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The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR). Comparative structure analysis revealed that distinct from vertebrate GPH β subunits, Sc-GPB5 was less conserved, showing an atypical N-terminal sequence with a type II transmembrane domain instead of a typical signal peptide. By investigating the presence of recombinant Sc-GPA2 and Sc-GPB5 in cell lysates and culture media of HEK293T cells, we confirmed that these two subunits could be secreted out of the cells via distinct secretory pathways. The deglycosylation experiments demonstrated that N-linked glycosylation only occurred on the conserved cysteine residue (N78) of Sc-GPA2, whereas Sc-GPB5 was non-glycosylated. Although Sc-GPB5 exhibited distinct topology and biochemical properties in contrast to its chordate counterparts, it could still interact with Sc-GPA2 to form a heterodimer. The Sc-GPHR was then confirmed to be activated by tethered Sc-GPA2/GPB5 heterodimer on the Gs-cAMP pathway, suggesting that Sc-GPA2/GPB5 heterodimer-initiated Gs-cAMP signaling pathway is evolutionarily conserved in chordates. Furthermore, in situ hybridization and RT-PCR results revealed the co-expression patterns of Sc-GPA2 and Sc-GPB5 with Sc-GPHR transcripts, respectively in ascidian larvae and adults, highlighting the potential functions of Sc-GPA2/GPB5 heterodimer as an autocrine/paracrine neurohormone in regulating metamorphosis of larvae and physiological functions of adults. Our study systematically investigated the GPA2/GPB5-GPHR system in ascidian for the first time, which offers insights into understanding the function and evolution of the GPH system within the chordate lineage.

In this paper, the structural and electronic properties of P/SnBr2 heterojunctions were investigated using the first-principles calculation method based on the density functional theory (DFT). The band alignment of the P/SnBr2 heterojunction was type I. The bandgap value was 0.71 eV in the DFT calculation. Furthermore, the bandgap of the heterojunction could be efficiently tuned by controlling an electric field and biaxial strain. The bandgap changed linearly with the electric field in a certain range; when the electric field was greater than 0.8 V/Å, the heterojunction was metallic. The bandgap could also be tuned when a biaxial strain was applied. Under tensile or compressive stress, significant effects such as the band alignment shift from type I to type III, and the transition from indirect to direct bandgap occurred. In conclusion, these research findings provide theoretical guidance for designing new heterojunctions based on SnBr2.

In this study, we performed the genome-wide domain analysis and sequence alignment on the genome of Styela clava, and obtained a repertoire of 204 putative GPCRs, which exhibited a highly reduced gene number compared to vertebrates and cephalochordates. In this repertoire, six Class C GPCRs, including four metabotropic glutamate receptors (Sc-GRMs), one calcium-sensing receptor (Sc-CaSR), and one gamma-aminobutyric acid (GABA) type B receptor 2-like (Sc-GABABR2-like) were identified, with the absence of type 1 taste and vomeronasal receptors. All the Sc-GRMs and Sc-CaSR contained the typical “Venus flytrap” and cysteine-rich domains required for ligand binding and subsequent propagation of conformational changes. In swimming larvae, Sc-grm3 and Sc-casr were mainly expressed at the junction of the sensory vesicle and tail nerve cord while the transcripts of Sc-grm4, Sc-grm7a, and Sc-grm7b appeared at the anterior trunk, which suggested their important functions in neurotransmission. The high expression of these Class C receptors at tail-regression and metamorphic juvenile stages hinted at their potential involvement in regulating metamorphosis. In adults, the transcripts were highly expressed in several peripheral tissues, raising the possibility that S. clava Class C GPCRs might function as neurotransmission modulators peripherally after metamorphosis. Our study systematically characterized the ancestral chordate Class C GPCRs to provide insights into the origin and evolution of these receptors in chordates and their roles in regulating physiological and morphogenetic changes relevant to the development and environmental adaption.

This study aimed to investigate the clinical efficacy of intracranial pressure (ICP) monitoring regarding the perioperative management of patients with severe traumatic brain injury (sTBI). This was a cohort study performed between Jan 2013 and Jan 2016 and included all patients with sTBI. All patients were split into ICP monitoring and non-ICP monitoring groups. The primary outcomes were in-hospital mortality and Glasgow Outcome Scale (GOS) scores 6 months after injury, whereas the secondary outcomes include rate of successful nonsurgical treatment, rate of decompression craniotomy (DC), the length of stay in the ICU, and the hospital and medical expenses. This retrospective analysis included 246 ICP monitoring sTBI patients and 695 without ICP monitoring sTBI patients. No significant difference between groups regarding patient demographics. All patients underwent a GOS assessment 6 months after surgery. Compared to the non-ICP monitoring group, a lower in-hospital mortality (20.3% vs 30.2%, P < 0.01) and better GOS scores after 6 months (3.3 ± 1.6 vs 2.9 ± 1.6, P < 0.05) with ICP monitoring. In addition, patients in the ICP monitoring group had a lower craniotomy rate (41.1% vs 50.9%, P < 0.01) and a lower DC rate (41.6% vs 55.9%, P < 0.05) than those in the non-ICP monitoring group. ICU length of stay (12.4 ± 4.0 days vs 10.2 ± 4.8 days, P < 0.01) was shorter in the non-ICP monitoring group, but it had no difference between 2 groups on total length of hospital stay (22.9 ± 13.6 days vs 24.6 ± 13.6 days, P = 0.108); Furthermore, the medical expenses were significantly higher in the non-ICP monitoring group than the ICP monitoring group (11.5 ± 7.2 vs 13.3 ± 9.1, P < 0.01). Intracranial pressure monitoring has beneficial effects for sTBI during the perioperative period. It can reduce the in-hospital mortality and DC rate and also can improve the 6-month outcomes. However, this was a single institution and observational study, well-designed, multicenter, randomized control trials are needed to evaluate the effects of ICP monitoring for perioperative sTBI patients.

Agonists of glucocorticoid receptor (GR) are frequently given to cancer patients with platinum-containing chemotherapy to reduce inflammation, but how GR influences tumor growth in response to platinum-based chemotherapy such as cisplatin through inflammation-independent signaling remains largely unclear. Combined genomics and transcription factor profiling reveal that MAST1, a critical platinum resistance factor that reprograms the MAPK pathway, is upregulated upon cisplatin exposure through activated transcription factor GR. Mechanistically, cisplatin binds to C622 in GR and recruits GR to the nucleus for its activation, which induces MAST1 expression and consequently reactivates MEK signaling. GR nuclear translocation and MAST1 upregulation coordinately occur in patient tumors collected after platinum treatment, and align with patient treatment resistance. Co-treatment with dexamethasone and cisplatin restores cisplatin-resistant tumor growth, whereas addition of the MAST1 inhibitor lestaurtinib abrogates tumor growth while preserving the inhibitory effect of dexamethasone on inflammation in vivo. These findings not only provide insights into the underlying mechanism of GR in cisplatin resistance but also offer an effective alternative therapeutic strategy to improve the clinical outcome of patients receiving platinum-based chemotherapy with GR agonists., Glucocorticoid receptor (GR) agonists - used in the treatment of solid malignant tumors to reduce inflammation - could potentially affect the anti-tumor activity of chemotherapy. Here, the authors identify a mechanism of cisplatin resistance observed with GR agonist treatment, and show the binding and activation of GR by cisplatin, which leads to MAST1 activation and subsequent MAPK re-activation.

Dysfunction of ionotropic glutamate receptors (iGluRs) is a key molecular mechanism of excitotoxic neuronal injury following traumatic brain injury (TBI). Edonerpic maleate is a low molecular-weight compound that was screened as a candidate neuroprotective agent. In this study, we investigated its effects on TBI and GluRs signaling. Traumatic neuronal injury (TNI) induced by scratch followed by glutamate treatment was performed to mimic TBI in vitro. Edonerpic maleate at 1 and 10 μM exerted protective activity when it was added within 2 h following injury. The protective activities were also confirmed by the reduction of lipid peroxidation and oxidative stress. In addition, edonerpic maleate inhibited the expression of surface NR2B, total GluR1, and surface GluR1, and mitigated the intracellular Ca2+ responses following injury in vitro. Western blot analysis showed that edonerpic maleate reduced the cleavage of collapsing response mediator protein 2 (CRMP2), but increased the expression of postsynaptic protein Arc. By using gene overexpression and silencing technologies, CRMP2 was overexpressed and Arc was knockdown in cortical neurons. The results showed that the effect of edonerpic maleate on NMDA receptor expression was mediated by CRMP2, whereas the edonerpic maleate-induced AMPA receptor regulation was dependent on Arc activation. In in vivo TBI model, 30 mg/kg edonerpic maleate alleviated the TBI-induced brain edema, neuronal loss, and microglial activation, with no effect on locomotor function at 24 h. However, edonerpic maleate improves long-term neurological function after TBI. Furthermore, edonerpic maleate inhibited CRMP2 cleavage but increased Arc activation in vivo. In summary, our results identify edonerpic maleate as a clinically potent small compound with which to attenuate TBI-related brain damage through regulating GluRs signaling.

The melanocortin-3 receptor (MC3R) is known to be involved in regulation of energy homeostasis, regulating feed efficiency and nutrient partitioning in mammals. Its physiological roles in non-mammalian vertebrates, especially economically important aquaculture species, are not well understood. Channel catfish (Ictalurus punctatus) is the main freshwater aquaculture species in North America. In this study, we characterized the channel catfish MC3R. The mc3r of channel catfish encoded a putative protein (ipMC3R) of 367 amino acids. We transfected HEK293T cells with ipMC3R plasmid for functional studies. Five agonists, including adrenocorticotropin, α-melanocyte stimulating hormone (α-MSH), β-MSH, [Nle4, D-Phe7]-α-MSH, and D-Trp8-γ-MSH, were used in the pharmacological studies. Our results showed that ipMC3R bound β-MSH with higher affinity and D-Trp8-γ-MSH with lower affinity compared with human MC3R. All agonists could stimulate ipMC3R and increase intracellular cAMP production with sub-nanomolar potencies. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation could also be triggered by ipMC3R. The ipMC3R exhibited constitutive activities in both cAMP and ERK1/2 pathways, and Agouti-related protein served as an inverse agonist at ipMC3R, potently inhibiting the high basal cAMP level. Moreover, we showed that melanocortin receptor accessory protein 2 (MRAP2) preferentially modulated ipMC3R in cAMP production rather than ERK1/2 activation. Our study will assist further investigation of the physiological roles of the ipMC3R, especially in energy homeostasis, in channel catfish.

Epilepsy is a neurological disorder which is characterized by brain hyper-excitability and manifests as seizure. Due to its complicated pathogenesis, treatment for epilepsy still remains a huge challenge for neurology in the whole world. MciroRNA-134 (miR-134) is one kind of miRNAs which was firstly found abundant in synapses. In this study, we tried to unveil the role of inhibiting MciroRNA-134-5p (miR-134-5p) in excitotoxicity induced by kainic acid (KA) in the hippocampal neurons (HT22) cells. The results showed that treatment of KA increased the expression of miR-134-5p significantly and caused marked neuron excitotoxicity, evidenced by risen cell death rate, higher LDH release and aggravated cell viability. After suppressing miR-134-5p expression via transfecting HT22 cells with miR-134-5p antisense (Anti-134), cell viability was promoted obviously, along with decreased LDH release and cell death rate. In addition, KA-induced lipid peroxidation, cytochrome c release and mitochondrial ROS generation were also attenuated by Anti-134. The level of Sirtuin 3 (Sirt3) and its downstream antioxidant enzymes, such as mitochondrial superoxide dismutase 2 (SOD2), isocitrate dehydrogenase 2 (IDH2) and glutathione peroxidase (GSH-Px), were significantly higher in Anti-134 group compared with the control and scramble group. After inhibiting Sirt3 expression with SiRNA targeting Sirt3 (Si-Sirt3) and 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), the positive role of Anti-134 was apparently reversed. In conclusion, this research highly suggests that inhibition of miR-134-5p could protect neurons from KA-induced excitotoxicity through Sirt3-mediated preservation of mitochondrial function.

The melanocortin-4 receptor (MC4R) is a member of the G-protein-coupled receptor (GPCR) superfamily, which has been extensively studied in obesity pathogenesis due to its critical role in regulating energy homeostasis. Both the Gs-cAMP and ERK1/2 cascades are known as important intracellular signaling pathways initiated by the MC4R. The DRYxxI motif at the end of transmembrane domain 3 and the intracellular loop 2 (ICL2) are thought to be crucial for receptor function in several GPCRs. To study the functions of this domain in MC4R, we performed alanine-scanning mutagenesis on seventeen residues. We showed that one residue was critical for receptor cell surface expression. Eight residues were important for ligand binding. Mutations of three residues impaired Gs-cAMP signaling without changing the binding properties. Investigation on constitutive activities of all the mutants in the cAMP pathway revealed that six residues were involved in constraining the receptor in inactive states and five residues were important for receptor activation in the absence of an agonist. In addition, mutations of four residues impaired the ligand-stimulated ERK1/2 signaling pathway without affecting the binding properties. We also showed that some mutants were biased to the Gs-cAMP or ERK1/2 signaling pathway. In summary, we demonstrated that the DRYxxI motif and ICL2 were important for MC4R function.

Cerebral ischemia results in severe brain damage, and is a leading cause of death and long-term disability. Previous studies have investigated methods to activate astrocytes in order to promote repair in injured brain tissue and inhibit cell death. It has previously been shown that N-myc downstream-regulated gene 2 (NDRG2) was highly expressed in astrocytes and associated with cell activity, but the underlying mechanism is largely unknown. The present study generated NDRG2 conditional knockout (Ndrg2-/-) mice to investigate whether NDRG2 can block ischemia-induced astrocyte necroptosis by suppressing receptor interacting protein kinase 1 (RIPK1) expression. This study investigated astrocyte activity in cerebral ischemia, and identified that ischemic brain injuries could trigger RIP-dependent astrocyte necroptosis. The depletion of NDRG2 was found to accelerate permanent middle cerebral artery occlusion-induced necroptosis in the brain tissue of Ndrg2-/- mice, indicating that NDRG2 may act as a neuroprotector during cerebral ischemic injury. The present study suggested that NDRG2 attenuated astrocytic cell death via the suppression of RIPK1. The pharmacological inhibition of astrocyte necroptosis by necrostatin-1 provided neuroprotection against ischemic brain injuries after NDRG2 knockdown. Therefore, NDRG2 could be considered as a potential target for the treatment of cerebral ischemia.

G protein-coupled receptors (GPCRs) play critical roles in transmitting a variety of extracellular signals into the cells and regulate diverse physiological functions. Naturally occurring mutations that result in dysfunctions of GPCRs have been known as the causes of numerous diseases. Significant progresses have been made in elucidating the pathophysiology of diseases caused by mutations. The multiple intracellular signaling pathways, such as G protein-dependent and β-arrestin-dependent signaling, in conjunction with recent advances on biased agonism, have broadened the view on the molecular mechanism of disease pathogenesis. This review aims to briefly discuss biased agonism of GPCRs (biased ligands and biased receptors), summarize the naturally occurring GPCR mutations that cause biased signaling, and propose the potential pathophysiological relevance of biased mutant GPCRs associated with various endocrine diseases.

Naphthenic acids (NAs) are cycloalkyl linear carboxylic acids primarily originating from oil sand tailings water (OSTW), and the exposure to NAs affects the photosynthesis of marine microalgaes. However, the transcriptional response upon the stress of NAs remains unclear. Herein, we investigate the transcriptome alterations of marine Phaeodactylum tricornutum induced by NAs using RNA-sequencing. In total 70 differentially expressed genes (DEGs) are enriched in seven biological process pathways, and 48 DEGs are enriched in four molecular functions. Differentially expressed genes of P. tricornutum are primarily concentrated in three photosynthesis-related pathways including the porphyrin and chlorophyll metabolism pathway, the photosynthesis pathway, and the carbon fixation pathway in photosynthetic organisms. Five DEGs such as hemE, chlM, TPI/GapC3, FbaC5, and CHLH are validated using quantitative real-time PCR assay. NAs at low concentrations affect the material energy conversion efficiency of P. tricornutum, such as chlorophyll synthesis, electron transfer efficiency, and carbon assimilation.

Although challenging, fabrication of porous conducting polymeric materials with excellent electronic properties is crucial for many applications. We developed a fast in situ polymerization approach to pure polyaniline (PANI) hydrogels, with vanadium pentoxide hydrate nanowires as both the oxidant and sacrifice template. A network comprised of ultrathin PANI nanofibers was generated during the in situ polymerization, and the large aspect ratio of these PANI nanofibers allowed the formation of hydrogels at a low solid content of 1.03 wt %. Owing to the ultrathin fibril structure, PANI hydrogels functioning as a supercapacitor electrode display a high specific capacitance of 636 F g–1, a rate capability, and good cycling stability (∼83% capacitance retention after 10,000 cycles). This method was also extended to the preparation of polypyrrole and poly(3,4-ethylenedioxythiophene) hydrogels. This template polymerization method represents a rational strategy for design of conducing polymer networks, which can b...

Objective To investigate clinical efficacy of and optimal therapeutic strategy for ventricular intracranial pressure monitoring (V-ICPM) in patients with traumatic bifrontal contusions (TBCs). Methods From 8760 patients with traumatic brain injury treated between January 2010 and January 2016, a retrospective analysis was performed on 105 patients with TBCs who underwent V-ICPM and 282 patients with TBCs who did not. All patients underwent treatment at the 101st Hospital of PLA, Wuxi, China. Rates of successful conservative treatment, decompressive craniectomy, and bifrontal craniotomy; incidence of neurologic dysfunction; length of stay; and medical expenses were compared between groups. Results Glasgow Outcome Scale was used to assess all patients during follow-up (range, 6 months to 5.5 years). There were no significant differences in prognosis between the 2 groups (P = 0.100). Compared with the patients who did not undergo V-ICPM, the V-ICPM group had a significantly better successful conservative treatment rate (64.8% vs. 47.2%, P = 0.002), decompressive craniectomy rate (8.1% vs. 22.1%, P = 0.008), and bifrontal craniotomy rate (5.7% vs. 15.6%, P = 0.01); shorter length of stay (P = 0.000); and lower medical expenses (P = 0.004). Conclusions Patients with TBCs should be strictly, closely, and dynamically observed by neurosurgery intensive care unit physicians and nurses. Patients should undergo ventricular intracranial pressure probe implantation in a timely manner. V-ICPM can help optimize treatment. Although V-ICPM did not significantly improve the prognosis of patients, it had many other advantages. V-ICPM warrants further clinical research and may be beneficial for patients with TBCs.

The dielectric spectra of sodium perfluorooctanoate (NaPFO), ammonium perfluorooctanoate (APFO) and tetraalkylammonium perfluorooctanoate (C7F15COON(CnH2n+1)4, n = 1, 2, 3, 4, namely, TMPFO, TEPFO, TPPFO and TBPFO) were studied in the frequency range from 40 Hz to 110 MHz. An obvious dielectric relaxation was observed in each aqueous system whose low-frequency limit of relative permittivity (el) was divided into two groups based on their dependence on concentration, except there were two relaxations for TBPFO. Furthermore, their relaxation mechanism was analyzed and attributed to the radial diffusion of the free counterions in the diffuse layer. What's more, combined with the average radius of these micelles obtained on the basis of the Grosse's model, the difference between these two groups and their structural information were speculated. It was proved that the type of counterion has an important influence on the structure and properties of fluorocarbon surfactants.

Tip-enhanced Raman spectroscopy (TERS), known as nanospectroscopy, has received increasing interest as it can provide nanometer spatial resolution and chemical fingerprint information of samples simultaneously. Since Ag tips are well accepted to show a higher TERS enhancement than that of gold tips, there is an urgent quest for Ag TERS tips with a high enhancement, long lifetime, and high reproducibility, especially for atomic force microscopy (AFM)-based TERS. Herein, we developed an electrodeposition method to fabricate Ag-coated AFM TERS tips in a highly controllable and reproducible way. We investigated the influence of the electrodeposition potential and time on the morphology and radius of the tip. The radii of Ag-coated AFM tips can be rationally controlled at a few to hundreds nanometers, which allows us to systematically study the dependence of the TERS enhancement on the tip radius. The Ag-coated AFM tips show the highest TERS enhancement under 632.8 nm laser excitation and a broad localized surface plasmon resonance (LSPR) response when coupled to a Au substrate. The tips exhibit a lifetime of 13 days, which is particularly important for applications that need a long measuring time.

Background and objectives: Previous studies have shown that deep brain stimulation can improve clinical symptoms in patients with mild Alzheimer’s disease, but the therapeutic effect in patients with moderate-to-severe Alzheimer’s disease remains unclear. Therefore, we intend to assess the therapeutic effect of deep brain stimulation on moderate-to-severe Alzheimer’s disease through a 24-month follow-up visit. Design: A prospective single-center, self-controlled study. Methods: This trial will be performed at the 101st Hospital of PLA, Wuxi, China. We will include 20 patients with moderate-to-severe Alzheimer’s disease who will be given bilateral deep brain stimulation via an implant located beside the fornical column. Outcome measures: The primary outcome measure is the percent of patients whose scores on the Mini Mental State Examination have improved after 24 months. The secondary outcome measures include the percent of patients whose scores on the Mini Mental State Examination Scale have improved at other visits, their Montreal Cognitive Assessment-Basic score, Rey-Osterrieth Complex Figure Test score, score on the delayed recall of the Rey-Osterrieth Complex Figure Test, trail making test score, Hamilton Rating Scale for Depression score, functional magnetic resonance imaging results, functional PET imaging results at each visit point, and the incidence of adverse events. Discussion: This trial will provide feasible, objective, and quantifiable evidence for deep brain stimulation in the clinical treatment of moderate-to-severe Alzheimer’s disease. Ethics and dissemination: This study protocol was approved by the Institution Review Board of the 101st Hospital of PLA in China (approval No. L2017002) in December 2016. Design of the study was finished in October 2016, and registered in August 2017. Participant recruitment was started at October 2017, and was expected to be finished within 12 months. Data analysis will be completed until October 2020. The results of the study will be disseminated through presentations at peer-reviewed publications. Trial registration: This trial was registered in the Chinese Clinical Trial Registry with registration No. ChiCTR-ONC-17012311 (version 2.0).

The aim of the present study was to assess the therapeutic effects of atorvastatin on cerebral vessel autoregulation and to explore the underlying mechanisms in a rabbit model of subarachnoid hemorrhage (SAH). A total of 48 healthy male New Zealand rabbits (weight, 2‑2.5 kg) were randomly allocated into SAH, Sham or SAH + atorvastatin groups (n=16/group). The Sham group received 20 mg/kg/d saline solution, whereas 20 mg/kg/d atorvastatin was administered to rabbits in the SAH + atorvastatin group following SAH induction. Changes in diameter, perimeter and basilar artery (BA) area were assessed and expression levels of the vasoactive molecules endothelin‑1 (ET‑1), von Willebrand factor (vWF) and thrombomodulin (TM) were measured. Neuronal apoptosis was analyzed 72 h following SAH by terminal deoxynucleotidyl-transferase‑mediated dUTP nick‑end labeling (TUNEL) staining. The mortality rate in the SAH group was 18.75, 25% in the SAH + atorvastatin treated group and 0% in the Sham group (n=16/group). The neurological score in the SAH + atorvastatin group was 1.75±0.68, which was significantly higher compared with the Sham group (0.38±0.49; P

The global prevalence of obesity highlights the importance of understanding on regulation of energy homeostasis. The central melanocortin system is an important intersection connecting the neural pathways controlling satiety and energy expenditure to regulate energy homeostasis by sensing and integrating the signals of external stimuli. In this system, neural melanocortin receptors (MCRs), melanocortin-3 and -4 receptors (MC3R and MC4R), play crucial roles in the regulation of energy homeostasis. Recently, multiple intracellular signaling pathways and biased signaling at neural MCRs have been discovered, providing new insights into neural MCR signaling. This review attempts to summarize biased signaling including biased receptor mutants (both naturally occurring and lab-generated) and biased ligands at neural MCRs, and to provide a better understanding of obesity pathogenesis and new therapeutic implications for obesity treatment.

We investigated whether the personality of patients with Parkinson's disease (PD) before subthalamic brain stimulation differed from patients receiving drug treatments and whether the personality of patients affected surgical decisions. We recruited 38 patients with advanced PD scheduled for deep brain stimulation (DBS), 40 patients with PD receiving the very best medical treatment, and 51 healthy control subjects. All participants were evaluated by the Minnesota multiphasic personality inventory-1 (MMPI-1). PD patients who were candidates for DBS did not exhibit any significant differences in personality when compared with PD patients who were treated with drugs. Compared with healthy controls, patients with PD had remarkably higher MMPI-1 scores for spiritual quality, neuroticism, and introversion, but significantly lower scores for socialization. In addition, patients with PD were more submissive, more dependent on others, and less active in social activities. Our data indicated that the main deciding factor relating to whether to undergo DBS was the disease itself and not the pathological personality. However, neurotic and psychotic symptoms accompanying PD may influence the effect of DBS. We found that greater benefit is obtained by surgical or medical interventions if abnormal neurotic characteristics are considered early in the course of PD.

Angiopoietin-like protein 2 (ANGPTL2), a member of the glycoprotein family, is mainly secreted by adipose tissues under normal conditions. Recently, ANGPTL2 has been found to be upregulated in some types of cancers and is considered to be a tumor promoter. However, the functional significance of ANGPTL2 in glioma has not yet been elucidated. In this study, we investigated the specific role of ANGPTL2 in glioma. The results showed that ANGPTL2 was highly expressed in glioma tissues and cell lines. Knockdown of ANGPTL2 reduced the proliferative and invasive abilities of glioma cells. Moreover, the tumorigenesis assay showed that ANGPTL2 knockdown inhibited glioma tumor growth in vivo. We also found that ANGPTL2 knockdown decreased the protein levels of p-ERK1/2 in glioma cells and thus blocked the activity of the ERK/MAPK signaling pathway. Taken together, our study provided the first evidence that ANGPTL2 played an oncogenic role in glioma development and might be considered as a new therapeutic target for glioma treatment.

Density functional theory calculations were used to elucidate the mechanism of the addition reaction of acetaldehyde to positively charged hydrogenated silicene (H-silicene). We found that the positively charged H-silicene plane could be partially restructured to form a vacant Si site, which enabled an additional nucleophilic addition reaction. After attachment of the acetaldehyde molecule to the H-silicene plane, two competing pathways were found to be involved in the hydrogen-abstraction process: a random-reaction mechanism and a chain-reaction mechanism. The theoretical results provided detailed information about stable structures and thermodynamic parameters of the reaction pathways, such as equilibrium geometries, Gibbs free energies, and the evolution of the spin densities and atomic charges. Our results reveal that the existence of a positive charge can significantly activate the grafting of unsaturated species on hydrogenated silicene, even if no silicon dangling bond is created proactively. The simulated Raman spectra of the two products were analyzed to elucidate the features of the competing mechanisms.

Spinal cord ischemia-reperfusion injury (SCI/R) is a rare but devastating disorder with a poor prognosis. Small conductance calcium-activated K+ (SK/KCa) channels are a family of voltage-independent potassium channels that are shown to participate in the pathological process of several neurological disorders. The aim of this study was to investigate the role of SK/KCa channels in experimental SCI/R in rabbits. The expression of SK/KCa1 protein significantly decreased in both cytoplasm and mitochondria in spinal cord tissues after SCI/R. Treatment with 2 mg/kg NS309, a pharmacological activator for SK/KCa channel, attenuated SCI/R-induced neuronal loss, spinal cord edema and neurological dysfunction. These effects were still observed when the administration was delayed by 6 h after SCI/R initiation. NS309 decreased the levels of oxidative products and promoted activities of antioxidant enzymes in both serum and spinal cord tissues. The results of ELISA assay showed that NS309 markedly decreased levels of pro-inflammatory cytokines while increased anti-inflammatory cytokines levels after SCI/R. In addition, treatment with NS309 was shown to preserve mitochondrial respiratory complexes activities and enhance mitochondrial biogenesis. The results of western blot analysis showed that NS309 differentially regulated the expression of mitochondrial dynamic proteins. In summary, our results demonstrated that the SK/KCa channel activator NS309 protects against SCI/R via anti-oxidative activity and inhibition of mitochondrial dysfunction, indicating a therapeutic potential of NS309 for SCI/R.

The β

The β3-adrenergic receptor (β3-AR) is an important regulator of various physiological functions, such as thermogenesis in brown adipose tissue, lipolysis in white adipose tissue, negative inotropic effect in cardiomyocyte, and relaxation in blood vessel. The activation of β3-AR by its agonists is shown to have metabolic (antiobesity and antidiabetic) and cardiovascular effects in animal models, highlighting β3-AR as a potential therapeutic target in the treatment of several human diseases. Moreover, a substantial number of studies performed on different populations have identified some β3-AR polymorphic variants associated with obesity, diabetes, cardiovascular diseases, and other disorders. The clinical phenotypes and functional characteristics of these variants provide insights into potential pathophysiological roles of β3-AR in the development of these diseases.

A simplified three-degree-of-freedom dynamic model with nonlinear friction torque and engine torque excitation, capable of identifying the effect of the engine excitation on clutch judder, is presented. The analysis of harmonic order is performed and a sinusoidal contact pressure between friction surfaces is considered, along with an analytical solution for the relative angular velocity of the clutch plates. The average fluctuation amplitude of the clutch relative angular velocity is used to evaluate the judder. Numerical calculations indicate that the clutch judder increases significantly when the angular velocity of the crankshaft, corresponding to the harmonic orders of the engine, is equal or close to the natural frequency of the driveline. An identical frequency of the engine excitation and the oil pressure fluctuation contributes little to the clutch judder, unless the excitation is at or near the resonance frequency. The amplitudes of oscillations due to the engine excitation grow when the pulsating torque of the engine increases. The mean torque of the engine has little influence on the judder, although it governs the clutch engagement time. The results further show that clutch judder attenuates as the torsional stiffness of the system increases.

The transient thermal and thermoelastic analysis of an automotive multidisc clutch is performed to investigate the thermal deformation and the contact pressure distribution of the friction surfaces. An alternating finite volume method (FVM) and finite element method (FEM) for temperature distribution and contact pressure distribution, including the coupling between temperature, displacement, and contact pressure, is employed in MATLAB. A penalty function method is used to impose the constraints on the contact boundary. The computational results indicate that the contact pressure distributions on the surfaces near the pressure plate are more uniform than those near the opposite plate, and the nonuniformity is enlarged with the temperature rise. The contact pressure and temperature distributions on the two friction surfaces of the separate plate are dissimilar and asymmetric, which is in good agreement with the test results. The results further show that the contact pressure peaks diminish and the n...

The therapeutic effects of atorvastatin on early brain injury (EBI), cerebral edema and its association with aquaporin 4 (AQP4) were studied in rabbits after subarachnoid hemorrhage (SAH) using western blot analysis and the dry-wet method. Seventy-two healthy male New Zealand rabbits weighing between 2.5 and 3.2 kg were randomly divided into three groups: the SAH group (n=24), sham-operated group (n=24) and the SAH + atorvastatin group (n=24). A double SAH model was employed. The sham-operated group were injected with the same dose of saline solution, the SAH + atorvastatin group received atorvastatin 20 mg/kg/day after SAH. All rabbit brain samples were taken at 72 h after the SAH model was established successfully. Brain edema was detected using the dry-wet method after experimental SAH was induced; AQP4 and caspase-3 expression was measured by western blot analysis, and neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining at 72 h after SAH. The results indicated that brain edema and injury appeared soon after SAH, while brain edema and EBI were ameliorated and increased behavior scores were noted after prophylactic use of atorvastatin. Compared with the SAH group, the level of AQP4 and the cerebral content of water was significantly decreased (P

Melanocortin-4 receptor (MC4R) plays critical roles in the regulation of various physiological processes, such as energy homeostasis, reproduction and sexual function, cardiovascular function, and other functions in mammals. Although the functions of the MC4R in fish have not been extensively studied, the importance of MC4R in regulation of piscine energy expenditure and sexual functions is emerging. Swamp eel (Monopterus albus) is an economically and evolutionarily important fish widely distributed in tropics and subtropics. We cloned swamp eel mc4r (mamc4r), consisting of a 981 bp open reading frame encoding a protein of 326 amino acids. The sequence of maMC4R was homologous to those of several teleost MC4Rs. Phylogenetic and chromosomal synteny analyses showed that maMC4R was closely related to piscine MC4Rs. qRT-PCR revealed that mc4r transcripts were highly expressed in brain and gonads of swamp eel. The maMC4R was further demonstrated to be a functional receptor by pharmacological studies. Four agonists, α-melanocyte stimulating hormone (α-MSH), β-MSH, [Nle4, D-Phe7]-α-MSH (NDP-MSH), and adrenocorticotropin, could bind to maMC4R and induce intracellular cAMP production dose-dependently. Small molecule agonist THIQ allosterically bound to maMC4R and exerted its effect. Similar to other fish MC4Rs, maMC4R also exhibited significantly increased basal activity compared with that of human MC4R. The high basal activity of maMC4R could be decreased by inverse agonist ML00253764, suggesting that maMC4R was indeed constitutively active. The availability of maMC4R and its pharmacological characteristics will facilitate the investigation of its function in regulating diverse physiological processes in swamp eel.

Traumatic brain injury (TBI) is a prominent public health issue that has a significant negative impact on patients and their family members. It is the leading cause of mortality and disability among young (below 50 years old) individuals. Intracranial hypertension (ICH) remains the single most difficult therapeutic challenge for the management of severe TBI. Therapeutic hypothermia may reduce intracranial hypertension and improve patient outcomes; however, the use of hypothermia is controversial. It has been reported that therapeutic hypothermia elicits no therapeutic benefit for patients with TBI. The present study presents two patients with severe(s) TBI who were admitted to 101st Hospital of the People's Liberation Army Between June 2017 to October 2017. Multimodal brain monitoring measurements of intracranial pressure, cerebral perfusion pressure (CPP) and bispectral index (BIS) were used during assisted hypothermia for management of patients with sTBI. The duration, degree of hypothermia treatment and speed of re-warming were assessed.

Reproducible fabrication of sharp gold- or silver-coated tips has become the bottleneck issue in tip-enhanced Raman spectroscopy, especially for atomic force microscopy (AFM)-based TERS. Herein, we developed a novel method based on pulsed electrodeposition to coat a thin gold layer over atomic force microscopy (AFM) tips to produce plasmonic TERS tips with high reproducibility. We systematically investigated the influence of the deposition potential and step time on the surface roughness and sharpness. This method allows the rational control of the radii of gold-coated TERS tips from a few to hundreds of nanometers, which allows us to systematically study the dependence of the TERS enhancement on the radius of the gold-coated AFM tip. The maximum TERS enhancement was achieved for the tip radius in the range of 60-75 nm in the gap mode. The coated gold layer has a strong adhesion with the silicon tip surface, which is highly stable in water, showing the great potential for application in the aqueous environment.

A novel, mild and effective method was designed for grafting of high-quality organic monolayers on a silicon surface to catalyze nanoparticles' growth. By using a white-light source, 3-mercaptopropionic acid (3-MPA) molecules were attached to hydrogen-terminated Si(111) surfaces at room temperature. The attached monolayers were characterized using X-ray photoelectron spectroscopy to provide detailed information. The in situ growth of Au nanoparticles (AuNPs) with dimensions below 20 nm was catalyzed on a silicon surface with highly uniform and compact structure morphology. The AuNPs can grow selectively in a certain region on a patterned Si-Si3N4 chip. p-Nitrothiophenol (p-NTP) was used as the probe to evaluate the SERS enhancement of the highly uniform and compact AuNP-Si substrate. In order to better understand the white light initiation of the addition reaction of 3-MPA on the Si(111)-H surface, the mechanism was elucidated by density functional theoretical (DFT) calculations, which indicated that the formation of the Si-O bond occurred at the PEC of the first singlet excited state (S1) with a very low activation barrier about 30% of the ground state (S0) value.

Density functional theory calculations have been used to elucidate the mechanism of ultraviolet-induced functionalization of H–Si(111) surfaces with ethylene. The initial steps of this reaction involve the formation of a hole in the surface through photoemission and a partial restructuring of the surface. The H atom bound to the vacant site exhibits a significant chemical activity. Two competing pathways for this process involve a stochastic response mechanism and a chain reaction mechanism. These findings are discussed in light of recent experimental results of covalently attached monolayer formation on H–Si surfaces. The simulated infrared spectra of the two products were analyzed to elucidate the feature of the competing mechanisms.

Electrooxidation of hypophosphite (H2PO2−) on Ni electrode was investigated at the molecular level by external-reflection Fourier-transform infrared spectroscopy (FTIR), surface-enhanced infrared absorption spectroscopy with attenuated total reflection (ATR-SEIRAS), and shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). The results of external-reflection FTIR demonstrated that H2PO2− could be oxidized to HPO32− at significantly low potentials (E

Cipangopaludina chinensis was exposed to Roxithromycin, and the first, the fifth and the tenth days of the C. chinensis were chosen, then the liver of the C. chinensis were made into slices. The results showed that the live treated by Roxithromycin had shown certain changes in the structure. The liver cells were disorganized, and the number of fat bubbles increased. What’s more, some nucleus deviated from the original position, and the number of ovarian follicles increased, too. This paper explored the effect of Roxithromycin in water on the morphology of tissues in C. chinensis in order to provide a reference about the environment of the growth of benthonic animals, and provide basis for the controlling and management of the water pollution as well as the bioremediations of water environment.

Arc/Arg3.1 is a unique immediate early gene whose expression is highly dynamic and correlated with various forms of synaptic plasticity. Many previous reports highlight the complexity of mechanisms that regulate Arc/Arg3.1 expression in neurons. In the present study, the expression and regulation of Arc/Arg3.1 after glutamate treatment in primary cultured cortical neurons were investigated. We found that both Arc/Arg3.1 mRNA and Arc/Arg3.1 protein dynamically increased within 24h after glutamate treatment. The results of immunostaining showed that abundant amounts of Arc/Arg3.1 protein are presented in both soma and dendrites. The glutamate-induced increase in Arc/Arg3.1 protein levels was partially prevented by the NMDAR inhibitor DL-AP5, but not the AMPAR inhibitor NBQX. The results of calcium imaging showed that glutamate induced significant increases in intracellular calcium levels in a NMDAR-dependent manner. However, the intracellular calcium chelator BAPTA-AM had no effect on glutamate-induced upregulation of Arc/Arg3.1 protein, and alteration of cytosolic calcium ion homeostasis with A23187 and TG did not change Arc/Arg3.1 protein levels. In addition, the phosphorylation of ERK and CREB, two downstream factors of NMDAR signaling, markedly increased after glutamate exposure. Blocking ERK and CREB activation via selective inhibitors partially prevented the glutamate-induced elevation of Arc/Arg3.1 protein levels. Combined observations support a NMDAR-mediated and calcium-independent mechanism by which glutamate increases Arc/Arg3.1 expression in cortical neurons.

The thermister based temperature measurement scheme is widely applied for its low cost, strong stability and well flexibility. As the property between resistance and temperature is nonlinear, the practical application of thermister usually relies on the method of table look-up. Inevitably, that leads to the problems of poor versatility and large memory cost. Based on the analyses of resistance and temperature property, we propose an optimal linearization method of parameter design for NTC thermister interface circuit in this paper. The proposed approach is simple, but has a good linearity and high sensitivity. Test results are given to support the theoretical analyses and conclusions.

The heavy metal content of water in the oil spill area of Bohai Bay had been evaluated though the determination results, the distribution and variation difference of the heavy metal content in water had been discussed, In 2013 spring, 32 water samples had been collected in the oil spill area of Bohai Bay to measure chromium(Cr), zinc(Zn), copper(Cu), arsenic(As), cadmium(Cd), mercury(Hg) and lead(Pb) content. In surface water the heavy metal content from high to low was Cu, Zn, Cr, As, Pb, Cd, Hg, and the same as it in bottom water. Cr, As, Cd, Hg and Pb were not beyond first class value of the seawater quality standard except Zn and Cu.

Long non-coding RNAs (lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101st Hospital of the People’s Liberation Army, China (specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups (P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs’ involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.

National Basic Research Program of China [2009CB930703]; National Natural Science Foundation of China [21021002]; Science and Technology Project of Fujian Province, China [2009H4020]

To determine the effects of dietary selenium (Se) supplementary on muscle superoxide dismutase (SOD) activity, oriental river prawn, Neocaridina heteropoda were exposed to sodium polyphosphate. For each concentration , the shrimps were grouped into control diet group, inorganic Se group and organic Se group. For each concentration, the order of total SOD activities were organic Se diet group > inorganic Se diet group > control diet group. With the increasing concentrations of sodium polyphosphate, the total SOD activities increased first and then decreased dramatically. This study indicated that Se supplementary in diet could enhance the resistance of shrimps against low concentrations of ambient Sodium polyphosphate.