Furfural tolerance of mutant Saccharomyces cerevisiae selected via ionizing radiation combined with adaptive laboratory evolution.

BACKGROUND: Lignocellulose is a renewable and sustainable resource used to produce second-generation biofuel ethanol to cope with the resource and energy crisis. Furfural is the most toxic inhibitor of Saccharomyces cerevisiae cells produced during lignocellulose treatment, and can reduce the ability of S. cerevisiae to utilize lignocellulose, resulting in low bioethanol yield. In this study, multiple rounds of progressive ionizing radiation was combined with adaptive laboratory evolution to improve the furfural tolerance of S. cerevisiae and increase the yield of ethanol. RESULTS: In this study, the strategy of multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution significantly improved the furfural tolerance of brewing yeast. After four rounds of experiments, four mutant strains resistant to high concentrations of furfural were obtained (SCF-R1, SCF-R2, SCF-R3, and SCF-R4), with furfural tolerance concentrations of 4.0, 4.2, 4.4, and 4.5 g/L, respectively. Among them, the mutant strain SCF-R4 obtained in the fourth round of radiation had a cellular malondialdehyde content of 49.11 nmol/mg after 3 h of furfural stress, a weakening trend in mitochondrial membrane potential collapse, a decrease in accumulated reactive oxygen species, and a cell death rate of 12.60%, showing better cell membrane integrity, stable mitochondrial function, and an improved ability to limit reactive oxygen species production compared to the other mutant strains and the wild-type strain. In a fermentation medium containing 3.5 g/L furfural, the growth lag phase of the SCF-R4 mutant strain was shortened, and its growth ability significantly improved. After 96 h of fermentation, the ethanol production of the mutant strain SCF-R4 was 1.86 times that of the wild-type, indicating that with an increase in the number of irradiation rounds, the furfural tolerance of the mutant strain SCF-R4 was effectively enhanced. In addition, through genome-transcriptome analysis, potential sites related to furfural detoxification were identified, including GAL7, MAE1, PDC6, HXT1, AUS1, and TPK3. CONCLUSIONS: These results indicate that multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution is an effective mutagenic strategy for obtaining furfural-tolerant mutants and that it has the potential to tap genes related to the furfural detoxification mechanism.

Improvement of Saccharomyces cerevisiae strain tolerance to vanillin through heavy ion radiation combined with adaptive laboratory evolution.

Vanillin is an inhibitor of lignocellulose hydrolysate, which can reduce the ability of Saccharomyces cerevisiae to utilize lignocellulose, which is an important factor limiting the development of the ethanol fermentation industry. In this study, mutants of vanillin-tolerant yeast named H6, H7, X3, and X8 were bred by heavy ion irradiation (HIR) combined with adaptive laboratory evolution (ALE). Phenotypic tests revealed that the mutants outperformed the original strain WT in tolerance, growth rate, genetic stability and fermentation ability. At 1.6 g/L vanillin concentration, the average OD600 value obtained for mutant strains was 0.95 and thus about 3.4-fold higher than for the wild-type. When the concentration of vanillin was 2.0 g/L, the glucose utilization rate of the mutant was 86.3 % within 96 h, while that of the original strain was only 70.0 %. At this concentration of vanillin, the mitochondrial membrane potential of the mutant strain recovered faster than that of the original strain, and the ROS scavenging ability was stronger. We analyzed the whole transcriptome sequencing map and the whole genome resequencing of the mutant, and found that DEGs such as FLO9, GRC3, PSP2 and SWF1, which have large differential expression multiples and obvious mutation characteristics, play an important role in cell flocculation, rDNA transcription, inhibition of DNA polymerase mutation and protein palmitoylation. These functions can help cells resist vanillin stress. The results show that combining HIR with ALE is an effective mutagenesis strategy. This approach can efficiently obtain Saccharomyces cerevisiae mutants with improved vanillin tolerance, and provide reference for obtaining robust yeast strains with lignocellulose inhibitor tolerance.

Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells.

Sequencing-based mapping of ensemble pairwise interactions among regulatory elements support the existence of topological assemblies known as promoter-enhancer hubs or cliques in cancer. Yet, prevalence, regulators, and functions of promoter-enhancer hubs in individual cancer cells remain unclear. Here, we systematically integrated functional genomics, transcription factor screening, and optical mapping of promoter-enhancer interactions to identify key promoter-enhancer hubs, examine heterogeneity of their assembly, determine their regulators, and elucidate their role in gene expression control in individual triple negative breast cancer (TNBC) cells. Optical mapping of individual SOX9 and MYC alleles revealed the existence of frequent multiway interactions among promoters and enhancers within spatial hubs. Our single-allele studies further demonstrated that lineage-determining SOX9 and signaling-dependent NOTCH1 transcription factors compact MYC and SOX9 hubs. Together, our findings suggest that promoter-enhancer hubs are dynamic and heterogeneous topological assemblies, which are controlled by oncogenic transcription factors and facilitate subtype-restricted gene expression in cancer.

Functionalized nano cellulose double-template imprinted aerogel microsphere for the targeted enrichment of taxanes.

Paclitaxel, a diterpenoid isolated from the bark of Taxus wallichiana var. chinensis (Pilger) Florin, is currently showing significant therapeutic effects against a variety of cancers. Baccatin III (Bac) and 10-Deacetylbaccatin III (10-DAB) are in great demand as important precursors for the synthesis of paclitaxel. This work aims to develop a simple, rapid and highly selective, safe, and non-polluting molecularly imprinted material for 10-DAB and Bac enrichment. In this study, we innovatively prepared molecularly imprinted materials with nanocellulose aerogel microspheres and 2-vinylpyridine (2-VP) as a bifunctional monomer, and 10-DAB and Bac as bis-template molecules. In particular, functionalized nanocellulose dual-template molecularly imprinted aerogel microsphere (FNCAG-DMIM) were successfully synthesized by the bifunctional introduction of functional nanocellulose aerogel microsphere (FNCAG) modified with Polyethyleneimine (PEI) as a carrier and functional monomer, which provided a large number of recognition sites for bimodal molecules. FNCAG-DMIM showed high specificity for 10-DAB and Bac specific assays. Under the optimal experimental conditions, the adsorption capacities of FNCAG-DMIM for 10-DAB and Bac reached 52.27 mg g-1 and 53.81 mg g-1, respectively. In addition, it showed good reliability and practicality in the determination of real samples. The present study extends the research on the synthesis of natural functional monomers by molecularly imprinted materials and opens up new horizons for the targeted isolation of plant compounds by dual-template molecularly imprinted materials.

CRISPR/Cas12a and aptamer-chemiluminescence based analysis for the relative abundance determination of tumor-related protein positive exosomes for breast cancer diagnosis.

Exosomes, as novel biomarker for liquid biopsy, exhibit huge important potential value for cancer diagnosis. However, various proteins show different expression levels on exosomal membrane, and the absolute concentration of exosomes in clinical samples is easily influenced by a number of factors. Here, we developed a CRISPR/Cas12a and aptamer-chemiluminescence based analysis (CACBA) for the relative abundance determination of tumor-related protein positive exosomes in plasma for breast cancer diagnosis. The total concentration of exosomes was determined through captured CD63 using a CRISPR/Cas12a-based method with the LoD of 8.97 × 103 particles/µl. Meanwhile, EpCAM and MUC1 positive exosomes were quantitatively detected by aptamer-chemiluminescence (ACL) based method with the LoD of 1.45 × 102 and 3.73 × 102 particles/µl, respectively. It showed that the percentages of EpCAM and MUC1 positive exosomes offered an excellent capability to differentiate breast cancer patients and healthy donors. The high sensitivity, strong specificity, outstanding anti-interference capability, and steady recovery rate of this approach offered higher accuracy and robustness than the commercialized method in clinical trial. In addition with good stability, easy preparation and low cost, this method not only provides a new approach to rapid analysis of exosome proteins, it may be quickly extended to the diagnoses of various cancers.

Weak Value Amplification-Based Biochip for Highly Sensitive Detection and Identification of Breast Cancer Exosomes.

Exosomes constitute an emerging biomarker for cancer diagnosis because they carry multiple proteins that reflect the origins of the parent cell. The highly sensitive detection of exosomes is a crucial prerequisite for the diagnosis of cancer. In this study, we report an exosome detection system based on quantum weak value amplification (WVA). The WVA detection system consists of a reflection detection light path and a Zr-ionized biochip. Zr-ionized biochips effectively capture exosomes through the specific interaction between zirconium dioxide and the phosphate groups on the lipid bilayer of exosomes. Aptamer-modified gold nanoparticles (Au NPs) are then used to specifically recognize proteins on exosomes to enhance the detection signal. The sensitivity and resolution of the detection system are 2944.07 nm/RIU and 1.22 × 10-5 RIU, respectively. The concentration of exosomes can be directly quantified by the WVA system, ranging from 105-107 particles/mL with the detection limit of 3 × 104 particles/mL. The use of Au NPs-EpCAM for the specific enhancement of breast cancer MDA-MB-231 exosomes is demonstrated. The results indicate that the WVA detection system can be a promising candidate for the detection of exosomes as tumor markers.

Ischemic stroke as an initial performance of polycythemia vera in young adults: A case report and literature review.

INTRODUCTION: As the second leading cause of death and disability worldwide, stroke is mainly caused by atherosclerosis and cardiac embolism, particularly in older individuals. Nevertheless, in young and otherwise healthy individuals, the causes of stroke can be more diverse and may include conditions such as patent foramen ovale, vasculitis, coagulopathies, genetic factors, or other undetermined causes. Although these other causes of stroke account for a relatively small proportion compared to ischemic stroke, they are becoming increasingly common in clinical practice and deserve attention. Here, we present a rare female patient with polycythemia vera (PV) who was admitted to the hospital as a stroke patient without any previous medical history. PATIENT CONCERNS: A 40-year-old young woman felt sudden dizziness and slow response. After 4 days of being admitted, she developed blurry vision on the right. DIAGNOSES: Cranial magnetic resonance imaging revealed aberrant signals in the left temporal and parietal lobe, as well as multiple small focal signal abnormalities were observed in the left frontal lobe. Magnetic resonance angiography revealed partial stenosis of the left internal carotid artery. The patient's blood routine examination revealed a significant elevation in complete blood counts, particularly the increase in red blood cells, as well as prolonged clotting time. An abdominal ultrasound and abdomen computed tomography showed splenomegaly. The outcome of the genetic testing was positive for the Janus kinase JAK2 exon V617F mutation (JAK2/V617F). The patient was diagnosed with PV-related stroke. INTERVENTIONS: The patient was treated with phlebotomy, cytoreductive therapy, and low-dose aspirin antiplatelet therapy and was regularly followed up in hematology and neurology clinics after discharge. OUTCOMES: The patient's red blood cell, leukocyte, and thrombocyte counts had fully normalized, with her hemoglobin level measuring at 146 g/L and hematocrit value at 43%. Furthermore, there had been a significant improvement in neurological symptoms. LESSONS: PV, a rare hematological disorder, can present with ischemic stroke as the initial performance, and the diagnosis mainly relies on routine blood tests, bone marrow biopsies, and genetic test. Therefore, clinicians should pay attention to PV, a low-prevalence disease, when encountering stroke in youth.

Spatial promoter-enhancer hubs in cancer: organization, regulation, and function.

Transcriptional dysregulation is a hallmark of cancer and can be driven by altered enhancer landscapes. Recent studies in genome organization have revealed that multiple enhancers and promoters can spatially coalesce to form dynamic topological assemblies, known as promoter-enhancer hubs, which strongly correlate with elevated gene expression. In this review, we discuss the structure and complexity of promoter-enhancer hubs recently identified in multiple cancer types. We further discuss underlying mechanisms driving dysregulation of promoter-enhancer hubs and speculate on their functional role in pathogenesis. Understanding the role of promoter-enhancer hubs in transcriptional dysregulation can provide insight into new therapeutic approaches to target these complex features of genome organization.

Alpha lipoic acid treatment in late middle age improves cognitive function: Proteomic analysis of the protective mechanisms in the hippocampus.

Alpha lipoic acid (ALA), a powerful antioxidant, has the potential to relieve age-related cognitive impairment and neurodegenerative disease. Clinical randomized controlled studies have demonstrated the cognitive improvement effects of lipoic acid in Alzheimer's disease (AD). In the present study, we examined the effects of ALA on cognitive function in ageing mice and its protective mechanisms. Eighteen-month-old male C57BL6/J mice received ALA or normal saline for 2 months. The Morris water maze test revealed improved cognitive function in animals that received ALA. Furthermore, tandem Mass Tags (TMT) based liquid chromotography with mass spectrometry/mass spectrometry (LC-MS/MS) was established to identify the target proteins. The results showed that 10 proteins were changed significantly. Gene Ontology (GO) analysis indicated that the upregulated proteins were enriched in terminal bouton, synaptic transmission and lipid transporter activity while the down-regulated proteins were involved in nuclear transcription factor-κB binding, apoptosis and mitogen-activated protein kinase binding. Based on the GO results, two upregulated proteins oxysterol-binding protein-related protein 10 (OSBPL10) and oligophrenin 1 (OPHN1), and one downregulated protein, CDK5 regulatory subunit-associated protein 3 (CDK5rap3), were validated through Western blotting. The results were consistent with the proteomic results. Modulation of synaptic transmission, lipid transporter activity and neuroinflammation appears to be the mechanisms of ALA in the aged brain.

A Chinese female patient with LGI1 and mGluR5 antibodies: A case report.

RATIONALE: Anti-LGI1 antibody encephalitis and anti-mGluR5 are both uncommon encephalitis, and we report the first case of autoimmune encephalitis (AE) with dual seropositive antibodies of leucine-rich glioma-inactivated 1 (LGI1) and mGluR5. PATIENT CONCERNS: We present a case of AE with dual seropositive antibodies of LGI1 and mGluR5 in a 65-year-old woman who presented with sudden onset left faciobrachial dystonic seizures and unresponsive for 5 hours. DIAGNOSIS: The patient was diagnosed with anti-LGI1 AE and anti-mGluR5 AE mainly based on the clinical symptoms and further test of the antibody in serum and cerebral spinal fluid (CSF). INTERVENTIONS AND OUTCOMES: The patient was treated with glucocorticoid intravenous drip. We also gave her the therapy of immunoglobulin (25 g q.d) for 5 days and anti-epileptic therapy. She had no more convulsions on the left side of the face and limbs. She did not complain of any uncomfort until July 18. LESSONS: Early recognition of AE is crucial. Specific autoantibodies are associated with corresponding syndromes. Our patient was initially diagnosed with acute ischemic stroke. Therefore, we should conduct further study on the related symptoms of AE.

EBF1 nuclear repositioning instructs chromatin refolding to promote therapy resistance in T leukemic cells.

Chromatin misfolding has been implicated in cancer pathogenesis; yet, its role in therapy resistance remains unclear. Here, we systematically integrated sequencing and imaging data to examine the spatial and linear chromatin structures in targeted therapy-sensitive and -resistant human T cell acute lymphoblastic leukemia (T-ALL). We found widespread alterations in successive layers of chromatin organization including spatial compartments, contact domain boundaries, and enhancer positioning upon the emergence of targeted therapy resistance. The reorganization of genome folding structures closely coincides with the restructuring of chromatin activity and redistribution of architectural proteins. Mechanistically, the derepression and repositioning of the B-lineage-determining transcription factor EBF1 from the heterochromatic nuclear envelope to the euchromatic interior instructs widespread genome refolding and promotes therapy resistance in leukemic T cells. Together, our findings suggest that lineage-determining transcription factors can instruct changes in genome topology as a driving force for epigenetic adaptations in targeted therapy resistance.

Klebsiella pneumoniae-related brain abscess and meningitis in adults: Case report.

INTRODUCTION: Klebsiella pneumoniae is once thought to be a less common cause of brain abscess in adults and is mainly hospital-acquired. Community-acquired CNS infection (brain abscess and meningitis) caused by K pneumoniae without other metastatic septic abscesses is exceedingly rare. Therefore, we present a rare adult patient with invasive cerebral abscess and meningitis without other invasive abscesses related to K pneumoniae. PATIENT CONCERNS: A 64-year-old woman experienced a sudden onset of severe continuous headache accompanied by intermittent nausea, vomiting, and fever. Meanwhile, she experienced tinnitus and had a feeling of swelling in the right ear. DIAGNOSIS: Cranial magnetic resonance imaging revealed abnormal hyperintensity signals in the left head of the caudate nucleus. The next generation sequencing of cerebral spinal fluid showed infection with K pneumoniae. The patient was diagnosed with K pneumoniae-related brain abscesses and meningitis. INTERVENTIONS: Antibacterial treatment was carried out for 2 months. OUTCOMES: The patient recovered well. CONCLUSION: Despite the progress of modern neurosurgical techniques, new antibiotics, and modern imaging techniques, brain abscesses are still a potentially fatal infection. Streptococci are common organisms that result in brain abscesses. Nevertheless, Klebsiella species, once thought to be a less common cause of brain abscess in adults, has become an increasingly important cause of brain abscess, especially in Asia.

Magnetic compression stricturoplasty in patients with severe stricture after simultaneous esophageal atresia and duodenal obstruction repair: A case report.

Combined esophageal atresia (EA), tracheoesophageal fistula (TEF) and duodenal obstruction result in various challenges in management, and a well-defined management protocol is still lacking. Esophageal stricture is the most common complication after EA repair. The use of magnetic compression alimentary tract anastomosis has been reported in children. By searching the literature, the present study reports the first case of simultaneous repair (EA repair followed by duodenal obstruction repair) and magnetic compression stricturoplasty for refractory esophageal stricture after EA repair in two male neonates. One of the neonates received delayed treatment of duodenal obstruction, and the other successfully underwent a simultaneous emergency operation of these combined anomalies. These two infants developed refractory strictures despite multiple endoscopic dilatation procedures during the postoperative follow-up period. Magnetic compression stricturoplasty procedures were successfully performed under fluoroscopic and endoscopic guidance without any leakage or complication. At the follow-up 10-months after stricturoplasty, the two patients achieved durable esophageal patency in the absence of dysphagia. Combination of early chest and abdominal X-ray detection is recommended to avoid a delayed diagnosis and treatment, as well as the synchronous operation for EA/TEF repair and duodenoduodenostomy in a single surgery for combined EA/TEF and duodenal obstructions. Therefore, magnetic compression stricturoplasty is a feasible and efficient method for establishing early patency of the esophagus in patients with refractory EA stricture.

Transcriptome analysis reveals antioxidant defense mechanisms in the red swamp crayfish Procambarus clarkia after exposure to chromium.

Chromium (Cr) as a chromate anion has a strong redox capacity that seriously threatens the ecological environment and human health. Cr can contaminate water and impart toxicity to aquatic species. Procambarus clarkii is an important food source that once represented a large proportion of the aquaculture industry due to its rapid reproduction and high economic value. However, there have been reports on the death of P. clarkii due to heavy metal pollution. The underlying mechanism regarding heavy metal toxicity was studied in this paper. The transcriptome data of hemocytes extracted from P. clarkii injected with Cr were analyzed by high-throughput sequencing and compared to the control group. In total, 48,128,748 clean reads were obtained in the treatment group and 56,480,556 clean reads were obtained in the control group. The reads were assembled using Trinity and the identified unigenes were then annotated. Then, 421 differentially-expressed genes (DEGs) were found, 170 of which were upregulated and 251 downregulated. Many of these genes were found to be related to glutathione metabolism and transportation. The glutathione metabolic pathway of P. clarkii was thus activated by Cr exposure to detoxify and maintain body function. Validation of DEGs with quantitative real-time PCR confirms the changes in gene expression. Thus, this study provides data supporting a glutathione-focused response of P. clarkii to exposure to heavy metals.

A three-dimensional nanostructure of NiFe(OH) X nanoparticles/nickel foam as an efficient electrocatalyst for urea oxidation.

Developing high-performance electrocatalysts for urea oxidation reaction (UOR) can not only solve the problem of environmental pollution, but also solve the problem of the energy crisis by producing hydrogen for electrodes. The preparation of porous three-dimensional nanostructures as efficient electrocatalysts has become important work. Here, we developed a novel three-dimensional (3D) nanostructure of NiFe(OH) X nanoparticles/nickel foam with a high active area by a simple electroplating method and a subsequent treatment with ferric ion solution. This structure shows much greater UOR activity than the control sample (Ni/Ni foam) with the potential of 1.395 V (vs. RHE) (with an overpotential of 1.025 V) for driving the current density of 100 mA cm-2 in 1.0 M KOH electrolyte with 0.33 M urea. This work not only provides rapid and large-scale preparation of a three-dimensional nanostructure, but also gives a new way to design and obtain high-performance electrocatalysts.

Magnetic compression for anastomosis in treating an infant born with long-gap oesophageal atresia: A case report.

RATIONALE: Neonatal long-gap esophageal atresia (LGEA) with tracheoesophageal fistula (TEF) is an uncommon but serious congenital malformation of the esophagus in newborns, and it remains challenging for pediatric surgeons. Magnetic compress has been shown to be effective for the treatment of LGEA in children and adults. However, the implementation of this unique technique for neonatal LGEA has not been evaluated. PATIENT CONCERNS: A female infant was born at 37 weeks of gestation. Prenatal ultrasound imaging revealed signs of esophageal atresia, including the absence of the gastric bubble and polyhydramnios. DIAGNOSES: A diagnosis of LGEA with TEF was confirmed at birth by contrast X-ray. INTERVENTIONS: She was treated with magnetic compression anastomosis (MCA) following an esophago-esophagostomy. Two magnetic rings were customized, and the MCA was conducted during the same stage surgery of ligating the TEF. Under the magnetic force, the 2 magnet rings pulled along the gastric tube to achieve anastomosis. The postoperative permanent suction of these 2 pouches was instituted, and spontaneous growth was awaited. Magnet removal was performed at 36 days, and enteral nutrition was continued via a gastric tube for 4 weeks at post-operation. OUTCOMES: The upper gastrointestinal contrast confirmed the anastomotic patency perfectly after 3 months. The patient was followed up for 18 months, and exhibited durable esophageal patency without dysphagia. LESSONS: These results suggest that MCA is feasible and effective for treating LGEA in infants.

Effects of CircRNA-ITCH on proliferation and apoptosis of hepatocellular carcinoma cells through inhibiting Wnt/ß-catenin signaling pathway.

PURPOSE: To explore the effects of circular ribonucleic acid (circRNA)-E3 ubiquitin protein ligase (ITCH) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells and its possible molecular mechanism. METHODS: To study the role of circRNA-ITCH in the occurrence and development of HCC. The relative expression level of circRNA-ITCH was detected via quantitative polymerase chain reaction (qPCR) in four kinds of HCC Huh-7, U251, HB611 and SMMC-7721 cell lines, and human normal liver L-02 cell line. Moreover, the effect of overexpression of circRNA-ITCH on the TCF luciferase activity was detected using ß-catenin/TCF-responsive luciferase reporter assay. Finally, the influences of overexpression of circRNA-ITCH on the protein levels of ß-catenin and Wnt3α and the mRNA levels of c-myc and cyclinD1 were determined using Western blotting and qPCR, respectively. RESULTS: Compared with that in human normal liver L-02 cell line, the expression of circRNA-ITCH was significantly down-regulated in HCC Huh-7, U251, HB611 and SMMC-7721 cell lines (p<0.05). According to the results of CCK-8 assay, colony formation assay and flow cytometry, the overexpression of circRNA-ITCH could obviously inhibit cell proliferation, suppress colony formation ability and induce apoptosis (p<0.05). The results of dual-luciferase reporter assay revealed that there was a significant interaction between circRNA-ITCH and miR-7 or miR-214 (p<0.05). CircRNA-ITCH was involved in the regulating of Wnt/ß-catenin signal transduction pathway and inhibited the expressions of c-myc and cyclinD1. CONCLUSIONS: CircRNA-ITCH affects the proliferation and apoptosis of HCC cells through inhibiting the Wnt/ß-catenin signal transduction pathway, thereby exerting a carcinogenic effect in the occurrence and development of HCC. The research results provide a new therapeutic target for HCC.

The bidirectional nature of microbiome-epithelial cell interactions.

The biogeography of the mammalian intestine is remarkable in that a vast microbial consortium exists inside the organism, surrounded by intestinal epithelial cells. The microbiome and the intestinal epithelium have developed a complex network of interactions that maintain intestinal homeostasis. We now recognize that functions of the epithelium are compartmentalized in specific intestinal epithelial cell subtypes. Furthermore, we are beginning to understand the ways in which microbes and their metabolic products impact the specific epithelial subsets. Here, we survey the mechanisms utilized by the microbiome to regulate intestinal epithelial function, and inversely, how different epithelial cell subtypes cooperate in regulating the microbiome.

SALL4 is a useful marker for pediatric yolk sac tumors.

BACKGROUND: SALL4 is a zinc finger transcription factor that exerts its physiological role during embryo-fetal development. Analyses of SALL4 expression have shown its oncogenic role in precursor B-cell lymphoblastic lymphoma, acute and chronic myeloid leukemia, gastrointestinal, breast, and lung cancers. The aim of this study was to determine the immunohistochemical profile of SALL4 in pediatric yolk sac tumors (YSTs). METHODS AND RESULTS: Immunohistochemistry detection of SALL4 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (> 90%). To compare its sensitivity and specificity with Glypican-3 and α-fetoprotein (AFP), we also stained tumors from these cases for Glypican-3 and AFP. In contrast to AFP and glypican-3, SALL4 staining in more than 90% of the tumor cells was seen in all 22 pediatric YSTs (100% sensitivity) (P < 0.001 for both SALL4 vs. AFP and SALL4 vs. glypican-3). CONCLUSIONS: SALL4 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. SALL4 is likely to become a new and valuable biomarker for the diagnosis of pediatric YST.

Iron dysregulation in vascular dementia: Focused on the AMPK/autophagy pathway.

Recent researches suggested that iron dysregulation play an important role in the pathogenesis of vascular dementia (VD). Iron deposition had been found in hippocampus in vascular dementia model in recent research. Nevertheless, the underlying mechanisms of iron deposition and its neurotoxicity in vascular dementia was still unclear. Thus, our research was aimed at whether the neurotoxicity of iron was associated with autophagy regulation. We established a chronic cerebral hypoperfusion model in the rat brain in order to mimic the vascular dementia using permanent bilateral common carotid artery occlusion (2VO). The preparation of iron overloaded rats model by intraperitoneal injection of iron dextran. Following, we tested the learning and memory function of each group using Morris Water Maze. Consequently, we analyzed the iron content and iron transport related molecules (TFR1, DMT1) in hippocampus. Furthermore, we examined the effect of iron deposition on autophagy-related molecules including AMPK, Beclin1 and LC3 and the number of autophagosomes in hippocampus. Last, we tested the apoptosis of neurons in hippocampus. We found that iron deposition in hippocampus in model groups which accompanied the decline of learning and memory function. And the expression of TFR1 and DMT1 were up-regulated in model groups. Moreover, iron deposition up-regulated the expression of AMPK, Beclin1 and LC3 and increase the number of autophagosomes in hippocampus. And the expression of Bax was up-regulated and Bcl-2 was down-regulated in iron deposition groups. To sum up, our data suggested that iron deposition increased AMPK/autophagy pathway associated molecules in the hippocampus and promoted neuronal apoptosis, which might be a new pathogenesis in vascular dementia.