractant protein-1(MCP-1) expression and activity, as well as super oxide dismutase-2 (SOD2) expression and activity in TNF-α-induced astrocytes. Additionally, we investigated whether the adenosine-monophosphate-activated protein kinase signaling (AMPK) pathway was involved in this process. Our data demonstrated that Curcumin inhibited TNF-α-induced astrocytes migration, decreased MCP-1 expression, and up-regulated SOD2 expression in TNF-α-induced astrocytes in vitro. Our study also indicated that this process was mediated through the AMPK signaling pathway, as addition of Curcumin significantly increased the level of phosphorylated AMPK protein. Furthermore, the specific AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-D-ribofuranoside) mimicked the effects of Curcumin, whereas a selective AMPK inhibitor Compound C (also called dorsomorphin) partially blocked its function. These results could shed light on understanding of the molecular basis for the inhibition of Curcumin on MCP-1 expression during the process of astrocyte activation, and provide a molecular mechanism for using Curcumin in neuropathic pain.

Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease.

BACKGROUND: In the last 20 years, China ramped up a DOTS (directly observed treatment, short-course)-based tuberculosis (TB) control program with 80% population coverage, achieving the 2015 Millennium Development Goal of a 50% reduction in TB prevalence and mortality. Recently, the World Health Organization developed the End TB Strategy, with an overall goal of a 90% reduction in TB incidence and a 95% reduction in TB deaths from 2015-2035. As the TB burden shifts to older individuals and China's overall population ages, it is unclear if maintaining the current DOTS strategy will be sufficient for China to reach the global targets. METHODS: We developed an individual-based computational model of TB transmission, implementing realistic age demographics and fitting to country-level data of age-dependent prevalence over time. We explored the trajectory of TB burden if the DOTS strategy is maintained or if new interventions are introduced using currently available and soon-to-be-available tools. These interventions include increasing population coverage of DOTS, reducing time to treatment, increasing treatment success, and active case finding among elders > 65 years old. We also considered preventative therapy in latently infected elders, a strategy limited by resource constraints and the risk of adverse events. RESULTS: Maintenance of the DOTS strategy reduces TB incidence and mortality by 42% (95% credible interval, 27-59%) and 41% (5-64%), respectively, between 2015 and 2035. A combination of all feasible interventions nears the 2035 mortality target, reducing TB incidence and mortality by 59% (50-76%) and 83% (73-94%). Addition of preventative therapy for elders would enable China to nearly reach both the incidence and mortality targets, reducing incidence and mortality by 84% (78-93%) and 92% (86-98%). CONCLUSIONS: The current decline in incidence is driven by two factors: maintaining a low level of new infections in young individuals and the aging out of older latently infected individuals who contribute incidence due to reactivation disease. While further reducing the level of new infections has a modest effect on burden, interventions that limit reactivation have a greater impact on TB burden. Tools that make preventative therapy more feasible on a large scale and in elders will help China achieve the global targets.

The TGFß1/SMADs/Snail1 signaling axis mediates pericyte-derived fibrous scar formation after spinal cord injury.

AIMS: The deposition of fibrous scars after spinal cord injury (SCI) affects axon regeneration and the recovery of sensorimotor function. It has been reported that microvascular pericytes in the neurovascular unit are the main source of myofibroblasts after SCI, but the specific molecular targets that regulate pericyte participation in the formation of fibrous scars remain to be clarified. METHODS: In this study, a rat model of spinal cord dorsal hemisection injury was used. After SCI, epigallocatechin gallate (EGCG) was intraperitoneally injected to block the TGFß1 signaling pathway or LV-Snail1-shRNA was immediately injected near the core of the injury using a microsyringe to silence Snail1 expression. Western blotting and RT-qPCR were used to analyze protein expression and transcription levels in tissues. Nissl staining and immunofluorescence analysis were used to analyze neuronal cell viability, scar tissue, and axon regeneration after SCI. Finally, the recovery of hind limb function after SCI was evaluated. RESULTS: The results showed that targeted inhibition of Snail1 could block TGFß1-induced pericyte-myofibroblast differentiation in vitro. In vivo experiments showed that timely blockade of Snail1 could reduce fibrous scar deposition after SCI, promote axon regeneration, improve neuronal survival, and facilitate the recovery of lower limb motor function. CONCLUSION: In summary, Snail1 promotes the deposition of fibrous scars and inhibits axonal regeneration after SCI by inducing the differentiation of pericytes into myofibroblasts. Snail1 may be a promising therapeutic target for SCI.

Molecular Characterization of the Acyl-CoA-Binding Protein Genes Reveals Their Significant Roles in Oil Accumulation and Abiotic Stress Response in Cotton.

Members of the acyl-CoA-binding protein (ACBP) gene family play vital roles in diverse processes related to lipid metabolism, growth and development, and environmental response. Plant ACBP genes have been well-studied in a variety of species including Arabidopsis, soybean, rice and maize. However, the identification and functions of ACBP genes in cotton remain to be elucidated. In this study, a total of 11 GaACBP, 12 GrACBP, 20 GbACBP, and 19 GhACBP genes were identified in the genomes of Gossypium arboreum, Gossypium raimondii, Gossypium babardense, and Gossypium hirsutum, respectively, and grouped into four clades. Forty-nine duplicated gene pairs were identified in Gossypium ACBP genes, and almost all of which have undergone purifying selection during the long evolutionary process. In addition, expression analyses showed that most of the GhACBP genes were highly expressed in the developing embryos. Furthermore, GhACBP1 and GhACBP2 were induced by salt and drought stress based on a real-time quantitative PCR (RT-qPCR) assay, indicating that these genes may play an important role in salt- and drought-stress tolerance. This study will provide a basic resource for further functional analysis of the ACBP gene family in cotton.

Micro-Bubble F-P Cavity and FBG Cascade Structure-Based Pressure Sensor With Temperature Self-Compensation for Minimally Invasive Surgery.

This paper presents a high-sensitivity optical fiber pressure sensor with temperature self-compensation for pressure measurement in minimally invasive surgery through a cascade structure of Fabry-Perot (F-P) interferometer and fiber Bragg grating (FBG). A micro-bubble is configured at the tip of the fiber to form an F-P cavity that is sensitive to pressure. A loose optical fiber inscribed with an FBG element is cascaded with the F-P cavity leading to temperature compensation for the designed sensor. The sensing theoretical model has been derived and combined with the finite element method (FEM) simulation the sensor structure has been determined as well. Fabrication processing of the designed sensor has been optimized and explored by experiments. Calibration experiment results indicate that the pressure sensitivity of the designed sensor is 8.93 pm/kPa, which is consistent with the simulated value. The temperature coupled error is less than 3.89% leading to a capability for temperature self-compensation. Several heart-vascular simulation experiments have been carried out to investigate the dynamic performance of the designed sensor, which shows the measured pressure errors within this confidence interval of [-2.56%, 2.54%] correspond to high confidence of 0.95. An in-vivo intracranial pressure (ICP) measurement experiment on the rat brain has been conducted to further validate the feasibility and effectiveness of the designed sensor.

Genome-wide characterization of the UDP-glycosyltransferase gene family reveals their potential roles in leaf senescence in cotton.

Uridine diphosphate (UDP) glycosyltransferases (UGTs) involved in many metabolic processes and are essential for plant growth and development. Although UGTs proteins have been studied in many plants, the biological functions of UGT genes in cotton leaf senescence are still unknown. In the present study, we performed a genome-wide survey and identified 157 GrUGT, 152 GaUGT and 261 GHUGT genes in Gossypium raimondii, G. arboreum, and G. hirsutum, respectively, that were classified into 15 groups. Analysis of protein motif and gene structure demonstrated that structural and functional conservation occurred within same groups but diverged among the different groups. Gene duplication analysis indicated the different duplication ways happened between tetraploid G. hirsutum and the two diploid species. Whole genome or segmental duplications played a main role in the expansion of the GHUGT family in cotton, and experienced purifying selection during the long evolutionary process in cotton. Cis-acting regulatory elements analysis indicated that they were associated with complex hormone regulatory networks and the stress response. Additionally, to identify GHUGT candidate genes responsive to leaf senescence, we analyzed the expression patterns of GHUGT genes using our transcriptome data from two cultivars of upland cotton with contrasting tolerance to leaf senescence. Subsequently, gene expression profiling based on real-time quantitative PCR showed that selected GHUGT candidate genes might be involved in ABA and JA regulation. Through further functional verification, silencing GHUGT116 gene via VIGS (Virus-induced gene silencing) delayed dark-induced leaf senescence. Overall, the results provide useful and valuable information for understanding the evolution of cotton UGTs genes and the function in leaf senescence.

Genome-Wide Identification and Expression Analyses of the Cotton AGO Genes and Their Potential Roles in Fiber Development and Stress Response.

Argonaute proteins (AGOs) are indispensable components of RNA silencing. However, systematic characterization of the AGO genes have not been completed in cotton until now. In this study, cotton AGO genes were identified and analyzed with respect to their evolution and expression profile during biotic and abiotic stresses. We identified 14 GaAGO, 14 GrAGO, and 28 GhAGO genes in the genomes of Gossypium arboreum, Gossypium raimondii, and Gossypium hirsutum. Cotton AGO proteins were classified into four subgroups. Structural and functional conservation were observed in the same subgroups based on the analysis of the gene structure and conserved domains. Twenty-four duplicated gene pairs were identified in GhAGO genes, and all of them exhibited strong purifying selection during evolution. Moreover, RNA-seq analysis showed that most of the GhAGO genes exhibit high expression levels in the fiber initiation and elongation processes. Furthermore, the expression profiles of GhAGO genes tested by quantitative real-time polymerase chain reaction (qPCR) demonstrated that they were sensitive to Verticillium wilt infection and salt and drought stresses. Overall, our results will pave the way for further functional investigation of the cotton AGO gene family, which may be involved in fiber development and stress response.

Differential gene expression and associated QTL mapping for cotton yield based on a cDNA-AFLP transcriptome map in an immortalized F2.

cDNA-AFLP techniques have found new applications in recent years. Currently, the methodology is used to establish differential gene expression and construct linkage maps. In the present study, a transcriptome map based on cDNA-AFLP techniques was constructed using an immortalized F(2) (IF(2)) population of 171 lines. The lines were derived from intercrosses between 180 recombinant inbred lines (RILs) of the cotton hybrid Xiangzamian 2 (Gossypium. hirsutum L.). A total of 302 transcriptome-derived fragments (TDFs) were mapped onto 26 linkage groups that covered 2,477.06 cM in length with an average distance of 8.23 cM between two markers. Seventy-one QTL for yield and yield component traits were detected by CIM procedures based on four environments, with 13 QTL identified in at least two environments. Some TDFs co-located with yield QTL were subsequently sequenced and analyzed by online homology searches. Potential candidate genes for yield and yield component traits were found to encode proteins involved in DNA replication, transcription, translation, and biosynthesis regulation. Furthermore, genes regulating metabolic processes signal transduction, transport, and structural components of organelles were identified. Correlation analysis between expression patterns of TDFs and trait performance detected six TDFs positively correlated to both yield and yield heterosis: six TDFs positively correlated to yield, and seven TDFs to yield heterosis. These TDFs have potential for cloning the functional genes responsible for each corresponding trait and have future value in marker-assisted selection.

Hypothermia Protects Mice Against Ischemic Stroke by Modulating Macrophage Polarization Through Upregulation of Interferon Regulatory Factor-4.

BACKGROUND: Therapeutic hypothermia (TH) has been proven to be protective in ischemic stroke (IS) due to its anti-inflammatory capacity. Recently, the interferon regulatory factor 4 (IRF4) has been characterized as a central regulator of neuroinflammation in IS. Here we aim to determine whether IFR4 contributes to the neuroprotective effects of TH in IS. METHODS: In the present study, IRF4 knockout (IRF4-/-) and wild-type (IRF4+/+) mice were treated with or without TH after IS. Cerebral IRF4 expression, the production of pro-inflammatory and anti-inflammatory cytokines and macrophage polarization were determined at 8 hours after reperfusion. In addition, cerebral infarct volume and neurological function were evaluated at 7 days after IS. RESULTS: TH attenuates IS together with enhanced IRF4 expression as well as reduced production of pro-inflammatory cytokines. In addition, TH increased M2 macrophage polarization while inhibited M1 macrophage polarization. However, IRF4 knockout worsens neurological outcomes of stoke mice. The expression of pro-inflammatory cytokines were markedly increased in IRF4-/- mice as compared with IRF4+/+ mice at 8 h after stroke. Moreover, IRF4 knockout driven the macrophage polarization toward M1phenotype at 8 h after stroke. Most importantly, IRF4 knockout abolished the neuroprotective and anti-inflammatory effects of TH in IS. CONCLUSION: Together, we report for the first time that TH attenuates neuroinflammation following IS by modulating M1/M2 macrophage polarization through the upregulation of IRF4 expression.

Peri-tumoral brain edema associated with glioblastoma correlates with tumor recurrence.

Glioblastoma is the most common malignant tumor of the brain. Despite advances in treatment, the prognosis for the condition has remained poor. Glioblastoma is often associated with peritumoral brain edema (PTBE), which can result in increased intracranial pressure and devastating neurological sequelae if left untreated. Surgery is the main treatment for glioblastoma, however current international surgical guidelines do not specify whether glioblastoma-induced PTBE tissue should be resected. In this study, we analyzed treatment outcomes of PTBE using surgical resection. We performed a retrospective analysis of 255 cases of glioblastoma between 2014 and 2016, and found that a significant proportion of patients had a degree of PTBE. We found that surgical resection led to reduction in midline shift that had resulted from edema, however, postoperative complications and KPS scores were not significantly different in the two conditions. We also observed a delay in glioblastoma recurrence in patients undergoing PTBE tissue resection vs patients without resection of PTBE tissue. Interestingly, there was an abnormal expression of tumor associated genes in PTBE, which has not been previously been found. Taken together, this study indicates that glioblastoma-induced PTBE should be investigated further particularly as the tumor microenvironment is a known therapeutic target and therefore interactions between the microenvironment and PTBE should be explored. This study also highlights the importance of resection of PTBE tissue to not only reduce the mechanical obstruction associated with edema but also to delay recurrence of glioblastoma.

Trauma infant neurologic score predicts the outcome of traumatic brain injury in infants.

To investigate the clinical features of infancy traumatic brain injury (TBI) and the prognostic value of the Trauma Infant Neurologic Score (TINS), infants < 2 years of age with TBI who were admitted from 2000 to 2007 were retrospectively studied. Fifty-six patients with a mean age of 13.3 ± 6.5 months (range = 2-24) were identified. The clinical diagnoses, in terms of the severest injury, included scalp hematomas (n = 2), skull bone fractures (n = 3), epidural hematomas (n = 21), subdural hematomas (n = 14), cerebral contusion and laceration (n = 4), intracerebral hematomas (n = 7), traumatic subarachnoid hemorrhage (n = 2), diffuse axonal injury (n = 2) and diffuse brain swelling (n = 1). The most common clinical presentations were vomiting (66.1%), paleness (55.4%), irritability (37.3%), pupillary abnormalities (35.7%) and altered consciousness (32.1%). The mechanism of injury included falls (n = 41), vehicle accident (n = 9), abuse (n = 4) and unknown (n = 2). The TINS score ranged from 1 to 10 with a mean of 3.6 (SD = 2.4) in the whole patient cohort. The Children's Coma Scores (CCS) on admission were 13-15 (n = 31), 9-12 (n = 7) and 3-8 (n = 18). Thirty-nine of the infants were operated on and the other 17 infants were treated nonsurgically. Forty-eight patients (86%) were followed up for a period of 1-8 years (mean = 4.4) after discharge. In the followed-up patient cohort, the mean TINS score at admission was 3.8 ± 2.5. The total clinical outcome, according to the Glasgow Outcome Scale (GOS), was: 37 (77.1%) good recovery, 4 (8.3%) moderately disabled, 1 (2.1%) vegetative and 6 (12.5%) dead. For those who were operated on the outcome was: 25 (78.1%) good recovery, 4 (12.5%) moderately disabled and 3 (9.4%) dead, and for those who were not operated on: 12 (75.0%) good recovery, 1 (6.3%) vegetative and 3 (25.0%) dead. At two years of follow-up, the GOS included 34 (73.9%) good recovery, 3 (6.5%) moderately disabled, 2 (4.3%) severely disabled, 1 (2.2%) vegetative and 6 (13.0%) dead. Statistical tests revealed that the TINS scores were highly associated with the GOS. Higher TINS scores resulted in worse clinical outcome. The CCS scores were also to some degree associated with the GOS score. However, the CCS score on admission was not as discriminating as TINS, predicting only the best and worst outcome in our series. Our study showed that the clinical features of TBI in infants were different from those seen in adults regarding both the distribution of the pathology type and the clinical presenting symptoms. We found that the TINS scoring system is useful for predicting prognosis and outcome in infancy TBI and suggest that it could be routinely used in the infantile population.

Adaptive Immunity Regulation and Cerebral Ischemia.

Stroke is a disease that occurs due to a sudden interruption of the blood supply to the brain. It is a leading cause of death and disability worldwide. It is well-known that the immune system drives brain injury following an episode of ischemic stroke. The innate system and the adaptive system play distinct but synergistic roles following ischemia. The innate system can be activated by damage-associated molecular patterns (DAMPs), which are released from cells in the ischemic region. Damaged cells also release various other mediators that serve to increase inflammation and compromise the integrity of the blood-brain barrier (BBB). Within 24 h of an ischemic insult, the adaptive immune system is activated. This involves T cell and B cell-mediated inflammatory and humoral effects. These cells also stimulate the release of various interleukins and cytokines, which can modulate the inflammatory response. The adaptive immune system has been shown to contribute to a state of immunodepression following an ischemic episode, and this can increase the risk of infections. However, this phenomenon is equally important in preventing autoimmunity of the body to brain antigens that are released into the peripheral system as a result of BBB compromise. In this review, we highlight the key components of the adaptive immune system that are activated following cerebral ischemia.

Tyrosine Kinase Inhibitors Could Be Effective Against Non-small Cell Lung Cancer Brain Metastases Harboring Uncommon EGFR Mutations.

Background: The significance of uncommon epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) and brain metastasis (BM) remains unclear. Cerebrospinal fluid (CSF) liquid biopsy is a novel tool for assessing EGFR mutations in BM. This study aimed to evaluate the EGFR mutations in patients with NSCLC and newly diagnosed BM and to examine the effect of EGFR tyrosine kinase inhibitors (TKI) on BM harboring CSF-tested uncommon EGFR mutations. Methods: This was a prospective study of 21 patients with NSCLC and BM diagnosed between 04/2018 and 01/2019. CSF was obtained to detect the BM EGFR mutations by next-generation sequencing. BM characteristics at magnetic resonance imaging (MRI) and EGFR-TKI response were examined. Results: Of 21 patients with NSCLC, 10 (47.6%) had leptomeningeal metastasis (LM), while 11 (52.4%) had brain parenchymal metastasis (BPM); 13 (61.9%) had confirmed EGFR mutation-positive primary tumors. The uncommon mutation rate in CSF ctDNA was 33.3% (7/21). Among those with EGFR mutation-positive primary tumors, the rate of uncommon EGFR mutations in CSF was 53.8% (7/13). Uncommon EGFR mutations were more common in patients with LM than in patients with PBM (6/11, 54.5% vs. 1/10, 10%), and included G719A, L861Q, L703P, and G575R. TKI was effective for four patients with BMs harboring uncommon EGFR mutations. Conclusion: In patients with NSCLC and LM, the rate of uncommon EGFR mutation was high. The BMs with uncommon EGFR mutations seem to respond to EGFR-TKI treatment. CSF liquid biopsy could reveal the EGFR genetic profile of the BM and help guide treatment using small-molecule TKI.

Systematic analysis of NAC transcription factors in Gossypium barbadense uncovers their roles in response to Verticillium wilt.

As one of the largest plant-specific gene families, the NAC transcription factor gene family plays important roles in various plant physiological processes that are related to plant development, hormone signaling, and biotic and abiotic stresses. However, systematic investigation of the NAC gene family in sea-island cotton (Gossypium babardense L.) has not been reported, to date. The recent release of the complete genome sequence of sea-island cotton allowed us to perform systematic analyses of G. babardense NAC GbNAC) genes. In this study, we performed a genome-wide survey and identified 270 GbNAC genes in the sea-island cotton genome. Genome mapping analysis showed that GbNAC genes were unevenly distributed on 26 chromosomes. Through phylogenetic analyses of GbNACs along with their Arabidopsis counterparts, these proteins were divided into 10 groups (I-X), and each contained a different number of GbNACs with a similar gene structure and conserved motifs. One hundred and fifty-four duplicated gene pairs were identified, and almost all of them exhibited strong purifying selection during evolution. In addition, various cis-acting regulatory elements in GbNAC genes were found to be related to major hormones, defense and stress responses. Notably, transcriptome data analyses unveiled the expression profiles of 62 GbNAC genes under Verticillium wilt (VW) stress. Furthermore, the expression profiles of 15 GbNAC genes tested by quantitative real-time PCR (qPCR) demonstrated that they were sensitive to methyl jasmonate (MeJA) and salicylic acid (SA) treatments and that they could be involved in pathogen-related hormone regulation. Taken together, the genome-wide identification and expression profiling pave new avenues for systematic functional analysis of GbNAC candidates, which may be useful for improving cotton defense against VW.

Corrigendum: Afatinib for Advanced Non-small Cell Lung Cancer in a Case With an Uncommon Epidermal Growth Factor Receptor Mutation (G719A) Identified in the Cerebrospinal Fluid.

[This corrects the article DOI: 10.3389/fonc.2019.00628.].