Neurosyphilis complicated by anti-γ-aminobutyric acid-B receptor encephalitis: A case report.

BACKGROUND: Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system, causing encephalitis. Few cases of anti-N-methyl-D-aspartate receptor autoimmune encephalitis (AE) secondary to neurosyphilis have been reported. We report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor (GABABR) AE. CASE SUMMARY: A young man in his 30s who presented with acute epileptic status was admitted to a local hospital. He was diagnosed with neurosyphilis, according to serum and cerebrospinal fluid (CSF) tests for syphilis. After 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin, epilepsy was controlled but serious cognitive impairment, behavioral, and serious psychiatric symptoms were observed. He was then transferred to our hospital. The Mini-Mental State Examination (MMSE) crude test results showed only 2 points. Cranial magnetic resonance imaging revealed significant cerebral atrophy and multiple fluid-attenuated inversion recovery high signals in the white matter surrounding both lateral ventricles, left amygdala and bilateral thalami. Anti-GABABR antibodies were discovered in CSF (1:3.2) and serum (1:100). The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE, and received methylprednisolone and penicillin. Following treatment, his mental symptoms were alleviated. Cognitive impairment was significantly improved, with a MMSE of 8 points. Serum anti-GABABR antibody titer decreased to 1:32. The patient received methylprednisolone and penicillin after discharge. Three months later, the patient's condition was stable, but the serum anti-GABABR antibody titer was 1:100. CONCLUSION: This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.

Application value of protein phase separation mechanism of flowering regulation in de novo domestication.

Global climate change and population growth pose a serious threat to world food security. The current crops varieties will be insufficient to meet food needs in the future, and there is an urgent need for high yielding and quality crops varieties with strong environmental adaptability. The rapid de novo domestication of wild species to create new germplasm that can be applied to crop breeding is a new strategy for ensuring food security. The flowering time is an important factor in determining the crop planting area and yield, and is a trait that is often selected in crop domestication. At present, the modification of flowering traits by de novo domestication is usually achieved by direct editing of the major genes that control flowering in crop, which are very limited in number and relatively homogeneous in function. Floral transition is regulated by the complex network of environmental and endogenous signals. Here, we propose a new strategy that using genome editing to precisely modify protein function by changing protein phase separation capacity of important proteins that regulate expression of flowering genes, which may provide new options for the design of flowering traits in de novo domestication.

Using Nonlinear Dynamics and Multivariate Statistics to Analyze EEG Signals of Insomniacs with the Intervention of Superficial Acupuncture.

OBJECTIVE: As a noninvasive and nonpharmacological therapeutic approach, superficial acupuncture (SA) is a special method of acupuncture. In this study, using nonlinear dynamics and multivariate statistics, we studied the electroencephalography (EEG) of primary insomnia under SA intervention to investigate how brain regions change. METHOD: This study included 30 adults with primary insomnia. They underwent superficial acupuncture at the Shangen acupoint. The EEG signals were collected for 10 minutes at each state, including the resting state, the intervention state, and the postintervention state. The data were conducted using nonlinear dynamics (including approximate entropy (ApEn) and correlation dimension (CD)) and multivariate statistics. RESULT: The repeated-measures ANOVA results showed that both ApEn and CD values were not significantly different at the three states (p > 0.05). The paired t-test results showed that the ApEn values of electrodes O2 (the right occipital lobe) at the postintervention state have decreased, compared with the resting state (p < 0.05), and no difference was detected in CD (p > 0.05). The cluster analysis results of ApEn showed that patients' EEG has changed from the right prefrontal lobe (electrode Fp2) to the right posterior temporal lobe (electrode T6) and finally to the right occipital lobe (electrode O2), before, during, and after the SA intervention. In addition, the factor analysis results of CD revealed that patients' EEG of all brain regions except for the occipital lobes has changed to the frontal lobes and anterior temporal and frontal lobes from pre- to postintervention. CONCLUSION: SA activated the corresponding brain regions and reduced the complexity of the brain involved. It is feasible to use nonlinear dynamics analysis and multivariate statistics to examine the effects of SA on the human brain.

[Effects of mild moxibustion on Beclin-1/Bcl-2 expression in spinal cord of rats with cervical spondylotic radiculopathy].

OBJECTIVE: To observe the effects of mild moxibustion on the expression of autophagy and apoptosis factors Beclin-1, Bcl-2 mRNA and protein in spinal cord (including nerve root tissues) of cervical spondylotic radiculopathy (CSR) rats, so as to explore the analgesic mechanism of mild moxibustion at "Dazhui" (GV14) on CSR. METHODS: SD rats were randomly divided into blank group, model group, mild moxibustion group and mild moxibustion+3-methyladenine(3-MA) group, with 10 rats in each group. CSR model was established by inserting the wire into the cervical nerve root. The rats in the blank group were only fed normally without any intervention.The rats in the mild moxibustion group and mild moxibustion+3-MA group were given mild moxibustion at GV14 for 10 min each time,and intraperitoneal injection of 1 mL 0.9% normal saline and 1 mL 3-MA(15 mg/kg)separately. Rats in the model group were given 0.9% normal saline every day. All the three interventions were started from the 3rd day after modeling for 7 days. The rat's behavioral reaction of gait was scored and the pain threshold of rat was measured with a pain analyzer; the expressions of Beclin-1 and Bcl-2 mRNA and protein in the spinal cord (including nerve root) were detected by fluorescence quantitative PCR and immunohistochemistry, separately. The autophagosome and ultrastructure of the spinal nerve root tissue were observed by transmission electron microscope. RESULTS: After modeling, the gait score was significantly increased (P<0.01) and the pain threshold significantly decreased (P<0.01) in the model group in comparison with the blank group. There was no statistical difference in Beclin-1 and Bcl-2 mRNA and protein expression between the blank and the model groups. After intervention, compared with the model group, the gait scores were significantly reduced (P<0.01), the pain threshold and the expressions of Beclin-1 and Bcl-2 mRNA and protein were significantly increased (P<0.01，P<0.05) in the mild moxibustion and mild moxibustion+3-MA groups. The improvement of the above indicators as more significant in the mild moxibustion group than that in the mild moxibustion+3-MA group (P<0.05). After modeling, the organelles in the spinal nerve root tissue cells of the model group were damaged and there were a small amount of autophagosomes. Compared with the model group, the ultrastructure of the spinal nerve root tissue cells in the mild moxibustion group were relatively complete, and the number of autophagosomes increased. CONCLUSION: Mild moxibustion at GV14 has a good analgesic effect on CSR rats, which may be related to its effects in up-regulation of Beclin-1 and Bcl-2 expressions and activation of autophagy and inhibition of apoptosis.

[Analysis on Insomniac Electroencephalogram Data After Treatment with Superficial Needling Based on Approximate Entropy and Correlation Dimensionality].

OBJECTIVE: To evaluate the influence of superficial needling on electroencephalogram (EEG) in patients with insomnia by using nonlinear kinetics measure. METHODS: Six patients (3 male and 3 female) suffering from insomnia for more than a month were recruited in the present study. EEG data before and during superficial acupuncture stimulation of Shangen point (the midpoint between the bilateral inner canthus) was recorded using an electroencephalograph for analyzing the correlation dimensionality (D 2) and approximate entropy (ApEn) of different cerebral regions. RESULTS: During superficial needling, the D 2 data of the right-forehead (Fp 2), anterior area of the left temple (F 7) and the anterior region of the right temple (F 8) were significantly increased (P<0.05), and ApEn data at the right anterior forehead(Fp 2), left occipital region (O 1), and F 8 region markedly decreased relevant to pre-acupuncture (P<0.05). Both paring test and trend analysis of D 2 data showed no significant changes. Only an obvious increase of D 2 was found in the Fp 2 region, suggesting a coherence of EEG activities in stability and synchronization during acupuncture treatment. Clustering analysis of D 2 data of various cerebral regions displayed a relatively concentrated tendency, particularly in the Fp 2, the right forehead (F 4) and F 8 regions. Factor analysis of ApEn data showed a significant change in Fp 2, F 8, O 1 and right occipital (O 2) regions. It suggests that during superficial needling stimulation of Shangen point, the EEG signals were lowered in complexity, and improved in synchronization, stabilization and ordering, favoring sleep at last. CONCLUSION: Superficial needling of Shangen point can make the EEG signals synchronized in insomnia patients, suggesting an improvement of sleeping.

Adiponectin reduces carotid atherosclerotic plaque formation in ApoE-/- mice: roles of oxidative and nitrosative stress and inducible nitric oxide synthase.

Adiponectin (APN) is an important anti­atherogenic adipocytokine. The aim of the present study was to investigate the role of adiponectin in atherosclerotic plaque formation and clarify its mechanisms. An atherosclerosis model was induced by in vivo perivascular constrictive silica collar placement on the left common carotid arteries in male apolipoprotein E­deficient (ApoE­/­) mice. All of the mice were fed a high­fat diet, and divided into phosphate­buffered saline, adenovirus (Ad)­ß­galactosidase and Ad­APN treatment groups. Compared with treatment of Ad­ß­gal or PBS, Ad­APN treatment markedly reduced inducible nitric oxide synthase (iNOS) protein expression, decreased in nitric oxide/superoxide production, blocked peroxynitrite formation and reversed the progression of atherosclerotic lesions. Adiponectin may be a natural molecule that reduces atherosclerosis by inhibiting iNOS and consequently diminishing oxidative/nitrative stress.

Mechanical stretch suppresses microRNA-145 expression by activating extracellular signal-regulated kinase 1/2 and upregulating angiotensin-converting enzyme to alter vascular smooth muscle cell phenotype.

Phenotype modulation of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of various vascular diseases, including hypertension and atherosclerosis. Several microRNAs (miRNAs) were found involved in regulating the VSMC phenotype with platelet-derived growth factor (PDGF) treatment, but the role of miRNAs in the mechanical stretch-altered VSMC phenotype is not clear. Here, we identified miR-145 as a major miRNA contributing to stretch-altered VSMC phenotype by miRNA array, quantitative RT-PCR and gain- and loss-of-function methods. Our data demonstrated that 16% stretch suppressed miR-145 expression, with reduced expression of contractile markers of VSMCs cultured on collagenI; overexpression of miR-145 could partially recover the expression in stretched cells. Serum response factor (SRF), myocardin, and Kruppel-like factor 4 (KLF4) are major regulators of the VSMC phenotype. The effect of stretch on myocardin and KLF4 protein expression was altered by miR-145 mimics, but SRF expression was not affected. In addition, stretch-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and up-regulated angiotensin-converting enzyme (ACE) were confirmed to be responsible for the inhibition of miR-145 expression. Mechanical stretch inhibits miR-145 expression by activating the ERK1/2 signaling pathway and promoting ACE expression, thus modulating the VSMC phenotype.

Two novel amphomycin analogues from Streptomyces canus strain FIM-0916.

Three lipopeptides, the known compound amphomycin, together with two novel compounds named aspartocin D (1) and aspartocin E (2) were obtained from the fermentation broth extraction of Streptomyces canus strain FIM0916 by using various column chromatography techniques. Their structures were elucidated by using spectroscopic methods, mainly by an extensive NMR analysis. It was demonstrated that compounds 1 and 2 are novel analogues of amphomycin, whose structures are similar to aspartocins. Compounds 1 and 2 share the same cyclic decapeptide core of cyclo (Dab2-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-), differing only in the side-chain moiety corresponding to Asp1-△3-isohendecenoic acid and Asp1-△3-isododecenoic acid, for aspartocin D and aspartocin E. In bioassays, compounds 1 and 2 exhibited antimicrobial activities against Gram-positive bacteria in the presence of Ca(2+) (1.25 mM); particularly, the activities were enhanced with higher concentrations of calcium.

Velocity vector imaging of longitudinal mechanical properties of upstream and downstream shoulders and fibrous cap tops of human carotid atherosclerotic plaque.

AIMS: Atherosclerotic plaque rupture is closely related to high regional mechanical stress in the plaque itself. We aimed to explore the longitudinal mechanical properties of upstream and downstream shoulders and fibrous cap tops of human atherosclerotic plaques in vivo by velocity vector imaging (VVI) combined with acoustic densitometry (AD) imaging. METHODS AND RESULTS: We included 135 patients with carotid atherosclerotic plaque. VVI and AD were used to examine 3 regions of carotid plaque along the longitudinal-axis view. A total of 405 regions were classified with low or high AD values by corrected averages image intensity (AIIc%) < or ≥50, respectively. Peak systolic strain, strain rate (SR), and velocity were significantly greater for upstream than downstream shoulders and fibrous cap tops of carotid plaque (P < 0.05 for both). AIIc% was significantly lower for upstream than downstream plaque shoulders (P < 0.05). Peak systolic SR of the plaque regions was negatively correlated with corresponding AIIc% (R(2) = 0.499, P < 0.05). CONCLUSIONS: The longitudinal strain of human carotid atherosclerotic plaques as derived by VVI is associated with its corresponding AD but also in part with the internal position of the strain, with values greater for upstream than downstream shoulders and fibrous cap tops.

Phenotypic variation caused by variation in the relative copy number of pDU1-based plasmids expressing the GAF domain of Pkn41 or Pkn42 in Anabaena sp. PCC 7120.

The cyanobacterium Anabaena (Nostoc) sp. PCC 7120 is a model for cyanobacterial cell differentiation studies. pDU1, an endogenous plasmid in Nostoc sp. PCC 7524, is used as the only cyanobacterial replicon for Anabaena (Nostoc) studies. However, the relative copy numbers of pDU1-based plasmids in Anabaena (Nostoc) sp. PCC 7120 are not well studied. We found that the relative plasmid copy number of one such vector, pRL25T, varied widely, especially when the vector carried a recombinant insert, under different conditions, ranging from 0.53 to 1812 per chromosome in different recombinant strains tested, either in independent clones of the same strain or in the same clone under different growth conditions. The phenotypes caused by pRL25T-driven expression of green fluorescent protein or the GAF domain of Pkn41 or Pkn42 varied depending on the independent clones analyzed. This phenotypic variation correlated with the relative plasmid copy number present in cells.

Interleukin 6 destabilizes atherosclerotic plaques by downregulating prolyl-4-hydroxylase α1 via a mitogen-activated protein kinase and c-Jun pathway.

Interleukin 6 (IL-6) is a pivotal cytokine that regulates extracellular matrix metabolism by ameliorating the modification of collagen content, important in fibrous caps of atherosclerotic plaque. Prolyl-4-hydroxylase α1 (P4Hα1) is a key intracellular enzyme required for synthesis of collagen in animals. We investigated the relationship of IL-6 and P4Hα1 in atherosclerosis-prone mice and human aortic smooth muscle cells (HASMCs). Apolipoprotein E (ApoE)-/- mice were fed a high-fat diet and a perivascular constrictive silica collar was placed on the right common carotid artery to induce atherosclerotic lesions, then mice were divided into two groups for transfection with empty lentivirus or IL-6 lentivirus. HASMCs were transfected with small interfering RNA or treated with recombinant human IL-6. IL-6 significantly downregulated collagen, P4Hα1 and smooth muscle cell contents in atherosclerotic mouse arteries. Macrophage and lipid contents in the atherosclerotic area were significantly increased with IL-6 treatment. IL-6 significantly downregulated P4Hα1 expression in HASMCs through an RAF-MEK1/2-ERK1/2 mitogen-activated protein kinase (MAPK) pathway, and c-Jun was involved in the process. Our findings highlight IL-6 destabilize atherosclerotic plaques in mice by downregulating P4Hα1 via an RAF-MEK1/2-ERK1/2 MAPK and c-Jun pathway.

Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells.

OBJECTIVES: Stretch affects vascular smooth muscle cell proliferation and apoptosis, and several responsible genes have been proposed. We tested whether the expression of microRNA 21 (miR-21) is modulated by stretch and is involved in stretch-induced proliferation and apoptosis of human aortic smooth muscle cells (HASMCs). METHODS AND RESULTS: RT-PCR revealed that elevated stretch (16% elongation, 1 Hz) increased miR-21 expression in cultured HASMCs, and moderate stretch (10% elongation, 1 Hz) decreased the expression. BrdU incorporation assay and cell counting showed miR-21 involved in the proliferation of HASMCs mediated by stretch, likely by regulating the expression of p27 and phosphorylated retinoblastoma protein (p-Rb). FACS analysis revealed that the complex of miR-21 and programmed cell death protein 4 (PDCD4) participated in regulating apoptosis with stretch. Stretch increased the expression of primary miR-21 and pre-miR-21 in HASMCs. Electrophoretic mobility shift assay (EMSA) demonstrated that stretch increased NF-κB and AP-1 activities in HASMCs, and blockade of AP-1 activity by c-jun siRNA significantly suppressed stretch-induced miR-21 expression. CONCLUSIONS: Cyclic stretch modulates miR-21 expression in cultured HASMCs, and miR-21 plays important roles in regulating proliferation and apoptosis mediated by stretch. Stretch upregulates miR-21 expression at least in part at the transcription level and AP-1 is essential for stretch-induced miR-21 expression.