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Background: Head and neck squamous carcinoma (HNSCC) is known for its high aggressiveness and susceptibility to cervical lymph node metastasis, which greatly contributes to its poor prognosis. During tumorigenesis, many types of cancer cells acquire oncogenic super-enhancers (SEs) that drive the overexpression of oncogenes, thereby maintaining malignant progression. This study aimed to identify and validate the role of oncogenic SE-associated genes in the malignant progression of HNSCC. Methods: We identified HNSCC cell-specific SE-associated genes through H3K27Ac ChIP-seq and overlapped them with HNSCC-associated genes obtained from The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) datasets using weighted gene coexpression network analysis (WGCNA) to identify hub genes. The expression of IGF2BP2 and KLF7 in HNSCC was detected using clinical samples. To determine the biological role of IGF2BP2, we performed CCK-8, colony formation assay, Transwell migration assay, invasion assay, and orthotopic xenograft model experiments. Furthermore, we utilized a CRISPR/Cas9 gene-editing system, small-molecule inhibitors, ChIP-qPCR, and dual-luciferase reporter assays to investigate the molecular mechanisms of IGF2BP2 and its upstream transcription factors. Results: Our study identified IGF2BP2 as a hub SE-associated gene that exhibited aberrant expression in HNSCC tissues. Increased expression of IGF2BP2 was observed to be linked with malignant progression and unfavorable prognosis in HNSCC patients. Both in vitro and in vivo experiments confirmed that IGF2BP2 promotes the tumorigenicity and metastasis of HNSCC by promoting cell proliferation, migration, and invasion. Mechanistically, the IGF2BP2-SE region displayed enrichment for H3K27Ac, BRD4, and MED1, which led to the inhibition of IGF2BP2 transcription and expression through deactivation of the SE-associated transcriptional program. Additionally, KLF7 was found to induce the transcription of IGF2BP2 and directly bind to its promoter and SE regions. Moreover, the abundance of KLF7 exhibited a positive correlation with the abundance of IGF2BP2 in HNSCC. Patients with high expression of both KLF7 and IGF2BP2 showed poorer prognosis. Lastly, we demonstrated that the small molecule inhibitor JQ1, targeting BRD4, attenuated the proliferation and metastatic abilities of HNSCC cells. Conclusions: Our study reveals the critical role of IGF2BP2 overexpression mediated by SE and KLF7 in promoting HNSCC progression. Targeting SE-associated transcriptional programs may represent a potential therapeutic strategy in managing HNSCC. [ABSTRACT FROM AUTHOR]

Recently, 9,10-anthraquinone (AQ) contamination in Chinese Liupao tea has attracted much attention because the tea for export must meet the EU limit (10 µg kg−1). In this study, a method was developed in which the sample was extracted with n-hexane-acetone solution, then purified with Florisil adsorbent, detected by GC-MS/MS and contamination levels of AQ determined using an internal standard. This method was found to be more suitable for Liupao tea and other dark tea complex substrates than the QuEChERS procedure. The sample pre-treatment method was optimized with respect to extraction reagent and clean-up column adsorbent and n-hexane-acetone selected as the optimal extraction solvent. When the content of Florisil in the column was 1.0 g, the optimum clean-up was achieved. The new method reduced the limit of quantification (LOQ) of AQ to 10 μg kg−1, and accuracy was also further improved. The recovery of AQ-fortified tea samples containing 20–100 µg·kg−1 was 94.5–100.4%, and the relative standard deviation (RSD) was less than 1.3%. In a small survey, 98 Liupao tea samples on the market were tested by the new method. It was found that 61 samples were positive (occurrence rate 63.3%), and thus exceeded the EU limit (10 µg kg−1). This study also found that the contamination of AQ in Liupao tea increased with the length of ageing. The source of AQ in the Liupao tea ageing process will be the focus of further research. [ABSTRACT FROM AUTHOR]

The association of exosomal RNA profiling and pathogenesis of moyamoya disease (MMD) and intracranial Atherosclerotic disease (ICAD) is unknown. In this study, we investigated the RNA profiles of sEV (small extracellular vesicles)/exosomes in patients with MMD and ICAD. Whole blood samples were collected from 30 individuals, including 10 patients with MMD, 10 patients with ICAD, and 10 healthy individuals. Whole transcriptome analysis was performed using the GeneChip WT Pico Reagent kit. Transcriptional correlation was verified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between functional dysregulation and candidate RNAs was studied in vitro. In total, 1,486 downregulated and 2,405 upregulated RNAs differed significantly between patients with MMD and healthy controls. Differential expression of six circRNAs was detected using qPCR. Among these significantly differentially expressed RNAs, IPO11 and PRMT1 circRNAs were upregulated, whereas CACNA1F circRNA was downregulated. This is the first study showing that the differential expression of exosomal RNAs associated with MMD pathogenesis, such as overexpression of IPO11 and PRMT1 circRNAs, may be related to angiogenesis in MMD. The downregulation of CACNA1F circRNA may be related to vascular occlusion. These results propose the utility of exosomal RNAs as biological markers in MMD. [ABSTRACT FROM AUTHOR]

Facial expression recognition plays a significant role in the application of man–machine interaction. However, existing models typically have shortcomings with numerous parameters, large model sizes, and high computational costs, which are difficult to deploy in resource‐constrained devices. This paper proposes a lightweight network based on improved MobileNetV3 to mitigate these disadvantages. Firstly, we adjust the channels in the high‐level network to reduce the number of parameters and model size, and then, the coordinate attention mechanism is introduced to the network, which enhances the attention of the network with few parameters and low computing cost. Furthermore, a complementary pooling structure is designed to improve the coordinate attention mechanism, which enables it to assist the network in extracting salient features sufficiently. In addition, the network with the joint loss consisting of the softmax loss and centre loss is trained, which can minimize the intra‐class gap and improve the classification performance. Finally, the network is trained and tested on public datasets FERPlus and RAF‐DB, with the best accuracy of 87.5% and 86.6%, respectively. The FLOPs, parameters, and the memory storage size are only 0.19GMac, 1.3 M, and 15.9 MB, respectively, which is lighter than most state‐of‐the‐art networks. Code is available at https://github.com/RIS‐LAB1/FER‐mobilenet. [ABSTRACT FROM AUTHOR]

Objective: Osteoradionecrosis of the jaw (ORNJ) is one of the most common and serious complications after radiotherapy of head and neck malignancies due to the high incidence of nasopharyngeal cancer in Southern China. Clinicians lack understanding and consensus on anti‐infective treatment in ORNJ lesions. This research aims to provide evidence for rational use of antibiotics by reviewing the bacterial spectrums and antimicrobial susceptibility test of ORNJ patients. Methods: We collected patient who was diagnosed with ORNJ from November 2012 to June 2019 in our hospital. Exudate or bone unexposed wound surface sampling, agar plates culturing, and susceptibility testing were analyzed. Descriptive statistics were used for data presentation. Results: A total of 219 samples were collected in our retrospective study. The most common cultured bacteria were Klebsiella pneumoniae (15.10%), Pseudomonas aeruginosa (13.54%), and Staphylococcus aureus (10.94%). Methicillin‐resistant Staphylococcus aureus (MRSA) accounted for 5.21% in the whole positive samples. Ticarcillin, Ofloxacin, Vancomycin, Tigecycline, and Meropenem were more susceptible than other antibiotics to treat uncontrollable infection. Conclusions: Our research provided objective evidence for understanding the types of local bacterial flora and drug susceptibility in ORNJ lesions and gave a guiding reference for empirical antibiotics medication. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) has high morbidity and mortality. The interaction between immune cells and tumor cells in the tumor micro-environment is an important factor affecting the tumor progression and prognosis of HNSCC patients. More biomarkers and targets need to be explored to improve patient outcomes. The m6A modification on enhancer RNAs (eRNAs) is associated with the signature of active enhancer, and the function of m6A driving eRNAs in tumor progression has not been reported. In this study, we screened and identified a risk model containing 5 m6A-related eRNA, which can better predict the survival and immunotherapy outcome of patients. The role of m6A-related eRNA in HNSCC cells was verified in vitro. We also combined the risk score and multiple clinical features to construct a nomogram for predicting OS of HNSCC patients, which provides an effective quantitative analysis tool for guiding the personalized precise treatment for patients. At present, the prognostic value of N6-methyladenosine (m6A)-related enhancer RNAs (eRNAs) for head and neck squamous cell carcinoma (HNSCC) still remains unclear. Our study aims to explore the prognostic value of m6A-related eRNAs in HNSCC patients and their potential significance in immune infiltration and immunotherapy. We constructed a 5 m6A-related eRNAs risk model from The Cancer Genome Atlas (TCGA) HNSCC dataset, using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the SRAMP website and in vitro experiments, it was verified that these 5 m6A-related eRNAs had m6A sites, the expression of which was regulated by corresponding m6A regulators. Moreover, we constructed a nomogram base on 5 m6A-related eRNAs and confirmed the consistency and robustness of an internal TCGA testing set. Further analysis found that the risk score was positively associated with low overall survival (OS), tumor cell metastasis, metabolic reprogramming, low immune surveillance, lower expression of immune-related genes, and higher expression of targeted genes. Finally, we verified that silencing MIR4435-2HG inhibited HNSCC cell migration and invasion. This study contributes to the understanding of the characteristics of m6A-related eRNAs in HNSCC and provides a reference for effective immunotherapy and targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Inhibitors of apoptosis proteins (IAPs) are a family of antiapoptotic proteins modulating cell cycle, signal transduction and apoptosis. Dysregulated IAPs have been reported to contribute to tumor progression and chemoresistance in various cancers. However, existing studies were sporadic and only focus on one specific cancer with one particular gene in the IAPs family. A systematic investigation on the co-expression pattern, regulation frameworks on various pathways, prognostic utility on patient outcomes, and predictive value on drug sensitivity among all the IAPs across multiple tumor types was lacking. Methods: Leveraging The Cancer Genome Atlas data with comprehensive genomic characterizations on 9714 patients across 32 tumor types and the Genomics of Drug Sensitivity in Cancer data with both genomic characterizations and drug sensitivity data on > 1000 cell lines, we investigated the co-expression pattern of IAPs, their regulations of apoptosis as well as other pathways and clinical relevance of IAPs for therapeutics development. Results: We discovered diverse expression pattern among IAPs, varied spectrum of apoptosis regulations through IAPs and extensive regulations beyond apoptosis involving immune response, cell cycle, gene expression and DNA damage repair. Importantly, IAPs were strong prognostic factors for patient survival and tumor stage in several tumor types including brain, liver, kidney, breast and lung cancer. Further, several IAPs were found to be predictive of sensitivity to BCL-2 inhibitors (BIRC3, BIRC5, BIRC6, and BIRC7) as well as RIPK1 inhibitors (BIRC3 and BIRC6). Conclusion: Together, our work revealed the landscape of regulations, prognostic utilities and therapeutic relevance of IAPs across multiple tumor types. [ABSTRACT FROM AUTHOR]

Background: The prognosis of glioma is poor, despite recent advances in diagnosis and treatment of the disease. It is important to investigate the clinical characteristics and prognostic factors of glioma so as to provide basis for treatment and management of patients.Method: A total of 335 patients with glioma were included in this study. These patients were admitted to the medical center between November 2015 and December 2018. The clinical data, including demographic data, tumor characteristics, treatment strategy, expression pattern of tumor markers, and survival data, were retrospectively reviewed. Survival data were analyzed using Kaplan-Meier curves with log-rank test, while multivariate analysis Cox regression model was used to investigate risk factors for mortality.Results: In this patient cohort, glioblastoma (40%), diffuse glioma (14.6%) and oligodendroglioma (9.6%) were the most common pathological types. The expression of Ki-67 was associated with several clinicopathological parameters (e.g. tumor type, grade, and number of lesions). In addition, Ki-67 correlated with the mortality within the first year of the post-treatment follow-up (P <  0.001). Kaplan-Maier analysis revealed that older patients (≥ 45 years) displayed worse prognosis than those aged under 45 years (P = 0.038). Dismal prognosis was also associated with clinical parameters, including high tumor grade, multiple lesions, and Karnofsky performance score (KPS). Multivariate analysis showed that low KPS (< 85) increased the risk of mortality by 2.3 folds with a 95% CI of 1.141 to 4.776 (P = 0.020). Low tumor grade (grade 1-2) oppositely reduced the mortality risk by 0.22 folds (95% CI, 0.065 to 0.763, P = 0.0168).Conclusion: KPS and tumor grade were independent prognostic factors in patients with gliomas. [ABSTRACT FROM AUTHOR]

Background and Purpose: Astrocytic excitatory amino acid transporters (EAATs) regulate extracellular glutamate concentrations and play a role in preventing neuroexcitotoxicity. As the δ-opioid receptor (DOP receptor) is neuroprotective against excitotoxic injury, we determined whether DOP receptor activation up-regulates EAAT expression and function.Experimental Approach: We measured mRNA and protein expression of EAAT1, EAAT2 and EAAT3 in cultured mouse astrocytes exposed to a specific DOP receptor agonist (UFP-512) with or without a DOP receptor antagonist, DOP receptor siRNA or inhibitors of PKC, PKA, PI3K, p38, MAPK, MEK and ERK, and evaluated the function of EAATs by measuring glutamate uptake.Key Results: Astrocytic DOP receptor mRNA and protein were suppressed by DOP receptor siRNA knockdown. DOP receptor activation increased mRNA and protein expression of EAAT1 and EAAT2, but not EAAT3, thereby enhancing glutamate uptake of astrocytes. DOP receptor-induced EAAT1 and EAAT2 expression was largely reversed by DOP receptor antagonist naltrindole or by DOP receptor siRNA knockdown, and suppressed by inhibitors of MEK, ERK and p38. DOP receptor-accelerated glutamate uptake was inhibited by EAAT blockers, DOP receptor siRNA knockdown or inhibitors of MEK, ERK or p38. In contrast, inhibitors of PKA, PKC or PI3K had no significant effect on DOP receptor-induced EAAT expression.Conclusions and Implications: DOP receptor activation up-regulates astrocytic EAATs via MEK-ERK-p38 signalling, suggesting a critical role for DOP receptors in the regulation of astrocytic EAATs and protection against neuroexcitotoxicity. As decreased EAAT expression contributes to pathophysiology in many neurological diseases, including amyotrophic lateral sclerosis, our findings present a new platform for potential treatments of these diseases. [ABSTRACT FROM AUTHOR]

Background and Purpose Astrocytic excitatory amino acid transporters ( EAATs) regulate extracellular glutamate concentrations and play a role in preventing neuroexcitotoxicity. As the δ-opioid receptor ( DOP receptor) is neuroprotective against excitotoxic injury, we determined whether DOP receptor activation up-regulates EAAT expression and function. Experimental Approach We measured m RNA and protein expression of EAAT1, EAAT2 and EAAT3 in cultured mouse astrocytes exposed to a specific DOP receptor agonist ( UFP-512) with or without a DOP receptor antagonist, DOP receptor siRNA or inhibitors of PKC, PKA, PI3K, p38, MAPK, MEK and ERK, and evaluated the function of EAATs by measuring glutamate uptake. Key Results Astrocytic DOP receptor mRNA and protein were suppressed by DOP receptor siRNA knockdown. DOP receptor activation increased mRNA and protein expression of EAAT1 and EAAT2, but not EAAT3, thereby enhancing glutamate uptake of astrocytes. DOP receptor-induced EAAT1 and EAAT2 expression was largely reversed by DOP receptor antagonist naltrindole or by DOP receptor siRNA knockdown, and suppressed by inhibitors of MEK, ERK and p38. DOP receptor-accelerated glutamate uptake was inhibited by EAAT blockers, DOP receptor siRNA knockdown or inhibitors of MEK, ERK or p38. In contrast, inhibitors of PKA, PKC or PI3K had no significant effect on DOP receptor-induced EAAT expression. Conclusions and Implications DOP receptor activation up-regulates astrocytic EAATs via MEK-ERK-p38 signalling, suggesting a critical role for DOP receptors in the regulation of astrocytic EAATs and protection against neuroexcitotoxicity. As decreased EAAT expression contributes to pathophysiology in many neurological diseases, including amyotrophic lateral sclerosis, our findings present a new platform for potential treatments of these diseases. [ABSTRACT FROM AUTHOR]

The radionuclide 125Xe plays an important role in diagnosing deuterium-tritium (DT) fuel areal density in inertial confinement fusion (ICF). Accurate data for the gamma emission intensities of 125Xe are highly desired. In this paper, after the 125Xe and 125I samples were prepared, the activity of 125I was determined by the sum-peak method using a high resolution well-type HPGe (High Purity Germanium) detector, and the activity of 125Xe was obtained by the decay relationship between 125Xe and 125I. The full-energy peak efficiencies of gamma-rays of 125Xe were accurately calibrated using standard radioactive sources. As a result, the absolute emission intensities of 125Xe for 12 gamma-rays were determined experimentally for the first time. • The absolute emission intensities of 125Xe have been determined experimentally for the first time. • High purity samples of 125Xe and its daughter 125I were prepared. • The activity of 125Xe was obtained based on 125I by the decay relationship between 125Xe and 125I. • The sum-peak method was adopted to determine the activity of 125I using well-type HPGe detector. [ABSTRACT FROM AUTHOR]

Abstract: Microglia are intrinsic immune cells in the central nervous system and play key roles in the pathogenesis of various central nervous system disorders. Microglia have been shown to attack damaged neurons by secreting a variety of neurotoxic factors including inflammatory cytokines, reactive oxygen species and glutamate. On the other hand, they can produce neurotrophic factors (NTFs) which support neuronal survival and growth. However, the precise mechanism that regulates microglial NTF production is not fully understood, and the relation between glutamate and NTFs remains unclear. In the present study, we show that glutamate significantly induces microglial NTF production by the activation of N-methyl-d-aspartate (NMDA) receptors, group III metabotropic glutamate receptors, and glutamate transporters. Activation of NMDA receptors and group III metabotropic glutamate receptors induces intracellular Ca2+ release from the endoplasmic reticulum. Further, stimulation of glutamate transporters leads to influx of extracellular Ca2+ in a Na+-dependent manner. This intracellular Ca2+ elevation activates the protein kinase C pathway which induces microglial NTF expression and production. These results suggest that microglia play a neuroprotective role during the excitotoxic state in neurodegenerative diseases. [Copyright &y& Elsevier]

The measurement of the 124Xe(n, 2n)123Xe reaction cross section at 14.8 MeV neutron has been performed by the activation method. Quasi monoenergetic neutron beams were produced at the Cockcroft Walton Accelerator of China Institute of Atomic Energy, by the T(d, n)4He reaction. A cell made of polymethyl methacrylate (PMMA) was used as the container of 124Xe (99.95% abundance) gas, and the mass of 124Xe in cell was determined by weighing method. Two high-purity thin 93Nb foils were attached to the cell and performed as monitors of the neutron flux determination by 93Nb(n, 2n)92mNb reaction. After the irradiation, the activities of 123Xe and 92mNb were measured by off-line gamma-ray spectrometric technique using a pre-calibrated HPGe detector. As a result, the cross section has been deduced at 14.8 MeV, and the result was compared with the literature data and evaluations. • The cross section of 124Xe(n, 2n)123Xe reaction has been measured at 14.8 MeV. • The method used were neutron activation and off-line gamma-ray spectrometry. • High purity 124Xe gas was used as the target sample, and low Z material cell was used as the container. [ABSTRACT FROM AUTHOR]

Abstract: We present a systematic study of local solutions of the ODE of the form near . Such ODEs occur in the study of self-similar radial solutions of some second order PDEs. A general theorem of existence and uniqueness is established. It is shown that there is a dichotomy between the cases and , where at . As an application, we study the singular behavior of self-similar radial solutions of a nonlinear wave equation with superlinear damping near an incoming light cone. A smoothing effect is observed as the incoming waves are focused at the tip of the cone. [Copyright &y& Elsevier]

Abstract: Glutamate-induced excitotoxicity is considered as a major cause of neurodegenerative disease. Excitatory amino acid transporters (EAATs) on glial cells are responsible for the homeostasis of extracellular glutamate in the central nervous system which may contribute to the prevention of excitotoxic neurodegeneration. However, the differential EAAT expression in astrocytes and microglia is not fully understood. In this study, we compared the expression of EAATs in astrocytes and microglia, and we assessed the neuroprotective and neurotoxic function of astrocytes and microglia by a co-culture system. RT-PCR analyses detected that astrocytes expressed each EAAT (EAAT1-5) whereas microglia did not express EAAT4. Western blot analyses demonstrated that astrocytes express a much larger amount of membrane-localized EAATs than microglia. Astrocytes prevented excito-neurotoxicity by the reduction of exogenous glutamate whereas microglia did not. Conversely, activated microglia released an excess of glutamate that induced excitotoxic neuronal death. Astrocytes rescued neurons from microglial glutamate-induced death in a ratio-dependent manner. Inhibition of EAATs abolished glutamate uptake and the neuroprotective effect of astrocytes, but it did not alter any microglial neurotoxic or neuroprotective effects. These results revealed that astrocytic EAATs can counteract microglial glutamate-induced neuronal death whereas microglial EAATs are inconsequential to neurotoxicity and neuroprotection. [Copyright &y& Elsevier]

Serofendic acid is a novel neuroprotective factor isolated from fetal calf serum. To elucidate the mechanisms how serofendic acid exerts neuroprotection, we examined its effects on glutamate-induced excito-toxicity in mouse cortical neurons. The effects of serofendic acid on inflammatory cytokine and neurotrophin production by glial cells were also examined to evaluate the indirect neuroprotection. Serofendic acid significantly and dose dependently increased survival of mouse cortical neurons after 10 μM N-methyl-D-asparate (NMDA) exposure. However, it did not affect production of inflammatory cytokines and neurotrophins by microglia as assessed by reverse transciption polymerase chain reaction (RT-PCR) for mRNA expression and ELISA for protein levels, though it suppressed tumor necrosis factor (TNF)-α production by astrocytes. Thus, serofendic acid works directly on neurons to protect against glutamate toxicity. Suppression of TNF-α production by astoryctes may also synergistically exert neuroprotective functions of serofendic acid. Serofendic acid may be of use for the future therapeutic strategy against ischemic and degenerative neurological disorders. [ABSTRACT FROM AUTHOR]

Drought stress is one of the crucial factors affecting plant growth and development in turfgrass species, especially during the summer season. Exogenous plant growth regulators are an effective and convenient approach to mitigating the adverse effects of drought stress on plant growth. The objectives of this study were to reveal the effects of exogenous carnosine or chitosan on turf performance and physiological indexes in bermudagrass (Cynodon transvaalensis × C. dactylon) in response to drought stress. Bermudagrass was foliar sprayed with carnosine or chitosan, and dose-dependent effects on turf quality were observed under drought stress. Under drought stress, foliar application of either carnosine (0.03%) or chitosan (10 mg L−1) significantly increased turf quality, chlorophyll content, leaf relative water content, and decreased electrolyte leakage, malonaldehyde, and hydrogen peroxide content in comparison with untreated control in bermudagrass. Moreover, exogenous carnosine treatment significantly enhanced the activities of both catalase and peroxidase, but chitosan application only increased catalase activity. The results of this experiment were beneficial to the development of new plant growth regulators and would provide helpful insights for turf management under drought-stressed conditions. [ABSTRACT FROM AUTHOR]

Background: Microvascular decompression (MVD) has become widely accepted for hemifacial spasm (HFS). The significance of facial nerve notch (FNN) for the outcome after MVD is still unknown.Objective: To investigate the correlative analysis between the FNN at the root exit zone (REZ) and the curative effect of MVD for HFS.Method: A prospective study was performed, which included 232 patients with Cohen score ≥2 who had undergone MVD. The patients were divided into two groups: the group with facial nerve notch (FNN) and the group without FNN, according to whether there is FNN caused by the offending vessels during the MVD operation. All the patients were followed up for 24 months.Results: The group with FNN caused by offending vessels at the REZ area was confirmed in 119 patients, of which 117 patients were immediately cured and two patients received partial relief on the 1st day of postoperation. The group without FNN at the REZ area was confirmed in 113 patients, of which 43 patients were immediately completely cured while 70 patients were not immediately completely cured after MVD operation. After 24 months of follow-up, 119 patients with FNN were all completely cured, 71 patients without FNN were completely cured, and 42 patients without FNN were not completely cured. Multivariate logistic regression analysis shows that compared with without FNN group, the FNN group had statistical significance for the clinical results both on the-1st -day (P < 0.01) and 2 years of follow-up (P < 0.05) after MVD operation.Conclusions: FNN is an important reference factor to evaluate both the short-term and long-term curative effect of microvascular decompression for hemifacial spasm. The postoperative effect of patients with FNN is much better than that of patients without FNN. [ABSTRACT FROM AUTHOR]

Cleft palate only (CPO) is one of the most common craniofacial birth defects. Environmental factors can induce cleft palate by affecting epigenetic modifications such as DNA methylation, histone acetylation, and non-coding RNA. However, there are few reports focusing on the RNA modifications. In this study, all-trans retinoic acid (atRA) was used to simulate environmental factors to induce a C57BL/6J fetal mouse cleft palate model. Techniques such as dot blotting and immunofluorescence were used to find the changes in m6A modification when cleft palate occurs. RNA-seq and KEGG analysis were used to screen for significantly differentially expressed pathways downstream. Primary mouse embryonic palate mesenchymal (MEPM) cells were successfully isolated and used for in vitro experimental verification. We found that an increased m6A methylation level was correlated with suppressed cell proliferation in the palatine process mesenchyme of cleft palate mice. This change is due to the abnormally high expression of m6A methyltransferase METTL14. When using siRNAs and the m6A methyltransferase complex inhibitor SAH to interfere with the expression or function of METTL14, the teratogenic effect of atRA on primary cells was partially alleviated. In conclusion, METTL14 regulates palatal mesenchymal cell proliferation and cycle-related protein expression relies on m6A methylation modification, affecting the occurrence of cleft palate. [ABSTRACT FROM AUTHOR]

The addition of zinc can induce the formation of polymetallic (Zn-Ni-Co) carbonate hydroxides/hydroxides (MCHs/M(OH) 2) heterostructure nanosheet array with rich defect structures on Ni foam as a superior cathode (ZNC/NF) for alkaline aqueous rechargeable Zn-based batteries (AAZBs). The as-made binder-free cathode offers an extremely high mass loading of 9.2 mg cm−2, exhibiting excellent areal capacities and energy densities. [Display omitted] Developing high mass loading cathodes with high capacity and durable life cycles is greatly worthwhile and challenging for alkaline aqueous rechargeable Zn-based batteries (AAZBs). Herein, we demonstrate an efficient zinc-induced strategy to rationally develop Zn-Ni-Co carbonate hydroxides/hydroxides heterostructure nanosheet array with an extremely high mass loading of 9.2 mg cm−2 on Ni foam (ZNC/NF) as such a superior cathode for AAZBs. It is discovered that Ni-Co hydroxide nanowires can be transformed into Zn-Ni-Co carbonate hydroxides/hydroxides heterostructure nanosheet with rich defect structures after the introduction of Zn during the synthetic process. The formed heterostructures and rich defect structures can enhance ion and electron transfer efficiency, thus ensuring the excellent electrochemical performance under high loading condition. Consequently, the ZNC/NF//Zn battery shows an outstanding areal capacity of 2.1 mAh cm−2 at 5 mA cm−2, with an ultrahigh energy density of 3.6 mWh cm−2. Moreover, the battery can still retain a high capacity of 0.42 mAh cm−2 after 5000 cycles at 50 mA cm−2, suggesting strong long-term cycling stability. This research enables pave the way for the rational design and manufacture of advanced electrode materials with large mass loadings. [ABSTRACT FROM AUTHOR]

Ferroptosis is a newly established form of regulated cell death characterized by intracellular lipid peroxidation and iron accumulation that may be a promising cancer treatment strategy. However, the function and therapeutic value of ferroptosis in oral squamous cell carcinoma (OSCC) remain inadequately understood. In the present study, we investigated the biological role of the fat mass and obesity-associated gene (FTO) in ferroptosis in the context of OSCC. We found that OSCC had greater potential for ferroptosis, and FTO is associated with ferroptosis. Furthermore, higher FTO expression sensitized OSCC cells to ferroptosis in vitro and in vivo. Mechanistically, FTO suppressed the expression of anti-ferroptotic factors, acyl-CoA synthetase long-chain family member 3 (ACSL3) and glutathione peroxidase 4 (GPX4), by demethylating the m6A modification on the mRNA of ACSL3 and GPX4 and decreasing their stability. Taken together, our findings revealed that FTO promotes ferroptosis through ACSL3 and GPX4 regulation. Thus, ferroptosis activation in OSCC with high FTO levels may serve as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

The glycolytic enzyme Hexokinase (HKII) participates in tumor glycolysis and the progression of various cancers, but its clinicopathological effect on the progression of tongue squamous cell carcinoma (TSCC) and its role in glycolysis, autophagy, and the epithelial-mesenchymal transition of TSCC in a hypoxic microenvironment remain unknown. Our results showed that HKII expression was dramatically increased in TSCC tissues and that its upregulation was significantly associated with the presence of pathological differentiation, lymph node metastasis, and clinical stage. The level of autophagy-specific protein LC3, EMT-related proteins, and the migration and invasion capabilities of TSCC cells all increased under hypoxia. Moreover, hypoxia increased the glucose consumption and lactate production of TSCC cells, and we demonstrated that the expression of the glycolytic key gene HKII was significantly higher than in that of the control group. Notably, the downregulation of HKII resulted in a significant decrease of TSCC cell glucose consumption lactate production and autophagic activity during hypoxia. HKII knockdown blocked the migratory and invasive capacity of TSCC cells and we specifically determined that the EMT ability decreased. Therefore, our findings revealed that the upregulation of HKII enhanced glycolysis and increased autophagy and the epithelial-mesenchymal transition of tongue squamous cell carcinoma under hypoxia. [ABSTRACT FROM AUTHOR]

We present an automated separation method to simultaneously isolate short-lived activation products 242g, 240Am, 237U, 72Ga from fresh fission products prior to gamma spectrometric analysis. On the basis of multi-column chromatographic units (HDEHP resin, TBP resin, DGA resin, TEVA resin, Al2O3, activated carbon) assembly, smart media compatibility between adjacent columns, chromatographic conditions optimization and process automation design, a modularized and streamline separation procedure was developed. The established method allows better recoveries of 93%, 91% and 97% for americium, uranium and gallium separately and excellent decontamination factors of more than 105 for fission products even for large volume of samples. Because of highly efficient removal of interferents, this method coupled with well-type high-purity germanium (HPGe) gamma spectrometers achieved highly sensitive and selective analysis of activation products in spiked complicated matrix samples. [ABSTRACT FROM AUTHOR]

• Suitable habitat and risk area of green tides around the world both have latitudinal zonality. • Sea surface wind is expected to aggravate green tides. • The dominant factors affecting green tides vary among different regions. • Revealing current and future development trend of green tide blooms. Green tides, which are widespread problems, are harmful issues that affect the protection of ocean ecosystems and natural resources. Scientific assessment and prevention of the green tides are essential for sustainable planning and the utilization of maritime traffic, tourism, and industry. However, the suitable or risk habitats and their dominant factors of green tides from global perspective are unknown. Here, this study proposed a novel framework to show the habitat suitability and risk of ocean green tides by considering marine environmental factors (i.e., sea surface temperature, sea surface salinity, solar irradiance, chlorophyll-a concentration, and sea surface wind). Through global remote sensing images and marine environmental factor data, this study found that (1) suitable and at-risk green tides areas are located in the north and south temperate zones; (2) marine physical factors are expected to weaken the green tide risk globally and enhance the green tide risk in coastal areas; (3) the green tides in the North Atlantic Ocean and the West Pacific Ocean are dominated by environmental factors and physical factors, respectively; and (4) when reducing carbon to promote sustainability, more potentially suitable green tide areas may appear at high latitudes. The results demonstrate the at-risk location and future trend of green tides, which are helpful for sustainable planning of ocean ecosystems. [Display omitted] [ABSTRACT FROM AUTHOR]

Gas insulated switchgears (GIS) have been widely used due to their high reliability, low maintenance and compact size. The field experiment is an important step to ensure the safety of GIS. The AC withstand voltage test and its corresponding partial discharge (PD) measurement are inadequate for the detection of all the hidden flaws in GIS. Such inadequacy can be compensated by additional impulse withstand voltage test and its PD detection measurement. This paper reports on experiments to study surface discharge over SF6/epoxy under impulse voltage. The TJ (triple-junction) model was used to study the characteristic of partial discharge (PD). The PD signals under four types of impulse voltages were detected by electrical methods. The 50% probability PD inception voltage (PDIV50), time lags and maximum discharge magnitude were analyzed as a function of gas pressure. The PD characteristics under AC voltage were investigated for comparison. The results indicate that the PD signals under impulse voltage can be detected using electrical method, the number of discharges under oscillating impulse voltage was significantly larger, which was due to the influence of source oscillation. The oscillating lightning impulse has the lowest impulse ratio and it is recommended as the best test waveform choice for the field impulse withstand test with PD detection. [ABSTRACT FROM PUBLISHER]

Cancer cells tend to live in hypoxic environment characterized by enhanced glycolysis and accumulation of lactate. Intracellular lactate is shown to drive a novel type of post-translational modification (PTM), lysine lactylation (Kla). Kla has been confirmed to affect the malignant progression of tumors such as hepatocellular carcinoma (HCC) and colon cancer, whereas the global lactylomic profiling of oral squamous cell carcinoma (OSCC) is unclear. Here, the integrative lactylome and proteome analyses by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 1011 Kla sites within 532 proteins and 1197 Kla sites within 608 proteins in SCC25 cells under normoxic and hypoxic environments, respectively. Among these lactylated proteins, histones accounted for only a small fraction, suggesting the presence of Kla modification of OSCC in a large number of non-histone proteins. Notably, Kla preferred to enrich in spliceosome, ribosome and glycolysis/gluconeogenesis pathway in both normoxic and hypoxic cultures. Compared with normoxia, 589 differential proteins with 898 differentially lactylated sites were detected under hypoxia, which were mainly associated with the glycolysis/gluconeogenesis pathway by KEGG analysis. Importantly, we verified the presence of lactylation modification in the spliceosomal proteins hnRNPA1, SF3A1, hnRNPU and SLU7, as well as in glycolytic enzyme PFKP. In addition, the differential alternative splicing analysis described the divergence of pre-mRNA splicing patterns in the presence or absence of sodium lactate and at different oxygen concentrations. Finally, a negative correlation between tissue Kla levels and the prognosis of OSCC patients was revealed by immunohistochemistry. Our study is the first report to elucidate the lactylome and its biological function in OSCC, which deepens our understanding of the mechanisms underlying OSCC progression and provides a novel strategy for targeted therapy for OSCC. [Display omitted] • Lysine-lactylation was prevalent in both histones and non-histones in OSCC. • Kla prefers to enrich in spliceosome, ribosome and glycolysis/gluconeogenesis pathway in OSCC under normoxic and hypoxic cultures. [ABSTRACT FROM AUTHOR]

Objective: The systemic inflammation response index (SIRI) is an independent prognostic factor for many malignant tumors. However, the value of this factor in patients with clinical T1‐2N0 (cT1‐2N0) oral squamous cell carcinoma (OSCC) is still unclear. Methods: We calculated SIRI of 235 cT1‐2N0 OSCC patients from 2013 to 2017. Multivariate cox regression analysis was applied to verify the prognostic significance of SIRI. Kaplan–Meier curves were plotted to analyze the overall survival (OS) and disease‐specific survival (DSS) for cT1‐2N0 OSCC patients. Results: According to the optimal cutoff point of SIRI, we divided cT1‐2N0 OSCC patients into high SIRI group (SIRI ≥ 1.3) and low SIRI group (SIRI < 1.3). SIRI was an independent prognostic indicator for OS (HR = 2.87; 95% CI = 1.35–6.10; p =.006) and DSS (HR = 2.17; 95% CI = 1.10–4.27; p =.025). High SIRI had a significantly poorer OS (p =.001) and DSS (p =.007) in survival analysis than the low SIRI. Moreover, the prognostic value of SIRI was significantly stronger than neutrophil‐to‐lymphocyte ratio (NLR) and monocyte‐to‐lymphocyte ratio (MLR). Conclusions: Preoperative SIRI can be regarded as a meaningful indicator for poor survival of cT1‐2N0 OSCC patients, and it is a promising tool to formulate the best individualized treatment for high‐risk patients. [ABSTRACT FROM AUTHOR]

To observe the protective effects of Salvia miltiorrhizae injection on multiple organs of rats with SAP or OJ. Two hundred eighty-eight rats were used for SAP-associated experiments and OJ-associated experiments. The rats were randomly divided into sham-operated, model control and treated group. According to the different time points after operation, the SAP rats in each group were subdivided into 3, 6 and 12 h groups while the OJ rats were divided into 7, 14, 21 and 28 days groups. The mortality rates, pathological changes and ICAM-1 (only in lung), TLR4 (only in liver), Bax and NF-κB proteins expression in multiple organs (liver, kidney, lung, intestinal mucosa, spleen, thymus and lymph nodes) were observed, respectively. The mortality rates of treated groups decreased in both SAP and OJ experiments. Compared to model control group, the pathological changes can be seen in treated groups including; (1) the pathological changes of multiple organs in SAP and OJ experiments were improved, the pathological severity scores of kidney (at 6 h), intestinal mucosa (at 12 h), spleen (at 6 and 12 h), thymus (at 3 and 6 h) and lymph nodes (at 3 and 6 h) in SAP experiment and of liver (on 21 and 28 days), lung (21 days), intestinal mucosa (on 21 and 28 days) and spleen (on 21 and 28 days) in OJ experiment significantly declined ( P < 0.05 or P < 0.01); (2) the positive rate of Bax protein in pancreas (at 3 h) and liver (on 6 and 12 h) in SAP experiment and in liver (on 28 days), kidney (on 21 days), and thymus (on 28 days) in OJ experiment were significantly lower ( P < 0.05 or P < 0.01); (3) the positive rate of NF-κB in liver (at 12 h) and kidney (at 6 h) in SAP experiment and in liver (on 21 days), kidney (on 28 days), intestinal mucosa (on 28 days) and thymus (on 14 days) in OJ experiment significantly decreased ( P < 0.05). (4) the positive rate of ICAM-1 in lungs (at 12 h) in SAP experiment was significantly less ( P < 0.05). Salvia miltiorrhizae injection can protect multiple organs of SAP or OJ rats and inhibit the expression of ICAM-1, TLR4, NF-κB and regulate Bax proteins. Salvia miltiorrhizae may relieve the inflammation response and enhance the immunity function of SAP and OJ rats. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the increasing trends of hypospadias and identify some of the perinatal risk factors that might be involved in Chinese newborns. Methods: The records from the neonatal intensive care unit were reviewed during a 10-year period. A case-control study was performed to compare the intrauterine growth status of the infants. Logistic regression analysis was used to assess the independent contribution of maternal factors to the risk of hypospadias. Results: Of 8364 male infants, 75 were diagnosed with hypospadias at birth. The overall incidence trend increased during the 10 years. Hypospadias was present more frequently in infants born small for gestational age (P < .0001), those with a very low birth weight (P < .0001), and preterm infants (P < .0001). An increased risk of hypospadias was found when mothers had had multiple births (odds ratio [OR] 2.58), were living in the countryside (OR 1.60), were engaged in outdoor (OR 1.62) or agricultural (OR 2.41) activities, and when the pregnancy was complicated by hypertension (OR 4.75), pre-eclampsia (OR 7.70), or hepatitis B antigen carrier status (OR 2.68). Maternal age (OR 0.98), parity (OR 0.93), and maternal occupational exposure as a housewife (OR 1.02), businesswoman (OR 1.1), or industrial/production worker (OR 0.84) were not associated with the risk of hypospadias. Conclusions: We found an increasing trend in the incidence of hypospadias among male infants in Chinese population in the past 10 years. Hypospadias was shown to be associated with poor intrauterine growth, maternal multiple births, living in a rural area, working outdoors and agricultural activities, hepatitis B antigen carrier status, hypertension, and pre-eclampsia of pregnancy. [Copyright &y& Elsevier]

Delta-opioid receptor (DOR) is widely distributed in the central nervous system, and its activation protects against ischaemic/hypoxic brain injury. However, the role of DOR in microglia in ischaemic stroke has not yet been fully investigated. We found that DOR was expressed in both human and mouse cerebral microglia, besides, it was upregulated in activated BV2 microglial cells by immunofluorescence staining and Western blot. DOR activation by the specific agonist TAN-67 significantly enhanced BV2 microglial cell viability and reduced apoptosis, as evidenced by decreased cleaved caspase-3 levels and TdT-mediated aUTP-X nick end labelling (TUNEL) staining after LPS stimulation. Furthermore, activation of DOR significantly inhibited inducible nitric oxide synthase (iNOS) production and dose-dependently inhibited the mRNA and protein expression levels of other pro-inflammatory cytokines, including IL-1β and IL-6, whereas it increased the expression of the anti-inflammatory cytokine IL-10 in LPS-stimulated BV2 microglial cells; these effects were correlated with diminished phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Moreover, these effects could be reversed by the DOR antagonist naltrindole. DOR activation can activate microglia to switch to the beneficial phenotype and inhibit LPS-induced inflammation and apoptosis via the mitogen-activated protein kinase (MAPK)/caspase-3 pathway in BV2 microglial cells. This study provides new insight into neuroprotection against and treatment of ischaemic stroke. [ABSTRACT FROM AUTHOR]

Highlights • Tigecycline was prescribed as for an 'off label' indication in 91% children. • Clinical success was reported in 86% of the patients. • No serious adverse effects of tigecycline were detected in the patients. Abstract Objective The aim of this study was to evaluate the efficacy and safety of salvage therapy of tigecycline in critically ill children with infections caused by multidrug-resistant (MDR)/extensively drug-resistant (XDR) bacteria after surgery. Methods A retrospective chart review was performed of critically ill children after surgery who had received tigecycline for ≥3 days between June 2012 and May 2016 in the surgical intensive care unit of a tertiary level children's hospital. Results Of 6442 consecutive children admitted after surgery, a total of 22 were enrolled. They had a median age of 7.5 months (interquartile range (IQR), 6 months to 4 years) and a median weight of 7.3 kg (IQR, 5.1–12.5 kg). Patients received tigecycline for a median 17 days (IQR, 12–20 days). The median intensive care unit stay was 56 days (IQR, 38–61 days) and median hospital stay was 78 days (IQR, 61–94 days). Tigecycline was prescribed as culture-directed therapy in 91% of patients and as empirical therapy in 9%. Clinical success was reported in 86% of the patients. The all-cause mortality in this cohort was 18%. No serious adverse effects of tigecycline were detected in these patients. Conclusions Tigecycline salvage therapy was successful in 86% of critically ill pediatric patients with MDR/XDR infections after surgery, with no severe adverse effects. [ABSTRACT FROM AUTHOR]

The tumor starvation microenvironment plays a pivotal role in the malignant progression of cancer, which is closely related to autophagy, glycolysis, and epithelial mesenchymal transition (EMT). Nevertheless, the underlying mechanisms of the starvation-mediated malignant phenotype are still not well documented. In this study, we aimed to investigate the effect of starvation on glycolysis, autophagy, and EMT in OSCC and to further elucidate the key metabolic modulator. The results showed that starvation can induce autophagy, EMT, and enhanced glycolysis in OSCC cells. We determined that the expression of the key glycolytic enzyme phosphofructokinase-platelet (PFKP) obviously increased under starvation conditions and that PFKP knockdown inhibited starvation-mediated glycolysis, autophagy and EMT in OSCC cells. Moreover, we confirmed that PFKP knockdown inhibited OSCC xenograft growth in vivo. In addition, PFKP expression was significantly increased in OSCC patients and its upregulation was associated with the presence of tumor pathological differentiation and lymph node metastasis. Taken together, our findings demonstrate that PFKP is necessary for starvation-mediated autophagy, glycolysis, and EMT, thereby promoting the malignant progression of OSCC. [ABSTRACT FROM AUTHOR]

Humic substances (HS) including humic acid (HA) and fulvic acid (FA) are ubiquitous in the natural waters. Although numerous studies documented their role in photodegradation of organic pollutants, the competitive effects of photosensitization and light-screening of HS on the photodegradation of pollutants are not yet clear. In this work, the role of HS in the photodegradation of the pharmaceutical naproxen (NP) was studied under simulated sunlight. The direct photodegradation quantum yield of NP in deionized water was 2.1 × 10 −2 , and the apparent quantum yields for photosensitized degradation of NP in the presence of FA and HA were 2.3 × 10 −4 and 2.6 × 10 −5 , respectively. Both direct and photosensitized photodegradation decreased with increasing pH, consistent with the trend of singlet oxygen ( 1 O 2 ) reaction rate constants of NP. HA inhibited the photodegradation of naproxen thoroughly. In contrast, FA accelerated the photodegradation of NP at lower substrate concentration and light intensity, and vice versa. Direct photodegradation of NP declined sharply with spectral radiation attenuation of UV region, when HS-mediated photosensitization predominantly accounted for the photodegradation. The direct photodegradation was ascribed to decomposition of excited triplet state of naproxen ( 3 NP ∗ ) and self-sensitization effect involving 1 O 2 . The FA-mediated photodegradation was mainly attributed to 1 O 2 oxidation in aerated solution. These findings are important for assessing the competitive effects of humic substances on the photodegradation of pollutants under various conditions in natural waters. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/β-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/β-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy. [ABSTRACT FROM AUTHOR]

Separation of Am from Sm is very important for gamma spectrometric analysis of 242gAm in some specific samples, and also represents a very difficult challenge due to their similar chemical properties. Here we report a novel automated separation procedure based on two-stage HDEHP extraction chromatography to achieve the fast and highly efficient separation of Am from Sm. The two-stage HDEHP extraction chromatography was established by using HDEHP resin as the stationary phase, and DTPA-lactic acid and HNO 3 as the mobile phases respectively. The automated separation method can be realized through process automation design. As a result, the recovery of Am is above 90%, and the decontamination factor (DF) for Sm reaches 2 × 107. The separation speed is improved and the radiation damage of radionuclides to the analysts is greatly reduced. So, this automated separation procedure developed in this work is certified to be convenient and efficient for the analysis of low activity 242gAm in the complex samples. [Display omitted] • A novel two-stage HDEHP extraction chromatography was developed to separation Am from Sm. • Automated separation technique was established to rapidly isolate short-lived nuclide in strong radiation sample. • It presents a good separation performance and repeatability with high recovery of Am (above 90%) and high DF for Sm (2 × 107). • This method is applicable for the gamma spectrometric analysis of 242gAm in some specific samples. [ABSTRACT FROM AUTHOR]

Summary Objectives The role of autophagy is still a controversy in cancer development. In our previous study, we confirmed that decrease of autophagy activity promotes malignant progression of tongue squamous cell carcinoma (TSCC). However, the role of autophagy-related protein, Beclin1, has not well been documented in TSCC. In this study, we aim to elucidate the role of beclin1 in TSCC progression and investigate its potential mechanisms. Materials and methods TSCC cell lines, SCC9 and SCC15 were used to generate the stable cells with transfection lentivirus BECN1 and sh-BECN1. Then, Beclin1 expression was detected with qPCR and western blot. Moreover, the expressions of autophagy-related proteins and tumor metastasis associated proteins were examined by western blot and ELISA. For functional analysis, MTT assay were performed to evaluate the proliferation activity and transwell assay was used to assess the migration and invasion ability. Finally, TSCC xenograft models were established to confirm the effect of Beclin1 on TSCC in vivo. Results The results showed that BECN1 and sh-BECN1 virus transfection significantly increased or decreased the mRNA and protein expression of Beclin1 in the transfected TSCC cells. Meanwhile, we also observed that Beclin1 could enhance the expression levels of LC3-II, ATG4 and ATG5. Then, we revealed that overexpression of Beclin1 inhibited proliferation, migration and invasion while knockdown of Beclin1 promoted proliferation, migration and invasion in TSCC cells. Furthermore, we demonstrated that vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 were involved in Beclin1-mediated inhibition of migration and invasion. More importantly, our data also confirmed that Beclin1 inhibited TSCC xenograft growth in vivo. Conclusion Taken together, the results indicate that autophagy regulating gene, Beclin1, may contribute to the malignant phenotypes of TSCC cells and can be a potential target for oral cancer gene therapy. [ABSTRACT FROM AUTHOR]

Abstract: The Gaijing Pb–Zn–Mo deposit and Shapinggou Mo deposit in the Yinshan region, Jinzhai, Anhui province, China, are hosted in various granitic intrusions with 40Ar/39Ar ages obtained for biotite and hornblende of 136.8±1.6Ma (medium-grained monzogranite), 130.4±1.2Ma (fine-grained granite), and 125.4±1.0Ma (fine-grained diorite). The modes of occurrence and cross-cutting relationships among the igneous intrusions indicate that alkali quartz-syenite and quartz-syenite porphyry (cryptoexplosive breccia) formed later than the calc-alkali monzogranite, granite, and diorite. Molybdenum mineralization occurs in pipe-like bodies hosted in cryptoexplosive breccia (pipe), quartz-syenite (porphyry), monzogranite, and granite, whereas Pb–Zn mineralization occurs in veins distally from the Mo mineralization. The Re–Os isotopic model ages of molybdenite from the Gaijing Pb–Zn–Mo deposit are 112.6±1.3 and 113.5±1.3Ma, consistent with the ages of other molybdenum deposits throughout the East Qinling–Dabie metallogenic belt. The geological characteristics and isotopic ages of the Gaijing Pb–Zn–Mo and Shapinggou Mo deposits indicate a genetic relationship to the emplacement of the quartz-syenite (porphyry) and to shallow-seated porphyry–cryptoexplosive breccia intrusions. The present results, combined with existing data, suggest that the Pb–Zn–Mo deposits and related igneous rocks were formed in a geodynamic setting of regional lithospheric thinning, delamination, and thermal erosion in East China. The deposits are part of the East Qinling–Dabie molybdenum belt, which in turn is part of a large-scale E–W-trending metallogenic belt in East China. [Copyright &y& Elsevier]

Background: Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases. Methods and Findings: In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid b deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model. Conclusions: Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal death in various neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Abstract: We have shown previously, that the most neurotoxic factor from activated microglia is glutamate that is produced by glutaminase utilizing extracellular glutamine as a substrate. Drugs that inhibit glutaminase or gap junction through which the glutamate is released were effective in reducing neurotoxic activity of microglia. In this study, to elucidate whether or not a similar mechanism is operating in macrophages infiltrating into the central nervous system during inflammatory, demyelinating, and ischemic brain diseases, we examined the neurotoxicity induced by macrophages, in comparison with microglia in vitro. LPS- or TNF-α-stimulated macrophage-conditioned media induced robust neurotoxicity, which was completely inhibited by the NMDA receptor antagonist MK801. Both the glutaminase inhibitor 6-diazo-5-oxo-l-norleucine (DON), and the gap junction inhibitor carbenoxolone (CBX), effectively suppressed glutamate production and subsequent neurotoxicity by activated macrophages. These results revealed that macrophages produce glutamate via glutaminase from extracelluar glutamine, and release it through gap junctions. This study demonstrated that a similar machinery is operating in macrophages as well, and DON and CBX that prevent microglia-mediated neurotoxicity should be effective for preventing macrophage-mediated neurotoxicity. Thus, these drugs may be effective therapeutic reagents for inflammatory, demyelinating, and ischemic brain diseases. [Copyright &y& Elsevier]

Mid- and long-half-life artificial radioisotopes in the earth's surface environment are of great concern to the environmental radiation risk assessment. As nuclear fuel and fission products, 239Pu, 240Pu, 241Am, 90Sr and 137Cs in soils from Inner Mongolia of China were analyzed with a modified systematic separation procedure combined with ICP-MS and LSC measurements, to study the level, distribution and source of artificial radionuclides in the region. The radioactivity and inventory of 137Cs (0.26–28.3 Bq/kg, 0.5–5.4 kBq/m2), 239+240Pu (0.05–1.26 Bq/kg, 20-229 Bq/m2), 241Am (0.036–0.35 Bq/kg, 11-81 Bq/m2) and 90Sr (1.2–7.6 Bq/kg, 0.39–1.7 kBq/m2) all lie in the range of the global fallout. Vertical distributions of these radionuclides were examined for two soil core samples SC14025 and SC14038, and great differences were observed between these two sample locations. For SC14025 where little human disturbance to soil occurred, both 137Cs and 239+240Pu have a subsurface activity maximum followed by an exponential decay. Fittings base on CDE model gives a small downward migration velocity of about 0.097 cm/y for both Pu and 137Cs. Source identification for SC14025 and SC14038 soil cores with 240Pu/239Pu (average of 0.180 ± 0.017 and 0.164 ± 0.035, respectively), 137Cs/239+240Pu (average of 25.3 ± 0.6 and 25.6 ± 3.0, respectively) and 241Am/239+240Pu (average of 0.56 ± 0.08 and 0.60 ± 0.09, respectively) ratios consistently indicated that anthropogenic radionuclides in Xilingol region are mostly from the global fallout of atmospheric nuclear weapons tests in the last century. According to the geographical distribution of the radioactivity level, the high radioactivity level in the east of Inner Mongolia probably results from enhanced deposition by the blocking of the Great Khingan Range. • Multi-fingerprints indicate the radionuclides in studied areas are mostly from the global fallout. • Downward migration of 239Pu and 137Cs is similar and low while 90Sr migrates much faster. • High radioactivity level might result from enhanced deposition by mountain blocking. [ABSTRACT FROM AUTHOR]

Abstract: Glutamate released by activated microglia induces excito-neurotoxicity and may contribute to neurodegeneration in numerous neurological diseases including ischemia, inflammation, epilepsy, and neurodegenerative diseases. We observed that the gap junction blocker carbenoxolone (CBX) or the glutaminase inhibitor 6-diazo-5-oxo-l-norleucine (DON) decreased glutamate release from activated microglia and rescued neuronal death in a dose-dependent manner in vitro. In gerbils, treatment with CBX or DON also prevented the delayed death of hippocampal neurons following transient global ischemia. Thus, blockade of microglial glutamate release may be an effective therapeutic strategy against neurodegeneration after ischemic injury. [Copyright &y& Elsevier]

As we all know, in the process of complex synthesis, the solvent and coordination environment can make a great change in the structure and properties of the complex. Here, we successfully obtained a series of Dy(III) complexes [Dy(H 2 L1)(H L1)] (1), [Dy 2 (H L1) 2 (CH 3 COO) 2 (DMF) 2 (2) and [Dy 4 (L1) 4 (CH 3 OH) 4 (3) by using (E)-2-hydroxy- N '-((8-hydroxyquinolin-2-yl)methylene)benzohydrazide (H 3 L1) and Dy(CH 3 COO) 3 ·6H 2 O under 80 ​°C in different solvent. In the complexes 1 and 2 , the O on the phenolic hydroxyl group of the ligands were not coordinated with Dy(III) ions. But for complex 3 , with the increase of the number of Dy(III) ions, in order to meet the coordination saturation of Dy(III) ion, the oxygen on the phenolic hydroxyl was twisted to N,O in the direction of the chelate point and participated in the coordination with them. AC magnetic susceptibilities exhibited that complexes 1 and 2 showed weak out-of-phase (χ ") component of ac-susceptibilities at zero Oe static magnetic field over the frequency range of 9–999 ​Hz. Complex 3 showed clear single-molecule magnetic behavior, which energy barrier was 19.3 (1) K. Three different Dy(III) ion complexes, which the ligands coordinated modes were different because of different solvent. The AC magnetic susceptibility studies suggested that complex 1 and 2 revealed weak slow magnetic relaxation at out of phase, but complex 3 exhibited a obvious SMM behavior. Image 1 • Synthesis a series of Dy (III) complexes in different solvent environments. • Complexes 1 and 2 exhibited weak SMM behavior, but complex 3 was an obvious SMM. • This paper provided an example for the study of solvent effected the complex of synthesis. [ABSTRACT FROM AUTHOR]

The world's largest macroalgal blooms, Ulva prolifera, have appeared in the Yellow Sea every summer on different scales since 2007, causing great harm to the regional marine economy. In this study, the Normalized Difference of Vegetation Index (NDVI) index was used to extract the green tide of Ulva prolifera from MODIS images in the Yellow Sea in 2016–2018, to investigate its spatiotemporal patterns and to calculate its occurrence probability. Using the standard deviational ellipse (SDE), the morphological characteristics of the green tide, including directionality and regularity, were analyzed. The results showed that the largest distribution and coverage areas occurred in 2016, with 57,384 km2 and 2906 km2, respectively and that the total affected region during three years was 163,162 km2. The green tide drifted northward and died out near Qingdao, Shandong Province, which was found to be a high-risk region. The coast of Jiangsu Province was believed to be the source of Ulva prolifera, but it was probably not the only one. The regularity of the boundary shape of the distribution showed a change that was opposite to the variation of scale. Several sharp increases were found in the parameters of the SDE in all three years. In conclusion, the overall situation of Ulva prolifera was still severe in recent years, and the sea area near Qingdao became the worst hit area of the green tide event. It was also shown that the sea surface wind played an important part in its migration and morphological changes. [ABSTRACT FROM AUTHOR]

Background: The association between intracranial aneurysms and arteriovenous malformations (AVMs) or dural arteriovenous fistulas (DAVFs) has been well documented, and the changes in cerebral blood flow dynamics were thought to be one of the major causes. There has not been a report on intracranial aneurysms associated with multiple DAVFs and AVMs in the same patient. Methods: The authors report a unique case of multiple intracranial vascular pathologies, including 5 aneurysms, 2 DAVFs, and 1 AVM coexisting in a single patient. The patient presented with headache and left hemiparesis and was found to have 4 bilateral internal carotid aneurysms, 1 ruptured right pericallosal aneurysm, 2 frontoparietal DAVFs, and 1 right temporal AVM. Results: Endovascular coiling and Onyx embolization successfully occluded 4 aneurysms and both DAVFs. The patient remained asymptomatic at 1-year follow-up. Conclusions: To our knowledge, this is the first report of a very rare case with a unique combination of cerebrovascular pathologies including multiple aneurysms, DAVFs, and 1 high-grade AVM. Analyzing the hemodynamic relationships of these concurrent lesions is essential to determine the hemorrhage risk of each lesion and the order of priority in management. Flow-related aneurysms with irregular morphology require early, aggressive treatment. [Copyright &y& Elsevier]