ATF3 downmodulates its new targets IFI6 and IFI27 to suppress the growth and migration of tongue squamous cell carcinoma cells.

Activating transcription factor 3 (ATF3) is a key transcription factor involved in regulating cellular stress responses, with different expression levels and functions in different tissues. ATF3 has also been shown to play crucial roles in regulating tumor development and progression, however its potential role in oral squamous cell carcinomas has not been fully explored. In this study, we examined biopsies of tongue squamous cell carcinomas (TSCCs) and found that the nuclear expression level of ATF3 correlated negatively with the differentiation status of TSCCs, which was validated by analysis of the ATGC database. By using gain- or loss- of function analyses of ATF3 in four different TSCC cell lines, we demonstrated that ATF3 negatively regulates the growth and migration of human TSCC cells in vitro. RNA-seq analysis identified two new downstream targets of ATF3, interferon alpha inducible proteins 6 (IFI6) and 27 (IFI27), which were upregulated in ATF3-deleted cells and were downregulated in ATF3-overexpressing cells. Chromatin immunoprecipitation assays showed that ATF3 binds the promoter regions of the IFI6 and IFI27 genes. Both IFI6 and IFI27 were highly expressed in TSCC biopsies and knockdown of either IFI6 or IFI27 in TSCC cells blocked the cell growth and migration induced by the deletion of ATF3. Conversely, overexpression of either IFI6 or IFI27 counteracted the inhibition of TSCC cell growth and migration induced by the overexpression of ATF3. Finally, an in vivo study in mice confirmed those in vitro findings. Our study suggests that ATF3 plays an anti-tumor function in TSCCs through the negative regulation of its downstream targets, IFI6 and IFI27.

Efficacy of non-invasive brain stimulation for post-stroke dysphagia: a meta-analysis.

BACKGROUND: Given the potential harms of dysphagia after stroke, we noticed the possibility of non-invasive brain stimulation treatments in the management process. METHODS: The meta-analysis search for articles published before May 2023 in databases. We used STATA 12.0 software to compute the standard mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The study showed a greater improvement in swallowing function in post-stroke dysphagia given transcranial direct current stimulation (tDCS) immediately after treatment, compared to those given sham tDCS (SMD = 2.99, 95% CI = 1.86-4.11). The study showed a greater improvement in swallowing function in post-stroke dysphagia given tDCS some days after treatment, compared to those given sham tDCS (SMD = 2.01, 95% CI = 0.87-3.16). The study showed a greater improvement in swallowing function in post-stroke dysphagia given repetitive transcranial magnetic stimulation (rTMS) immediately after treatment, compared to those given sham rTMS (SMD = 4.17, 95% CI = 3.11-5.23). The study showed a greater improvement in swallowing function in post-stroke dysphagia given rTMS some days after treatment, compared to those given sham rTMS (SMD = 1.77, 95% CI = 0.94-2.60). CONCLUSIONS: In conclusion, our study showed the beneficial effects of non-invasive brain stimulation on difficulty swallowing for stroke patients and speculated about the potential application of non-invasive brain stimulation on post-stroke dysphagia improvement.

Different responses of Japanese encephalitis to weather variables among eight climate subtypes in Gansu, China, 2005-2019.

This study evaluated epidemic temporal aspects of Japanese encephalitis (JE) and investigated the weather threshold of JE response across eight climate subtypes between 2005 and 2019 in Gansu Province, China. Epidemiological data were collected from the China Information System for Disease Control and Prevention (CISDCP). Three epidemic temporal indices [frequency index (α), duration index (ß), and intensity index (γ)] were adopted for the comparison of epidemic features among different climate subtypes. In addition, the local indicators of spatial association (LISA) technique was used to detect the hot-spot areas. The category and regression tree (CART) model was used to detect the response threshold of weather variables in hot-spot areas across climate subtypes. Among eight climate subtypes in Gansu, in most hot-spot areas (i.e., high-high clusters), α, ß, and γ were detected in the climate subtypes of subtropical winter dry (Cwa), temperate oceanic continental (Cwb), and continental winter dry (Dwa and Dwb). According to the CART analysis, a minimum monthly temperature is required for Japanese encephalitis virus (JEV) transmission, with different threshold values among the climatic subtypes. In temperate climate zones (Cwa and Cwb), this threshold is 19 °C at a 1-month lag. It is lower in continental winter dry climate zones: 18 °C in Dwa (snow climate, dry winter, and hot summer) and 16 °C in Dwb (snow climate, dry winter, and warm summer). Additionally, some areas of the areas with temperate arid (BWk and BSk) had the first JE cases. Further studies to detect whether the climate change influence the JEV's distribution in Gansu Province are needed.

Effects of repeated manganese treatment on proton magnetic resonance spectra of the globus pallidus in rat brain.

Excessive manganese is neurotoxic, which means that it can affect the concentrations of metabolite in 1 H MRS. In addition, manganese is paramagnetic and it may influence the relaxation times of the metabolite. The aim of this study is to assess the sensitivity of the metabolite relaxation properties and concentrations to exogenous manganese deposition in the globus pallidus (GP) of rat brain after repeated manganese injection. Proton magnetic resonance spectroscopy (1 H MRS) experiments in vivo and ex vivo were carried out to evaluate the changes in the metabolite concentration and the major metabolite relaxation times, and histological experiments were also performed after repeated manganese administration. Only the T1 value for N-acetylaspartate (NAA) of the GP was significantly reduced after 1 day of manganese injection compared with that of the control group (p < 0.025). The T1 and T2 values for NAA and total creatine (tCr) (p < 0.025), along with the amounts of NAA, tCr, myo-inositol, choline, and glutamate (p < 0.0086) in the GP, were all significantly decreased after 5 days of manganese administration compared with that of the control group. The changes in the concentration and relaxation properties of NAA and tCr in the GP of rat brain indicated that manganese represented paramagnetism and neurotoxicity after repeated administration. Accurate knowledge of relaxation properties and concentrations of NAA and tCr in this study could help appropriate selection of sequence parameters to improve the ability to distinguish the brain regions affected in cases of manganese poisoning.

Comparative Transcriptome Analysis Reveals Mechanisms of Folate Accumulation in Maize Grains.

Previously, the complexity of folate accumulation in the early stages of maize kernel development has been reported, but the mechanisms of folate accumulation are unclear. Two maize inbred lines, DAN3130 and JI63, with different patterns of folate accumulation and different total folate contents in mature kernels were used to investigate the transcriptional regulation of folate metabolism during late stages of kernel formation by comparative transcriptome analysis. The folate accumulation during DAP 24 to mature kernels could be controlled by circumjacent pathways of folate biosynthesis, such as pyruvate metabolism, glutamate metabolism, and serine/glycine metabolism. In addition, the folate variation between these two inbred lines was related to those genes among folate metabolism, such as genes in the pteridine branch, para-aminobenzoate branch, serine/tetrahydrofolate (THF)/5-methyltetrahydrofolate cycle, and the conversion of THF monoglutamate to THF polyglutamate. The findings provided insight into folate accumulation mechanisms during maize kernel formation to promote folate biofortification.

Mapping accumulative whole-brain activities during environmental enrichment with manganese-enhanced magnetic resonance imaging.

An enriched environment (EE) provides multi-dimensional stimuli to the brain. EE exposure for days to months induces functional and structural neuroplasticity. In this study, manganese-enhanced magnetic resonance imaging (MEMRI) was used to map the accumulative whole-brain activities associated with a 7-day EE exposure in freely-moving adult male mice, followed by c-Fos immunochemical assessments. Relative to the mice residing in a standard environment (SE), the mice subjected to EE treatment had significantly enhanced regional MEMRI signal intensities in the prefrontal cortex, somatosensory cortices, basal ganglia, amygdala, motor thalamus, lateral hypothalamus, ventral hippocampus and midbrain dopaminergic areas at the end of the 7-day exposure, likely attributing to enhanced Mn2+ uptake/transport associated with brain activities at both the regional and macroscale network levels. Some of, but not all, the brain regions in the EE-treated mice showing enhanced MEMRI signal intensity had accompanying increases in c-Fos expression. The EE-treated mice were also found to have significantly increased overall amount of food consumption, decreased body weight gain and upregulated tyrosine hydroxylase (TH) expression in the midbrain dopaminergic areas. Taken together, these results demonstrated that the 7-day EE exposure was associated with elevated cumulative activities in the nigrostriatal, mesolimbic and corticostriatal circuits underpinning reward, motivation, cognition, motor control and appetite regulation. Such accumulative activities might have served as the substrate of EE-related neuroplasticity and the beneficial effects of EE treatment on neurological/psychiatric conditions including drug addiction, Parkinson's disease and eating disorder.

Asperosaponin VI Injection Enhances Orthodontic Tooth Movement in Rats.

BACKGROUND This study was performed to investigate the effect of local injection of asperosaponin VI (ASA VI) on the orthodontic tooth movement in rats. MATERIAL AND METHODS A total of 64 healthy female Sprague-Dawley rats were selected and divided into 2 groups randomly: the ASA VI group and the control group. For the ASA VI group, 10 mg/kg ASA VI solution was injected into buccal submucoperiosteal of bilaterally first maxillary molars, and the same volume of normal saline was given to the control group. The orthodontic force was applied to the maxillary first molars. All rats were sacrificed on days 3, 7, or 14. Tooth movement effects on the periodontium were analyzed through hematoxylin and eosin (H&E) staining, tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemistry analysis. Tooth movement measurements and alveolar bone volumetric changes were analyzed using a micro-computed tomography (CT) scan. Molecular changes were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. RESULTS The ASA VI group presented with a significant increase of tooth movement, osteoclast number, and the expression of osteoclast differentiation factor (ODF) compared with the control group. ASA VI also induced a significant decrease in bone volume and density and an increase in trabecular spacing and RANKL (receptor activator of nuclear factor kappa-B ligand) expression at the compression side. Furthermore, ASA VI stimulated bone formation on the tension side by enhancing OCN (osteocalcin) expression and RUNX2 (runt-related transcription factor 2) expression, increasing bone volume and density and decreasing in trabecular spacing. CONCLUSIONS Injection of ASA VI may accelerate tooth movement via increasing the activity of osteoclasts, stimulating bone resorption at the compression side. Furthermore, ASA VI has a positive effect on bone formation at the tension side.

NGT1 Is Essential for N-Acetylglucosamine-Mediated Filamentous Growth Inhibition and HXK1 Functions as a Positive Regulator of Filamentous Growth in Candida tropicalis.

Candida tropicalis is a pathogenic fungus that can cause opportunistic infections in humans. The ability of Candida species to transition between yeast and filamentous growth forms is essential to their ability to undergo environmental adaptation and to maintain virulence. In other fungal species, such as Candida albicans, N-acetylglucosamine (GlcNAc) can induce filamentous growth, whereas it suppresses such growth in C. tropicalis. In the present study, we found that knocking out the GlcNA-specific transporter gene NGT1 was sufficient to enhance C. tropicalis filamentous growth on Lee's plus GlcNAc medium. This suggests that GlcNAc uptake into C. tropicalis cells is essential to the disruption of mycelial growth. As such, we further studied how GlcNAc catabolism-related genes were able to influence C. tropicalis filamentation. We found that HXK1 overexpression drove filamentous growth on Lee's media containing glucose and GlcNAc, whereas the deletion of the same gene disrupted this filamentous growth. Interestingly, the deletion of the DAC1 or NAG1 genes impaired C. tropicalis growth on Lee's plus GlcNAc plates. Overall, these results indicate that HXK1 can serve as a positive regulator of filamentous growth, with excess GlcNAc-6-PO4 accumulation being toxic to C. tropicalis. These findings may highlight novel therapeutic targets worthy of future investigation.

Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients.

BACKGROUND: The development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells. However, it is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. In this study, we aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients. RESULT: Fifty refractory SLE patients and 70 healthy controls were enrolled and followed up for 24 weeks. We found that compared with HC, the refractory SLE patients had a lower number of Tregs, a similar number of Th17 cells, but an increased ratio of Th17/Treg. After the treatment, the number of Tregs of the patients at 12th and 24th week was significantly increased. While the number of Th17 cells was unchanged, the ratio of Th17/Treg was significantly decreased at both 6 weeks and 24 weeks. After 6, 12 and 24 weeks of treatment, the SLEDAI score was significantly reduced. The prednison dosage at 6th,12th and 24th week post treatment was significantly decreased. CONCLUSION: Our results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE. Low dose of IL-2 combined with rapamycin was able to restore the number of Tregs and the balance of Th17/Treg cells. As a result, this approach was able to induce immune tolerance and promote disease remission, allowing for the reduction in prednisone dosage. TRIAL REGISTRATION: ChiCTR-IPR-16009451 Registration date: 2016/10/16.

Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.

The inflammatory process in stroke is the major contributor to blood-brain barrier (BBB) breakdown. Previous studies indicated that semaphorin 4D (Sema4D), an axon guidance molecule, initiated inflammatory microglial activation and disrupted endothelial function in the CNS. However, whether Sema4D disrupts BBB integrity after stroke remains unclear. To study the effect of Sema4D on BBB disruption in stroke, rats were subjected to transient middle cerebral artery occlusion and targeted injection of lentivirus-mediated clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene disruption of PlexinB1. We found that Sema4D synchronously increased with BBB permeability and accumulated in the perivascular area after stroke. Suppressing Sema4D/PlexinB1 signaling in the periinfarct cortex significantly decreased BBB permeability as detected by MRI and fibrin deposition, and thereby improved stroke outcome. In vitro, we confirmed that Sema4D disrupted BBB integrity and endothelial tight junctions. Moreover, we found that Sema4D induced pericytes to acquire a CD11b-positive phenotype and express proinflammatory cytokines. In addition, Sema4D inhibited AUF1-induced proinflammatory mRNA decay effect. Taken together, our data provides evidence that Sema4D disrupts BBB integrity and promotes an inflammatory response by binding to PlexinB1 in pericytes after transient middle cerebral artery occlusion. Our study indicates that Sema4D may be a novel therapeutic target for treatment in the acute phase of stroke.-Zhou, Y.-F., Li, Y.-N., Jin, H.-J., Wu, J.-H., He, Q.-W., Wang, X.-X., Lei, H., Hu, B. Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.

Using structural equation modeling to detect response shift in quality of life in patients with Alzheimer's disease.

ABSTRACTBackground:Our study aims to detect different types of response shifts (RS) and true changes of quality of life (QOL) measurement in patients with Alzheimer's disease (AD) using structural equation modeling (SEM) in domain level. METHODS: Patients with AD aged over 60 years old were collected from the Department of Neurology and Geriatrics in Taiyuan Central Hospital, China. The 12-item Short Form (SF-12) Health Survey was measured in 238 patients with AD prior to hospitalization and one month following discharge. RS was detected by SEM approach. The statistical process consisted of four steps and fitted four models. We interpreted changes of parameters in models to detect RS and to assess true change. RESULTS: The results showed reprioritization of social functioning (SF) (χ2 = 4.13, p < 0.05), reconceptualization of role limitations due to emotional problems (RE) (χ2 = 17.03, p < 0.001), uniform recalibration of bodily pain (BP) (χ2 = 12.24, p < 0.001), and non-uniform recalibration of mental health (MH) (χ2 = 4.41, p < 0.05), respectively. The true changes of common factors were deteriorated in general physical health (PHYS) (-0.10, χ2 = 8.30, p < 0.005) and improved in general mental health (MENT) (+0.29, χ2 = 20.95, p < 0.001). The effect-sizes of RS were only small. CONCLUSION: This study showed that patients with AD occurred three types of RS and true changes one month following discharge. RS had effects on the QOL of patients. Better understanding of potential changes in QOL in patients with AD is crucial.

Metabolic profile of visual cortex in diabetic rats measured with in vivo proton MRS.

The purpose of the present study was to characterize the metabolic profile of the visual cortex in streptozotocin-induced Type 1 diabetic rats by means of in vivo proton MRS. Several metabolite concentration ratios in the visual cortex were calculated. In addition, postmortem histologic analyses for retinal ganglion cell (RGC) loss, optic nerve injury and visual cortex alterations were monitored. The results showed that diabetes induced several changes in visual cortex metabolites, such as reduced N-acetylaspartate, glutamate, γ-aminobutyric acid, taurine and choline-containing compound levels. Nevertheless, myo-inositol levels increased significantly as compared with controls. Remarkable RGC loss and optic nerve degeneration were observed by morphological analysis. Moreover, the results showed significant neuronal loss and glial activation in the visual cortex. These findings indicated that, besides vascular abnormalities, neuronal loss and degeneration in the visual pathway were induced due to disrupted glucose homeostasis in diabetes. Metabolic or functional abnormalities were induced in cerebral neurons of the visual cortex by diabetes.

Clinical and prognostic significance of HIF-1α overexpression in oral squamous cell carcinoma: a meta-analysis.

BACKGROUND: Recent studies have indicated an association between hypoxia inducible factor-1 alpha (HIF-1α) expression and poor prognosis in patients with oral squamous cell carcinoma (OSCC); however, definitive evidence of this association is yet to be obtained. We performed a meta-analysis to evaluate the association of HIF-1α expression with clinicopathological characteristics and overall survival (OS) of patients with OSCC. METHODS: A literature search for relevant studies published in English language as of February 05, 2016, was performed on PubMed, Web of Science, and EMBASE databases. Eighteen studies with a combined study population of 1474 patients with OSCC are included in the meta-analysis. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was calculated using random-effects model or fixed-effects model. RESULTS: HIF-1α overexpression was significantly associated with larger tumor size (OR = 2.28, 95% CI = 1.49-3.50, P = 0.017), advanced TNM stage (OR = 2.29, 95% CI = 1.50-3.49, P = 0.158), and lymph node metastasis (OR = 2.05, 95% CI = 1.19-3.53, P < 0.001), but not with poor differentiation (OR = 1.21, 95% CI = 0.55-2.64, P = 0.024). These results demonstrated an association between HIF-1α expression and biological behavior of OSCC. On pooled analyses, high expression of HIF-1α was associated with worse OS (HR = 1.70, 95% CI = 1.10-2.61, P < 0.001). On subgroup analyses, overexpression of HIF-1α was significantly associated with poor prognosis in Asian population (HR = 2.33, 95% CI = 1.72-3.15, P = 0.862). CONCLUSIONS: Our findings demonstrate an association of HIF-1α overexpression with tumor size, tumor stage, lymph node metastasis, and overall survival. HIF-1α could be an independent prognostic marker in patients with OSCC.

Report: Small cell neuroendocrine carcinoma (SCNEC) of the tongue: A case report.

Small cell neuroendocrine carcinoma (SCNEC) of the tongue is very rare. We here present a SCNEC impatient with distant metastasis. A 74-year-old Chinese male went to hospital to treat a tongue tumor, which was founded at a conventional physical examination in Weifang Stomatology Hospital. The check of positron emission tomography-computer tomography (PET-CT) by Weifang people's hospital revealed a tumor in the right root of tongue, and distant metastasis in the right submandibular area, neck, mediastinum, right hilar, abdominal, retroperitoneal multiple lymph nodes, left thyroid, right lower lung, right scapula and bilateral adrenal. The patient was diagnosed tongue SCNEC by the pathological analysis of the tissue section. Conforming to the diagnosis of tongue SCNEC, the patient received adjuvant chemotherapy for 6 cycles with etoposide and carboplatin, and is alive now 9 months after the diagnosis.

Expression and clinical implications of HAb18G/CD147 in hepatocellular carcinoma.

AIM: HAb18G/CD147 is an important factor in invasion and metastasis of hepatocellular carcinoma (HCC). However, the clinical implications of HAb18G/CD147 expression in HCC are still unclear. In this study, we clarify the clinical significance of HAb18G/CD147. We characterize the association between HAb18G/CD147 expression and presentation of fibrosis or chronic hepatitis B, as well as its effect on HCC development. METHODS: The expression of HAb18G/CD147 in human hepatocarcinoma cell lines was analyzed by reverse transcription polymerase chain reaction and western blotting. Tumor tissues were obtained from HCC patients who underwent surgical resection between 2002 and 2006. All patients who had received previous therapy were excluded. HCC tissues were analyzed by immunohistochemistry using anti-HAb18G/CD147. RESULTS: HAb18G/CD147 was widely expressed in Hep-G2, SMCC-7721 and BEL7402 cell lines, but not expressed in L-02, a human normal hepatic cell line. HAb18G/CD147 was mainly localized to the membrane of tumor cells in 74.0% (37/50) HCC patients. We found that higher HAb18G/CD147 expression and poor tumor differentiation were correlated with patient survival (P = 0.026 and P = 0.014, respectively). Furthermore, the distribution of HAb18G/CD147 was similar to that of hepatitis B virus (HBV) infection, but negatively related to hepatic cirrhosis. CONCLUSION: HAb18G/CD147 has shown its potentials in HCC development and patient survival. Moreover, it may also cooperate with chronic HBV infection and cirrhosis during HCC development. Its functions in the two factors may be different. Therefore, HAb18G/CD147 may be a marker for poor prognosis in HCC patients and could be a useful therapeutic target for interfering with or reversing HCC progression.

Assessing changes in quality of life using the Oral Health Impact Profile (OHIP) in patients with different classifications of malocclusion during comprehensive orthodontic treatment.

BACKGROUND: The objectives of this study were to investigated changes in OHRQoL among patients with different classifications of malocclusion during comprehensive orthodontic treatment. METHODS: Clinical data were collected from 81 patients (aged 15 to 24) who had undergone comprehensive orthodontic treatment. Participants were classified 3 groups: Class I (n = 35), II (n = 32) and III (n = 14) by Angle classification. OHRQoL was assessed using the Oral Health Impact Profile (OHIP-14). All subjects were examined and interviewed at baseline (T0), after alignment and leveling (T1), after correction of molar relationship and space closure (T2), after finishing (T3). Friedman 2-way analysis of variance (ANOVA) and Wilcoxon signed rank tests were used to compare the relative changes of OHRQoL among the different time points. A Bonferroni correction with P < 0.005 was used to declare significance. RESULTS: Significant reductions were observed in all seven OHIP-14 domains of three groups except for social disability (P > 0.005) in class I and class II, Handicap in class II and class III (P > 0.005). Class I patients showed significant changes for psychological disability and psychological discomfort domain at T1, functional limitation, physical pain at T2. Class III patients showed a significant benefit in all domains except physical pain and functional limitation. Class II patients showed significant changes in the physical pain, functional disability, and physical disability domains at T1. CONCLUSIONS: The impact of comprehensive orthodontic treatment on patients' OHRQoL do not follow the same pattern among patients with different malocclusion. Class II patients benefits the most from the stage of space closure, while class I patients benefits the first stage (alignment and leveling) of treatment in psychological disability and psychological discomfort domains.

Antitumor activity of a sulfated polysaccharide from Enteromorpha intestinalis targeted against hepatoma through mitochondrial pathway.

A sulfated polysaccharide (EI-SP), extracted from Enteromorpha intestinalis that is a kind of algae, is found to have anticancer activity. This study was designed to investigate the anti-tumor effect of EI-SP on human hepatoma HepG2 cell line and its possible mechanisms. An MTT assay showed that EI-SP could specifically inhibit the growth of human hepatoma HepG2 cells in a dose-dependent manner. Analysis by flow cytometry indicated that the apoptosis of tumor cells increased after treatment with EI-SP in range of 100-400 µg/ml. Furthermore, Western blot analysis showed that EI-SP treatment led to decreased protein expression of Bcl-2 and an increase in Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, it was found that EI-SP caused a loss of mitochondrial membrane potential (Δψ m) and the release of cytochrome c to the cytosol. Collectively, our results showed that the EI-SP induces apoptosis in HepG2 cells involving a caspases-mediated mitochondrial signalling pathway.

Decyanative Heteroarylations of Glycine Derivatives.

Amino acids and aromatic nitrogen heterocycles are widely used in pharmaceuticals. Herein, we present an effective visible-light-driven thiobenzoic acid (TBA)-catalyzed decyanative C(sp3)-H heteroarylation of glycine derivatives. This process occurs under mild and straightforward conditions, affording a range of valuable yet challenging-to-obtain α-heteroaryl amino acid derivatives. Moreover, this organocatalytic C(sp3)-C(sp2) bond formation reaction is applicable to the late-stage modification of various short peptides.

Synthesis and evaluation of Bingel-Hirsch multiadducts of paramagnetic gadofullerene as potential magnetic resonance imaging contrast agents.

Water-soluble malonate multiadducts of paramagnetic gadolinium endohedral metallofullerene, Gd@C82[C(COOH)2]6 and Gd@C82[C(COOH)2]8, were synthesized by Bingel-Hirsch reaction. Gd@C82 was firstly reacted with diethyl bromomalonate in the presence of alkali metal hydride to produce malonic ester multiadducted derivatives, Gd@C82[C(COOCH2CH3)2]x (x = 3-8), by Bingel reaction. They were isolated and purified to obtain Gd@C82[C(COOCH2CH3)2]6 and Gd@C82[C(COOCH2CH3)2]8 by silica-gel column chromatography with a gradient elution method, which were subsequently hydrolyzed to yield water-soluble Gd@C82[C(COOH)2]6 and Gd@C82[C(COOH)2]8 by Hirsch reaction. The structures of the derivatives were characterized by Fourier transform infrared spectrometry and matrix assisted laser desorption ionization time-of-flight mass spectrometry. The longitudinal relaxivities of Gd@C82[C(COOH)2]8 and Gd@C82[C(COOH)2]6, in buffer solution, were found to be 18.20 and 11.08 mM(-1) s(-1) at concentration range between 0.001-0.025 mM Gd, and to be 12.71 and 6.73 mM(-1) s(-1) between 0.050-0.200 mM Gd, respectively. The results showed that the measured relaxivities for malonate derivatives of Gd@C82 were dependent on the concentration of these solutions and the number of hydrophilic carboxyl groups appended on the surface of the Gd@C82 cage.

[Analysis of pathogen spectrum of Encephalitis/Meningitis in northwestern area of China].

OBJECTIVE: To learn the characteristics of pathogen spectrum of Encephalitis /Meningitis in northwestern area of China. METHODS: Between January 1st 2009 and March 31st 2011, a total of 569 patients with clinical symptoms of Encephalitis/Meningitis were selected from the hospitals in Gansu, Qinghai,Inner Mongolia and Xinjiang province. 1514 samples of specimen were collected from the 515 patients, to detect the IgM of Japanese encephalitis virus (JEV), enterovirus (EV, including Coxsackie virus, ECHO virus and enterovirus 71), Mumps virus, Herpes simplex virus (HSV) in blood and cerebrospinal fluid. Meanwhile, Neisseria meningitis (Nm), Haemophilus influenzae Type B (Hib), Staphylococcus, Streptococcus pneumonia, Streptococcus Suis, E. Coli and Cryptococci were also identified. The detection results were analyzed by different region, time and age range. RESULTS: Pathogenic bacteria were identified in the specimen from 16 patients, with the rate at 3.65%, of which the dominant ones were Streptococcus pneumonia (7 patients, 43.75%). Virus were identified in the specimen from 132 patients, with the rate at 27.05%, of which the dominant types were EV and HSV, accounting for 33.33% (44 cases) and 31.82% (42 cases) respectively. The detection rate of virus showed a significant seasonal trend, with the peak appearing between June and November each year. The peak of EV detection was between July and September, with 24 cases detected out; the peak of HSV was between June and August (11 cases detected out); mumps virus was mainly found between July and December (25 cases). There was no significant time-distribution found in the detection of bacteria. The EV and HSV were mainly distributed in Gansu and Qinghai province (70 cases) ;most of mumps virus were found in Gansu province (24 cases);and JEV were only found in Gansu province (20 cases). The viral pathogen spectrum was identified in all ages, and the EV and mumps virus were mainly found in children aged 0-14 years old (42 and 17 cases respectively) ; JEV were identified in people over 15 years old, with 13 detected out of the 20 patients. CONCLUSION: The main pathogen of acute encephalitis and meningitis in northwestern area of China was virus, and the main pathogens of encephalitis and meningitis in children under 15 years were Herpes simplex virus and Mumps virus.